Synthesis and photobiological properties of 4,8-dimethyl-5'-carboxypsoralen: a major metabolite of 4,5',8-trimethylpsoralen. Recently a major metabolite of 4,5',8-trimethylpsoralen (TMeP) (a photochemotherapeutic agent), was isolated from the urine of mice and human volunteers receiving the drug orally; it was identified as 4,8-dimethyl-5'-carboxypsoralen. The synthesis of this compound has been carried out to obtain a distinct confirmation of the structure of the urinary metabolite and to study its photochemical and photobiological properties. The results obtained showed that this interaction and photoreaction with DNA are very poor; this fact can be correlated with the presence of the ionizable carboxylic group that undergoes a repulsion by the phosphate residues of the macromolecule. This hypothesis is confirmed by the higher interaction and photoreaction with DNA of the 4,8-dimethyl-5'-carboxypsoralen methyl ester in which, of course, the ionizable character is no more present. In connection with this very low photoreacting capacity with DNA, the synthesized metabolite proved lacking of photosensitizing effects on human and guinea pig skin. This fact provides an explanation of the very low photosensitizing properties of TMeP when given orally in contrast with the high activity after topical application.


[Immunological treatment of sarcoid skin lesions by old tuberculin, blood, and BCG (author's transl)]. The effectiveness of an immunological treatment of sarcoidosis by repeated subcutaneous injections of a mixture of old tuberculin and blood from a highly tuberculin sensitive donor with appropriate bloodgroup, and additional BCG is demonstrated in a group of 8 patients with sarcoid skin lesions. The average time of therapy was 2 1/2 years until healing was obtained.


[Impetigo herpetiformis and PUVA-treatment (author's transl)]. Report on a 20 years old pregnant woman, who fulfilled the criteria of the impetigo herpetiformis as well as later those of the pustular psoriasis Zumbusch in her clinical course. The impetigo herpetiformis is interpreted as a variant of the pustular psoriasis occurring during the pregnancy with lowered calcium-level, which increases the endogeneous eruption pressure. After negative attempts of treatment with Prednisolon, antibiotics, and later with Methotrexat an excellent therapeutic effect could be achieved by oral PUVA-treatment.


[Optimal measurement technic for the vasoconstrictor effect of corticosteroids. Comparative studies with reflection photometry and flow measurement]. In 20 healthy male test subjects, a non-specific ointment base was applied to the back of the hand over 16 hours. Two days later, the same ointment base with 0.25% triamcinolone acetonide was once more applied to the back of the hand over 16 hours. The light reflection of the skin was measured by reflection photometry and the heat transport coefficient was measured fluvographically under the condition of the tourniquet test. The results show that the vasoconstrictor effect of triamcinolone acetonide is best detected by the reflection photometric measurements. In fluvographic measurement, the heat transport coefficient is most affected in maximal reactive hyperemia when the tourniquet has been removed. Application of the base led to a reduction of the blood flow and the water content of the skin after 16 hours, whereas the water content of the skin was unaffected in the presence of triamcinolone acetonide.


Enzymatic modulation of the cell surface in malignant transformation of normal human mammary epithelial cells and in conversion of mammary carcinoma cells. The effect of treatment with trypsin and neuraminidase on morphology, proliferation pattern, adhesiveness and ultrastructure of human normal mammary and carcinoma cell lines has been investigated. These criteria were chosen because they reflect on the cell surface function. Active enzymes were required to produce changes. If trypsinized and then allowed to grow in culture media supplemented with 'fibroblast growth-promoting factor', human normal mammary epithelial cells proliferated in a disorganized pattern with cells overlapping and piling up and developing ultrastructural characteristics of neoplastic cells. On the other hand, if treated with neuraminidase and then permitted to grow in presence of the 'fibroblast growth-promoting factor', mammary carcinoma cells proliferated in an organized pattern, forming one-cell-thick, fibroblast-like monolayers and ultrastructural characteristics of normal epithelial cells.


Slow versus fast postthaw dilution for the recovery of lymphocytes in whole blood frozen in either dimethyl sulfoxide or glycerol. It was previously shown by the authors that human whole blood was cryoprotected by dimethyl sulfoxide (DMSO) for use as inoculum in short-term lymphocyte cultures. That procedure utilized a fast postthaw dilution where the cryoprotective agent was diluted in two steps. In this paper it is shown that a five-step 'slow' dilution technique is much superior to the two-step 'fast' dilution procedure, which significantly revises our original report of 1972. This method has strikingly improved the degree of blastogenic response to phytohemagglutinin as measured by 3H-thymidine incorporation. The increase in amount of tritium incorporation was seen in cultures which were protected with either DMSO or glycerol. A similar effect was observed in unfrozen control cultures exposed to either cryoprotectant.


Inhibition of spindle assembly by colchicine and of cell cycle by cycloheximide. Comparison and combination of their cytological action on cleavage mitoses. In cleavage mitoses colchicine (2 x 10(-3) M) does not interrupt the cycle of chromatin and its action is exerted on all the mitotic phases. Cycloheximide (10(-3) M) prevent normal condensation of the chromosomes and breakdown of the nuclear envelope; it brings on various nuclear abnormalities, particularly irregularities in chromosome condensation. At 10(-4) M, cycloheximide allows some mitoses, often abnormal ones, but anaphase is inhibited. The action of colchicine, more efficient upon the spindle, obscures the action of cycloheximide when both substances are associated. In return, cycloheximide imposes its action upon chromosome condensation, so that the structure of the nuclei treated by both substances is determined by cycloheximide.


A scanning electron microscope study of developing hamster tracheal epithelium in organ culture. The ultrastructural surface features of tracheal epithelium at various times of development in organ culture were compared with those in the trachea of Syrian golden hamsters of similar age using scanning electron microscopy. Whole tracheal organ cultures, prepared from 3-day-old hamsters, were maintained in HEPES buffered CMRL 1066 medium with 0.2% bovine serum albumin. The ventral epithelial surface of trachea from 3-day-old animals was characterized by numerous microvillous cells, occasional well-developed cilia, and cells containing short cilia representing various stages of ciliary differentiation. After seven days in culture, an increased number of ciliated cells as well as developing cilia were seen. The epithelium after 14 days in culture appeared to have equal numbers of ciliated and microvillous cells, a pattern strikingly similar to that observed in vivo. After 21 days in culture, groups of well-developed cilia were interspersed with nonciliated cells covered with short, poorly developed surface microvilli. A similar pattern was found in the trachea of comparable age (24 days), with the exception of the microvillous cells; many being dome-shaped containing cluster of microvilli with prominent outlines. The tracheal organ culture, as developed in this investigation, appears to represent an excellent model for studying age-related effects of toxic and infectious agents on ciliated epithelial cells.


Activation of satellite cells induced by chronic neostigmine administration in the rat. Muscle fibrillation has been suggested as a possible trigger for activation of satellite cells, a well known phenomenon associated with denervation. In order to test such a hypothesis fibrillation has been induced in normally innervated muscles by chronic administration of neostigmine and the response of satellite cells has been observed with a scanning electron microscope. The results show that satellite cells protrude from the profile of the muscle fiber, become partially separated from the latter, and align in rows. Elongated structures and presumable new muscle fibers are observed after 14 days of treatment. It is concluded that the overactivity of muscle fibers which is induced during fibrillation causes activation and differentiation of satellite cells. This result is consistent with that of a previous experiment showing that satellite cells are activated during acute increase in workload.


In vitro inhibition of oocyte and follicular maturation and spawning in starfish (Asterias forbesi) by 2-4-dinitrophenol. The in vitro effects of 2-4-dinitrophenol (DNP) on spawning and follicular and oocyte maturation in starfish ovaries and its various cellular components were investigated. Spawning and oocyte and follicular maturation induced by starfish gonadotropin radial nerve factor (RNF) in isolated ovarian fragments were all inhibited by appropriate doses of DNP. DNP inhibits processes which occur shortly after addition of the gonadotropin; in ovarian fragments insensitivity to DNP inhibition occurred shortly after addition of RNF but prior to initiation of spawning. Spontaneous follicular and oocyte maturation which occurred following release of ovarian follicles into sea water was prevented by DNP. In non-spontaneously maturing follicles released from the ovary, DNP inhibited both follicle and oocyte maturation induced by the secondary stimulator of spawning and maturation, 1-methyladenine (1-MA). DNP also inhibited 1-MA induced meiotic maturation in isolated immature oocytes incubated in the absence of follicle cells. Inhibition of oocyte maturation was not associated with inhibition of 3H-1-MA incorporation by isolated oocytes. Immature oocytes incubated in the presence of DNP underwent maturation following washing and subsequent exposure to 1-MA. Immature oocytes initially exposed to both 1-MA and DNP, however, showed decreased maturation responsiveness following washing and re-exposure to 1-MA. The results suggest that the inhibitory effects of DNP on spawning and oocyte maturation are the result of direct effects on the oocytes and possibly other cells and tissues within the ovary.


Variation of DNA polymerase activities in chick neural retina as a function of age. The activities of DNA polymerases alpha, beta, and gamma and of thymidine kinase were determined in the chick neural retina at different stages of embryonic development (starting at seven days) and after hatching (up to five years). Crude extracts of neural retinae were fractionated by centrifugation on sucrose gradients and the enzymatic activities measured using specific assays. The DNA polymerase alpha activity decreases greatly between 7 and 11 days of incubation. This decrease parallels the decline in mitotic activity. However, a constant residual activity remains after hatching, even in the oldest animals. DNA polymerase beta activity increases slightly between 7 and 14 days of incubation; it then decreases slowly until seven days after hatching and remains constant thereafter. DNA polymerase gamma activity is maximal between 7 and 14 days of incubation and then decreases until hatching. The activity of thymidine kinase increases slightly during the embryonic life until hatching and remains almost constant thereafter. The implication of these enzymes in DNA replication and repair processes is discussed.


Changes of DNA ligases in chick neural retina as a function of age. In the course of chick neural retina development, several forms of DNA ligase have been found. During embryonic life the major DNA ligase activity that is found at seven days is form I (8.2 S) which gradually decreases and disappears by 14 days after incubation, whereas form II (6.2 S) increases to reach a maximum at the time of hatching. Form II then decreases reaching a constant level by Day 7 and from that time new slow sedimenting forms also appear (forms III and IV). Form III(2 S) is first detectable at seven days and increases up to 90 days, whereas form IV (3 S) is the only form detected in the 17- and 18-month-old and also in the 5-year-old birds. These four forms display different elution patterns on phosphocellulose column chromatography. They also differ in their thermal stability and sensitivity towards N-ethylmaleimide.


An experimental study on histamine H2-receptor antagonist on calcium, gastrin and histamine induced gastric acid secretion in rat. The suppressive effect of histamine H2-receptor antagonist, cimetidine, on gastric secretion was investigated in Ghosh-Schild rat. The study above was done in basal state under infusing normal saline (1 ml/h) and stimulated state by histamine-di-chloride (3.5 mg/kg-h), tetragastrin (50 mcg/kg-h) or calcium chloride (4 mg/kg-h). Dose related increase of cimetidine (1.7, 3.5, 7.0 and 14.0 mg/kg-h) were observed and correlated with the degree of inhibition of acid secretion. Cimetidine had a potent inhibitory activity on either basal and stimulated acid output by the agents above. Basal acid secretion was completely abolished by 3.5 mg/kg-h of cimetidine to the level of anacidity. The degree of inhibition by the same dose of cimetidine was different among the agents used as stimulant on acid secretion and it followed in the order of calcium, gastrin and histamine subsequently. This study indicated that histamine H2-receptor participated the gastric secretion induced by either gastrin or calcium other than histamine itself. This fact indicated the important role of endogenous histamine in gastric secretion induced by calcium and gastrin.


Studies on circulating soluble immune complexes of the liver disease. 2. Serum inhibitory activity of polyclonal rheumatoid factor binding to IgG-sepharose. Circulating immune complexes were tested in the liver disease by measuring polyclonal rheumatoid factor (pRF) inhibition activity. The test is based on the inhibition of 125I-pRF binding to IgG-p-azobenzamidoethyl Sepharose 6B. Normal levels of the test were less than 23%. The inhibition activity in sera with liver disease was found to correlate with severity of the disease, as defined by histological criteria. There were correlations of the activity with serum gamma-globulin concentration, seropositivities for rheumatoid factor and hepatitis B antigen.


A giant gallbladder.

A giant gallbladder. A case of giant gallbladder is presented. A 36-yr-old female complaining of colicky pain and a mass in the right upper quadrant underwent cholecystectomy, when the giant gallbladder, 18 cm in length and 4 cm in maximum diameter, and an extremely long cystic duct was confirmed. Since neither marked biliary inflammation nor biliary obstruction was observed, this giant gallbladder is considered to be congenital.


Statistical considerations on the parameters in drug evaluation. Some fundamental considerations are described on the parameters in clinical drug evaluation, and on the combination of them into a judgement on the usefulness of the drug. Regardless of the types of study, informal exploratory or formal controlled study, we must recognize that we work in the clinical field where many pitfalls of variability and bias are ambushing us.


Clinical features of silent stones at onset. Abnormal laboratory findings and abnormal functional and morphologic findings of the bile duct are infrequent in silent stones, and the course and prognosis are favorable in the cases of silent stones with no such abnormalities. These cases can therefore be followed up internally, but because onset becomes frequent in the prolonged follow-up, early operation is mandatory when the laboratory study shows any abnormality.


Quantitative study of mucosal structure, enzyme activities and phenylalanine accumulation in jejunal biopsies of patients with early and late onset diabetes. A study of the three-dimensional structure of the upper jejunal mucosa in diabetics has been carried out. The structural findings were related to 14C-L-phenylalanine uptake in vitro, sucrase activity in mucosal homogenates, and the enzyme content of the absorptive cells as measured cytophotometrically. A low grade mucosal transformation of the sprue-type was found, which was associated with decreased sucrase activity, and with no reduction in phenylalanine accumulation. On the other hand the specific activities of alkaline phosphatase, non-specific esterase, and succinic dehydrogenase in the surface cells remained unchanged.


Breath hydrogen in pneumatosis cystoides intestinalis. Pneumatosis cystoides intestinalis (PCI) is an uncommon condition of unknown aetiology. Bacterial gas production may be an important aetiological factor, but experimental evidence in humans has been lacking. We have studied breath hydrogen excretion as an index of bacterial gas production in 12 patients with PCI and have shown that four out of five with demonstrable cysts produced unusually high levels of hydrogen while fasting. This abnormality has not been previously reported. One patient showed resolution of PCI after antibiotic treatment. These findings confirm the importance of bacterial gas production in the pathogenesis of PCI.


Clq metabolism in ulcerative colitis and Crohn's disease. The metabolism of pure radioiodine labelled Clq has been observed in five patients with ulcerative colitis, five patients with Crohn's disease, and in five control subjects. Both the fractional catabolic rate and the synthesis rate of Clq were increased in the five patients with Crohn's disease and in four of the five patients with ulcerative colitis. The fifth patient was in remission and had a normal synthesis rate. These results support the hypothesis that complement activation plays a role in the pathogenesis of these disease states and that the increased complement activation is primarily via the classical pathway.


Studies in primary hypomagnesaemia: evidence for defective carrier-mediated small intestinal transport of magnesium. A 4 year old male with primary hypomagnesaemia was studied using balance and steady-state perfusion techniques. Magnesium balance was negative and could be accounted for by increased faecal losses, renal conservation being normal; calcium balance was normal. After oral magnesium therapy magnesium balance became positive. The perfusion studies demonstrated net loss of magnesium into the intestinal lumen when low concentrations (1 and 2 mmol/l) of magnesium were perfused in contrast with control subjects; whereas at high concentrations (10 mmol/l a net absorption of a magnitude similar to control values was observed. In the control subjects sequential perfusion of increasing concentrations of magnesium demonstrated a curvilinear relationship between rates of absorption and the lower concentrations (1, 2, and 4 mmol/l) with an apparent Km and Vmax of 4.5 mmol/l and 91 nmol/min/cm respectively. At the higher concentrations (6 and 10 mmol/l) the relationship was linear. These data suggest that two separate transport systems participate in the absorption of magnesium from the proximal small intestine; a carrier-mediated system which saturates at low intraluminal concentrations, and a simple diffusional process. The possibility of the second transport system being a carrier-mediated process with a very much higher Km cannot be excluded. In primary hypomagnaesaemia the results suggest that the primary abnormality is a defect in carrier-mediated transport of magnesium from low intraluminal concentrations of magnesium.


Big and little gastrin responses to food in normal and ulcer subjects. In normal, duodenal ulcer, and gastric ulcer subjects the two main forms of gastrin, G17 and G34, were estimated by radioimmunoassay in fasting serum and after feeding. Two antisera were used: one showing high specificity for G17, the other specific for the common COOH-terminus of G17 and G34 and so allowing estimation of G34 by difference. Basal G17 was similar in gastric ulcer, duodenal ulcer, and normal subjects and the increases of G17 after feeding were also similar in these groups. In contrast, basal G34 was similar in normal and duodenal ulcer subjects but raised in gastric ulcer subjects. After a meal the G34 concentration in both gastric and duodenal ulcer patients was significantly higher than normal. It is concluded that the higher post-prandial gastrin responses in peptic ulcer that have been previously described are due largely to increased G34.


Simultaneous measurement of antroduodenal motility, gastric emptying, and duodenogastric reflux in man. In six healthy individuals, the relationship between antroduodenal motor activity, duodenogastric reflux, and gastric emptying were simultaneously examined by combined use of multiple marker perfusion and miniature strain gauge transducers. An interdigestive pattern of motor activity was observed during the fasting period;duodenogastric reflux was of variable magnitude, but reproducible in each individual. Fasting reflux was significantly reduced during phase III of the interdigestive complex. Administration of 0.15 M sodium chloride into the stomach resulted in minor and inconsistent changes in antroduodenal motility, despite the rapid and similar pattern of gastric emptying in the six subjects. This study supports the concept that motor activity in the antroduodenal region does not affect gastric emptying of inert, isotonic fluids but may be involved in the regulation of duodenogastric reflux.


Trypsin and lactoferrin levels in pure pancreatic juice in patients with pancreatic disease. Levels of immunoreactive trypsin were measured in pure pancreatic juice obtained endoscopically from 44 patients with suspected pancreatic disease. Patients with pancreatic cancer all had low trypsin concentrations (median 3.6 micrograms/ml, range 0.6--12.0), but those with chronic pancreatitis had very variable levels (median 14.2 micrograms/ml, range 3.2--76.8), showing a considerable overlap with patients without pancreatic disease (median 37.1 micrograms/ml, range 10.4--66.0). When levels of lactoferrin in pancreatic juice were measured, all patients with chronic pancreatitis were found to have much higher levels (all greater than 900 ng/ml) than control subjects or patients with pancreatic cancer (all less than 400 ng/ml). The combined measurement of trypsin and lactoferrin in pure pancreatic juice appeared to be more promising than any other currently available test for the separation of patients with pancreatic cancer from those with chronic pancreatitis.


Peroperative transduodenal biopsy of the pancreas. Peroperative transduodenal biopsy of the pancreas was performed in 65 patients with the disposable Trucut needle. The technique described is simple, effective, and may reveal unsuspected malignancy. A histological diagnosis of malignancy is reliable but false negative diagnosis may arise because of failure to obtain representative samples.


Secretion of biliary lipids in young Chilean women with cholesterol gallstones. The early appearance of cholesterol gallstones is very common in Chile. To elucidate the mechanisms involved in this phenomenon, the size of the bile acid pool and the secretion of biliary lipids were studied in two groups of young women with normal weights and radiologically functioning gallbladders: nine with cholesterol gallstones and 14 healthy volunteers. The bile acid pool was similar in control and gallstone patients. The secretory rates of bile acids and phospholipids were comparable and significantly correlated in both groups. On the other hand, cholesterol output was higher in gallstone patients. In controls there was a significant correlation between the output of bile acids and cholesterol, but no correlation was found in the gallstone group. This study suggests that cholesterol hypersecretion into the bile is a major factor in the pathogenesis of cholesterol gallstone disease in young Chilean women with normal weights.


Occurrence and polymorphism of bombesin-like peptides in the gastrointestinal tract of birds and mammals. The gastrointestinal tract of mammals and birds, especially stomach and upper small intestine, contains bombesin-like peptides. This has been unequivocally demonstrated by radioimmunoassay and bioassay. Concentrations of bombesin-like activity may range from a few ng to 500-600 ng per g fresh tissue. Last values refer to the chicken proventriculus, which has been the object of a more thorough investigation. The bombesin-like peptide of the chicken proventriculus showed a marked heterogeneity. All forms probably stem from a pro-bombesin, a large precursor molecule which is insoluble in methanol, acetone, and even boiling water, but may be cleaved by acid hydrolysis. Methanol extracts contain at least two forms of the bombesin-like peptide; HCl extracts at least three forms; HCl extracts of the residue of methanol extraction at least four forms. Whereas some forms--for example, the methanol extractable forms--probably pre-exist in the tissue, other forms may be artefacts arising from acid treatment. The various forms may be distinguished from each other not only by their elution profile, but also by bioassay. In fact, though all forms show the activity spectrum characteristic for the amphibian bombesin-like peptides, they present considerable quantitative differences in activity. Pro-bombesin(s) probably occur also in the rat and guinea-pig stomach; similarly, a clear-cut heterogeneity is appreciable for the bombesin-like peptide of the human gastric mucosa.


Virus isolation studies in Crohn's disease: a negative report. Homogenates of gut and mesenteric lymph node tissue from patients with Crohn's disease, ulcerative colitis, and control patients were tested for cytopathic effect (CPE) production in a series of cell lines including rabbit ileal and W138 cells. A CPE was produced in W138 cells by tissue homogenates from patients with Crohn's disease, ulcerative colitis, and control patients. Evidence was obtained to suggest that this effect, although superficially similar to a viral CPE, was due to toxic protein constituents of inflamed tissue homogenate.


Pancreatic response to secretion+CCK-PZ in European and North African adults and children. Pancreatic response to intravenous secretin GIH (1CU/kg) +CCK-PZ (3CHRU/kg) was investigated in European and North African normal subjects. The pancreatic responses were compared in two groups of 38 normal male adults and in two groups of nine normal nurslings (less than 1 year). Body weight and age were similar in the two adult groups and in the two nursling groups. The peaks of volume, electrolytes, and enzymes were determined in samples of duodenal aspirate after hormonal stimulation. In adult subjects the flow rate and electrolytes were not statistically different in the two groups, while enzyme outputs were lower in the North African group -73% for lipase (P less than 0.001), -54% for phospholipase (P less than 0.01), and -35% for chymotrypsin (P less than 0.05). On the other hand, in both groups of nursling subjects all parameters of pancreatic secretion were identical. The difference in the pattern of the pancreatic response to exogenous hormonal stimulation observed between the two groups of adult subjects could be related to genetic or acquired differences. The second hypothesis is, however, the most probable because the pancreatic secretion was similar in both groups of nursling subjects.


Clinical relevance of an unfused pancreatic duct system. In man, the main pancreatic duct is normally derived from ventral and dorsal embryological buds of the pancreas. In a minority of people, failure of fusion of the two buds results in separate drainage of the dorsal and ventral pancreas, so that the accessory duct provides the main drainage for the gland. Patients with this anomaly demonstrated at endoscopic retrograde pancreatography (ERP) have been investigated to assess whether non-fusion of the main pancreatic duct predisposes to the development of pancreatitis. A failure of fusion of the pancreatic ducts was seen in 21 out of 449 (4.7%) successful pancreatograms; four of these 21 patients had definite clinical evidence of pancreatitis and two patients had possible pancreatic disease, but in the remainder the anomaly was not considered to be clinically relevant. An abnormal pancreatogram suggesting pancreatitis was present in 116 out of the 428 patients (27.1%) with a normally fused duct system. The anomaly was found as frequently in the whole series as it was seen in patients with pancreatitis. These findings suggest that embryological failure of pancreatic duct fusion does not predispose to the development of pancreatitis. However, the presence of this anomaly may lead to misinterpretation of ultrasonographic and CT scan findings.


Bile acid studies in patients with Crohn's colitis. Bile acid studies were performed in patients with Crohn's disease, radiologically confined to the colon. The bile acid pool size of 10 patients with isolated Crohn's colitis was significantly lower than that of 10 normal control subjects (P less than 0.001) and of 10 ulcerative colitis patients (P less than 0.005). Measurements of 14C-excretion in breath and in 24 hours stool collections after the administration of 5 muCi 14C-glycocholate showed a normal 14C-excretion in breath and usually a markedly increased loss of 14C in the stool (greater than 7% of the dose). The simultaneous administration of 5 muCi 3H-polyethylene glycol MW 4000 (3H-PEG) as a marker indicated that the 14C/3H ratio in the patients with Crohn's colitis was significantly greater than in a control series of patients with diarrhoea not due to bile acid malabsorption. Studies on the composition of duodenal bile showed a significantly decreased concentration of deoxycholic acid in duodenal bile. These observations suggest bile acid malabsorption in patients with Crohn's disease apparently confined to the colon.


Enterohepatic circulation rates of cholic acid and chenodeoxycholic acid in man. The rate of enterohepatic cycling of cholic acid and chenodeoxycholic acid was determined in five male subjects. Pool sizes were measured by isotope dilution technique after intraduodenal administration of 14C-labelled cholic and chenodeoxycholic acid. The hourly hepatic secretion rate of bile acids was determined by an intestinal perfusion technique. From these data the cycling frequency was calculated. Chenodeoxycholic acid circulated on an average 1.34 (range, 1.13--1.57) times faster than cholic acid, probably because chenodeoxycholic acid to a larger extent than cholic acid is absorbed from the proximal small intestine and thus partly bypasses the hepaticoileal circuit. This difference in cycling rate may have methodological as well as physiological implications.


Bile acid clearance in liver disease.

Bile acid clearance in liver disease. The disappearance of intravenously administered cholylglycine-14C was studied in the fasting and postprandial states in seven subjects with healthy livers and 10 patients with liver disease. In neither group was there any significant difference in the pattern of 14C disappearance. In another 10 patients with liver disease there was no significant change when a loading dose of cholylglycine was given orally two hours beforehand. Clearance of bile acids seems to be unimpaired in all except severe liver disease. The apparent deterioration in endogenous bile acid removal after meals may be due simply to the increased amount of bile acids which are in circulation and available for portosystemic shunting.


Oxalate loading test: a screening test for steatorrhoea. To investigate the possibility of measuring urinary oxalate output instead of faecal fat excretion as an outpatient screening test for steatorrhoea, we determined 24 hour urinary oxalate and five day faecal fat excretion before and during an oral load of sodium oxalate 600 mg daily (oxalate 4.44 mmol), in 32 patients with suspected malabsorption on a diet containing oxalate 30 mg (0.33 mmol), fat 50 g (180 mmol), and calcium 1 g (25 mmol). Nineteen patients proved to have steatorrhoea (mean faecal fat 62 mmol/24 h, range 19--186 mmol) of varying aetiologies. On the diet alone, urinary oxalate was raised in only nine of these patients (mean 0.25 mmol/24 h, range 0.08--0.59 mmol) (normal less than 0.20). By contrast, when the diet was supplemented with oral sodium oxalate, all 19 patients with steatorrhoea had hyperoxaluria (mean 0.91 mmol/24 h, range 0.46--1.44 mmol) (normal less than 0.44). There was a significant positive linear relationship between urinary oxalate and faecal fat when the 32 patients were on the high oxalate intake (r = 0.73, P less than 0.001), but not when they were on the low oxalate intake. Mean percentage absorption of orally administered oxalate was 5.8 +/- 0.99% (+/- 1 SD) in normal subjects and 14.7 +/- 6.0% (P less than 0.002) in patients with steatorrhoea. Measurement of urinary oxalate output during oral sodium oxalate loading appears to be a reliable and convenient screening test for steatorrhoea.


Motor activity of the sigmoid colon in chronic constipation: comparative study with normal subjects. Manometric studies of the sigmoid colon were performed on 17 healthy volunteers and on 49 constipated patients, after a long period of fasting (18--20 hours). Motility was recorded using perfused catheters at basal level during 45 minutes, then 60 minutes after a 0.5 mg intravenous injection of neostigmine, and, finally, 30 minutes during and after a meal. Motor activity was assessed by a motility index (per cent of activity x mean amplitude of waves). In both normal and constipated patients, the basal motility index was very low (respectively 82 +/- 16 and 110 +/- 113). This low level of activity was due to the long fasting period imposed on all the subjects. After neostigmine the motility index increased in both controls (347 +/- 256) and constipated patients (311 +/- 325); this test, however was found to be unreliable. The meal increased the motility index to significantly higher values than after neostigmine in controls (538 +/- 215). In constipated patients the mean meal motility index was comparable with that of controls (577 +/- 549) with a large distribution of individual values. Using the mean meal motility index +/- 2 SD of the control group as a term of comparison, the patients were segregated into three groups: 'hypomotor' patients (eight cases), 'normomotor' patients (33 cases), and 'hypermotor' patients (eight cases). From the evidence of this series of clinically well-defined constipated patients, it was concluded that only the meal test is able to segregate three significant patterns of sigmoid activity and that a large number (68%) of constipated patients exhibit normal sigmoid motor activity.


Recurrent unilateral swelling of the parotid gland. The clinical features of 109 patients with recurrent unilateral parotid swelling (24 patients with Sjögren's disease were excluded) have been analysed to explore the best system of management. The cause was definitely a parotid duct calculus in 36 patients, and evidence is presented that the same diagnosis probably applied to another 59 patients. Features suggesting a diagnosis of calculus included age (greater than 29 years); duration of the attacks of pain (less than 24 hours); cessation of salivation on the affected side; and a spurt of saliva heralding the relief of symptoms. Only three patients in the definite calculus group (8.3%) had no physical signs. However, had physical examination not included inspection and palpation of the parotid duct and its orifice from within the mouth 75% of the proven calculi would have been missed. The intraoral and anteroposterior plain radiographs are likely to be helpful, and sialography even more so. A sialographic appearance of a stricture in the main duct with proximal dilatation is usually due to a claculus. It would appear that calculi are the cause of recurrent unilateral parotid swelling (after exclusion of Sjögren's disease) in an overwhelming proportion of patients with this symptom.


Cervical mucus and prediction of the time of ovulation. 12 normal ovulatory women were studied during 17 menstrual cycles. The first day on which the women had increasing quantities of 0.1 ml or more clear cervical mucus (IQCCM) was closely related to the time of ovulation as monitored by basal body temperature and radioimmunoassay of serum-luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone. The results show that the time of ovulation can be predicted clinically without specialized tests by observing the day of onset of IQCCM.


Ultrastructure of the syncytiotrophoblast of the human term placenta in EPH-gestosis. The ultrastructure of normal full-term placentae and of placentae of patients with EPH-gestosis was studied. To minimalize artificial changes puncture biopsies during cesarian section were performed. The main ultrastructural alterations in cases of EPH-gestosis can be summarized as follows: loss of the characteristic three-zonal pattern, increased deposits of fibrinoid, rarefication of microvilli, dilatation of the endoplasmic reticulum and of the Golgi apparatus.


Significance of urinary enzymes in gestosis. The levels of five enzymes were examined in the urine and the serum of pregnant women. They included leucine aminopeptidase (LAP), alkaline phosphatase (AP), N-acetyl-beta-glucosaminidase (ABG), lactic acid dehydrogenase (LDH) and glutamic-oxaloacetic transaminase (GOT). After establishing the normal curve and upper confidence limits in healthy pregnant patients (138 examinations in 52 women), the the enzymes were examined in the urine and the serum of 21 severe and 23 mildly toxemic cases. The mean urinary levels of ABG, AP and LAP in the severe cases were significantly higher than in the normals, and by examining all three enzymes, at least one of them was found to be above the upper confidence limit in 95% of the severely ill women. The changes did not show up early enough to form a good diagnostic and prognostic sign in moderate pregnancy-induced hypertension, but severe kidney damage may be revealed earlier than by the regular kidney function tests, and patients with a bad remote prognosis can be singled out by this method.


[Treatment of arthroses of the carpal bones and the first carpometacarpal joint with liquid silastic implants]. In cases of resection arthroplasties of the carpometacarpal joint of the thumb we implant liquid silastic. This implant provides a good adaptation to the individual local situation and shows a good resistance to deformation. On the basis of our initial experience with this procedure we regard it as highly apt to provide an exactly fitting substitute in the wrist--especially in cases of an extirpation of the lunate bone.


[Congenital arteriovenous fistula of the hand and its treatment by means of microvascular anastomosis]. In the management of arterio-venous fistulas in the extremities one is confronted with technical difficulties due to the small caliber of the vessels. Excision of the abnormal segment precludes direct reanastomosis. A case is presented in which the vessel defect was bridged by microsurgical arterial interposition.


[The ultrastructure of ganglia and newly formed tendon sheaths]. Comparative electron microscopic examination of ganglions (from the tendon sheaths and joint capsules of the hand) as well as that of newly formed tendon sheaths (after resection of digital flexors and their tendon sheaths) indicate that both are the result of an adaptive effect of the mesenchyma which enables the formation of a new synovial organ in the presence of an adequate stimulus.


[Radial nerve paralysis in congenital angioleiomyoma]. An isolated paralysis of the radial nerve in a newborn was reported. The displaced growth of the histologically proved angioleiomyoma caused a circumferential compression with subsequent atrophy of the nerve (Fig. 4). During operative treatment of the tumor, the damaged part of the nerve was resected, too. In a second stage the defect in the nerve was closed by suralis grafts. Possibly due to scar adhesions a good result was not obtained.


[Local-antibiotic treatment with gentamycin-PMMA-minichains in surgery of hand infections]. In bone and soft tissue infections surgical treatment is often indicated. Gentamycin-containing plastic beads permit an additional, highly effective local antibiotic therapy. Beads of smaller caliber have been developed for the use in hand surgery.


[Differential diagnosis of tumors of the soft tissue of the forearm: an atypical palmaris longus muscle]. Bellies of the palmaris longus which are situated in an atypical position can appear as tumors of soft tissues on the flexor side of the forearm. Besides a central position a distal bicipital and a doubled variant can be observed. We report the case of a 22 years old female patient, with a "tumor" on the flexor side of the forearm of plum-size. Previous surgery had been interrupted when musculature appeared. During the revision we found a belly of the palmaris longus in a central position, situated proximal to the flexor retinaculum. The belly of musculature was 5 cm long and 2 cm wide. After extirpation of the tendinous and muscular parts the patient was free of symptoms.


[Treatment of amputation of the distal finger phalanx with a neurovascular flap]. A method of covering defects of the distal phalanx with a sensible full thickness transposition flap is demonstrated using clinical cases. A laterally based full thickness flap with its palmar neurovascular bundle is mobilized in the injured finger. By stretching and displacing the neurovascular bundle the sensible full thickness flap can be placed on the defect.


[Functional results after reconstruction of severed flexor tendons by means of free flexor tendon grafts]. From 93 free flexor tendon grafts which have been performed in the years 1959--1976 because of flexor tendon laceration 85% could be reinvestigated after 6 years 10 months (average intervall). Three reinvestigation schemes for classification of the functional results were used (VERDAN/MICHON 1961, McKENZIE 1967, BUCK-GRAMCKO 1976). This had the advantage that marked differences in the classification schemes could be demonstrated. With 56% of very good and 22% of good results according to the classification of McKENZIE or 30% of very good and 26% of good results according to the classification of BUCK-GRAMCKO the results of free flexor tendon graft in the area of the thumb are significantly better than those in the fingers. In addition the relationship between the objective reinvestigation results of the operation and the subjective results appraised by the patients is demonstrated and shows that BUCK-GRAMCKO's classification comes closest to the patients evaluation.


[The monodigital recognition test (MRT)--a sensitivity-specific variant of Moberg's pick-up test]. The Test for Mono-digital Recognition (MRT) is a procedure specifically designed for the measurement of gnostic performance. The new test was derived from MOBERG's Pick-up Test with the aim of eliminating its shortcomings. Additional injuries do not restrict the applicability of the MRT and the test is not confined to the skin area supplied by the median nerve. The MRT expresses the degree of gnostic disturbances by means of a point system. For testing a patient only two to four minutes are needed.


Identification of helminth species by means of disc electrophoresis. Soluble proteins of 25 helminth species of the classes Trematoda, Cestoidea and Nematoda, were separated by disc electrophoresis using polyacrylamide gel columns. Differences between the species were investigated on the basis of Rm values of the bands. Protein spectra were complemented by the detection of lipoproteins and glycoproteins and by identification of LDH, SHD, peroxidase, esterase and alkaline phosphatase. On the basis of comparison of protein spectra of parasitic worms belonging to three taxonomic classes it was found by means of numerical taxonomy that individual classes are characterized by a certain number of proteins of the same migration properties.


Tissue reaction to Cysticercus bovis in the lung of artificially infected cattle. The tissue reaction to Cysticercus bovis in the lung of cattle with an experimental infection was an inflammatory rim originating in the immediate vicinity of the cysts. The cysts recovered at days 83 and 102 p.i. contained living cysticerci. The rim was composed either of a layer of high histiocytes organized in palisades (at day 83 p.i.), or a lyer of flat histiocytes (at day 102 p.i.). The outer layer of the rim consisted of fibroblasts, reticular cells and a different number of eosinophil- and neutrophil luekocytes. On the periphery, the rim was formed by granulation tissue infiltrated with lymphoplasmocytes. At the border between the layers of the inflammatory rim there were conspicuous foci of a necrotic appearance typical of a tissue reaction to C. bovis.


Is Tettnang virus a possible arbovirus?

Is Tettnang virus a possible arbovirus? The paper describes the isolation of 21 identical virus strains during virus isolation experiments in SPF suckling mice strain ICR. The isolated strains were first identified as closely related or identical to Tettnang virus and later as closely related to mouse hepatitis virus. Tettnang virus seems not to be an arbovirus.


Scanning electron microscopic studies on males of trichinella species. Ultrastructure of the cuticle and pseudobursa of adult males of four species of Trichinella has been studied by SEM. T. nativa differs markedly from T. spiralis, T. nelsoni and Trichinella sp. in the form of the pseudobursa. Trichinella sp. differs only slightly from T. spiralis and T. nelsoni. The ultrastructure of the cuticle revealed no characters suitable for the differentiation of the taxons under study.


Growth and production of anthracyclines in wild-type and mutant strains of Streptomyces galilaeus. The course of growth curves with respect to the biosynthesis of anthracyclines was followed in the wild low-producing strain Streptomyces galilaeus JA 3043 and in its mutants G-167 (producing increased quantities of glycosides of epsilon-pyrromycinone) and J-14 (accumulating free epsilon-pyrromycinone). A two-phase type of fermentation (growth phase, production phase) was observed in strains JA 3043 and J-14. The maximum production of anthracyclines occurred only after the end of intense growth of the culture. Two phases of rapid growth separated by a phase of stagnation were observed in strain G-167. The second growth phase proceeded only during late hours of cultivation and was (as compared with the first phase) associated with an intensive biosynthesis of anthracyclines.


Effect of aeration efficiency and carbon source on the production of anthracyclines in Streptomyces galilaeus. Biosynthesis of anthracyclines in Streptomyces galilaeus during submerged cultivation is considerably influenced by aeration and by the concentration of glucose in the medium. At higher values of oxygen absorption rate both the production of epsilon-pyrromycinone glycosides in the wild strain JA 3043 and its production mutant G-167 and accumulation of free epsilon-pyrromycinone in the blocked mutant G-162 were found to be higher; the production of 7-deoxyaglycones was lower in all strains. The studied strains differed in the rate of glucose consumption and in the ability to utilize starch for the biosynthesis of anthracyclines. A two-fold concentration of glucose in the medium resulted in the G-162 strain in an increase of the yield of epsilon-pyrromycinone by 120%. The production of glycosides in strain G-167 increased even after exhaustion of glucose from the medium and the amount of 7-deoxyaglycones simultaneously decreased.


Nitrosoguanidine-induced mutations in Streptomyces indicus. The mutagenic activities of five 1-alkyl derivatives of 3-nitro-1-nitrosoguanidine, viz. methyl, ethyl, propyl, isopentyl and octyl, were tested on Streptomyces indicus. All the compounds were found to be mutagenic. The methyl and ethyl derivatives were most effective regarding mutational frequency. The effectiveness decreased with increasing number of C-atoms in the alkyl group of the mutagens. The compounds tested had a much higher mutagenic efficiency that UV-rays. A marked variation existed in antibiotic activity among the biochemical mutants: increase, decrease or complete absence of such activity were seen.


Electron microscopy of some rock phosphate dissolving bacteria and fungi. Bacteria Pseudomonas striata, Bacillus polymyxa, B. megaterium and B. pulvifaciens, and fungi Aspergillus awamori, A. niger and Penicillium digitatum dissolve tricalcium phosphate and, much less, Mussorie and Udaipur rock phosphate. The solubilizing power of fungi was higher than that of bacteria, the highest being with A. awamori and A. niger, and with P. striata. Electron microscopy of the various cultures showed an electron-dense layer on the bacterial surface after negative staining. The size of phosphate particles decreased by the microbial action, with tricalcium phosphate from 140--250 to 30--90 nm after three weeks of incubation.


Morphology, serology and biochemical characters of phage CVX-5, isolated from a patient with colitis. Electronmicroscopic observations indicate that bacteriophage CVX-5 has an angular head with long spiral tail which is noncontractile, possibly having 2--3 tail fibres attached at the distal part of the tail. This phage is antigenically unrelated to any of the T-phages. Inhibition of phage CVX-5 multiplication by mitomycin C and incorporation of 3H-thymidine into this phage indicate that phage CVX-5 is a DNA phage.


Effect of the nonilluminated part of suspension on biomass production in an algal reactor. The production of algal biomass in the illuminated and nonilluminated part of the suspension in an algal reactor was analyzed with regard to the biological inertia of the algae. The calculations indicate a considerable effect of nonilluminated part of the reactor on algal biomass production. The intensity of suspension stirring affects biomass production only slightly.


Semicontinuous cultivation of autotrophic algae. Mathematical expressions were derived for the dilution rate and concentration of algae determining the maximum biomass production in a semicontinuous algal culture.


Cell morphology and flagellation of nitrogen-fixing spirilla. Twenty isolates of N2-fixing spirilla were isolated from the rhizosphere of maize and sugar cane grown in Egyptian and Belgian soils. Electron microscopy distinguished two morphological groups. The first includes short and thick curved rods with an unipolar flagellum while cells of the second group are much longer with the typical appearance of spiral cells and most probably possess a bipolar tuft of flagella.


Morphogenic effect of 2-deoxy-D-arabino-hexose on Rhodosporidium toruloides. The presence of 2-deoxy-D-arabino-hexose in the growth medium caused marked morphological changes in the cells of Rhodosporidium toruloides. The originally elongated ellipsoidal cells grew spherically in the presence of the deoxy-sugar, displayed differences in cell division and separation, and were larger than the control cells. After exhaustion of glucose from the medium the cells died, although no lysis was observed. The morphological changes were accompanied by significant alterations in the carbohydrate composition of the cell wall. The wall of R. toruloides grown in the presence of the deoxy-sugar contains higher proportions of chitin and glucan, while the relative contents of mannose and galactose polymers decreased drastically in comparison to normal cells.


Thermomonospora sp. T-SA-125 and its production of a growth promoting antibiotic. Thermomonospora sp. T-SA-125 is a true thermophilic actinomycete isolated from a soil sample collected from the Saudi Arabian desert. It is characterized by the formation of single spores at the tips of dichotomously branched aerial mycelium and differs from Thermomonospora curvata and T. viridis in certain aspects. It produces a basic water-soluble antibiotic which is active against Gram-positive bacteria, moderately active against Gram-negative bacteria and inactive against fungi. At high concentrations, this antibiotic, stimulated the growth of both Hordeum coleoptile and lettuce hypocotyl.


Evidence of microchoerine evolution from Dielsdorf (Zürich region, Switzerland)--a preliminary report. Further evidence of parallel evolution of Necrolemur and Microchoerus is put forward. The two forms were found in a fissure filling of Upper Eocene age (Fons 4) from Dielsdorf (Zürich region, Switzerland). Not only the dentition shows different morphs, but also postcranial material represents two vertical clingers and leapers of different size.


Morphometric studies in the taxonomy of the orang-utan (Pongo pygmaeus. L. 1760. The purpose of this study is to verify the subspecific level of the two recent refugial groups of Orang-utan on Borneo and Sumatra. A total of 47 skulls from both regions were studied by means of 32 craniometric characters. Univariate analysis showed highly significant differences only in males, whereas multivariate statistical analysis led to complete discrimination in both sexes. These results support the assumption that the geographically isolated Orang groups are subspecies.


[Studies on medico-legal diagnosis in cold district. 2. Cadaveric phenomena in low temperature surroundings (author's transl)]. The authors have investigated 14 kinds of findings of 15 cadavers in low temperature surroundings which had remained at known postmortem interval and had been subjected to medico-legal autopsies in our laboratory, comparing with those at normal temperature. In low temperature surroundings, the onset and progress of the findings due to autolysis or putrefaction are retarded in a marked degree but the turbidity of the cornea which is considered to be due to physical or chemico-physical phenomenon is retarded merely in a slight degree. Hence, an erroneous determination of the postmortem interval can be avoided by taking care of the peculiarity. Even the cadavers at low temperature display in 3 to 5 months after death the findings whose degrees correspond to those of the cadavers at normal temperature in 4 to 7 days after death. Some fly-larvae pass the winter on cadavers demonstrating that the time of death was towards the end of autumn of the preceding year.


[Studies on medico-legal diagnosis in cold district. 3. Autopsy findings of the victims of cold exposure (author's transl)]. The authors have investigated the autopsy findings of 8 bodies died from cold. The conclusions are as follows: Pink colour of the blood in the left ventricle or the pulmonary veins, pink colour of the lungs and pink patches of the skin are fairly pathognomic findings of death from cold. Seven out of eight bodies have presented at least one of these findings. Subserous or submucous hemorrhage is less pathognomic and has been presented less frequently.


[Studies on medico-legal diagnosis in cold district. 4. An experimental study on the rise of temperature of dead body caused by the radiation of sunlight (author's transl)]. A sausage of 4 cm diameter and 15 cm length was chosen as a model of a part of human extremities. On the snowfield the model was stood on end and its temperature was recorded continuously by means of thermistor thermorecorder. The conclusions are as follows: In fine weather the temperature directly under the sunny surface of a model rose higher than the air temperature by 18 degrees C in the most remarkable case. Even in cloudy weather it rose fairly though lower than in fine weather. The rise of a model temperature became higher in February than in January. Even at a depth of 1.0 cm the temperature rose fairly though lower than directly under the surface. The temperature of the shady side of a model was equal to air temperature or snow temperature. It is presumed from these data that the temperature of a human dead body on snowfield becomes higher and reaches a optimum temperature for putrefaction at least partly by the radiation of sunlight. The presumption is supported by our experiences at the autopsies in cold district.


[Milk spots on the parietal peritoneum over the pancreas in the mouse (author's transl)]. In adult dd-mice of both sexes, milk spots on the parietal peritoneum over the pancreas were studied by light and transmission and scanning electron microscopy. The milk spots appeared like a leaf with a slender stalk adhering to the peritoneum or like a flat or disc-shaped mass on the pancreas. They varied in number from case to case, but they were, on the average, 2.1 +/- 0.6 in males and 4.0 +/- 0.7 in females. They were supplied with capillary vessels which had fenestrated endothelium. The milk spots were the same in structural details as the omental type I spots preveiously described.


[Experimental and clinical studies on ribosephosphate isomerase (author's transl)]. In order to know the clinical significance of serum ribose-5-phosphate isomerase (RPI), the activity of this enzyme was determined in sera of normal subjects and patients with hepatic disorders or malignant tumors. Experimentally, the enzyme activity in sera and liver tissue was followed in rats with acute hepatic damage induced by carbon tetrachloride (CCl4) or rats with hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The following results were obtained: 1) Serum RPI activity increased markedly in rats with CCl4-induced liver damage, whereas the activity in liver tissue decreased, both being related with reciprocally. 2) In the early phase of acute hepatitis, serum RPI activity increased and gradually decreased thereafter. No significant increase was observed in other hepatic disorders. 3) Both serum and liver RPI activity increased in rats with hepatoma induced by 3'-Me-DAB. 4) An increase in serum RPI activity was seen in higher percentage in cancer patients. Higher enzyme activity and its higher incidence were observed in patients with hepatic metastasis or primary hepatoma than in patients without metastasis. From these results it is concluded that serum RPI activity as a diagnostic aid is useful in estimating clinical course of hepatic disorders and also in diagnosing malignant tumors, especially in substantiating a diagnosis of metastasis to the liver.


[Studies on medico-legal diagnosis in cold district. 5. The blood shed on the snow (author's transl)]. By using bovine blood as a model, the authors have observed the forms and patterns of the blood drops shed or spurted on the snow and the extent of a large amount of blood absorbed in the deep snows, investigating the influence of the properties of snow upon them. It has been demonstrated that the polarographic method is most excellent for the purpose of determining the amount of blood absorbed in the snow.


[Medico-legal studies on the deaths from coal-mine accidents. 2. Exogenous findings (author's transl)]. Thirty-four deceased who were killed from twenty cases of coal-mine accidents during fourteen years from 1965 to 1978 were autopsied in our laboratory and the following conclusions have been obtained, summarizing the exogenous findings on the bodies. At the explosion of methane gas and coal dust chemical energy stored in coal or methane is converted to mechanical energy and thermal energy which act upon the human bodies. Mechanical energy produces diverse injuries in the human bodies, among which only the coal-particle impression demonstrates directionality. Thermal energy produces burns when it acts directly upon the human bodies and among diverse substances produced by heat from the explosion coal-tar like substance adheres to the skin, soot adheres to the inside of the air passage, carbon monoxide produces carbon-monoxide hemoglobin after entering the blood through the lung. At gas spurt mechanical energy stored in methane which is adsorbed on coal under high pressure is set free to produce injuries on the human bodies, but thermal energy does not develop. The action of diverse sorts of energy upon the body differs extraordinarily according to the distance from an epicenter or the irregularities of pit, producing various exogenous findings on the bodies. Accordingly, general rules cannot be established to assume the sort and mode of an accident and it should be considered on a case-by-case basis.


[Medico-legal studies on the deaths from coal-mine accidents. 3. Causes of death (author's transl)]. Thirty-four deceased who were killed from twenty cases of coal-mine accidents during fourteen years from 1965 to 1978 were autopsied in our laboratory and their causes of death have been discussed. In the explosion of methane gas and coal dust chemical energy stored in coal or methane is converted to mechanical energy and thermal energy which act upon the human bodies to bring about seven sorts of causes of death. Deaths are caused more frequently by thermal energy directly or indirectly than by mechanical energy. It is a characteristic found in the explosions of coal mines which are large and closed underground spaces consisting of inflammable material. In gas spurt major cause of death is asphyxia from the lack of oxygen resulting from the substitution of air by methane gas and the effects of mechanical energy developed by gas spurt is slight in degree. In the coal-mine accidents the causes of death are so much concurred that is is difficult to certify the cause of death. A new concept of a cause of death has been proposed to solve such a problem.


Nicotinic acid metabolism. 2,3-Dimethylmalate lyase. 1) A new enzyme, 2,3-dimethylmalate lyase, was purified from Clostridium barkeri to about 80% homogeneity. Some of the properties of the enzyme are described. 2) It is shown that the 2,3-dimethylmalic acid (m.p. 143 degrees C) described in the literature represents only one racemic pair. This pair is not attacked by 2,3-dimethylmalate lyase. 3) The isolation of both racemic pairs of 2,3-dimethylmalic acid is described. Half of one pair, m.p. 104-106 degrees C, was converted to propionate and pyruvate by 2,3-dimethylmalate lyase. 4) In combination with earlier work performed by E.R. Stadtman and coworkers the results given under points 1--3 establish 2,3-dimethylmalate as an intermediate in the degradation of nicotinic acid by C. barkeri. 5) Experimental evidence indicates the 2,3-dimethylmalate lyase is no acyl-S-enzyme and that it is different in this respect as well as in quaternary structure from the apparently related enzymes citrate lyase and citramalate lyase.


Properties and substrate specificities of two neuraminidases from Trichomonas fetus. Trichomonas fetus, a protozoon belonging to the class of flagellates causes vaginal infections in cows, leading to sterility or abortion in early stage of pregnancy. Two neuraminidases were isolated from the culture medium and purified by various procedures of gel chromatography, ion exchange chromatography, and by affinity chromatography on N-(4-nitrophenyl)-oxamic acid-Sepharose 4B. The molecular weights of the two neuraminidases were determined as 320 000 (enzyme I) and 38 000 (enzyme II) respectively. However, enzyme I seems to consist of two isoenzymes containing four subunits of almost equal molecular weight. The pH optima of both enzymes depend on the substrates and range from pH 4.7 to 5.5. Due to the type of substrate, the Michaelis constants (Km) vary between 5.0 x 10(-2)M and 6.6 x 10(-3)M for enzyme I and between 1.4 x 10(-2)M and 4.9 x 10(-3)M for enzyme II. Among the different groups of NeuAc-containing substrates, i.e. glycoproteins, glycolipids, oligosaccharides and synthetic ketosides, enzyme I preferably cleaves high molecular weight glycoprotein type substrates whereas enzyme II shows higher affinities to low-molecular weight oligosaccharides. The ganglioside II3NeuAcGgOse4Cer is susceptible to both enzymes only after removal of the lipophilic ceramide residue. Both enzymes show differences in the specificity towards alpha 2 leads 3 to 3, alpha 2 leads to 6, and alpha 2 leads to 8 glycosidic linkages of NeuAc. Taking the rate of cleavage of the alpha 2 leads to linkage in II3NeuAc-Lac as 100, enzyme I reveals 65 for the alpha 2 leads to 6 linkage in II6NeuAc-Lac, and 15 for the alpha 2 leads to 8 linkage in II3(comes from 2 alpha NeuAc8)2-Lac, whereas enzyme II exhibits values around 50 for both the alpha 2 leads to 6- and the alpha 2 leads to 8-linked substrates. The activity of neuraminidase I and II is not influenced by Ca2 but is inhibited by Cu2, Hg2, ann 4-hydroxymercurisulfonic acid. The inhibition by Hg2 and by the latter is reversible with enzyme I by addition of dithioerythritol.


Purification and characterization of a mitogenic lectin and a lectin-binding protein from Vicia sativa. From the seeds of Vicia sativa, a novel mitogenic lectin was isolated. Purification was carried out by affinity chromatography on Sephadex G-100. The tetrameric lectin is a glycoprotein with a molecular weight of Mr 40 000; it consists of two large beta-subunits (Mr 14 000) and two small alpha-subunits (Mr 6000). The N-terminal sequence of both subunits and their amino acid compositions were determined. The lectin agglutinates human erythrocytes, preferring group B, and erythrocytes from rabbits and horses; no agglutination takes place with sheep erythrocytes. Agglutination is inhibited by mono-, di- and tri-saccharides with the configuration of glucose at the free 4-hydroxyl group. The lectin stimulates mitosis in lymphocytes of mice. From the seeds of the same plant, a protein was isolated which binds to the lectin described above. The lectin binder consists of subunits with a molecular weight of 53 500.


Studies of the specific role of the subunits of choriogonadotropin for biological, immunological and physical properties of the hormone. Digestion of choriogonadotropin and its isolated subunits with serine carboxypeptidase. The residues 90-92 can be split off from the C-terminal region of the isolated alpha-subunit of choriogonadotropin (residues 88--92: -Tyr-Tyr-His-Lys-Ser-OH) by means of serine carboxypeptidase (des-Lys91,Ser92-alpha-subunit; des-(90-92)-alpha-subunit). However, when choriogonadotropin is digested by serine carboxypeptidase, only the residues 143-145 (-Leu-Pro-Gln-OH) form the C-terminus of the beta-subunit are released (des-(143-145)-choriogonadotropin). Depending on the pH conditions, glutamine 145 and the residues 143-145, respectively, are liberated by digestion of the isolated beta-subunit (des-Gln145-beta-subunit and des-(143-145)-beta-subunit, respectively). The present study provides evidence that the C-termini of both the isolated subunits and those in choriogonadotropin are probably arranged on the surface of the molecules. The biological activity of des-(143-145)-choriogonadotropin is not significantly decreased. The immunological activity, however, is reduced when measured by complement fixation. In comparison to the native hormone, a four-fold amount of des-(143-145)-choriogonadotropin has to be applied to obtain highest complement fixation. The conformation of des-(143-145)-choriogonadotropin does not seem to differ from that of the native hormone, when estimated both by CD measurements and by Ans-choriogonadotropin fluorescence. The respective determinant therefore seems to depend, at least to some extent, on the sequence of the C-terminal region of the beta-subunit of the hormone; complement fixation, however, does not seem to be affected significantly, when the des-(143-145)-beta-subunit is compared with the native beta-subunit using an antiserum against the native beta-subunit. This provides evidence that this C-terminal determinant is possibly more immunogenic at the hormone than at the isolated beta-subunit. The biological activity of recombined choriogonadotropin in vivo as well as in vitro is markedly reduced when serine 92 is removed from the C-terminus of the alpha-subunit (des-Ser92,Lys91-alpha-native beta-subunit: 36% residual activity in vivo). Biological activity is lost when the residues 88-90 are removed by digestion of the des-Ser92,Lys91-alpha-subunit with carboxypeptidase A. Recombination products between a modified alpha-and the native beta-subunit show a reduced Anschoriogonadotropin fluorescence (des-Lys91,-Ser92-alpha + native beta-subunit: 52%; des-(88-92)-alpha- + native beta-subunit: 23%). The Ans-induced aggregation of choriogonadotropin, however, also takes place in those recombination products which display a low Ans-choriogonadotropin fluorescence, indicating that the reduction is probably not caused by a portion of the molecules losing their binding sites for Ans. Therefore the diminished Ans-choriogonadotropin fluorescence seems to signal small conformational changes. The CD spectra of the native and the des-(90-92)-alpha-subunit, however, seem not to differ significantly. It is shown that the release of amino acids from the C-terminus of the alpha-subunit causes a disturbance of the interaction between the subunits. This seems to prevent an effective conformational change of the beta-subunit which probably is a prerequisite for the binding of the hormone to the receptors of Leydig cells.


The lectin binding sites on the membranes of the nuclear envelope, mitochondria and the cell surface of human lymphoblastoid cells. The membranes of the cell surface, the endoplasmic reticulum, outer and inner mitochondrial leaflet and nuclear envelope were isolated from three human lymphoblastoid cell lines. Membrane components were separated by dodecyl sulfate polyacrylamide gel electrophoresis and the gels incubated with the radioiodinated lectins from lentil, castor bean, scarlet runner bean, gorse seed and Roman snail. After gel slicing and counting, the molecular weights of the lectin binding sites were determined. About 20 glycoproteins were identified as constituents of the plasma membrane, a similar glycoprotein distribution was observed in the endoplasmic reticulum. The outer mitochondrial membrane contained some impurities from the plasma membrane, the inner mitochondrial membrane lacked specific lectin receptors. Two prominent glycoproteins with molecular weights of 70 000 and 60 000 were identified with the castor bean lectin in the nuclear envelope.


Purification and characterization of an activator protein for the degradation of glycolipids GM2 and GA2 by hexosaminidase A. The activator protein for the degradation of glycolipids GM2 and GA2 by hexosaminidase A was purified some 2 500-fold from normal human kidney. It has a molecular weight of approximately 25 000 is heat-stable up to 60 degrees C, possesses an isoelectric point of pH 4.8 and is digestible by proteases. Enzymic degradation of the lipid substrates in the presence of this activator proceeds optimally at pH 4.2. The mode of action of the activator was also studied: the protein most probably complexes lipid molecules and presents them to the enzyme which otherwise cannot attack the aggregates formed by the lipids in aqueous solution. The hydrolysis of water-soluble synthetic substrates is not affected by the activator protein. The activator is highly specific for hexosaminidase A: hydrolysis of glycolipids GA2 and GM2 by the hexosaminidase B isoenzyme is almost not enhanced by this protein. The isoenzymes' lipid substrate specificity measured in the presence of the activator is entirely different from that obtained with detergents and can satisfactorily account for the lipid storage pattern observed in patients with variant forms of infantile GM2- gangliosidosis.


[Respiration at high altitudes, phosphate-protein interaction: the sequence of hemoglobins from guinea pig and dromedary (author's transl)]. The sequence of the main hemoglobin component of the guinea pig (Cavia aerea f. porcellus, Caviidae) and that of the hemoglobin of the dromedary (Camelus dromedarius, Camelidae) is given. The sequence is obtained automatically by the sequenator using the quadrol and the propyne programme. The sequence of the alpha-and beta-chains of the guinea pig is compared with that of the human hemoglobin; the sequence of the dromedary in comparison to the Ilama shows in the alpha-chains five amino acid exchanges, in the beta-chains there are only two exchanges in beta 2 and beta 76. Beta 2 in dromedary is the P2-glycerate contact histidine. This sustains the interpretation of the high altitude respiration of the Ilama as mutation beta2His leads to Asn.


[Increased urinary excretion of neopterin in patients with malignant tumors and with virus diseases (author's transl)]. Heightened urinary concentrations of neopterin were detected in patients with malignant tumors. The levels of neopterin were quantified by high performance liquid chromatography. The normal range for male individuals was 280 +/- 1,7 ng neopterin/mg creatinin, for women 340 +/- 116 ng neopterin/mg creatinin. The values found in patients with malignant tumors were 1370 +/- 495 ng neopterin/mg creatinin and in patients with virus diseases 1637 +/- 696 ng neopterin/mg creatinin.


Mapping of the urinary bladder: its impact on the concepts of bladder cancer. The results of mapping of the urinary bladder are reported and discussed. It has been shown that Brunn's nests, cystitis cystica, and the vaginal type of squamous metaplasia are commonly found in normal bladders and thus cannot be considered as precancerous lesions. Mapping of cancerous bladders and related histologic and clinical observations strongly suggests that there are two distinct pathways in bladder neoplasia: the papillary pathway and the nonpapillary pathway. Papillary tumors with thin stalks must be considered as a focal expression of the proliferative potential of the urothelium. They are per se quite harmless but may be followed by other manifestations of neoplasia. Broad based papillary tumors, regardless of grade, may have "pushy borders," which extend into the lamina propria but rarely invade the muscularis. Nonpapillary flat lesions, notably atypical hyperplasia and carcinoma in situ, appear to be the principal source of invasive and metastasizing bladder cancer. The presence of the flat lesions puts the patient at high risk for the development of invasive carcinoma. Methods of assessment of the cancerous bladder are suggested and discussed.


Intracytoplasmic lumina in bladder carcinomas. Intracytoplasmic lumina were identified in neoplastic cells from four human and three canine "spontaneous" bladder carcinomas. They were also found in N-[4-(5-nitro-2-furyl)-2-thiazoly] formamide induced bladder carcinomas in rats as well as in cultured tumor cell lines derived from these experimental tumors. Intracytoplasmic lumina were readily recognized in 5 micrometer. paraffin embedded and 1 micrometer. epoxy embedded sections. Histochemically, intracytoplasmic lumina were strongly positive with PAS and alcian blue-PAS; mucicarmine stain was positive as unevenly distributed droplets. Ultrastructurally lumina were defined by a symmetric unit membrane; they displayed abundant pleomorphic microvilli, which contained prominent cytoskeletal elements. Step section electron microscopic study revealed continuity between intracytoplasmic lumina and the extracellular space in only one case of experimental bladder carcinoma; otherwise they appeared to be entirely encompassed within the cytoplasm. No instance of exocytosis in relation to intracytoplasmic lumina was found. Our observations suggest that intracytoplasmic lumina may be rather frequent in several forms of urothelial carcinoma. They appear to be predominantly but not invariably intracytoplasmic. The mechanism that may determine the development of continuity between intracytoplasmic lumina and the extracellular space and the adduced relationship between intracytoplasmic lumina and the process of secretion remain undetermined.


Vascular ectasias of the right colon in the elderly: a distinct pathologic entity. Vascular ectasias (angiodysplasias, arteriovenous malformations) of the cecum and ascending colon are a frequent cause of lower intestinal bleeding in the elderly that has been overlooked by clinicians and pathologists. Their nature and etiology have been poorly understood until recently. This article reviews the previous literature and presents a complete and detailed description of these lesions based on the examination of 87 areas showing vascular ectasia from 26 colons. Their morphology spans a spectrum from small focal early lesions to multiple large late lesions. The early lesions are characterized by markedly dilated, large, tortuous submucosal veins with minimal dilatation of their tributaries in the mucosa. The late lesions showed further dilatation of submucosal veins and venules and extensive replacement of the overlying mucosa by racemose collections of dilated and thin walled venules and capillaries, three of which demonstrated rupture into the colonic lumen. The pathology of these lesions is considered to be specific enough to establish vascular ectasias of the colon as a distinct entity.


Peripheral spindled carcinoid tumor: a review of its ultrastructure, differential diagnosis, and biologic behavior. The ultrastructure, differential diagnosis, and biologic behavior of the peripheral pulmonary spindled carcinoid tumor are reviewed. Electron microscopy is useful in distinguishing the spindled carcinoid from a variety of neoplasms with similar histologic features. The spindled morphology is a rare expression of the carcinoid tumor that is almost exclusively confined to the lung periphery. It appears that the spindled carcinoid without atypical features is fully capable of regional lymph node metastases in approximately 20 per cent of the cases.


Unusual ultrastructural features in a case of acute diffuse proliferative glomerulonephritis. A case consistent with recurrent acute poststreptococcal glomerulonephritis but with atypical features is described. Light microscopy revealed a diffuse proliferative glomerulonephritis. A spectrum of ultrastructural features, from the typical "humpy bumpy" subepithelial deposits to the apparent disappearance of the deposits within the epithelial cells, is presented. An unusual piling up of basement membrane material around the deposits is described, together with some areas showing an appearance reminiscent of membranous glomerulopathy. Resorption of the dense deposits within epithelial cells is suggested and a hypothesis advanced that the basement membrane reaction may indicate an incipient chronic immune complex lesion.


Intrarenal vascular alterations in hemodialysis patients. A semiquantitative light microscopic study. The intrarenal arterial and arteriolar changes in the kidneys of 80 patients with chronic renal insufficiency maintained on hemodialysis were studied semiquantitatively by light microscopy and histochemistry. Intimal proliferation was common and accounted for thickening of vessel walls and luminal narrowing. Fibrocollagenous and fibroelastotic intimal changes were located predominantly in the interlobular and arcuate arteries, whereas the fibromucinous intimal lesion was found mainly in the interlobar arteries. Thickening of the media was encountered in 25 per cent, and adventitial fibrosis in 20 per cent of the kidneys. Necrotizing arterial of arteriolar lesions were not seen. The significance of these alterations as a possible cause of renal ischemia and their role in the perpetuation of hypertension are discussed.


Ultrastructural and morphometric study of the human heart muscle cell in acute coronary insufficiency. In 13 patients with acute coronary insufficiency (intermediate syndrome, postinfarction angina, and progressive angina), samples of the ischemic area of the myocardium were studied with the electron microscope and by morphometric methods in order to describe quantitatively the mitochondrial population. Three indices were measured: the fractional volume of the mitochondrial compartment of the cytoplasm, the number of mitochondria per unit volume of heart tissue, and the average individual mitochondrial volume. As a control, the same study was performed on samples obtained from patients with chronic coronary insufficiency and mitral stenosis. In all the ischemic hearts the most conspicuous ultrastructural modification of the muscle cells consisted in an irregular distribution of the mitochondriranules. Generally, odd shaped mitochondria were found. The modifications were not diffuse, and almost normal heart muscle cells were seen alongside deeply altered ones. In addition a definite decrease in the fractional volume of the mitochondrial compartment was found, which was apparently due to a decrease in the number of mitochondria per unit volume of cytoplasm. The average individual mitochondrial volume was similar in acute coronary insufficiency and in the control cases. On the basis of this evidence it is postulated that in sublethal ischemia definite ultrastructural modifications of the heart muscle cells are associated with a decrease in the number of mitochondria per unit volume of cytoplasm.


The histiocytoid hemangiomas. A unifying concept embracing several previously described entities of skin, soft tissue, large vessels, bone, and heart. The proposal is made that a number of previously described entities of skin, soft tissue, large vessels, bone, and heart actually constitute different manifestations of the same basic process, characterized by the proliferation of a highly distinctive type of cell descriptively identified as a "histiocytoid endothelial cell." The entities in question are angiolymphoid hyperplasia with eosinophilia and related cutaneous and subcutaneous disorders, atypical vascular proliferation of large vessels, hemangioendothelioma of bone, and endocardial benign angioreticuloma of the heart. The main cell that proliferates in all these conditions has the basic features of an endothelial cell, but also exhibits histochemical and ultrastructural characteristics that are more akin to those of a histiocyte. These unusual features could be the expression of a morphologic abnormality or represent an overgrowth of a specific and as yet undefined subpopulation of endothelial cells, such as Majno's "contractile endothelial cell." Whether this group of proliferative diseases is of a reactive or a neoplastic nature is not immediately apparent, although the latter seems more likely. However, it is clear that the behavior of these lesions, as a group, is quite indolent and even self-limited, in contrast to the aggressive behavior and often fatal outcome of the true angiosarcomas that they so closely resemble on microscopic grounds. The term "histiocytoid hemangioma" is suggested for this group of disorders.


Nerve growth factor in medullary carcinoma of the thyroid. In a case of medullary carcinoma of the thyroid gland assay was performed for nerve growth factor bioactivity. The tumor extract showed significant amounts of nerve growth factor bioactivity, but extracts of normal thyroid and other types of thyroid neoplasms showed no such bioactivity. Nerve growth factor may be useful as a tumor marker in the diagnosis and management of medullary carcinoma of the thyroid. It may play a role in the development of associated tumors of neural crest origin and may contribute to the development of cachexia in patients with medullary carcinoma of the thyroid.


Electron microscopic identity of talc in the liver of a narcotic addict. In this report we identify the ultrastructural correlate of birefringent crystals that we found in biopsy specimens from an intravenous drug addict and that were presumed to be talc. By electron microscopy the crystals were electron dense and elongated with sharp edges and had an apparent lamination. The crystals were found within portal or granuloma macrophages and were often displaced or associated with section tears and knife marks. Weak electron diffraction patterns were obtained that were consistent with talc.


11q aneuploidy: partial monosomy and trisomy in the children of a mother with a t(3;11)(p27;q23) translocation. A woman with a balanced translocation t(3;11)(p27;q23) has had three abnormal children. The first child died in infancy, and of the two survivors who show segregation of the derivative maternal translocated chromosomes, one exhibits partial trisomy 11q and the other partial monosomy 11q. The two cases are compared with each other and with reported examples. Moreover, 11q break points are discussed.


Sister chromatid exchange in cell lines from malignant lymphomas (lymphoma lines). The frequency of sister chromatid exchanges (SCEs) was studied in cells from three freshly established lymphoma lines, derived from two patients with Hodgkin's disease and one patient with non-Hodgkin lymphoma. These values were compared to SCE rates found in cells from two long-established lymphoma lines (Raji and BJAB) and to those recorded in control cell lines of normal human donors. The highest SCE levels were demonstrated in the freshly established lymphoma lines, the lowest SCE values separated the lymphoblastoid cell lines from healthy controls, and the older lymphoma lines Raji and BJAB presented rates in between. The influences of BUDR concentration and of the duration of BUDR treatment on the frequency of SCEs were tested. Furthermore, the dependence of the SCE rate on the time interval between establishment of the cell line and its SCE investigation was considered. The connection between elevated SCE rates and the neoplastic nature of lymphoma lines is discussed.


Quantitative studies on the arrangement of human metaphase chromosomes. VII. The association pattern of acrocentric chromosomes in carriers of Robertsonian translocations and in their relatives with normal karyotypes. The pattern of association of acrocentric chromosomes was examined in ten and five carriers of a 15/21 and a 13/14 Robertsonian translocation, respectively, and was compared with that of the same numbers of relatives with normal karyotypes. In the carriers of 15/21 translocation, the number of large associations (involving more than two acrocentrics) and the association frequencies for individual acrocentric chromosomes, were significantly higher than in the control group. The mean number of associations of the single homologs of the translocation chromosomes was much higher than that of the other acrocentrics. In the carriers of 13/14 translocations, only the association frequency for chromosome 13 was higher than in the normal relatives. The uninvolved chromosomes homologous to those involved in translocation showed an insignificant increase in associations in comparison with the other acrocentrics. These results suggest that some mechanism within the cells compensates for the effect of missing acrocentrics or of acrocentrics lacking NORs on the number of associations. The possible relations of this phenomenon to the activity of the nucleolus organizing regions are discussed.


Chromosomal radiosensitivity of ataxia telangiectasia cells at different cell cycle stages. X-ray induced chromosomal aberrations in peripheral blood lymphocytes as well as in skin fibroblasts from ataxia telangiectasia patients, and from normal individuals were studied. At all stages of cell cycles-namely G0, G1, and G2, more aberrations were induced in AT cells than in normal cells. In addition, AT cells were sensitive to induction of chromosomal aberrations by tritium beta rays from incorporated radioactive thymidine. Possible reasons for the increased sensitivity of AT cells for induction of chromosomal aberrations by ionizing radiations are discussed.


A comparison of constitutive heterochromatin staining methods in two cases of familial heterochromatin deficiencies. Using DAPI staining after pretreatment with distamycin A we detected a familial deficiency of chromosome 16 heterochromatin. A distinct positively staining band, however, was seen after C-banding. Thus, by using these different heterochromatin staining methods, heterogeneity of the constitutive heterochromatin in the centromeric region of human chromosome 16 was indicated. The same C-banding procedure was also applied to a previously described familial deficiency of chromosome 9 heterochromatin evidenced using distamycin A/DAPI staining and G 11 staining (Buys et al., 1979). In this case a C-band appeared to be virtually absent on the relevant chromosome. These staining methods may be valuable tools in the study of chromosome polymorphisms.


High incidence of the silent allele at cholinesterase locus I in Vysyas of Andhra Pradesh (S. India). Four-hundred and ninety individuals belonging to the Vysya caste from Andhra Pradesh were screened for pseudocholinesterase variants at the E1 and E2 locus. A high incidence of the silent allele (gene frequency=0.1112) was recorded with homozygotes exceeding 2% of the population. Dibucaine- and fluoride-resistant alleles were found in a heterozygous form with the usual alleles in four individuals each. No C5+ variant at the E2 locus was found.


X pentasomy: a case and review.

X pentasomy: a case and review. A 49,XXXXX girl is reported. The most typical features of the patient are: severe mental retardation, serious dental anomalies, various anomalies of the bones, and a high rate of gonadotropins. The few similar cases so far described are reviewed to aid in delineation of this rare syndrome. The implications of Lyon's hypothesis on X-aneuploidies are also discussed.


Lateral asymmetry of constitutive heterochromatin in human chromosomes. Variations in lateral asymmetry of constitutive heterochromatin were studied in 30 normal individuals with reference to the chromosomal regions 1q12, 9q12, 15p11, 16q12 and Yq12. The technique consisted of growing human lymphocytes for one cell cycle in BrdU, staining with 33258 Hoechst, exposing them to UV light, treating them with 2 x SSC, and staining with Giemsa. This procedure revealed asymmetric staining in the region of constitutive heterochromatin in these chromosomal regions. Chromosomes 15, 16, and Y showed simple lateral asymmetry, whereas chromosome 1 showed both simple and compound asymmetry. In 15 cases, compound lateral asymmetry was evident in both homologues of chromosome 1, 12 cases showed compound lateral asymmetry in one homologue and simple lateral asymmetry in both the homologues. The centromere region of chromosome 9 stained symmetrically with this technique. The lateral asymmetry is presumed to reflect the strand bias in the distribution of thymine in satellite DNA fractions.


Partial trisomy 4q: two cases resulting from a familial translocation t(4;18)(q27;p11). Partial trisomy of the long arm of chromosome 4 was observed in two related patients, a child aged 2 years and a woman aged 42. Cytogenetic investigation revealed that their chromosome anomalies were due to segregation of a familial balanced translocation t(4;18)(q27;p11). Some clinical and cytogenetic considerations are noted.


Partial trisomy 13q21toqter de novo due to a recombinant chromosome rec(13)dup q. A female is described who has a karyotype with an additional distal half of 13q in a recombinant rec(13)dup q chromosome. Since her parents have normal karyotypes, the origin of her karyotype is assumed to be a premeiotic pericentric inversion de novo with crossing-over within the inversion loop at meiosis. By means of various banding techniques, the breaks preceding the rearrangement could be located exactly. The joint between the duplicated segment and the satellites of the receptor chromosome is of special note. The phenotype of the patient stated at the age of 9 months and at the age of 7 1/2 years was found to be related to the segments involved in the partial trisomy. The clinical features were largely in accordance with previous case reports having an identical extent of the triplicated 13q segment.


Serum-induced chromosome damage and neoplastic transformation of mouse cells in vitro. In previous studies, mouse cells grown in medium supplemented with horse serum (HS) developed more chromosomal aberrations and underwent malignant transformation earlier than cells from the same pool grown with fetal bovine serum (FBS) supplement. In the present study cells derived from C3Hf/HeN mouse embryos were grown in medium NCTC-135 supplemented with various combinations of large- and small-molecule fractions of HS and FBS in an effort to determine the effective components. The results indicate that the large-molecule fraction of HS (mare or stallion) produces alterations in  chromosome number and structure. HS is also shown to cause chromatid breaks and exchanges at or near the centromere in contrast to fluorescent-light-induced breaks and exchange at or near the centromere in contrast to fluorescent-light-induced breaks which occur randomly along the chromatid. However, efforts to control completely chromosome stability and malignant transformation through the use of large- and small-molecule fractions of HS and FBS or combinations thereof were unsuccessful. In connection with this study, diagnosis of malignant transformation in vitro was made by a direct sampling method based on cytologic criteria previously described and documented. With one exception, the diagnoses of 11 different cell lines were consistent with results of in vivo assays.


Lactoperoxidase-catalyzed iodination of cell cultures infected with mycoplasma. Hamster BHK cells or secondary cultures of mouse embryo fibroblasts are not iodinated by lactoperoxidase in the absence of hydrogen peroxide. When such cell cultures are infected with a noncultivable strain of M. hyorhinis, endogenous peroxide generation is sufficient to permit nearly maximal iodination. The SDS-polyacrylamide gel pattern of iodinated cell surface polypeptides is essentially the same regardless of the source of peroxide and whether or not the cultures are infected with mycoplasma.


Studies of alpha-protein in human cell cultures. alpha-Protein growth fraction (AGF) eliminates the 60- to 90-day adaptive phase required to establish actively growing cultures of HeLa (Gey), human heart (Girardi), KB (Eagle) and other established cell lines in serum-free chemically defined medium A3. AGF is effective at less than 0.4 microgram per ml. By using the procedures described in the text, it is possible to culture HeLa cells in very simple media such as Eagle's basal medium. The properties of AGF are such that it may be adsorbed on glass or plastic flasks. Glass flasks treated with AGF retain full activity after washing with acetone, and treatment with ethyl ether and chemically defined medium. Adsorbed AGF is destroyed by trypsin. AGF can detoxify protamines, polylysines or histones. It will reverse the aggregation response induced by adding complexes composed of carboxymethylcellulose (CMC) and basic proteins. The results support the contention that highly adsorptive AGF functions at the cell surface and is capable of modifying the response of the cell to its environment.


Cell cultures derived from embryos and melanoma of poeciliid fish. In poeciliid fish, melanoma of different degrees of malignancy can be produced by crossing specific genotypes. For a detailed investigation of the processes leading to proliferation or differentiation of the melanoma cells, it is necessary to establish cell cultures. The aim of the present study was to find out the optimal conditions for initiating and culturing poeciliid fish cells for the purpose of establishing cell cultures of melanoma. The optimal method was developed by using small pieces of late embryos as starting material and includes: (a) dispersion of tissue by mild stepwise treatment with a trypsin-EDTA mixture at low temperature; (b) culture of cells in the complex medium 199; (c) supplementation of medium with high percentage (20%) of fetal bovine serum; and (d) stabilization of pH by buffering the medium with HEPES. Under these conditions, primary and secondary cultures of embryonic cells have been initiated. An epithelial-like cell line has been subcultured for more than 80 passages. The method developed for embryonic tissues was used to start cell cultures from melanoma of platyfish-swordtail hybrids. Until now, only cells of rapidly growing malignant albino melanoma could be maintained in primary cultures. Secondary cultures could not be initiated since the melanoma cells tended to differentiate and stopped growing before a confluent monolayer was formed.


L-Lactate or pyruvate stimulated growth of Novikoff rat hepatoma cells. Novikoff rat hepatoma cells (subline N1S1-67) grew when 30 mM L-lactate or pyruvate was substituted for D-glucose in Swim's medium 67 supplemented with dialyzed calf bovine serum. A 2.6-fold increase in cell number (1.34 generations) was obtained. RNA, DNA, protein and dry weight increased in proportion to the cell number. In control medium lacking L-lactate, pyruvate or D-glucose, cell growth of 0.42 generation was obtained. Growth with L-lactate was dependent on the L-lactate concentration up to 30 mM at which the greatest increase in cell number occurred. Significant growth did not occur when D-lactate, glycerol, acetate, alpha-ketoglutarate, succinate or malate, each at 30 mM, was substituted for D-glucose. Growth in the medium containing L-lactate was not due to the utilization of D-glucose or some other substrate carried into the culture with the inoculum. Medium contamination by D-glucose was insufficient to explain the growth obtained in the medium containing L-lactate, but could have accounted for growth in the control medium. Throughout growth, the concentration of L-lactate in the medium remained unchanged. The increase in cell number cannot be explained by L-lactate triggering the utilization of glycogen, nor by oxidation and degradation of protein, amino acids, fatty acids, or carbohydrate moieties of glycoprotein in the medium. L-Lactate does not serve as a significant carbon or energy source in the growth of these cells.