Radioimmunoassay of a human serum growth factor for Balb/c-3T3 cells: derivation from platelets. A radioimmunoassay has been developed for the detection and quantification of a human serum polypeptide that has growth-promoting activity for confluent Balb/c-3T3 cells. Antiserum to this growth factor does not recognize antigens in mouse, guinea pig, or bovine serum but does detect some crossreacting antigen in the serum of the New World monkey Cebus albifrons and more in the serum of the Old World rhesus monkeys Macaca mulatta and M. fascicularis, demonstrating that the antigenic determinants of the growth factor have a degree of species specificity. Serum derived from whole human blood contains approximately 770 pg of the growth factor per mg of protein; serum derived from platelet-poor blood contains about 112 pg of the growth factor per mg of protein. As much as 1 microng of the growth factor per mg of protein has been recovered from human platelets by heating them at 100 degrees for 2 min. Approximately 1-2 ng of the growth factor, in either whole serum or platelets, stimulates 5 to 10 X 10(3) confluent Balb/c-3T3 cells to replicate. The heat treatment of platelets allows the purification and quantitative recovery of the growth factor from blood.


Interaction of different egg parts in determination of various body regions in Drosophila melanogaster. When Drosophila melanogaster embryos were ligated at very early stages of nuclear multiplication (45-60 min after egg deposition) for the entire period of embryogenesis, egg fragments of variable sizes were able to continue development up to the hatching stage. These ligated embryos differentiated larval structures; anterior fragments formed larval head and posterior fragments formed larval abdominal structures. Ligation always prevented the differentiation of some of the intermediate larval bands whereas the terminal ones were always formed. Identical results were obtained when embryos (45-60 min after egg deposition) were temporarily ligated for only 5 min. However, puncturing with a fine glass needle immediately after temporary ligation through the ligated area could give rise to complete differentiation of all the bands. Since puncturing disrupted the barrier produced by ligation, we propose that interaction between anterior and posterior egg regions is necessary to allow complete development.


Localization of RNA polymerase in polytene chromosomes of Drosophila melanogaster. RNA polymerase (RNA nucleotidyltransferase) B (or II) and histone H1 of Drosophila melanogster were localized on salivary gland polytene chromosomes using the indirect immunofluorescence technique. RNA polymerase B is present almost exclusively in puffs and interband regions, whereas histone H1 is found primarily in bands. The puff at region 3C, known to be transcriptionally active in larval salivary glands, gives a bright fluorescence with antibodies against RNA polymerase B. This fluorescence disappears after exposure of the larvae to 37 degrees for 45 min. The heat shock treatment results in a general reduction of fluorescence intensity with the appearance of brightly staining heat shock puffs. Heat-induced removal of RNA polymerase molecules from a puff does not immediately alter its morphology. We propose than an interband represents that fraction of the total number of gene copies in a band that are active, the inactive copies being present in a condensed form in the adjacent band. Large puffs would originate through the decondensation and activation of most or all gene copies in a band.


Structure-function relations in phosphorylcholine-binding mouse myeloma proteins. The binding site interactions between the phosphorylcholine (phosphocholine)-binding mouse myeloma proteins TEPC 15, W3207, McPC 603, MOPC 167, and MOPC 511 and the isotopically substituted hapten phosphoryl[methyl-13C]choline have been investigated using 13C and 31P nuclear magnetic resonance (NMR) spectroscopy. Each protein exhibits a unique NMR pattern, but extensive similarities in chemical shift parameters upon binding of hapten to immunoglobulin suggest a significant degree of conservation of important hapten-binding site interactions. Moreover, independent binding studies, in conjunction with the NMR data, allow construction of a simple model of the binding sites of these antibodies, analyzed in terms of the relative strength of interaction between hapten and two main subsites. The NMR evidence supports the view that the heavy chains of these proteins dominate in interacting with bound phosphorylcholine; the various subspecificities of these proteins for phosphorylcholine analogues can be accounted for by amino acid changes in the hypervariable regions of the heavy chains.


Direct demonstration of murine thymus-dependent cell surface endogenous immunoglobin. Antisera raised in mammals to murine immunoglobulin (Ig) do not detect surface Ig on thymus-dependent (T) lymphoma cells as assessed by immunofluorescence analysis. In contrast, chicken antibodies, produced against the (Fab)2 fragment of normal mouse IgG and purified by binding to and elution from IgG-Sepharose 4B, give strong indirect fluorescence with murine T cells and cultured T lymphoma cells. The surface Ig caps, is shed, and reappears, indicating that it is of endogenous origin. Nonlymphoid tumor cells of various myeloid types do not bind this reagent, even though they bear avid Fc receptors. The capacity of chicken antibodies to bind to both bone-marrow-dependent and T cell lymphomas was abolished by adsorption with myeloma-derived kappa chains coupled to Sepharose. The kappa antigenic determinant recognized by the chicken antibodies may thus be different from that seen by mammalian antibodies, and the degree of exposure of Ig on the T lymphoma surface might also affect ease of detectability with these reagents. These data provide direct evidence that T lymphocytes and T lymphoma cells express and synthesize a surface Ig containing determinants that at least 'crossreact with bone-marrow-cell-derived kappa chains.


Effect of ergot alkaloids on sulfonylurea-stimulated insulin secretion in dogs. The insulinogenic response to a standard i.v. dose of a sulfonylurea can be markedly augmented in normal, conscious dogs if they are given 30 min earlier a single i.v. dose of dihydroergotamine (DHE). Since the parent substance ergotamine posssed no such amplifying properties, further experiments were conducted to clarify the essential structural requirements that have to be fulfilled for an ergot alkaloid to act as an amplifier of sulfonylurea-stimulated insulin secretion. Amine alkaloids ergonovine, dihydroergonovone and dihydromethylergonovine had no amplifying potency, but the hydrogenated amino acid alkaloids dihydroergocornine, dihydroergocristine and dihydroergokryptine (Hydergine) were almost as potent amplifiers as was DHE. The data indicate that (a) DHE, Hydergine and by inference all hydrogenated amino acid alkaloids are potent amplifiers of sulfonylurea-stimulated insulin secretion; (b) saturation of the double bond at C9 and C10 of the lysergic acid moiety and the pressence of an amino acid side chain are essential structual requirements for an ergot alkaloid to function as an amplifier of the action of sulfonylureas; and (c) it appears that these compounds are acting chiefly by mechanisms other than alpha-adrenergic and serotonergic receptor blockade, perhaps as regulatory molecules inducing positive cooperative changes in integral proteins of the plasma membrane of beta cells.


Serial study of the urinary metabolites in newborn children. Study on 24-hour, 30- and 60-day urine collected from 1500 newborn infants pointed out in some cases an abnormal excretion of some of the 40 urinary metabolites investigated. The analysis of urinary metabolites allows to detect a relation between abnormal excretion of urine metabolites and various types of "inborn errors of metabolism".


Investigations concerning the changes induced by deuterium for hydrogen substitution in bioelectric activity of the frog retina. D2O effects on various ERG parameters in frog were followed up. The OFF response itself proved to be less influenced by H leads to D substitution than the ON response, while the latency of the OFF response was more strongly altered than that of the ON response; this shows the independence of the mechanisms underlying the two responses.


Why there are only levo amino acids in the chemical composition of the living organisms. In the structure of the DNA-histone system there are three kinds of elements which present spatial asymmetries: a) the D-deoxyribose molecules; b) the two strands of DNA which are wound counter-clockwise around the helical axis; c) the levo amino acids of the histones. This paper presents data and arguments which demonstrate that all these spatial asymmetries are interdependent and compose a unique system.


Studies on the sensitizing activity of alpha-chymotrypsin in man. The sensitizing effect of alpha-chymotrypsin was followed up in a group of 116 women to whom parenteral treatment with this drug was associated to antibiotic therapy for various chronic inflammatory gynecopathies. The mean antibody titre to alpha-chymotrypsin, assayed by a passive hemagglutination technique, and the mean intensity of the intradermal tests with this drug were found significantly higher in 15 patients previously treated with alpha-chymotrypsin by comparison with 16 non-treated controls. A significant direct correlation was found between the titre of anti-alpha-chymotrypsin antibodies and the intensity of the intradermal tests. In 12 patients who had not previously been treated with alpha-chymotrypsin the antibody titre and the intensity of the intradermal tests rose significantly after a series of 10 injections with this drug. Eight of 116 patients (approximately 7%) treated with alpha-chymotrypsin developed overt symptoms of sensitization to the drug. The symptoms announcing the sensitization, the relation with the amount of the drug administered and the diagnostic value of intradermal tests are analysed. No relation was found between the presence of atopy and the sensitization to other drugs, on the one hand, and the sensitization to alpha-chymotrypsin, on the other hand.


Investigations concerning the metabolic adaptation of rats to cold. Investigations were performed in 40 male albino rats, mean weight 150 g, fed a standard diet and subjected to the action of cold for 8 days. The histological picture of the thyroid gland indicated a hyperfunction in accordance with the increase of oxygen intake, weight loss, an increase in glycemia, lactate, pyruvate and cholesterol.


Investigations on certain blood parameters in adrenalectomized rats. Investigations were performed in male rats weighing 120-200 g, fed a standard diet and kept at a temperature of 22 degrees C +/- 2. Of these rats 20 belonged to the control batch and 20 were subjected to bilateral adrenalectomy in one single time. Seven days following adrenalectomy natremia, potassemia and total blood cholesterol were determined, as checking parameters of the lack of the adrenal gland and the values of glycemia, lactacidemia and pyruvemia were studied, the lactate/pyruvate ratio being computed. A significant decrease in glycemia, lactacidemia and pyruvemia, as well as in the lactate/pyruvate ratio was found.


Effects of a high-tension electric field on the secretion of antidiuretic hormone in rats. White male Wistar rats exposed a single time for 120 minutes to the action of an electric field of 100 kV/m and 50 Hz present a very important increase of the plasma concentration of antidiuretic hormone (ADH). In the case of a 360-minute exposure a 30 per cent reduction of the diuresis as compared with the control takes concomitantly place.


The erythrocyte cytochrome b5.

The erythrocyte cytochrome b5. Cytochrome b5 was isolated from large volumes of human and pork erythrocytes. The present study shows that the absorbance spectra of the oxidized and reduced forms of the erythrocyte cytochrome b5, of the solubilized one and of that of microsomes are similar.


Modification of the radiation resistance of Aspergillus flavus mycelial units by some chemicals. Survival curves for the mycleium of Aspergillus flavus Link var. columnaris Raper and Fennell were constructed after irradiation with gamma rays in the presence of NaCl, NaBr, NaI, KCl, KBr, KI, CaCl2, CaBr2, CaI2, Ca(NO3)2, NaNO2, NaNO3, KNO2, iodoacetic acid, iodoacetamide and vitamin K5. In addition iodized salt was also tested. All the chemicals tested exhibited initial toxicity at zero dose. However, most of the chemicals demonstrated a synergism when present during irradiation. Compounds containing iodine were invariably the strongest radiosensitizers. The iodine present as an admixture in salt also retained its radiosensitizing character. Sodium bromide and calcium bromide behaved in a different way. The initial toxicity was reduced along with an increase in radiation dose resulting in more survival.


The use of CT scanners in megavoltage photon-beam therapy planning. Several problems related to the true value of quantitative information from CT scanners in improving estimates of photon-beam isodose distribution remain unanswered. The authors conclude that two widely used correction factors provide satisfactory isodose corrections behind heterogeneities of simple geometry. Lateral perturbations were found to be small for megavoltage photon beams, indicating that complex computational schemes are uncalled for. It appears doubtful that the use of CT information in megavoltage photon-beam isodose curve generation requires (a) larger computers than those currently available either in existing therapy planning systems or on the scanner itself or (b) direct access to the CT numbers.


Implications of computed tomography for inhomogeneity corrections in photon beam dose calculations. Patient inhomogeneity information is investigated for use in radiotherapy planning. Absorbed doses measured in a phantom are compared to doses calculated for photon beams using various treatment planning inhomogeneity correction methods. Delineation of inhomogeneities with a spatial resolution of 5 mm and with an electron density accuracy of 2% in usually sufficient to allow doses to be calculated with a mean accuracy of better than 2% for 60Co and 3% for 25-MV x rays if the authors' Equivalent Tissue-Air Ratio Method is used.


Financial expenditures for the care of cerebrovascular disease patients in an urban setting. A study was undertaken to determine the magnitude of the charges and costs and the sources of reimbursements for the care of cerebrovascular disease (CVD) patients in an urban setting, Orleans Parish (County), Louisiana, in 1971. The study helps to put national data on the cost-burden of cerebrovascular disease into perspective at the community level. It is thought that such data may prove useful in planning and evaluation of intervention programs and more coordinated approaches to care. All hospitals, nursing homes, extended care facilities, and noninstitutional sources of care (home health and rehabilitation agencies) that were identified as providing services to CVD patients were invited to participate in the study, and a sample of such cases was selected from each participating facility. The billing records for these cases were then reviewed and analyzed to determine charges by category of service and sources of reimbursement. At government institutions, per diem rates were used to determine costs. Total charges for care of the CVD patients amounted to $6,070,000. Hospital care generated the major charge, amounting to $5,159,000 (85 percent of the total charges) during the study year. Nursing home care charges totaled $391,000 (6.5 percent), extended care services $373,000 (6.1 percent), and home health care and noninstitutional rehabilitation services $147,000 (2.4 percent). Analysis of the data according to type of service revealed that only a small percentage of the care dollar was spent for rehabilitation services. The greatest amounts were spent for room and board in institutional facilities and for drugs, diagnostic services, and miscellaneous other services in hospitals. Average expenditures per CVD case for rehabilitation services in institutions were highest in extended care facilities, being much lower in hospitals and negligible in nursing homes. Average expenditures for care by noninstitutional health service agencies were highest for home aide services, followed by nursing and rehabilitation services.


The effect of pelvic irradiation on ileal function. Thirty-three patients with gynecological neoplasms undergoing radiotherapy to the pelvis had cholyl[1-14C]glycine breath tests to assess ileal function. Breath tests were performed on each patient in the first and fifth weeks of treatment and 19 of the patients had a third test three months post-treatment. In the first test, 29.9+/-16.8%  (mean+/-SD) of the administered dose was excreted in breath 14C in 24 hours. This rose to 47.3+/-15.9% (t=6.08; p less than .001) in the fifth week and fell to 36.6+/-16% (t=2.29; p less than .05) at three months post-treatment. Eight patients had breath tests performed one year post-treatment and the test percentages were 32.7+/-7.8% (t=1.19; p less than .10). The increase in 14CO2 excretion in the fifth week of treatment occurred at a time when most patients were having diarrhea. The data suggest that bile acid malabsorption due to ileal dysfunction may be a factor in radiation-induced diarrhea which occurs in nearly all patients during pelvic irradiation.


Serum magnesium and irradiation.

Serum magnesium and irradiation. Serum magnesium determinations were obtained on 10 dogs and 11 patients undergoing fractionated irradiation to the pelvis and lower abdomen. Five of dogs received oral prednisone during irradiation. There was no significant change in magnesium concentration in either the control dogs or the patients, but there was a significant increase in stool frequency in both the dogs and patients. A significant increase in magnesium concentration was noted in the dogs receiving prednisone. It is concluded that radiation-induced diarrhea is not caused by reduced serum magnesium concentration.


Radiation therapy for pineal tumors and suprasellar germinomas. Data on all patients with pineal body tumors and suprasellar germinomas seen at the University of California--San Francisco over a 25-year period were reviewed. Of 19 patients treated, 15 are still alive. Although treatment techniques varied, all patients received irradiation to the primary tumor site but not to the spinal cord. The tumor dose ranged from 4,000 to 5,500 rads using megavoltage equipment. The authors recommended a dose of 4,500-5,000 rads given over a period of five to six weeks.


Desmoid tumors--treatment and prognosis. Desmoid tumors are locally invasive benign tumors arising from musculoaponeurotic structures which are classified as fibromatoses and which have generally high post-surgical recurrence rates. Sixteen patients with desmoid tumors were treated with irradiation and evaluated for 2 to 6 years post-treatment. Of the 16, 13 cases have been controlled without recurrence. Virtually complete resolution of the tumor mass has been accomplished without the disfigurement and dysfunction characteristic of the radical surgical approach to treatment.


Double contrast urethrography for evaluation of abnormalities of the male urethra. Double contrast examination of the male urethra can be performed with a combination of sodium diatrizoate solution and air. In a patient with an anterior urethral diverticulum, improved definition of anatomic relationships was obtained.


Long-term results following extensive small intestinal resection in the neonatal period. At Alder Hey Children's Hospital in Liverpool there have been 8 children who survived long-segment intestinal resection in the neonatal period for more than 10 years, and there has been one further case at the University Children's Hospital in Zürich. The total of 9 children who were left with residual lengths of small intestine of between 26 and 75 cm form the basis of this report. Seven of these children have been personally followed up. One patient, although apparently perfectly well, is now an adult, has left home and refused to be re-examined. One child has been followed up by another paediatrician. In general it can be said that, provided these children are treated with care postoperatively over a period which may extend for many months or even a few years, the ultimate prognosis is extremely good. These children will grow up perfectly normally and will have no absorption difficulties. If the child is left with less than 30 cm of small intestine, the initial treatment becomes very difficult, but with adequate management even these infants can finally grow up into perfectly normal children with little or no absorption difficulties. The critical length of intestine lies in the neighbourhood of 20 cm. Correct initial treatment is all important and the one case in this series where this was not carried out is the only child who has still considerable difficulties. In some of the children under discussion, a hemicolectomy was performed as well as the small intestinal resection. This does not seem to have made much difference to the ultimate satisfactory outcome.


Immunochemistry of prostaglandin endoperoxide-forming cyclooxygenases: the detection of the cyclooxygenases in rat, rabbit, and guinea pig kidneys by immunofluorescence. Rabbit antiserum has been prepared against the prostaglandin endoperoxide-forming cyclooxygenase (EC 1.14.99.1) purified from sheep vesicular glands. Ouchterlony double diffusion and immunoelectrophoretic analyses indicate that the anti-cyclooxygenase serum is monospecific for the enzyme. The anti-cyclooxygenase serum reacts with both active and inactivated forms of the sheep vesicular gland (SVG) cyclooxygenase. Furthermore, the immune serum precipitates solubilized microsomal cyclooxygenases from each of six other tissues examined, including bovine seminal vesicle, rabbit kidney medulla, guinea pig lung, dog spleen, sheep uterus, and human platelets. Anti-SVG cyclooxygenase serum was used in combination with fluorescein isothiocyanate )FITC)-labeled goat anti-rabbit IgG to detect cyclooxygenases in cryostat sections from rat, rabbit and guinea pig kidneys by immunofluorescence. Highly prominent fluorescence was associated only with the epithelial cells lining the collecting ducts in rabbit and guinea pig kidneys, and except for the nucleus, was uniformly distributed within the interior of these cells. In rat kidney, fluorescence was detected not only in collecting tubules but also in the interstitial cells of the renal papilla. Our results are consistent with the emerging hypothesis that PGE2 produced intrarenally plays a physiological role in natriuresis.


Problems of therapeutic surgery in penis carcinoma. Very often penile cancer occurs histologically as a squamous cell carcinoma. Its treatment is based on radiation therapy and surgery and depends on the stage of the tumor, age of patient, and anatomy and pathology of the lymph system of the male genitalia. In evaluation of 69 cases, the problems of therapy and prognosis are discussed. Preventive circumcision for the purpose of facilitating genital hygiene is reputed to be the operative prophylaxis.


Diagnosis and treatment of primary malignant tumors of the seminal vesicles. The author, after suggesting that malignant tumors of the seminal vesicles are not as rare as usually believed, considers the best method of early diagnosis to be deferentovesiculography carried out in all suspected cases. Surgery of these tumors includes vesiculectomy by the transvesical route which permits simultaneous treatment of vesicular, ureteral, vesical, and prostatic lesions. A place of choice is reserved for high-energy radiotherapy.


[Rehabilitation of myocardial infarction (author's transl)]. The rehabilitation of patients with myocardial infarction starts at an early stage of the disease, with an activation programme. In the post-acute phase this is substituted by the early rehabilitation programme carried out in cardiological centres. When the patient is discharged from hospital he undergoes an approximately one year out-patient long-term rehabilitation programme, which encompasses all sorts of secondary prevention with respect to risk factors (i.e. carbohydrate and lipid metabolism disturbances, nicotine abusus, and hyperalimentation) as well as phychosocial assistance and adequate physical therapy. These procedures have yielded positive results. In a series of 800 patients who underwent long-term rehabilitation 75.8% had resumed work. Also important is that with the help of the long-term treatment the patients became less anxious and could hence be re-integrated more easily.


Unusual radiographic manifestations of cystic fibrosis. The authors report 2 radiographic findings that have not previously been described in patients with cystic fibrosis: (1) the linear form of pneumatosis coli (2) large pancreatic concretions which resembled the pancreatic calcificaitons of hereditary pancreatitis. The patient with pancreatic calcification also had labile diabetes and episodes of ketoacidosis, unusual complications of cystic fibrosis.


An initial report on a double-blind trial comparing small and large doses of gold in the treatment of rheumatoid disease. A double-blind clinical trial on 60 patients with rheumatoid disease comparing 10 mg sodium aurothiomalate weekly to 50 mg weekly is continuing. An initial report on thirty of these patients, who had completed a year of treatment, shows no statistically significant difference in the response between the two groups. No conclusions can be drawn about toxic reactions in this number of patients having received treatment for only one year.


Endotoxic activities of lipopolysaccharides of microorganisms isolated from an infected root canal in Macaca cynomolgus. Lipopolysaccharides (LPS) prepared from a strain of Bacteroides oralis, a strain of Fusobacterium necrophorum, and a strain of F. nucleatum, all isolated from an infected root canal in monkey (Macaca cynomolgus), were examined for endotoxic activities using primary skin reactions in rabbits and induction of leukocyte chemotaxis in rats. LPS of B. oralis showed considerably lower ability to cause skin inflammation than LPS of the fusobacteria. However, the leukotactic effect of the LPS preparations as determined by the wound chamber method in rats was approximately of the same proportion. In both tests the reactions were compared with those of commercial LPS of Salmonella typhi. This study shows that endotoxic LPS can be isolated from oral Gram-negative bacteria, which have infected the root canal. Therefore LPS may play a role in the development and maintenance of chronic inflammation of the periapical tissues.


Juxtapapillary duodenal diverticula and abnormalities by endoscopic retrograde cholangio-pancreatography (ERCP). In a consecutive series of 174 patients the biliary and pancreatic ducts were demonstrated by endoscopic retrograde cholangio-pancreatography (ERCP). In 84 patients with normal duct systems, juxtapapillary diverticula were found in 5 patients (6%). In 90 cases with ductal abnormalities due to biliary concrements, dilated common bile duct and pancreatitis, diverticula were found in 35 patients (39%). In patients with abnormalities in both duct systems, diverticula were found in 52%, and in patients with changes in one duct system diverticula were found in 33%. The difference in occurrence of diverticula in patients with normal duct systems and pathological duct systems was statistically significant (p less than 0.02). The findings indicate a correlation between juxtapapillary diverticula and pathological changes due to biliary concrements, dilated common bile duct without concrements and pancreatitis.


[Venerology in the everyday work of the internist]. The worldwide increase in the incidence of sexually transmitted diseases confronts the physician to an increasing extent with this group of infections. The high morbidity and the change in the clinical picture of gonorrhea, especially its asymptomatic form, give rise to extragenital complications which frequently lead the patient to the internal specialist in the first instance. Non-gonorrheal urethritis, in particular the infectious form, is undergoing intensive research. A number of organisms may be responsible, but a non-infectious origin must also be kept in mind. Syphilis is still important. The late stages of the disease have become rare thanks to highly effective therapy with antibiotics. The early stages of the infection, however, must always be considered in the differential diagnosis of any genital or anal affection, and also in generalized exanthemas of unknown origin. Homosexual transmission presents diagnostic problems of its own. Serological mass screening is essential. Interpretation of the results must take into account the different specificity of the various serological tests and their indication.


[Blood transfusion and kidney transplantation]. The non-transfusion policy for potential recipients of kidney allografts that has been followed in recent years has not proven successful. There is now ample clinical evidence of improved transplant function in the transfused recipients category. This has also been confirmed in recipients of a first cadaver kidney in Basel and Geneva. If the conditions valid for human kidney transplantation are matched as closely as possible in animal experiments, prolongation of graft function rather than accelerated rejection is usually observed after blood transfusions. Potential kidney graft recipients should be more liberally transfused and experimental evidence ought to be accumulated in order to establish a rationale for optimal host conditioning, while avoiding the hazards of blood transfusions to the greatest extent possible.


Asymptomatic gonorrhea in men: caused by gonococci with unique nutritional requirements. In a retrospective case-control study, gonococci with nutritional requirements for arginine, hypoxanthine, and uracil were recovered from 24 of 25 men with asymptomatic gonorrhea and 10 of 25 men with symptomatic gonorrhea (P = .0001). These strains represent a smaller proportion of gonococcal isolate from blacks than from whites. Asymptomatic urethral infection is important in the epidemiology of gonorrhea, particularly among whites.


Fibrosing alveolitis with autoimmune haemolytic anaemia: two case reports. Two patients with fibrosing alveolitis and autoimmune haemolytic anaemia are described. One patient also had neurofibromatosis. The haematological associations of fibrosing alveolitis are discussed, and a possible relationship between autoimmune haemolysis and fibrosing alveolitis is suggested.


Neuronal activity in cortical efferent zones projecting to wrist extensors during voluntary wrist extension in the monkey. Three monkeys were trained to make rapid wrist extension on presentation of a cue light. After training the animal sufficiently, unit activity was recorded from the cortical efferent zones corresponding to the wrist extensors. Most neurons in the wrist extensor zone were increased in their discharge rate during the wrist extension. Their activation pattern, especially the onset time, varied among different neurons. The earliest neuron was activated 65 msec before the EMG onset of the wrist extensors, while the latest did 30 msec after the EMG onset. About 80% of them activated before the EMG onset. In contrast, variation of the discharge onset of each neuron was rather small and 5-15 msec in quartile deviation. These findings may suggest that each neuron in the cortical efferent zone functions in different timing in the voluntary phasic contraction of the target muscle.


Cidal and subcidal effect of triethylene thiophosphoramide on cell kinetics of human bladder carcinoma cells in vitro. In view of increasing topical use of various chemotherapeutic agents for bladder carcinoma, an experimental study concerning the effect of triethylene thiophosphoramide (Thio-Tepa) on cell kinetics of bladder carcinoma cells was performed, working on an established cell line of human bladder carcinoma. This polyfunctional alkylating agent, which is most widely used for instillation chemotherapy of bladder carcinoma, revealed a concentration dependent cytotoxicity against the cells. DNA precursor incorporation suggested that repair mechanism occurred following subcidal dose of this compound and faulty repair took place following cidal dose. The cell cycle was prolonged after subcidal treatment, the main effect being seen in DNA synthetic phase, and the changes in the cell cycle parameters returned to the normal within 2 cell cycle time. Repeated treatment with subcidal dose at an interval of 48 hr led to more extensive changes in the cell cycle as compared with that of single dose. Repeated exposures to subcidal dose, however, did not show any differences in the growth curves from those of the controls.


Estimation of cell damage in monolayer culture using 14C-leucine incorporation. A comparison was made of 14C-leucine incorporation and cell viability of T24 human bladder carcinoma cells after treatment with Thio-Tepa, a potent alkylating agent. It was found that Thio-Tepa produced concentration-dependent damage in these cells and also that 14C-leucine incorporation correlated well with cell viability. 14C-leucine incorporation can be used as a reliable and rapid screening test for the assessment of the relative potencies of anticancer drugs.


Cytotoxic effects of normal sera on lymphoid cells. II. Requirements for inhibition of nonspecific serum cytotoxicity by agarose. Agarose is known to inhibit nonspecifically the cytotoxic effects of normal sera on xenogeneic lymphoid cells. To find an explanation for this agarose effect we have studied its requirements using guinea pig and human sera as the source of activity and rat thymocytes as target cells. Control assays were performed using heat-inactivated (56 C, 30 min) normal rat serum. The inhibitory effect of agarose was readily reproduced with untreated sera and also when sodium ethyleneglycoltetraacetate, a selective chelator of calcium ions, was added to the sera together with excess magnesium. However, the agarose effect failed to occur in the presence of 0.01 M EDTA unless magnesium ions were restored. Abrogation of cytotoxicity in human serum by incubation with a large number of target cells instead of agarose was also found to be magnesium dependent. Titrations of human serum, performed after absorption with agarose in the presence of EDTA, which does not interfere with antigen-antibody binding, and subsequent restoration of divalent cations, revealed no significant change in its cytotoxic titer when compared with that of mock-absorbed serum not subjected to the agarose treatment. Incubation of human serum with either agarose or rat thymocytes resulted in the conversion of factor B, essential for complement activation via the alternative pathway, previously shown to provide the complement activity necessary for the cytotoxic reaction. These results suggest that the agarose effect is mainly attributable to complement consumption via the alternative pathway rather than to the absorption of "natural" antibodies.


Myocardial fibrinolytic activity in allogenic cardiac rejection. The relationship between alterations in myocardial fibrinolytic activity and the degree of graft tolerance or rejection was studied in 22 nonimmunosuppressed heterotopic cardiac transplants in chacma baboons. Fibrinolysis was evaluated on tissue sections and tissue extracts. Fibrinolytic activity was compared with electrocardiographic voltage alterations and multiple myocardial biopsies and terminal heart specimens were examined by light and electron microscopy. Histopathology and reduction in fibrinolytic activity proved superior to electrocardiographic voltage reductions in assessing early cardiac rejection. The two former modalities correlated well with one another. Myocardial histology showed rejection change earlier than fibrinolytic activity reduction.


The opsonic activity of stored blood.

The opsonic activity of stored blood. Experiments were performed to measure the stability of opsonins during storage of whole blood collected in CPD solution and stored at 4 C. Three units were collected, and aliquots removed and recalcified on days 0, 3, 7, 14, 21, and 28. Reconstituted serum was immediately frozen and stored at -70 C. The ability to opsonize Escherichia coli 075 and Pseudomonas aeruginosa immunotype 1, both of which require activation and utilization of the alternative pathway of complement for opsonization, were performed simultaneously for each organism and for each unit. Results showed that there was a slight but insignificant reduction in opsonic strength during storage for up to 28 days. The results indicate that standard collection and storage conditions using CPD as the anticoagulant retains functional activity of the alternative pathway. C3 measured by radial immunodiffusion using antisera against the B antigenic determinant showed that C3 had not been converted during storage.


Whole antilymphocyte serum: a potent safe immunosuppressive agent for intravenous use in man. Fifty-one renal and marrow graft recipients have been treated with whole, absorbed rabbit anti-human-lymphocyte serum. Such sera are potent nontoxic immunosuppressive agents. Preexisting sensitivity can be erased, and early rejection episodes are essentially eliminated. Prolonged treatment is necessary and safe, and it ensures a sustained depression in circulating T cells. Adaptation between kidney graft and host then occurs, so that the combination of prednisone and Imuran alone can sustain graft viability.


Experimental and clinical therapy of diabetes by transplantation. Prevention, delay, or reversal of the microvascular complications of diabetes is the ultimate goal of pancreatic islet cell transplantation. Advances in surgical techniques and in islet isolation procedures have made the achievement of this goal a practical possibility. Microvascular lesions have indeed been prevented and even reversed in successful islet cell transplantation experiments in rats. Successful application of pancreatic islet cell transplantation in the human now awaits the development of effective suppression of rejection.


Islet of Langerhans allotransplantation in the rat. Normoglycemia in rats allotransplanted with islets of Langerhans was studied. It was found that pretreatment with donor liver extract and pertussis followed by a short course of ALS treatment results in much better overall survival of functioning islets of Langerhans allotransplants than with other forms of immunosuppression tested.


In vitro anti-mycobacterial activity of some new amino-glycoside antibiotics. Four new aminoglycoside antibiotics, namely gentamycin, amikacin, tobramycin and sisiomycin were tested against several pathogenic strains of so-called 'typical' and 'atypical' mycobacteria. Only amikacin exhibited considerable in vitro anti-mycobacterial activity against Mycobacterium tuberculosis and not against other mycobacterial pathogens. None of the other three antibiotics exhibited activity against any of the mycobacteria at low concentrations.


Rubeosis iridis generated by insulin hypersensitivity. There are important similarities between human and experimental monkey rubeosis iridis. We believe that we have developed a useful primate model to study iris neovascularization and that the possible role of immunity to insulin in the pathogenesis of human diabetic rubeosis iridis warrants further detailed consideration.


[Aminopeptidase system of Aspergillus flavus]. The aminopeptidases system contained in a complex of exocellular peptidhydrolases synthetized by Asp. flavus was studied. Separation of the system into individual enzymes of the type of leucin aminopeptidase, aminotripeptidase and specific leucyl-glycyl-glycine-aminopeptidase by the methods of salt fractionation. DEAE-Sephadex A-50 and DEAE-cellulose chromatography. These enzymes are characterized by a different degree of purification as well as by the presence of the multiple forms, anion and cation ones. The multiple forms differ in solubility, specific activity, chromatographic properties, thermostability. The presence of individual triglycine-aminotripeptidase is shown in the system. The differences are found in the properties of the enzymes splitting leucinamide and leucyl-glycine. There may be two different leucine aminopeptidases. Studies in correlation during hydrolysis of leucinamide and leucyl-glycyl-glycine and comparison of the fractions properties displaying the activities showed that there are no reasons to ascribe these both reactions to the effect of the same enzyme.


[Effect of thiophosphamide on copper concentration in rabbit tissues]. The copper in different tissues, blood, urine and feces was studied in experiments on rabbits 30 min, 6 h, 1, 3, 7, 15 and 30 days after intravenous administration of thiophosphamide in a dose of 6 mg per 1 kg of weight. The samples of the mentioned tissues were dried and ashed in the muffle furnace. The quantitative determination of copper in ash solution was performed by the diethyldithiocarbamate method using the spectrophotometer Cphi-4A. The thiophosphamide action is shown to cause regular changes in the copper content in the studied tissues of animals in the periods from 6 h up to 30 days inclusive. The occuring shifts are of bilateral character in different periods of the chemical effect, but in most cases a decrease in the copper content in the tissues under study is dominating.


[Comparative immunologic and physico-chemical properties of neurospecific antigens--bull antigen D and rat antigen alpha]. Immunological and physicochemical properties were compared for water-soluble acid neurospecific antigens: D of the bull and alpha of the rat. During immunoelectrophoresis in agar gel antigen D migrates as two immunologically indentical fractions having a position of prealbumins and alpha-globulins of blood serum. Antigen D from the bull brain is incompletely immunologically identical with antigen alpha from the rat brain. The molecular weight of antigen D determined under conditions of Sephadex G-100 column gel chromatography is 73000.


Laboratory methods of equine pregnancy diagnosis. Rectal examination is a reliable method of diagnosing pregnancy in the mare. Also, test kits are available for the simple quick detection of pregnant mare serum gonadotrophin. Nevertheless there is a considerable demand by practitioners for an independent laboratory service in equine pregnancy diagnosis, particularly during the gestational phase when placental gonadotrophin is concentrated in the blood. An initial attempt to provide a service by means of the agar gel diffusion test was disappointing and alternatives were sought. The primary requirements for an ideal alternative technique were defined as: accuracy, sensitivity, applicability to the optimum request period, elimination of subjective interpretation and a minimal inconclusive rate. Additional considerations included cost, practicality and test duration. The various tests available are summarised and their published accuracies are discussed. It was decided to reverse the current trend from biological to immunological techniques and to modify the test by which Cole and Hart announced the discovery of PMSG in 1930. The utero-ovarian response in the immature female mouse was quantified simply to produce a numerical result. The reason for this is explained, the method is described and its accuracy is evaluated. The primary requirements, defined above, were achieved.


Studies on cellular recovery from injury. II. Ultrastructural studies on the recovery of the pars convoluta of the proximal tubule of the rate kidney from temporary ischemia. The pars convoluta of the proximal tubule of the rat kidney was studied by light and electron microscopy during the recovery phase from transient ischemia. The left kidney was made ischemic by clamping the aorta just above the left renal artery leaving the blood supply to the right kidney and the intestine intact. The pars convoluta (P1 and P2 segments) of the proximal tubule was examined both immediately after various periods of ischemia (15, 30, 60 and 120 min) and after the same ischemic periods followed by 3, 6, 12 and 24 h of blood reflow (= recovery phase). It was found that ischemia for periods up to 60 min were compatible with cell survival whereas 120 min of ischemia gave rise to irreversible cellular changes. Before regaining a normal conformation during the recovery phase, cells made ischemic for 15 min were characterized by slightly decreased cell height, dispersed nuclear chromatin, mitochondria in orthodox conformation and increased numbers of digestive vacuoles and of lipid droplets (stage A2). Most cells made ischemic for 15 min appeared normal when examined after 24 h of reflow. Cells made ischemic for 30 min were also characterized by stage A2 changes after 3 h of reflow and remained in this stage during all recovery periods studied. Cells made ischemic for 60 min first passed into a stage designated A1 and then later during the recovery phase into stage A2. Stage A1 cells were characterized by decreased height, condensed mitochondria, apparently increased numbers and sizes of secondary lysosomes and slightly dilated rough surfaced endoplasmic reticulum; 120 min of ischemia followed by reflow was not compatible with cell survival. Cells made ischemic for 120 min showed the following alterations denoted as stages C and D: shrunken with pyknotic nuclei, swollen mitochondria with large flocculent densities, and filled with different sized vesicles in the apical portion (stage C). Stage D included cells which had undergone necrosis, i.e., phasma membranes and organelles were fragmented and occurred as debris in the tubule lumens.


Atypical T cells in rheumatoid synovial membranes. Atypical mononuclear cells (AMC) with Sézary-cell-like morphology were demonstrated to be present in rheumatoid synovial membranes. These cells have exclusively T cell membrane characteristics, like identical cells previously found in rheumatoid synovival fluids. AMC were predominantly present in transitional areas between nodular lymphocytic aggregates and plasma cell rich areas. In ultrathin sections AMC accounted for approximately 30% of all lymphocyte cells; in studies of cells isolated from rheumatoid synovial membranes AMC comprised 30--40% of the E-rosette-forming cells. The hypothesis that these cells represent reactive T cells is discussed.


Lipopigment fine structure in human seminal vesicle and prostate gland epithelia. The fine structure of lipopigments normally found in prostatic and seminal vescile epithelial cells of elderly men is described and compared to findings in human fetal and hypophysectomized rat accesory sexglands. In the prostate gland lipopigments are supposed to be a sign of reduced metabolic activity, whereas in the seminal vesicle lipopigment formation seems to indicate not only high functional activity but also regressive changes.


Activity of lactate dehydrogenase, acid and alkaline phosphatases in measles virus-infected monkey kidney cell cultures. The influence of wild (Co-69) and attenuated (L-16) measles virus infection on the activity and activation energy of lactate dehydrogenase (LDH), acid and alkaline phosphatases (P-ase) was tested in R9CA monkey kidney cells at various time intervals after inoculation. With both virus strains significant changes in enzymatic activity occurred especially within the first 24 hours post inoculation. The two stains have a different influence on alkaline P-ase activity variation, which might therefore be used as a differentiation marker. Variations in LDH activation energy might be an early indicator of virus infection. LDH activity is significantly higher in cellular homogenates diluted 1:10, the dilution effect being more obvious in infected cells after a longer time interval post inoculation.


Metabolism and cytotoxicity of 7,12-dimethylbenz[a]anthracene by hamster, rat and rabbit embryo cell cultures. 1. The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) by rat, hamster and rabbit fibroblasts has been studied and compared with the metabolism of the hydrocarbon by liver homogenates. The metabolsim of DMBA by cell cultures and by liver homogenates was very similar. The ethyl acetate-soluble metabolites identified included dihydrodiols, phenols and hydroxymethyl derivatives. Other more polar metabolites and unidentified water-soluble metabolites were also formed. 2. High yields of phenols and other more polar metabolites, which may be tetrahydrotetrols, were produced by rabbit fibroblasts. 3. Kinetic studies showed that the metabolic activity of rabbit fibroblasts was high but that the conversion of DMBA into water-soluble metabolites was lower than with hamster and rat fibroblasts. 4. 7,12-Dimethylbenz[a]anthracene-induced cytotoxicity was inversely related to the conversion of metabolized DMBA to water-soluble derivatives.


[Relationship between aminoacyl-tRNA synthetases (AAA) and cell division in temperature-sensitive filamentous mutants of Bacillus subtilis SB 19. III. Characterization of pre-incubation effect and effect of AAA-inhibitor produced by Agrostemma githago seedlings]. Further results on the correlations between the regulation of bacterial cell division and amino-acyl-tRNA synthetase are presented. Activity of aminoacyl-tRNA synthetases, extracted from a filamentous mutant of Bacillus subtilis SB 19, may be stimulated by preincubation of crude extracts. The mechanism of this stimulating effect has been studied by means of an inhibitor of amino-acyl-tRNA synthetases produced during the growth of Agrostemma githago-seedlings. According to preliminary results we suggest, this inhibitor can reduce the activity of subunits only, but not that of higher associates. Association of subunits to oligomers will be prevented by the inhibitor, too. Our results may be indicative of the assumption that the increase of enzyme activity during subunits with a low catalytic activity to functional oligomers. As to the verification of these hypotheses further work will still have to be done.


[New aspects in the control of tuberculosis in GDR (AUTHOR'S TRANSL)]. The development of the epidemiology of tuberculosis in GDR from 1949 is evaluated. The factors deeply influencing incidence and prevalence of tuberculosis in GDR are: the socioeconomic development of a socialist society with continuous increase of living standard and social fonds, the state of the socialist public health system in general, and the special services and methods for the control of tuberculosis in the chest clinics and hospitals. Tuberculosis is no more a common disease in GDR. Tubercle bacilli are more ubiquitous, but are confined to distinct sources. Highest attention must be paid to the sources of infection, among them to those with tubercle bacilli already found by smear examination in the infectious cases. Microscopic examination is a very important method to find these cases. Cough and sputum exist in most cases of pulmonary tuberculosis already positive by smear examination. All these conditions must be regarded in the control of tuberculosis. The risk groups of tuberculosis (patients in the 5 years after treatment, patients with silicosis diabetes, long lasting treatment with corticosteroids, persons with contacts to infectios cases, and the so-called "Gesunde Befundträger" (healthy carriers of lesions), persons older than 65 years) amount to 7% of the population but yield more than 50% of all new cases. BCG-vaccination is of no more high importance at an annual infection rate of only 0,25% (1975), but newborns will be vaccinated. Mass X-ray examinations are no more important for finding tuberculosis; but other pulmonary diseases including bronchial carcinoma are detected by this way. X-ray examinations will remain of value in the form of aimed examinations in intervals according to the risk of disease (for tuberculosis, bronchial carcinoma). The most important method in the control of tuberculosis is the immediate treatment of all new cases. The results depend on the quality of therapy. It has to be still improved. It is the aim, to eliminate tuberculosis as a special problem of public health in GDR till 1982, 100 years after the discovery of the tubercle bacilli by ROBERT KOCH.


[The different inactivation of isoniazid in intermittent chemotherapy (author's transl)]. A ratio-test (Isoniazid: acetyl-isoniazid) is used for phenotyping the Isoniazid-inactivation. The border-line between both the phenotypes is determinated. The influence of age and weight of the patients is studied. Usefully results are obtained after application per os of an uniform dosage and a sampling period for urine of 4 hours. Increasing the dosage to 900 mg the portion of isoniazid arises mmore than proportionally, more distinct in rapid than in slow inactivators. Therefore the differences between the two phentoypes are diminished. The clinical importance of these results is discussed.


Deviated lysis (d.l.): III. Kinetics of interaction of d.l. activity with chicken erythrocytes: evidence for E formation. The interaction of d.l. activity with chicken red cells (CE) generates a cell intermediate with the properties of classical E*. Generation of CE* by d.l. activity at 37 degrees C is rapid, while there is a considerable lag in the conversion of CE* to ghost and hemoglobin. Conversion of CE* to ghosts can be blocked by high concentration of EDTA and/or 0 degrees C. CE* contain at least C6 and C9 on their surface.


[Diagnostic and treatment of prostatic cancer (author's transl)]. The diagnosis of prostatic cancer must be proved by biopsy. Transrectal fine needle biopsy and punch biopsy are also useful methods for the outpatient clinic. Besides X-ray examination scanning angiography and lymphography may be used to identify metastases. Combined antiandrogenic therapy is still the treatment of choice and is based on endocrinologic analysis of testosterone, LH levels and testosterone-binding beta-globulin. Radionuclids (32P, 89Sr) should be used for treating metastases of the bone. Chemotherapeutic substances showed unsatisfactory results. Radical prostatectomy can only be performed in 5 to 10% of all patients with prostatic cancer to metastases in T1 and T2 cases. Since 1965 the radiation therapy (linear accelerator or (60Co-source) gives more hope. We treat patients free from metastases with a 60Co-source (right and left lateral 120-degree arc rotational therapy with 5000 rads over 5 weeks) combined with hormonal therapy. The therapeutic effect is checked by fine needle aspiration biopsy.


[Propionate negative saccharolytic bacteroides strains (B. oralis)-occurrence, identification, antimicrobial susceptibility and serological behaviour (author's transl)]. Twenty-three propionate negative non-pigmented Bacteroides strains were isolated from mixed infections (peritonitis, endometritis, abscess of the abdominal wall etc.) as well as vaginal secretions of healthy parturients in the course of 3 years. The cultures were indole negative, produced acetic, isobutyric and isovaleric acids and had a final pH of 5.0-5.5 in glucose broth; they were assigned to B. oralis as described by LOESCHE and coworkers in 1964. tpathogenic significance of this organism may be assumed in those cases of mixed infection where the microbial association consisted solely of gram-positive species with low virulence (lactobacilli, Staphylococcus epidermidis, Peptococcaceae). Antibiotic susceptibility of 12 B. oralis strains was studied by tube dilution tests. Resistance to cephalosporins was detected in 8 strains, about half of them were resistant to ampicillin and penicillin G. Like other Bacteroides species, the B. oralis strains showed resistance to aminoglycosides and sensitivity to clindamycin, chloramphenicol and erythromycin. The serological behaviour of 9 B. oralis strains was studied in cross-agglutinationation and gel-diffusion experiments. Cross-reactivity was particularly pronounced in immunodiffusion tests with autoclaved extracts. According to the results obtained, the strains belonged to a homogeneous group with 1-2 identical antigens. These B. oralis antigens were shared by B. melaninogenicus ss. intermedius 2965. There were, however, no cross-reactions between the aforementioned strains and B. melaninogenicus ss. melaninogenicus 8117/1. The taxonomic implications of a close relationship between B. oralis and B. melaninogenicus ss. intermedius are discussed.


[Relationship between the culture medium and the fatty acid composition of diphtheria and non-pathogenic corynebacteria]. The gasochromatic method was applied to the study of the cellular fatty acids composition in diphtheria and nonpathogenic corynebacteria (diphtheroids and psendo diptheria bacillus). Marked differences in the content of unsaturated fatty acids were revealed in them. Thus, palmito leic acid served the preponderant unsaturated fatty acid in Corynebacteria diphtheriae, and unsaturated fatty acids with 18 carbon atoms (octadeconoic and linoleic)--in nonpathogenic corynebacteria. The mentioned changes permit use this sign as differential. When grown on Loeffler's medium all the corynebacteria under study had a similar fatty acid composition characterized by the prevalence of unsaturated fatty acids with 18 carbon atoms. On the basis of studying the fatty acid spectrum of the nutrient media used it is supposed that one of the factors determining the revealed dependence of the corynebacterial fatty acid composition on the culture medium was the fatty acid composition of the latter.


[Differentiation of several species of lactobacilli of the subgenus Thermobacterium according to their bacteriocin sensitivity spectra]. The method of retarded antagonism was applied to the study of L. acidophilus (187 cultures), L. salivarius (65 cultures), L. jugurti (16 cultures), L. helveticus (4 cultures) sensitivity to the action of 39 bacteriocines produced by various lactobacilli species. By the sensitivity spectra to bacteriocines L. ècidophilus cultures were divided into 76, L. salivarius--22, L. jugurti--15, and L. helveticus into 2 bacteriocines. By bacteriocine typing it was possible to differentiate into a number of bacteriocine types L. acidophilus and L. salivarius variants with the same biochemical and physiological properties.


[Comparative neurochemical and physiological characteristics of catalepsy-like rest and sleep]. In vertebrates (excluding mammals), the rest is presented also by a special functional condition of the catalepsy type. In hens, its total duration is higher in the day-time, than in the twilight; it is completely absent at night. This natural condition in hens may be imitated by photogenic catalepsy which is developed in response to rhythmic illumination of animals. Cytospectrophotometric investigation of single cells of the supraoptic nucleus indicates that with respect to absence of changes in absolute content (per 1 cell) of protein in the neurons cataleptiform rest in hens does not differ from the sleep in rats. However, in contrast to sleep this immobilization is associated with the decrease of RNA content of the neurons, as well as with the absence of accumulation of proteins and RNA in gliocytes. During cataleptiform rest, insiginficant changes were found in the content of proteins and RNA in cells of ectomammilar nucleus of the additional optic system and thalamic round nucleus. Cataleptiform (photogenic) immobilization in hens is presumably a metabolically passive form of rest as compared to the sleep in rats, which is characterized by anabolic processes in the brain.


[Submicroscopic organization of listeriae during L-transformation]. A study was made of the ultrastructural organization of listeria at the early stages of L-transformation, beginning from the first passage of the bacterial culture on solid nutrient medium with pencillin. The use of potassium benzylpenicillin salt in the capacity of an L-transforming agent permitted to observe the cells at various stages of L-transformation, beginning from the bacterial forms and ending with the typical L-colonies. It was shown that at the earliest stage of L-transformation there occurred not only destruction of the cell wall and the discharge of the mesosomes from the cell, but also significant changes in the nuclear apparatus of the cell. As soon as the second passage the freshly isolated L-forms displayed an internal membrane system in the form of myelin-like structures located under the external membrane, and of individual membranes in the cytoplasm not forming mesosomes. A substance of a medium electrone density resembling the material of the cell wall appeared on the cytoplasmic membrane (in some of its regions).


[Standardization of chemical cholerogen-toxoid cholera vaccine according to the content of somatic O-antigen]. The authors discuss the results of studies on the choice of highly-reproducible and sufficiently informative methods of 9-antigen standardization in a new chemical vaccine against cholera (cholerogen-toxoid); materials were collected under conditions of controlled epidemilogical trial. Titration of O-antigen in industrial batches of the preparation with the aid of precipitation in gel against standard O-cholera serum could be used for its standardization. Quantitative limits of O-antigen responsible for the formation of vibration (antimicrobial) antibodies in the persons vaccinated were found by studying the immunogenicity and reactogenicity of a number of cholerogen-toxoid batches contrast by O-antigen content described by means of the precipitation test.


[Structural organization of the prefrontal cortex in cats and differences between it and the same area in monkeys]. It has been demonstrated that similar to that in monkeys, prefrontal dorso-lateral cortex in cats significantly differs from the medio-basal cortex not only in the structure and level of differentiation, but also in its thalamic projections. In cats, definite topography in the distribution of projections from the medio-dorsal thalamic nucleus to the lobe pole cortex of the hemisphere was demonstrated which in general features is similar to the mode of projection of this nucleus in monkeys. This rendered it possible to homologize separate parts of the medio-dorsal thalamic nucleus and preforntal cortex in these animals. Together with these similarities, considerable differences were found as well. In cats, predominance of phylogenetically ancient medio-basal fields was noted, whereas in monkeys--the predominance of more young dorso-lateral fields was observed. In cats, parvocellular portion is absent from the medio-dorsal thalamic nucleus, its homologue being very small; therefore dorso-lateral cortex to which this portion of the nucleus is projected, is developed very poorly. In monkeys, this portion occupies up to 2/3 of the nucleus, dorso-lateral cortex being perfectly developed. These data suggest that progressive evolution of the prefrontal cortex, associated with a higher behavioural level, followed mainly the development of dorso-lateral surface, this development being closely related to the onset and projection of parvocellular portion of the medio-dorsal thalamic nucleus to this region.


Antifertility properties of bovine pineal extracts: reduction of ovulation and pre-ovulatory luteinizing hormone in the rat. Bovine pineal glands were extracted with acetic acid and partially purified on Sephadex G-25. Three fractions, F3, F4 and F5, were each administered to cycling female rats for 4, 2 or 1 day prior to ovulation to determine their effects on fertility, ovulation and the pro-oestrous surge of luteinizing hormone (LH). The incidence of pregnancy and the mean number of foetuses were reduced in animals after treatment with F3 or F4 but not in those treated with F5. Each of the F3 and F4 fractions significantly reduced the mean number of ova shed and the pre-ovulatory concentration of serum LH. The F5 fraction caused a moderate reduction of the pro-oestrous rise of serum LY but had no significant effect on ovulation. The data suggest that fertility in rats can be reduced by more than one substance of low molecular weight present in bovine pineal extracts through a modifying effect on LH secretion and subsequent ovulation.


Long-term treatment with 2-Br-alpha-ergocryptine in acromegaly. Thirty acromegalic subjects underwent chronic CB154 therapy (10-20 mg daily) for periods ranging from 3 months up to 2 years. In 18 out of 21 patients, who exhibited consistent HGH reduction following acute administration of the drug, there was also during chronic treatment, a suppression of the plasma HGH levels exceeding 50% of base line values, e.g. from mean daily values between 14-197 ng/ml (mean +/- SEM = 57.8 +/- 12.4 ng/ml pre-treatment) to 2-19 ng/ml (mean 8.3 +/- 1.2 ng/ml post-treatment). In 12 of the subjects who responsed to chronic CB154 treatment, the mean daily values of HGH were below 10 ng/ml. The suppression of plasma HGH was maintained unaltered throughout the whole course of therapy. In the 9 subjects, in whom no consistent HGH decrease was evidenced with acute CB154 administration, there was accordingly a minor or no suppression of HGH values during the chronic treatment. In 13 subjects, irrespective of the degree of their GH responses, the plasma prolactin levels were constantly inhibited by CB154; instead the drug failed to modify significantly the TRH or insulin-induced GH release. These changes in the hormonal parameters were paralleled by marked clinical amelioration and improvement of some of the metabolic alterations frequently encountered in acromegaly, e.g. reduced carbohydrate tolerance, increased insulin resistance, diminished fall of plasma phosphorus after insulin, decreased urinary excretion of phosphate, hyper-hydroxyprolinuria and hyper-calciuria. Collectively, these data demonstrate that CB154 thrapy is effective in reducing HGH hyper-secretion in many acromegalic patients during long-term treatment.


Serum thyroxine-binding globulin: determination by competitive ligand-binding assay in thyroid disease and pregnancy. Serum thyroxine-binding globulin (TBG) concentrations were measured by competitive ligand-binding assay in normal subjects and patients with a variety of abnormalities of thyroid hormone production or TBG production. The mean serum TBG concentration in 73 normal adults was 3.4 +/- 0.6 mg/100 ml. No correlations with age, sex or serum thyroxine (T4) or triiodothyronine (T3) concentrations were found. Serum TBG concentrations were normal in patients with hyperthyroidism. They were significantly elevated in hypothyroid patients, and fell to normal with thyroxine treatment. In pregnant women, serum TBG concentrations were markedly increased, being 7.1 +/- 1.2 (mean +/- SD) mg/100 ml in women in their first trimester, 9.0 +/- 1.0 mg/100 ml in the second trimester and 8.9 +/- 1.6 mg/100 ml in the third trimester. There was a positive correlation between serum TBG concentration and both serum T4 and serum T3 concentrations in pregnant women. Competitive ligand-binding assay is a simple and reliable method for TBG asay and yields results similar to those of electrophoretic saturation techniques.


The thyrotrophin response to thyrotrophin releasing hormone during treatment in patients with Graves' disease. Thyrotrophin releasing hormone (TRH) tests were performed at 4 or 8 weeks intervals, after the initiation of anti-thyroid treatment in 15 patients with Graves' disease. All TRH test were negative as long as the serum levels of thyroxine (T4) and triiodothyronine (T3) were elevated, and normalization of the serum levels of these hormones always occurred before the response to iv TRH was restored. In 13 patients the time from the patients for the first time were registered as biochemically euthyroid varied from 0-9 months (mean 3.1 months), before TRH response was restored. Two patients were still TRH non-responsive at the end of the study, even though they had been biochemically euthyroid for as long as 17 and 18.5 months. The TRH test, therefore, is not helpful in the evaluation of the effect of anti-thyroid treatment in patients with Graves' disease. There was an increase in the serum level of (TSH) from 3.4 +/- 0.3 (SEM) to 4.3 +/- 0.5 (SEM) ng/ml (P less than 0.05), and a decrease in the serum level of total T4 from 19.4 +/- 1.1 (SEM) to 5.8 +/- 0.8 (SEM) microng/100 ml in 13 patients from the first examination until the last time they were examined before restored TRH response. This finding shows that the pituitary gland has retained its ability to synthesize and secrete TSH even though no TSH could be released by iv TRH. In 6 TRH non-responsive patients with Graves' disease, serum TSH levels were suppressed from 2.5 +/- 1.2 (SEM) ng/ml before the administration of a single dose of 3 mg T4 orally, to 0.9 +/- 0.2 (SEM) ng/ml, 7 days after the T4 administration. Thus, the negative feed-back effect on the pituitary gland of the thyroid hormones is operating in these patients. This finding indicates that the TRH non-responsiveness in euthyroid patients with Graves' disease is not due to pituitary depletion of TSH, since the negative feed-back effect of the thyroid hormones is operating normally.


Effect of thyrotrophin releasing hormone (TRH) in patients with pituitary disorders. The secretion and biological activity of thyroid stimulating hormone (TSH) were studied in 22 patients with a pituitary tumour (17 acromegalics and 5 patients with a chromophobe adenoma) and in 36 hypophysectomized patients (16 acromegalics and 20 with a chromophobe adenoma). Thyroid function was assessed by serum thyroxine (T4), serum triiodothyronine (T3), and thyroxine-binding globulin (TBG) concentration. Serum TSH was measured before and after injection of TSH releasing hormone (TRH), and in 19 hypophysectomized patients the T3 response after TRH was measured. In addition a TRH test was performed 1-2 weeks after surgery in 11 patients. The basal serum TSH did not differ from euthyroid control values in any of the groups and no late effect of hypophysectomy was observed. Subnormal peak TSH values were seen in 10 out of 37 euthyroid patients, whereas 9 out of 11 hypothyroid patients responded normally. Hypophysectomy caused an immediate but transient decrease in peak TSH in patients with a chromophobe adenoma only. The rise in serum T3 after TRH was significantly lower in hypophysectomized patients than in controls. An increase in TSH was followed by a T3 response in all patients except in 4 out of 8 euthyroid acromegalics. In patients operated on for a chromophobe adenoma the T3 response was correlated with serum T4, whereas this was not the case in acromegalics.


Intravenous and peroral TRH stimulation in sporadic atoxic goitre. Thyrotrophin releasing hormone (TRH) stimulation test with 200 microng iv was performed in 35 patients with atoxic sporadic goitre. In 23 patients with diffuse goitre 7 showed a lack of increase in serum thyrotrophin (TSH) at a significantly increased frequency compared to controls (P = 0.0028). In 4 patients with solitary nodules 2 showed no significant response to TRH (negative), while 3 of the 8 patients with multinodular goitres had negative TRH test. Only 6 of the 12 TRH negative patients also had non-suppressible 131I uptake following T3. No significant difference in age and thyroid parameters was found between the TRH negative and TRH positive patients. In 7 TRH negative patients the test was repeated with 400 microng TRH but all remained negative. Five of these patients were given TRH perorally 80 mg daily for 2 weeks resulting in a significant increase in serum T4 and T3. No detectable increase in TSH was found. The response to iv bovine TSH in 4 TRH negative patients was found to be normal, suggesting that there was normal thyroid sensitivity to TSH. Our findings suggest that patients with TRH negative atoxic goitre can release biological active TSH following prolonged TRH stimulation. The high frequency of a negative standard TRH test in atoxic goitre seems to diminish the diagnostic value of the standard TRH test.


Fate of foreign DNA taken up by tonsillar lymphocytes. The uptake of heterologous (B. cereus) DNA by tonsillar lymphocytes was followed for 22 hours. Acid-precipitable DNA became associated with the cells as soon as they were mixed with DNA. The uptake was linear from 0 to 3 hours, between 3 to 6 hours part of the cell-associated DNA was released into the incubation medium, and at 22 hours the amount of label in the cells reached the values measured at 2--3 hours. In respect of the size of DNA the uptake seemed to follow the same saturation curve. There was no difference between the uptake pattern of native DNA and that of heat-denatured DNA. The decrease of size of foreign DNA in the cells in the incubation medium was followed by agarose-gel electrophoresis. In tonsillar lymphocytes enzyme activities capable of degrading heterologous DNA were found. The enzyme activities present in the cells could be detected in the culture medium as well for at least 24 hours.


Sodium acetylsalicylate and the role of prostaglandins in the mechanism of intradental pain. In order to study the effect of sodium acetylsalicylate and the role of prostaglandins on intradental nerve impulse activity experiments were performed on the teeth of anaesthetized cats. Nerve impulse activity was induced by mechanical and chemical stimuli and recorded by means of electrodes inserted into dentinal cavities. It was shown that such activity could not be blocked by sodium acetylsalicylate or indomethacin given locally or i.v. PGE2 failed to excite the sensory units when given locally (3.5 microng/ml) or intraarterially (35-140 ng/min) alone or in combination with mechanical and thermal stimuli or combined with local application of histamine (10 mg/ml) or bradykinin (10 mg/ml). Intraarterial infusion or arachidonic acid, a precursor to PGE2, PGF2 alpha PGG2 and PGH2 failed to change the excitability even on applying local stimuli to the pulp or with local application of histamine or bradykinin. These findings seem to indicate that the increased sensitivity of the tooth to thermal stimuli seen during acute pulpitis is not due to formation of prostaglandins.


Disseminated arthritis and osteitis by Candida albicans in a two month old infant receiving parenteral nutrition. The case of a two-month -old female infant, who after a severe diarrhoea treated with prolonged intravenous infusion in peripheral veins alternated with total parenteral feeding, developed a Candida albicans septicemia (accompanied by disseminated intravascular coagulation syndrome) is reported. The course of her disease was also complicated by multiple foci of osteoarthritis in both knees, in the left hip and in several long-bones. Radiographically the foci of Candida osteitis appeared as fine erosion of the cortex and minute round areas of osteolysis in the spongiosa, surrounded by a rim of perifocal sclerosis. During the acute stage of Candida sepsis a transitory cellular immunodeficiency was present. Treatment of Candida infection by 5-fluorocytosine was followed by complete recovery.


Xeroradiography in radiation therapy.

Xeroradiography in radiation therapy. The xerographic technique has been introduced at Radiumhemmet for direct field control in therapy with high energy photon radiation (60Co-unit, 6 MV linear accelerator and 42 MeV betatron). The xerograms are of a sufficiently good quality for this purpose. The advantages and disadvantages connected with the xerographic facilities at present available are discussed.


Extrapolation chamber measurements of electron depth absorbed dose distributions. An extrapolation ionization chamber was constructed and used to measure depth absorbed dose distributions of electron beams from the electron therapy units in Finland. Particular attention was payed to the surface dose, the build-up region, and the energy calibration. Differences between various units are discussed.


A 22 MeV microtron for radiation therapy. The first 22 MeV micron installation for radiation therapy is described with regard to the general design, the beam transport and the gantry. The first measurements of the electron depth dose curves indicate that the distributions obtained are superior to those of most betatrons and linear accelerators. For the same electron beam energy the depth of dose maximum and the 90 or 80 per cent dose level is considerably increased. The 20.9 MV photon beam has similar depth dose characteristics as a 20 MV betatron.


Accuracy of megavolt radiation dosimetry using thermoluminescent lithium fluoride. The relative light output per Gy in polystyrene for roentgen beams of 6 and 42 MV and electrons between 2.2 and 34.5 MeV relative to 60Co gamma radiation is reported for different kinds of LiF dosemeters. The distribution of the absorbed dose inside a 0.25 and 0.4 mm thick LiF-teflon disc surrounded by polystyrene and irradiated with 60Co, 42 MV roentgen radiation and 39 MeV electrons was measured using 0.01 and 0.02 mm thick Lif-teflon discs. The measurements show that the absorbed dose distribution in the dosemeter depends on the energy of the radiation. When flat dosemeters were used, differences between the signals measured at the two orientations possible during read-out could easily amount to several per cent, and for this reason 0.4 mm and 0.5 mm LiF-Teflon discs were not trusted when the highest accuracy was required. The cavity theory by Burlin does not account for the phenomena caused by differences in electron scattering properties of the dosemeter and the phantom material. Some suggestions are presented for a different cavity theory for flat dosemeters dealing also with these phenomena. It describes the results to about the same degree of approximation as the Burlin theory, and fails to explain the observed energy dependence for electrons.


Ionization chamber dosimetry for photon and electron beams. Theoretical considerations. New Clambda-values (Cair,lambda) are proposed which should be applied for ionization chambers with an inner wall of air-equivalent material, air eq. plastic or graphite. The new values are up to approximately 3 per cent lower, and apply for a chamber with an inner wall lining of water-equivalent material.er cent higher than those published in the ICRU Report No. 14 and here named Cwater,lambda as the inner wall is considered water-equivalent. Also two sets of CE-values are proposed, namely Cair,E which is given in ICRU No. 21 and Cwater,E which is approximately 3 p


Carotid endarterectomy: results, complications, and monitoring techniques. A system of grouping patients according to preoperative evaluation of risk of carotid endaterectomy is presented. The primary complications of this surgical procedure were myocardial infarction and residual mild to severe neurologic deficit. Neurologically stable patients without medical or angiographically determined risk factors (group 1) have a risk of 1%. Neurologically stable patients without medical risk but with angiographically determined risks (group 2) have a risk of 2%. Neurologically stable patients with significant medical illness and with or without angiographically determined risks (group 3) have a risk of 7%, primarily related to cardiac disease. Neurologically unstable patients (group 4) have a 6% risk for a neurologic deficit. Current monitoring techniques using continuous electroencephalograms, cerebral blood flow measurements, and arterial stump pressure are considered. The prevention and management of complications are presented in some detail.


Laser application to the angle structures in animals and in human glaucomatous eyes. Argon laser lesions were induced in the structures of the anterior chamber angle of rabbits, cats and monkeys and in a pre-enucleated infnat's eye. Histopathological changes produced by this mode of treatment at different follow-up periods were analysed. The argon laser beam has also been applied in 28 selected, uncontrolled glaucomatous eyes. 25 eyes responded by an abrupt hypotensive effect, but in 21 of them, the elevated pressure returned during the 20- to 40-day follow-up period. Eight eyes sustained low intraocular pressure throughout the 12- to 20-month follow-up period. Of these, 3 were babies with congenital glaucoma, and 3 had simple glaucoma following an unsuccessful filtering operation. Seven eyes were medically controlled post-operatively and 13 eyes were failures which had to undergo further surgery.


Male contraception.

Male contraception. Although the modern era of contraception has focused attention on the female, research into male contraception is continuing on several fronts. Despite the widespread use of premature withdrawal, the condom and vasectomy, there is no acceptable drug for controlling fertility in the male. New advances have been made in influencing the maturation and fertility capacity of sperm. Techniques are being developed for reversibly blocking sperm transport. The functions of seminal fluid are under intensive investigation.


Rational management of diabetic ketoacidosis. After a definite diagnosis, rational management begins with the construction of a grid flow sheet on which can be recorded vital signs, urine sugar and acetone, blood glucose and electrolytes, arterial blood gases and treatment (fluids, insulin, potassium). Fluids correct the hyperosmolar state, sodium deficit and hypovolemia. Hypokalemia is aggravated by insulin therapy and potassium levels must be monitored chemically and with the electrocardiogram. High-dose and low-dose insulin regimens have been used. Sudden hypoglycemia must be avoided.


Arrangement of connective tissue components in the walls of seminiferous tubules of man and monkey. In primates the membrane separating the seminiferous epithelium from the interstitial space is composed of one to three (monkey) or two to six layers (man) of myoid cells associated with one to two layers of fibrocyte-like adventitial cells. All these cells are separated from each other by irregular spaces filled with various connective tissue intercellular components. Subjacent to the elements of the seminiferous epithelium is a continuous, often redundant, basement membrane. A similar basement membrane-like material forms a layer next to and over small areas of the plasma membrane of myoid cells. Collagen fibrils grouped in bundles of various sizes are seen in all connective tissue layers but are particularly abundant in the space between the seminiferous epithelium and the innermost layer of myoid cells. Elastic fibrils demonstrated by the Verhoeff iron hematoxylin technique are also present. Composed of a homogeneous material, the elastic fibrils are short, irregular, branching entities with a diameter comparable to or smaller than that of collagen fibrils. In addition, an abundance of microfibrils with a diameter of 12-15 nm is present in the various connective tissue layers. These microfibrils have a densely stained cortex and a lightly stained core. When seen close to the myoid cells, bundles of micro fibrils appear to insert on well defined areas next to the plasma membrane. These areas commonly face the patches of electron-dense material observed on the inner aspect of the plasma membrane of the myoid cells and in which the actin filaments are inserted. Bundles of microfibrils often span the gap between myoid cells of the same layer as well as those of adjacent layers. Microfibrils are also closely related to the surface of elastic fibrils and are seen intertwining with collagen fibrils. Thus microfibrils appear to bridge and bind together adjacent myoid cells and anchor the surface of these cells to the bundles of elastic and collagen fibrils present in the intercellular spaces of the limiting membrane.


Restoration of hemoglobin function in stored EDTA blood. Application in identification of hemoglobin variants with abnormal oxygen affinity. The incubation of stored blood in a mixture of inosine, pyruvate, glucose, and phosphate restores the O2 affinity of hemoglobin to physiologic levels, as measured by the configuration of the dissociation curve and the P50. This regeneration of normal hemoglobin function not only is consistent for samples anticoagulated with EDTA and stored eight days at 4 C but also is demonstrable for at least 19 days of 4 C storage of EDTA-anticoagulated whole blood. This regeneration procedure is simple to perform and makes it possible to measure reliably O2 affinity in blood samples transmitted by mail.


Thoracic dysplasia in spondyloepiphyseal dysplasia congenita. Spondyloepiphyseal dysplasia congenita (SED congenita) can involve the ribs. The result is rib shortening, a dysplastic thorax that is not only short but also narrowed, and respiratory failure. This case involves an infant who died of respiratory failure 36 hours after birth. A dysplastic small volume thorax in infancy, leading to serious respiratory embarrassment, must be included into the clinical and radiological pictures of SED congenita. To my knowledge, rib shortening and thoracic dysplasia in SED congenita have not been previously described.


Estimation of mutation rate from rare protein variants. A method for estimating the mutation rate for protein loci from the number of rare alleles in the population is presented. It seems to have a number of advantages compared with Kimura and Ohta's method. Applying this method to Neel's data from American Indians in South America and to Nozawa's data from Japanese macaques, the mutation rate for electrophoretically detectable alleles is estimated to be (2 approximately 3) x 10(-6) per locus per generation. This estimate may not include many severely or substantially deleterious mutations.


New opportunities for the public to shape the nation's institutional health care services. The author of this Comment describes how recent federal legislation (P.L. 93-641, signed into law in January, 1975)--and improved scientific techniques for integrating (1) community medical needs assessment, (2) institutional budgeting linked to regional/state health plans, and (3) budget ceilings--have given the public new authority and technology to shape the nation's institutional health services. He urges administrators and trustees of health institutions--both proprietary and charitable--to become aware of recent developments in this area, and says that active consumer and provider participation in Health Systems Agencies and Statewide Coordinating Councils is necessary if the new federal expectations concerning health planning and regulation are to be met. Given the rising costs of medical care, stronger federal control might be forthcoming if the purposes of P.L. 93-641 are not achieved.


Prospects for prevention and amelioration of mental retardation: a guest editorial. The view of the President's Committee on Mental Retardation (1972) that the incidence of mental retardation can be reduced by 50 percent before the end of the century was critically examined. We concluded that only in the minority of cases, where biomedical etiologies are implicated, is this forecast support by existing trends. The major group of milder cases pose immense difficulties for prevention, and desirable social changes are unlikely to make an immediate impact. We also considered the argument that levels of functioning of most retarded persons can be substantially improved. While research gives a clear indication that this is potentially so, such knowledge is rarely applied. Implications for policy and practice were considered.


Comparing radioactive and trephine-disk bioassays of dicloxacillin and gentamicin in ocular tissues in vitro. Trephined disks of tissue (6 mm diameter) from fresh rabbit eyes were immersed overnight in solutions of radioactive carbon (14C)-dicloxacillin or gentamicin, then assayed by one of two methods: agar-diffusion bioassay, using filter-paper disks immersed in known concentrations of antibiotic as standards, or radioactive assay. The bioassay underestimated the concentrations of antibiotic in sclera and iris by 38 to 72%, and slightly overestimated those in the cornea. A corrected bioassay was calculated, based on the differences in fluid mass between tissue specimens and filter-paper disks; this value was within 20% of the radioactive assay in 18 of 24 experiments with dicloxacillin, and in 14 of 24 with gentamicin. There was evidence of pronounced binding of gentamicin to ocular tissues (iris greater than sclera greater than cornea); this appeared to be a saturable and reversible phenomenon. Less marked binding of dicloxacillin to iris and sclera was noted. The results indicated that, depending on the degree of accuracy required, the corrected trephine-disk agar-diffusion bioassay provides a reasonable estimate of the antibiotic content of ocular tissues.


Aplasia of the optic nerve and disk.

Aplasia of the optic nerve and disk. To clarify the nature of aplasia of the optic nerve and disk, a rare congenital anomaly defined as absence of the optic nerve and disk, retinal ganglion cells, and retinal blood vessels, we evaluated all the cases with this designation in the files. Thirteen cases demonstrated that optic nerve aplasia typically occurs uniocularly in an otherwise healthy person. There was no sexual or racial predilection, or any evidence of an inherited factor. We believe typical aplasia of the optic nerve results from abnormal invagination of the ventral fissure and that the multiple associated ocular anomalies may also be attributed in part to this same mechanism. Two cases were atypical: they were bilateral, there was an associated hydrocephalus in one case and a possible familial history in the other, they apparently had a different pathogenesis from the typical cases, and possibly represent an extreme form of hypoplasia of the optic nerve.


Listeria monocytogenes endocarditis: report of a case and review of the literature. Endocarditis due to Listeria monocytogenes is rare with only 13 cases cited in the world's literature. We report an additional case with a review of the previously reported patients. In contrast to other clinical forms of listeriosis, endocarditis does not tend to occur in patients with severe underlying disorders or those on immunosuppressive regimens. Listeric endocarditis has a predilection for left-sided cardiac involvement (100 percent), and systemic embolization is a major clinical feature (58 percent). Prognosis of listeric endocarditis is unfavorable and the mortality rate (43 percent) exceeds that for bacterial endocarditis with more common pathogens (23 percent). Antibiotic sensitivity data suggest that ampicillin or penicillin may be the chemotherapeutic agents of choice.


Proton irradiation of small choroidal malignant melanomas. Five patients with choroidal malignant melanomas were treated with proton irradiation with a cyclotron. We developed an accurate method of aiming the proton beam within the eye. Four to five tantalum rings, 2 mm in diameter, were sutured to the sclera at the edges of the tumor, which is localized by indirect ophthalmoscopy and transillumination. The rings were used as markers for stereotactic radiography to align precisely the tumors with the proton beam. The patients were given a total tumor dose of 4,730 to 6,670 rads, delivered in five equal fractions, over a period of eight to nine days. All patients tolerated the treatments well without any adverse effects. The tumor response to therapy could not be evaluated at the completion of treatment since there was no immediate observable reaction of the tumor or of the surrounding retina. Although there has been no definite regression in any patient, we observed a change in the "color" of the tumor in the first two patients and resolution of two serous retinal detachments.


The histologic basis of optic disk pallor in experimental optic atrophy. We studied the clinical and microscopic appearances of the optic nerve head in squirrel monkeys with optic nerve degeneration produced by optic nerve transection at the orbital apex. The ophthalmoscopic development of optic disk pallor coincided with the loss of nerve fiber bundles and the rearrangement of the remaining disk astrocytes into dense parallel layers across the nerve head. No astrocytic mitoses were observed and the estimated volume of astrocytes increased only slightly from normal. Among the astrocytes in atrophic disks, many capillaries had patent lumens and ultrastructurally normal endothelial cells. Pallor of the optic disk seems to result from a decrease in the transmission of light into the cytoarchitecture of the atrophic nerve head, not from the absence of capillaries or from extensive astrocytic proliferation.


The influence of reserpine and ethylenediaminetetraacetic acid (EDTA) on serotonin storage organelles of blood platelets. The present investigation has evaluated the influence of reserpine on the serotonin-rich organelles bodies) in platelets from dogs, rabbits, and humans. Reserpine markedly depresses the levels of stored serotonin in human and animal platelets, accompanied by a small decrease in platelet ATP but no change in platelet ADP content. Thin sections of human platelets showed no change in the number or morphology of serotonin storage organelles during reserpine therapy, whereas a profound decrease in the size and number of dense bodies occurred in platelets from rabbits treated with reserpine. Dog platelets also showed a decrease in the number and density of serotonin storage organelles after reserpine therapy. The basis for the difference between rabbit and human platelets was explored by fixing platelets in glutaraldehyde and osmium in the presence or absence of the chelating agent ethylenediaminetetraacetic acid (EDTA). Most of the dense bodies in fixed human platelets were removed by EDTA while rabbit platelet dense bodies remained essentially intact. The results suggested that the opacity of rabbit platelet dense bodies following fixation with glutaraldehyde and osmium relate primarily to their serotonin content, while the electron density of human serotonin storage organelles in fixed cells is due primarily to their calcium content. Further confirmation of this concept came from studies of platelets using the whole mount technique. Rabbit platelet serotonin storage organelles were found to lack the inherent opacity of the human dense bodies, a finding consistent with the lower concentration of calcium in the rabbit organelles.


Ectopic ossification.

Ectopic ossification. Ectopic ossification is a biologic process in which new bone is formed in tissues which normally do not ossify. Three cases of this disease are described. The literature on this subject has been extensively analysed and organized. Classification, etiology, clinical and radiological features and laboratory tests are discussed. The paper also discusses the histopathology, differential diagnosis and management of this disease.


Attempts to immunize monkeys against Plasmodium knowlesi by using heat-stable, serum-soluble antigens. Thirty-six Macaca mulatta monkeys were immunized with different concentrations and regimens of heat-stable, serum-soluble (S-) antigens of Plasmodium knowlesi prior to challenge with the homologous parasite via sporozoite inoculation. Fewer deaths and reduced maximum parasitemias occurred in those animals inoculated with 10 to 40 mg of S-antigen compared to nonimmunized monkeys or those receiving only Freund's adjuvant. Protection was incomplete, however, suggesting that atibodies to S-antigens may have a limited role in protection of hosts to malarial infection.


Effect of length of treatment with Bayer 2502 on isolation of Trypanosoma cruzi and resistance to challenge in the mouse. The effect of length of treatment of Trypanosoma cruzi with Bayer 2502 (Bay 2502, Lampit, Nifurtimox) on resistance to challenge and parasite isolation was studied in two experiments. In each, 200 mice were divided into groups of 20, infected with T. cruzi, and then treated with Bay 2502 for 1 to 8 consecutive weeks. Sixteen weeks after exposure, 10 mice from each experimental group were challenged with 150,000 trypomastigotes. The remainder were maintaned for 8 more weeks and killed for isolation of parasites. Mice treated with Bay 2502 for up to 8 consecutive weeks were uniformly resistant to challenge, and parasites could not be isolated from groups treatef for over 6 weeks. Results suggest that prolonged treatment with Bay 2502 eliminates T. cruzi from infected hosts and that resistance to challenge is not dependent on the presence of the organisms in mice.


Development and verification of a schistosomiasis transmission model. Development of a model to predict the impact of water resource projects on transmission of schistosomiasis is described and verified with data from 54 villages in Khuzestan Province, Iran. Changes in disease prevalence following construction of an irrigation project are related to the linear extent of snail habitats and size of the infected human population. The model is used to compare the costs and effectiveness of alternative disease control measures. Results indicate that a combined controls program is most cost-effective but further work is needed to determine the optimal combination of controls.


Cell-mediated immune responses to Pseudomonas aeruginosa. Of six healthy laboratory workers with no history of illness caused by Pseudomonas aeruginosa, four exhibited positive skin responses at 24 hours, strong inhibition of leukocyte migration, and marked stimulation of blastogenesis of peripheral lymphocytes when exposed to a "cocktail" of three phenol-killed strains of P aeruginosa. There was no correlation between the extent of these responses with serum hemagglutinin titers. It is postulated that cell-mediated immunity against P aeruginosa may have a biologic role in host defense.


Extracorporeal membrane oxygenation in the treatment of respiratory failure--a review. Extracorporeal membrane oxygenation (ECMO) can be used for the treatment of acute respiratory failure. Based on recent experience in establishing such a method of treatment, this paper reviews those aspects of ECMO that need careful consideration before it can be undertaken. Methods of patient selection for ECMO and the physiological changes associated with it are also discussed.