Field evaluation of New York City medium in the biological environment-CO2 chamber in recovery of Neisseria gonorrhoeae and urogenital mycoplasmas. The biological environment-CO2 chamber containing New York City (NYC) medium was evaluated in a clinical field trial in comparison with Transgrow and NYC medium in plates for the recovery of Neisseria gonorrhoeae and with NYC medium for urogenital mycoplasmas. The results of the study indicated that the biological environment chamber-CO2 culturing system with NYC medium is an effective method for the handling, transport, and culture of N. gonorrhoeae, large-colony mycoplasmas, and T-mycoplasmas if the delay in transport and incubation does not exceed 24 h.


Radiometric detection of bacteremia: requirement for terminal subcultures. A radiometric procedure for rapid detection of bacteria in clinical blood specimens was utilized over a period of 1 year in this laboratory. Although in initial studies it was felt that all positive bacteremias would be detected by radiometric examination of cultures for 14CO2 evolution over a 7-day period, we found in the present study that a significant number of bacteria were not detected, except by blind subculturing on day 7 before discarding the culture sample. Microorganisms were detected in 490 individual specimens from 348 patients after examination of 6,200 individual blood specimens, both anaerobically and aerobically. All but 30 of the positive specimens were detected by the radiometric procedure, with an average detection time of 30.5 h. Thirty organisms, representing 6% of the total organisms isolated, were not detected by the BACTEC apparatus. The predominating organisms missed by the radiometric method were group D streptococci, both enterococcal and non-enterococcal species. These isolates represented two-thirds of the total number of organisms not detected by the radiometric procedure. A majority of bacteria detected only upon terminal subculture were isolates from a very small number of patients, suggesting that these organisms might have specific properties that preclude their detection by radiometric assay. Nevertheless, our study results indicate that it is essential that all radiometrically examined blood culture specimens be subcultured prior to discard in order to lessen the likelihood of missing a microbial pathogen.


Evaluation of a simple device for bacteriological sampling of respirator-generated aerosols. The Aerotest sampler (Olympic Medical Corp., Seattle, Wash.) is designed to detect bacterial contamination of respirator-generated aerosols in a simple one-step process. The sampler was evaluated by controlled contamination of Bennett AP-5, PR-2, and MA-1 respirators with Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter. Bacteria present as viable 1.4 to 3.5-mum particles in each of 77 aerosols were quantitated by using the Andersen viable-particle sampler, and the results were compared with those of colonies obtained from 10-s or 15-cycle Aerotest samples. All aerosols containing counts greater than expected in hospital air were detected by the Aerotest method. Thirteen of 14 aerosols containing less than 20 bacteria/0.028 m3 showed fewer than 5 colonies, whereas all aerosols containing greater than 1,000 bacteria/0.028 m3 showed at least 40 colonies. Aerosols with intermediate counts fell in between. Under the conditions described here, the Aerotest sampler was able to discriminate between the low levels of bacteria commonly found in hospital air and the bacterial contamination associated with nosocomial pneumonia. The Aerotest sampler provides a practical method for surveillance sampling of respirator nebulizers.


Comparison of Counterimmunoelectrophoresis and electron microscopy for laboratory diagnosis of human reovirus-like agent-associated infantile gastroenteritis. Counterimmunoelectrophoresis was compared with electron microscopy for detection of human reovirus-like agent in fecal specimens. Both tests gave very similar results.


Correlations between the detection of e antigen or antibody and electron microscopic pattern of hepatitis B surface antigen (HBsAg) associated particles in the serum of HBsAg carriers. The distribution of HBsAg associated particles, especially the presence of Dane particles, was studied by electron microscopy in coded sera of 68 chronic HBsAg carriers. Results were correlated with the detection of eAg or Ab and clinical diagnosis. Sera from haemodialysis and chronic hepatitis patients showed a high prevalence of e antigenaemia (9/13, 69-2% and 8/19, 42-1%) and Dane particles (11 and 16 respectively, 84%). By contrast, out of 36 chronic asymptomatic carriers of HBsAg, 28 (77-7%) were positive for e antibody but only 1 (2-7%) had eAg. Dane particles were found in 13/36 (36-1%). A statistically significant correlation was observed between the detection of eAg and the presence of Dane particles (94-4%) in the serum. However, Dane particles were still observed in 10/28 (35-7%) of anti-e positive sera. The data suggest that eAg may be linked to complete HB virions.


A population of lymphocytes in human blood distinctive in morphology and other characteristics. Evidence is presented that lymphocytes characterised by being large and having abundant feebly staining, and usually profusely granulated cytoplasm ('pale' cells) are a group which is distinct from the other small basophilic ('dark') cells. In patients with genetic storage disorders characterised by abnormalities of lymphocyte structure, the structural peculiarites were confined to the basophilic cells, and cytochemical differences were found between the 'pale' and 'dark' cells in normal subjects.


Observations on the use of the double diffusion test in the diagnosis of vaginal candidiasis. Precipitins to mannan and cytoplasmic antigens of three Candida species were determined in an unselected series of 289 non-pregnant women. Precipitins were present in 20% of sera of women with vaginal candidiasis, in 23% of women harbouring yeasts in the vagina without clinical signs of infection, and in 21% of women harbouring yeasts in sites other than the vagina. Of the 47 patients who reacted with Candida albicans mannan or cytoplasmic antigens, 98% reacted with mannan antigen but only 13% with cytoplasmic antigen. The inclusion of mannan and cytoplasmic antigens of C. guilliermondii and C. parapsilosis did not increase the specificity or sensitivity of the test in the diagnosis of vaginal candidiasis. It is suggested that the double diffusion test is of doubtful value as an adjunct to the diagnosis of vaginal candidiasis.


Efferent connections of cortical, area 8 (frontal eye field) in Macaca fascicularis. A reinvestigation using the autoradiographic technique. The efferent projections from the cortical area 8 (frontal eye field) have been re-examined in four adult monkeys (Macaca fascicularis) by injecting small amounts of H3-proline into the rostral bank of sulcus arcuatus and using the autoradiographic tracing technique. Ipsilateral cortical projections could be traced into specific areas of the depths of sulcus principalis, sulcus temporalis superior and sulcus intraparietalis. Label was found contralaterally in area 8. Subcortical connections were observed ipsilaterally to n. caudatus, putamen, claustrum, n. ventralis anterior pars magnocellularis, n. medialis dorsalis pars multiformis and pars densocellularis, n. centralis lateralis and paracentralis, n. parafascicularis, n. pulvinar oralis, zone incerta, n. subthalamicus, pretectal area, colliculus superior and griseum pontis as well as the ipsi- and contralateral n. reticularis tegmenti pontis. Negative results were obtained with respect to the oculomotor nuclei, n. interstitials and Darkschewitsch as well as to the paramedian pontine reticular formation.


Cells of origin and terminal distribution of corticostriatal fibers arising in the sensory-motor cortex of monkeys. The cells of origin of the corticostriatal projection have been identified in squirrel monkeys by the use of the retrograde horseradish peroxidase method. In the subfields of the somatic sensory, motor, parietal and frontal areas of the cortex, cells projecting to the ipsilateral striatum are relatively sparsely distributed and form a group of small- to medium-sized pyramidal cells with an average somal diameter from area to area of 14-16 mum. Such cells are found only in layer V of the cortex (mainly in the more superficial parts of the layer). Since they are consistently smaller than the pyramidal cells of layer V that project to the brainstem and spinal cord and since they lie outside layer VI which gives rise to corticothalamic axons, the corticostriatal axons are unlikely to be collaterals of axons projecting to other sites. The cells of origin of the crossed corticostriatal projection are also found in layer V and are pyramidal cells with somal diameters in the same range as above. They are found only in areas 4, 8, and 6. Studies with the anterograde, autoradiographic method in rhesus, cynomologous and squirrel monkeys, indicate that the somatic sensory areas project to most of the antero-posterior extent of the ipsilateral putamen. Subareas 3a, 3b, 1 and 2 of the somatic sensory cortex project to the same region and the projection overlaps similarly extensive projections from the motor and certain other areas of the cortex. However, in each case the pattern of terminal labeling is in the form of interrupted clusters, strips and bands. A single small injection of the cortex is associated with only one or two such clusters of terminal labeling. This seems to imply that individual corticostriatal fibers end in a very restricted manner and that the terminal ramifications of fibers from one cortical area may alternate in the putamen with those arising in other areas.


Effect of cobalt-60 radiation on the pulp of restored teeth. The effect of cobalt-60 teletherapy on the pulps of restored teeth of monkeys was studied. Gold crowns and amalgam and composite resin restorations were placed in 28 teeth of two Macaca speciosa monkeys. One monkey then received cobalt-60 radiation to both maxillary and mandibular teeth and bones, with a total dose of 7,600 rads. Decalcified semiserial paraffin sections, 7 mum thick, of the teeth and supporting tissues were prepared and stained with hematoxylin and eosin. Microscopically, there was no discernible difference between the irradiated and the non-irradiated pulps.


Stool viruses in babies in Glasgow. I. Hospital admissions with diarrhoea. Stools from 183 babies under 2 years of age admitted to Ruchill Hospital with diarrhoea were examined by electron microscopy, virus culture, bacterial culture and light microscopy. As far as possible, several stools were examined from each patient and the results showed rotaviruses, astroviruses and other viruses in association with symptoms, as well as the expected bacterial pathogens. Examination of several stools from the same patient also showed that in this age group the viral flora of the gut changes rapidly and that the viruses seen by electron microscopy were only rarely grown in cell culture and vice versa. This phenomenon was particularly noted with adenoviruses. In 30% of cases no microbial pathogen was identified and in the remainder the presence of the infecting organism did not always coincide with the symptoms. It is concluded that, with viruses at least, presence of the organism does not constitute proof of causation.


Complete humoral immunosuppression of mice by rabbit anti-mu antibodies passing the murine placenta. Female BALB/c mice were immunosuppressed with a series of neonatally initiated rabbit anti-mu serum injections, which eliminated serum IgM and greatly delayed production of antibodies against normal rabbit serum (anti-NRS). Females thus prepared maintained circulating anti-mu levels for several months. Study of the progeny from pregnancies completed during this maintenance period revealed that rabbit anti-mu antibodies readily cross the murine placenta but are not passed in murine colostrum at levels detectable by the technique used. Anti-NRS antibodies actively produced in NRS-injected control females do cross the placenta, but do so only irregularly and poorly; these antibodies may, however, be detected consistently at relatively low levels in colostrum. Suppression of humoral immunoglobulin synthesis in most mice prenatally exposed to anti-mu antibodies by transplacental passage appeared complete, even including loss of the remnant IgG levels which are consistently seen in mice first exposed to anti-mu at birth. The appearance of serum IgG and anti-NRS antibodies along with the complete absence of serum IgM in mice recovering from suppression suggests that active IgM synthesis and secretion may not be a prerequisite for the IgM to IgG "switch". Immune recovery occurred even in completely immunosuppressed mice after anti-mu injections were discontinued; the mechanism of recovery is not certain.


Mitogen activation of human chronic lymphatic leukemia cells. I. Synthesis and secretion of immunoglobulin. The response of CLL (chronic lymphatic leukemia) lymphocytes to PHA, PWM, and Con A with respect to changes in surface markers and synthesis and secretion of immunoglobulin were examined. After PHA stimulation the percentage of cells bearing readily detectable surface immunoglobulin (SmIg) diminished rapidly whereas cells forming rosettes with sheep erythrocytes (E-rosettes) increased from less than 1% to 30 to 50%. The great majority of blast-transformed cells were E-rosette-positive cells with a small population of SmIg-positive blast cells also observed. Ig production in four of seven CLL lymphocyte populations was increased 2.5 to greater than 40-fold after 4 to 6 days of culture in the presence of PHA. In contrast, pokeweed mitogen did not affect Ig synthesis. Furthermore, the Ig secreted into the culture supernatant fluids from seven of eight CLL cases examined consisted almost entirely of free light chain molecules. In contrast, the cell lysates contained a significant proportion of intact Ig molecules. These results indicate that CLL cells can, under certain circumstances, be stimulated to synthesize and secrete increased amounts of Ig, but that there is a basic defect in the biosynthetic mechanism of these cells which result in the secretion of free light chains rather than intact immunoglobulin molecules.


Murine and rat IgE: relationships in terms of binding to cell receptors and to antibodies against rat epsilon chain. The similarity between murine and rat IgE was examined in terms of their fixation to target cells and interaction with monospecific antibodies to rat epsilon-chain (anti-epsilon). Purified rat monoclonal IgE (IgEr) was found to block the fixation of murine reagin (IgEm) to mouse and rat skin and to rat basophilic leukemia (RBL) cells. The capacities of mouse reaginic serum (MRS), rat reaginic serum, and IgEr to inhibit the binding of radiolabeled 125I-IgEr to RBL cells were shown to be similar. These results suggest that the binding of IgE of either species occurs on the same or on adjacent receptor sites of mast cells and RBL cells. The antigenic cross-reactivity between IgEm and IgEr was established by depletion of the reaginic activity from MRS by treatment of MRS with anti-epsilon. The reaginic activity of MRS could be recovered by the addition of IgEr to anti-epsilon:IgEm complexes. From these findings it may be inferred that i) IgEm and IgEr share some antigenic determinants and ii) the regions of the immunoglobulins responsible for fixation to receptors on mast cells and RBL cells are identical or similar.


B lymphocyte colony-forming cells in the SJL/J mouse. Mercatoethanol-induced B lymphocyte cloning in semi-solid agar has been used to study lymphocyte colony formation by cells from the SJL/J mouse thymus. From the 3rd month of life, the SJL/J mouse thymus. From the 3rd month of life, the SJL thymus develops an increasing frequency of cells forming B lymphocyte colonies in agar. The peak frequency in 6- to 12-month-old mice was one colony per 1000 to 2000 cultured thymus cells. In contrast, 10 to 100 times lower frequencies were found in the thymus of five other inbred mouse strains. The rise in B lymphocyte colony-forming cells correlated well with the age-related rise in Ig-positive cells and approximately 50% of the colony cells reacted with anti-micron-serum indicating the B lymphocyte nature of the colony cells. Colony-forming cells from the thymus showed higher sensitivity than colony-forming spleen cells to cortisol and irradiation. Cell transfer experiments and thymus grafting suggested that the increased frequency of colony-forming cells in the thymus is caused by development of special thymus-seeking B lymphocytes in ageing SJL/J mice. Finally, B lymphocyte colony-forming cells were found to be more frequent in the thymus, spleen, and lymph nodes from healthy aged mice than in lymphoid organs from mice with spontaneous reticulum cell tumors.


Human autologous and allogeneic rosettes. Human red blood cells can bind to human peripheral blood lymphocytes. The percentage of these rosette-forming cells (TEh) depends on various conditions including temperature and the use of selected foetal calf serum. It is improved by toluidine blue. Prior incubation at 37 degrees C is not necessary. ABO and rhesus antigen D have no influence on rosette formation. Analysis of human rosettes in T and B cell rich populations, in patients with chronic lymphatic leukaemia or T cell lymphoma provides further evidence that human autologous and allogeneic rosette-forming cells belong to a T cell subpopulation.


Immunodiffusion and agglutination tests for Candida in patients with neoplastic disease: inconsistent correlation of results with invasive infections. A serological study of candidiasis was conducted with use of (1) sera sent to the laboratory by clinicians who suspected infections due to various organisms including Candida species, and (2) sera available in our serum bank from patients with candidiasis proven at autopsy and from those with documented candidemia. With this population of patients, we were able to evaluate both potential false-negative and false-positive results. Microimmunodiffusion and slide agglutination tests were used. In many cases, serial specimens were available for measurement of rises or falls in titers of agglutinating antibody. Sera from less than one-half of the patients with disseminated or invasive gastrointestinal candidiasis exhibited positive immunodiffusion reactions, titers of agglutinating antibody of greater than 1:16, or fourfold rises in titer of agglutinins. Sera from several patients with pharyngitis due to Candida and from several who were only colonized with Candida or for whom clinical or cultural evidence of candidiasis was lacking showed positive immunodiffusion reactions or agglutinin titers of greater than 1:16, and some showed fourfold rises in titer. Conversions from negative to positive immunodiffusion reactions were not consistently correlated with invasive candida infection. Using the methods described, we have not found immunodiffusion tests and titers of agglutinating antibody to be reliable indicators of invasive candida infection, since false-positive as well as false-negative reactions occur. Greater specificity for invasiveness as well as greater sensitivity in immunosuppressed patients are necessary before these tests can become important adjuncts to the evaluation of patients with suspected invasive candidiasis.


Experimental pneumonia due to Pseudomonas aeruginosa in leukopenic dogs: prolongation of survival by combined treatment with passive antibody to Pseudomonas and granulocyte transfusions. Treatment with type-specific IgG antibody to Pseudomonas aeruginosa significantly increased rates of survival after experimental induction of pseudomonas pneumonia in leukopenic dogs. Longer survival times were correlated with higher titers of circulating antibody in serum; however, no animals treated with antibody alone were long-term survivors. Subsequent development of sepsis or the recovery of Pseudomonas from infected lung tissue was not altered by treatment with antibody. Therapy with granulocyte transfusions plus gentamicin was associated with a 27% rate of long-term survival. Passive immunization with IgG (reciprocal mean hemagglutination titer, 52) in addition to granulocyte transfusions and treatment with gentamicin resulted in a rate of long-term survival of 67% (P less than 0.05). Dogs that died while receiving this combination therapy still had a survival time significantly longer than those of controls or animals treated only with granulocytes and antibiotic.


Treatment of mixed bacterial infections with clindamycin and gentamicin. Thirty-eight patients with severe mixed bacterial infections were treated with clindamycin and gentamicin. In vitro, all staphylococci and streptococci (other than enterococci) and 96% of anaerobes were susceptible to clindamycin; all staphylococci and 92% of Enterobacteriaceae and Pseudomonas aeruginosa were susceptible to gentamicin. Enterococci were usually resistant to both antibiotics. Significant synergy was only occasionally observed with this combination of antibiotics; there were no instances of antagonism. Among the patients treated with both drugs, there were four patients with pneumonia and empyema, 15 with infections of the skin, soft tissue, and/or bone, and 19 with intraabdominal infection. Nine patients had bacteremia, and 29 had failed to respond or had developed infections during previous antibiotic therapy. The results of treatment with clindamycin and gentamicin were considered to be excellent: 30 patients were cured, four improved, and four failed to respond. Concentrations of clindamycin in serum greatly surpassed minimal inhibitory concentrations (MICs) of clindamycin-susceptible pathogens; these organisms were eradicated from foci of infection. Concentrations of gentamicin in serum did not consistently surpass MICs for gentamicin-susceptible pathogens; these organisms and enterococci often persisted in foci of infection. In patients with complicated infections that required prolonged courses of treatment, Enterobacteriaceae, Pseudomonas aeruginosa, and enterococci occasionally emerged as predominant pathogens. Adverse reactions frequently occurred but were mild and reversible; treatment was discontinued in only two patients who developed rashes.


L-Dopa peroxidase activity of human erythrocyte catalase. The human red cell hemolysate was found to have 3-(3',4'-dihydroxphenyl)-L-alanine (L-dopa) peroxidase activity. During the purification of glutathione peroxidase and catalase by ammonium sulfate precipitation, ion exchange chromatography. Sephadex gel filtration, and preparative polyacrylamide disc electrophoresis, the L-dopa peroxidase activity was found to be associated with catalase. Both sodium azide, 8 mM, and 3-amino-1,2,4-triazole, 50 mM, besides inhibiting catalase, inhibited the L-dopa peroxidase activity in each fraction. Ethylenediamine tetraacetic acid (EDTA), 4 mM, had no effect on catalase or L-dopa peroxidase activity, indicating that the oxidation of L-dopa is not a nonenzymatic process mediated by metal ions. Although the electrophoretic mobility of catalase, L-dopa peroxidase, and glutathione peroxidase are similar, a homogeneous preparation of glutathione peroxidase was free of L-dopa peroxidase activity. L-Dopa peroxidase in human red cells was co-purified with catalase.


A rapid radiometric method for determining the sensitivity of clinical isolates of Mycobacterium tuberculosis to several chemotherapeutic agents. Current methods of performing antibiotic susceptibility tests on M. tuberculosis require 4 to 6 weeks for completion and in some cases have a poor correlation with clinical results. We have developed a rapid radiometric method of sensitivity testing which utilizes the incorporation of 3H-uracil into ribonucleic acid (RNA) as a measure of mycobacterial growth. The radiometric method is sensitive and reproducible and the results are completed in 48 hours. An excellent correlation was found between the radiometric method of sensitivity testing and the traditional agar plate technique when the two were compared with respect to isoniazid, streptomycin, and rifampicin sensitivities. There was no correlation between the two methods when ethambutol was tested. These results have confirmed our previous experiments on the usefulness of the radiometric method for the rapid determination of antibiotic susceptibilities of mycobacteria.


Pulp changes after anterior mandibular subapical osteotomy in a primate model. Subapical osteotomy of the anterior mandible was carried out on 10 adult Macaca Irus monkeys with and without open bite. Teeth were extracted at 8 weeks, 12 weeks, 24 weeks and 1 year after surgery and the pulps examined histologically. No normal pulps were found. Progressive fibrosis and calcification was noted in all teeth. Patent pulp blood vessels were found up to 24 weeks after surgery. Pulp damage to teeth distal to the osteotomy site was found in 50% of cases. Control teeth extracted from the opposing jaw at the same intervals were all found to have normal pulps.


[Artefacts of lipid electrophoresis: edge zoning effects in agarose gel (author's transl)]. The evaluation of lipid electropherograms obtained by electrophoresis in agarose gel is sometimes difficult owing to methodological errors, e. g. the artificial mal-formation of individual lipoprotein bands. It was shown that this "edge zoning effect", e. g. resulting from broadened bands with irregular boundries, can be abolished by the addition of EDTA (0,36 g/l buffer) to the gel.


Spinal cord potentials evoked by cutaneous afferents in the monkey. 1. Negative intermediary cord potentials and the equivalent field potentials were recorded from the surface or within the monkey lumbosacral spinal cord in response to stimulation of myelinated afferent fibers in cutaneous or mixed nerves of the hindlimb. 2. Cord potentials resembling the N1 and N2 potentials described in the cat spinal cord were found but, in addition, activation of small myelinated fibers produced a later potential named here the N3-wave. By use of a subtraction technique, it is estimated that the N3-wave has a latency of 11.4 (+/- 3.5 SD) ms from the time of arrival of the volley in the largest affs at 9 (+/- 3) ms after its onset, and the wave lasts 23 (+/- 5.7) ms. 3. The N3-wave is not lost following spinal cord transection, but may instead be enhanced. It is thus due to neural circuitry intrinsic to the lumbosacral spinal cord. 4. The longitudinal distribution of the N3-wave is similar to that of the N1- and N2-waves. 5. The field potential associated with the N3-wave and recorded from within the spinal cord has two negative foci in some animals: near the dorsalmost part of the dorsal horn and in an area equivalent to Rexed's laminae IV-VI. The field potential reverses in sign in the ventral horn. 6. The N3-wave is evoked by Adelta fibers. This was shown by grading the stimulus strength, by measuring the conduction delay for producing the wave when stimuli are applied either proximally or distally on the sural nerve, and by showing that the N3-wave persists when the Aalphabeta fibers are anodally blocked. 7. There is often a late burst discharge in spinal neurons, including spinothalamic tract neurons, which can be attributed to Adelta fibers and which corresponds in time to the N3-wave. 8. It is proposed that the N3-wave can be used as a monitor of the central effects of Adelta fibers in the spinal cord.


Response characteristics of cutaneous cold receptors in the monkey. 1. The receptive fields of 48 specific cold units, located in the hairy and glaborous skin of fore- and hindlimbs of rhesus monkeys, were mapped and scale drawings made. Forty-five percent had single spotlike receptive fields of 1-2 mm diameter or were up to 2 mm wide and 3-5 mm long, and formed straight, crescent, or right-angle shapes. The remaining 55% had two to five discrete spots or small areas innervated by a single fiber. Area or number of receptive fields per unit did not vary significantly along the limb axis. 2. Of the 48 specific cold units, 15 were held sufficiently long to record their dynamic responses to intensity-rate series of temperature changes from several adapting temperatures (ATs) between 20 and 45 degrees C. Six cold units showed a paradoxical increase in the steady-state response at the 45 degrees C compared to that at the 40 degrees C AT. Of the 15 cold units, 7 discharged in bursts at the 35 degrees C or lower ATs. The proportion of short intervals (intraburst intervals) increased as the adapting temperature decreased. 3. Both the latency and the temperature change at the onset of the dynamic response to cooling remained relatively constant for ATs up to and including 35 degrees C. The response latencies were approximately 200-400 ms, while the temperature changes at response onset were -0.02 to -0.06 degrees C. Both increased sharply at the 40 degrees C and still more at the 45 degrees C ATs. 4. The rate of increase in the frequency of the dynamic response to cooling by the fast rate increased to maximum at the 30 degrees C AT and then decreased at the higher ATs. For the slow rate the highest rate of increase in frequency occurred at the 20 degrees C AT. The fast rate of cooling always induced a faster rate of increase in frequency than slow rate of cooling. 5. Four indices of response magnitude were used in the analysis of the dynamic responses. These were peak frequency, cumulative impulses in the first 4 s following stimulus onset, average frequency during stimulations plus 3 s, and the total impulses during stimulation. The first three indices gave similar representations of the dynamic responses to the rate and intensity of cooling and the effect of the AT. The slow rate of cooling invariably yielded a smaller index of response magnitude than the fast rate. The difference became more pronounced as the intensity of cooling increased. The stimulus intensity-response magnitude functions were nonlinear. This nonlinearity was more pronounced at the low than at the high ATs. As the AT was increased, the response indices approached linearity at the 35 and 40 degrees C ATs. The greatest sensitivity of cold units to cooling was from the 35 degrees C AT. The fourth index, total impulses during stimulation minus steady state, gave a different picture. This index of response magnitude was linearly related to stimulus intensity for both rates of cooling from all adapting temperatures except for the slow rate of cooling from the 45 degrees C AT...


Parietal lobe mechanisms for directed visual attention. 1. Experiments were made on the cortex of the inferior parietal lobule in 10 hemispheres of six alert, behaving monkeys. The electrical signs of the impulse discharges of single cortical cells were recorded as the monkeys executed tasks requiring them to fixate stationary visual targets, track those which moved slowly, and to make saccadic movements to foveate those which suddenly jumped from one locus to another within the field of view. A total of 907 neurons of area 7 were identified in terms of their physiological properties, particularly the correlation of their activity with the oculomotor components of these behavioral acts of directed visual attention; 480 of these were located by cytoarchitectural layer. Most identifiable cells of area 7 are visuomotor neurons, in a special and conditional sense. Their discharge frequencies increase before and during those steady fixations and movements of the eyes which secure and maintain foveation of objects, but only if the visual targets engaged are linked by a strong motivational drive; in our experiments, one between thirst and the light whose dimming the animal has learned to detect for liquid reward. We have identified and studied three major classes of neurons in area 7. 2. The visual fixation neurons (57%) accelerate discharge synchronously with fixation of a visual object the animal desires. The incremented discharge continues until reward, but then declines abruptly even when there is no immediate shift of the line of gaze. Fixation neurons are relatively inactive during those casual fixations by which the animal insepcts the surrounding environment. Mist fixation neurons subtend gaze fields limited to one quadrant or half of the total gaze field. The sum of the gaze fields of the fixation neurons in one hemisphere is weighted moderately toward the contralateral side. Fixation cells also discharge during slow pursuit movements in any direction so long as the movement stays within the gaze field of the neuron under study. About 40% of fixation cells are suppressed before and during saccadic movements of the eyes to a new target within the gaze field of the fixation cell. Those suppressed are located preferentially in layer V of the cortex. Suppression is maximal for saccades directed contralaterally to the hemisphere under study. 3. Visual tracking neurons are active during oculomotor pursuit of slowly moving visual objects, not during steady fixations. They show a marked directional but no laterality relation, and are suppressed before and during a visually evoked saccade superimposed on the smooth pursuit movement. The rate of discharge is a flat function of tracking speed so that these cells do not appear to emit signals which specify the speed of smooth pursuit movements. 4. The saccade neurons are active before and during visually evoked saccadic movements of the eyes but not before spontaneous saccades, no matter whether made in light or near darkness. The discharge of saccade neurons leads the eye movement by as much as 150 ms (mean, 73 ms)...


Properties and tectal projections of monkey retinal ganglion cells. 1. Extracellular single-unit recordings were undertaken in the retina of the rhesus monkey in order to assess the receptive-field properties of those ganglion cells which project to the superior colliculus. Cells were tested for antidromic activation from the superior colliculus, lateral geniculate nucleus, and the optic chiasm. 2. The majority of retinal ganglion cells could be classified as color opponent or broad band. A small, heterogeneous group could not be so classified and were collectively referred to as "rarely encountered" cells. 3. Color-opponent cells responded in a sustained fashion and broad-band cells in a transient fashion to visual stimuli. Quantitative assessment of response transiency shows that this measure reliably differentiates these two classes. 4. To moving sinusoidal gratings broad-band cells responded more vigorously and with greater temporal modulation than did color-opponent cells. 5. The distributions of conduction velocities of different classes of neurons showed considerable overlap. On the average, axons of broadband neurons conducted most rapidly and rarely encountered types, most slowly. 6. The population of cells projecting to the superior colliculus does not contain color-opponent cells. The retinotectal cells respond predominantly in a transient fashion. Only 3.9% of broad-band cells (26 of 663) were antidromically driven from the superior colliculus, while 29% of the rarely encountered group (5 of 17) could be so activated. 7. The relative distribution of color-opponent and broad-band cells does not appear to change with retinal eccentricity within the central 20 degrees.


Release of antidiuretic hormone during mass-induced elevation of intracranial pressure. There are complex osmotic and non-osmotic factors regulating release of antidiuretic hormone  (ADH). A wide variety of intracranial pathological processes may trigger ADH release sufficient to produce clinically recognizable hyponatremia, or the "inappropriate ADH syndrome." We systematically studied one non-osmotic trigger, namely mass-induced elevated intracranial pressure (ICP). Initial experiments established baseline data in normal rhesus monkeys: anesthetized animals displayed appropriate rises and falls in immunoreactive urinary ADH in response to intravenously administered hypertonic and hypotonic infusions. Next, ballon catherters were implanted subdurally over temporal lobes and the animals were allowed to recover. The final experiment consisted of anethetizing the animals, monitoring arterial blood pressure and blood gases, and retrieving timed urinary specimens while continuously recording ICP during infusion-pump expansion of the subdural ballon. A nonlethal and a lethal series of ballon-expansion experiments were done. Control values of urinary ADH were 783 +/- 125 muU/15 min, and ICP was less than 10 mm Hg. During nonlethal mass expansion ADH output rose of 3433 +/- 269 millimicronU/15 min while ICP averaged 65 mm Hg (measured at completion of mass expansion). While the mass was maintained, hypotonic infusion produced unchanged urinary ADH output of 3452 +/- 277 muU/15 min. During lethal experiments, urinary ADH rose still higher to 4339 +/- 1887 muU/15 min associated with ICP averaging 100 mm Hg. We concluded that there is a direct relationship between the magnitude of ICP and the amount of ADH release, and that during elevated ICP the ADH release is not suppressed by hypotonic infusion.


Orbital cortical influences on cardiovascular dynamics and myocardial structure in conscious monkeys. The posterior orbital cortex of the frontal lobes in conscious monkeys was stimulated electrically to study the influence of this structure on cardiovascular hemodynamics and cardiac morphology. Stimulating electrodes, cardiac output flow probes, and arterial blood pressure transducers were chronically implanted by aseptic procedures into eight Macaca fascicularis monkeys. Cardiovascular changes induced by stimulating the orbital cortex included both biphasic and unidirectional alterations in cardiac output, blood pressure, heart rate, stroke volume, and total systemic resistance. Electrode position and the rate (Hz) of applied stimulation were the primary determinants of the direction and magnitude of the response. All animals stimulated demonstrated acute, discrete interventricular septal myocytolysis, characteristic of early ischemic lesions. Since the orbital cortex is a part of the limbic system, changes induced by its stimulation suggest a pathophysiological mechanism whereby emotional expression may effect dynamic shifts in cardiovascular functions and may thus induce permanent and manifest myocardial lesions.


The effect of cerebellar stimulation on focal seizure activity and spasticity in monkeys. Experiments were carried out in awake, unmedicated monkeys to determine the effect of application of current to the cerebellar hemispheres on electrically induced focal motor seizures and surgically induced spasticity. Application of current at various frequencies and pulse amplitudes did not significantly alter focal motor seizures but did significantly reduce spasticity. Analysis of evoked potential recordings carried out during various experimental procedures suggests that application of current to the cerebellar hemispheres may reduce cortical neuronal responsiveness.


Site and extent of thiamin absorption in the rat. The site and extent of absorption of thiamin hydrochloride was determined in rats using 51Cr-EDTA as a non-absorbed reference substance. The main site of absorption of thiamin was found to be the proximal 22 cm of the small intestine with relatively little absorption occurring distally, particularly at low dietary thiamine levels. Concentration of thiamin in the intestinal contents increased along the intestine reaching maximum levels in the distal small intestine. The results are compatible with two concurrent mechanisms of thiamin absorption with the active absorptive process being saturated at 0.5 to 1.0 muM.


Use of EDTA to produce zinc deficiency in the pregnant rat. The effectiveness of EDTA in reducing the endogenous zinc supply in pregnant rats was determined by two experiments. In experiment 1, a high level of zinc (100 ppm) was given to rats days 15 through 17 of gestation. In experiment 2, a low level of zinc (3 ppm) was given from days 1 through 17. On day 18, half the rats were given EDTA in two intraperitoneal injections 6 hours apart with or without zinc supplementation. The -Zn + EDTA group lost weight continuously after the injections, had increased hematocrit levels prior to parturition,and showed greater stress at parturition than did the -Zn group. Weight gains, hematocrit level, and parturition in the +Zn + EDTA group did not differ significantly from those of the +Zn controls. Spleen weights were decreased in the -Zn + EDTA and -Zn groups and zinc concentration in the spleen increased in the -Zn + EDTA group. Iron concentration decreased in the spleen and increased in the liver of EDTA-treated rats. Use of EDTA to remove endogenous zinc appears to offer a mechanism for study of the effects of short-term zinc supplementation at critical periods in the pregnant zinc-deficient rat.


Incorporation of 15NH4Cl into histidine in adult man. An adult male fed by parenteral alimentation for 48 days had successive intakes of a complete mixture of essential amino acids, and then lysine- and histidine deletion to test for the essentially of histidine. After 22 days of histidine-free-intake, 15NH4Cl was ingested orally with subsequent measurement of the time patterns for the appearance of 15N in total plasma proteins, globin from hemoglobin and urine. The 15N was incorporated into glutamate, aspartate, tyrosine, and histidine, but not lysine, of plasma proteins and globin. Urinary histidine and Ntau-methylhistidine, but not lysine, also contained 15N. Degradation of several histidine samples by two methods and two Ntau-methylhistidine samples demonstrated the presence of 15N in both the alpha-amino nitrogen and the imidazole ring. The incorporation of 15N into the ring indicates limited synthesis of histidine in an adult man under the above stated conditions.


Metabolic and development changes in growing rats born to dams restricted in protein and/or energy intake. During gestation and lactation, the food intake of female rats was restricted to 50% of the ad libitum stock diet intake of controls (C). One restricted group (M1) was fed stock diet while another restricted group (M2) was fed casein-supplemented stock diet containing 66% protein. Observations were directed to their progeny. After weaning at 21 days, all progeny were fed the stock diet ad libitum for 2 weeks. Mean birth weight of M2 was lower than M1 which was lower than C. Weight gain of progeny was faster in M2 than M1 but both were less than C. At 5 weeks, M2 had normal brain weight but lower mg protein/g brain than either M1 or C. M1 had the lowest brain weight. Livers of M1 and M2 were smaller than C, and M2 had higher RNA and protein, and lower DNA per g liver than either M1 or C. Both M1 and M2 had about three-fold elevation in hepatic serine dehydratase and slightly lower phosphoglycerate dehydrogenase than C. The lower birth weight and normal brain size of M2 suggested that some of the protein consumed by M2 dams was conserved for synthesis of vital components despite energy restriction.


Biologic basis for modification of the sagittal ramus split operation. Ten adult rhesus monkeys were used as experimental models to investigate revascularization and bone healing associated with sagittal splitting of the mandibular rami by two different techniques. Microangiographic and histologic studies showed intraosseous ischemia in the margins of the osteotomized segments and areas where the pterygomasseteric sling had been detached. When the mucoperiosteum and pterygomasseteric sling were minimally detached from the proximal segment, intraosseous ischemia and necrosis were significantly reduced. The results support the use of a clinical technique of sagittally splitting the mandibular ramus, which maximizes attachment of the pterygomasseteric sling and mucoperiosteum.


Host range characteristics of the primate coccidian, Isospora arctopitheci Rodhain 1933 (Protozoa: Eimeriidae). Studies were conducted on 35 primates, 12 carnivores, and 2 marsupials to determine their susceptibility to the primate coccidian, Isospora arctopitheci. Patent oocyst infections resulted in 12 of the 14 species of animals investigated. These included 6 genera of New World primates native to Panama: Saguinus geoffroyi, Aotus trivirgatus, Ateles fusciceps, Cebus capucinus, Alouatta villosa, and Saimiri sciureus. In addition 4 families of carnivores (2 domestic and 2 sylvatic) and 1 species of marsupial became infected following experimental exposure. These animals are represented respectively by the following 6 genera and species: Canis familiaris; Felis catus; Nasua nasua, and Potos flavus; Eiria barbara; and Didelphis marsupialis. Four Old World rhesus monkeys, Macaca mulatta, and 1 carnivore, Bassaricyon gabbii, did not become oocyst positive. This unusually large host range makes this isosporan unique among the coccidia that have been investigated to date.


Nomenclature of Sarcocystis in the ox and sheep and of fecal Coccidia of the dog and cat. The nomenclature of Sarcocystis and related protozoan genera is reviewed, and modern diagnoses of the genera Isospora, Toxoplasma, Besnoitia, Sarcocystis, and Frenkelia in the coccidian family Eimeriidae are given. S cruzi (Hasselmann 1926) comb. n., S. hirsuta Moulé 1888, and S. hominis (Railliet and Lucet 1891) comb. n. are recognized in the muscles of the ox Bos taurus; S. ovicanis Heydorn, Gestrich, Melhorn, and Rommel 1975, and S. tenella Railliet 1886 are recognized in the muscles of the sheep Ovis aries; S. bigemina (Stiles 1891) comb. n., S. cruzi, S. ovicanis, S. bertrami Doflein 1901, S. miescheriana (Kühn 1865) Lankester 1882, I. ohioensis Dubey 1975, I. canis Nemeséri 1959, Isospora sp. n. Dubey, and Isospora sp. n. Trayser and Todd are recognized in dog (Canis familiaris) feces; and S. hirsuta, S. tenella, S. muris (Blanchard 1885) Labbé 1899, B. besnoiti (Marotel 1912) Henry 1913, Besnoitia sp. n. Frenkel, T. gondii (Nicolle and Manceaus 1908) Nicolle and Manceaux 1909, T. hammondi (Frenkel 1974) Levine and Nye 1976, I. rivolta (Grassi 1879) Wenyon 1923, and I. felis Wenyon 1923 are recognized in cat (Felis catus) feces. Hoareosporidium Pande, Bhatia, and Chauhan 1972 is considered a synonym of Sarcocystis.


Studies on the Santa Lucia (El Salvador) strain of Plasmodium falciparum in Aotus trivirgatus monkeys. The Santa Lucia strain of Plasmodium falciparum was isolated from El Salvador, Central America, and established in Aotus trivirgatus monkeys. Transmission from monkey to monkey via the bites of infected Anopheles freeborni, A. maculatus, and A, albimanus mosquitoes was obtained in 20 of 27 attempts. Prepatent periods in the monkeys ranged from 17 to 46 days with a mean of 24.3 days. Parasitemias and mortality were higher following sporozoite inoculation into animals which had been previously infected with P. vivax than in those with no previous malaria experience. Monkeys previously infected with P. vivax and P. cynomolgi had lower maximum parasitemias than those previously infected with P. vivax only.


Infectivity of the Santa Lucia (El Salvador) strain of Plasmodium falciparum to different anophelines. Anopheles freeborni mosquitoes were much more heavily infected with the Santa Lucia strain of Plasmodium falciparum from coastal El Salvador than were any of the other species tested. Of 5 strains of A. albimanus examined, the most heavily infected was the CA-109A and the least was the Melara, both of which come from coastal El Salvador. Of the exotic anophelines, the A. maculatus was infected at a slightly higher level than was the A. balabacensis. The incidence of highly infected individual mosquitoes was greatest in the Panama-Escobal strain of A. albimanus from the Republic of Panama; the incidence was lowest in the Melara strain from El Salvador. All strains of A. albimanus developed infected salivary glands, but the A. freeborni and A. maculatus mosquitoes appeared to develop infected glands more effeciently. Infection rates in A. freeborni mosquitoes were highest if mosquitoes were fed on Aotus trivirgatus monkeys between the 19th and 25th days of patent gametocytemia.


Computer utilization for intravenous nutrition in surgical neonates preliminary report. A program was developed to store important numerical clinical data such as daily weights, intravenous caloric intake, and laboratory test results on surgical neonates who required total intravenous nutrition. Preliminary experience with the data from the first 5 surgical neonates requiring intravenous nutrition indicated that this data processing is easily achieved. Data retrieval by the development of output programs provided rapid access to stored records, rapid data tabulation, and graphic print-out of parameters, such as intravenous calories per kilogram per day and weight gain, that can be placed in the patient's record.


Peripheral intravenous nutrition without fat in neonatal surgery. During a 1 yr period, 19 infants less than 2 mo of age were fed intravenously with an infusate composed of glucose, amino acids, electrolytes, and vitamins. The solution was infused at a rate of 200 ml/kg/day or more for periods ranging from 5-247 days. No central venous catheters were utilized; the solutions were always administered through a needle in a peripheral vein. Weight gains similar to those seen with other techniques of intravenous nutrition were observed in all of the patients studied. No instance of fluid overload in the form of pulmonary edema, peripheral edema, or congestive heart failure was seen, and osmotic diuresis was not observed because of the lower tonicity of the infusate. Phlebitis was seen in 1/5 of the infusions, but was reversed by stopping the infusion and applying warm soaks. Three cases of skin slough were observed and two of these healed spontaneously without the need of skin grafting. The advantages of this technique over central venous nutrition are the elimination of the complications related to the central venous catheter, namely, sepsis and superior vena cava thrombosis.


Use of chlorhexidine gluconate to inhibit dental plaque accumulation in Macaca speciosa. Oral swabbing with 2% aqueous chlorhexidine gluconate together with thorough approximal flossing effectively reduce plaque accumulation to negligible levels in M. speciosa.


Fluorescent inhibitors of thymidylate synthetase. Two fluorescent derivatives of 2'-deoxy-5-fluorouridine 5'-p-aminophenyl phosphate were prepared by treatment of this compound with fluorescein isothiocyanate in dimethyl sulfoxide or 5-(dimethylamino)naphthalene sulfonyl chloride in pyridine. The products of the reactions were isolated by diethylaminoethylcellulose chromatography and were shown to be homogeneous by polyacrylamide electrophoresis and TLC. Confirmation of the structure was provided by elemental analysis, absorption and fluorescence spectra, PMR measurements, and liberation of nucleotide upon hydrolysis with snake venom phosphodiesterase. The fluorescent derivatives are good competitive inhibitors (Ki approximately10(-6) M) of thymidylate synthetase from a methotrexate-resistant strain of Lactobacillus casei.


Concentration-time effects of quinidine disposition kinetics in rhesus monkeys. The effects of dose and duration of drug administration (time) on the disposition kinetics of quinidine were investigated in unanesthetized rhesus monkeys. A specific thin-layer chromatography-fluorometric assay was developed for the determination of quinidine in plasma, blood and urine. After the monkeys receive an i.v. bolus dose of 3 to 7 mg/kg, quinidine distributes rapidly in the body (T 1/2alpha = 2 minutes). The half-life associated with elimination (T 1/2 beta) was 27 to 35 minutes and primarily involved metabolic transformation. The volume of distribution varied between 0.2 and 0.65 liters/kg and total clearance between 4.8 and 13 ml/min/kg. Similar estimates of T 1/2 beta, clearance and volume of distribution were obtained following constant infusions producing steady-state concentrations less than 6 microng/ml. Prolonged infusion of quinidine at rates producing plasma concentrations in the range of 6 to 13 microng/ml resulted in increases in the elimination half-life whereas drug clearance remained constant. This observation suggests an increased volume of distribution. Both concentration and time were demonstrated to be important in producing changes in quinidine disposition kinetics. The precise mechanism underlying this phenomenon remains unanswered.


Effects of morphine, methadone, nalorphine and naloxone on responding under schedules of electric shock titration. Under two titration schedules, responses of squirrel monkeys adjusted the intensity of a continuous electric shock. In one schedule, responses produced food pellets but also increased a shock intensity which otherwise was decreased at a fixed rate (punishment titration). In another schedule, responses decreased a shock intensity which otherwise was increased at a fixed rate (escape titration). Responding maintained under the punishment titration schedule was only decreased by morphine, methadone, nalorphine and naloxone. This decrease in response rate was associated with a decrease in intensity of continous electric shock. Comparable rates of responding maintained under the escape titration schedule were either unaffected or increased over the same dose range of the same drugs. These effects on rate of responding were associated with either no effect or a slight decrease in intensity of continuous electric shock. When control rate of responding under the escape titration schedule was then increased by requiring five responses to decrease shock intensity, morphine, but not d-amphetamine, decreased responding at doses which had no effect or even increased responding when only one response was required to decrease shock intensity. These findings indicate that titration schedules are not always useful for studying the analgesic effects of drugs, but that specific effects of drugs are determined by specific details under which responding is maintained.


Reinforcing properties of perphenazine, haloperidol and amitryptiline in rhesus monkeys. Possible negative reinforcing effects of perphenazine, haloperidol and amitryptiline were studied in rhesus monkeys previously trained to avoid electric shock by responding. Responding extinguished a light associated with an intravenous drug infusion scheduled to occur 30 seconds after the light was switched on. A response occurring when the light was on switched the light off for a period of 1 minute (time-out period). a response during the infusion terminated the infusion. Under these conditions, the monkeys tolerated a large number of saline infusions. Saline was replaced by different doses of perphenazine, haloperidol and amitryptiline, each for 12 successive daily 2-hour sessions. Infusions of perphenazine (0.50-1.6 microng/kg) and to a lesser extent infusions of haloperidol (2.5 microng/kg) generated and maintained responding. Most of the infusions of amitryptiline in the dose range of 1.0 to 10.0 microng/kg were tolerated. Haloperidol and perphenazine in doses higher than 10.0 micmitryptiline (500-3000 microng/kg i.v.) had no influence on shock avoidance behavior. Positive reinforcing effects of these compounds were studied in a group of monkeys trained to respond under a 10 response fixed ratio of intravenous infusions of codeine. None of the three compounds maintained responding previously engendered by codeine.


Effects of cocaine and d-amphetamine on behavior maintained under various schedules of food presentation in squirrel monkeys. Dose-response functions were determined for the effects of cocaine and d-amphetamine on lever-pressing responses maintained under three schedules of food presentation: 1) a simple fixed-ratio schedule, 2) a multiple fixed-ratio, fixed-interval schedule and 3) a second-order fixed-interval schedule with fixed-ratio components. These schedules generated a variety of rates and patterns of responding. The effects of the drugs on response rate depended on the control rates of responding. The highest overall rates of responding were maintained under the fixed-ratio schedule and under the fixed-ratio component of the multiple schedule. Both cocaine and d-amphetamine produced dose-related decreases in these high response rates. Lower overall rates of responding were maintained under the second-order schedule and under the fixed-interval component of the multiple schedule. Intermediate doses of cocaine or d-amphetamine (0.1-1.0 mg/kg) increased these lower rates of responding. Under the second-order schedule and the multiple schedule, local response rates during successive segments of the fixed-intervals were differentially affected by the drugs. Cocaine and d-amphetamine markedly increased low response rates that occurred during initial segments of the fixed intervals, but either had little effect on or decreased higher responses rates that occurred during later segments of the fixed intervals. Cocaine and d-amphetamine had similar qualitative and quantitative effects on responding, but d-amphetamine was longer lasting than cocaine.


Isolation, synthesis, and biological activity of five metabolites of danazol. Metabolites of danazol (17 alpha-pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol), an orally effective pituitary gonadotropin inhibitory agent devoid of estrogenic and progestational activites, were isolated from urine of a female subject who had taken danzol orally at a dose of 800 mg/day for 7 days, The metabolites isolated were 17-hydroxy-17alpha-pregn-4-en-20-yn-3-one (11), 17-hydroxy-2alpha-(hydroxymethyl)-17alpha-pregn-4-3n-20-yn-3-one (5), 17-hydroxy-2-(hydroxymethyl)-17alpha-pregna-1,4-dien-20-yn-3-one(7), 6beta,17-dihydroxy-2alpha-(hydroxymethyl)-17alphapregn-4-en-20-yn-3-one(8), and 6beta, 17-dihydroxy-2(hydroxymethyl)-17alphapregna-1,4-dien-20yn-3-one(10). None of these metabolites exhibited pituitary inhibiting activity comparable to danazol.


3-Aminotetrahydrocarbazoles as a new series of central nervous system agents. 3-Dimethylamino-1,2,3,4-tetrahydrocarbazole, a structurally modified tryptamine, prevented amphetamine-induced stereotyped behavior in rats and prevented reserpine-induced ptosis in mice. Further study of this compound and a number of substituted derivatives indicated that either imipramine-like or chlorpromazine-like profiles were obtainable by changing substituents and their positions.


Beta-Lactam antibiotics derived from nitrogen heterocyclic acetic acids. 1. Penicillin derivatives. In an attempt to synthesize antibacterial agents effective against gram-negative bacteria, penicillin derivatives were prepared from substituted and unsubstituted 1,4-dihyro-2-oxopyridine-1-acetic acids, 1,4-dihydro-4-oxopyridine-1-acetic acids, and 1,2,3,4-tetrahydro-2,4-dioxopyrimidine-1-acetic acids. The unsubstituted derivatives displayed moderate activity against gram-negative bacteria; however, substitution (alkyl, chloro, nitro, acetyl, and cyano) on the heterocyclic ring of these acetic acids and (alkyl, phenyl) in the alpha position decreased the activity of the penicillin derivatives against gram-negative organisms.


The oral apparatus of Tetrahymena pyriformis, strain WH-6. IV. Observations on the organization of microtubules and filaments in the isolated oral apparatus and the differential effect of potassium chloride on the stability of oral apparatus microtubules. This report is an ultrastructural analysis of the organization of the isolated oral apparatus of Tetrahymena pyriformis, strain WH-6, syngen 1. Attention has been focused on the organization of microtubules and filaments in oral apparatus membranelles. Oral apparatus membranellar basal bodies were characterized with respect to structural differentiations at the distal and proximal ends. The distal region of membranellar basal bodies contains the basal plate, accessory microtubules and filaments. The proximal end contains a dense material from which emanate accessory microtubules and filaments. There are at least two possibly three different arrangements of accessory structures at the proximal end of membranellar basal bodies. All membranellar basal bodies appear to have a dense material at the proximal end from which filaments emanate. Some of these basal bodies have accessory microtubules and filaments emanating from this dense material. A possible third arrangement is represented by basal bodies which have lateral projections, from the proximal end, of accessory microtubules and filaments which constitute cross or peripheral connectives. There are at least three examples of direct associations between oral apparatus microtubules and filaments: (1) filaments which form links between basal body triplet microtubules, (2) filaments which link the material of the basal plate to internal basal body microtubules, (3) filaments which link together microtubule bundles from membranellar connectives. KCl extraction of the isolated oral apparatus resulted in the selective solubilization of oral apparatus basal bodies, remnants of ciliary axonemes and fused basal plates. Based on their response to KCl extraction two distinct sets of morphologically similar micro tubules can be identified: (a) microtubules which constitute the internal structure of basal bodies and ciliary axonemes, (b) microtubules which constitute the fiber connectives between basal bodies.


Effect of trichloropropene oxide on the ability of polyaromatic hydrocarbons and their "K-region" oxides to initiate skin tumors in mice and to bind to DNA in vitro. The potent epoxide hydrase inhibitor, 1,1,1-trichloro-2,3-propene oxide (TCPO), enhanced the tumor-initiating ability of benzo[alpha]pyrene (BP) and 3-methylcholanthrene (MCA) but had no effect on 9,10-dimethyl-1,2-anthracene (DMBA) initiation in a two-stage system of tumorigenesis in female Charles River CD-1 mice. The tumor-initiating ability of dibenz[alpha,h]-anthracene (DBA) was decreased by prior topical treatment with 10 mumoles of TCPO. The tumor latency period of BP and MCA was decreased by TCPO but had no effect on DMBA or DBA. Topical treatment with 10 mumoles of TCPO did not initiate tumors in a two-stage system in mouse skin nor did it cause any histopathologic changes in the skin. The "K-region" epoxides of BP, DMBA, and MCA were weak tumor initiators when compared to the parent compounds. TCPO only slightly increased or had no effect on the tumor-initiating activity of the above epoxides. Pretreatment with Croton oil 18 hours prior to initiation with BP-4,5-epoxide also slightly enhanced the tumorigenic response in mouse skin. DBA-5,6-epoxide, when tested as a complete carcinogen at high doses (1 mg daily/10 days), was found to be a weak carcinogen but with activity comparable to that of DBA. TCPO only slightly increased the in vitro epidermally mediated covalent binding of the above parent polycyclic hydrocarbons to DNA.


Effect of age of non-skin tissues on susceptibility of skin grafts to 7,12-dimethylbenz[alpha]anthracene (DMBA) carcinogenesis in BALB/c mice, and effect of age of skin graft on susceptibility of surrounding recipient skin to DMBA. The influence of age-dependent alterations in non-skin tissues on chemical carcinogen-induced skin papilloma development was studied by treatment with 7,12-dimethylbenz[alpha]anthracene (DMBA) of 4-month-old skin grafts sewed onto 4- and 20-month-old syngeneic recipients. Skin of 4- and 20-month-old BALB/c female mice differed in susceptibility to DMBA carcinogenesis, but the 4-month-old grafts showed the same papilloma incidence independent of the age of the recipient mice. In a different experiment, the influence of age of skin grafts on papilloma development on DMBA-treated recipient skin was studied. Fourteen- and 26-month-old skin grafts were carried by 14-month-old recipients. Grafts of those two ages are known to differ in susceptibility to DMBA carcinogenesis, but no effect of the grafts on papilloma development on DMBA-treated recipients was detectable. It was concluded that certain age-dependent differences in skin susceptibility to chemical carcinogens are solely a reflection of alterations in the skin at the site of carcinogen treatment.


Antimetastatic effects of N-diazoacetyl-glycine derivatives in C57BL mice. When three diazoacetyl-glycine derivatives, N-diazoacetyl-glycine amide (DGA), N-diazoacetyl-glycine hydrazide (DGI), and N-diazoacetyl-glycine ethyl ester (DGE), were tested against Lewis lung carcinoma in C57BL mice, DGA reduced sharply the number and weight of pulmonary metastases; the effects of DGI and DGE were less pronounced. The growth of the primary tumor was reduced slightly by DGA, but the greater effect was produced by DGI. The absence of correlation between the reduction of the growth of the primary implant and the number of lung secondary tumors for the tested compounds indicated that DGA possesses antimetastatic properties.


A comparative study of experimental and spontaneous emphysema. Normal lung architecture of the rat, mouse, hamster, horse, and human was compared to that of emphysematous lungs from the same species by utilizing a light microscope and a scanning electron microscope (SEM). The results obtained by SEM examination of normal and emphysematous lungs corresponded to those obtained with the light microscope. However, the SEM provided a view of alveoli and airway morphology not obtainable with the light microscope. Because of the variability in pore size and number of pores per alveolus, a pore-to-alveolus ratio was determined with the SEM on the normal lungs of the above species plus the rabbit, dog, guinea pig, and rhesus monkey. Depending on the extent of other pathways for collateral ventilation, differences in number of pores per alveolus may affect a species' susceptibility to a given mechanism in the genesis of spontaneous or induced emphysema. The small number of pores per alveolus in the rat, mouse, rabbit, and hamster suggests that they would not be responsible for emphysematous changes. Pores do appear to be involved in human and horse emphysema.


Trichloroethylene. I. An overview.

Trichloroethylene. I. An overview. Trichloroethylene (TCE) has been an industrial chemical of some importance for the past 50 years. First synthesized by Fischer in 1864, TCE has enjoyed considerable industrial usage as a degreaser and limited medical use as an inhalation anesthetic and analgesic. This TCE overview provides a narrative survey of the reference literature. Highlights include history, nomenclature, physical and chemical properties, manufacture, analysis, uses, metabolism, toxicology, carcinogenic potential, exposure routes, recommended standards, and conclusions. Chemically, TCE is a colorless, highly volatile liquid of molecular formula C2HCl3. Autoxidation of the unstable compound yields acidic products. Stabilizers are added to retard decomposition. TCE's multitude of industrial uses center around its highly effective fat-solvent properties. Metabolically, TCE is transformed in the liver to trichloroacetic acid, trichloroethanol, and trichloroethanol glucuronide; these breakdown products are excreted through the kidneys. Most toxic responses occur as a result of industrial exposures. TCE affects principally the central nervous system (CNS). Short exposures result in subjective symptoms such as headache, nausea, and incoordination. Longer exposures may result in CNS depression, hepatorenal failure, and increased cardiac output. Cases of sudden death following TCE exposure are generally attributed to ventricular fibrillation. Current interest in TCE has focused on recent experimental data that implicate TCE as a cause of hepatocellular carcinoma in mice. No epidemiological data are available that demonstrate a similar action in humans. The overall population may be exposed to TCE through household cleaning fluids, decaffeinated coffee, and some spice extracts. The NIOSH recommended standard for TCE is 100 ppm as a time-weighted average for an 8-hr day, with a maximum allowable peak concentration of 150 ppm for 10 min.


Adsorption of bacteriophages phi 29 and 22a to protoplasts of Bacillus subtilis 168. Adsorption of bacteriophages phi 29 and 22a to protoplasts of Bacillus subtilis 168 is described. The number of binding sites on bacilli and protoplasts is determined for each phage. Bacilli and protoplasts possess roughly the same number of sites per unit area for phi 29, i.e., approximately 700 sites per bacillus. There are also approximately 700 sites per bacillus for 22a, but only about one-third as many sites per unit area on the protoplast surface. A model for phi 29 adsorption is proposed.


Isolation of a variant of human adenovirus serotype 2 that multiplies efficiently on monkey cells. A variant of adenovirus serotype 2 (Ad2) that overcomes the block to multiplication of the wild-type Ad2 on monkey cells is described. The variant was selected, after nitrous acid mutagenesis, by sequential passage on monkey cells. This variant forms plaques with similar efficiency on human and monkey cells cells. The kinetics of its growth and its burst size on human and monkey cells are similar. These growth properties are similar to those found for wild-type Ad2 on monkey cells when the block is overcome by coinfection with simian virus 40.


Requirement of cell nucleus for African swine fever virus replication in Vero cells. The role of the cell nucleus in the development of African swine fever virus in Vero cells has been studied. No viral growth could be detected in enucleated cells under conditions that allow normal development of Sindbis virus. Furthermore, African swine fever virus DNA synthesis was inhibited more than 95% after infection of enucleated Vero cells as compared with normal cells.


Effect of antibiotics on certain aspects of bacteriophage SP-15 development in Bacillus subtilis W23. Bacillus subtilis W23 was infected with bacteriophage SP-15. Two waves of phage-specific RNA synthesis were observed. Wave I was prereplicative, and wave II was coincident with replication of the viral genome. To determine the temporal appearance of general classes of phage-coded messengers and proteins, we studied the dependence of lysozyme synthesis, phage production, and DNA synthesis on time of addition of transcriptional and translational inhibitors. Lysozyme synthesis started to become refractile to a variety of transcriptional inhibitors (rifampin, streptolydigin, and actinomycin D) between 20 and 22 min postinfection and was completely refractile by 30 min. Nevertheless, functional enzyme did not appear until 45 to 47 min postinfection; lysozyme was maximal by 65 min. Rna isolated from SP-15 phage-infected cells was used to program the cell-free synthesis of lysozyme. The messenger was synthesized exclusively between 20 and 30 min postinfection. Lysozyme messengers were stable. The data imply that lysozyme messengers were present 52 min prior to their translation. Progeny virus formation remained sensitive to transcriptional inhibitors until 40 to 50 min postinfection, and sensitivity to chloramphenicol lasted 65 min. The first progeny viruses appeared at 75 min. Again, an unusually long lag between completion of functional messengers and their translation was evident. The aforementioned data indicated that transcription of lysozyme messengers and, at least, some messengers, whose products are essential for phage production, are uniquely associated with waves I and II of RNA synthesis, respectively. However, messengers whose products are essential for normal amounts of DNA synthesis were apparently synthesized during both waves; transcription of these messengers was transiently repressed (using the term broadly) between 30 and 40 min postinfection. Judging from the dependence of DNA synthesis on time of chloramphenicol addition, proteins essential for normal amounts of DNA synthesis were also synthesized in two discrete waves, each yielding sufficient protein for half-maximal levels of DNA synthesis. An hiatus in the synthesis of the proteins in question was evident between 45 and 65 min postinfection; evidence cited in this paper indicates that this hiatus did not result from messenger depletion, which, in turn, implied some type of translational-level control. This latter conclusion is substantiated by the lysozyme synthesis that occurred during the same interval when synthesis of certain proteins for DNA replication was transiently repressed.


One-stage radical cystectomy for bladder carcinoma: operative mortality, cost/benefit analysis. An analysis of cystectomies performed between September 1, 1969 and December 31, 1974 was conducted to determine the rates of morbidity (59 per cent) and operative mortality (4.1 per cent). Comparison of these figures for single operations with data published form other sources concerning staging of the therapeutic procedures suggests that there is no benefit for the patient relative to surgical morbidity or mortality if the latter course is followed. Conversely, prolongation of hospital experience, multiple operations, absence from productive activity and increased health care cost are associated with the staged procedures. Application of cost-benefit analysis suggests that this experience may act as a model to evaluate competing forms of therapy involving other disorders. When costs are not equivalent and benefits are the same the more expensive form of therapy should not be offered except for unusual circumstances.


Convulsions complicating colectomy in inflammatory bowel disease. Convulsions have complicated the surgical management of life-threatening inflammatory bowel disease in five patients. These patients experienced a transient, generalized convulsive disorder and toxic ambylopia. Results of neurological examination were unremarkable. Treatment included metabolic stabilization along with the administration of oxygen and anticonvulsive medication. Various factors, such as hypoxia, fluid overload, cerebral edema, steroid administration, and deficits in calcium, magnesium, and potassium, may have contributed to the cause of this complication.


The changing American health scene. Sometimes things get better. Since the increased efforts to improve medical care for Americans were initiated 15 years ago, it is generally believed they had little impact on the problems addressed. Review of national data suggests otherwise. American medical care and health status are getting better. We have improved the availability of physician services and largely eliminated the gap between visits made by rich and poor, or white and black citizens. We have greatly expanded the number of health professionals who provide medical care. Better organized programs to provide care to groups with special health problems have reduced both mortality and morbidity. Age-adjusted death rates, infant and maternal mortality, and death rates from coronary artery disease have fallen. While there remains an important agenda for the future, there seems room for cautious optimism about the abilities of American society to make forward progress.


Industrial hypertension program in a rural state. Efficacy and cost effectiveness. A program was designed to evaluate the efficacy and cost of detecting and treating hypertension in an industrial population of a rural state. Original screening and evaluation was initiated by a trained blood-pressure technician team, but initiation of therapy was the responsibility of the private physician. Follow-up data were obtained at one year by rescreening in 83% and by telephone contact in 91% of the original hypertensive patients. Eighty-three percent of those patients with moderate or severe hypertension complied with physician visits. The condition of 60% of the treated patients was controlled, and the condition of 74% was improved. The total cost per patient treated for one year was 250 dollars; per patient with controlled hypertension, 446 dollars; and per patient with controlled or improved hypertension, $362.


Continuous assessment of left ventricular volume by ultrasonic analogue conversion system. Applicability of ultrasonic analogue conversion system devised by us for assessments of left ventricular volume was examined in patients with and without heart disease. The conversion system could sample the echoes from the endocardial surfaces of the interventricular septum and the posterior left ventricular wall. The conversion system could also calculate automatically the minor axis and volume of the left ventricle. End-diastolic, end-systolic, and stroke volumes calculated by the conversion system were close to those calculated from biplane ventriculograms and to those calculated from photographic records of B-mode echo-display. Change in left ventricular volume caused by respiration ranged up to 17.5%. Spontaneous variations in left ventricular volume during continuous monitoring was up to 7.5%. End-diastolic, end-systolic, and stroke volumes were reduced by sublingual administration of nitroglycerin. The results indicate applicability of the ultrasonic analogue conversion system for continuous assessments of left ventricular volume in man.


Effects of coronary vasodilators on large and small coronary arteries of dogs. Using the isolated perfused heart preparation supported by a donor the effects of vasodilators on the large conductance artery were studied and were compared with those on the small resistive artery and arterioles. Nitroglycerin produced a preferential dilation of the large conductance artery, while dipyridamole produced a dilation only of the small resistive artery and arterioles. Among the "calcium antagonistic" vasodilators tested, only diltiazem produced a dilatation of the large conductance artery, verapamil and nifedipine producing a dilatation only of the small resistive artery and arterioles. These findings indicate that the mechanism of contraction of the large conductance artery is different from that of the small resistive artery and arterioles.


[Ocular involvement due to the juice of Dieffenbachia plants (author's transl)]. Upon breaking the stem or the branches of a Dieffenbachia plant juice is released in an explosive manner and may thus involve the eye. A myriad of fine calcium-oxalate crystals penetrate into all layers of the cornea, and an iritis can develop. The latter ceases within 6 days, the corneal cristals vanish within about three weeks.


Studies of rhesus monkey (Macaca mulatta) hemoglobin. One hemaglobin was found in the adult rhesus monkey (Macaca mulatta) by the technique of isoelectric focusing. In addition to the adult hemoglobin, one fetal hemaglobin was observed in neonates of the same species. The alpha and non-alpha globins of rhesus monkey hemoglobins showed similar electrophoretic mobilities as those of human hemoglobin A by cellulose acetate membrane electrophoresis. It appeared that the rhesus monkey hemoglobin system is a good model system for the study of human hemoglobin development.


Murine amyloid protein AA in casein-induced experimental amyloidosis. Amyloidosis was induced in mice by 25 subcutaneous injections of casein. The splenic amyloid fibrils were identified by electron microscopy to be closely associated with reticular cells. After isolation of the fibrils by simple physical techniques, their ultrastructure revealed single filaments of 80 to 100 A width, which were rigid, nonbranching, and of indeterminate length. This is comparable to previous studies on human preparations. The amyloid fibrils were dissociated by solution in guanidine and chromatography. The resultant amyloid fibril protein was characterized as to its molecular weight, amino acid analysis, and amino-terminal sequence. It was thus definitely identified as protein AA, the major component of secondary amyloidosis. An antibody to this protein, murine AA, identified a cross-reacting mouse serum protein SAA and indicated a species specificity when tested against human preparations. A comparison is made with the AA protein in another murine model as well as AA proteins from human, guinea pig, monkey, and mink amyloidosis.


Cost factors in urban telemedicine.

Cost factors in urban telemedicine. This paper reports on the cost effectiveness of a pediatric primary care system utilizing nurse practitioners (NPs) linked to a physician consultant through bidirectional interactive cable television. In addition, it discusses ways in which multiple uses enhance the economic feasibility of a telemedicine consultation link in a given geographic area. The overall consultation rate during periods of remote physician coverage was 21 per cent, compared with 24 per cent during on-site coverage. The telephone became a partial substitute for the TV for some uses but could not replace it in diagnostic decisions. As telemedicine is obviously underutilized in a one-satellite system, we compare a five-satellite network with other ways of delivering service. The resulting estimated cost of $18.50 an hour, or 2/3 of the cost of a physician providing direct care, includes a TV component of $5.30 an hour of use in a 1,750-hour year. The critical factor is that the NP can be a physician substitute if there is TV backup. The TV appears to prevent unnecessary referrals compared to a physician on site. Whether TV increases the length of the consult compared to the phone for conditions of equal severity is not entirely clear. If TV is compared to transporting a patient to a central place, the implicit value of transport time and disutility required to justify using TV is $7.55 per consult in a five-clinic network. Geographic and other barriers to physician availability enhance the potential for application fo telemedicine.


[Current state of space biorhythm study]. The paper presents a review of the literature covering a new branch of science--space biorhythmology--that evolved in the 1960s. The paper surveys briefly publications on general biorhythmology that formed the basis for the new branch of science. The paper discusses specifically the investigations that formulated the basic concepts of space biorhythmology in theory and practice. It describes the problem of desynchronosis as one of the most important problems and outlines its involvement in the general adaptation syndrome as a necessary component. The paper gives a scheme of measures developed in the USSR with the purpose of preventing desynchronosis and stresses the advantages of further study of space biorhythmology.


Evaluating cost-effectiveness using episodes of care. To test the feasibility of defining episodes of care as a cost-effectiveness measure, a pilot study was carried out in conjunction with an ongoing quality assessment program which involved abstracting prospective data from charts of patients treated for hypertension in the Primary Care Clinic of Hahnemann Medical College and Hospital. For comparison, data were abstracted retrospectively on hypertensive patients treated by faculty general internists in a fee-for-service private practice. The 12-month course of each patient was divided into controlled and uncontrolled episodes for which visit frequency rate and mean laboratory test utilization was calculated. Patient cost for each type of episode in each setting was calculated using standard charges. Results indicate that the episode definition is feasible and provides a measure for comparing the cost-effectiveness of different delivery systems treating the same health care problem. Factors omitted from the study that could affect cost-effectiveness are also discussed.


Lipid metabolism in early development using labeled precursors incorporated during oogenesis and in cell-free embryo homogenates. Embryos of the toad, Bufo arenarum, Hensel, taken during early stages of development were used to survey the [U-14C]glycerol and 32P lipid labeling. When precursors were supplied at the time of oogenesis, large differences in specific activities of phospholipid were observed. Using 32P, a steep rise as a function of development was evidenced. Triglycerides contained much higher proportions of [U-14C] glycerol than phospholipids when administered to the female toad along with a pituitary homogenate. However, lack of [U-14 C] glycerol uptake into lipids was observed when cell-free homogenates of eggs at different stages of development ranging from unfertilized oocyte to midgastrula were incubated in unsupplemented amphibian Ringer. At the later stage, significant de novo biosynthesis of lipids from glycerol began to be measurable, whereas during cell cleavage intracellular redistribution of preformed phosphoglycerides was used for membrane assembly.


A simple method for the preparation of pure 9-D-hydroperoxide of linoleic acid and methyl linoleate based on the positional specificity of lipoxygenase in tomato fruit. Incubation of linoleic acid with crude homogenate of tomato fruit gave a high yield (69%) of linoleic acid hydroperoxides with a ratio of 9- to 13-hydroperoxide isomers of 96:4. After chromatography of the products, as free acids or methyl esters, hydroperoxides with 9- to 13-isomeric ratios of greater than 99:1 were obtained. The major product was characterized as 9-D-hydroperoxy-octadeca-trans-10,cis-12-dienoic acid. The results demonstrate the positional specificity of lipoxygenase from tomato fruit.


Acute cerebral dysfunction in diabetic ketoacidosis: survivial followed by panhypopituitarism. We report a unique case of a 15-yr-old diabetic patient who survived ketoacidosis complicated by acute severe encephalopathy, hypopituitarism, and optic atropy. We reviewed our 25-yr experience with fatal diabetic ketoacidosis; three additional cases resembled the "cerebral edema" syndrome. We observed that (1) cerebral edema is not often documented in this syndrome, (2) the cause of the acute neuronal disturbance in these patients may be hypoxic, with cerebral edema a secondary development, and (3) development of encephalopathy was probably unrelated to overvigorour correction of acidosis and hyperglycemia in our cases.


Human splanchnic metabolism during diabetic ketoacidosis. Splanchnic exchange rates of glucose, acetoacetate, beta-hydroxybutyrate, lactate, pyruvate, glycerol, alanine, glutamine, glutamate, free fatty acids, and triglycerides were measured in eight patients during moderate to severe diabetic ketoacidosis. Their arterial glucose concentration was 20.68 (9.80-52.79) mumole/liter and tic glucose release was 0.77 (0.09-2.44) mmole/min. Gluconeogenesis accounted for about one-half of net splanchnic glucose release, assuming quantitative conversion of net splanchnic extracted lactate, pyruvate, glycerol, alanine, and alpha-ketoglutarate equivalents to glucose. Net splanchnic free fatty acid extraction was 0.24 (0.09-0.52) mmole/min. There was a positive correlation between free fatty acid uptake and ketone-body release. Net splanchnic acetoacetate release was 0.50 (0.05-0.92) mmole/min and beta-hydroxybutyrate release was 0.35 (-0.16 to 0.84) mmole/min. Total ketone-body release was 0.84 (0.37-1.61) mmole/min. The wide ranges of net splanchnic glucose and ketone-body production rates show the heterogeneous characteristics of the diabetic patient in ketoacidosis. It is concluded that the hyperglycemia and hyperketonemia of diabetic ketoacidosis is due to the lack of reciprocity among rates of hepatic glycogenlysis, gluconeogenesis, and ketogenesis resulting in inappropriate net splanchnic release of glucose and ketone bodies.


Glucagon infusion in normal man: effects on 3-methylhistidine excretion and plasma amino acids. In order to assess the role of glucagon in human protein metabolism and to examine its action as a "catabolic" hormone, studies were conducted in two normal male subjects over an 8-day period. After minimum and stable urinary nitrogen excretion had been produced by the continuous nasogastric administration of carbohydrate (720 g/day) for 8 consecutive days, a continuous intravenous infusion of glucagon (1.0 mg/24 hr) was superimposed on days 7 and 8. Excretion of total nitrogen (N) and urea-N increased significantly (p less than 0.05). Excretion of 3-methylhistidine was unaltered, suggesting that the source of the N losses produced by glucagon did not derive from increased muscle proteolysis. Although striking hypoaminoacidemia was produced, the reductions of extracellular amino acids alone could not account for all of the extra urea excreted. These data suggest that hyperglucagonemia in normal man induces mild nitrogen losses by stimulation of hepatic ureogenesis from free intracellular amino acid pools and not by increased rates of muscle protein breakdown.


Proinsulin and C-peptide: a review.

Proinsulin and C-peptide: a review. The recent work on proinsulin and C-peptide has been reviewed with major emphasis on the most significant findings since 1972. Proinsulin has now been established as the biosynthetic precursor of insulin in all species examined, including man, with a preproinsulin as a possible precursor of the prohormone. The conversion of proinsulin which appears to occur exclusively in the pancreas leads to equimolar production of insulin and C-peptide. Although proinsulin has a direct biologic effect which is one-tenth as much as that of insulin, C-peptide has no biologic activity on homologous or heterologous tissue and no ability to modify the action of insulin and/or proinsulin. Previous work on proinsulin immunoassay suggested that this prohormone, but not C-peptide, cross-reacts with insulin antiserum. On the other hand, in the C-peptide immunoassay, proinsulin but not insulin cross-reacts with the antiserum. Up to this time, therefore, it has not been possible to immunoassay human proinsulin or C-peptide specifically. The very recent work from the laboratory of Heding, however, has brought about major advances in this area in which human C-peptide and proinsulin can be separated in the plasma by the use of Sepharose particles. With this recent major advancement, it is now possible to measure human C-peptide specifically. This measurement has been shown to be a useful tool for the assessment of beta-cell function in diabetic patients treated with insulin and in insulinoma patients in whom endogenous C-peptide secretion is not suppressed with exogenous insulin-induced hypoglycemia. With the use of a specific enzyme which degrades insulin but not proinsulin, postprandial plasma proinsulin values have been measured in a large number of subjects under a variety of physiologic and pathologic conditions. These results, which are comparable to those obtained by the more laborious column chromatography, could be summarized as follows: (1) proinsulin values in lean, young normal subjects do not vary greatly in response to insulin secretagogues; (2) proinsulin secretion in response to glucose results in a greater percentage of proinsulin in the older age group than in the younger group; (3) in lean adult and juvenile diabetic patients, the percentage of proinsulin is not excessive, whereas obese diabetics and pregnant diabetics appear to secrete relatively greater proinsulin than their diabetic controls; and (4) whereas most hyperinsulinemic states (Cusing's syndrome, adult-onset diabetics, acromegaly, and glucocorticoid therapy) are not associated with an increase in percentage of proinsulin, hyperinsulinemia of insulinoma, selected cases of functional hypoglycemia, and genetic hyperproinsulinemia are associated with a greater percentage of proinsulin. Identification of a possible new proinsulin intermediate(s) in these conditions deserves further investigation...


Sodium valproate for the treatment of childhood epilepsies. An uncontrolled trial of sodium valproate in 25 severe epileptics uncontrollable by conventional antiepileptic drugs is presented. Excellent control was achieved in petit mal, myoclonic and minor motor seizures. No serious side effects were encountered, but hyperactivity may be aggravated and interaction with other anticonvulsants does occur.


Antibiotic sensitivity of gonococci in South Australia, 1974 to 1975. Routine testing of gonococci isolated from patients attending the Venereal Diseases Control Centre in Adelaide during the year July, 1974 to June, 1975, with a plate dilution method, showed that 93-8% of the 947 infecting strains were relatively sensitive to penicillin at a minimum inhibitory concentration (MIC) of 0-12 units/ml or less, and that 90% of the 648 strains tested were relatively sensitive to tetracycline at an MIC of 1-0 mug/ml or less. A small proportion only of isolates were relatively insensitive to penicillin and/or tetracycline. The routine treatment schedules which were used at the Centre proved adequate for infections over the whole range of sensitivities encountered. A significant proportion of the less sensitive strains were isolated from people infected in South-East Asia, most of whom had been inadequately treated there.


[Combined treatment of lung carcinoma. Report on a prospective randomized study with radiotherapy and ICRF 159 (1,2-(3,5-dioxopiperazines-lyl)propane) (author's transl)]. In a clinical randomized trial of 40 patients with inoperable lung carcinoma the success of radiotherapy alone (5000 rads) was compared with a combined modality with radiotherapy (5000 rads) and ICRF 159 (250 mg p.d.). There was no difference in survival rates but haematological toxicity (leucocytes, erythrocytes, platelets and haemoglobin) was marked in patients with combined treatment. In patients with oat-cell-carcinoma survival rates seem to be better after combination therapy.


Corrections to megavoltage depth-dose values due to reduced backscatter thickness. Multiplicative corrections for percent depth-dose values were measured for situations with nonmaximal backscatter because of reduced thickness of the irradiated phantom. Data were obtained for common clinical field sizes for a 60Co beam as well as beams from a 2.5-MV and a 4.0 MV generator. Functional forms, which summarize the results and include field size effects, depth, and thickness of the backscatter medium as variables, were obtained by regression analysis.


On the choice of material for half-value-layer measurements for megavoltage x rays. The relative sensitivity of various materials for the measurement of half-value-layer thickness has been calculated for bremsstrahlung x ray spectra in the energy range 5-40 MeV. It is concluded that low-atomic-number materials such as water are more sensitive to changes in spectral quality of megavoltage x rays than high-atomic-number materials such as lead.


Physical characterization of 45-MV photon beams for use in treatment planning. Central-axis percentage depth doses and tissue-maximum ratios (TMR) for 45-MV photon beams from a betatron have been measured in water. Also the influence of field size and collimator scatter on the dose in the buildup region have been investigated. The maximum dose for TMR has been shown to occur at a point about 2 cm deeper than the maximum dose for percentage depth dose. This difference is significant in the characterization of the photon beam at this high energy. The measured physical data have been computerized for use in routine treatment planning. Computer-gererated beams have been found to be in close agreement with measured isodose curves. Computer-generated isodose distributions for typical clinical irradiation techniques have been verified using RP/V film in an Alderson phantom.


Practical dosimetric considerations of a 10-MV photon beam. An overall practical dosimetric study of a 10-MV photon beam produced by a Varian Clinac-18 linear accelerator is presented. In particular measurements were made to provide data which could be utilized in computerized dosage calculations using the concept of dividing the radiation beam into primary and scatter components. From the measured percentage depth doses, tissue-phantom ratios are calculated. Special consideration is given to the derivation and mesurement of zero-area tissue-phantom ratios such that scatter-phantom ratios could be obtained. The computer techniques were tested under a number of specified conditions by comparing the calculated results to the measured data. The variation of dose with field size and distance is considered and attenuation data for shielding, wedge and compensating materials is provided.


Characterization of a combined DNA initiation and cell division mutant of Bacillus subtilis. The temperature-sensitive mutation in Bacillus subtilis 168-134ts, a conditional lethal DNA initiation mutant, was transferred to the minicell producing strain, CU 403 div IV-B1, to study he relationship of DNA synthesis to cell division. Markers in the combined mutant were verified by transduction. DNA replication kinetics, genome location by autoradiography, and clonal analysis of cell division patterns during spore outgrowths were investigated. Growth of the double mutant at the restrictive temperature results in an impressive reduction of the percentage cell length covered by DNA grain clusters (60.2% at 30 degrees C compared to 8.6% after 2 h at 45 degress C). The probability of a minicell producing division in double mutant clones is essentially the same at 30 degrees C and during the initial 2-3 h growth at 45 degrees C at which time lysis begins. Residual division at 45 degrees C is attributable to processes initiated at 30 degrees C. The CU 403 div IV-B1, 134ts, double mutant divides about 25% as frequently relative to growth as do wild type CU 403 clones when incubated at permissive temperature. This is approximately 15% greater division suppression than previously found in the CU 403 div IV-B1 mutant strain, and is presumably due to interactions of the mutant gene products both of which affect DNA.


[Intracellular endosymbiose in lower animals - its dissemination and adaptation (author's transl)]. Numerous species of animal, both protozoa and metazoa, regularly with live intracellularly associated microorganisms (bacteria, fungi, algae). The metabolic and physiological dependence frequently goes so far that the one symbiosis partner is incapable of life without the other. Numerous mechanisms therefore take care of the adequate accomodation of the microorganisms and for the symbiosis partners to remain together from generation to generation. Selected examples show the wide dissemination of intracellular symbiosis in the animal kingdom and particular types of mutual adaptation. The cellular biological aspects permit comparisons with the behavior of pathological milcroorganisms.