Altered lysosomal glycohydrolase activities in juvenile diabetes mellitus. Studies have been carried out on activities of lysosomal beta-N-acetylhexosaminidase (hex), beta-galactosidase (beta-gal), alpha-glucosidase (alpha-glu), and acid phosphatase (AP) in serum and urine from patients with juvenile diabetes and matched controls. There is a large increase in blood and urinary hex activity (the former presenting three distinct patterns of abnormality), a moderate increase in urinary beta-gal, and a small increase in urinary alpha-glu activity, but no elevation of blood or urinary AP in the diabetics. Urinary alpha-glu activity in the diabetics shows striking inhibition by glucose, and this may reflect a similar phenomenon in vivo. Although glycohydrolase activities are elevated in patients with no detectable microangiopathy, more striking changes may be observed in patients with severe small-vessel disease. These alterations may be associated with increased glycoprotein catabolism in the diabetic, an area in need of further studies in the human and experimental diabetic animal.


Insulin and growth-hormone responses in neonatal hyperglycemia. Glucose, insulin, and growth hormone values were studied prospectively in 75 premature infants during the first five days after birth. Intravenous glucose was given at a mean rate of 4.7-4.9 mg./kg./min. (range 3-7). Mean birth weight was 1,394+/-47 gm. (mean+/-S.E.M.). Blood glucose values were significantly higher on days 1 and 2 than on days 3 to 5. Hypoglycemia (blood glucose less than 20 mg./100 ml.) occurred in two SGA and one AGA infants. On the other hand, hyperglycemia (greater than 125 mg./100 ml.) was found in 32 of the 75 (42.7 per cent) infants. A significantly greater number of deaths occurred in infants with hyperglycemia (19/32) than in those with normoglycemia (19/32) than in those with normoglycemia (5/43). Mean plasma insulin values were significantly higher on days 1 and 2 (15+/-3 and 18+/-4 muU./ml.) than on days 3 and 4-5 (6+/-1 and 7+/-2 muU./ml.). In addition, mean insulin levels were significantly higher during hyperglycemic than during normoglycemic glucose levels at similar postnatal age. Growth hormone values were higher during the first three days than subsequently, but the values were similar in normoglycemic and hyperglycemic groups. Significant negative correlations were seen between glucose values on the first two days of postnatal life and birth weight, gestational age, and Apgar scores, whereas positive correlations were found with FiO2 and respiratory distress score (RDS).


Significant muscle capillary basement membrane thickening in spontaneously diabetic Mystromys albicaudatus. Skeletal muscle capillary basement membrane thickness was determined in age- and sex-matched normal and spontaneously diabetic Mystromys albicaudatus. In nondiabetic animals the average basement membrane thickness was 482.6+/-48.7 A as against 779.0+/-319.9 A in the diabetic ones. This difference was statistically significant at P less than 0.005.


Ocular palsies in children with diabetes mellitus. The findings in three children with ocular palsies are reported in this paper. Two had insulin-requiring diabetes and one demonstrated only an abnormal I.V. glucose tolerance test. In the first patient the condition resolved in four weeks; in the second it had not fully resolved after 21 months, and in the third patient surgery was required for correction after seven months. We suggest that any child who develops a sudden ocular palsy should be examined for diabetes mellitus.


Effect of multiple daily insulin injections on the course of diabetic retinopathy. Forty-two diabetic patients on insulin once a day in the early stage of diabetic retinopathy were randomly assigned to one of two kinds of insulin regimen, i.e., single or multiple daily injections. Retinal changes were quantitatively estimated by counting the microaneurysms (MAs) observed on fluorescein angiograms at the posterior pole of the more diseased eye. Baseline characteristics of the two groups were not significantly different. These included duration of diabetes, age at diagnosis, daily dose of insulin, amount of urinary sugar excreted in 24 hours, fasting blood sugar (FBS), and number of MAs. During the follow-up (mean duration of three years) the mean yearly progression in the number of MAs was significantly less in the multiple- than in the single-injection groups: 1.8 +/- 0.7 versus 7.2 +/- 1.9 (p less than 0.01; nonparametric test: p less than 0.02). Final values were, respectively, MAs: 15.2 +/- 4.9; 33.0 +/- 7.9; glycosuria (gm./24 hrs): 20.6 +/- 2.5; 27.5 +/- 4.3; FBS (mg./100 ml.): 154 +/- 15; 195 +/- 11. P values comparing the two groups were less than 0.02, less than 0.02, and less than 0.05. Thus, in this clinical trial, made under routine treatment conditions, the use of divided daily insulin injections was effective in improving diabetic control and delaying retinal changes.


A study of the morphological changes in the small intestine of the spontaneously diabetic Chinese hamster. Several morphological changes were observed microscopically in the small intestine of some diabetic Chinese hamsters. Although some alterations lacked statistical significance due to variation, most diabetics displayed a greater incidence and severity compared with nondiabetic controls. The following structural deviations were seen in the small intestines of some diabetics: increased surface area, elevated number of goblet cells per villus, decreased muscle thickness with connective tissue infiltration, reduced number of Auerbach's plexuses, lymphocyte aggregations accompanied by blunted villi, blood vascular lesions and deformed villi due to excessive loss of epithelial cells.


Pancreatic blood flow in conscious dogs after oral administration of glucose. Dogs with electromagnetic flowprobe implanted around the superior pancreaticoduodenal artery and with an hydraulic occluder implanted upstream from the flowprobe were examined between the 3rd and the 8th postoperative day. During an oral glucose load, blood flow increased from the beginning of administration to about 25 minutes, but not when blood glucose and plasma IRI exhibit their maxima. The rise of pancreatic blood flow is assumed to be produced by reflexes similar to those stimulating insulin secretion and exocrine pancreatic function during the early phase of an oral glucose load.


Secretin and insulin: response to intraduodenal acid. Immunoreactive secretin (IRS) and immunoreactive insulin (IRI) levels were measured in humans and dogs following the intraduodenal instillation of hydrochloric acid. IRS levels rose after acid in both instances, but a concomitant rise in peripheral IRI levels was not noted. Premedication of the humans with Scopolamine prevented a rise of IRS in the human subjects. It is concluded that the endovenous release of IRS alone does not result in increased IRI levels in peripheral blood and that IRS release may be under vagal control.


Activity of pyruvate dehydrogenase complex in the mammary gland of normal and diabetic rats. After parturition there is a 10 fold increase in the actual and total activity of the PDH complex in the mammary gland, which can be explained by an increased amount of enzyme protein. There is a marked difference between the activity state of the PDH complex in the suckled and unsuckled gland of the same animals. In fasting rats the active form of the PDH complex is decreased. This effect is further enhanced by inhibition of suckling. In the diabetic state the PDHa activity is reduced, but the change is statistically insignificant. The decreased milk production during diabetes results from the reduction of the total mass of gland. The total activity of the PDH complex is the same in fetal and neonatal liver of the rat. Whereas the PDH complex is fully activated before parturition, there is a significant decrease in the active form of the pyruvate dehydrogenase complex in the liver of the newborn rats.


Effect of high fat vs. high carbohydrate feeding on the development of obesity in weanling ob/ob mice. Mice with hereditary obesity (ob/ob) were fed isocaloric, isoprotein diets with varying proportions of carbohydrate-to-fat from the time of weaning to 18 weeks of age. Body weight, plasma glucose,and plasma insulin were determined at frequent intervals; body lipid and pancreatic insulin were determined at termination. Obesity developed when only carbohydrate was provided as caloric source (and in the presence of essential fatty acid deficiency), but obesity was greatly enhanced when 5% fat was added. Obesity also developed in the absence of dietary carbohydrate, even though hyperinsulinism was significantly reduced by this regimen. It is concluded that 1) both enhanced storage of dietary fat and lipogenesis contribute to obesity, the former more so than the latter; 2) the degree of hyperinsulinism does not determine the degree of obesity; 3) the development of hyperinsulinism does not require stimulation by exogenous oral carbohydrate.


The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics. The microvascular permeability to small and large molecules was studied during good and poor metabolic regulation in ten short duration juvenile diabetics. The following variables were measured; daily urinary albumin and beta2-microglobulin-excretion rates, whole body transcapillary escape rate of albumin (TER), glomerular filtration rate (GFR), capillary filtration coefficient (CFC), and capillary diffusion capacity (CDC). The urinary albumin and beta2-microglobulin concentration were measured by sensitive radioimmunoassays; TER was detemined from the initial disappearance of intravenously injected 125I-labelled human serum albumin; GFR was measured on the forearm by straingauge plethysmography and CDS for 51Cr-EDTA clearance; CFC was measured on the forearm by straingauge plethysmography and CDC, for 51Cr-EDTA was determined in the jyperaemic anterio tibial muscle by the local clearance technique. All the above mentioned variables, except CDC, were significantly increased during poor metabolic regulation, indicating a functional microangiopathy. The mechanisms of these alterations appear to be increased filtration pressure in the microcirculation and/or increased porosity of the microvasculature. The findings of increased microvascular albumin passage are compatible with the hypothesis that the organic - histologicallly demonstrated - diabetic microangiopathy is a long-term effect of periods of increased extravasation of plasma proteins, with subsequent protein deposition in the microvascular wall, i.e. the concept to plasmatic vasculosis.


Experimental study on the effect of large-dose intratumoral OK-432 administration in mice. This experimental study was undertaken to evaluate the effectiveness of a large-dose intratumoral administration of OK-432, which has already been found to be effective when combined with Mitomycin-C, 5-fluorouracil, and cytosine arabinoside, and/or small-dose of OK-432 in clinical use. Large-dose of OK-432 was administered intratumorally 15 days after the subcutaneous inoculation of 2.5 X 10(6) Ehrlich carcinoma cells. At the same time, 2.5 X 10(6) tumor cells were re-challenged intraperitoneally. A combined treatment with a small-dose of OK-432 and Mitomycin-C, cyclophosphamide, or 5-fluorouracil was also made. As a large-dose of OK-432, three-dose regimen of 1,000, 500, and 100 KE/kg was tested. As a small-dose of OK-432, 4 consecutive daily intramuscular injection of 50 KE/kg was examined. From the results obtained the initial intratumoral administration of a large-dose of OK=432 was found to be beneficial for the following combined treatment with a small-dose of OK-432 and Mitomycin-C or cyclophosphamide. The change of phytohemagglutinin (PHA) responsiveness of spleen cells after intratumoral injection of a large-dose of OK-432 was investigated in mice. These results indicated a decrease of PHA responsiveness of spleen cells according to the tumor growth. The intratumoral large-dose administration of OK-432 suggested inhibition of the decrease in PHA responsiveness. The most effective and suitable dose in this experiment was found to be 500 KE/kg in the three-dose regimen.


Induction of tumors in female Donryu rats by a single administration of 1-propyl-1-nitrosourea. Three groups of female Donryu rats were given a single gastric intubation of 800, 400, or 200 mg/kg body weight of 1-propyl-1-nitrosourea and one group of female Donryu rats was given a single subcutaneous injection of 1-propyl-1-nitrosourea. The incidence of tumors was highest for mammary tumors and leukemia, and next for tumors of the ovary, thyroid, and adrenal glands, and in the digestive tract in rats given the chemical by oral administration. There were also scattered tumors in various other organs. Mammary and subcutaneous tumors were found in some rats given a subcutaneous injection of 1-propyl-1-nitrosourea.


Carcinogenic activity of coltsfoot, Tussilago farfara l. The carcinogenicity of young, pre-blooming flowers of coltsfoot, Tussilago farfara L., which is a herb of the tribe Senecioneae, family Compositae, and widely used as a herbal remedy, was studied in inbred strain ACI rats. Rats were divided into 4 groups: Group I received 32% coltsfoot diet for 4 days, and subsequently 16% diet until the termination of experiment. Groups II and III respectively received 8% and 4% coltsfoot diet for 600 days. Group IV was fed a normal diet as a control group. The experiments were terminated 600 days after the start of administration of coltsfoot diet. All the rats in Group I survived beyond 380 days after the start of feeding and 8 out of 12 rats developed hemangioendothelial sarcoma in the liver, whereas only one out of 10 rats developed the tumor in Group II, and no tumors were observed in Group III. Chemical studies on the dried, young flowers used in this experiment suggested that the carcinogenicity of coltsfoot is most probably due to senkirkine, a hepatotoxic pyrrolizidine alkaloid.


Transplantable sarcomas induced by 3-methylcholanthrene in inbred guinea pigs of JY-1 and Hartley/F strains. Inbred strains of guinea pigs, JY-1 and Hartley/F, established in this Institute, were injected subcutaneously with 3-methylcholanthrene. During 1972 to 1974, 15 solid tumors (7 fibrosarcomas, 6 liposarcomas, and 2 atheroma-like tumors) have been induced in 12 animals out of 30 employed. Among the 15 tumors, 1 fibrosarcoma induced in JY-1 and 2 liposarcomas and 1 fibrosarcoma induced in Hartley/F were transplantable and established as the syngeneic lines named J4, H10, H12, and H9A, respectively. In addition, a transplant of J4 into the Hartley/F strain animal was established as an allogeneic subline and named JH4. Pathological and biological characteristics of these tumors are described and differences between these tumors and line 10 hepatoma, established by Rapp et al. in strain-2 guinea pig, are discussed.


Large bowel carcinoma in strain-2 guinea pigs by intrarectal instillation of N-methyl-N'-nitro-n-nitrosoguanidine. Intrarectal instillation of 0.5 ml of a 0.125% solution of N-methyl-N'-nitro-N-nitrosoguanidine twice weekly for 53 weeks to female inbred strain-2 guinea pigs induced multiple large bowel adenocarcinomas in 13 of 15 animals in 52 to 85 weeks. The lesions were plaque-shaped in small tumors and infiltrative or constrictive in large advanced tumors. The neoplasms showed histological features in varied grades of differentiation and invasiveness similar to those of human cases. These findings distinquished them from large bowel cancers chemically induced in rats and mice.


Effect of fundic ulcers induced by iodoacetamide on development of gastric tumors in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine. The effect of ulcers induced by iodoacetamine on the development of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine was studied in male Wistar rats. The ulcerative lesions induced by iodoacetamide were confined symmetrically to the fundic region along the limiting ridge in the stomach and the pyloric region was unaffected. Animals treated with iodoacetamide and N-methyl-N'-nitro-N-nitrosoguanidine produced a high incidence of tumors including adenocarcinoma in the fundic region. The incidence of tumors in the pyloric region in the control group was 80% but there were no tumors in the fundic region. The tumors in the fundic region were most frequently found in the same areas that ulcers had previously been induced. These findings suggest that ulceration and regeneration of the mucosa are important factors in gastric carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine.


Analysis of incipient growth of Yoshida sarcoma in vivo after transplantation of a small number of tumor cells. Incipient growth of Yoshida sarcoma in ascitic and solid forms was analyzed after transplantation of a small number of tumor cells varying from 1 to 10(6). Growth curves of the ascites tumors revealed that the duration of the incipient growth was much longer than the length of subsequent advanced stage and that the ascites tumor during its incipient stage appeared to grow exponentially and most rapidly in the entire course of the tumor development. Growth rate analyses of the ascites and solid tumors showed that, during their incipient stage, the population doubling time prolonged gradually as the inoculum size increased. This phenomenon was thought to suggest probable cell death on account of the transplantation procedure.


Histological classification of urinary bladder cancers in rats induced by N-butyl-n-(4-hydroxybutyl)nitrosamine. Histological types and grades of 613 urinary bladder cancers induced in rats by N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) were analyzed. Most of them (95.1%) were transitional cell carcinomas, the remainder being squamous cell carcinomas (3.3%), undifferentiated carcinomas (2.5%), and carcinosarcomas (0.3%). Among the transitional cell carcinomas, 23.3% were Grade I anaplasia, 55.2% Grade II, and 21.5% Grade III. Among the squamous cell carcinomas, 20% each were Grade I and II, and 60% Grade III. Most of the undifferentiated carcinomas were Grade III. Some of the cases of transitional cell carcinoma had areas of squamous metaplasia and/or glandular metaplasia, and the incidence of metaplasia increased with the grade of anaplasia. Approximately 36% of the cases of transitional cell carcinoma were of the invasive type. Invasive types were twice as numerous among cases of squamous cell carcinoma as among those of transitional cell carcinoma and all of undifferentiated carcinomas were invasive. The incidence of invasive type was closely related to the grade of anaplasia. These results show that the morphological characteristics of urinary bladder carcinomas induced by BBN in rats are similar to those seen clinically in humans.


The effect of betazole on serum group I pepsinogen levels: studies in symptomatic patients with and without recurrent ulcer after vagotomy and gastric resection or drainage. Serum group I pepsinogen (PG I) levels have been determined before and at intervals after the administration of betazole hydrochloride (Histalog) in 50 symptomatic postoperative patients, 20 with and 30 without recurrent ulcer, after either a vagotomy and gastric resection or a drainage procedure. In patients with recurrent ulcer, mean serum PG I levels increased after betazole and reached a maximum of 116.5 +/- 2.2% (SE) of basal at 2 hr; range 98.9 to 135.7%. In contrast, mean serum PG I levels decreased in patients without recurrent ulcer and reached a nadir of 75.0 +/- 4.3% of basal at 2 hr; range 46.9 to 142.4%. All 20 patients with recurrent ulcer and 5 patients without recurrence had a 2-hr serum PG I level of more than 98% of basal, while each of the remaining 25 patients without recurrent ulcer had a 2-hr level of less than 92% of basal. A 2-hr serum PG I level of more than 98% of basal was also correlated with a vagotomy and drainage, a peak acid output of more than 11 mEq per hr, and a positive insulin test, while a level of less than 92% of basal was correlated with a vagotomy and gastric resection, a peak acid output of less than 11 mEq per hr, and a negative insulin test. In addition, basal serum PG I and serum gastrin levels were significantly higher (P less than 0.001) in patients with the former type of PG I response than in those with the latter type of response. The cause of each type of response is not certain, but the data suggest that one of the determinants may be the completeness of vagotomy.


Serum lysozyme in inflammatory bowel disease. Serum lysozyme (muramidase) concentrations were measured in three groups of patients: control, ulcerative colitis and proctitis, and Crohn's disease. The mean +/-SD for each group was: control, 7 +/- 2; ulcerative colitis and proctitis, 7 +/- 2; and Crohn's disease, 10 +/- 4. Although a significant difference was seen between values in patients with Crohn's disease and values observed in those with ulcerative colitis or control patients, an important overlap was found between these groups. Further studies are necessary to explain the disparate results between this study and previous reports.


Thrombocytosis in patients with celiac sprue. In 57% of the patients (12 of 25) seen with celiac sprue, as shown by clinical course and small bowel biopsy, peripheral blood thrombocytosis was present (range: 350,000 to 815,000 platelets per mm(3); mean: 546,000 +/- 44,060 SE). After clinical and histological remission, the platelet counts in these patients fell significantly (range: 188,000 to 300,0000 platelets per mm(3); mean 252,750 +/- 13,211 SE). There was no correlation between thrombocytosis and serum iron, folate, or vitamin B12 levels. Celiac sprue joins inflammatory bowel disease among gastrointestinal disorders as a consideration in the differential diagnosis of thrombocytosis. In these patients, thrombocytosis reflected active disease and was not present during remission. Evaluation of peripheral blood platelets may be useful in the assessment of patients with celiac sprue.


Tissue plasminogen activator in the pathogenesis of protein-losing gastroenteropathy. Tissue fibrinolytic activity, mainly due to activator of tissue plasminogen was increased in the biopsied gastric mucosa of patients with protein-losing gastropathy. Antiplasmin therapy with trans-AMCHA (trans-4-aminomethyl cyclohexane carboxylic acid) was dramatically effective, except in the case of a patient with intestinal lymphangiectasia. These findings suggest that increased fibrinolysis in the gastrointestinal mucosa may play an important role in enhancing mucosal permeability to plasma proteins.


What the gastroenterologist does all day. A survey of a state society's practice. Members of a state society of gastroenterologist collected information about their pattern of practice. Twenty-two of the 41 members voluntarily kept a list of 25 sequential new patients seen during the spring of 1973. Five hundred and fory-nine diagnoses were accumulated; 369 (67%) of these diagnoses were gastroenterological. The five most common gastroenterological diagnoses were: functional disorder, duodenal ulcer, hiatus hernia, biliary tract disease, and esophagitis. The five most common over-all diagnostic areas were: functional disorder, cardiovascular disease, "other" nongastroenterological diagnoses (including obesity), duodenal ulcer, and endocrine malfunction. Geographically dispersed gastroenterologists in Virginia make more than one-half of their primary diagnoses in the area of their subspecialty interest. The primary gastroenterological problems seen are "upper gut" lesions and biliary tract disease. These observations may be of value in planning education, training, or research activities, especially if verified by a broader sample of gastroenterological practitioners.


Quantitative measurement of lactose absorption. The quantity of lactose not absorbed by 4 normal and 6 lactase-deficient subjects was determined by three indirect methods which involved: (1) measurement of pulmonary hydrogen (H2) excretion, (2) pulmonary (14)CO2 excretion, and (3) stool (14)C excretion, after ingestion of 12.5 g of 1-(14)C-lactose and 4 g of polyethylene glycol (PEG). Results were compared with absorption determined directly from the (14)C:PEG ratio of multiple terminal ileal aspirates. The fraction of lactose not absorbed determined by ileal aspiration ranged from 0 to 8% in normals and 42 to 75% in mild-intolerant subjects. Whereas all three indirect methods were useful in qualitatively separating normal from deficient subjects, the quantity of lactose absorbed as determined by H2 excretion correlated most closely with ileal measurements (r = 0.94). Pulmonary (14)CO2 excretion for 24 hr after (14)C-lactose ingestion did not distinguish normal (17 +/- 4% (SEM) of ingested (14)C per 24 hr) from lactase-deficient subjects (21.1 +/- 3%). Likewise, stool (14)C:PEG ratios grossly underestimated malabsorption with less than one-quarter of the nonabsorbed (14)C appearing in the stool. This study suggests that individual differences in susceptibility to diarrhea after milk ingestion by lactase-deficient subjects may be due to differences in the quantity of lactose not absorbed and/or differences in the rate of bacterial metabolism of lactose in the colon. Analysis of ileal fluid collected during passage of the lactose meal indicated that about two-thirds of the osmotic load delivered to the colon consists of endogenous electrolytes. Thus the water load delivered to the colon is about 3 times that calculated to be osmotically held by the nonabsorbed sugar.


Histamine receptors in esophageal smooth muscle of the opossum. Esophageal smooth muscle was examined for histamine receptors. The effects of histamine, the histamine analogs 4-methylhistamine (4-MH) and 2-(2-pyridyl) ethylamine (PEA), the histamine receptor antagonists mepyramine and metiamide, and the histamine-releasing substance compound 48/80, on lower esophageal sphincter (LES) and esophageal body (EB) smooth muscle of the opossum were studied in a superfused tissue bath. Histamine, PEA, an H1 receptor agonist, and compound 48/80 caused a dose-related increase in LES basal tension and in EB off response amplitude, the threshold for histamine being 6.7 X 10(-8) M and that for PEA being 6.7 X 10(-7) M. In the presence of mepyramine, and H1 receptor antagonist, the effects of histamine and compound 48/80 were reversed to inhibition of both LES basal tension and EB off response amplitude, while the effect of PEA was abolished. Metiamide, an H2 receptor antagonist, did not alter responses to histamine, PEA, or compound 48/80. The H2 receptor agonist 4-methylhistamine caused a reduction of LES tension and EB off response amplitude, but caused an increase in those parameters in the presence of metiamide. A combination of mepyramine and metiamide abolished responses to all agonist drugs. The results indicate that LES and EB smooth muscle contain both excitatory H1 and inhibitory H2 receptors for histamine. Endogenous histamine released from storage sites in LES and EB and exogenous histamine both preferentially activate H1 receptors.


After vagotomy atropine suppresses gastrin release by food. Changes in serum gastrin in response to feeding a meal of beef liver (15 g kg(-1)) were studied in 5 gastric fistula dogs with and without administration of atropine sulfate (0.2 mg kg(-1) intravenously). The studies were repeated after a truncal vagotomy that abolished acid secretion in response to 2-deoxyglucose. Before vagotomy atropine had little effect on the gastrin response to a meal. After vagotomy the gastrin response to feeding was greatly enhanced, but now atropine depressed the gastrin response at all times after the meal. It is concluded that vagotomy enhances the serum gastrin response to feeding and that atropine counteracts this enhancement.


Transmissible gastroenteritis. Mucosal ion transport in acute viral enteritis. Ion transport in the jejunal mucosa of 14-to 16-day-old piglets with severe diarrhea 40 hr after infection with transmissible gastroenteritis (TGE) virus was studied. In infected pigs Na+ transport failed to respond normally to glucose when studied either in Ussing short-circuited chambers or in suspensions of enterocytes isolated selectively from jejunal villi. Theophylline, 10mM, added to the chambers produced the same brisk electrical responses and increments in net Cl- secretion in tissue from both infected and control groups. A defect in glucose-stimulated Na+ absorption in the acute stage of a viral enteritis has been identified which probably contributes to the impaired lumen-to-extracellular fluid flux of Na+ found previously in the jejunum of intact TGE-infected pigs. The mechanisms causing diarrhea in this invasive viral enteritis differ from those causing toxigenic diarrhea.


Effect of bile salts and fatty acids on the colonic absorption of oxalate. These studies were designed to evaluate the effect of bile salts and fatty acids on colonic oxalate absorption. Five millimolar deoxycholate significantly increased oxalate absorption from 34.2 +/- 9.4 nmoles per min per g dry weight to 330.4 +/- 47.3 (P less than 0.001) and changed water absorption to water secretion. Deoxycholate also increased the absorption of urea, decreased the electrical potential difference, and increased colonic clearance of oxalate, observations which are consistent with an increase in colonic mucosal permeability. In contrast, taurocholate did not increase oxalate absorption. Ricinoleic acid also significantly increased the absorption. These results suggest that bile salts and fatty acids increase colonic absorption of oxalate. Oleic acid had similar effects on oxalate absorption but was less effective than ricinoleic acid. Octanoic acid, a medium chain fatty acid, did not alter oxalate absorption of oxalate by a nonspecific alteration of mucosal permeability. These observations may further explain many of the clinical phenomena associated with enteric hyperoxaluria.


Augmentation of ethanol absorption by mono- and disaccharides. Assessment of the influence of nutritional substrates on the disposition of ingested ethanol from the blood requires, first, an understanding of the influence that these may exert upon ethanol absorption from the gastrointestinal tract. In this report, the effects of various carbohydrates on the intestinal absorption of ethanol were studied. When carbohydrates (50 mM) were perfused simultaneously with ethanol (50 mM) in vivo in the rat small bowel, ethanol absorption increased up to 34% (P less than 0.005) above controls receiving ethanol alone. Of the monosaccharides, fructose, 3-O-methylglucose, glucose, or galactose added to an ethanol perfusate, only glucose or galactose increased ethanol absorption over control animals receiving ethanol alone. Of the disaccharides tested, sucrose and maltose, but not lactose, enhanced ethanol absorption. Addition of varying concentrations of maltose to an ethanol perfusate augmented ethanol absorption in a direct proportion to the quantity of glucose absorbed, rather than to the quantity of maltose hydrolyzed. Augmentation of ethanol absorption by carbohydrates appears to be dependent upon sugar-active transport. Ethanol, dissolved in intraluminal water, may cross the mucosa in water absorbed during sugar-active transport. This quantity of ethanol is absorbed in addition to that which normally crosses the mucosa by diffusion down its concentration gradient.


Effects of phototherapy on hepatic function in human alcoholic cirrhosis. Phototherapy has been used to treat neonatal jaundice, but little assessment has been made of possible beneficial effects on adult liver disease. Effects of phototherapy on bile acid turnover, biliary lipid concentration, liver function tests, and bromosulfophthalein (BSP) kinetics were studied in 8 alcoholic cirrhotics. Phototherapy initially increased biliary specific activity of both primary bile acids and then produced an acceleration of cholic and chenodeoxycholic acid decay curves. Pruritus was relieved in the 3 patients who had this symptom. The proposed mechanism for these changes is mobilization of bile acids from an expanded cutaneous bile acid pool with augmented bile acid excretion. No significant change in serum liver function tests or BSP plasma disappearance curves was seen. Phototherapy causes little improvement in intrinsic liver function, but produces specific changes in bile acid metabolism; these changes may be related to effects of light on a cutaneous bile acid pool.


Coproporphyrin isomers in Dubin-Johnson syndrome. To shed light on the nature of abnormal porphyrin metabolism in Dubin-Johnson syndrome (DJS), coproporphyrin isomer distribution in urine and bile was investigated in carriers and patients with DJS selected from among the families in the cluster area of the syndrome in Japan. Urinary total coproporphyrin content in patients with DJS exceeded that of normal controls (P less than 0.01). However, the increase in urinary excretion of total coproporphyrin was of a much lesser degree compared to a remarkable increase in urinary total coproporphyrin reported for erythropoietic porphyria in which a deficiency of uroporphyrinogen III cosynthetase had been demonstrated. Urinary total coproporphyrin content in carriers was significantly smaller than that of normal controls (P less than 0.05). This paradoxical decrease of urinary total coproporphyrin concentration in DJS carriers was observed in consequence of a decrease in coproporphyrin III excretion without concomitant increase in type I isomer. Administration of griseofulvin, in the dose which had been shown to precipitate attacks of acute porphyria in susceptible subjects, to carriers and patients with DJS did not elicit clinical signs suggestive of porphyria, and urinary total coproporphyrin concentration and the percentage of coproporphyrin I remained unchanged. These results were interpreted to demonstrate an aspect of DJS that was not consistent with the hypothesis that a partial defect in uroporphyrinogen III cosynthetase of the liver might be the cause of DJS. Coproporphyrin in the bile of DJS patients was preponderantly type I.


Influence of cholic and chenodeoxycholic acid on canalicular bile flow in man. Hepatic bile flow was measured and hepatic [(14C]mannitol clearance was calculated during depletion of the bile acid pool and during duodenal administration of cholic or chenodeoxycholic acid in 10 patients 7 to 12 days after operation for uncomplicated gallstone disease. The relationship between [(14)C]mannitol clearance and bile flow was linear, with a regression coefficient which was not significantly different from unity. This finding supported the assumption that mannitol clearance can be used as a measure of canalicular bile flow in man. Linear relationships between bile acid secretion rate and bile flow and bile acid secretion rate and [(14)C]mannitol clearance were found during depletion of the bile acid pool (secretion of cholic, chenodeoxycholic, and deoxycholic acids; relative concentrations, 1.0:1.0:0.5) as well as during cholic acid infusion (73 +/- 3% cholic acid in the secreted hepatic bile) and during chenodeoxycholic acid infusion (88 +/- 2% chenodeoxycholic acid in the secreted hepatic bile). The bile flow dependence on bile acids 0.011 +/- 0.002 ml mumoles(-1)) was not significantly different for "mixed" bile acid secretion, mainly cholic acid secretion, or mainly chenodeoxycholic acid secretion. Neither was the ductular bile flow (0.08 +/- 0.03 ml min(-1)) significantly influenced by the various experimental conditions. The canalicular flow--the bile acid-independent (0.17 +/- 0.05 ml min(-1)) and the bile acid-dependent flow--constituted 70 to 85% of the total bile flow. It is concluded that secretion of cholic acid and of chenodeoxycholic acid promote the same bile flow volume per micromole in man.


Effects of ethinyl estradiol and phenobarbital on bile acid synthesis and biliary bile acid and cholesterol excretion. Bile acid synthesis calculated from respiratory (14)CO2 derived from the catabolism of [26 or 27-(14)C]cholesterol to bile acids in rats with intact enterohepatic circulations decreased 50% after 5 days of ethinyl estradiol treatment (5 mg per kg per day). Maximal derepressed bile acid synthesis, measured as biliary bile acid excretion after bile acid pool depletion, was also reduced 50% by ethinyl estradiol treatment. Because ethinyl estradiol did not alter biliary cholesterol excretion, bile contained less bile acid relative to cholesterol. Hepatic bile acid concentration was not increased by ethinyl estradiol treatment. Because the inhibitory effect of ethinyl estradiol on bile acid synthesis required 5 days of treatment it is concluded that bile acid synthesis probably was not reduced by negative feedback repression of 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis, which has a half-life of 2 to 3 hr. During the first 14 hr after bile duct cannulation, before bile acid pool depletion, ethinyl estradiol-treated rats excreted less than one-half as much bile acid and the same amount of cholesterol as controls. The bile acid to cholesterol ratio was therefore decreased. Rats treated simultaneously with phenobarbital and ethinyl estradiol excreted significantly more bile acid than rats treated with ethinyl estradiol alone, but biliary cholesterol excretion was not increased. The proportion of biliary bile acid relative to cholesterol was thereby restored to the control value. In contrast, after 14 hr of bile drainage and depletion of the bile acid pool, rats treated with ethinyl estradiol and those treated with phenobarbital-ethinyl estradiol excreted the same amount of bile acid. Thus, when phenobarbital is administered with ethinyl estradiol, it increases the bile acid pool size and biliary bile acid excretion, but it does not increase bile acid synthesis. The increase in pool size and biliary bile acid excretion might be due to the phenobarbital-induced increase in ileal absorption of bile acids.


Quinidine hepatotoxicity. A report of a case and review of the literature. A case is described of presumed quinidine hepatotoxicity, characterized by the development of fever, abnormal serum transaminase values, which improved after cessation of the drug but recurred after a challenge dose, and centrizonal hepatocellular necrosis detected on liver biopsy. Morphological changes on electron microscopy, consistent with a drug reaction, are also described. Pertinent features of previous case reports are analyzed, and the histological findings by light microscopy of the present and past cases are discussed. It is suggested that the development of unexplained fever within 1 month of quinidine administration should lead to consideration of possible hepatotoxicity.


Piperazine hepatitis.

Piperazine hepatitis. The first reported case of piperazine toxicity resembling viral hepatitis is described in a 25-year-old woman. The illness, which was severe, occurred after administration of the drug on two separate occasions. The evidence favors a hypersensitivity mechanism rather than a direct toxic effect of piperazine or its metabolites on the liver. The humoral or cellular immune basis for such hypersensitivity has not been elucidated.


Return of esophageal peristalsis in idiopathic achalasia. A 47-year-old male was diagnosed as having idiopathic achalasia on the basis of clinical, roentgenographic, and manometric criteria. He was on no medication and had no disorders known to impair esophageal motility. He was treated by pneumatic dilation with a good clinical response. On reexamination 7 years later, several features considered to be typical of achalasia were no longer present. Changes included return of peristaltic activity throughout most of the body of the esophagus, failure of a direct-acting cholinergic agent to produce an increase in base line intraesophageal pressure, and failure of a direct-acting cholinergic agent to produce a heightened response at the lower esophageal sphincter (LES). Incomplete LES relaxation in response to swallowing persisted. This represents the first reported case of return of esophageal peristalsis in idiopathic achalasia.


Rupture of a splenic artery aneurysm into the pancreatic duct. A patient with hemorrhage into the pancreatic duct from a splenic artery aneurysm is presented. The angiographic, retrograde pancreatographic, and pathological findings are demonstrated. The diagnosis was established by demonstrating an enlarging aneurysm by serial angiograms. The location of the splenic artery aneurysm was confirmed by retrograde pancreatography before surgery. The distal pancreas containing the aneurysm was resected.


[The clinical importance of magnesium during neonatal life (author's transl)]. By atomic absorption spectrophotometry (ASS) the magnesium levels in the serum of 50 mothers, their mature healthy infants and the umbilical vein and the umbilical artery were determined. The differences between maternal and neonatal levels and between umbilical vein and umbilical arteries are statistically significant. The results were as follows: Antecubital venous blood of the mother 1.41 +/- 0.38 mval/1, umbilical vein serum 1.59 +/- 0.35 mval/1, umbilical artery 1.65 +/- 0.36 mval/1, neonate 1.68 +/- 0.45 mva1/1. The magnesium concentration in the erythrocytes of neonates was determined for the first time by AAS analysis. A marked variation of the normal was found. It is possible that the determined low magnesium concentrations in the erythrocytes of neonates were due to latent magnesium deprivation in these infants. The mean values for the erythrocytes of the mother (4.38 +/- 1.16 mva1/1) and the erythrocytes from the umbilical vein (3.99 +/- 1.50 mva1/1) differed significantly, whereas the erythrocytes from the umbilical vein and from the peripheral venous blood of the neonate showed no statistically significant difference. Hypomagnesiumia and hypermagnesiumia are described in brief.


[The effect of different types of oral contraceptives upon ovarian function (author's transl)]. An investigation on the influence of different types of oral contraceptives upon serum gonadotropins, estradiol and progesterone was carried out in 10 volunteers. The effect of a change from a normophasic type preparation to a sequential preparation (Ovanon and Kombiquens) and from a combined preparation to a minipill (Neogynon and Exlutona) was studied. Two new 3-phase step-up preparations were also tested. Ovulation was inhibited in each case as the preovulatory LH-peak and the subsequent rise of serum progesterone were found to be missing. The basal LH- and FSH-secretion and serum estradiol were demonstrated to be significantly diminished in the volunteers taking combined and sequential preparations. The release of gonadotropines was not inhibited as much when the 3-phase step-up preparations (SHB 261 AB and SHB 264 AB) were used. When Exlutona was taken, the basal LH-secretion was lower than during the pre- and postovulatory phase of the normal cycle, but follicular development did not appear to be inhibited much as both FSH and estradiol were found to be in the normal range.


[Clinical and morphological studies in patients with a progesterone-releasing intrauterine contraceptive device (Progestasert-System) (author's transl)]. We studied in twenty women the effectiveness of a new type of intrauterine device, which is coated with progesterone. Since the progesterone-coating is estimated to last one year, we studied the women for that period of time. None of them became pregnant. Most complained of some disturbances of menstrual bleeding during the first three months. A few experienced these disturbances for the whole year of observation. No other side effects developed like those experienced with oral contraceptives. Six hysterectomy specimens and one complete curettage became available for us to examine the histological changes produced by this new type of intrauterine device. The endometrium in all revealed a distinct division into two horizontal layers produced by progesterone absorbed from the device. The upper layer of endometrium next to the device showed a decidual change with sparse atrophic glands, like those of an arrested secretion. The underlying layer exhibited either normal proliferative or secretory changes consistent with the phase of the menstrual cycle. The remarkably circumscribed decidual change led us to refer to it as "perifocal arrested secretion", a term emphasizing that the gestagen inserted into the uterine cavity acts locally on the endometrium. Foci of endometrium in the myometrium (adenomyosis) are not affected.


[Presence of the husband in the delivery room (author's transl)]. For the past 7 years a single delivery room was available for all patients in labour. Our unit delivers approximately 1200 babies yearly. It was therefore possible to encourage the husbands progressively to be present during the delivery of their wives. Almost one half of the husbands have since been present during the delivery of their wives. The majority of the couples responded positively to the offer of the husband's presence in the delivery room. 650 couples were extensively questioned following the experience and over 90% of these couples were happy with the experience. Doubtful husbands were advised to remain. Husbands with pronounced aversion against remaining in the delivery room were not persuaded to stay. The husbands had the possibility to leave the room for short breaks and to leave the room during examinations and procedures. Delivery room clothing was supplied. For the psychic benefit of the husband, the husband was kept busy with mild services. Presence of the husband during the actual delivery of the infant was always voluntary since there was no psychologic benefit to remain during the short anaesthesia used during delivery. In many cases husbands who had not even planned to remain stayed during the actual delivery and were very impressed. Late questioning after discharge from the hospital showed that almost all couples valued the experience as positive and planned to have the husband present for the next delivery. The presence of the husband during the delivery of his infant offers a chance for the additional humanization of obstetrics which appears to be very important because of the increasing danger of depersonalization of the labour and delivery process due to the new technology. Presence of the husband during the delivery in the hospital permits a partial return to the "idyllic" state of domicilary obstetrics.


Mutations masking the lambda cin-1 mutation. A lambda cnc mutation masks the phenotype of the lambda cin-1 mutation. Eleven cnc mutations have been found. All appear to be identical and all map at a site just to the right of the cin-1 site. It is probable that cin-1 and cnc affect adjacent, or almost adjacent nucleotide pairs. Neither the cin-1 nor the cnc mutation involves large additions or deletions of genetic material.


Linkage relationships and chromosome assignment of four esterase loci in the mosquito Anopheles albimanus. Although anopheline mosquitoes are important vectors of malaria, their genetic makeup has not yet been extensively investigated. The present studies concentrate on the genetic basis of esterases in Anopheles albinomanus. Nine zones of esterase activity activity have been resolved by gel electrophoresis. Four of these esterases: EST-2, EST-4, EST-6, and EST-8 are present throughout all developmental stages and also posess allelic variation. Mass matings were carried out with homozygous males and females heterozygous for two or more loci. The analyses of the progeny from single egg batches revealed that the four esterase systems mentioned above are encoded in separate loci with codominant allels. Analyses of two-point and three-point crosses have indicated the following linkage relationships: Est-8--12%--Est-4--22%--Est-2--9%--Est-6. The assignment of this linkage group to chromosome 3 has been accomplished by the use of a Y-2 chromosome translocation.


Genetics of natural populations, XLIII. Further studies on rates of dispersal of Drosophila pseudoobscura and its relatives. The amount of gene flow among local populations of a species is determined by the dispersal capacity of that species. Population samples of Drosophila pseudoobscura, D. persimilis, D. azteca, and D. miranda were collected, marked with ultraviolet fluorescent dusts, and released as soon as possible after capture. One and two days after release, recaptures were made on baits placed at 40-meter intervals in straight lines intersecting the release point. On alternative days, the baits were placed in North-South or in East-West directions. The distribution of the recaptured flies about the release point is very nearly normal. No significant differences between the dispersal rates of the four species are observed; however, males disperse slightly further than females. The variances averaged 50,822 m2 on the first day and 80,048 m2 on the second day and the estimated mean distances from the release point averaged 263 m and 361 m respectively. The genetic implications of the results are discussed.


The population genetics of parthenogenetic strains of Drosophila mercatorium. II The capacity for parthenogenesis in a natural, bisexual population. Drosophila mercatorum is a bisexual species, but certain strains are capable of parthenogenetic reproduction in the laboratory. We investigated the parthenogenetic capacity of the virgin daughters of females captured from a natural, bisexual population in Hawaii. An isozyme survey indicated the natural population is polymorphic at about 50% of its loci, and its individuals heterozygous at 18% of their loci. The predominant mode of parthogenesis in D. mercatorum causes homozygosity for all loci in a single generation. Despite this radical change in genetic state, 23% of the virgin female lines produced adult parthenogenetic progeny, and 16% produced parthenogenetic progeny themselves capable of parthenogenetic reproduction. The parthenogenetic rats as measured by the number of parthenogenetic progeny themselves capable of parthenogenesis divided by the number of eggs laid is arougn 10(-5) for the virgin female lines. We argue that one of the major reasons for this low rate is that very few of the impaternate zygotes have a genotype that can survive and reproduce under the genetic conditions imposed by parthenogenetic reproduction. This intense selective bottleneck can be passed in a single generation if enough unfertilized eggs are laid, and once passed is accompanied by a large (perhaps a thousandfold) increase in the rate of parthenogenesis and by modifications in many phenotypic traits such as morphology and behavior.


More on Nei and Roychoudhury's sampling variances of heterozygosity and genetic distance. The inequality relationship between the expected values of (j(x)-g)2 and (ĝ-g)2, where j(x) is a biased and ĝ is an unbiased estimate of population homozygosity g, were examined earlier by Nei and Roychoudhury (1974) and later by Mitra (1975). The improvement in the inequality still left much to be desired. In this paper a lower boundary of g has been obtained which may be regarded as ultimate for ensuring a smaller expected value of (j(x)-g)2 than the corresponding value of (ĝ-g)2.


The effects of hitchhiking on a gene for recombination. This paper proposes that alleles increasing recombination rates may be selected for as a result of the perturbing effects of the spread of selectively favored alleles on neighboring loci maintained polymorphic by sleection. The recombination genes are favored since their presence increases the production of selectively advantageous types of gametes with which they tend to remain associated. Numerical examples are presented, and some consequences of this model discussed. One such consequence is the wicespread existence of polymorphism for genes affecting recombination values.


Gamma-ray mutagenesis in bacteriophage T4. 137Cs-gamma irradiation of bacteriophage T4 induces large deletions plus a variety of types of point mutations. All mutations arise with single-hit kinetics, and all by a misrepair process. The estimated point mutation rate is 1.5 X 10(-9) per locus per rad.


On recombination between close and distant markers in phage lambda. The contribution of parental DNA to progeny phages genetically recombinant for close markers, distant markers, or both simultaneously was studied in biparental and triparental replication-blocked crosses. The data are compatible with the previously proposed view that heterozygous overlaps at the sites of crossing over are sometimes about as long as the lambda chromosome. However, about half of the close marker recombinants have enjoyed triparental interactions, attenuating that conclusion and obscuring predictions of the long overlap model.


Suppression of the killer phenotype in Ustilago maydis. Nineteen sensitive cell lines of U. maydis were crossed with three killer strains and sample progenies were screened for killer segregation patterns. Crosses involving 11 lines gave killer frequencies ranging from 71%-100% of the progeny and 4:0 segregations in tetrads. Segregations in some crosses involving each of the remaining 8 lines gave killer frequencies from 0%-58% and mixed tetrads containing both non-killer and killer meiotic products. Many of the killers were unstable on further culture. Killer suppression showed varying degrees of specificity, appeared to be cytoplasmically determined for at least one strain, and was associated with possession of dsRNA in this strain and one other. No dsRNA was detected in two other suppressive strains. There was no evidence for segregation of nuclear maintainer genes for any of the killer determinants.


Selection in reference to biological groups. V. Analysis of full-sib groups. Previous studies in this series have dealt with the consequences of truncation selection operating with respect to random groups within which geno-full-sib group structure. The objective is to compare the results of individual and group selection as these methods operate on populations of random versus typic interaction may exist. The present study deal with a non-random, full-sib groups. In almost all comparisons individual selection is found to be qualitatively and quantitatively superior when used in conjunction with full-sib groups. This is due to the fact that the change in gene frequency for full-sib groups is a function of both direct and associate effects, whereas with random groups it is a function of direct effects only. With regard to group selection the efficiency is invariably superior when selection operates on non-random, full-sib rather than random groups.


Selection in reference to biological groups. VI. Use of extreme forms of nonrandom groups to increase selection efficiency. The strategy of using non-random groups to increase the efficiency of truncation selection is discussed. The present study, which considers extreme forms of non-rnadom groups, complements a previous study involving full-sib groups. It is shown that of the two kinds of non-randomness, i.e. that due to homozygosity or that due to homogeneity (as represented by cloning), the latter is the most effective. This suggests that with those plant crops in which intense competition among plants exists, use of clonal propagation to produce non-random groups should be investigated.


Alcohol dehydrogenase-negative mutants in Drosophila: defects at the structural locus? Sixteen Adh-negative mutants (induced by ethyl methanesulfonate) were examined for the presence of inactive alcohol dehydrogenase (ADH) protein. Four techniques were utilized in an effort to detect this protein: hybrid enzyme formation, intra-cistronic complentation, sodium dodecyl sulfate electrophoresis and antibody precipitation. Eleven of the sixteen negative strains showed evidence of inactive ADH protein and are preseumably mutations in the strutural element. These results are discussed in light of some recent models of gene organization in higher organisms.


Galactokinase mutants of Chinese hamster somatic cells resistant to 2-deoxygalactose. The growth of Chinese hamster somatic cells was inhibited by 0.2 mg/cc of 2-deoxygalactose. Mutants partially or fully resistant to 2-deoxygalactose were isolated in a single-step or two-step selection. Some of them did not grow as well as the wild type; one of them which lacked galactokinase(EC.2.7.1.6) activity did not grow at all in galactose medium. The galactokinase kinetic properties (Vmax & kmax of the other mutants and of the wild type were different. Therefore resistance resulted either from the possible absence of galactokinase synthesis or from a structural mutation, possible a missence mutation, in the galactokinase gene.- A simple diagnostic test for juvenile cataract is proposed.


Hidden alleles at the alpha-glycerophosphate dehydrogenase locus in Colias butterflies. By varying polyacrylamide gel pore size, the alpha-glycerophosphate dehydrogenase locus of Colias butterflies is shown to contain at least five alkeles, rather than the two which had been reported previously. Two of the alleles have the same apparent net charge, and presumably are detected electrophoretically because of the conformational differences. Additional variation occurs in the isoelectric points of the proteins. It is suggested that electrophoresis employing a single gel of intermediated pore size will fail to discriminate between many alleles, and that the concept of electrophoretic alleles as differing simply in charge may not always be appropriate.


The distribution of enzyme and inversion polymorphism over the genome of Drosophila: evidence against balancing selection. In species of repleta group of Drosophila about 70% of the electrophoretic variability is absorbed by the same chromosome which absorbs about 70% of the cytological variability of the group. However, this does not imply that inversions are actively involved in the maintenance of protein variation. A comparison of cytological and electrophoretic variation of homologous chromosomes points out that the amount of cytological polymorphism varies greatly over species of Drosophila while electrophoretic variation does not. This suggests that allelozymes do not constitute part of the coadapted complexes of genes characterizing the inversions. Rather, the amount of electropheptide molecule and is largely independent of factors such as background genotype and differences in the environment.


Recombination modification in a flucturating environment. This paper examines the theory of the evolution of increased recombination between two loci subjected to interactive selection in a temporally fluctuating environment. Both cyclical and stochastic environments are considered. It is shown that temporal variation in the linkage disequilibrium coefficient for the pair of selected loci, due to fluctuations in the selective values of the genotypes at these loci, can give rise to selection in favor of modifier genes increasing recombination. The equilibrium level of recombination established in a given population depends on several factors; it is highest for intermediate values of the environmental periodicity or autocorrelation, for cases when the modifier genes are themselves linked to the selected loci, and for high levels of environmental variation. In general, it seems that the rate of modification of recombination values by this process will be low except when the modifiers are tightly linked to the selected loci. The possible evolutionary significance of this process is discussed in relation to observations on genetic systems of plants and animals.


Further studies on the ribosomal RNA cistrons of Sciara coprophila (Diptera). Additional experiments with homologous as well as heterologous hybridization confirmed our previous finding in Sciara coprophila that XX females have nearly twice the number of ribosomal RNA cistrons as XO males. A comparison between two different X' chromosomes revealed that only the one carrying the irradiation-induced Wavy mutation has a deletion of 70% of its ribosomal RNA cistrons as compared to the standard X. The deletion is relatively stable, and the remaining ribosomal RNA cistrons donot appear to undergo disproportionate replication or magnification as in Drosophila. Homologous hybridization experiments revealed an unusually low reiteration of ribosomal RNA cistrons in this fly, 45 gene copies per X chromosome. The question is raised as to whether such a low number of cistrons may be related to the unusual nucleolar condition encountered in the Sciaridae.


Chromosome rearrangements in Caenorhabditis elegans. A method for selecting unlinked duplications of a part of the X chromosome of C. elegans is described. Five such duplications have been identified. One of them, Dp (X;V)1, is translocated to linkage group V, where it suppresses crossing over along the left half of linkage group V. Dp(X;V)1 homozygotes grow slowly and are sterile. The other four duplications are associated with chromosome fragments, as observed cytologically by fluorescence microscopy, and tend to be lost. Their frequency of loss is higher in strains homozygous for a mutation that promotes nondisjunction of X chromosomes. The recombination frequencies between two of these duplications and the X have been measured: the frequencies are at least 50 times less than for X-X recombination in the same region. The duplications may prove useful as balancers of recessive lethal mutations.


[Dynamics of population genetics parameters and their statistical during assessment selection for quantitative characters. I. An additive model. One character]. The selection for a single additively inherited quantitative character is studied using computer models of 3 types: 1) all the individuals had the same viability, and the paratypic deviation does not depend on their genotype; 2) differential viability of genotypes is taken into account with respect to a number of heterozygous loci; 3) differential paratypic deviation is estimated, it is introduced like viability in the model 2. Two types of trancation selection, stabilizing and directed, under the selection coefficient of approximately 0.5 are studied. There are studied dynamics of genotypic (omega2gamma) and phenotypic (omega2phi) variances, the heritability index and it estimates (for the correlation progeny-parent--rho; for the regression progeny-parent--b; for half-sibses--v), and the non-equilibrium of a population for the models. The number of generation was 10; the population number in every generation was 200; the number of loci in the main experiment was 10.h2 values were calculated in the progeny before selection (p1, b1, v1) and after selection (p2, b2, v2). It is shown that stabilizing selection results in the formation of balanced gene complexes; the rate of decreasing omega2phi depends on the genetic length of a chromosome region in which genes, determining the character, are located, and not on the number of genes. The distribution of a character under directed selection depends on the type of the model. p2, b2, and v2 values are the worst. The best is the b1 value. It is concluded that the problem of predicting the selection effect using statistical estimates of heretability is connected with the problem of investigation of population heterogeneity and integrating their genetical structure.


[Genetic polymorphism of the serum transferrins of the northern reindeer (Rangifer tarandus L.) of northwestern Siberia]. On the basis of the examination of random samples of seven populations of reindeer inhabiting the Montane-Taiga Zone and of nine population inhabiting the Tundra Zone of the Magadan Region 8 alleles of transferrin locus described earlier (TfA, TfC, TfE, TfG, TfH, TfJ, TfK and TfM) were identified and the ninth hitherto unknown allele (TfN) was discovered. Gene concentrations of all these alleles in populations studies were determined. The reindeer of the North-East of Siberia differ in frequencies of Tf alleles from those of Norway and, apparently, also from the reindeer inhabiting the northern regions of the European part of the USSR and from the American caribou. The allele TfK is possibly associated with the resistance of reindeer to necrobacteriosis.


[Comparative characteristics of phenotypes in numerical anomalies of human X-chromosomes (morphologic and psychological features)]. On the basis of data on antropological and psychological investigation of 30 XXY males, 30 X0 females and 10 XXX females comparative characteristics of phenotypes of patients are given. The persons with X monosomy (the absence X- or Y-chromosomes) are observed to have decreased total sizes of body, to retain the ability to compensate congenital mental defects, to use standard methods of the adaptation to social environment and to assimilate standard norms of social behaviour. The persons with trisomies XXY and XXX (the presence of the additional heterochromatic X-chromosome) have the tendency to an increase of the longitudinal body sizes independently on sex; they have a delayed development of mental functions and reduced possibilities to compensation of these functions; they also have different degrees of disorganization of the social behaviour and the disadaptation to social environment. It is found that the patients with numerical anomalies of human X-chromosome (both the lack and the excess of chromosome material) have a disturbance of development of the sex dimorphism and sex dipsychism.


[Cystamine and the chromosome vesting phenomenon]. The effect of radioprotector cystamine on structural chromosome mutations induced in Crepis capillaris cells by gamma-rays 137Cs is studied. Cystamine at the concentration of 0,1% causes a two-fold decrease in the frequency of structural mutations. In the "vesting" phenomenon of ring chromosomes, under the same experimental conditions, it also leads to a two-fold decrease in the frequency of exchanges, in relation to the frequency of fragment units in the initial stage, by repair of normal chromosome structure. Cystamine provides protection in structural mutagenesis at the moment of realization of primary mutagenic changes into mutations due to enzyme ligazing chromosome fragments.


[Undulating kinetics factors in radiation mutagenesis]. Air-dry Crepis capillaris seeds, soaked for 14 and 20 hours, were dried to the moisture content of 1,1% with the following gamma-irradiation at a dose of 1500 r. Irradiated seeds were stored in the state of identical moisture for 38 days. The drying of three groups of seeds to moisture content of 1,1% provided their identical initial radiosensitivity. In the course of the storage mutability of treated seeds significantly increased as compared with the yield of mutations in non-stored seeds, and revealed undulating kinetics that involved all types of arising chromosome and chromatid rearrangements. The character of undulating kinetics is due to a correlation between functional state of nucleus (early G1, late G1, S) and water content in seeds.


Ambulation and self-care are goals of rehabilitation after stroke. Successful rehabilitation of the elderly hemiplegic patient means achievement of ambulation of self-care. The patient's potential for reaching this goal can be determined shortly after the stroke by the stand-up test. Delay of an adequate rehabilitation program, often caused by administrative obstacles to proper care, decreases the potential. Rehabilitation of the elderly hemiplegic also is often hampered by impairment of communication. However, with correction of organic abnormalities causing mental disturbance and with use of simple techniques to facilitate communication, it is possible to achieve ambulation even in patients with marginal ability to communicate.


Aging of the neuromuscular apparatus.

Aging of the neuromuscular apparatus. With age marked changes in metabolism and function of muscle fibers appear: electroexcitability thresholds rise, critical polarization level and membrane resistance decrease, time of action potential increases and its amplitude decreases, lability is reduced. The level of intracellular sodium increases and that of potassium decreases. Shifts in ionic asymmetry of muscle fibers are connected with changes in their membrane permeability and a modified function of the sodium-potassium pump. Along with the impairment of nervous influences on muscle fibers in old age, their sensitivity to many hormonal factors increases. Loading levels all age differences in the regulation of skeletal muscle vascular tone. The relationships between the activity of the genetic apparatus and electrical properties of the cell are altered.


Fast and slow motor units in ageing.

Fast and slow motor units in ageing. The differences in onset and degree of old age changes in different muscles are explained by the differentiation and different reactivity of fast and slow motor units with respect to physiological, structural and biochemical characteristics. The main changes in the motor units in old age are described. The general basic change is a progressive random disturbance of neuromuscular contact ascribed to a decrease of the trophic function of the neuron. The main motor disturbances in old age, i.e; slowness, decrease of muscle strength and lack of fine coordination are explained in terms of physiological changes in senescent motor units. The reactions of senescent motor units differ from one unit to another as shown, e.g. in denervation, reinnervation and regeneration (transplantation) studies. The trend to a shift from a heterogeneous to a more uniform muscle fibre pattern and the defficiencies in recovery of the original muscle fibre pattern in reinnervation and regeneration of senescent muscle is demonstrated and explained by a decrease of the differentiating capacity of different motor units. The changes in the heterogeneous fibre pattern of skeletal and the homogeneous fibre pattern of the papillary heart muscle in old age are contrasted.


Aging changes in insect flight muscle.

Aging changes in insect flight muscle. Age-associated changes in the flight muscles of higher insects, using male housefly as an example, have been discussed. The duration of sustained flight activity declines with age. During the first trimester of adult life, the mitochondrial volume in the flight muscles increases by additional biosynthesis. Individual mitochondria become further enlarged by the fusion of adjacent organelles. In old flies, a small proportion of mitochondria show degenerative changes. In senile flies, focal areas of the flight muscles undergo cytolytic changes. A variety of metabolic changes involving enzyme activities, protein synthesis, substrate levels and bioenergetics have been reported in flight muscles of aging insects. The mechanism of the loss in flight capacity of old insects, however, remains unknown.


Insect flight muscle: maturation and senescence. That holometabolous insects undergo a number of post-emergent morphological, physiological, and biochemical maturational processes, termed metachemogenesis, is unquestionable. This is readily evident as regards the capacity for flight. The maturational processes demonstrated in mitochondria and/or mitochondrial enzyme systems, myofibrils, as well as other biochemical systems have been sufficiently documented in a number of species, directly correlated with the attainment of optimal flight ability in terms of both wing beat frequency and the duration of sustained flight; suggesting that the phenomena is a general one, particularly in the orders Diptera and Hymenoptera. Subsequent to the time-dependent maturational processes which are species-specific, there is an observed relatively stable period of flight performance during adult life. With advancing age, flight performance declines, most noticeably in the duration of sustained flight. This diminution, as the maturation of flight ability, is also correlated with a decline in a number of biochemical parameters, i.e. levels of and/or ability to utilize glycogen, various enzyme systems, mitochondrial efficiency, particularly in dipteran insects. Furthermore, as the morphological degenerative changes observed in aging flight muscle are variable and do not appear to be of sufficient magnitude to account for the substantial decline in the physiological expression of flight, one may assume that neurophysiological and/or biochemical mechanisms are responsible. A more fundamental question as regards the mechanisms of agins is whether or not the decrease in flight performance with advancing age is due to random error, or is in some way genetically controlled as the post-emergent maturational changes must be. The orderly sequential pattern of enzyme changes associated with the maturation and senescence of flight ability, particularly in the male housefly, and the demonstration of an identical sequential pattern of change in two of these enzymes, again correlated with the maturation and decline in flight performance in two other dipteran insects, suggest that the senescence of flight ability may also be manifested in an orderly programmed manner.


Hepatitis B antigen (HBSAg) and/or antibodies (anti-HBS and anti-HBC) in fulminant hepatitis: pathogenic and prognostic significance. Hepatitis B surface antigen (HBSAg) and antibodies to both the surface and core antigens of the hepatitis B virus (anti-HBS and anti-HBC) have been studied in 64 consecutive cases of fulminant hepatitis. HBSAg was detected by counterelectrophoresis in 23 (35-9%) but by radioimmunoassay in 38 (59-3%). Anti-HBS was detected by passive haemagglutination in 26 (40-6%), coexisting HBSAg and anti-HBS were found in 16 cases (25%). Using an indirect immunofluorescence technique, anti-HBC was found in all of the cases in whom either HBSAg or anti-HBS was present. The highest survival rate was observed in patients with no evidence of HBV infection (31-3%) and was lowest in those who had both HBSAg and anti-HBS detected simultaneously (6-2%). The prognosis of those who exhibited anti-HBS only was no better than those with HBSAg alone. In a further case, transient interruption of the asymptomatic chronic HBSAg carrier state with seroconversion to anti-HBS was associated with the development of a fulminant hepatitis syndrome. The results suggest that an unusually strong and rapid immune clearance of HBSAg may be involved in the pathogenesis of fulminant hepatitis.


Assessment of endoscopic retrograde cholangio-pancreatography (ERCP) and pure pancreatic juice cytology in patients with pancreatic disease. Pure pancreatic juice has been collected from 61 patients at the time of endoscopic retrograde cholangio-pancreatography (ERCP) for the purpose of cytodiagnosis. The ERCP and cytological findings are discussed. Pure pancreatic juice cytology may help in the interpretation of the pancreatogram in both pancreatitis and pancreatic carcinoma. In patients with pancreatic carcinoma, ERCP alone was diagnostic in 65%, cytology alone in 54%. By combining these two approaches, a diagnostic result was obtained in 92% of patients.


Prostaglandin release in canine acute haemorrhagic pancreatitis. Acute haemorrhagic pancreatitis was induced in greyhound dogs by a bile salt/trypsin injection into the main pancreatic duct. Prostaglandin-like activity in the pancreatic venous blood, right atrial blood, and arterial blood was measured by bioassay. Activity rose significantly in the pancreatic venous blood of test dogs but not in controls. Chromatographic analysis of the peritoneal exudate from the dogs with pancreatitis showed high levels of prostaglandin E-like material (mean 43 ng/ml prostaglandin E2 equivalents). It seems likely that prostaglandins contribute to the induced pancreatitis.


Oral administration of a chymotrypsin-labile peptide--a new test of exocrine pancreatic function in man (PFT). One gram N-benzoyl-L-tyrosyl PABA was orally administered to 24 controls, 15 patients with chronic exocrine pancreatic disease, 13 patients after an attack of acute pancreatitis, two patients with gluten-sensitive enteropathy, and 10 patients with biliary tract disease, peptic ulcer, or other pathology of the gastrointestinal tract. In the presence of chymotrypsin, PABA is split from the peptide and excreted in the urine. The amount of PABA excreted serves as a parameter of exocrine pancreatic function. In 51 patients, exocrine pancreatic secretion was also assessed by the Lundh test. In the control group a mean of 59-6 +/- 12-2% (mean +/- 2 SD) of the peptide-PABA was excreted over a period of six hours. PABA excretion in exocrine pancreatic deficiency was significantly less (P less than 0.001) than in controls. With one exception no overlap of data was noted. In the group with exocrine pancreatic deficiency, a significant relationship was shown between the PFT and the Lundh test. Reproducibility in duplicate test was excellent. The present data justify further investigations of this procedure as a possible new oral test of exocrine pancreatic function.


Review of five cases of early gastric carcinoma. Five cases of early gastric carcinoma (EGC) were seen in 12 months. The clinical features did not provide guide-lines to diagnosis, which depends on air contrast barium studies, endoscopic recognition of early malignancy, adequate biopsies, and their interpretation. Malignancy was present in an average of 60% of the biopsies taken. The most common type of lesion was IIc. The superficial nature of the malignancy was predicted at endoscopy in four cases but was unsuspected in one case which was considered to be advanced carcinoma until the resected specimen was throughly examined microscopically. The excellent prognosis of EGC was discussed. Only conservative surgery need be performed if the superficial nature of the lesion is recognized before operation.


Effect of vagotomy on the gastric secretory response to intraduodenal osmotic agents in man. The effect of intraduodenal infusion of hypertonic saline and glucose on pentagastrin-stimulated gastric secretion was investigated in 35 normal subjects, 32 duodenal ulcer patients and 32 patients after truncal vagotomy and pyloroplasty. A significant gastric inhibitory response occurred after 0.51 M saline and 1-03 M glucose in the normal subjects and duodenal ulcer patients but after vagotomy there was no inhibition. This finding suggests that the inhibitory effect of these agents depends, at least in part, on a vagal reflex in man. The response to very high glucose concentrations persisted after vagotomy and it seems likely that a humoral mechanism may be involved in this situation.


Effects of aspirin on gastric prostaglandin E (PGE) and acid output in normal subjects. Aspirin administration to normal subjects resulted in a reduction in gastric prostaglandin E (PGE) output. Both PGE concentration and gastric juice volume were decreased. Gastric acid output also decreased, although the difference was not statistically significant. An increased sensitivity of the PGE system to inhibition by aspirin at 11 p.m., midnight, and 1am was observed.


Abnormal intestinal bile acid distribution in azotaemic man: a possible role in the pathogenesis of uraemic diarrhoea. Proximal intestinal bile acids have been studied in 14 ambulatory patients with varying degrees of azotaemia. When compared with normal subjects, the azotaemic patients showed a significant decrease in deoxycholic acid. Analysis of faecal bile acids of a patient with low intestinal deoxycholic acid also showed low deoxycholic acid with a preponderance of primary bile acids, and contrast with faecal bile acids of a normal subject and a patient with normal intestinal deoxycholic acid. It is suggested that impairment of deconjugation or 7alpha-dehydroxylation might be contributing to the low deoxycholic acid observed in azotaemic patients. Unusual bile acids: ursodeoxycholic acid, 3-hydroxy-7-keto-cholanic acid, and 3,12-dihydroxy-7-keto-cholanic acid were also noted in intestinal aspirates of azotaemic patients. The presence of these bile acids in conjunction with low deoxycholic acid correlates with the symptom of diarrhoea in azotaemic patients, and may contribute to the pathogenesis of diarrhoea in these patients.


Limitations of ultracentrifugation and in vivo dialysis as methods of stool analysis. Extracellular stool fluid has been sampled by in vivo dialysis, in vitro dialysis, and high speed centrifugation. Detailed comparisons of amino acids and electrolytes have been made between each fluid; normal values and significant differences are summarized. Evidence is provided which suggests that there is release of intracellular contents during normal handling of stool in the laboratory. The amino acids which display the greatest differences between centrifugate and dialysate from given stool specimens are those which are liberated by ultrasonication or aerobic incubation of stool. Factors affecting the chemical stability of stool are discussed. In most circumstances in vivo dialysis would seem to provide the closest approximation to extracellular fluid, providing the faeces remain in the descending colon or rectum for at least two hours.


Role of the granuloma in recurrent Crohn's disease. The clinical significance of sarcoid-like granulomata in recurrent Crohn's disease has been investigated in 90 patients. The recurrence rate for non-granulomatous disease was double that of granulomatous disease. In granulomatous disease, involvement of the mesenteric lymph nodes did not affect the recurrence rate. This suggests that sarcoid-like granulomata reflect the patients' immune response and support the view that excision of the lymphatic drainage en bloc with affected bowel is not indicated.


Duodenal ulcers: early and late onset.

Duodenal ulcers: early and late onset. A hospital series of 1042 duodenal ulcer patients was examined to determine the relationship of the age of onset of ulcer dyspepsia with the blood group and with the family history of ulcer dyspepsia. It was found that those patients whose symptoms begin in the first two decades of life (early onset patients) contain a significantly larger proportion of group A, B, and AB subjects and a significantly stronger family history of dyspepsia than those whose symptoms begin from the fourth decade of life onwards (late onset patients), in whom blood group O prevails. The group O status is shown to be associated with a significant proneness to duodenal ulceration and a significant proneness to bleed, and in the late onset patients a significant proneness to bleed recurrently and severely. Bleeding is the predominent complication in the early onset patients. There is a significantly increased tendency for the late onset ulcers to perforate, to become stenosed, to have severe pain, and to be virulent--that is, to be multiple, post-bulbar, or giant. While these features do not appear to be related to the effect of ageing, the occurrence of associated gastric ulceration and the mortality rate was shown to be related.


Simple clinical method of measuring gastric emptying of solid meals. The radioisotope techniques used for the measurement of gastric emptying of solid meals in man require complex and expensive scintiscanners of cameras. We have evaluated a simple technique which uses a fixed scintillation detector and compared the results with those obtained from a gamma camera. The rates and patterns of gastric emptying recorded by the two methods correlated well in both healthy volunteers (mean r= 0.95) and patients with duodenal ulcer (mean r =0.89). The scintillation detector provides a reliable and inexpensive method for measurement of gastric emptying of solid meals.


Course and prognosis of Crohn's disease. During the period 1938-70 there were 303 patients at the Radcliffe Infirmary, Oxford, diagnosed as suffering from Crohn's disease. Of these, 82 have been excluded, leaving 221 with a firm diagnosis. These patients have been divided into 'new cases', in which the disease was diagnosed at the Radcliffe Infirmary, and 'referred cases' in which the diagnosis was already made at the time of referral. In this series, there were three main sites of involvement: small intestinal, large intestinal, and both small and large intestinal. Ileocolitis was the commonest anatomical distribution. The disease showed progression to new, sites in a considerable number of the patients during the period under study. There was a fivefold increase of new cases between the first and third decades covered by the study and this applied equally to patients presenting as an acute abdomen, which supports the idea that the disease is truly increasing. Survival curves have been plotted and compared with expected survival curves. In terms of mortality, Crohn's disease emerges as a disease which becomes progressively more dangerous as the years go by, which is in sharp contrast with the findings in ulcerative colitis in which the main risk of dying is in the early years.


Cell mediated immunity to corn starch in starch-induced granulomatous peritonitis. Two patients with histologically diagnosed starch induced granulomatous peritonitis (SGP) have been shown to have cell mediated immunity to corn starch using the techniques of macrophage migration inhibition and lymphocyte DNA synthesis. Control groups of normal subjects, patients with uncomplicated laparotomy, and patients with Crohn's disease were negative in both tests. Lymphocytes from two patients with band adhesions, one of whom had biopsy evidence of a granulomatous reaction to starch, were sensitized to starch. Cell mediated immunity to starch may contribute to the pathogenesis of SGP, and some band adhesions may be a chronic low grade manifestation of this disorder.


Malignant melanoma metastases to the alimentary tract. Seven patients are presented each with symptomatic malignant melanoma metastases to the alimentary tract. Where practicable, surgical excision of the metastases is justified because two patients have had worthwhile periods of survival.


Measurement of the mean transit time of dietary residue through the human gut. A new method is described for measuring the mean transit time (MTT) of digesta through the human gut in which a constant amount of marker (radio-opaque pellets) is fed to subjects with each meal over a period of weeks, and its excretion measured in the stools. The MTT measured by this method (MTT-C) has been compared with MTT measured by giving single doses of similar markers to the same subjects (MTT-S) and with the 80% transit time (80% TT). Mean values on three dietary regimes for the MTT-C (54.2 h +/- 2.5) and MTT-S (54.2 +/- 2.6) were lower than that for 80% TT (63.1 +/- 3.0). The average MTT-C in a group of six healthy young men on an ad libitum diet was 2-3 days (range 0-7-4-0). When additional dietary fibre was added to a standard diet the average MTT-C fell (in all of five subjects) from 2-4 to 1-6 days. A continuous record of MTT-C is obtained by this new method which shows wide variations from week to week even on controlled dietary intakes. Using the single dose technique, evidence is produced which suggests that the MTT-S is a more accurate and reproducible method than the 80% TT.


Transit through the gut measured by analysis of a single stool. A method is described for measuring transit time through the gut which requires the collection of only one stool. A dose of 20 radio-opaque markers is given to the subject on each of three consecutive days with breakfast, each dose of marker being of a different type. The first stool passed after rising on the fourth day is collected and its marker content analysed. The method has been validated in 15 subjects by comparing it on  36 occasions with mean transit time measured by a continuous marker technique (MTT-C). In 35 of these studies transit measured from a single stool (SST) and MTT-C were significantly correlated R = 0.78 P less than 0.001. In one study the designated stool contained none of the SST markers. An alternative way of validating the SST method is described by comparing it with the average of the three mean transit times from three separate doses of marker (MTT-S). The average MTT-S agreed very closely with MTT-C in 36 studies R = 0.94 P less than 0.001 and proved a satisfactory alternative method for validating transit techniques. In a total of 66 studies in 22 subjects average MTT-S correlated significantly with SST, R = 0.85 P less than 0.001.


Physiopathology of megarectum: the association of megarectum with encopresis. Studies of both rectosphincteric reflex threshold and conscious rectal sensitivity threshold were performed on 15 control subjects and 61 children with a radiological megarectum, 70% of whom were encopretics. In control subjects, the reflex threshold and the sensitivity threshold were obtained with a comparable volume of rectal distension. In the megarectum patients, sensitivity was often considerably reduced, the incidence of encopresis increasing proportionally with the decrease in conscious rectal sensitivity. Patients were segregated in three functional groups, according to measurements of the sensitivity threshold.


An evaluation of echography in the diagnosis of pancreatic disease. In the present study an attempt to evaluate the efficacy of echography as a diagnostic tool has been made. A total of 52 patients (chronic pancreatitis (42); pancreatic cysts (three); and carcinoma of the pancreas (seven)) were studied and the results compared with those from other diagnostic techniques. In 65.7% of chronic pancreatitis patients, and in all cases of carcinoma of the pancreas, echography provided evidence of pancreatic abnormality but in no case could an unambiguous diagnosis of the disease be made. However, in all cases of pancreatic cyst, echography gave precise and unequivocal diagnostic information. There was good agreement between the echographic picture and surgical findings. Cholangiography and duodenography indicated duodenal and choledochal compression in a high proportion of cases in which echography revealed enlargement of the head of the pancreas. It is concluded that echography is a simple, safe, and valuable addition to the techniques available for studying the pancreas.


Endoscopic pancreatography in evaluating results of pancreatico-jejunostomy. It has been difficult, employing clinical methods, to establish whether pancreatico-enteric drainage shunts for chronic pancreatitis have remained patent and how the operation has affected the inflammatory changes and ductal pathological morphology. In an attempt objectively to evaluate postoperative results, 13 patients with two different types of pancreatico-jejunostomies were examined with endoscopic pancreatography. Progress of the inflammatory changes was noted to a varying degree in the majority of cases. In four patients subjected to longitudinal split of the pancreatic duct, shunt patency was evidenced. In the remaining nine patients with caudal pancreatico-jejunostomy, no contrast medium could be made to pass the shunts in six cases, whereas passage was clearly demonstrated in one and uncertain in two. All the patients reported clinical improvement after operation.


A comparative study of the effect of oral contraceptives and cigarette smoking on platelet adhesiveness. The aim of this work was to discover to what extent cigarette smoking and oral contraceptives, either separately or in association, are responsible for platelet adhesiveness changes in humans. Platelet adhesiveness has been measured in 77 subjects, smokers and nonsmokers. 47 of these subjects were women both using and not using oral contraceptives. Cigarette smoking significantly increases platelet adhesiveness both in men and women. On the contrary, if no distinction is made in the smoking habits of female volunteers and they are only divided into two groups according to the use or nonuse of oral contraceptives, no significant change in platelet adhesiveness occurs following intake of oral contraceptives.


Platelet function after the administration of chlorpromazine to human subjects. Chlorpromazine is known to inhibit platelet function in vitro. The intramuscular injection of 50 mg to human volunteers caused only minor changes in platelet function. There was a small, but significant, reduction in the platelet count, the second phase of the double-wave of adenosine diphosphate-induced aggregation and the rate of 5-hydroxytryptamine-induced aggregation. Patients on high doses of chlorpromazine had no demonstrable abnormality of platelet function. This suggests that chlorpromazine, despite its inhibitory effect on platelet function in vitro, is unlikely to interfere with either haemostasis or thrombogenesis after its administration to man.


Interference on the haemostasis in dogs with induced coagulopathies by drugs affecting the platelet function. Acetylsalicylic acid and phenylbutazone increased the bleeding significantly from standardized wounds in dogs defibrinogenated with Defibrase. Administration of dipyridamole and Xylocain had no effect. The results were the same in dogs treated with warfarin sodium. The results demonstrate the value of using laboratory animals with an induced coagulopathy when establishing the effect on the haemostasis exerted by drugs known in vitro to interfere with platelet functions. Acetylsalicylic acid and dipyridamole did not alter the activity of the K-vitamin-dependent coagulation factors, factors V, VIII, platelet count or fibrinogen concentration.


Reduced aggregability of platelets in rat anaphylaxis. In the PRP of anaphylactic rats, ADP, collagen and thrombin induced platelet aggregation was considerably reduced. Reduced aggregability could be transferred to normal platelets by suspending them in the PPP of anaphylactic animals and the impaired aggregation of platelets from animals undergoing anaphylaxis could be restored by exchanging their plasma for that of normal controls. Ellagic acid, a known activator of factor XII, produced similar alterations as obtained in anaphylactic shcok. It is suggested that the inhibition of platelet aggregation is due to the anaphylactic activation of factor XII and this mechanism may be of importance in rat anaphylaxis.


Influence of atropine and carbachol on the fluorescence of catecholaminergic structures in selected areas of the rat brain. Using the formaldehyde-fluorescence technique, the authors studied the influence of atropine and carbachol, administered intraventricularly to Wistar rats, on the fluorescence of catecholaminergic structures in 20 areas of the CNS, situated within the range of the 10th-46th frontal plane according to KONIG and KLIPPEL. 1. A confirmation of the antagonistic action of atropine and carbachol was obtained. It was expressed by mutually opposed occurrence of the specific fluorescence of the catecholaminergic structures. 2. In 16 out of 20 studied areas of the CNS, carbachol abolished or considerably weakened the specific fluorescence. In 3 areas it was increased by this drug, and one area proved insensitive. 3. Atropine increased the specific fluorescence in the DA (dopaminergic system) areas, while it had varying effects in the NA (noradrenergic system areas. In some areas of the CNS it increased and in others reduced the specific fluorescence of the catecholaminergic structures. 4. An interference between atropine and carbachol is observed, but it seems that the results of the present experiment speak in favour of an interaction between the catecholamine transmitters and ACh in the particular areas of the CNS under the influence of atropine and carbachol. 5. The authors discuss in detail the reactions of the catecholaminergic structures in the particular areas of the CNS, in which, as compared with the control, an increase or a decrease of the specific fluorescence under the influence of the administered drugs was observed.


Effect of extraction of histones and their reconstitution on [3H] actinomycin D binding to isolated nuclei of the root of Pinus silvestris. The purpose of the study presented was to investigate the effect of the extraction of histones on the template activity of DNA, measured by the autoradiographically evaluated intensity of [3H]actinomycin D ([3H]AMD) binding. The study was carried out on nuclei isolated from the root meristem of Pinus silvestris. Histones were removed selectively from them and reconstituted in the nuclei deprived of these proteins. The greatest rise in radioactivity was found after the extraction of the arginine fraction and that of lysine-rich and moderately lysine-rich fractions removed together, whereas the extraction of the lysine-rich fraction does not cause such a considerable increase in radioactivity. The reconstitution of particular histone fractions induced a fall in radioactivity to the level of controls in all the cases examined. No [3H]AMD binding to the nucleolus was found. The extraction of lysine histones results in the decondensation of chromatin and their reconstitution in the formation of complexes of compact chromatin.


Radiation-induced histochemical and ultrastructural changes in the enterocytes in the rabbit. Ultrastructural changes and enzyme activities in the cell organelles of rabbits were studied within 1, 3, 6, 9, 15 and 30 days of the irradiation with 550 rads of gamma-radiation. Between the 1st and 3rd day after irradiation there was a fall in the succinate dehydrogenase activity in the swollen and frequently tigroidal mitochondria whose number distinctly diminished. By the 15th day these changes disappeared. In the hyaloplasm there was weakening of the reaction for lactate dehydrogenase after 1 day, and an increase in number of polysomes, glycogen granules and smooth vesicles after 3-9 days after irradiation. The glucose-6-phosphatase activity was unchanged and so was the shape of the Golgi apparatus. The activity of lysosomal enzymes and the number of lysosomes in the experimental groups was approximately normal. By the 6th day the activity of alkaline phosphatase in the striated border was lowered, subsequently normal. On the whole, the intensity of postradiation changes in the intestinal mucosal epithelium is correlated with the rhythm of proliferation and shedding of epithelial cells, although some signs of injury persist for longer time periods.