Development of insulin resistance in normal dogs following alloxan-induced insulin deficiency. Insulin resistance was measured in 16 normal dogs by a method involving the continuous intravenous infusion of epinephrine, propranolol, glucose and insulin. With this approach, endogenous insulin secretin is inhibited, similar steady state levels of exogenous insulin are achieved in all doags, and the resultant steady state plasma glucose level provides a direct estimate of the ability of insulin to dispose of the infused glucose load. Thus, the higher the steady state plasma glucose level, the more the insulin resistance. Different amounts of alloxan were then administered to these dogs in order to produce insulin deficiency of varying degrees. Insulin resistance was then measured again in each dog. The results indicated that insulin resistance did not develop in dogs with only a moderate degree of insulin deficiency (fasting plasma glucose levels less than 150 mg/100 ml). On the other hand, a significant degree of insulin resistance developed in dogs with severe insulin deficiency (fasting plasma glucose greater than 150 mg/100 ml). Furthermore, the insulin resistance that developed in dogs with severe insulin deficiency could be returned to normal with insulin replacement for one week. These results indicate that insulin resistance can occur as a secondary manifestation of insulin deficiency.


Serum free insulin concentrations during the treatment of diabetic coma and precoma with low dose intramuscular insulin. Fifty patients in diabetic coma or precoma, 33 of whom had previously received insulin and had circulating insulin antibodies, were studied during treatment with a low-dose intramuscular insulin regime. In the presence of insulin antibodies, serum free insulin was separated from bound insulin by steady-state gel filtration. The initial mean serum free insulin concentration in the group of patients without insulin antibodies was 9 mU/1, 1 to 2 hours after intramuscular therapy it had risen to 22 mU/1, and after 7 to 8 hours to 73 mU/1. The corresponding concentrations for the group with insulin antibodies were 13, 23 and 74 mU/1. No relationship was found between the concentrations of serum free insulin attained and the age of the patients, their initial degree of acidosis, dehydration, and systolic blood pressure, the insulin antibody characteristics of their sera, nor the rate of decline of the blood glucose.


The effect of intraportal and peripheral infusions of glucagon on insulin and glucose concentrations and glucose tolerance in normal man. The effect of peripheral and intraportal infusions on 0.86 pmol/kg-min-1 of glucagon on plasma glucose, plasma insulin, and glucose tolerance was examined in four normal subjects. Peripheral glucagon concentrations increased by 60--90 pmol/1 during intraportal and 70--180 pmol/1 during peripheral infusions. The infusions caused increases in plasma glucose levels of approximately 1 mmol/1, and in plasma insulin levels of 75--100%, regardless of route of administration. Intravenous glucose tolerance tests carried out during the glucagon infusions showed that glucose tolerance remained within the normal range and was uninfluenced by the route of administration.


The effect of cigarette smoking on blood sugar, serum insulin and non esterified fatty acids in diabetic and non diabetic subjects. The effect of cigarette smoking on carbohydrate metabolism has been investigated in 10 diabetic and 18 non-diabetic subjects. All were habitual smokers. Neither the fasting plasma sugar nor the plasma sugar response to an oral glucose load was significantly altered by smoking. Serum insulin, free fatty acids, cholesterol and triglyceride were measured in 10 non-diabetic patients, and were not significantly altered by smoking. It is concluded that in habitual smokers at least, cigarette smoking does not impair carbohydrate metabolism. In addition, it seems that smoking before or during oral glucose tolerance test is unlikely to influence the diagnostic value of the test.


Plasma glucagon suppression by phenformin in man. In an attempt to elucidate the mechanism of action of phenformin, eleven juvenile-onset, insulin-requiring diabetic subjects underwent four different treatment regimens during standard breakfast tests. These four treatments were: control (no insulin or phenformin); insulin alone (15 U regular insulin administered subcutaneously one-half hour before breakfast); phenformin alone (50 mg of the timed-release capsule given twice daily for three days before the study and two and one-half hours before breakfast on the day of study); and phenformin plus insulin (in the amounts and at the times stated above). Phenformin was found to decrease postprandial hyperglycaemia significantly when compared with control values, and its addition to insulin further decreased the postprandial glucose rise below that found with insulin alone (p less than 0.005). These effects were associated with a reduction in early (30-min) postprandial hyperglucagonaemia (p less than 0.05). Triglyceride levels, gastrin secretion, growth hormone levels, and increments of alpha-amino nitrogen were not affected by phenformin. Thls, suppression of postprandial hyperglucagonaemia may be an additional mechanism in the reduction of postprandial hyperglycaemia after phenformin.


Glucagon secretion in diabetic patients with idiopathic haemochromatosis. The aim of the present investigation was to determine in patients with idiopathic haemochromatosis whether diabetes is of the primary type or secondary to pancreatic injury due to iron deposition. For this purpose, plasma glucagon concentrations were determined following arginine infusion or an oral glucose load in eight patients with diabetes and idiopathic haemochromatosis. The enhanced glucagon response to arginine and the nonsuppressibility of glucagon secretion by oral glucose found in these patients were similar to the results found in the same tests performed in our previous series of patients with "idiopathic" diabetes and at variance with those reported by others in patients with chronic pancreatitis.


Enzyme activities in quadriceps femoris muscle of obese diabetic male patients. In biopsy samples of the lateral part of the quadriceps femoris muscle of 6 obese diabetic male patients and of 11 obese males with a normal glucose tolerance, the activities of 7 enzymes of energy metabolism were estimated: hexokinase, cytoplasmic glycerol-3-phosphate: NAD dehydrogenase, triosephosphate dehydrogenase, lactate dehydrogenase, citrate synthase, malate dehydrogenase and 3-hydroxyacyl-CoA dehydrogenase. The obese diabetic male patients exhibited decreased activities of enzymes of carbohydrate breakdown and cytoplasmic NAD regeneration. Enzymes connected functionally with aerobic metabolism were less affected. The unchanged activity of 3-hydroxyacyl-CoA dehydrogenase points to an increased role of fatty acid catabolism in the muscle.


Clinical evaluation of somatostatin as a potential ajunct to insulin in the management of diabetes mellitus. To determine whether somatostatin, an inhibitor of glucagon and growth hormone secretion, might be useful as an adjunct to insulin the management of diabetic hyperglycaemia, seven insulin-requiring diabetic men were given somatostatin (100 microgram/h, IV) continuously for 3 days after their diabetes had been treated intensively by diet and insulin on a metabolic ward. During infusion of somatostatin and despite reduction in average insulin dose exceeding 50%, there was improvement in diabetic control as assessed by postprandial hyperglycaemia, 24-h glycosuria and the average daily serum glucose level and its fluctuation; when somatostatin was discontinued, but insulin doses held constant, diabetic control rapidly worsened. No adverse effects were observed. These results indicate that somatostatin plus insulin can be a more effective regimen than insulin alone in controlling diabetic hyperglycaemia. A longer acting and more selective somatostatin preparation may prove useful as an adjunct to insulin in the management of diabetes.


Causes of death in duodenal and gastric ulcer. An analysis has been made of 235 deaths that occurred among 1905 patients with peptic ulcer who constituted a random sample of the occurrence of ulcer disease in an area of Denmark comprising half a million inhabitants. The disease itself, according to the death certificate, was considered the primary cause of death in 10% of the cases; half of these had been operated on immediately before death. The other patients died more frequently than expected from the following causes: chronic bronchitis, pulmonary emphysema, cancer of the lung, cirrhosis of the liver, and cancer of the pancreas. Although the comorbidity with chronic bronchitis and emphysema was especially pronounced in patients with gastric ulcer, the association with liver cirrhosis and cancer of the pancreas occurred only in patients with duodenal ulcer. In women the mortality rate attributable to cardiac and vascular diseases was lower than expected. No excess coincidence of suicide was found. Berkson's fallacy is considered to be of much less importance as a possible explanation of the comorbidity found in the present study than in the majority of publications concerned with this question.


Relationships between fasting and postprandial pancreaticoduodenal pressures, pancreatic secretion, and duodenal volume flow in the dog. We have developed a canine model which allows simultaneous quantification of pancreatic enzyme outputs, duodenal volume flow, and pancreatic and duodenal pressures under physiological circumstances. Twelve studies on 4 conscious healthy dogs demonstrated that mean fasting pancreatic pressure was 5 to 10 cm H2O higher than mean fasting duodenal pressure. Furthermore, 8 min after ingestion of a meal, both the pancreatic and the duodenal pressure increased. Surprisingly, the mean duodenal pressure was higher than the mean pancreatic pressure 20 min after feeding. This relationship lasted for 30 min. Lastly, elevation of postprandial pancreatic pressure occurred concomitantly with increased pancreatic enzyme output, and duodenal pressure increased with increased duodenal volume flow. The observed large postprandial duodenal volume flows associated with duodenal pressures greater than pancreatic duct pressures may favor reflux of duodenal contents into the pancreatic duct. These relationships may be important in the pathogenesis of postprandial pancreatitis and in the induction of pancreatic cancer.


Endoscopic aspiration biopsy of the pancreas. Preoperative endoscopic aspiration biopsies were performed on 51 patients with pancreatic lesions using either a duodenal or gastric fiberscope and a newly designed biopsy needle. The accuracy of this method in the diagnosis of carcinoma of the pancreas was 84.0%. Although there were three false-negative diagnoses, there were no false-positives. No complications that could be attributed to this procedure were encountered.


Pancreatic duct cells in rats: secretory studies in response to secretin, cholecystokinin-pancreozymin, and gastrin in vivo. In rats given a copper-deficient diet plus penicillamine to destroy the acinar tissue selectively, the sensitivity and secretory pattern of pancreatic duct cells to a variety of hormones has been investigated. Resting flow rate of this pancreatic duct model was in the same range as in the intact gland. The duct cells responded to increasing doses of secretin by producing more juice with increasing outputs of bicarbonate, sodium, potassium, and chloride. Bicarbonate concentration increased with the lowest dose of secretin up to values of 64 mEq per liter and did not further increase with higher doses of secretin and increasing secretory rates. The concentration of potassium increased with increasing doses of secretin and flow rates, whereas chloride concentration decreased in a reciprocal fashion to bicarbonate. Gastrin and cholecystokinin-pancreozymin did not significantly stimulate the duct cells. Atropine did not inhibit the action of secretin on the flow rate or on bicarbonate secretion.


On the cause of the increased Heidenhain pouch secretion and serum gastrin concentration after gastrojejunostomy in dogs. With a statistical appendix. In 10 dogs with Heidenhain pouches (HP) a gastrojejunostomy (GEA) was constructed and later converted into a Roux en-Y anastomosis in order to abolish or reduce transstomal reflux. Next, duodenal inhibition was abolished by duodenal transection, and finally the duodenal bulb was excised. Twenty-four hour HP acid output increased after GEA, some 70% of the increase being attributable to transstomal reflux, the rest to decreased duodenal inhibition. Abolished duodenal inhibition caused a new rise, not significantly different from that caused by the combined effect of reflux and decreased duodenal inhibition after GEA. Twenty-four hour fasting HP acid output and 5 hr food-stimulated HP acid output rose after GEA by the same amount as that caused by abolished duodenal inhibition. A significant correlation was found between integrated gastrin and total HP acid output after food stimulation. Both fasting and food-stimulated gastrin concentration rose after GEA, the latter caused by reflux alone. Elimination of duodenal inhibition caused an unexpected rise in both fasting and food-stimulated gastrin concentration.


Lower sphincter of the opossum esophagus in pseudopregnancy. To seek a possible role of estrogen and progesterone in the development of changes in esophageal function during pregnancy, we produced a state of pseudopregnancy by administration of hormones to a suitable animal model. Twenty-two female opossums weighing an average of 2.5 kg, were divided into two groups. The treated group received intramuscular injections of 100 microgram of estradiol valerate daily from day 1 to day 12 and 15 mg of medroxyprogesterone acetate from day 7 to day 12. The control group received no injections. Both groups underwent manometry on days 1, 7, and 12. Lower esophageal sphincter pressure decreased (P less than 0.05) in treated animals from 58 +/- 13 mm Hg and 57 +/- 11 on days 1 and 7, respectively, to 44 +/- 10 mm Hg on day 12. The lower esophageal sphincter pressure remained unchanged in control animals. In both groups, there was no change in peristaltic wave pressure, duration, or velocity in the distal 6 cm of the esophagus. No abnormal peristaltic phenomena were observed. Esophageal muscle strips prepared from treated animals showed responses to electrical field stimulation of intrinsic nerves that were like those from control animals. The same was true for responses to acetylcholine and pentagastrin. Total tissue water and total tissue potassium content did not differ in treatment and control animals.


Effects of abdominal surgery on the development of radiation enteropathy. A controlled, retrospective study was undertaken to ascertain whether or not abdominal surgery at any time before radiation therapy might result in an increased incidence of radiation enteropathy. One hundred and five patients in three groups were studied; 24 had radiation enteropathy which developed an average of 12.5 months after radiation therapy, and 28 were matched controls without this complication. The records of a further group of 53 unmatched controls, who survived more than 2 years after irradiation were also examined. In the group with radiation enteropathy, 18 (75%) had a history of prior surgery, whereas only 3 (10.7%) of the matched controls had been operated before irradiation (chi2 = 3.52, P less than .005). The incidence of prior surgery in the unmatched control group was 13.2%. These data indicate that abdominal surgery before radiotherapy does increase the risk of subsequent development of radiation enteropathy.


Control of ascites absorption in anesthetized cats: effects of intraperitoneal pressure, protein, and furosemide diuresis. There is considerable evidence that fluids are removed from the peritoneal cavity by drainage into lymphatics lining the surface of the diaphragm, but there is little quantitative information on the rate of reabsorption as affected by conditions which exist in cirrhotic ascites. In the present study a plethysmographic technique was utilized to record the rate of absorption of fluid from the peritoneal cavity of anesthetized cats. The results of studies in 33 cats showed that the rate of fluid absorption from the peritoneal cavity was directly proportional to the intraperitoneal pressure regardless of whether the intraperitoneal fluid was free from protein or contained a protein concentration equivalent to that of plasma. Fluid was absorbed with a protein concentration equivalent to that present in the peritoneal cavity. Thus it is apparent that the intraperitoneal pressure is an important factor controlling the accumulation of ascitic fluid but the protein concentration of the intraperitoneal fluid does not affect the rate of reabsorption. In addition, marked diuresis induced by intravenous furosemide does not appear to mobilize ascites by an effect on the reabsorption process.


Elevations in skin tissue levels of bile acids in human cholestasis: relation to serum levels and topruritus. To define the relationship of bile acid retention to the pruritus of cholestasis, we quantified individual bile acids in serum, acetone swabs of skin, and skin tissue in 13 patients with cholestasis undergoing laparotomy and in 8 controls. There was no consistent relationship between pruritus and concentrations of either total or individual bile acids in serum. Skin tissue concentrations of bile acids were elevated in patients with cholestasis, were linearly related to serum levels, and did not differentiate between those patients with and those without pruritus. Concentrations of bile acids on the skin surface, which were lower than those reported by others, did not correlate with pruritus, and were decreased by simple soap and water washing. These data indicate that the pruritus of cholestasis is not directly related to the skin tissue concentration of any of the major bile acids, although a relationship to a particular molecular form of bile acids could not be excluded.


Evidence that acetaldehyde irreversibly impairs glycoprotein metabolism in liver slices. When liver slices were incubated for 1 hr in a medium containing either acetaldehyde or ethanol and then switched to a fresh medium free from acetaldehyde but containing the appropriate radioactive precursors and reincubated for 3 additional hr, a decreased incorporation of both [14C]glucosamine and [14C]leucine into hepatocellular and secretory proteins was observed. Further studies were carried out comparing the inhibitory effects of ethanol and acetaldehyde on drug metabolism. Higher concentrations of ethanol were necessary to impair aniline hydroxylation when compared to its effect on glycoprotein metabolism. Acetaldehyde did not affect aniline metabolism, suggesting some specificity for its effect on intracellular metabolic functions. Our results show that the acetaldehyde-induced inhibition of glycoprotein synthesis is irreversible under these short term experimental conditions and is not dependent on the physical presence of acetaldehyde in the incubation medium.


Percutaneous embolization for the management of hepatic artery aneurysms. The significant mortality and morbidity of hepatic artery aneurysms indicate the need for new approaches to therapy. Seven cases of intrahepatic aneurysms diagnosed by percutaneous arteriography over a 7-yr period are discussed. Three patients were treated surgically and 4 by percutaneous embolization. The latter method appears to enjoy certain advantages and it may prove to be the treatment of choice for this often fatal condition.


Decreased uptake of 67gallium citrate (67Ga) by a bacterial hepatic abscess. Report of a case. A case of anaerobic bacterial hepatic abscess presenting as a "cold" lesion with 67Ga is presented. Its implications in the differential diagnosis and overreliance in metronidazole treatment are discussed.


"Pseudostone" of the gallbladder. Ultrasound findings and case report. The ultrasonic criteria for the diagnosis of gallbladder calculi are: (1) echo-dense structures which disturb the smooth contour of the posterior border of the gallbladder; (2) sonic shadowing, and (3) echoes from within the gallbladder. Diagnostic confidence increases greatly in cases in which internal echoes, contour irregularities, and sonic shadows have occurred simultaneously. A case is presented in which all three criteria are fulfilled, but which represents an artifact, i.e., "pseudostone." This was confirmed by varying the patient's respiration and showing that the "pseudostone" represented echoes from a loop of bowel which produced a significant impression on the posterior wall of the gallbladder during deep inspiration. The absence of cholelithiasis was confirmed by oral cholecystography.


Thoracic spinal cord tumor presenting with dysautonomic diarrhea. A patient, presenting with incapacitating diarrhea of 1-month duration, developed orthostatic hypotension and progressive long tract central nervous system signs. No enteric disease was found to account for the diarrhea. An intramedullary midthoracic spinal cord tumor (ependymoma) was found. Diarrhea and hypotension resolved after local cord decompression and irradiation of the tumor. Dysmotility caused by interruption of thoracic sympathetic pathways to the gut was considered responsible for the diarrhea, and altered splanchnic hemodynamics for the hypotension. The regional autonomic neuroanatomy and the known effects of the autonomic nervous system upon bowel function and the splanchnic circulation explain the patient's symptoms.


Hepatitis B surface antigen and e antigen in pleural effusion: a case report. Hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were demonstrated in pleural fluid obtained from a 40-year-old dialysis patient who had HBSAg and HBeAg in her serum. The titers of HBsAg and HBeAg were similar in serum and pleural fluid. Examination of the pleural fluid by electron microscopy revealed the presence of intact hepatitis B virus particles. These findings underline the potential hepatitis B virus infectivity of other body fluids besides blood, especially for medical and laboratory personnel.


Serum albumin levels in patients with the Zollinger-Ellison syndrome. Serum albumin concentrations in 20 patients with proved or presumed Zollinger-Ellison (ZE) syndrome (4.1 +/- 0.8 g per 100 ml; mean +/- SD) were significantly (P less than 0.01) lower than the levels observed in 40 normal controls (5.1 +/- 0.3 g per 100 ml), 40 duodenal ulcer patients (5.1 +/- 0.4 g per 100 ml), and 20 stomal ulcer patients (5.1 +/- 0.3 g per 100 ml). Six ZE patients with metastatic gastrinoma had slightly lower (P less than 0.10) serum albumin concentrations (3.5 +/- 0.9 g per 100 ml) than did 14 ZE patients without evidence of metastatic lesions (4.3 +/- 0.7 g per 100 ml). In a small group of patients studied more extensively, the mechanism of hypoalbuminemia was found to be complex. In addition to metastatic tumor growth, both gastrointestinal protein loss and impaired albumin synthesis may be factors in the pathogenesis of hypoalbuminemia. Inadequate nutrition was only evident in 1 patient with esophageal stricture and in 2 patients with extensive tumor growth after total gastrectomy. Total gastrectomy induced a rise in serum albumin in all 8 patients studied (P = 0.01). It is concluded that low serum albumin concentrations in peptic ulcer patients may be a clue to the diagnosis of ZE syndrome.


Effect of bile on lysosomal stability in the mucosa of the canine gastric antrum. The bound and free acid hydrolases from bile and bile- then acid-treated canine antral mucosa were compared with control tissue, using explants held in a series of Lucite chambers. Normal levels of activity of bound mucosal enzymes decreased as a result of bile acid insult, but "free" activity in the cytosol increased markedly. Organelle membrane stability was "tested" by submitting isolated particulate matter containing lysosomes, to hypoosmotic shock and to mechanical stress. Release of cathepsin D, only, was observed after bile treatment in vivo. Bile, followed by acid, however, damaged organelle integrity causing release or "leakage" of seven acid hydrolases.


Family studies of lactase deficiency in the American Indian. To determine the pattern of inheritance of lactase deficiency, we studied 104 American Indian and 2 white subjects in 19 families. Subjects were considered deficient in lactase if breath-hydrogen excretion exceeded 0.20 ml per min above fasting at 2 hr after a lactose load of 2 g per kg of body weight (maximum 50 g). Seventy-one per cent of the males and 75% of the females were lactase deficient. In three families in which both parents were lactase normal, 40% of the children were lactase deficient; and in the three families with one parent lactase normal and the other lactase deficient, 65% of the children were deficient in lactase; and finally, in the seven families with both parents lactase deficient, 93% of the children were lactase deficient. This distribution of lactase deficiency in the families suggests that this trait shows an autosomal-recessive pattern of inheritance.


[Central action of beta-phenylethylamine derivatives (10). Effect of L-Dopa on metaraminol induced motor activity (author's transl)]. The present experiments were undertaken in investigate the effects of Ro4-4602 plus L-Dopa on biphasic action induced by metaraminol (MA) in mice. The following results were obtained: Spontaneous motor activity (SMA) suppressed by MA was recovered by pretreatment of Ro4-4602 plus L-Dopa and increased by more than 100 mg/kg of L-Dopa. However, SMA was increased by more than 400 mg/kg of L-Dopa in saline pretreated mice. In MA pretreated mice, SMA by L-Dopa markedly increased in proportion to the doses of MA. The peak time of SMA by L-Dopa in MA pretreated mice was observed to be faster than that in saline pretreated mice. When L-Dopa was injected into MA and saline pretreated mice, there was no significant difference of brain dopamine content between the two groups. From the above results, it is considered that the enhanced effect of L-Dopa in MA pretreated mice may be due to production of a supersensitivity to catecholamines in the central nervous system. MA induced hyper-motor activity was enhanced by pretreatment of Ro4-4602 plus L-Dopa which have no influence on SMA.


[Studies on sulfhemoglobin formation by various drugs (2) (author's transl)]. Sulfhemoglobin (SHb) and methemoglobin (MHb) formations by various aniline erivatives were examined by a single and three consecutive intraperitoneal administrations to mice. It was found that with a single administraion, methemoglobinemia was induced by aniline, 2-methylaniline, 3-methylaniline, 4-methylaniline, 3-trifluoromethylaniline (3-TFMA), 4-trifluoromethylaniline (4-TFMA), 2, 3-dichloroaniline, 2-aminopehnol, acetanilide (AA), 2-hydroxyacetanilide, N-methylaniline (NMA), N,N-dimethylaniline (NDMA), N-ethylaniline (NEA) and N,N-diethylaniline, and was not observed with 2, 3-dimethylanilnie, 2-trifluoromethylaniline, 3-aminophenol, 4-aminophenol, 2. 6-dichloroaniline, 3-hydroxyacetanilide (3-HAA), 4-hydroxyacetanilide (4-HAA), 2-aminobenzoic acid, 3-aminobenzoic acid, 4-aminobenzoic acid and 4-chloro-2-aminobenzoic acid. On the other hand, sulfhemoglobinemia which appeared much more delayed than MHb, with a single administration, was found to be induced by 3-TFMA, 4-TFMA and NMA. Furthermore, with three consecutive administrations, such was induced by AA, 3-HAA, NDMA and NEA even though SHb was not demonstrated with a single administration. Structure-SHb and MHb forming property relationships were discussed.


[Electroencephalographic effects of chlorphenesin carbamate, a new central muscle relaxant, in rabbits (author's transl)]. Electroencephalographic (EEG) effects of chlorphenesin carbamate were investigated in rabbits with chronic electrode implants, and compared with those of chlormezanone and methocarbamol. Chlorphenesin carbamate (50 mg/kg i.v., 100 mg/kg i.d.) induced a drowsy pattern of spontaneous EEG consisting of high voltage slow waves in the cortex and amygdala, and desynchronization of hippocampal theta waves. Chlormezanone also elicited similar EEG changes but such were much more potent than chlorphenesin carbamate. Methocarbamol showed no effect on spontaneous EEG. Chlorphenesin carbamate caused sedation in this period and muscle relaxation was more potent than that of chlormezanone. The EEG arousal response to auditory stimulation and to electric stimulation of the posterior hypothalamus, centromedian thalamus and mesencephalic reticular formation was slightly depressed by chlorphenesin carbamate. Chlorphenesin carbamate, as with chlormezanone, markedly depressed the limbic afterdischarges elicited by hippocampal stimulation. These EEG effects of chlorphenesin carbamate were qualitatively similar to but much weaker than those of chlormezanone, whereas the muscle relaxant effect of chlorphenesin carbamate was more potent than that of chlormezanone.


[Effects of prostaglandin E2 and F2alpha on the phospholipid metabolism in cotton pellet granuloma (author's transl)]. Effects of prostaglandin (PG)s on phospholipid metabolism in cotton pellet granuloma were studied. Fifty ng of PGE2 or PGF2alpha was injected twice a day for 3 days into cotton pellet which was implanted into the interscapular region of rats. Phospholipid content in granuloma tissue treated with PGE2 was about 3 times that of control. The incorporation of 32P-orthophosphate into phosphatidylcholine in granuloma treated with PGE2 was about 6 times that of control. The incorporation of 32P-orthophosphate into phosphatidylethanolamine was increased by PGF2alpha but not by PGE2. These results suggest that PGE2 and PGF2alpha have a different site of action in the proliferative inflammatory process.


[Statistical studies on the resected gastric cancer of 1538 cases in Hokkaido (author's transl)]. 1538 cases with resected gastric cancer in 1974 were registered by the group of surgeons from 76 main hospitals in Hokkaido, who wished to clarify the present situation of the operation of gastric cancer in Hokkaido. The results were as follows; The ratio of male to female was 1.9 to 1.0. The frequency of the resection was 76.9%. The frequency of the early cancer was 13.5%. The frequency of the total gastrectomy was 15.3%. No remarkable differences were found between the above-mentioned results and the results from the whole country. However, the differences between the operable cases estimated by the mortality returns and so forth and the actual cases of the operation amounted to more than 500. Therefore it was clarified that a large number of cases with the gastric cancer for which the operation was indicated failed to be operated. Thus these studies have given out an important subject for the operation on the gastric cancer.


Demonstration of glucocorticoid receptors in human mammary carcinomas. Tumor regression is sometimes observed during glucocorticoid treatment of patients with breast cancer. The possibility of a direct tumor-growth-suppressing effect, mediated by steroid-hormone receptors, cannot be excluded. A 3H-dexamethasone-binding component in the cytoplasmatic fraction of human breast cancers was studied by agar-gel electrophoresis. Of 90 samples, 51% contained a significant amount of an apparent glucocorticoid receptor. In two specimens from metastases, in which a preexisting lymph node structure was almost completely replaced by tumor tissue, the glucocorticoid receptor character of the binding component was studied extensively. The component satisfied the steroid-hormone receptor criteria in being a high affinity (Kd approximately 4--9 X 10(9) M), low capacity binder. Competition studies with excess unlabelled steroids of different classes confirmed the specific glucocorticoid receptor character of the component. Both tumors contained also estrogen and androgen receptors and one contained an apparent progestin receptor.


The effects of pineal indoles given late in the light period on reproductive organs and pituitary prolactin levels in male golden hamsters. Intact and pinealectomized adult male hamsters kept in light:dark cycles of 14:10 (in hours) were given daily injections of either 25 microgram melatonin, 5-methoxytryptophol, N-acetylserotonin, or 6-hydroxymelatonin at 19.00 hours (13h after lights on). The injections were continued for 50 consecutive days. The daily melatonin injections significantly elevated body weights and depressed the growth of the testes and accessory sex organs and pituitary prolactin levels in intact hamsters. By comparison, in pinealectomized animals daily afternoon melatonin injections failed to alter body or testicular weights or pituitary prolactin levels. These findings indicate that for single injections of melatonin to be antigonadotrophic in the male hamster, the pineal must be intact. In intact animals, 5-methoxytryptophol and N-acetylserotonin slightly depressed the growth of the reproductive organs and pituitary prolactin levels, respectively. Again, these effects were negated by removal of the pineal gland. 6-Hydroxymelatonin was without influence on any of the parameters of reproduction that were measured.


Abnormalities in growth hormone and insulin release in short but otherwise normal patients. The arginine-insulin-glucose (AIGT) stimulation and suppression test. Arginine-insulin stimulation and IV glucose suppression (AIGT) tests were used to evaluate release of insulin and growth hormone. Adult patients responded normally. Hypopituitary patients showed no hGH response. One third of short normal patients showed abnormal hGH responses to glucose suppression. Two thirds of the short normal patients showed poor insulin responses to either amino acid or glucose stimulation. Such patients might have abnormalities in release mechanisms for insulin and suppression mechanisms for hGH and this might contribute to their growth failure.


Metabolism of prostaglandin F2alpha in early human placenta in vitro. The authors were investigating the metabolism of prostaglandin F2alpha in human early placenta, in in vitro incubation experiments. They have identified both major metabolites, 15-keto-PGF2alpha and 15-keto-13,14 dehydro PGF2alpha. They have examined the change in the percentage of these, taken as a function of time. They have established that the main site of inactivating the endogenous PGF2alpha is the early human placenta. They suppose that the considerable Pg-inactiviting effect of the placenta has a part which acts as a protecting mechanism in preventing the uterotonic influence of the endogenous prostaglandins.


Deletion of the long arm of chromosome 8 resulting from a de novo translocation t(4;8) (q13;q213). Report is given of a mentally retarded and dysmorphic patient with a partial monosomy 8q, resulting from a de novo translocation t(4;8)(q13;q213). Oetermination of erythrocyte glutathione reductase (E-GSR) activity in the proposita shows activity in the normal range. Previous evidence for of the assignment of E-GSR locus to the short arm of chromosome 8 is confirmed.


Mosaic trisomy 9: two additional cases.

Mosaic trisomy 9: two additional cases. Two unrelated patients were found to be mosaic for an extra chromosome 9 (46,XX/47,XX,+9). The first patient showed a prominent nose, deep set eyes, carp shaped mouth and complex congenital cardiac anomalies. She died of congestive cardiac failure at the age of 10 days. The second patient, was a 7 1/2 year old female who had persistent alacrimia and mental retardation.


Monosomy 21 in a human spontaneous abortus. Morphogenetic disturbances and phenotype at the cellular level. Complex investigation of a spontaneous abortus with monosomy 21 was carried out. Phenotypic expression at the organism and tissue level was characterized by the pathology of the external form of the embryo and by abnormalities of the embryonic facial structures, the stomodeum, the anterior part of the primary gut, and neural tube development. The anomalies found in the embryo indicate primary morphogenetic disturbances arising at the initial stage of organogenesis. Investigation of LHC-431 strain cells derived from musculocutaneous embryonic fragments revealed a complex of cytophenotypic alterations similar to the cellular syndrome of trisomic cells and indicating an insufficient biologic maturity of the mutant cells (alterations of cellular form, disturbances in their contact orientation, underdevelopment of fibrillar apparatus and decreased collagen formation, changes in the accumulation of intracellular metabolic products, decreased growth capacity and alterations of mitotic cycle parameters). It was found that the single chromosome 21 takes part in assocations twice as frequently as would theoretically be expected.


Unusually long survival in a case of full triploidy of maternal origin. A female newborn with full triploidy and multiple malformations, who survived for 2 months, is presented. In all examined lymphocytes and fibroblasts a 69,XXX karyotype was found. Banding studies showed the presence of one 9qh in the mother and two 9qh chromosomes in the child, indicating that the triploidy arose from the failure to expel the second polar body.


Hirschsprung's disease and congenital deafness. Familial assocation. A family is described showing deafness in three consecutive generations. Hirshchsprung's disease was present in at least two of the affected patients and a history of bowel dysfunction was present in the third. The assocation of the two disorders in this family may be due to a single autosomal dominant gene and in this regard differs from previously reported isolated patients with Hirschsprung's disease and deafness.


Genetic aspects of febrile convulsions.

Genetic aspects of febrile convulsions. A total of 6706 children 3 years of age (3491 boys, 3215 girls) in a particular geographical area in Fuchu (population approximately 182 000), Tokyo, was investigated. Some 654 children (9.8%; 10.5% for male, 9.0% for female) had had at least one convulsion, and the incidence of febrile convulsions was 6.7% (7.2% for male, 6.2% for female). The 450 FC children with febrile convulsions and 620 randomly selected control children were analyzed on the mode of inheritance. The incidence of the disease among siblings was 21.9% (29.7% after age correction), which rose greatly with increasing numbers of affected family members, and the segregation ratio among siblings was higher (36.5%) with one FC parent, and lower (18.5%) if neither parent had had a seizure. The more severe the illness in FC children, the larger the incidence among siblings. Population and family studies indicated that heredity plays an important role in febrile convulsions and that multifactorial inheritance is most likely.


Genetic considerations on association between HLA and disease. A statistical method has been developed which can be used to distinguish between various possible explanations for the associations that have been observed between HLA and certain diseases. By analyzing the numbers of B27 positives with and without a second detectable B locus antigen in patients with ankylosing spondylitis and in a control series, three possible hypotheses have been tested: 1. the B27 antigen itself makes an individual more susceptible; 2. a recessive susceptibility gene is closely linked with HLA; 3. a dominant susceptibility gene is closely linked with HLA. In four groups of patients suffering from another disease the procedure has also been applied and it turns out that at least in some of these the second hypothesis can be rejected while the third seems to be the most likely.


Length of human constitutive heterochromatin in relation to chromosomal contraction. Linear measurement of blocks of constitutive heterochromatin and the euchromatin portion 1q-h in three members of a family was used to study the dependence of the size of C blocks on the degree of chromosomal contraction. The results demonstrate that the size of heterochromatin portions decrease regularly with an increases of the degree of euchromatin contraction. The dependence was found to be linear, except for mitoses with an extremely high or low degree of contraction. The finding was used for the development of a new method of evaluation of constitutive heterochromatin.


Psoralen/UVA treatment and chromosomes. I. Aberrations and sister chromatid exchange in human lymphocytes in vitro and synergism with caffeine. Treatment of human lymphocytes in vitro with trimethylpsoralen or 8-methoxypsoralen and UVA irradiation (PUVA) induced chromosome damage, mainly constrictions and gaps, but also breaks and exchanges, and increased the frequency of sister chromatid exchange (SCE). The localization of the chromosome aberrations was nonrandom. The coincidence of many PUVA hits with mercaptoenthanol hits suggest that PUVA may have other targets in the cell than the DNA, perhaps the folding proteins of the chromosomes and the nuclear membrane/chromatin attachment organelles. Caffeine increased in a synergistic way the chromosome aberration yield if added after PUVA treatment, but there was no effect when caffeine was present before and during PUVA treatment. The SCE frequency was increased in the presence of caffeine.


Electrophoretic and kinetic studies of human erythrocytes deficient in pyrimidine 5'-nucleotidase. A new case of a defect in red cell pyrimidine 5'-nucleotide (P5N) activity was found in a large family from Guadeloupe in the West Indies. The propositus presented a characteristic hemolytic anemia with red cell basophilic stippling, an increased GSH level, and a shift of the peak in absorbance of nucleotide. The enzyme activity from the deficient red cells differed from that of the normal. The P5N activity of the deficient red cells was about 14% that of normal. The electrophoretic pattern of P5N activity of the deficient red cells was distinct from that of the control in terms of its Km and of the effects of pH on its maximum activity and heat stability. The significance of such differences is discussed.


Linkage between phosphoglycerate kinase and Xg in a large German kindred. In a family with an extremely rare PGK variant, linkage with Xg was investigated. The analysis suggested that linkage might prove measurable. The estimate of the recombination fraction was 0.07 and the 90% probability limits were 0.05--0.28. The height of the antilog curve was 19.


Glyoxalase I polymorphism in South African Bantu-speaking negroids. The newly described genetic polymorphism of glyoxalase I (GLO) is studied in seven ethnically defined Negroid samples from South Africa (total: n = 843). The allele frequencies between the different Negroid samples studied vary only marginally. However, the allele frequency of GLO1 for the South African Negroid samples combined (i.e., p = 0.259), is highly significantly lower than that for Caucasoid samples.


No evidence for linkage disequilibrium between Bf and GLO in African negroids. A sample of South African Negroids (n = 791) was scored for each individual's Bf and GLO phenotype. (The genes for the Bf and GLO olymorphisms are included in a known cluster of linked genes on chromosome 6.) Following a x2-test the respective two series of alleles were found to be disturbed at random, i.e., there was no evidence for a linkage disequilibrium. This result is discussed in terms of the linkage relationships and map distances of the genetic markers involved.


Size variation polymorphisms of the short arm of human acrocentric chrosomes determined by R-banding by fluorescence using acridine orange (RFA). One hundred normal Caucasians were studied by the RFA technique to estimate the frequencies of size variation of the short arm of acrocentric chromosomes. Each size variation was classified into one of five levels. The most frequent size level(code) was 3; therefore, this was regarded as the 'average' size. If one excludes the average size, the frequencies of size variation by RFA for chromosome 13, 14, 15, 21, and 22 were 22.5, 19.5, 14.5, 19, and 17% respectively. There was no significant difference for the overall frequencies of size variation between sexes. Furthermore, the RFA technique detects more variation in the size of human acrocentric chromosomes than any other method.


A rare adenosine deaminase allele (ADA6) in an Arab moslem village in Israel. The rare allele ADA6, was detected in seven members of an Arab Moslem family from northern Israel. All had the electrophoretic pattern of heterozygotes ADA6--1. This phenotype was formerly described in a small German family. The individuals examined in this study are a small branch of a much larger family only part of which lives in Israel. The origin of the family was traced back to a tribe which migrated to Jordan in the XVIII th century from the Kingdom of Hegaz in the northern part of the Arabian peninsula.


Partial 9q trisomy associated with a 9,21 translocation. A new case of partial trisomy 9q was found in a child presenting two de novo aberrations: a deletion of the long arms of 9 and a 9,21 translocation. A tentative cytogenetic explanation is put forward.


X inactivation pattern in an unbalanced X-autosome translocation with gonadal dysgenesis. An unbalanced X-autosome translocation was observed in a patient with primary amenorrhea, Turner phenotype and bilateral streak gonads. The karyotype of the proposita was 45,X,-X,+der(6),t(X;6). Autoradiography and BUDR pretreatment revealed differential inactivation of the X chromosomes. Sex chromatin pattern was in good agreement with the types of the X inactivation. Our finding brings out some further questions regarding inactivation of the human X chromosome and the human X chromosome and the related phenotypical changes.


Population studies in northern Sweden. VIII. Ethnic heterogeneity and prenatal selection in the esterase D polymorphism. The esterase D polymorphism was studied in samples of red cells from different populations and in extracts of chorionic tissue from abortuses and placentae at term. No frequency differences were found between Finns, Lapps, and Swedes. The high frequency of the ES D2 gene previously observed among Lapps was not confirmed in this study. The distribution of ES D phenotypes was very similar in spontaneously aborted fetuses, newborns and adults, hence there was no evidence for prenatal selection operating in this polymorphism.


Red cell enzyme types in psoriasis.

Red cell enzyme types in psoriasis. Seven red cell enzyme systems were examined for electrophoretic variation in a series of psoriatic patients. In two polymorphic (ADA, ES D) and four non-polymorphic systems (SOD, MDH, LDH, Dia) no deviations from normal controls were found. In the acid phosphatase system the frequency of the pa gene was found to be decreased.


HLA types, blood groups, serum protein and red cell enzyme types among Samoans in New Zealand. 101 Samoans living in New Zealand, of whom 77 had no known non-Samoan ancestry, have been typed for nine blood group systems, four serum protein and 23 red cell enzyme systems, for haemoglobin variants and antigens at the HLA A nad B loci. The frequencies of genes in these various systems suggest that Samoans fall partly into an island Melanesian-Micronesian pattern, and partly are unique. Their uniqueness is most distinctive for the HLA system.


Atypical (Ea1) and fluoride-resistant (Ef1) cholinesterase genes: absent in a native American Indian population. A population of 358 Navajo Indian children screened for serum cholinesterase variants failed to show the presence of either atypical or fluoride-resistant genes. This is the first significant anthropological observation of the absence of both variants in a native North American population.


Effect of the elimination of suppressor cells on the development of DNCB contact sensitivity in guinea-pig. The effect of suppressor cells on the formation of effector cells was studied by comparing the development of DNCB contact sensitivity in cyclophosphamide-treated (suppressor cells eliminated) and non-treated (suppressor cells present) guinea-pigs. From experiments in four different models of generation of effector cells the following conclusions are drawn: (1) impulses activating the formation of effector cells also activate suppressor cells; (2) under conditions of conventional immunization, suppressor cells are activated later than effector cells; (3) elimination of suppressor cells results in an increase in the intensity and duration of specific skin reactions.


Activation of the alternative pathway by gluten. A possible aetiological factor in dermatitis herpetiformis. Gluten fractions are shown to activate the alternative pathway of complement when added to normal human serum. Breakdown of C3 and Factor B occur in a manner analogous to that when activated by zymosan, in the presence of MgEGTA and in serum devoid of classical pathway activity. The suggestion is made that bypass activation may be the primary event when gluten enters the serum across a damaged gut mucosa. Immune complexes containing non-complement fixing IgA antigluten antibody are carried to the skin where it is proposed that complexed gluten activates C3 and initiates an inflammatory reaction.


Macromolecular inhibitory factor for lymphoid cells produced by mouse macrophages. Supernatants of high density cultures of mouse peritoneal macrophages were inhibitory to homologous lymphoid cells in vitro by a number of parameters: proliferation and survival of lymphoma cells was impaired, the immune response of spleen cells to sheep red cells and to Concanavalin A (Con A) was decreased. Inhibition was due to factor(s) with mol. wt of approximately 110,000 as estimated by gel filtration. Activity was stable to heating at 56 degrees, and was resistant to trypsin but not to pronase.


Antibodies to Acholeplasma laidlawii membrane lipids in normal guinea pig serum. Acholeplasma laidlawii is killed and lysed by fresh normal guinea pig serum (GPS) without additional antibodies. Prior incubation of GPS with whole A. laidlawii organisms abolishes the killing activity of GPS. In the present study it was demonstrated that antibodies are present in normal GPS. The classical pathway, not the alternative pathway, of the complement sequence was activated by these antibodies in fresh normal GPS. The antibodies in GPS belong to the IgG class of immunoglobulins. They are directed predominantly against the membrane phospholipids of A. laidlawii. These antibodies may be induced either by natural infection of guinea pigs with A. laidlawii or by antigenic determinants of other microorganisms of food antigens.


Factors influencing the appearance of antibody in tracheal washes and serum of young chickens after exposure to Newcastle disease virus. The development of plaque-neutralizing antibody in tracheal washes and hemagglutination inhibition antibody in serum was followed after intratracheal and intranasal or intramuscular inoculation of 1-, 14-, or 28-day-old chicks with a lentogenic strain of Newcastle disease virus (NDV). Serum antibody could be detected between 7 and 10 days after intratracheal and intranasal vaccination in birds either with or without maternal antibody to NDV. However, among the 1-day-old group only birds without maternal antibody showed an antibody response after intramuscular inoculation. All birds possessing either actively or passively acquired serum antibody showed a sharp rise and subsequent decline of anti-NDV activity in tracheal washes between 4 and 10 days after intratracheal or intranasal vaccination. Using radiolabeled chicken immunoglobulin injected intravenously as a tracer, it was shown that this initial peak of anti-NDV activity in tracheal washes could be accounted for by enhanced transudation of serum antibody. The transudation of serum antibody coincided with the course of viral pathology observed in the tracheae of infected birds. Neutralizing antibody in tracheal washes beyond 10 to 14 days postvaccination was, most likely, porduced locally, in the respiratory tract.


Effect of bursectomy and depletion of immunoglobulin A on antibody production and resistance to respiratory challenge after local or systemic vaccination of chickens with Newcastle disease virus. Surgical removal of the bursa of Fabricius from newly hatched chicks resulted in a depletion of immunoglobulin A (IgA) from serum and bile of 55 and 67% of the birds, respectively, up to 11 weeks of age. The occurrence of IgG and IgM in serum and IgG in bile was not affected by neonatal bursectomy (Bx). A slight compensatory increase in the occurrence of IgM in bile was noted in Bx birds. When exposed to a lentogenic strain of Newcastle disease virus by either intramuscular or intratracheal routes, the Bx group produced a level of serum hemagglutinating antibody and tracheal wash neutralizing antibody indistinguishable from that reached in the sham-Bx group. All of the vaccinated Bx birds challenged by intratracheal exposure to a velogenic strain of Newcastle disease virus remained healthy. These results suggest that IgA is not essential for the development of immunity in the chicken and that other locally produced immunoglobulins or transuded serum antibody may protect the tracheal mucosa in the absence of IgA.


Role of host immune response in the development of either encephalitic or paralytic disease after experimental rabies infection in mice. The clinical and histopathological manifestations of the infection of immunosuppressed (cyclophosphamide-treated) and immunocompetent (control) adult mice with the CVS ts 2 strain of fixed rabies virus were correlated with the kinetics of virus multiplication in the central nervous system and with the development of serum antibody. In immunocompetent mice severe paralytic disease causing 80% mortality was accompanied by marked inflammation and degeneration of the central nervous system parenchymatous tissue. Antirabies antibody was detected in all immunocompetent mice severely paralyzed from postinoculation day 6 on; virus was rarely isolated. In contrast, immunosuppressed mice developed encephalitic symptoms with only minor paralysis; the infection was 100% fatal. Histopathological changes in immunosuppressed mice were confined to degeneration and necrosis of individual neurons and mild microglial reaction; virus was isolated from all of these mice. No significant level of antibody was detected. Similar manifestations were seen after infection of immunodeficient (athymic) mice except that the athymic mice developed levels of antibody similar to those of control mice on day 6; antibodies in athymic mice were predominantly of immunoglobulin class M.


Arginine catabolism by Mycoplasma meleagridis and its role in pathogenesis. A thin-layer chromatography technique was used to study the arginine metabolism of Mycoplasma meleagridis. The technique reflected the enzyme activity of the dihydrolase pathway through detection of readily visible end products on X-ray film. Strains of M. meleagridis differing in their pathogenicity for turkeys did not vary in arginine metabolism. In addition, no significant difference was observed in plasma arginine concentrations between M. meleagridis-infected and uninfected poults. It was concluded that the pathogenesis of M. meleagridis infection in turkeys was not based on its competition with the host for arginine.


Purification, resolution, and interaction of the glucosyltransferases of Streptococcus mutans 6715. The extracellular glucosyltransferase produced by Streptococcus mutans 6715 was purified from culture supernatant fluids to a specific activity of 9.6 IU/mg of protein, with an overall recovery of 87%. The purified enzyme preparation, designated unfractionated enzyme (UFE), synthesized only water-insoluble glucans from sucrose during the initial stages of the reaction, although some water-soluble polymers accumulated after extended periods of incubation. It was free from measurable fructosyltransferase activity. The UFE preparation was resolved into two different catalytically active components by ethanol fractionation. One fraction (designated insoluble product enzyme [IPE]) synthesized water-insoluble glucans, whereas the other (designated soluble product enzyme [SPE]) produced primarily water-soluble glucans. The difference between the insoluble glucans made by the UFE preparation and those made by the IPE fraction appeared to be due to interaction of the SPE and IPE components in the UFE preparation. Addition of commercial dextrans or enzymatically prepared glucans to the glucosyltransferase assay altered the amounts of soluble and insoluble glucans synthesized by the UFE preparation. The molecular weights of the major enzymatically active proteins producing insoluble and soluble glucans were estimated by gel filtration chromatography to be 150,000 and 175,000, respectively.


Immunoglobulin E anti-Candida antibodies and candidiasis. Elevated levels of immunoglobulin E anti-Candida antibodies were observed in the sera of patients with systemic and vaginal candidiasis and in cervicovaginal washings of the latter.


Role of sialic acid in saliva-induced aggregation of Streptococcus sanguis. The ability of saliva to induce aggregation of Streptococcus sanguis was destroyed by treating the saliva with protease or neuraminidase. Loss of aggregating activity could be correlated with the appearance of free sialic acid. Clarified saliva contains an endogenous neuraminidase that modifies aggregating activity. Aggregation was inhibited by mixed ganglioside preparations but less effectively by acid-hydrolyzed gangliosides. The aggregating activity of S. sanguis was not related to the rhamnose or phosphorous content of the cell wall or to antigen a, b, c, d, or e.


Quantitative immunoelectrophoretic assay for murine oncornavirus p30: noncovalent facilitation by sodium dodecyl sulfate. Treatment of Rauscher murine leukemia virus lysates with the anionic detergent sodium dodecyl sulfate (SDS) at concentrations between 0.2 to 2.0% SDS per mg of viral protein greatly increased the anodal electrophoretic mobility of p30, the major internal polypeptide. SDS treatment did not reduce p30 antigenicity or cause nonspecific precipitation of normal serum proteins during subsequent immunoanalysis. The increased anodal electrophoretic mobility allowed assay of Rauscher murine leukemia virus p30 by Laurell rocket immunoelectrophoresis. An SDS-facilitated rocket immunoelectrophoresis assay is described that was highly reproducible (coefficient of variability, less than 3.0%) and capable of detecting 125 ng of viral protein. To our knowledge, this is the first report of a quantitative immunoelectrophoretic assay for an oncornavirus antigen. Since SDS binding is a general property of proteins, this method of noncovalently altering electrophoretic mobility appears to be applicable to other antigen-antibody systems.


Tuberculin-specific transfer factor in dogs. Five mongrel dogs were sensitized to tuberculoprotein with Freund adjuvant, as determined by responses to tuberculin skin tests and by in vitro lymphocyte cultures. These animals served as blood donors for production of transfer factor. Nine mongrel dogs received single doses of transfer factor that was tuberculin specific. Successful transfer of tuberculin sensitivity as measured by lymphocyte transformations was achieved in five of nine animals. Canine lymphocyte cultures frequently showed relatively low transformations to mitogens as compared with responses noted in other animals. Dissociation between skin test reactivity and in vitro lymphocyte transformation to tuberculoprotein was noted in two of nine animals. Increases in lymphocyte transformations to phytochemagglutinin were seen in three of nine recipient animals after transfer factor administration. Successful transfer from an animal sensitized by prior transfer factor administration was achieved in one instance. These data indicate that transfer factor-like substances are present in dogs. The reasons why successful transfer was achieved in only half of the recipient animals needs further explanation.


Evaluation of live attenuated plague vaccines in Praomys (Mastomys) natalensis. A live attenuated Yersinia pestis vaccine designated EV76-51f, which had previously been shown to be pathogenic in vervet monkeys but not in guinea pigs, was tested in the multimammate mouse Praomys (Mastomys) natalensis. Doses of 10(6) viable organisms inoculated subcutaneously as either a lyophilized suspension or an agar-grown culture resulted in vaccination fatalities in Praomys but not in white mice. Hemagglutinating antibodies to the fraction 1 antigen were not stimulated by doses lower than 10(4) viable organisms. Agar-grown cultures of the vaccine gave better protection against a virulent Y. pestis challenge than did a lyophilized suspension. All Praomys vaccinated with a dose of 10(6) agar-grown EV76-51f protected against a virulent challenge, whereas even doses up to 10(8) lyophilized bacilli failed to give complete protection. The pathogenicity of a live attenuated plague vaccine derived from the Y. pestis EV76 vaccine strain can be detected in Praomys (Mastomys) natalensis, a rodent species highly susceptible to plague. This animal species may therefore be valuable for the testing of live attenuated plague vaccines before they are tested in costly nonhuman primates.


Corneal endothelium bicarbonate transport and the effect of carbonic anhydrase inhibitors on endothelial permeability and fluxes and corneal thickness. Unidirectional fluxes of bicarbonate across the corneal endothelium were determined. A net flux of bicarbonate from the stromal to aqueous-facing surface was demonstrated. Under conditions of carbonic anhydrase inhibition the net bicarbonate flux was reduced by 54 percent and the passive water permeability of the endothelium was increased. Experiments with the specular microscope demonstrated an increased rate of corneal swelling under conditions of carbonic anhydrase inhibition. Attempts to identify H+ as the cation moving with the bicarbonate ion to maintain electroneutrality were not successful because of the impossibility of sustaining a differential H+ concentration difference across the endothelium.


A microculture technique for the evaluation of corneal cell metabolism in vitro. A microculture technique for the evaluation of the metabolic activity of corneal cells is described and analyzed. The extent of DNA synthesis in microcultures with 10(3) to 2.5 X 10(3) cells per well was initially low during day 1, increasing steadily thereafter. Higher initial concentration of 10(4) to 2 X 10(4) cells per microculture demonstrated a high metabolic activity during days 1 and 2 in culture, followed by a rapid and marked decrease on days 3 and 4. The origin and concentration of serum in the system have been found to be crucial. Xenogeneic serum (fetal calf serum--FCS) had the most potent stimulatory effect on DNA and protein synthesis. Syngeneic serum (guinea pig serum, strain 13--SGpS) or allogeneic serum (guinea pig serum strain 2--AGpS) had a generally less stimulatory effect on the metabolic activity. However, both sera had a relatively much stronger effect on the protein synthesis.


Electrophysiologic and morphologic effects of ophthalmic preparations on rabbit cornea epithelium. The effects of several components of ophthalmic preparations on isolated rabbit cornea were studied by continuous electrophysiologic monitoring followed by fixation for scanning electron microscopy (SEM). Benzalkonium chloride (0.001 percent), thimerosal (0.0004 percent), and amphotericin B (0.0025 percent) all briefly increased ion transport, then greatly decreased epithelial resistance. Severe disruption of surface cell layers occurred simultaneously with resistance decrease. Silver nitrate (0.00017 percent) stimulated transport with less accompanying morphologic damage. Tetracaine (0.05 percent) disrupted epithelial function and caused exfoliation of several cell layers. Chlorobutanol (0.1 percent) produced a nearly complete loss of the squamous cell layer. Chloramphenicol, epinephrine, and pilocarpine produced minor changes in structure and electrophysiology at full clinical concentration. It was concluded that low concentrations of preservatives in ophthalmic preparations disrupt the barrier and transport properties of the corneal epithelium.


The scleral spur and scleral roll.

The scleral spur and scleral roll. The scleral spur and scleral roll together form a fibrous hoop which may be detached from adjacent structures as a unit. Tensile tests of the spur-roll resemble reported data on sclera. It is proposed that the circular structure of the spur-roll prevents action of the meridional portion of the ciliary muscle on the trabecular meshwork from collapsing the canal of Schlemm.


Ocular effects of ultraviolet radiation from 295 to 365 nm. A 5,000 watt Xe-Hg source and a double monochromator were used to produce  6.6 nm. full band-pass ultraviolet (UV) radiation. Pigmented rabbit eyes were exposed to the 6.6 nm. band-pass UV radiant energy in 5 nm. steps from 295 to 320 nm. and at random intervals above 320 nm. Corneal and lenticular damage was assessed and classified with a biomicroscope. Corneal threshold radiant exposure (Hc) rose very rapidly from 0.022 Jcm.-2 at 300 nm. to 10.99 Jcm.-2 at 335 nm. Radiant exposures exceeding 2 x Hc resulted in irreversible corneal damage. Lenticular damage was limited to wavebands above 295 nm. The action spectrum for the lens began at 295 nm. and extended to about 315 nm. Permanent lenticular damage occurred at radiant exposure levels approximately twice the threshold for lenticular radiant exposure. The importance in establishing both corneal and lenticular damage criteria is emphasized.


Effects of hypophysectomy, pituitary gland homogenates and transplants, and prolactin on photoreceptor destruction. Prepubertal removal of the pituitary gland, which in young animals influences sexual maturation, reduces significantly the amount of retinal photoreceptor destruction when the rats are exposed to continuous illumination in adulthood. When crude pituitary gland homogenate is administered to adult rats hypophysectomized prior to puberty, photoreceptor destruction is more severe. Transplantation of whole pituitary glands to the kidney capsule of hypophysectomized rats also reduces the effect of pituitary gland removal and results in more extensive damage to receptor cells than found in hypophysectomized, adult animals. Hypophysectomized rats treated with prolactin had more severe retinal damage than untreated, hypophysectomized rats. The injection of pregnant mare serum and human chorionic gonadotropic hormones into hypophysectomized rats was not effective in reversing the protection afforded by hypophysectomy. Results of these studies indicate the hormones of the pituitary gland have a regulatory influence on the severity of light-induced, retinal photoreceptor damage in the rat.


Retinal ultrastructure in advanced retinitis pigmentosa. An ultrastructural study of the retina of a patient with advanced retinitis pigmentosa revealed an orderly process of cone degeneration with more advanced stages in the perifovea and less advanced stages in the fovea. No rod photoreceptors were seen. Remaining cones had enlarged nuclei with autophagic vacuoles and bundles of parallel undulating 12 nm. filaments in the cytoplasm. In the foveola and fovea, cone outer segments were very truncated or absent, although synaptic pedicles were intact. In the perifovea, many cone cell bodies were rounded with loss of synaptic pedicles. Pigment epithelial cells underlying remaining cones were enlarged with apically displaced nuclei, occasional phagosomes, and large amounts of melanolysosomes. The pigment epithelial cell layer anterior to the perifovea contained flattened pigment epithelial cells without melanolysosomes and macrophage-like cells without pigment. Pigment-laden epithelial cells around atrophic blood vessels in the midperipheral retina showed only round pigment granules unlike the smaller elongated pigment granules observed in retinal pigment epithelial cells in situ. The advanced stage and structural abnormalities in both photoreceptors and pigment epithelial cells preclude assigning a primary site for the defect.


Evaluation of applanation tonometers for the dog eye. The Mackay-Marg, pneumatonograph, TonAir, and EMT-20 tonometers were evaluated in the normal dog eye. Tonometric scale readings were compared to the manometric recordings from the anterior chamber. The Mackay-Marg tonometer evaluated in open and closed systems was the most reliable (goodness of fit [r2] = 0.96) with intraocular pressure up to 100 mm. Hg. The pneumatonograph also exhibited high reliability (r2 = 0.92) but tended to underestimate intraocular pressures above 40 to 50 mm. Hg. The TonAir and EMT-20 tonometers were the least satisfactory for the dog, with r2 of 0.77 and 0.66 to 0.81, respectively. The Mackay-Marg is the most satisfactory tonometer for the dog.


Enhancing fluid secretion by the corneal epithelium. Swollen rabbit corneas incubated in vitro with their posterior surfaces blocked with silicone oil maintained fairly constant thickness over an 11 hr. period. Increasing the simulated intraocular pressure from 10 to 30 mm. Hg did not produce stromal thinning. When theophylline was added to stimulate epithelial Cl secretion by increasing the Cl permeability of the tear-facing epithelial membrane, corneas thinned at the average of 1.3 micrometer/hr. over a 6 1/2 hr. period. When the epithelial perfusion solution was made Cl-free by SO4 substitution to favor the passive flow of Cl from the cells to the tear solution, thinning of 3.91 micrometer/hr. over a 7 hr. period was observed. When corneas were perfused with Cl-free medium plus theophylline, thinning at the average rate of 6.20 micrometer/hr. over an 8 hr. period was achieved. Therefore the corneal epithelium is capable of thinning a swollen stroma by transport of fluid coupled to its Cl secretion, which can be enhanced by simple substitutions in the tear-side bathing solution.


Specific glucocorticoid receptor in the iris--ciliary body of the rabbit. The cytoplasm of the iris--ciliary body of the rabbit contains a receptor capable of specifically binding dexamethasone. This binding protein has a high affinity for dexamethasone (average KD = 2.0 X 10(-8) M), a low capacity (average 4.8 X 10(-13) mol of steroid bound per milligram of protein), and extreme heat sensitivity; it exhibits a pattern of competition virtually identical to that obtained with glucocorticoid receptors from other tissues and shows characteristic physicochemical behavior in various salt concentrations. The demonstration of a specific dexamethasone receptor in the iris--ciliary body provides the first direct biochemical evidence that these tissues may function as a target organ for glucocorticoids.


Intraocular IgE antibody induced in guinea pigs with Ascaris suum larvae. The systemic and local (intraocular) IgE antibody responses to infective and heat-killed Ascaris suum larvae were examined in guinea pigs. IgE antibody, demonstrated by the 6-day P-K test, was found in anterior chamber fluid following primary intravitreal injection of live second-stage A. suum larvae and in some instances occurred when no serum P-K activity was demonstrable. No intraocular IgE antibody was induced by primary intravitreal injection of heat-killed larvae. A brisk intraocular and systemic IgE antibody response followed the secondary intravitreal injection of either live or heat-killed larvae into animals systemically infected with A. suum. The guinea pig system promises to be a useful model for studying the immunopathology of human ocular parasite infections.


Some features of secretory systems in plants. Recent work on secretion in plants is reviewed, with emphasis on the anatomy and physiology of root cap cells in higher plants, the stalked glands of Drosera capensis, and the secretory mechanism of Dionaea muscipula. Cells of the root cap of higher plants switch from a geo-perceptive role to one of mucilage secretion at maturation. Features of this process, the role of the Golgi and the pathway for mucilage distribution are reviewed. In contrast, the stalked glands of the leaves of Drosera capensis are much longer lived and have a complex anatomy. The mechanisms for mucilage secretion, protein absorption and the role of the cell membranes in the internal secretion of the protein are described, using data from X-ray microscopv. The secretion of fluid and protein by Dionaea is stimulated by various nitrogen-containing compounds. Uric acid, often excreted by captured insects, is particularly effective in this respect.


The multiple forms of brain acetylcholinesterase. I. Micro-electrophoresis and topochemical analysis of the pattern. Micro-polyacrylamide gradient electrophoresis followed by active staining is applied for the demonstration of the multiple forms of acetylcholinesterase. Among other advantages the very small samples that enable the analysis of well-defined brain material as well as the almost histochemical conditions of incubation enable its successful use in topochemical investigations of the multiple form pattern of brain acetylcholinesterase. The acetylcholinesterase of bovine nc. caudatus could be separated into 4 multiple forms and the pattern was analysed microdensitometrically. These forms differ in their molecular weight as well as in their degree of membrane binding. Increasing ionic strength (NaCl) is followed by changes in the pattern. This result is discussed as caused by aggregation of enzyme subunits.


DNA synthesis in immunreactive glandular cells in pituitary intermediate lobe cultures. Cell suspensions were prepared from adult rat pituitary intermediate lobes and grown in medium TC 199 supplemented with foetal calf serum. 7 or 8 days old cultures were pulse labelled with tritiated thymidine and thereafter processed for immunostaining using an antiserum against a synthetic alpha-1-28-ACTH-analogue. Immunreactivity was mainly confined to epithelial cells, but some spindle-shaped cells were also immunopositive. Thymidine incorporation was observed in some immunpositive cells which shows that cells committed to hormone production may enter the mitotic cycle.


[The caloric vestibular examination: a simplified technique and its normal values (author's transl)]. A simple modification of caloric vestibular stimulation and its documentation is described to improve the coordination of vestibular investigation in clinics and practice. A volume of 50 cc. 30 degrees and 44 degrees C water is used to irrigate the ear and is administered within a 10 s period. The patient is then evaluated for the rate and duration of nystagmus, using Frenzel lenses. 1182 patients were investigated in this manner and their results were computerized. It was then shown that irrigation with 30 degrees C water was followed by a greater nystagmus reaction (including vertigo and vegetative signs) than with the 44 degrees water.


[A new method of testing directional hearing (author's transl)]. Directional hearing is demonstrated by a test in which a model "hears" loudspeaker impulses at known changes of angle. The sounds are recorded and then presented via headphones to listeners. If the subject notices a change he gives a visual signal and the appropriate change of direction is noted by the tester. -In 40 normal hearing test subjects, 20 who were blind recognized more than 50% of changes of direction of 4 degrees, and 20 with normal vision achieved similar success with direction changes of 5 degrees. Utilizing tape recorder and headphones the advantage of this method is its simplicity.


[Critical notes on the fitting of hearing-aids in children (author's transl)]. The fitting of hearing-aids in hearing-impaired children in the Federal Republic of Germany is insufficient. Misfittings are harmful to the children and cause unnecessarily high costs. Unfortunately there are no clinical experiences with competent controls to be found. Consequently, medical responsibility should be encouraged and a panel of experts created for the evaluation of all patients who require hearing aids. This system can then be used annually to maintain an effective quality cost control.


[Do neomycin ointment dressings damage the inner-ear when used in the external auditory canal or the radical mastoidectomy cavity? (author's transl)]. When in low concentration (0.38%) in an ointment base neomycin within the middle ear does not damage the inner ear. Animal experiments show that doses 10 times greater do not damage the hair cells, but when in aqueous solution all hair cells are destroyed. Many years experience has confirmed that neomycin ointment packing for postoperative ears and infected radical mastoid cavities does not produce inner ear damage. These patients have been carefully monitored by audiometry.


Biotransformation of antitumor agents by a strain of Whetzelinia sclerotiorum. Antitumor antibiotics of the olivomycin and chromomycin class were transformed when incubated with a culture of Whetzelinia sclerotiorum. The products, when purified by counter-current distribution and column chromatography, were shown, by their physical properties, to be the deacylated analogues.


Streptomyces laurentii, a new species producing thiostrepton. The taxonomic description of Streptomyces laurentii, a new species related to but distinguishable from the S. fradiae group, is presented. This new species produces thiostrepton but bears no taxonomic relationship to the known producers of the antibiotic: S. azureus, S. hawaiiensis, and Streptomyces X-14b.


Plasmid-mediated pristinamycin resistance. PAC IIA: a new enzyme which modifies pristinamycin IIA. A wild strain of Staphylococcus aureus which inactivates a wide variety of antibiotics has been found to inactivate pristinamycin IIA, an antistaphylococcal antibiotic. This phenomenon has been demonstrated to be plasmid mediated. The plasmid directs the biosynthesis of an acetyltransferase which is able to O-acetylate the drug. We propose to call the new enzyme PAC (IIA): Pristinamycin acetyltransferase.


Spontaneous activity and heat avoidance of mice. Experiments were conducted with eight female mice on the avoidance of heat stress over the ambient temperature range from 25 to 34 degrees C. Significant avoidance behavior of the animals was observed at Ta = 30 degrees C, becoming more noticeable as the ambient temperature was raised. When exposed to heat, the animals showed peaks of avoidance during the second half of the dark period. This result seemed closely related to the spontaneous activity pattern of mice which reached a maximum between 1800 and 2000 at each experimental temperature. In this experiment, mice were more apt to choose a comfortable place during their inactive period than during their active period. This hypothesis on the relation between mice's heat avoidance and spontaneous activity was supported by the results of an additional experiment conducted in a cold environment of Ta = 18 degrees C.


Effect of ozone on bronchomotor response to inhaled histamine aerosol in dogs. To study the effect of ozone on bronchial reactivity to inhaled histamine diphosphate aerosol, we performed 14 experiments on 5 dogs anesthetized with pentobarbital sodium (25-30 mg/kg, iv) and ventilated with a Harvard respirator. Prior to ozone exposure, inhalation of histamine aerosol (2% solution; 5 breaths) increased total pulmonary resistance (RL) 5.1 +/- 0.5 cmH2O/1 per s (mean +/- SE). One day after ozone exposure (0.7-1.2 ppm; 2 h), the base-line RL was not significantly changed (P greater than 0.05), but the increase of RL caused by histamine (10.7 +/- 1.1 cmH2O/1 per s) was greater than in the control state (P less than 0.01). When the dogs were pretreated with atropine sulfate aerosol (1.5% solution; 10 breaths), the increase of RL after histamine was decreased to 3.8 +/- 0.3 cmH2O/1 per s before ozone, and this was not significantly different after ozone (4.5 +/- 1.1 cmH2O/1 per s; P greater than 0.5). Cooling blockade of conduction in the vagus nerves diminished the increase of RL after histamine to 3.9 +/- 0.5 cmH2O/1 per s before ozone, and this was not significantly different after ozone (4.4 +/- 0.6 cmH2O/1 per s; P less than 0.5). Since both atropine and vagal cooling abolished the ozone-induced bronchial hyperirritability, we conclude that it is mediated via vagal cholinergic pathways.


Bronchial reactivity: interaction between vagal stimulation and inhaled histamine. The interaction between the effects of vagal stimulation and inhaled histamine on the bronchi was studied in anesthetized dogs. Reactivity was assessed by measuring changes in bronchial caliber visualized with tantalum bronchograms. In seven vagotomized dogs the bronchoconstrictor response to a combination of electrical stimulation of the vagus nerves and inhaled histamine solution produced a mean reduction in airway diameter (Daw) of 2.21 mm which was significantly greater than the additive results of the two stimuli applied separately (mean decrease in Daw 0.29 +/- 0.91 mm). In three dogs the effect of vagal stimulation was to produce a shift in the dose-response curve to inhaled histamine. These results indicate that the effect of the base-line bronchomotor tone must be considered in the evaluation of the effect of vagal blockade on airway reactivity. An increase in the resting degree of bronchomotor tone may contribute to the hyperreactivity observed in patients with asthma.


Behavior of artificially produced holes in lung parenchyma. Spherical and cylindrical holes were cut in the parenchyma of isolated dog lung lobes. The holes were insufflated with tantalum dust and the hole diameters were measured along the deflation limb of the lobe pressure-volume curve from transpulmonary pressures of 20 to 0 cmH2O. Hole volume as a fraction of lobe volume was found to be independent of transpulmonary pressure. The hole volume relative to the amount of tissue removed was used to determine the displacement at the hole boundary. A comparison of this displacement with the displacement predicted by a continuum mechanics analysis provides evidence for the applicability of the methods of continuum mechanics and further evidence that the shear modulus of the parenchyma is relatively small.


Potentiation of pulmonary vasoconstrictor response with repeated intermittent hypoxia. To determine the consistency of the pulmonary vasoconstrictor response to hypoxia, dogs were anesthetized, intubated, and ventilated alternately with air and 10% oxygen. Catheters were placed in the pulmonary artery for measurement of pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, and cardiac output and in the femoral artery for monitoring systemic blood pressure and arterial blood gases. Arterial PCO2 and pH were kept at steady levels throughout by ventilating the dogs with a respirator so that only the isolated effect of hypoxia on the pulmonary vasculature was studied. It was found that there was a progressive rise in the PAP with repeated exposure to the same hypoxic stimulus. In 12 dogs, the mean increase in the PAP was 28% above the base line on the 1st hypoxic exposure, rising to 99% by the 10th exposure over the course of 5 h. It was concluded that interpretation of action of agents blocking or enhancing the hypoxic response must take into account this inherent potentiation of the response on repeated exposure to hypoxia.


Thermal effects of reproductive hormones on the sheep udder. The thermal effect of reproductive hormones on the sheep udder was tested in five ewes at the end of their breeding season. Radiotelemetry was used to provide continuous recordings of deep body temperature (Tb), udder skin temperature (Tud), and back skin temperature (Tbk) while the animals were held in a controlled-environment isolation chamber. Injections of estradiol (1.0 and 2.5 mg, im) resulted in an increase in Tud, but not in Tb, and only occasionally in Tbk. The amplitude of the rise in Tud varied from 0.4 to 3.8 degrees C and the rise persisted over 48 h following injection. Injections of saline, prostaglandin (PGF2alpha), or progesterone did not affect Tud, and injections of pyrogen (typhoid vaccine) elicited only an insignificant change in Tud concurrent with substantial increases in Tb and Tbk.


Muscle fiber activity as a function of speed and gait. These experiments were designed to test the hypothesis that locomotory gait transitions occur when some critical cross-sectional area of active muscle is reached as animals increase speed within a gait. We used glycogen depletion as evidence of muscle fiber activity and selected an experimental animal in which all muscle fibers in the locomotory muscles rely extensively on glycogen as a substrate--the lion. We found a high correlation between biochemically and histochemically determined rates of glycogen depletion (r = 0.906). Rates of glycogen depletion in the biceps femoris and triceps brachii muscles increased logarithmically with speed with no discontinuities at the gait transitions. However, we found large discontinuities both in the total cross-sectional area of muscle that showed depletion and in the rates at which the different types of fibers depleted glycogen at the trot-gallop transition. Our results indicate that 1) gait transition did not occur at a maximum tension level either for a particular type of fiber or the whole muscle, and 2) different configurations of motor units within an individual muscle may be recruited as an animal changes gait.


Prediction of heat tolerance from heart rate and rectal temperature in a temperate environment. To determine if heat tolerance could be predicted from responses to exercise in temperature conditions, 51 young men performed 15 min of bench stepping at an average work load of 80 W at 23 degrees C. On the following day they attempted to perform 3 h of bench stepping at 40 W in heat (39.3 degrees C dry bulb, 30.3 degrees C wet bulb). Of these subjects, 4 were heat intolerant, judged by previous heat stroke episodes during field marches, 12 were heat acclimated, and 35 were unacclimated. The heat-intolerant subjects showed the highest heart rates (HR) and rectal temperatures (Tre) at 23 degrees C and in heat, and the acclimated subjects showed the lowest corresponding values. HR and Tre in each environment were combined into a single score, from 10, indicating the poorest responses, to 100, indicating the best responses. These scores at 23 degrees C when correlated with the corresponding scores in heat resulted in a linear correlation coefficient of r = 0.94 with a standard error of estimate of 8.6%. Scores of the heat-intolerant subjects were below 35, and those of the acclimated subjects were between 70 and 100. Thus heat tolerance can accurately be predicted for HR and Tre responses to exercise at room temperature.


Effects of elevated plasma FFA and insulin on muscle glycogen usage during exercise. Seven men were studied during 30 min of treadmill exercise (approximately 70% VO2 max) to determine the effects of increased availability of plasma free fatty acids (FFA) and elevated plasma insulin on the utilization of muscle glycogen. This elevation of plasma FFA (1.01 mmol/1) with heparin (2,000 units) decreased the rate of muscle glycogen depletion by 40% as compared to the control experiment (FFA = 0.21 mmol/1). The ingestion of 75 g of glucose 45 min before exercise produced a 3.3-fold increase in plasma insulin and a 38% rise in plasma glucose at 0 min of exercise. Subsequent exercise increased muscle glycogen utilization and total carbohydrate (CHO) oxidation 17 and 13%, respectively, when compared to the control trial. This elevation of plasma insulin produced hypoglycemia (less than 3.5 mmol/1) in most subjects throughout the exercise. These data illustrate the regulatory influence of both plasma insulin and FFA on the rate of CHO usage during prolonged severe muscular activity.


Biochemical adaptation of human skeletal muscle to heavy resistance training and immobilization. Nine healthy subjects were studied under control conditions and following 5 mo of heavy resistance training and 5 wk of immobilization in elbow casts. Needle biopsies were taken from triceps brachii and analyzed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), creatine (C), creatine phosphate (CP, and glycogen concentrations. Training resulted in an 11% increase in arm circumference and a 28% increase in maximal elbow extension strength. Immobilization resulted in decreases in arm circumference and elbow extension strength of 5% and 35%, respectively. Training also resulted in significant increases in resting concentrations of muscle creatine (by 39%), CP (by 22%), ATP (by 18%), and glycogen (by 66%). Conversely, immobilization significantly reduced CP concentration by 25% and glycogen concentration by 40%. It was concluded that heavy-resistance training results in increases in muscle energy reserves which may be reversed by a period of immobilization-induced disuse.


Kinetics of gas exchange and ventilation in transitions from rest or prior exercise. Seven normal subjects each performed three transitions to a subanaerobic threshold work rate on a cycle ergometer: 1) from rest, 2) from a low work rate (both at 60 rpm), and 3) from a low work rate at 40 rpm to the high work rate at 80 rpm. Oxygen uptake (VO2), carbon dioxide output (VCO2), and ventilation (VE) were computed breath-by-breath and response kinetics extracted. The mean half-times of VO2, VCO2, and VE were 32, 44, and 49 s, respectively, and were not appreciably affected by the prior exercise or by variation of pedal rate. The kinetics of VE was highly correlated with VCO2 (r = 0.94), with VCO2 leading VE, providing further description of the relation of the exercise hyperpnea to CO2 flow to the lungs.


Fatty acid profile and cholesterol in skeletal muscle of trained and untrained men. To compare the fatty acid distribution and cholesterol composition in trained and untrained isolated skeletal muscle membranes, a needle biopsy was performed on the vastus lateralis of the 10 distance runners and 10 sedentary men. The muscle sample was homogenized and centrifuged at 100,000 X g; the resulting pellet was analyzed by gas-liquid chromatography for individual fatty acids and cholesterol. The percentage of palmitic acid was significantly lower in the trained muscle tissue. Samples from the distance runners also tended to have a more frequent appearance of linolenic and eicosatrienoic acids, longer fatty acid hydrocarbon chains, and lower cholesterol concentration. It was concluded that trained muscles have an increased membrane fluidity which could beneficially affect the activity of membrane-bound enzymes and active transport. Longer chain length in the membrane lipids may be a means of producing an inner membrane cohesiveness in muscles of trained individuals.


End-respiratory pressure ventilation and sulfobromophthalein sodium excretion in dogs. Sulfobromophthalein sodium (BSP) 25 mg/kg body wt was given as a single iv injection to 32 fasted dogs. Serum samples at 3, 5, 10, 20, 30, 45, 60, 80, and 120 min postinjection were analyzed for total concentration of BSP and from 30 to 120 min for percent conjugated BSP. Four groups were compared: spontaneous ventilation; intermittent positive-pressure ventilation (IPPV) and continuous positive-pressure ventilation (CPPV) (2 groups). During CPPV, one group of dogs was given a continuous infusion of cholecystokinin octapeptide (CCK-8, 1 ng/kg per min). Central venous pressure averaged 11.3 +/- 0.7 (SE) cmH2O in dogs with CPPV + CCK-8 and 11.8 +/- 0.8 (SE) cmH2O in dogs with CPPV alone. At 3, 5, and 10 min postinjection serum BSP levels were similar in all groups. From 30 to 120 min postinjection serum levels of both free and conjugated BSP were higher in dogs ventilated with CPPV alone than in any other group (P less than 0.01). Dogs given CCK-8 during CPPV had serum BSP levels that were statistically similar to dogs breathing spontaneously or ventilated with IPPV. We conclude that CPPV impairs BSP excretion. This effect is counteracted by CCK-8.


Instrumentation for measuring functional residual capacity in small animals. A system for measuring functional residual capacity (FRC) by the dilution method was evaluated to determine its suitability for use in neonates and small animals. The system makes use of rapid, automatically triggered valves for precise closure at end expiration. Results of a theoretical error analysis and experimental in vitro tests are presented and indicate that the measuring error in FRC is related to the FRC-to-initial rebreathing bag volume ratio. With a 200-ml bag volume one standard deviation of the calculated error was 16% for a 50-ml, 9.1% for a 100-ml, and 5.8% for a 200-ml FRC.


Use of video-taped patient interview simulation in psychiatric medical education. Described is the development of several video-taped simulated psychiatric patient interviews, how they are used in the medical school curriculum at the University of Southern California, and the advantages of simulating patients for medical educational purposes.


Biochemical and metabolic characteristics of articular cartilage from osteonecrotic human femoral heads. The cartilage from nine osteonecrotic femoral heads (six post-traumatic and three corticoid-induced) was obtained at the time of total hip replacement and studied by biochemical and metabolic techniques. The data obtained were compared with those previously obtained in normal hips and were correlated with diagnosis, topographical site, histology, and grading according to a histological-histochemical technique previously described. The results demonstrated surprisingly good preservation of cartilage and no significant alteration in the biochemical and metabolic parameters. These findings showed limited correlation with the topographical site and no correlation with the cause of the necrosis or histological alteration. The results do not support concepts of either accelerated metabolic activity or chondrolytic change.


Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits. Large doses of cortisone were given to growing and adult rabbits over a five-month period to produce avascular necrosis of the femoral head. The cortisone caused an increase in the serum cholesterol, fatty metamorphosis of the liver, and fat emboli visible in sections of the femur and humerus. These emboli partially obliterated the microcirculation of the subchondral vessels of both femoral and humeral heads. The average diameter of the marrow fat cells also increased more than ten micrometers. This increase in cell volume might be significant because in the closed chamber of the femoral head it could increase tissue pressure, diminish perfusion, and be the mechanism for avascular necrosis induced by cortisone.


Patellar-tendon transfer by the slot-block method for recurrent subluxation and dislocation of the patella. In sixty-five knees followed for an average of 4.5 years after treatment of subluxation or dislocation of the patella by the slot-block method of medial patellar-tendon transfer, the results were satisfactory in fifty-four (83%) and unsatisfactory in eleven (17%). Recurrent subluxation or dislocation occurred in three (5%) of the knees and was attributed to insufficient displacement. Chondromalacia of the patella became worse after transfer in three of the sixty-two knees in which the distal realignment was technically correct. Two knees (3%) required patellectomy because of patellofemoral symptoms and there were nineteen complications in seventeen knees, including loss of motion in six, wound infection in six, displacement of the bone block in three, recurrent dislocation in three, and rupture of the patellar ligament in one. The method is believed to give superior results but it is technically demanding.


Fractures of the distal femoral epiphyses. Factors influencing prognosis: a review of thirty-four cases. In a review of thirty-four fractures through the distal femoral epiphyseal plate followed for an average of four years, limb-length discrepancy of 2.0 centimeters or more (measured roentgenographically) occurred in 36% and varus or valgus deformity measured as a difference of 5 degrees or more between the involved and uninvolved extremities occurred in 33%. Reconstructive procedures (osteotomy, epiphyseodesis, or both) were required in 20%. Limitation of knee motion (eleven patients), ligament laxity (eight patients), and quadriceps atrophy (five patients) were also observed. Prognoses made on the basis of the Salter-Harris classification alone were not reliable. The development of deformity appears to be related to the degree of initial displacement of the fracture, the exactness of the reduction, and the type of fracture.


Total hip replacement and femoral-head bone-grafting for severe acetabular deficiency in adults. We performed total hip replacement in twenty-seven hips of twenty-two patients with osteoarthritis secondary to congenital dislocation, congenital dysplasia, or acetabular insufficiency due to persistent fracture-dislocation. The femoral head was used as a bone graft, attaching it to the acetabular wall to provide bone stock for reconstruction. There were few postoperative complications. In thirteen hips followed for over one year, all grafts appeared to be united and none showed evidence of resorption. Eleven of the thirteen hips were pain-free and two were slightly painful. Eleven hips had a range of motion of 90 degrees or more.


Partial or total meniscectomy: a comparative analysis. We studied a total of 128 cases of meniscectomy, eighty-nine total and thirty-nine partial, and evaluated the relative postoperative morbidity. The patients who had a partial meniscectomy had a shorter hospital stay and spent less time using crutches. Those with a total meniscectomy had four times the incidence of major postoperative complications. Partial meniscectomy gave better subjective functional results and better anatomical results in all the criteria studied.


Stress fractures of the medial tibial plateau. In a review of thirty-six patients with fifty-seven stress fractures of the medial tibial plateau, I found that limitation of activity was universally successful in treatment. Neither displacement of the fracture nor recurrence of symptoms after healing were seen. The main danger in this entity is misdiagnosis and inappropriate treatment.