The cancer-family syndrome: a pragmatic basis for syndrome identification. We report a family manifesting the cancer-family syndrome in which 11 family members had colonic carcinomas (predominantly involving the proximal colon, in the absence of polyposis), with an average age at onset of 35 years. Three women had endometrial or endocervical cancers. The kindred is notable in that its full evaluation was predicated upon the recognition of features consistent with the cancer-family syndrome in only two sisters. The ascertainment and evaluation of the kindred demonstrates the clinical utility of regarding such criteria (early cancer onset, multiple primary cancers, proximal colonic involvement) as a basis for selecting cases for more thorough family-history evaluation. Although such selection criteria are not pathognomonic for the syndrome, identification of a more extensive family cancer history sometimes enables the initiation of a highly specific cancer surveillance program. Specific attention has been given to the problems of screening patients at risk for the development of proximal colonic cancer, an important feature of the cancer-family syndrome. Innovative operative management is also indicated, such as total colectomy for initial colonic cancer, and consideration of prophylactic hysterectomy for women with colonic cancer (because of the high risk of development of endometrial carcinoma).


Prolapse of the rectum in young men: treatment with a modified Roscoe Graham operation. Twenty-two cases of massive rectal prolapse were treated by the modified Roscoe Graham procedure. In this series, the disease was more common in young men. Intestinal schistosomiasis was present in most cases. The value of the technique in maintaining normal ejaculatory function is discussed.


Late development of colorectal cancer subsequent to pelvic irradiation. Two cases of irradiation-associated carcinoma of the colon are reported and the literature reviewed. The clinical courses and operative difficulties in treating these patients are emphasized. The necessity for life-long follow-up examinations with proctoscopic and barium-enema evaluations in high-risk patients is stressed. Irradiation-associated carcinoma of the colon occurs almost exclusively in women, but should be investigated in patients of either sex who live for long periods after pelvic irradiation.


Intussusception with incarceration of a cystadenoma of the appendix: case report and review of the complications of appendiceal adenomas. Fifty benign epithelial neoplasms were encountered during the examination of more than 30,000 appendectomy specimens in the Laboratory of Surgical Pathology, Columbia University. In 44 cases, the neoplasms were papillary cystadenomas; in 11 of these cases, there were complications, all thought to have been caused by abnormal accumulations of mucus. We have reported a unique case of an incarcerated intussusception, and attempted to explain the pathogenesis of this unusual complication. We have also summarized the existing medical literature on the subject of intussusception of adenomatous lesions of the appendix.


The significance of a "positive" rectal examination in acute appendicitis. The results of rectal examinations of 495 patients with suspected acute appendicitis were correlated with six other variables from the patients' histories and results of physical examinations. Positive rectal examination results were recorded for 46 per cent of all patients with acute appendicitis and for 53 per cent of those with normal appendices. The diagnosis of acute appendicitis should not be based solely or primarily on the results of the rectal examination. The examination should, however, be performed in all suspected cases of appendicitis to rule out gynecologic and urologic disease.


Effect of bovine pancreatic polypeptide on basal pancreatic and biliary outputs in man. Basal pancreatic and biliary outputs were examined in seven healthy volunteers during intravenous infusion of bovine pancreatic polypeptide (BPP) at a mean dose of 320 pmol/kg/hr. BPP significantly (P less than 0.02) inhibited outputs of trypsin and bilirubin, without affecting bicarbonate. These studies suggest the possibility that pancreatic polypeptide may have a role in the regulation of biliary and pancreatic enzyme secretion in man.


Renal hemodynamics and the renin--angiotensin system in cirrhosis: relationship to sodium retention. Renal hemodynamics and the renin-angiotensin-aldosterone system were investigated in 15 cirrhotic patients without renal failure on controlled sodium intake of 140-160 mEq/day and related to the degree of sodium retention as measured by urinary sodium excretion. Fourteen patients were free of clinical ascites when studied. The distribution of renal blood flow was measured by the noninvasive technique of computerized radioisotope renography. In 11 patients, outer cortical renal plasma flow, expressed as a percentage of total effective renal plasma flow, was directly proportional to sodium excretion (P less than or equal to 0.01). Three patients with severe sodium retention (UNa.V less than or equal to 10 mEq) had estimated outer cortical renal plasma flows of less than or equal to 274 ml/min/1.73 M2 as compared to eight cirrhotics with better (UNa.V greater than or equal to 50 mEq) sodium tolerance (mean = 438 ml/min/1.73 M2). A significant inverse correlation (P less than or equal to 0.01) existed between outer renal cortical blood flow and plasma renin activity. No significant relationship was observed between glomerular filtration rate, total effective renal plasma flow, plasma aldosterone concentration and sodium excretion. These results provide further evidence that a renal vascular abnormality exists in cirrhosis, and that diminished outer cortical renal perfusion is related to the elevated renin levels and sodium intolerance observed in cirrhotic patients.


Sensitivity of bile acid breath test in the diagnosis of bacterial overgrowth in the small intestine with and without the stagnant (blind) loop syndrome. The bile acid breath test was studied to examine its sensitivity for establishing the diagnosis of bacterial overgrowth in comparison to that of the Schilling test and small-intestinal cultures in 12 patients with a stagnant (blind) loop syndrome, as well as in 38 patients who had other conditions with suspected bacterial contamination of the small intestine. The presence of bile acid malabsorption was excluded in all 50 patients by studies of fecal excretion of radioactively labeled bile acids. The bile acid breath test was positive in 100% (12/12) of the patients with a stagnant (blind) loop syndrome, whereas 92% (11/12) had a positive Schilling test and 75% (9/12) a positive small-intestinal culture. The abnormal tests improved only in 2 of 4 patients treated with tetracycline. In the group of 38 patients without demonstrable dilated or blind loops of small bowel who were suspected of having bacterial contamination of small bowel, the bile acid breath test was positive in 53% (20/38), the Schilling test in 39% (15/38), and the small-intestinal culture in 45% (17/38). The difference in the incidence of positive results between the tests in the two patient groups was statistically not significant. The findings of these studies have the following diagnostic implications: (1) Bile acid breath test, Schilling test, and cultures of aspirates from the upper small bowel are of comparable sensitivity in the detection of bacterial overgrowth in the small intestine. (2) A negative bile acid breath test makes the diagnosis of a stagnant (blind) loop syndrome very unlikely.


Liver involvement in secondary syphilis. The results of biochemical assessment of liver function are reported in 18 patients with secondary syphilis. In 9 of the patients, enzyme abnormalities were found and the most consistant abnormality was an elevated alkaline phosphatase. Six of the patients had a liver biopsy before treatment and the main findings were mononuclear cell infiltration around the central veins and portal tracts. In all patients, the biochemical abnormality returned to normal with treatment of the syphilis.


Gastritic glandularis et cystica profunda: a report of three cases with discussion of etiology and pathogenesis. Three cases of gastritis glandularis et cystica profunda are presented, two associated with severe chronic gastritis and the other with invasive gastric carcinoma and chronic gastritis. This poorly known entity consists of benign downgrowths of deep gastric glands through the muscularis mucosae into the submucosa. The pattern is primarily adenomatous with secondary cyst formation, which varies in extent and severity. The lesion is related to the chronic gastritis but why it should occur so rarely in such a common condition as chronic gastritis remains obscure. More documented cases are needed before a meaningful analysis can be attempted.


Value of pancreatic-type isoamylase assay as an index of pancreatic insufficiency. The study here reported was undertaken to assess the value of assay of the specific isoamylase form arising from the pancreas (P-type) as an index of pancreatic exocrine insufficiency. Measurements were made of serum total amylase activity, serum P-type isoamylase activity, and the amount of P-type isoamylase relative to creatinine (Upam/Ucr) in the urine in a series of patients with clinically suspected chronic pancreatitis and pancreatic insufficiency as determined from the pancreatic secretory response to secretin stimulation. Abnormally low values for P-type isoamylase in the serum and urine of these patients were infrequent. Conversely, values within the normal ranges for serum P-type isoamylase and Upam/Ucr were common. It is concluded that while subnormal values for P-type isoamylase in the serum and urine may be viewed as supportive evidence for pancreatic insufficiency, failure to find such values does not exclude this condition.


Afferent loop obstruction presenting as obstructive jaundice. The first case of obstructive jaundice secondary to a chronic afferent loop obstruction has been reported. The cause of the obstructed afferent loop was found to be a carcinoma of the gastric pouch occurring 25 years after surgery for peptic ulcer disease. The failure to develop any evidence of pancreatitis despite marked dilatation of the biliary tree and gall bladder suggests the existence of an independent functioning pancreatic sphincter, perhaps the sphincter of Boyden.


Twelve-year history of gastrointestinal bleeding in a patient with calcific aortic stenosis and hemorrhagic telangiectasia. A case has been presented of a patient with a 12-year history of unexplained gastrointestinal bleeding who developed severe aortic stenosis. Small telangiectasia were finally noted on his lip and gastroscopy revealed gastric and duodenal telangiectasia though he had no history of epistaxis and an unremarkable family history. Patients with aortic stenosis and unexplained gastrointestinal bleeding should be carefully evaluated for hemorrhagic telangiectasia in spite of a negative family history and no visible evidence of telangiectasia.


Effect of ursodeoxycholic acid administration on biliary lipid composition and bile acid kinetics in cholesterol gallstone patients. The effect of ursodeoxycholic acid (UDCA) on bile lipid composition and bile acid kinetics was evaluated in seven cholesterol gallstone patients following one month of UDCA administration (12 mg/kg/day). UDCA administration induces a significant reduction in the cholesterol saturation index (SI). After UDCA treatment, UDCA becomes the predominant biliary bile acid while chenodeoxycholic, cholic, and deoxycholic acid are significantly reduced. UDCA pool significantly increases, and chenodeoxycholic, cholic, and total bile acid pools significantly decrease. The reduction in bile lithogenicity during UDCA administration suggests that UDCA may be useful for cholesterol gallstone treatment in man.


Ischemic hepatitis.

Ischemic hepatitis. Seven patients with cardiovascular disease had clinical episodes and marked transaminase elevations that suggested viral hepatitis, but all had morphologic evidence (from liver biopsy or autopsy specimens) that documented centrilobular necrosis (ischemic hepatitis) with no evidence of viral or drug injury. Several also had moderate or marked passive congestion of the liver so the liver biopsies of 15 additional patients were retrospectively reviewed. In this latter group congestion alone was associated with normal or minimal elevation in transaminases while all patients with notable (greater than 5 times normal) transaminase elevations had centrilobular necrosis. Congestion alone, no matter how severe or prolonged, seems to do little if any damage to the liver. Centrilobular necrosis, or ischemic hepatitis, correlates with significant hypertransaminasemia, appears to result from failure of hepatic perfusion (with or without preceding hypotension), and presents with clinical and laboratory manifestations that suggest viral hepatitis.


Analysis of ascitic fluid in cirrhosis.

Analysis of ascitic fluid in cirrhosis. In order to determine the composition of "normal" ascitic fluid, the results of analysis of the first paracentesis on 347 consecutive cirrhotic patients with ascites at the West Haven Veterans Administration Hospital between 1955 and 1976 were examined. The ascites was considered "normal" in 259 patients. Bacterial peritonitis was present in 51, malignant ascites in 18, pancreatitic ascites in 15, and ascites of other types in 4 patients. Normal ascites is sterile, usually clear, and contains 281 +/- 25 leukocytes/mm3 (mean +/- SEM), 27 +/- 2% of which are polymorphonuclear. In spontaneous bacterial peritonitis the fluid is usually cloudy, contains 6084 +/- 858 white blood cells/mm3, 77 +/- 4% of which were PMN and culture is positive for a single bacterial species, usually enteric in origin. Malignant and pancreatitis ascites are sterile, often cloudy, and contain an average of 696 +/- 273 and 1821 +/- 833 leukocytes/mm3, respectively, about half of which are polymorphonuclear. Amylase activity is increased in pancreatitic ascites, but not in other types of ascites. Stained smears of sediment for bacteria are often positive in bacterial peritonitis, but not in the other categories. Neither the specific gravity, protein concentration, nor glucose level is useful in the differential diagnosis of ascites. Based on the critical number of leukocytes alone, (500/mm3), one can accurately differentiate infected from uninfected fluid in over 90% of ascitic patients.


Rapid development of cirrhosis secondary to squamous cell carcinoma of the common bile duct. A 68-year-old male underwent cholecystectomy with a normal operative wedge liver biopsy. Five months later he presented with secondary biliary cirrhosis and signs of portal hypertension and hepatocellular failure. At autopsy, a squamous cell carcinoma of the bile duct was found. This case represents an unusually rapid development of cirrhosis secondary to extrahepatic biliary obstruction with documentation of normal liver histology five months prior to his last admission.


[Skateboards: a dangerous toy? (author's transl)]. Eighteen persons (average age 12.4 years) with injuries from skateboard accidents were admitted between 1 March to 5 June, 1977--4.4% of all accidents and 7.5% of all sports accidents treated during this interval. These kinds of accidents are now in fourth place as to frequency, after accidents during play (81), bicycling (45), football (35) and motorcycling (28). To avoid skateboard accidents attention must be paid to technically high-grade equipment, reasonable skill and training, and restriction of skateboarding to enclosed areas, as well as protective clothing.


[Percutaneous transhepatic cholangiography with the Okuda or Chiba needle (author's transl)]. Introduction of the thin flexible needle (Chiba or Okuda needle) has revived percutaneous transhepatic cholangiography, even though there are more recent methods of investigating the biliary tract. Personal results in 65 patients demonstrate that the needle can be successfully introduced in all instances, as long as the biliary tracts are dilated, the success rate being 68% if they are not. The complication rate was 9.2%, but there was no death.


[Eosinophilia and reticulo-nodular lung changes: a problem in differential diagnosis (author's transl)]. A 55-year-old patient with reticulo-nodular infiltrations of both lungs and eosinophila had previously been living in the tropics for several months. The clinical triad suggested filarial infection. But the final diagnosis proved to be metastasizing adenocardinoma of the lung, as demonstrated at autopsy.


[Participation of health centers in the training of technical and auxiliary personnel]. The authors propose that the training of technicians and auxiliaries for health institutions must be geared to the historic, economic, and cultural setting of the health problems in a given region. To this end, training and health establishments must set for themselves coordinated, specific objectives designed to meet the community's real health needs. They suggest that a training service be set up in health centers, with programs based on the participation of teachers and trainees and designed to bring the latter into direct contact with the health problems they will encounter in their future employment.


Implications of off-shore medical schools in the Commonwealth Caribbean. Facilities existing and planned in the University of the West Indies for training the medical manpower requirements of the Caribbean Commonwealth are adequate and can be extended to meet additional future needs. No valid justification exists, therefore, for the development in the area of off-shore medical schools promoted by profit-oriented entrepreneurs who have little or no experience in medical education and aimed principally at students from the United States who have failed to secure admission to an American medical school. Such students are liable to experience serious disappointments either in transferring to the United States for the clinical half of their course or in qualifying for entrance to postgraduate training programs sponsored by American educational authorities. Participation in the establishment of such medical schools has already generated unfavorable publicity, which can be ill-afforded by the countries of the English-speaking Caribbean.


[Development of human resources for working in environmental health]. This paper was presented as a reference document in the First Meeting of the PAHO/WHO Textbook Program Committee for the Teaching of Sanitary Engineering and Environmental Sciences, held in Santo Domingo, Dominican Republic, from 24 to 26 November 1977. It analyzes the human resource development process in terms of the basic components: planning, development itself, and utilization. Its principal objectives are: to encourage the performance of studies and research on human resources in environmental health as sources of information for taking decisions, making policy, and drawing up training plans; to suggest ways of improving the quality of education and training services; to encourage the development of suitable techniques and methods for determining human resource needs; and to highlight some recent studies and publications on human resources in relation to environmental problems.


Follow-up study of chronic gastric erosions. Chronic gastric erosions were detected with a frequency of 4.4% in 8,468 patients over the six year period from 1971 to 1977. The lesions were usually multiple, chain-like or clustered, along the greater curvature. The age group most often afflicted was the 50-60 year olds, and male predominance were three to one. In one-third of the cases, chronic erosions were found in combination with gastric or duodenal ulceration. Longterm observation of 64 patients over a period of four and a half years revealed no change in the condition in 50%, increase, decrease or complete disappearance of the lesions were found in the remaining 50%. In 10% chain-like multiple erosions developed into a persisting fold in the gastric mucosa. No evidence suggesting that erosive lesions lead to chronic ulceration or development of either polyps or malignancy within 4 1/2 years was recorded, nor was there any association with gastric protein loss.


Gastroduodenal candidiasis occurring without underlying diseases (primary gastroduodenal candidiasis). Report on two cases. Two cases of primary and isolated gastroduodenal candidiasis are described. The diagnosis of the mycotic infection was based on the discovery of hyphae in the biopsy obtained through the gastroscope (Olympus GIF-K). Clinical, endoscopic and histologic appearances are discussed.


Endoscopic monitoring of the gastric lesser curve following proximal gastric vagotomy. The lesser curve gastric mucosa was examined endoscopically in 60 patients, 3 to 6 days after performing proximal gastric vagotomy. Minor and equivocal changes were seen in only 3 patients. Three patients had adjunctive splenectomy but did not show any evidence of mucosal vascular insufficiency in the proximal stomach. Our findings do not confirm a report from other investigators of lesser curve gastric ulceration attributed to partial ischaemia short of lesser curve necrosis. Endoscopy should be considered in patients developing unexplained features following proximal gastric vagotomy.


The choledochoscopic and histopathological grading of choledochitis. The choledochoscopic photographs of 91 and 119 patients with cholecystolithiasis and choledocholithiasis respectively were reviewed on the basis of endoscopic grading. By analogy with the system of the grading, the diseases were also divided into four histopathological gradings. Choledochoscopy provides an alternative approach to the diagnosis of choledochitis, which is also corroborated by the histopathological data in calculous diseases.


Diminutive colonic polyps--clinical significance and management. Of 300 diminutive polyps (up to 5 mm) found at colonoscopy, 114 were neoplastic (37 per cent) and thus possible precursors of carcinoma. This suggests that all colonic polyps, regardless of size, should if possible be extirpated or coagulated. As polyps of this small size often escape detection roentgenologically, especially by conventional technique, colonoscopy should be extended to involve the entire colon. This is because diminutive polyps, especially of neoplastic type, are common also in the proximal part of the colon.


Endoscopic duct obstruction in chronic pancreatitis. Ligation of Wirsung's duct or obstruction with a glue may be an alternative to pancreatectomy in patients with intractable pain due to chronic relapsing pancreatitis. In 10 patients obstruction of Wirsung's duct was performed via endoscopic retrograde instillation of an alcoholic aminoacid solution into the ductal system. All patients became free of symptoms within one week; no complications were seen. Long-term follow-up data, however, suggest that clinical improvement may be persistent in only about 50 per cent of the patients. Further data are necessary before endoscopic obstruction of Wirsung's duct can be recommended as a conservative method in the treatment of chronic pancreatitis.


Bipolar snare polypectomy--a safer technique for electrocoagulation of large polyp stalks. Conventional colonoscopic snare polypectomy for large polyps with stalk diameter of 1.5 cm or more carries a significant risk of haemorrhage after transection, probably due to "leak currents". The use of a return-electrode applied to the base of the polyp after snaring instead of the conventional patient-plate permits bi-polar polypectomy which is both safer and more efficient.


Mediastinal lymph node biopsy in sarcoidosis. Mediastinoscopy, in the skilled hands of a thoracic surgeon has proved to be a safe, cosmetically accepted procedure with negligible complications. It has yielded a high rate of diagnostic lymph node tissue; overall greater than 82% among patients with sarcoidosis, including patients presenting with pulmonary mottling only or with a normal chest radiograph. Among patients with lymphatic tuberculosis it enabled the isolation of human M. tuberculosis following culture of the lymph node removed on Löwenstein-Jensen medium in greater than 79% of cases. A precise histological diagnosis was obtained in all 14 patients presenting with hilar and/or paratracheal lymphadenopathy attributable to malignant disease.


Endoscopic perforation of the hypopharynx: anatomy of a disaster. An initially unrecognized endoscopic perforation of the hypopharynx provided a rare photograhic record of endoscopic appearances from within the mediastinum. The problem of endoscopic perforations is briefly reviewed and analyzed.


Leiomyosarcomatosis of the gastrointestinal tract. A case report of a patient suffering from diffuse leiomyosarcomatosis of the gastrointestinal tract is presented. The endoscopic features of the lesions localized in the stomach, the small bowel and the colon are compared with the radiological data. A description of the pathology of these polypoid lesions is given. The origin of this widespread leiomyosarcomatosis of the gastrointestinal system is discussed.


Purulent cholangitis and hepatic abscess after choledochoduodenostomy diagnosed by ERCP. The authors report on a case of purulent cholangitis and hepatic abscess developing 5 years after choledochoduodenostomy, diagnosed by means of ERCP. They believe viscous pus adhering to the wall of the bile ducts to be responsible, as a mechanical factor, for causing the inhibiting bile discharge. After the ERCP examination, the patient became free from complaints, and could be discharged.


Phonocardiography in the horse: 1. The intracardiac phonocardiogram. Using microtransducers, the intracardiac phonocardiogram was recorded in 8 horses from the right heart and in 6 of them also on the left side. All 4 heart sounds were recorded but not in all sites. Their timing was related to pressure events. Systolic ejection murmurs were recorded in both the pulmonary artery and the aorta. Diastolic murmurs were recorded in 2 horses with aortic regurgitation, with maximum amplitude in the left ventricle. The findings were similar to those reported in man and agree with some of the recent concepts on heart sound production.


Atresia of the nasolacrimal orifice in two thoroughbreds. Two cases of bilateral atresia of the nasolacrimal orifice are described. The presenting sign was a persistent ocular discharge, clear in the one case and purulent in the other. Treatment by the creation of a fistula between the distal extremity of the blind ending duct and the nasal cavity was successful in both cases.


Radiographic evidence of impaired pulmonary function in laterally recumbent anaesthetised horses. Studies in conscious and anaesthetised ponies demonstrated that starvation, anaesthesia and changes in body position influence the radiographic appearance of the lungs in the lateral and dorsoventral views. Radiographic appearances could not be closely correlated with blood gas values, but they suggested that the volume of the lowermost lung of the laterally recumbent animal is greatly reduced.


Treatment of periocular tumours of horses using radioactive gold198 grains. The literature is briefly reviewed concerning the clinical features of equine cutaneous tumours. The data from 19 horses with periocular skin tumours are reported together with the results of their treatment by implantation with radioactive gold198. The principles governing the implantation of radioactive sources are explained and a method for computing the initial activity of the sources is outlined. Five histologically different tumour types were treated in this series of 19 horses, 2 horses were bilaterally affected. The techniques of implantation using a simple needle/stillette combination and a purpose built gold grain implantation gun are described and the postoperative course of the animals is traced. The treatment was successful in ablating the tumour mass and preventing regrowth in 19 of 21 periocular tumour groups. The cosmetic effects of the treatment were found to be satisfactory. Emphasis is laid on the care needed in handling the radioactive material and on the need for a thorough understanding of the principles involved in radiotherapy. Doses received by the operator during an implantation procedure are quoted which show that the technique is safe as well as being effective.


Paradoxical excitement following the intravenous administration of azaperone in the horse. The rapid intravenous administration of the butyrophenone tranquilliser, azaperone, at a dose rate of 0.29-0.57 mg/kg body weight resulted in the immediate onset of excitement and ataxia of varying degree in over half the animals. The severity of the reaction appeared to be related to the size of the animal. Other side effects such as salivation, sweating, muscle tremor and vocalisation were also observed. The possible causes of this paradoxical reaction to the tranquilliser are discussed.


Body composition of the horse.

Body composition of the horse. Seventeen horses were dissected and their organs and tissues weighed. The results of these dissections are presented together with comparisons of the data with that already available in the literature. Predictive equations for organs and tissue weights are also given which were derived by comparison of linear and allometric regression models using 4 different body weight indices.


Fractures of the proximal sesamoid bones in thoroughbred foals. Eighteen cases of fractures of the proximal sesamoid bones in Thoroughbred foals are described. Most of the fractures were in foals under 2 months old and all but one occurred in the forelegs. The bones commonly fractured when the foal galloped to exhaustion trying to keep up with its dam in the paddock. The types of fracture varied but a simple fracture of the medial sesamoid was most frequent and the majority were towards the base of the bone. Six foals sustained a fracture of more than one sesamoid bone and one foal fractured all 4 proximal sesamoid bones in its front legs. Treatment included box rest and the surgical removal of the separated piece of sesamoid bone. Only 3 of the foals treated have raced. One of these was treated surgically.


Pre-renal azotaemia in a pony with an oesophageal obstruction. A case of pre-renal azotaemia is described in a 12 year old pony resulting from oesophageal obstruction of 8 days duration. Blood urea nitrogen, creatinine, calcium, inorganic phosphate, sodium, potassium, chloride and bicarbonate concentrations were monitored throughout the recovery period. After relief of the obstruction normal blood concentrations were quickly restored.


Foreign body obstruction of the small colon in six horses. Six horses, which had a foreign body obstruction of the small colon showed abdominal pain of progressing severity and intestinal tympany. On rectal examination the caecum and large colon were distended with ingesta and gas but the obstructing mass could be palpated in only 3 cases. All horses had elevated indirect blood pressure and in 3 there was also fluid distension of the stomach. Only one horse had known access to foreign material in the diet, but a further 3 were related to an exceptionally dry climate period. Five of the 6 horses recovered following surgery.


A three-year study of the effects of exercise on active young men. The changes occurring in leanness-fatness, physical working capacity, isometric strength, and motor ability have been followed in 20 highly active young adult males over a period of 3 years. Body weight and estimated percentage of fat increased over the 3-year period but there were no significant changes in the other variables. Within the 3-year period physical working capacity and relative leanness-fatness showed significant variations which are attributed to the state of training of the subjects. Strength was found to be highly related to somatotype but was apparently not influenced by the state of training; changes in relative leanness-fatness occurring with training were found to be influenced by somatotype.


[Adrenergic response to intense muscular activity in sedentary subjects as a function of emotivity and training]. Seven male sedentary human subjects were studied during intense muscular work (80% of maximal oxygen uptake) performed either for 15 min or until exhaustion (mean duration: 47 +/- 2 min). Plasma catecholamines were estimated before and after the experiment by means of an original fluorimetric assay. Epinephrine or norepinephrine were individually isolated from plasma and assayed in single extracts by a highly sensitive fluorimetric method. Epinephrine and norepinephrine levels as low as 15 ng per liter were detectable by this procedure in human plasma. The adrenergic pattern was found to be greatly different from one subject to another and related to emotivity: the effect of this factor was revealed by the predominance of epinephrine in plasma at rest or under exercise (ratio NA/A less than 1). In nonemotive subjects (ratio NA/A greater than 1 at rest) plasma epinephrine and norepinephrine increased progressively during exercise. Increments after exercise were higher for norepinephrine changes; however, the fact that epinephrine concentrations correlated significantly with norepinephrine suggests a simulataneous and coordinated stimulation of adrenal glands and orthosympathetic nervous system. In emotive subjects (ratio NA/A less than 1 at rest) the apprehension of muscular work promoted a difference in catecholamine responses: norepinephrine release was not affected by subject's anxiety, while epinephrine secretion, already elevated before the test, reached a high degree of magnitude in the first minutes of muscular work, remaining nearly constant until exhaustion. Physical training of nonemotive subjects, during 2 months with two intense exercises by a week, reduced strongly norepinephrine release after exhaustive muscular work. In the same conditions, the adrenal-medullary response was not significantly modified when compared with untrained subjects. Our results suggest that the adrenergic behaviour during exercise is a function of effort intensity to be supplied; catecholamines seem to be important factors in regulating body homeostasy during muscular work in man. In addition, emotive subjects exhibit amplified adrenal-medullary response, which may be related to psychological stimuli.


The effect of a four-month physical fitness program on a young and an old group matched for physical fitness. A young (X = 36.8 years) and an old (X = 52.9 years) group (n = 12) matched for physical fitness performed a graded exercise test at the beginning and after a 4-month physical fitness program consisting of calisthenics, jogging, and recreational activities. The purpose of the study was to determine if there were any differences in response to physical training in the two age groups of similar fitness. Sixteen physiological and four biochemical variables were measured. There was no significant difference in VO2 max between the young and old groups. Also, there were no significant differences between groups for serum total lipids, cholesterol, triglycerides, or glucose levels. The effects of the training program were similar for both the young and old groups.


Aerobic fitness and body fat of young British males entering the army. Aerobic fitness and percent body fat were measured in a sample of 438 male Army recruits between the ages of 17 and 30 prior to the commencement of training. The sample came from all areas of England and Wales. Aerobic fitness, as represented by maximal oxygen uptake (VO2 max), was predicted from the Astrand submaximal bicycle heart rate test. Body fat was predicted from four skinfold measurements. Total group means +/- SD were: age, 19.5 +/- 2.5 years; VO2 max 41.7 +/- 8.3 ml/kg . min; and body fat, 14.5 +/- 4.8% of body weight. VO2 max varied with age, athletic participation and aptitude score. No relationship was found with occupation of parent, prior civilian occupation or smoking severity. When adjusted for methodological differences, VO2 max was slightly below similar Army entrants in Norway and the United States.


Specificity of maximal aerobic power.

Specificity of maximal aerobic power. Several types of work tasks are used to assess maximal aerobic power (MAP) in humans. Although it is well established that these work tasks may yield different absolute MAP values, little is known about the extent of the specificity of each MAP work task. 30 moderately active young men were tested at random for MAP with five commonly used work tasks: cycling supine, cycling sitting, alternate arm cranking standing, walking on a treadmill, and stepping on a bench. Statistical analyses show that these five tests do not give equal MAP means, equal variances or equal covariances. Various correlation techniques indicate, furthermore, that the common variance between the five aerobic power measurements is at best moderate. It was estimated that the overall common variance for Max ml O2 . kg-1 . min-1 reached about 50% of the total variance. The most efficient linear loading of each test in the first principal component could account only for 75% of the observed variance in MAP. It is concluded that these five work tasks do not yield parallel test forms, that the practice of transforming one MAP value into another should be abandoned, and that the practice of generalizing from one MAP value to a theoretical general MAP of the human body is not justified.


The effect of weight-lifting exercise related to muscle fiber composition and muscle cross-sectional area in humans. Isometric and dynamic strength and endurance of knee extensors were tested in 18 young males. The relative composition of slow (ST) and fast twitch (FT) fibers in the vastus lateralis muscle was registered from needle biopsies. Thigh muscle volume was evaluated from ultrasonic measurements. Six subjects served as controls, six trained with 50%, and six with 80% dynamic strength three times per week for 7 weeks with 20 and 12 repetitions per session, respectively. The training load was adjusted to the increases in strength observed during training. Dynamic strength increased by 42.3% in the 80% group (p less than 0.01). In the control group and 50% group no significant increases were observed. Dynamic endurance: Controls showed no change. There was an over-all increase in the 50% group, while the 80% group only increased dynamic endurance for heavier loads. Isometric strength and endurance and fiber composition did not change in any group. In the 50% group the area of FT-realtive to ST-fibers increased 12.4% (p greater than 0.05). Dynamic strength relative to muscle cross section increased by 30% in the 80% group (p less than 0.01) positively correlated to relative content of FT fibers. The present results confirm the specificity of training and indicate that a high content of FT fibers is a prerequisite for a successful strength training.


Metabolic and temperature responses to physical exercise in thyroidectomized dogs. The purpose of the present work was to further elucidate the role of thyroid hormones in the control of body temperature and metabolism during physical exercise. Changes in rectal temperature (Tre), some parameters of exercise-metabolism and in the plasma noradrenaline (NA) levels were examined in eight dogs performing submaximal treadmill exercise to exhaustion before and after thyroidectomy (THY). The metabolic 'responses to adrenaline (A) infusion were also compared in intact and THY dogs. During the exercise performed by THY dogs Tre increases were markedly attenuated, plasma FFA level increases were reduced and the pattern of plasma NA changes was modified in comparison with control runs. The reduced exercise-induced FFA mobilization in THY dogs might be attributed to a lower activation of the adrenergic system in the later stage of exercise and to the weaker lipolytic action of catecholamines. The attenuated Tre increases during exercise performed by THY dogs and the exercise-hyperthermia described previously in dogs treated with thyroid ormones suggest that an optimum level of thyroid hormones is necessary to induce typical changes in body temperature during physical exercise.


[Calculation of thermally caused blood flow changes in a finger using thermographic skin temperature measurements (author's transl)]. The skin temperature changes of the third finger were registered with the help of an infrared camera during a cooling process of the hand and forearm of a male, 38-years-old subject. Using the system of formulae, explained in previous publications [4-7], it was possible to describe the blood flow changes in the finger. The results are: 1. A formula for the "pseudo thermal conductivity" (material constant of the thermal conductivity plus the convective contribution), which is similar to the formula used for theat release of the whole body [4], describes well the experimental results. The "pseudo thermal conductivity" is a measure for the specific blood flow and can be converted into it. 2. The "pseudo thermal conductivity" has a local maximum. 3. The position of the maximum is independent of the tissue temperature. The anatomical properties of the finger seem to determine the position of the maximum. 4. The maximum of the "pseudo thermal conductivity"--and therefore the maximal blood flow--increases stronger than linearly with the tissue temperature.


Biochemical changes in a 100 km run: proteins in serum and urine. Eleven male subjects took part in a 100 km running competition. Alterations in the total plasma protein and in ten individual plasma protein concentrations in blood and urine were measured prior to the run, immediately after and after 1 day of recovery. Five individual proteins showed a 7-10%, and lysozyme a 40%, increase in the plasma after the run. On the contrary, the haptoglobin concentration fell to 40% of its pre-race level. None of these variations were correlated with the plasma volume change. The present data showed a moderate hemolysis, as evidenced by plasma lysozyme and hemoglobin-haptoglobin binding. The urinary excretion of plasma proteins was slightly increased, especially albumin and alpha1-acid-glycoprotein. The renal clearance of plasma proteins revealed that the 100 km run induced a moderate increase of glomerular permeability without any signficant change in the tubular reabsorption process.


[Investigations of the validity of e.a. müller's "leistungspulsindex" (author's transl)]. In order to obtain a critical review of E.A. Müller's "Leistungspulsindex", we worked out a functional representation of that index, using a simple physiologic-mathematic model of the oxygen transport system. We found that the LPI is influenced by the economy of the oxygen transport system and that it is inversely proportional to stroke volume, caloric coefficient, and to the efficiency of muscular work. Based on the theoretic analysis we tried to interpret the results of an investigation carried out with pupils of an coeducative intermediate school (years of birth 1964, 1965, 1966). We obtained statistically significant correlations (p less than 0.1%) between LPI and parameters characterizing performance capacity (PWC170, heart rate at 100 W work load) and between LPI and body weight. The results of both the theoretic and experimental investigation indicate a dependence of the LPI on factors influenced by physical training processes, but no evidence was found, however, on an interrelationship between LPI and congenital factors of physical performance.


The amplitude distribution of surface EMG in static and intermittent static muscular performance. A measure of the variation of load on individual muscles or parts of muscles may be obtained by estimating the amplitude probability distribution function (APDF) of the myoelectric signal. In a study of elbow flexor muscular performance in static and intermittent static low level muscular contractions, the APDF was computed from the surface EMG obtained from the belly of the brachial biceps muscle. The APDF was also computed from the simultaneously recorded force signal. The APDF of the myoelectric signal and of the force signal were similar, indicating that the APDF of the myoelectric signal closely reflects the muscular load in non-fatiguing muscular contractions. The effect of the time constant in lowpass filtering when processing the surface EMG-signals was also studied. A suitable time constant appears to be in the range of 50-100 ms.


DNA polymerases of anucleated cells. Isolation and characterization of two DNA polymerases from human platelets. Two different DNA polymerases have been purified and characterized from human platelets. In the mitochondrial fraction a unique activity of the polymerase gamma type has been found. The same enzyme is found in the extramitochondrial supernatant. A second DNA polymerase, called 'cytoplasmic' DNA polymerase has been found in the 10000 x g supernatant of human platelets. The following properties of the latter DNA polymerase from human platelets are identical to those of DNA polymerase alpha from normal cells: DEAE-cellulose and phosphocellulose chromatography, size, thermal stability, phosphonoacetic acid and ethidium bromide inhibition. However, some of its properties, like high resistance to N-ethylmaleimide and the lack of DNA polymerization using synthetic RNA primers, are those of DNA polymerase beta.


Photoreactions of cytochrome b563 and f554 in intact spinach chloroplasts: regulation of cyclic electron flow. In intact spinach chloroplasts cytochrome b563 and cytochrome f show an antagonistic redox behaviour in the extent and kinetics of light/dark-induced absorbance changes. The extent of cytochrome b563 photoreduction appears to be influenced by the redox state of plastoquinone suggesting a regulation of cyclic electron flow at this level. Far-red illumination induces a membrane state with altered redox reactions of both cytochromes at a more oxidized level.


Response of specific transfer-ribonucleic-acid levels to amino-acid deprivation in Friend leukemia cells. In eukaryotes, the levels of specific tRNAs are closely correlated with the demands for their cognate amino acids in protein synthesis. To account for this phenomenon, we have proposed that the extent of aminoacylation of a given tRNA species in vivo controls the relative rate of synthesis or turnover of that species. Previously, we reported that Friend leukemia cells respond to histidine deprivation by increasing their relative level of tRNAHis by as much as two-fold, with no change in the relative level of tRNALeu. In this paper, we show that deprivation of leucine or tryptophan also causes a specific increase in the relative level of tRNAs cognate to the deprived amino acid. At least in the case of tRNATrp, the increases in relative tRNA levels are preceded by extensive declines in the steady-state extent of aminoacylation of the tRNA in vitro. We also find that different isoacceptors may respond differently to amino acid deprivation. These results suggest that decreased extents of aminoacylation of a given tRNA species in vivo cause increases in the relative rate of synthesis or decreases in the relative rate of degradation of that species.


Properties of two molecular forms of beta-glucuronidase from the mollusc Littorina littorea L. The occurrence of the two molecular forms, I and II, in the beta-glucuronidase of the liver (hepatopancreas) from the marine mollusc Littorina littorea L. has been demonstrated for the first time. The two forms have been purified 355-fold and 1262-fold, respectively. Form I and II of beta-glucuronidase behave differently on DEAE-cellulose chromatography, polyacrylamide gel disc electrophoresis, isoelectric focusing (pH 5.5 and 4.2, respectively), optimum pH (4.4 and 3.4--4.1, respectively), thermal stability, Km (1.2 mM and 0.5 mM with p-nitrophenyl beta-D-glucuronide, 0.3 mM and 0.15 mM with phenolphthalein beta-D-glucuronide as substrates for form I and II, respectively) and V. Their molecular weight, estimated by gel filtration through Sephadex G-200, was about 250000 for both forms. Several subunits were separated by polyacrylamide gel electrophoresis in presence of sodium dodecyl sulphate. This beta-glucuronidase is a glycoprotein, but sialic acid(s) were not detected. The enzyme was very active on synthetic substrates and also on hexasaccharides and tetrasaccharides containing glucuronic acid residues with beta 1 leads to 3 linkages; it had practially no activity on certain glycosaminoglycans. Hg2+ and glucaro-1,4-lactone were very effective inhibitors of this enzyme; the latter by a competitive mechanism.


Singlet oxygen formation by a peroxidase, H2O2 and halide system. Evidence for singlet oxygen formation has been obtained for the lactoperoxidase, H2O2 and bromide system by monitoring 2,3-diphenylfuran and diphenylisobenzofuran oxidation, O2 evolution, and chemiluminescence. This could provide an explanation for the cytotoxic and microbicidal activity of peroxidases and polymorphonuclear leukocytes. Evidence for singlet oxygen formation included the following. (a) Chemiluminescence accompanying the enzymic reaction was doubled in a deuterated buffer and inhibited by singlet oxygen traps. (b) The singlet oxygen traps, diphenylfuran and diphenylisobenzofuran, were oxidized to their known singlet oxygen oxidation products in the presence of lactoperoxidase, hydrogen peroxide and bromide. (c) The rate of oxidation of diphenylfuran and diphenylisobenzofuran was inhibited when monitored in the presence of known singlet oxygen traps or quenchers. (d) Oxygen evolution from the enzymic reaction was inhibited by singlet oxygen traps but not by singlet oxygen quenchers. (e) The traps or quenchers which were effective inhibitors in the experiments above did not inhibit peroxidase activity, were not competitive peroxidase substrates and did not react with the hypobromite intermediate since they did not inhibit hydrogen peroxide consumption by the enzyme. Using these criteria, various biological molecules were tested for their reactivity with singlet oxygen. Furthermore, by studying their effect on oxygen release by the enzymic reaction, it could be ascertained whether they were acting as singlet oxygen traps or quenchers.


Binding of oligonucleotides to the disk of tobacco-mosaic-virus protein. The trinucleoside diphosphate A-A-G and the hexanucleotide fraction from a ribonuclease I digest of yeast RNA have been soaked into crystals of the disk aggregate of tobacco mosaic virus protein. At high concentrations these cause disruption of the crystal, probably by mimicking the normal nucleation of assembly. At lower nucleotide concentrations the crystals remain intact and the differences caused by nucleotide binding have been studied by X-ray diffraction. The most obvious change is an upwards movement of about 0.3 nm at the low-radius end of the left radial helix in the protein with some stiffening of the helix so that it now extends visibly in from 4 nm to 6 nm radius. Similar shifts also occur in the right radial and left slewed helices. A positive peak, which is tentatively identified with the bound oligonucleotide, is seen around 4 nm radius and below the right radial helix. The amino acid residues in possible contact with this feature are discussed.


Interaction of human serum albumin with fatty acids. Role of anionic group studied by affinity partition. The interaction of human serum albumin with fatty acids has been determined using the method of affinity partitioning in aqueous biphasic systems containing dextran, poly(ethylene glycol) and esters of dicarboxylic acids with poly(ethylene glycol). The difference in the partition of albumin in phase systems with and without the poly(ethylene glycol)-bound fatty acid group provides a measure of the interaction of fatty acids with the protein. The relative contribution of the polar and non-polar interaction to the binding of fatty acids to albumin has been estimated by comparing the present data with that obtained earlier using poly(ethylene glycol)-bound straight chain aliphatic hydrocarbons. In both cases, the aliphatic chain should contain a minimum of 8 carbon atoms to affect the partition of albumin and that the maximum effect is obtained with chains containing 16 carbon atoms. The effect of the polymer-bound fatty acid group is higher than the corresponding hydrocarbon only when the number of carbon atoms in it exceeds 12. The relative effect of polymer-bound 16-carbon chains, with and without a carboxyl group in the terminal position is independent of pH in the range 5--9.


Affinity labelling of rat-muscle hexokinase type II by a glucose-derived alkylating agent. The glucose-derived alkylating agent N-bromoacetylglucosamine (GlcNBrAc) is shown to cause a time-dependent irreversible inactivation of rat muscle hexokinase type II. The kinetics of inactivation are in accord with the reversible formation of an enzyme-inhibitor complex prior to modification, indicating that the reagent is active-site-directed. A Ki of 0.57 mM obtained for this reversible complexing is in agreement with a Ki of 0.65 mM obtained for the inhibition caused by N-propionylglucosamine, an isosteric analogue of GlcNBrAc and a competitive inhibitor with respect to glucose. Glucose itself protects competitively against inactivation. A KG of 0.26 mM obtained for the formation of enzyme-glucose complex from these studies is in agreement with the kinetically-determined Km of 0.2 mM. The substrate-unrelated but chemically similar alkylating agents bromoacetic acid and N-bromoacetylgalactosamine inactivate the enzyme at 20% of the rate caused by GlcNBrAc. The inactivation rate increases rapidly over the pH range 7--9. Analysis of this pH dependence shows that a single residue of pKa 8.9 is reacting with GlcNBrAc with a kmax (pH corrected, pseudo-first-order rate constant) of 1.5 x 10(-3) S-1. These values are typical of the reaction of model thiols with alkylating agents and suggests the reacting residue is probably a cysteine. Use of radioactively labelled GlcNBrAc indicates that uptake of 1 mol of reagent per mol protein causes complete activity loss. Finally the behaviour of this enzyme with active-site-directed alkylating agents is compared with published results of similar experiments carried out with yeast hexokinase and bovine brain hexokinase type I.


Anisotropy decay of labelled actin. Evidence of the flexibility of the peptide chain in F-actin molecules. G actin, labelled presumably on cysteine-373 with the fluorescent chromophore N-iodoacetyl-N'-(5 sulfo-1-napthyl)-ethylenediamine and purified by Sephacryl S-200 gel chromatography, migrated in one band on polyacrylamide gel electrophoresis and had the same polymerizability as unlabelled purified G actin. Anisotropy decays of labelled actin solutions have been studied at different ionic strengths and protein concentrations. It was found that these anisotropy decays could be fitted by a sum of two exponential functions. Under low ionic strength or below the critical concentrations the longer correlation time (45 ns at 3.5 degrees C) was independent of protein concentration and ionic strength. Above the critical concentration, the longer correlation time increased with ionic strength and protein concentration. In order to take into account that, under these conditions, the solutions contained a mixture of F and G actin at the critical concentration, the anisotropy decays were analysed as a sum of three exponential functions in which the longest correlation time characterized F actin. Since F actin correlation time also depended on actin concentration, an analysis with a sum of four exponential functions was performed, in which two fixed correlation times (100 ns and 900 ns at 3.5 degrees C) were introduced in order to characterize the F actin motions. The lower of these correlation times was attributed to regions where two actin filaments interact side by side, while the shorter one was attributed to filament regions free from intermolecular interactions. The small value of the free F actin correlation time indicates that the protomer peptide chain is very flexible around its C terminus, probably involving the motion of a molecular lobe. This flexibility might be an important factor in the interaction of actin with myosin during the muscular contraction.


Isolation and characterization of phosphorylated oligosaccharides from alpha-N-acetylglucosaminidase that are recognized by cell-surface receptors. Adsorptive endocytosis of lysosomal enzymes by fibroblasts and hepatocytes involves binding to cell surface receptors that recognize on lysosomal enzymes a phosphorylated carbohydrate, most likely a mannose 6-phosphate residue [Kaplan et al. (1977) Proc. Natl Acad. Sci. U.S.A. 74, 2026-2030; Ullrich et al. (1978) Hoppe-Seyler's Z. Physiol. Chem. 359, 1591-1598]. Loss of alpha-N-acetylglucosaminidase endocytosis after treatment with endoglucosaminidase H indicated that the recognition site of alpha-N-acetylglucosaminidase is located on N-glycosidically linked oligosaccharides of the high mannose type. Acidic oligosaccharides with an average molecular weight of 2200 were liberated from alpha-N-acetylglucosaminidase by endoglucosaminidase H. These oligosaccharides were susceptible to degradation by alkaline phosphatase, alpha-mannosidase and beta-N-acetylglucosaminidase. At the non-reducing terminal these oligosaccharides bear phosphorylated mannose and/or N-acetylglucosamine residues.


The inhibition of photosynthetic electron transport in spinach chloroplasts by low osmolarity. The reversible inhibition, by low osmolarity, of the rate of electron transport through photosystem 1 has been investigated in spinach chloroplasts. By use of different electron donor systems to photosystem 1, inhibitors of plastocyanin, and by measurement of the extent of photooxidation of the photosystem 1 reaction center P700, the inhibition site has been localized on the electron donor side of this photosystem. From comparison of the influence of impermeant and permeant salts on the electron transport rate, and from the effect of ionic strength on the oxidation of externally added plastocyanin by subchloroplast preparations, it is concluded that low ionic strength within the thylakoids inhibits the photooxidation of endogenous plastocyanin by P700. The results are taken as evidence that plastocyanin is oxidized by P700 at the internal (lumen) side of the osmotic barrier in the thylakoid membrane.


Translation of biologically active messenger RNA from human placenta in Xenopus oocytes. Polysomal RNA was extracted from human term placenta and total poly(A)-containing RNA purified by affinity chromatography on oligo(dT)-cellulose. Poly(A)-containing RNA constituted approximately 1.2% of the total polysomal RNA and 8% of this purified preparation was able to anneal with [3H]poly(U). When injected into Xenopus oocytes, this poly(A)-rich RNA directed the synthesis of a polypeptide which is immunoprecipitable with a specific antiserum to human placental lactogen. The identity of authentic human placental lactogen and the immunoreactive polypeptide synthesized in the oocytes is suggested by their identical behaviour in dodecylsulfate gel electrophoresis and by the formation of identical cyanogen bromide peptides. No precursor of human placental lactogen can be detected in the oocytes. The messenger RNA for human placental lactogen is very stable in oocytes; it is translated efficiently for a period of at least 7 days.


The physiological role of pyruvate carboxylation in hamster brown adipose tissue. 1. Pyruvate carboxylase is present in brown adipose tissue mitochondria. 2. In isolated mitochondria, pyruvate, bicarbonate and ATP, the substrates for pyruvate carboxylase, are able to replace added malate in supplying a condensing partner for acetyl-CoA formed from beta-oxidation of fatty acids. 3. In brown adipocytes, pyruvate and CO2 increase the rate of norepinephrine-stimulated respiration synergistically. 4. The norepinephrine-stimulated respiration in brown adipocytes is diminished when pyruvate transport into the mitochondria is inhibited. 5. Pyruvate carboxylation increases the intramitochondrial level of citric acid cycle intermediates, as shown by titrations of malonate inhibition of respiration. 6. Pyruvate carboxylation can continuously supply the mitochondria with citric acid cycle intermediates, as evidenced by its ability to maintain respiration when oxoglutarate conversion to glutamate is stimulated. 7. Pyruvate carboxylation is necessary for maximal oxygen consumption even when drainage of the citric acid cycle for amino acid synthesis is eliminated. 8. Pyruvate carboxylation explains observed effects of CO2 on respiration in brown adipocytes, and may also explain the increased glucose uptake by brown adipose tissue during thermogenesis in vivo.


Localisation of an endonuclease specific for double-stranded RNA within the nucleolus and its implication in processing ribosomal transcripts. Nucleoli of both chick embryos and mouse Ehrlich ascites cells contain an enzymatic activity that is very similar to RNase DII, an enzyme isolated from total chick embryos for its ability to degrade double-stranded RNA. The enzyme can be extracted by low salt/EDTA from nucleoli and is associated with pre-ribosomal 80-S and 55-S particles. Under ionic conditions which are inhibitory for the nucleolytic activity the transcript in vitro of nucleoli is not processed and sediments around 45 S. Under salt conditions which are optimal for the nucleolar enzyme the nucleolar transcripts are cleaved to distinct intermediate-sized molecules. Addition of the chicken RNase DII or RNase III to the nucleolar transcription system results in a similar shift of the chain length of the RNA molecules. It is concluded that a nucleolar RNase recognizing double-stranded regions in the pre-ribosomal RNA is involved in the maturation of ribosomal RNA.


The formate dehydrogenase involved in electron transport from formate to fumarate in Vibrio succinogenes. 1. The formate dehydrogenase of Vibrio succinogenes, which is involved in electron transport with fumarate as terminal acceptor, was solubilized with Triton X-100 and purified some 200-fold by means of chromatography on hydroxyapatite, sucrose-density-gradient centrifugation and chromatography on DEAE-Sephadex. Gel filtration failed to increase the specific acitivity of the enzyme while gel electrophoresis in the presence of dodecylsulfate revealed that 73% of the protein of the preparation consisted of a polypeptide of Mr 110 000. The Mr of the functional enzyme was found to be 263 000 on the basis of the Stokes radius (5.8 nm) and the sedimentation coefficient (11.3 S). 2. The preparation contained 9 micronmol molybdenum/g protein and about 170 mumol iron-sulfur/g protein. The contents of b and c cytochromes varied and were lower than that of molybdenum. The low-potential cytochrome b [Kröger, A. and Innerhofer, A. (1976) Eur. J. Biochem. 69, 497-506] present in the preparation was reduced by formate. 3. The preparation catalyzed the reduction of a variety of dyes by formate, but not of NAD, FMN, ferredoxin or oxygen. The reduction of CO2 or bicarbonate by reduced methyl viologen was not catalyzed. The reaction with benzyl viologen obeyed the rate law consistent with a ping-pong mechanism. The Km for formate was 1.5 mM at infinite concentration of benzyl viologen while that for benzyl viologen was 0.53 mM at infinite formate concentration. Enzymic activity was inhibited by azide, KCN and HgCl2, but not by 4-chloromercuriphenylsulfonate or 2-(n-nonyl)-4-hydroxyquinoline-N-oxide, both of which inhibit overall electron transport. The inhibition by azide was competitive with formate; the Ki was 45 micron. 4. The midpoint potential of the low-potential cytochrome b of the membrane fraction was shifted -40 mV by the presence of 2-(n-nonyl)-4-hydroxyquinoline-N-oxide. 5. It is concluded that the formate dehydrogenase of V. succinogenes is isolated as a dimer consisting of two identical subunits of Mr 110,000, each of which carries one atom of molybdenum and iron-sulfur groups. The low-potential cytochrome b is the direct acceptor for the electrons of formate dehydrogenase in the electron transport of formate-fumarate reduction of V. succinogenes. Inhibition of electron transport of the membrane fraction between formate dehydrogenase and menaquinone by 2-(n-nonyl)-4-hydroxyquinoline-N-oxide [Kröger, A. and Innerhofer, A. (1976) Eur. J. Biochem. 69, 487-495] is caused by the inhibitor binding to the low-potential cytochrome b.


Metal ion/buffer interactions. Stability of binary and ternary complexes containing 2-amino-2(hydroxymethyl)-1,3-propanediol (Tris) and adenosine 5'-triphosphate (ATP). The interaction of 2-amino-2(hydroxymethyl)-1,3-propanediol (Tris) with the metal ions (M2+) Mg2+, Ca2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Pb2+ was studied by potentiometry and spectrophotometry in aqueous solution (I = 0.1 or 1.0 M, KNO3, 25 degrees C). Stability constants of the M(Tris)2+ complexes were determined; those constants which were measured by both methods agreed well. Ternary complexes containing ATP4- as a second ligand were also investigated and it is shown that in the presence of Tris, mixed-ligand complexes of the type M(ATP)(Tris)2- are formed. The values for delta log KM, where delta log KM = log KM(ATP)M(ATP)Tris--log KMM(Tris), are all negative, thus indicating that the interaction of Tris with M(ATP)2- is somewhat less pronounced than with M2+. However, it should be noted that even in mixed-ligand systems complex formation with Tris may still be considerable, hence great reservations should be exercised in employing Tris as a buffer in systems which also contain metal ions. Distributions of the complex species in dependence on pH are shown for several systems, and the structures of the binary M(Tris)2- and the ternary M(ATP)(Tris)2- complexes are discussed. The participation of a Tris-hydroxo group in complex formation is, at least for the M(Tris)2- species, quite evident.


Chemical modification of taipoxin and the consequences for phospholipase activity, pathophysiology, and inhibition of high-affinity choline uptake. Treatment of taipoxin with p-bromophenacyl bromide resulted in modification of single histidine residues in the alpha and beta subunits. The modification decreased the neurotoxicity (lethality) 350-fold, but the inhibitory action on high-affinity choline transport was reduced only threefold. The phospholipase activity and Ca2+-association constants for taipoxin and its subunits were determined. A model for the neurotoxicity of taipoxin indicates the alpha subunit as the ultimate cause of the disruption of synaptic transmission.


Purification and reverse transcription of the messenger RNA coding for the insect protein, calliphorin, isolated from larvae of the blowfly, Calliphora vicina R.-D. Starting from poly(A)-containing RNA prepared from the fat body of larvae of the blowfly Calliphora vicina, we have purified an mRNA coding for the protein calliphorin, which is a major blowfly protein accounting for approximately 9% of the total poly(A)-containing mRNA activity in the fat body of 5-days-old larvae, as demonstrated by translation in vitro. The mRNA for this protein was purified by sucrose gradient centrifugation under denaturing conditions and identified by cell-free translation. The peak fraction of the gradient shows three bands of about 20 S after formamide/acrylamide gel electrophoresis. Using reverse transcriptase and Calliphora mRNA isolated directly from the acrylamide gel electrophoresis or from sucrose gradients, we synthesized a cDNA probe. This cDNA hybridizes with the template, showing a major kinetic component with a molecular weight of 2.8 x 10(6), fitting well with the three bands observed in the electrophoresis. Hybridization of the cDNA with total sonicated Calliphora DNA shows annealing only at very high c0t values, indicating that Calliphora mRNA is transcribed from the unique portion of the fly genome.


Amino acid sequence of neurotoxin III of the scorpion Androctonus austrialis Hector. The amino acid sequence of neurotoxin III, purified from the venom of the North African scorpion Androctonus australis Hector, has been determined by Edman degradation using a liquid-phase sequencer. Carboxypeptidase A hydrolyses confirmed not only the sequence of the five last residues but also the presence of a free alpha-carboxylic group at the C-terminus. Edman degradation was conducted on one hand with the Quadrol [N,N,N',N'-tetrakis(2-hydroxypropyl)ethylene diamine] program and S-alkylated protein before or after coupling with sulfophenylisothiocynate (the first 34 residues were thus identified), on the other hand on tryptic and chymotryptic peptides with a dimethylbenzylamine program (residues 1--23 and 31--34 were confirmed, the positions of residues 35-64 were established). Neurotoxin III was found to belong to the same group of scorpion toxins active on mammals as neurotoxin I purified from the same venom (50 homologous positions exist in the two proteins).


Transport and metabolism of bromosulfophthalein by isolated rat liver cells. Kinetics of transport and metabolism of bromosulfophthalein have been studied in isolated liver cells in a dose-dependent manner obtaining the following results. The disposition of bromosulfophthalein in suspensions of isolated liver cells is similar to the turnover in the whole liver. The initial maximal rate of uptake of bromosulfophthalein is 2--3 times faster than intracellular conjugation with glutathione. Conjugation proceeds to an equilibrium between intracellular substrate (bromosulfophthalein) and product (bromosulfophthalein-glutathione conjugate) which are both transiently accumulated in the cell. Formation of bromosulfophthalein-glutathione is accompanied by an equimolar decrease of glutathione. The bromosulfophthalein-glutathione conjugate is slowly released from the cells in an energy-dependent and saturable transport process. The maximal velocity of excretion amounts to only 6% of the maximal velocity of uptake and to 20% of the maximal velocity of conjugation. Excretion, therefore, represents the slowest step in the overall turnover.


Therapy of urothelial bladder tumors. Results of a retrospective study of 615 cases. 615 urothelial bladder tumors are evaluated retrospectively after reclassification of histological and cytological specimens according to the recommendations of the World Health Organization (1973) and International Union Against Cancer (1974). The reason for a subdivision of the T1 category for exophytic noninfiltrating carcinomas is discussed. The importance of stage and grade is demonstrated as well as the different prognosis of patients with primary or recurrent tumors of the same T category. The results of the study demand a differentiated therapeutic regimen for urothelial bladder tumors.


Revaluation of the advancement operative technique for the cure of vesicorenal reflux. In a series of 180 neoureterocystostomies, 177 were successful. Only 3 failure occurred: 1 remaining reflux and 2 obstructions. The operative technique is described and discussed. The advancement procedure of Glenn and  Anderson is found to be an excellent technique for the cure of nearly all cases of vesicorenal reflux.


On the pathogenesis of stone formation in stone-eliminating patients. The clinical peculiarities, and the etiological and pathogenetic factors of urolithiasis in 296 patients suffering from spontaneous stone elimination were studied. It was established that 209 patients eliminated stones consisting of uric acid, sodium salts and ammonium salts. Moderate hypocalcemia and hyperphosphatemia and also hyperuricemia and hyperuricuria were present. There were 39 'eliminators' of calcium stones. Their blood calcium content was higher, hypercalciuria, inorganic phosphorus and normal uric acid, were noted. Compound stones were present in 48 observations. When carrying out additional biochemical tests in 57 patients with calcium and compound stones, primary hyperparathyroidism was diagnosed in 34 observations; and parathyroidectomy was successfully performed.


Epidemiology of urinary stone colic.

Epidemiology of urinary stone colic. Epidemiological study of urinary stone colics was done for 5 years in a defined basin located in the center of Japan. It was 2.5 times more frequent in males than in females. The difference was observed only in the age over 30 years. Recurrence occurred in 24.5% of the cases. Climatic factors were also analysed. The incidence was significantly high in summer and low in autumn. Days of decreasing air pressure and high temperature were frequently associated with stone colic.


Resorptive and absorptive hypercalciuria. Therapy with sodium cellulose phosphate or thiazides. Patients with recurrent stone disease and hypercalciuria were cleared up according to Nordin's schedule. In cases of absorptive hypercalciuria, an ion exchanger operating in the intestine, sodium cellulose phosphate (SCP), is applied under strict control of oxalate, calcium and magnesium excretion as well as ionized calcium in serum. Under treatment with SCP (27 patients), we found a reduction in the renal excretion of calcium and magnesium, and, as a side effect, a significant augmentation of the renal oxalate excretion. In cases of resorptive or resorptive/absorptive hypercalciuria, except in patients with primary HPT, 23 patients were mediated by thiazides (Esidrix). This drug effects a marked decrease of urinary calcium based on a higher rate of reabsorption of calcium in the distal tubule. No severe side effects especially primary HPT were observed.


Investigations on flow dynamics and microstructure and their contribution to urolith genesis. Stones originating in the tubular system may grow in the renal calyces without being excreted. From the analysis of flow dynamics nearly steady turbulences with long retention times should be expected, in which particles with a density of about 1.0 can grow. By this, hydrodynamics would support the matrix theory of stone genesis. Microscopic structures of the central stone regions also support 'organic early stages in urolith genesis.'


Evoked response of the bulbocavernosus reflex. The bulbocavernosus reflex can be elicited either by penile or urethral stimulation. The mean signal transit time after electrostimulation of the dorsal penile nerve to evoked response in the anal sphincter (35 msec) was only half the signal transit time after stimulation in the posterior urethra (60 msec). Thus, the modified bulbocavernosus reflex elicited either by squeezing the glans penis or by pulling a urethral balloon catheter represents two different reflexes with differenct afferent and probably different intraspinal pathways. In the clinic it is therefore important, when testing the bulbocavernosus reflex, to report how it is elicited.


The metabolic situation in ureterosigmoidostomy. At reexamination 67 patients with ureterosigmoidostomies showed no significant alteration of their acid-base and electrolyte metabolism as compared to the preoperative situation and 39 patients with a colonic conduit. If required these patients had received an oral alkali substitution therapy; this proved to be necessary as a permanent measure only in cases with functional and morphological defects of the upper urinary tract. Spells of hyperchloremic acidosis had occurred in 13 patients during the follow-up period and always coincided with attacks of acute pyelonephritis and renal deterioration, often accompanied by irregularities in the substitution. Obviously metabolic problems arise only with a deteriorating urinary tract and timely discovery and treatment of these patients is the main task of the supervising doctor. Although the metabolic imbalances usually respond promptly to an adaptation of the substitution therapy, patients with a predamaged upper urinary tract should not be subjected to ureterosigmoidostomy.


Malignant lymphoma of the urinary bladder. A report of 2 cases. 2 cases of primary, malignant lymphoma of the urinary bladder are reported. Diagnostic difficulties caused by a deep, intramural location and accompanying severe inflammation are discussed. From a review of the literature and also from the authors experience, resection of the bladder and postoperative radiotherapy seen to constitute sufficient therapy.


Sacrococcygeal dysgenesis.

Sacrococcygeal dysgenesis. Congenital sacrococcygeal dysplasia is an uncommon though important cause of neuropathic bladder disease leading to progressive renal damage. In 2 cases described herein and featuring long-standing incontinence and recurrent infections, the concomittant musculoskeletal abnormalities had been treated for years, while the urinary tract condition had been largely neglected until urinary diversion or unilateral nephrectomy were required.


Obstruction of a ureter by isolated primary focal amyloidosis. A rare case of obstruction of the pelvic segment of the ureter by an isolated focus of primary amyloidosis is described. The operation consisted of resection of the constricted segment of the ureter and end-to-end anastomosis, with very good early and late results. The differential diagnosis and therapy of this type of ureteral obstruction are discussed.


Foreign body stone of the ureter as a complication of acupuncture. A case of spontaneous passage of a foreign body in the upper urinary tract is reported. Approximately 60 cases have been collected and reported in the world, 18 in Japan. Our case is, however, the first with spontaneous passage. As complications may occur if these foreign bodies are left behind, we advocate the surgical removal as treatment of choice.


Bilateral total ureteric bypass in the management of renal tubular acidosis. Nephrocalcinosis and the subsequent obstruction of the ureters by urinary calculi can be a major problem in the management of a patient with renal tubular acidosis. We describe the case history of a girl with this condition in whom the interposition of segments of ileum between the kidneys and bladder, thus bypassing the ureters, had been used in an attempt to overcome the problem of recurrent ureteric obstruction by calculi.


Cervical aortic arch with ventricular septal defect. A differential diagnosis from interrupted aortic arch. A case of right cervical aortic arch with a large ventricular septal defect and a bicuspid aortic valve is reported. The angiographic diagnosis was interruption of the aortic arch type II, with aberrant right subclavian artery, a closed ductus arteriosus and retrograde vertebral-subclavian flow to the descending aorta. The cervical arch, demonstrated post mortem, was located high and deep in the neck. This differential diagnosis may have potential importance, as reported experience shows that a surgical aortic anastomosis is not required in cervical aortic arch.


Paroxysmal atrioventricular tachycardia involving an anomalous pathway with antegrade unidirectional block. 37 consecutive patients with frequent episodes of palpitation and/or dizziness underwent electrophysiological study. They had no signs of ventricular preexcitation during either sinus rhythm or atrial pacing. In 17 (46%), the supraventricular tachycardia was sustained by a reentry mechanism involving an anomalous AV pathway with unidirectional antegrade block (AV tachycardia). Some findings were accepted to demonstrate the existence of the anomalous pathway (AP) and others, its participation in the reentry circuit. The possible location of the AP was established in 15 cases at the following sites: left lateral in 5 cases, left posterior in 5 cases, left posteromedial in 1 case, right posterior in 1 case, right anterior in 1 case, posterior septal in 1 case, and anterior septal in 1 case. The rate of the AV tachycardia can be influenced not only by the ventriculoatrial interval but also by the other pathways included in the reentry circuit. It may change conspicuously in cases with dual AV pathway and anomalous AV pathway in relation to the modality of antegrade conduction by the AV node.


Antidiuresis induced by infusions of histamine into the brain ventricles of conscious hydrated goats. Histamine was infused into the third or lateral ventricle of conscious hydrated goats, and urine samples were analyzed for volume, osmolality and electrolytes. Doses of 10--1000 microgram of histamine induced dose-dependent antidiuretic responses both as to the maximum osmolality and the duration of the osmolality increase. Urine osmolality began to rise within a few minutes, reached its maximum within 0.5--2 h and was elevated for 1.5--4 h, depending on the dose. Thereafter a second increase in osmolality often occurred, which lengthened the effect of histamine dose-dependently up to about 10 h with the largest dose of histamine. Histamine (50--300 microgram) and the control solution given into the lateral ventricle increased the excretion of Na+ into the urine. After the largest dose of histamine (1000 microgram), however, the excretion of Na+ was significantly lower than in the control experiments. After the larger doses of histamine, effects on motor or autonomic functions were seen. These included decreased spontaneous motor activity, increased respiratory rate, defecation and miosis. It is suggested that the site of action of histamine is central, and that the release of vasopressin through the activation of the neurosecretory system is probably involved. In addition the changes in electrolytes may suggest an involvement of the release of other factors such as prolactin.


The local anesthetic effect of cyproheptadine on mammalian nerve fibres. The local anesthetic effect of cyproheptadine on nerve fibres in the rabbit's cervical vagus and sciatic nerve was studied by the single sucrose-gap technique. Local anesthetics such as procaine and tetracaine, and an antihistaminic with local anesthetic activity, diphenhydramine, were studied for comparison. Increasing concentrations of cypropheptadine, starting from 5 x 10(-5) M, produced a dose-related fall in the amplitude of the compound action potential of the vagus nerve without significant change in the resting membrane potential. A complete reversibility of the local anesthetic effect was difficult or impossible to obtain when doses greater than 1 x 10(-4) M were used. Cyproheptadine was more potent than procaine and diphenhydramine, and less potent than tetracaine in producing nerve conduction block. Frequency-dependent block was observed with cyproheptadine and the other agents at frequencies that can be considered low (1--5 Hz). Myelinated fibres of the sciatic nerves were also blocked by cyproheptadine within the same range of concentrations (1 x 10(-4) to 1 x 10(-3) M). Our results provide an additional explanation for the mechanism underlying the actions of cyproheptadine as an antiarrhythmic and an antipruritic agent.


Biotransformation and cardiovascular effects of arachidonic acid in the dog. The biotransformation and cardiovascular effects of arachidonic acid (AA) were studied in the circulation of anaesthetized dogs. Arterial blood was continuously bioassayed for arachidonate metabolites using the blood-bathed organ technique of Vane. AA (5-10 microgram/ml) infused into an incubation coil of flowing blood was converted into a labile substance which contracted the vascular tissues (rabbit aorta, RbA; rabbit coeliac and mesenteric arteries, RbCA and RbMA; bovine coronary artery, BCA) and the gastrointestinal smooth muscle strips (rat stomach strip, RSS; rat colon, RC). These effects could be mimicked by exogenously generated thromboxane A2 (TXA2). Conversion of AA was inhibited by indomethacin and the selective thromboxane synthetase inhibitor, imidazole (100 microgram/ml). The half-life of TXA2 in blood was 30-47 sec, a similar value to that found in aqueous solutions at 37 degrees C. PGH2 was also converted in blood to other product(s) which contracted RSS and RC, relaxed RbCA and RbMA but had little effect on RbA. Intravenous infusion of AA (50-800 microgram kg-1 min-1) caused effects on the bioassay tissues which could be mimicked by prostacyclin. The AA infusion also induced falls in pulmonary and systemic arterial pressures and bradycardia. All effects were abolished by indomethacin (5 mg/kg) or aspirin (200 mg/kg). Radioimmunoassay confirmed that the major product of intravenously infused AA was 6-oxo-PGF1alpha, the chemical degradation product of prostacyclin. Thus, although AA is transformed to the vasoconstrictor TXA2 when incubated for sufficient time with blood alone, on rapid pulmonary transit it is transformed into a prostacyclin-like substance.


Effects of L-dopa on putrescine levels in the brain and the liver of the rat. The pharmacological effects of several amino acid precursors of putative neurotransmitters on putrescine levels in the brain and the liver of the rat were studied. L-dopa increased brain and liver putrescine levels in a dose-dependent manner that reached its maximum effect in 4-6 h. The increase in liver putrescine was associated with a concomitant increase in ornithine decarboxylase activity. L-5-hydroxytryptophan increased liver putrescine but had no effect on brain putrescine levels. D-DOPA and D-5-hydroxytryptophan were both ineffective in altering brain or liver putrescine. The effects of L-DOPA persisted after hypophysectomy and were not associated with changes in tissue levels of S-adenosylmethionine. The repeated administration of L-DOPA for periods of 48 and 96 h resulted in a sustained elevation of putrescine levels in the brain but not in the liver.


Effects of neuronal polypeptides on intestinal smooth muscle; a comparison with non-adrenergic, non-cholinergic nerve stimulation and ATP. Substance P, somatostatin, enkephalin and vasoactive intestinal polypeptide (VIP) did not mimic the inhibitory responses to non-adrenergic, non-cholinergic nerve stimulation. Substance P (0.1-10 microgram/ml) always caused contraction, enkephalin (0.1-10 microgram/ml) and somatostatin (0.1 microgram/ml) were inactive, while VIP (0.1-1 microgram/ml) produced very slow relaxation, taking about 4 min to reach a maximum after a latency of about 60 sec. Low concentrations of neurotensin (1-10 ng/mg) caused contraction, but at higher concentrations (50-1000 ng/ml) it produced a biphasic response which consisted of an initial contraction followed by a slow relaxation. In high tone preparations, the slow relaxation did not mimic the nerve-mediated response, taking approximately 43 sec. to reach maximum, after a long latency of about 15 sec. In contrast, ATP (0.1-50 microgram/ml) mimicked closely the rapid responses to non-adrenergic, non-cholinergic nerve stimulation in all preparations, whether the tone was low, medium or high. The time for the inhibitory response to reach maximum was about 15 sec after a latency of approximately 1 sec. Indomethacin (3.4-34 microgram/ml) did not unmask any inhibitory responses to any of the peptides. It is concluded that ATP remains the most likely substance to be the inhibitory transmitter released from non-adrenergic, non-cholinergic nerves supplying the smooth muscle of the taenia coli.


Non-adrenergic, non-cholinergic (purinergic?) inhibitory innervation of the rabbit rectococcygeus muscle. A powerful non-adrenergic, non-cholinergic inhibitory innervation of the rabbit rectococcygeus was unmasked by atropine in preparations in which tone had been raised either by carbachol or prostaglandin E2-Flourescent histochemical localization of quinacrine (which binds ATP) revealed ganglia and associated nerve bundles which were neither adrenergic nor cholinergic both on the surface and within the rectococcygeus muscle. Treatment of the rabbit with 6-hydroxydopamine abolished catecholamine fluorescence without affecting quinacrine-stained neural elements. Release of ATP from the rectococcygeus increased 2-4 times above background levels during stimulation of intramural inhibitory nerves. In preparations in which the tone was raised, ATP caused an inhibitory response comparable to that produced by non-adrenergic, non-cholinergic nerve stimulation. Indomethacin reduced the increase in tone and spontaneous activity following washout of ATP in low tone preparations, and potentiated the relaxations produced by ATP in high tone preparations. These results suggest that the rabbit rectococcygeus, as well as receiving a cholinergic excitatory innervation and an adrenergic inhibitory innervation, is also innervated by purinergic inhibitory nerves.


Effects of baclofen on striatal 5-HT mediated by the nigrostriatal dopamine system. In rats, baclofen injected unilaterally into the substantia nigra increased dopamine (DA) and serotonin (5-HT) levels in the ipsilateral striata. Homovanillic acid levels first decreased and then increased to a maximum after 4 h. The content of 3,4-dihydroxyphenylacetic acid also increased after a latency of about 1 h. The effects of baclofen on striatal DA metabolism are consistent with the assumption that impulse flow in these DA neurones was diminshed by the drug. DA metabolites were also found in greater quantities in the contralateral striata, probably owing to compensatory activation of these DA neurones. Baclofen injected intranigrally did not increase the striatal 5-HT content in rats with a 6-hydroxydopamine-induced lesion of the nigrostriatal DA pathway. Our results suggest the presence of DA receptors on striatal 5-HT terminals or on interneurones synapsing axo-axonally with them.


Potentiating mechanism of bradykinin action on smooth muscle by sulfhydryl compounds. (4R)-3-[(2S)-3-Mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (YS-980), a potent angiotensin I (AI) converting enzyme inhibitor, inhibited the contractile response of isolated guinea-pig ileum to AI but not to AII, while it potentiated the response to bradykinin. Other sulfhydryl compuonds also produced inhibition of AI action, and the effects were closely correlated with their potentiating activities against bradykinin action. These results suggest that it is mainly inhibition of the enzyme in the tissue which participates in the mechanism of potentiation of kinin action by YS-980.


[Vaginal smear cycle in 4-day cyclic Chinese hamsters, Cricetulus griseus]. The contents of vaginal smear of 4-day cyclic Chinese hamster (Cricetulus griseus) was investigated every 3 hours for 5 days. A light-dark cycle of 14--10 hr was used with the lights turned on at 6 : 00 a.m. Estrous cycle of the Chinese hamster determined by vaginal smears can be divided into 6 periods. The proestrous phase started at about 0 : 00 of day 1, the day of the proestrous phase was designated as day 1 of the estrous cycle. In the afternoon of the same day 1, nucleated epithelial cells gradually increased in number (proestrus : I), and the vaginal contents became to consist solely of nucleated epithelial cells at about 18 : 00 to 21 : 00 (estrus : II). At about 0 : 00 of day 2, however, nucleated epithelial cells were superseded suddenly by cornified epithelial cells, and this phase lasted for 9 to 12 hr (metestrus I : III). Towards the end of the cornified stage, nucleated cells appeared in short duration (metestrus II : IV). And then, in the evening of day 2, leucocytes gradually increased in number with degeneration of nucleated cells (diestrus I : V-1). On day 3, vaginal smear contained a large amount of mucus as well as degenerated nucleated cells and leucocytes (diestrus II : V-2). At about 21 : 000 of day 4, some cornified epithelial cells were seen and then proestrous stage was returned. The females were mated with 3 to 5 males in the evening of day 1, copulation was confirmed in 83.7% females in the next morning,thus the copulation in the Chinese hamster may be thought to occur during the vaginal smear stage of nucleated epithelial cells (estrous phase), i.e. about 18 : 00 to 24 : 00 of day 1.


[Cross-sectional anatomy of miniature "Shiba" goat]. The anatomical relations of visceral organs and other tissues in the thoracic, abdominal and pelvic cavities of the male miniature "Shiba" goat are illustrated as thirteen semi-diagramatic representations of cross sections.


A guinea pig cage for easy cleaning.

A guinea pig cage for easy cleaning. A simple cage and rack system was designed for  holding guinea pigs in a laboratory environment. The shoe box solid floor cage, made of plastic, has 2 holes for "outside of cage" watering and "outside of cage" feeding. All of the accessory equipments such as automatic watering devices and feeders were set on rack shelves to design the cage simply. This system has satisfactorily functioned for about one year in our laboratory and has substantially saved labor in the washing process.


[Hand-rearing of cats using commercial milk powder, Teo milk]. Hysterectomy derived neonatal cats were given three times a day commercial milk diet, Teo milk (SANKYO Co. Ltd.), and showed a good growth comparable to conventional breast-fed cats with high weaning rate (85%) at 5 weeks of age.


[Observation on the air-borne bacteria and ammonia (NS3) gas in laboratory animal facility with rotary heat exchanger]. The number of air-borne bacteria in air ducts and barrierred laboratory animal rooms with the so-called econovent rotary heat exchanger, were checked monthly during a year by the pin-hole sumpler method for air ducts and Koch method for animal rooms. Also, concentration of ammonia was checked with the same samples by gas impinger. No significantly difference in number of air-borne bacteria was seen between before and after passing the econovent. Those passing through HEPA filter was not detected. There were more air-borne bacteria in animal rooms, outside locker room and shower room than in the corridor, utensil storage, inside locker room and pass box. No ammonia were detected in the outdoor, but exhaust air duct after passing the econovent contained very small amount of ammonia. On the other hand, high concentration of ammonia were preserved in the supplying air duct, exhaust air duct and mice and rats rooms, about 86% of ammonia in exhaust air duct returned back into the supplying air duct. No influences on reproduction in mice and rats were recognized.


Enhancement of erythroid colony growth in culture by hemin. Hemin was found to enhance the growth of murine erythroid colonies in culture. In the presence of 100 mU/ml erythropoietin (EPO), the addition of hemin (0.05-0.2 mM) resulted in the growth of twice as many colonies as were obtained with EPO alone. Hemin also significantly increased erythroid colony formation in culture in the absence of added EPO. Hemoglobin synthesis as measured by the incorporation of 59Fe into cyclohexanone extractable heme was augmented in culture by hemin. Neither delta-aminolevulinic acid, a hemin precursor, nor FeCl3 increased colony number.


Colony stimulating activity and continuous flow centrifugation leukapheresis induced proteinuria. Urinary granulocyte colony stimulating activity (CSA) was studied in normal individulas donating granulocytes. Donors were given corticosteroids 2 h prior to a 4-h leukapheresis using an Aminco celltrifuge in which hydroxyethyl starch was introduced into the donor line. Urine was collected 12-24 h prior to the procedure and 12-24 h beginning at the time of administration of corticosteroids. Colony stimulating activity was measured using mouse marrow cells grown in soft agar. After leukapheresis a significant increase in protein excretion was noted (139.94 +/- 28.1 to 288.69 +/- 63.8 mg per gram of creatinine) and the bulk of the protein was albumin. CSA isolated from G-75 Sephadex columns was increased in five donors, decreased in five donors and undetectable in nine donors. No CSA inhibitors were detectable. There was a significant correlation between the quantity of protein recovered from G-75 Sephadex column and CSA.


In vitro proliferation of haemopoietic cells in the presence of adherent cell layers. II. Differential effect of adherent cell layers derived from various organs. Mouse bone marrow-derived adherent cell populations promoted proliferation of haemopoietic cells in vitro in a liquid culture system for at least 4 weeks. Adherent cell layers derived from other haemopoietic organs (foetal liver, adult spleen) and fibroblasts from embryonic tissues did not maintain haemopoietic cells in this system. Medium, conditioned by adherent cells derived from foetal liver, spleen and embryonic tissues displayed a considerable colony stimulating activity (CSA). Marrow-derived adherent cells produced no detectable CSA. A possible relationship between the in vitro expression of a growth-promoting activity of an adherent cell population on haemopoietic cells, and its endogenous CSA production, is discussed.


Suppression of mouse erythroid colony formation by L1210 leukemia cells. The effect of L1210 transplantable leukemic cells on in vitro formation of erythroid colonies from CD2F1 mouse bone marrow progenitor cells (CFU-E) was investigated. Clonal cell culture was carried out by a methylcellulose technique. Human urinary erythropoietin served as the stimulator. After 44 hours of incubation aggregates of eight or more erythroid cells were scored as colonies. The number of CFU-E which could be demonstrated in marrow cells from mice that had been injected intravenously 6 days before with 5 x 10(4) L1210 cells was far below that obtained from normal marrow cells. When 1.3 x 10(5) marrow cells from leukemic mice or L1210 ascites cells were cultured with an equal amount of normal cells, the number of CFU-E expressed was reduced by 51% and by 86%, respectively, relative to controls with normal cells only. Neither lethally irradiated L1210 cells (4500 rad) nor L1210 cell conditioned media suppressed erythroid colony formation. It is suggested that in L1210 leukemia erythropoiesis is decreased because of a cell-to-cell inhibitory action of the leukemia cells on CFU-E.