AMP analogs: their function in the activation of glycogen phosphorylase b.

A series of AMP analogs has been selected in order to better understand the structural requirements (a) for the efficient binding of the activator molecule at the correct site on phosphorylase b from rabbit skeletal muscle and (b) for the activation which is observed. Two types of activation are known, according to Black and Wang [J. Biol. Chem. 243, 5892-5898 (1968)]: either a cooperative response with respect to the activator concentration (like the one which is obtained for AMP itself) or a non-cooperative response observed in the case of IMP. It is shown that the 5'-phosphate moiety is absolutely required for the analog to bind at the correct site (adenine or adenosine bind at another enzymic site), and that the free enthalpy, delta G, corresponding to the association process varies in a complex manner with respect to the substitution of the different positions of the AMP molecule. Moreover, the differences delta G (analog) - delta G (AMP) = delta G obtained for two types of substitution separately do not add up to the same energy difference as the one obtained when the two substitutions are made simultaneously on the AMP molecule. It appears that all the mononucleotides which have been tested up to now may be divided into two classes. Class I (AMP class) is characterized, apart from a strong activation, by the following features: (a) one molecule of analog expels two molecules of bound glucose 6-phosphate as it binds on the enzyme; (b) bound analog protects slowly one crucial cysteinyl residue against attack by 5,5'-dithio-bis(2-nitrobenzoic acid) at 4 degrees C; (c) association of two molecules of dimer is strengthened at 4 degrees C in the presence of the analog. Class II (IMP class) is associated with a weak activation and with the following set of properties: (a) a single molecule of bound glucose 6-phosphate is released as the first molecule of analog binds on the dimer; (b) two slowly reacting cysteinyl residues per subunit are immediately protected against 5,5'-dithio-bis(2-nitrobenzoic acid) by the binding of the analog at 4 degrees C; (c) the analog dissociates the low amount of tetramer which is present at 4 degrees C in the absence of AMP into two molecules of dimer. These results are discussed according to a plausible scheme of transconformations taking place in glycogen phosphorylase b, a model which has been derived earlier by relaxation studies.


The state of ADP or ATP fixed to the mitochondria by bongkrekate.

The reported studies are intended to clarify the binding state of ADP fixed to mitochondria under the influence of bongkrekate, and thus to discern between the affinity increase and reorientation mechanism proposed for the bongkrekate effect. (a) The composition of the intramitochondrial adenine nucleotide pool is not changed under the influence of bongkrekate with and without added nucleotides. (b) The added ADP and ATP fixed by bongkrekate can be identified as AMP, ADP and ATP in the same proportions as in the endogenous pool. (c) The bound nucleotides respond to oxidative phosphorylation or uncoupler stimulated dephosphorylation similar as endogenous nucleotides. It can be concluded that the ADP or ATP fixed under the influence of bongkrekate to the mitochondria are equilibrated with the intramitochondrial adenine nucleotide pool and are active in intramitochondrial phosphate transfer reactions. The results disagree with the affinity increase mechanism but support the reorientation mechanism which postulates that ADP and ATP are trapped in the mitochondria under the influence of bongkrekate in the same amount as there are carrier sites available outside before bongkrekate addition.


Mortality among Parkinson patients treated with L-dopa combined with a decarboxylase inhibitor.

Since L-dopa in combination with a decarboxylase inhibitor is currently the most effective therapy available for treatment of Parkinson's disease, the authors compare the actual causes of death in a large series of treated Parkinson patients with a normal population and with previous studies. This investigation shows that the mortality of correctly treated Parkinson patients lies within the range of the expected mortality of a group of a normal population comparable in age and sex. The risk of death for a Parkinson patient is therefore no longer higher than for the normal population.


Surgical management of multiple neuraxial ependymomas. Case report.

A case is reported of a 13-year-old girl who required four operations in 4 years for the removal of multiple spinal, supratentorial and infratentorial ependymoma seedlings, and who remains well 2 1/2 years after the last operation. The place of radiotherapy and surgery are discussed.


Transient neurogenic urinary retention.

A patient is described who developed painless urinary retention, which resolved spontaneously within 2 weeks. At the onset of his illness neurological examination did not manifest definite abnormalities, but the cerebrospinal fluid contained excess of protein and lymphocytes. Cystonometry was normal throughout the illness.


Polymorphonuclear leukocyte lysosome activities and lymphocyte transformation in multiple sclerosis and some other central nervous system chronic diseases.

The role of PMNL lysosomes was studied in some lesions of the central nervous system with speical regard to multiple sclerosis patients. The significant decrease of acid hydrolases was observed in multiple sclerosis (MS) peripheral blood PMNL lysosomal granula and, in parallel, the increase of lysosome proteins mitogenic potency. The other lesions of the central nervous system such as apoplexy, brain tumors, brain trauma and epilepsy have not shown the MS-like activities of PMNLs. The role of PMNLs in pathogenesis of MS and in the stimulation of immunocompetent cells is suggested.


Ascorbic acid and cholesterol: effect of graded oral intakes on cholesterol conversion to bile acids in guinea-pigs.

A significant correlation between liver ascorbic acid (AA) and total bile acids or liver bile acids has been established in guinea-pigs by direct determination of the bile acids, confirming an earlier hypothesis. The oxidation of cholesterol to bile acids is dependent on the AA status, but it cannot be further stimulated by AA when the animals are already on an adequate intake of the vitamin. This suggests that AA has a hypocholesterolaemic effect over a limited range of AA status.


Affinity chromatography of soluble galactosyltransferases using an easily synthesized N-acetylglucosamine-agarose bead.

Agarose derivatized wtih phi-nitrophenyl-N-acetyl-beta-d-glucosamine was used for affinity chromatography for soluble galactosyltransferase from various sources. Moreover, this adsorbant acts as an acceptor for galactose when incubated with prepurified galactosyltransferase.


Abnormally soluble collagen produced in fibroblasts cultures.

Abnormally soluble collagen is synthesized in vitro not only by skin fibroblasts of Marfan patients but also by those of patients with Ehlers-Danlos type V and cutis laxa. The excessive solubility of collagen is corrected by the addition to the culture medium of a synthetic flavonoid, (+)- catechin.


Heavy metal hydrolysis of polyisoprenoid-phosphate mono- and oligosaccarides.

Mono- and oligosaccharide derivatives of dolichol phosphate can be hydrolyzed by heavy metal, preferably Zn++ at 100 degrees C or 65 degrees C. The reactions follow first order kinetics. The reaction proceeds through hydrolysis of the sugar phosphate bond.


Activation of particle associated rat liver guanine deaminase by lecithin and interferences of lecithin in protein precipitation.

Guanine deaminase solubilized from the "light" mitochondrial fraction of rat liver was activated by lecithin. The activation was proportional to the concentration of lecithin taken in the system. A ratio of 1:1 between the two constituents (protein and lecithin) was at least necessary for complete precipitation.


Ultrastructural changes of the luminal plasma membrane of the transitional epithelium of the rat urinary tract in essential fatty acid deficiency.

Rats fed an essential fatty acid deficient diet (EFAD) showed a statistically significant decrease in the thickness and ultrastructural asymmetry of the luminal membrane and cytoplasmic vesicles of transitional epithelium of the urinary tract, due to a marked thinning of the peculiar thick luminal leaflet. These changes were reversed by adding EFA to the diet. This indicates that the unusual EM appearance of urothelial membrane depends on its content in EFA.


Hybridization in the Mexican and 13-lined ground squirrels, Spermophilus mexicanus and Spermophilus tridecemlineatus.

Evidence of hybridization between the ground squirrels, Spermophilus tridecemlineatus and S. mexicanus is presented on the basis of chromosomal and protein data. The hybrids produced appear to be completely interfertile. Based on the evidence of hybridization and the recent reestablishment of contact between these two species, they are considered to be semispecies.


Changes in the distensibility of the cat aortic arch induced by noradrenaline.

In the isolated preparation of the aortic arch of the cat, noradrenaline (NA) reduced at low pre-loads, and increased at high pre-loads, the arterial wall distensibility. For each dose of NA, the changes were directly related to the pressure level in the system.


Influence of gonadal hormones on the developing amphibian brain: changes in ribonucleic acid, protein and activity levels of acetylcholinesterase on in vivo administration of progesterone.

The levels of RNA and protein and activity levels of acetylcholinesterase decreased in the brain of developing tadpoles of 13-15-day-old Bufo melanostictus on in vivo administration of progesterone (200 mug/0.1 ml refined peanut oil). These changes suggest decelaration in the activity of the protein-synthetic machinery in progesterone administered animals.


[Sephadex G 100- Separation of the mucicrinic and the mucimitiginic factors from an extract of duodenal mucosa (author's transl)].

The mucicrin stimulating the hexosamine gastrointestinal secretion and extracted form porcine duodenum, was concentrated in the zone 7 using sephadex G 100. The molecular weight of 4000-5000 corresponds to this zone. An opposite activity was detected in zone 3. The factor from digestive mucous origin being able to diminish the hexosamine gastric secretion and not influencing the arterial pressure was called mucimitigin. The molecular weight of about 35000 corresponds to this factor.


The physiological effects of ionic lanthanum on the insect blood-brain  barrier.

Lanthanum had a small effect on the barrier, but did not significantly increase its sodium or potassium permeability. There was no effect on nerve conduction unless the barrier was deliberately damaged. The results lend confidence to the use of lanthanum as an extracellular tracer.


[Reversal of the pressor effect of PGF2alpha in the rat (author's transl)].

In normal rats, prostaglandin F2alpha is a potent vasoconstrictor. The corresponding systemic hypertension is progressively attenuated by tachyphylaxis, revealing a longlasting fall of blood pressure. Tachyphylaxis is accelerated by previous injection of arachidonic acid and bradyskinin. The vasodepressive activity of PGF2alpha is inhibited by indomethacin.


Ouabain-induced release of extraneuronal catecholamine in the isolated guinea-pig vas deferens.

It was found that ouabain (10(-5) M) was effective in releasing the extraneuronal catecholamine which was taken up by uptake 2 process in the guinea-pig vas deferens. This result shows that a Na-K ATPase is essential for the storage of catecholamine in the extraneuronal site.


Extravascular cells within the perisinusoidal space of the avian liver.

Ultrastructural studies of the perisinusoidal space in the avian liver have demonstrated the presence of 2 extravascular cell types--a fat-storing cell and a free mesenchyme cell or histiocyte. This latter cell type is capable of participating in the formation of a bile canaliculus with the hepatic parenchymal cell. The possibility of the fat-storing cell differentiating from the histiocyte is suggested.


Mitochondrial derivation of centrioles in some endocrine adenomas.

Fine structural studies of various endocrine adenomas indicate that mitochondria may serve as progenitors of centrioles and cilia.


A new substrate for cultures of dissociated primary rat brain.

Different substrates were used to coat plastic petri dished for the cultivation of dissociated fetal rat brain cells. Only on surfaces which were coated with a mixture of serum and non-reconstituted collagen, did the majority of the inoculated cells attach singly or as aggregates within 24 h. The attachment of the cells was followed by the outgrowth of cellular processes either from single cells or from aggregates in the same time period. This did not occur on collagen or serum treated or on regular plastic dishes. Under the latter conditions a similar outgrowth was observed only after 3-5 days.


Conservative treatment of endometriosis: the effects of limited surgery and hormonal pseudopregnancy.

This study compares the effects of limited surgery or hormonal pseudopregnancy, or a combination of these two, upon fertility and the need for subsequent surgery with respect to the extent of the disease at the time of initial diagnosis in patients with endometriosis externa. Of the 61 patients who desired to enhance or preserve reproductive capacity, 20 patients became pregnant, for a pregnancy rate of 33%. The pregnancy rate in all categories, that is, those patients treated with pseudopregnancy, conservative surgery, and combined pseudopregnancy and surgery, was found to be in direct relationship to the initial extent of disease. In such patients, conservative surgery alone seemed to give the best results in the achievement of pregnancy. There seemed to be little difference between pseudopregnancy alone and conservative surgery in regard to the need for subsequent surgery after initial therapy, although there seemed to be a significantly greater chance for the need for subsequent surgery in patients receiving a combination of the two forms of therapy. The need for subsequent surgery after initial therapy in 80 patients increased in direct relationship to the initial extent of disease present, despite the form of therapy used. Fifty-nine other patients with endometriosis, who did not desire to preserve fertility and presented for relief of other symptoms, underwent initial "radical" therapy. Forty-six patients underwent complete operation, including removal of uterus, tubes and ovaries, and none required subsequent reoperation. Of the 13 remaining patients, who underwent incomplete surgical removal, leaving one or both ovaries in situ, 11 required subsequent reoperation for recurrent pelvic endometriosis.


Temporal relationship between basal body temperature nadir and luteinizing hormone surge in normal women.

Basal body temperature (BBT) as a predictor of ovulation was assessed by examining the temporal relationship between the BBT shift and the luteinizing hormone (LH) surge in individual cycles of 27 normal women. For 22 of the subjects, the LH surge occurred on the same day or within one day of the BBT nadir. For the remaining five subjects, the surge fell within 2 days after or 3 days before the nadir. Despite the BBT nadir's close temporal association with the LH surge, daily examination of BBT for the purpose of predicting the day of ovulation during a given cycle is unsatisfactory. By 48 hours following the nadir, when one could usually be certain that temperature elevation had occurred, all subjects had already exhibited the LH surge.


Plasma sex steroid and gonadotropin levels in control and silastic vaginal medroxyprogesterone acetate-impregnated ring cycles.

The concentrations of sex steroid hormones in plasma were determined daily in 14 young adult women, during both a control cycle and a treatment cycle. During the latter a Silastic ring into which 100 or 200 mg of medroxyprogesterone acetate (Provera) had been incorporated was worn intravaginally. During the treatment cycles, plasma levels of estradiol, progesterone, and 17-hydroxyprogesterone remained within the range observed during the early follicular phase. Testosterone and androstenedione levels did not show any cyclic variation during the treatment cycle; however, the mean levels were decreased by about 25% compared with the over-all plasma levels of the control cycle, whereas dehydroepiandrosterone levels were decreased by about 15%. It is concluded that these Provera-containing Silastic intravaginal rings inhibit ovulation and decrease androgen secretion by the ovaries significantly.


Retrograde ejaculation: pathophysiologic aspects and report of two successfully treated cases.

The ejaculatory process consists of two stages. During the first stage the semen is pumped into the posterior urethra and during the second stage the semen is propelled via the urethra through the external meatus. A pathologic second stage may lead to retrograde ejaculation of the semen into the urinary bladder. Attempts to achieve fertility in such patients can be made in two ways; namely through procedures to restore antegrade ejaculation (mainly using alpha-sympathomimetic agents) and procedures to regain viable and fertile sperm from the urinary bladder after sexual intercourse, with subsequent artificial insemination. The latter way of treatment was used in two patients who were referred for infertility and in whom retrograde ejaculation had been diagnosed. Postcoital urinary specimens were obtained by micturition and centrifuged. In one patient the sediment was washed with a nutrient solution; the other patient received alkalizing agents prior to intercourse in order to neutralize the urinary pH. The wives were inseminated on appropriate days and conceived. Both delivered healthy babies after uneventful pregnancies.


Response of adnexal glands to testosterone stimulation in the normal adult male.

Normal male volunteers were studied in order to set up a functional exploration test based on administration of testosterone propionate for use on the adnexal glands of the male genital tract. Seminal acid phosphatase and citric acid levels showed no significant variations compared with spontaneous physiologic oscillations. Concentration and total quantity of fructose were considerably reduced. Alkaline phosphatase showed an intermediate pattern with constant values of concentration and decrease of total quantity. The hypothesis is advanced that adnexal glands possess a secretory metabolism with a maximal basal response to androgen stimulation, but with a different mechanism of action: partly adaptable at the level of the prostate and of the "all or nothing" type at the level of the vesicles.


Impaired Leydig cell reserve and altered serum androgen binding in the aging male.

The hormonal profile of the aging male reveals an associated decrease in free testosterone and 5 alpha-dihydrotestosterone (DHT) levels and increased luteinizing hormone levels. Later events consist of a decrease in total testosterone, stable DHT, and increased follicle-stimulating hormone and estradiol levels. Although most available information supports the concept of impaired Leydig cell reserve, our study suggests some degree of hypothalamic-pituitary dysfunction. The signal for increased androgen binding with age is not clear. There is a great deal of individual variation in the time of onset of these events.


Lactate and malate dehydrogenase and alpha-esterases in oligospermia.

Lactate dehydrogenase (LDH), malate dehydrogenase, and alpha-esterase were studied electrophoretically in a total of 99 semen samples obtained from normal, vasectomized, oligospermic, and infertile males. The enzymatic patterns were compared with total sperm count and percentage sperm motility. Lactate dehydrogenase X was absent in semen samples from oligospermic as well as vasectomized males. An extra LDH band (between the second and third LDH bands) was detectable in samples which had a low sperm count but higher motility (80 to 90%). This extra band was absent in samples with higher sperm count regardless of the level of percentage motility, suggesting that the extra band possibly may be related to motility factors of low sperm count but not normal sperm count. The fastest moving alpha-esterase bands were absent in samples from oligospermic or vasectomized males. These bands were also absent in samples from infertile patients having a very low sperm count. It is not clear whether the fast-moving esterase bands are related to sperm count or possible differences in hormonal levels of individuals with low or zero sperm count samples. The patterns of malate dehydrogenase did not differ in individuals with zero, low, or normal sperm count.


Postcoital luteinizing hormone release in male and female rabbits as determined by radioimmunoassay.

We have developed a homologous radioimmunoassay for rabbit luteinizing hormone (LH), which was used to measure LH levels in sera of male and female rabbits before and after copulation. The results demonstrated the following: (1) LH concentrations in male and estrogen-primed female rabbits are similar prior to coitus; (2) following coitus, LH levels rise within 3 minutes in both sexes and reach a peak or plateau within 15 minutes; (3) elevated LH concentrations are maintained at a plateau for at least 1 hour in females and then fall toward base line values; (4) an increase in serum LH to 300 ng/ml (10- to 11-fold) or greater is sufficient to cause ovulation and the formation of corpora lutea; and (5) the postcoital rise in LH levels is greater in estrogen-primed females than in nontreated males.


In vitro fertilization, culture, and transfer of rabbit ova.

Ovulated rabbit oocytes were fertilized in vitro in chemically defined media supplemented with bovine serum albumin and either cultured up to the expanding blastocyst stage or transferred to recipients after varying periods of culture. Embryos transferred after up to 72 hours of in vitro culture were born as viable young. Oocytes from young virgin does were superior to oocytes from nonvirgin does for the purpose of in vitro fertilization (54% versus 26% fertilized, P less than 0.01). Capacitated sperm from artificially inseminated capacitators resulted in fertilization rates slightly lower than those from naturally mated does (46% versus 57% fertilized, P less than 0.025). Removal of cumulus and corona cells from oocytes with hyaluronidase and repeated aspiration through a fine pipette resulted in lowered fertilization rates (51% versus 73%, P less than 0.025). Linbro Disposo Tray wells were as good as glass tissue-culture dishes for the in vitro mixing of gametes and were more convenient to use. Modified Ham's F10 medium was used to culture the in vitro-fertilized embryos. However, when a modified Brackett's medium was used instead of modified Ham's F10 for the initial 4-hour period after mixing gametes, more oocytes were fertilized (52% versus 28%, P less than 0.01).


Renal and hepatic lysosomal catabolism of luteinizing hormone.

Following an intravenous injection of tritiated ovine lutenizing hormone (LH) into mature male rats, the liver and kidneys accumulate a significant portion of the non-excreted hormone. The subcellular distribution of total radioactivity in both tissues was found to be similar to that of beta-galactosidase, a lysosomal enzyme marker. Moreover, the subcellular fraction with the highest relative specific activity of beta-galactosidase exhibited the highest degradation rate of endogenous hormone under in vitro conditions. Based on these and other observations, it is concluded that the intracellular catabolism of LH by these tissues is due to lysosomal enzymes. An analysis of the radioactive degradation products produced by a lysosomal-rich subcellular fraction showed the presence of free amino acids and oligopeptides. Thus, the uptake and degradation of the hormone by these tissues appear to occur by endocytosis followed by lysosomal catabolism. This phenomenon may represent a regulatory role in the control of (circulating) hormone concenttrations.


Specificities in the synthesis of a cytoplasmic estrogen-induced uterine protein.

The earliest known induction by estrogen of a specific uterine protein is that of the induced protein (IP) of Gorski and colleagues, which is demonstrable within 40 min after treatment. We found that this protein is not restricted to the rat; it was detected i  the uterus of prepuberal C3H/eB and SWR mice, 1 h after injection of 4 B5g/rat) and coumestrol (300B5g/rat) and the synthetic estrogen diethylstilbestrol (5 B5/rat). We found no significant increase in the stimulation of the rate of IP synthesis by estrogen in uteri from either 10- or 20--day-old rats on subsequent treatment with actinomycin D, indicating that there was no superinduction of IP, despite a previous claim.


Exocrine pancreatic function in man after treatment with oxytetracycline and chloramphenicol.

The exocrine pancreatic function was studied in humans by performing a secretin-cholecystokinin test before and after treatment with oxytetracycline or chloramphenicol. In the oxytetracycline-treated patients there was a depression of the amylase and lipase outputs in the duodenal secretion, chymotrypsin decreasing only slightly. After treatment with the two antibiotics the calcium secretion was reduced. The other parameters measured in the duodenal secretion remained essentially unchanged. The enzyme dissociation observed in the present studies is considered to reflect the onset of pancreatic dysfunction due to antibiotic administration. As in the previous animal onset of pancreatic dysfunction due to antibiotic administration. As in the previous animal experiments, the suggested explanation for the changes in enzyme secretion is an inhibition of protein synthesis in the exocrine pancreas due to oxytetracycline and chloramphenicol.


Gastric acid secretory responses to graded intravenous doses of histamine in hookworm anemia.

Dose-response curves for the effect of continuous infusion of histamine on gastric acid secretion were obtained in 10 patients with iron deficiency anemia due to hookworm infection. Each patient was studied with 4 doses (40, 60, 80 and 100 mug/kg/h) of histamine acid phosphate administered for 3 h, on separate days, in random fashion. The acid output increased with the dose of histamine, the maximal acid output was reached in all patients at the dose of 100 mug/kg/h. The dose of histamine when calculated according to body weight correlated well with the maximal acid output; the absolute dose of histamine had no correlation with the maximal acid response. The dose-response curve of stimulated acid output in anemia patients was much flatter than in control patients.


Effect of jejunal resection on the gastric acid secretory response to pentagastrin, histamine and feeding in dogs.

In dogs with gastric fistulas and denervated pouches from the oxyntic area, the acid secretory responses to a meal and to graded doses of histamine and pentagastrin were measured before and after resection of the upper half of the small bowel. Intestinal resection caused a small but significant increase in submaximal and maximal response from the pouch to histamine and pentagastrin without modification of the ED50. This effect was not observed in the innervated stomach. The response from the pouch to feeding was markedly increased and prolonged. These data indicate that both an increase in stimulation and an increase of the response to this stimulation are responsible for the increased acid secretion observed in the pouch when resected dogs were fed. These effects could be explained by the withdrawal of inhibitors of intestinal origin.


Marked increase in serum levels of liver enzymes in patients receiving chenic acid and phenobarbital for gallstone dissolution.

In a group of 16 patients, receiving chenic acid (20 mg/kg/day) and phenobarbital (60 mg/day) for gallstone dissolution, three patients were observed to develop a marked increase in serum levels of SGOT-SGPT and alkaline phosphatase without associated symptoms. Liver biopsy in one patient showed cellular infiltration with neutrophils and eosinophils, suggestive of a hypersensitivity reaction. Enzyme levels returned to normal, following cessation of chenotherapy, and a second biopsy 3 months later was normal. In that patient a challenge with chenic acid, at 250 mg/day, was again followed by a marked elevation in levels of SGOT-SGPT and alkaline phosphatase. These patients are the first to show marked elevation in liver enzyme levels during chenotherapy; the mechanism and significance are unclear.


A rapid method of relating protein to flow in human pancreatic secretions.

A method of obtaining linear plots of protein-flow data from human pancreatic ductal secretions is described. The protein concentration in pancreatic secretions, when related to flow rates in two individuals, gave similar regression lines, with the correlation coefficients or r = -0.97 and -0.98, respectively, and slopes m = -1.02 and -0.82.


The nitroblue tetrazolium test in Crohn's disease and ulcerative colitis.

In subjects with Crohn's disease and ulcerative colitis, an increased percentage of peripheral blood neutrophils reduces the dye nitroblue tetrazolium. This is probably a non-specific index of inflammatory activity. There is no evidence that defective neutrophil function, as measured by this test, contributes to granuloma formation in Crohn's disease.


Gastric reflux measurements during duodenal infusion with saline, acid and fat.

Duodeno-gastric reflux measured in 18 patients without gastrointestinal complaints showed a wide variation of regurgitation rates. Duodeno-gastric reflux was significantly diminished during duodenal acidification. The effect was more intense and lasted longer after olive oil infused intraduodenally, leading practically to a closed pylorus.


Influence of hyperglycaemia on maximal gastric secretion in healthy subjects.

The influence of a single intravenous glucose load on maximal gastric acid secretion in 25 healthy men when stimulated with pentagastrin was studied. Under the influence of hyperglycaemia, a highly significant decrease of maximal acid output was found. Moreover, in the gastric juice an increase of chloride and calcium concentrations was noted. On the other hand, the output of potassium, chloride and magnesium was lowered. The above differences were statistically significant.


Investigation of exocrine pancreatic function by continuous infusion of caerulein and secretin in normal subjects and in chronic pancreatitis.

Exocrine pancreatic function has been evaluated in 24 controls and 29 patients with confirmed chronic pancreatitis by continuous infusion (90 min) of synthetic caerulein, 100 ng/kg/h, plus GIH secretin, 1 CU/kg/h. Mean secretory values of the controls were comparable to those obtained by others using maximal doses of secretin and CCK. Unlike the controls, patients suffering from chronic pancreatitis demonstrated a progressive reduction in secretion during infusion. Thus, the comparison of responses for the final 30-min period gave much clearer and more complete discrimination between normal and abnormal pancreatic function than the preceding 30-min period.


Ulcerative colitus and Crohn's disease of the colon - a comparison of the long term postoperative courses.

Patients with colitis and ileocolitis of unknown etiology from two previously reported series have been combined and the follow-up studies have been extended to compare the long term postoperative courses of ulcerative colitis (UC) and Crohn's disease of the colon (CDC). The combined and updated series of 176 patients, 99% of whom could be traced, provided a mean postoperative follow-up period for UC of 14 years (5 to 31) and CDC of 13.1 years (5 to 36). There were highly significant associations between generally accepted clinical and distributional features of UC and CDC and microscopic findings generally regarded as reliable for each. However, because of spectrum of features was found in each entity, neither clinical and distributional nor microscopic features alone are sufficient for diagnosis in every case. There were no differences in gross or disease-related mortality in UC and CDC whatever the method of diagnosis. After anastomotic procedures in CDC a recurrence rate of 73% was found. After proctocolectomy the ileostomy revision rate (considering all types of those which required further excision of ileum) was higher in CDC than UC whether the diagnoses were based on microscopic, clinical, or combined criteria, but the differences reached statistical significance only in the comparison of "clinical UC", with "clinical CDC". Moreover, after the first 2 postoperative years, the risk of having an ileostomy revision in UC and CDC (combined criteria) per patient year follow-up was virtually identical and there were no cases of short bowel syndrome. Differences in the clinical courses of UC and CDC after colectomy and ileostomy are of degree and do not reflect the ultimate course or potential for rehabilitation. Decisions regarding surgical therapy should be made independent of the diagnosis of UC or CDC.


Case-control method for seeking evidence of contagion in Crohn's disease.

All cases of Crohn's disease in the Nottingham area were ascertained and dates and places of domicile and work before and after onset of symptoms were noted. Similar information was taken from matched control subjects and the Pike and Smith (Biometrics 30:263-279, 1974) case control technique for evaluating clustering of patients in time and space was applied. These results do not support the infectious hypothesis.


The mechanism of increased renal clearance of amylase in acute pancreatitis.

Amylase isoenzymes, separated by polyacrylamide gel electrophoresis, were measures in 25 normal persons (mean amylase to creatinine clearance ratio 3.0%), 15 patients with acute pancreatitis (mean clearance ratio 9.5%, P less than 0.0001), and 6 patients with hyperamylasemia due to common duct stones (mean clearance ratio 4.1%). Two isoamylases (P1, P2) resembling pancreatic isoenzymes and three isoamylases (S1, S2, S3) resembling salivary isoenzymes appeared regularly in normal serum and urine. Salivary amylases predominated in serum, but pancreatic amylases predominated in urine. This finding is consistent with renal clearance of pancreatic amylases exceeding that of salivary amylases under normal conditions. In patients with pancreatitis or common duct stones, essentially all of the increased amylase activity in serum and urine was due to pancreatic isoamylases (P1 and P2) in their normal proportions. No new or altered amylase isoenzymes were detected. The fraction of pancreatic amylases in the serum or urine was identical for the two diseases. Whereas the difference in amylase to creatinine clearance ratios observed between the two groups of patients is not a function of different amylase isoenzymes presented to the kidney, we conclude that the increased amylase clearance in acute pancreatitis is caused by an alteration of renal transfer of amylase, either at the glomerulus or tubule.


Ion transport changes during calcitonin-induced intestinal secretion in man.

Previous studies have shown that synthetic salmon calcitonin (SCT) infused intravenously causes secretion of water and electrolytes in the jejunum of normal human subjects. The present experiments were carried out to learn more about the nature of this intestinal secretory process. During SCT- or synthetic human calcitonin (HCT)-induced intestinal secretion, the following observations were made: (1) There was no change in potential difference; (2) Cl was secreted against an electrochemical gradient; (3) unidirectional Na flux out of the lumen was decreased while the opposite flux was normal; (4) luminal pCO2 fell; (5) addition of glucose to the jejunal contents stimulated Na abdsorption, and this in turn counteracted the secretory effect of calcitonin. These findings suggest that calcitonin induces active Cl secretion and inhibits active Na absorption, and that HCO3 absorption is reduced by virtue of OH secretion; furthermore, jejunal glucose absorption and glucose-stimulated Na absorption are intact during calcitonin-induced secretion. Intravenous infusion of HCT caused intestinal secretion only when blood levels were much higher than occur physiologically; therefore, calcitonin is probably not a mediator of spontaneous variations of intestinal transport in normal people. However, because calcitonin induces secretion in the ileum as well as in the jejunum, hypercalcitonemia (within the range commonly found in patients with medullary carcinoma of the thyroid) could be a cause of severe secretory diarrhea.


Inhibition of digoxin absorption by neomycin.

The effect of the administration of the antibiotic neomycin sulfate on the absorption of digoxin was assessed in crossover studies in normal human volunteers. Doses of neomycin (1 and 3 g) markedly depressed serum digoxin concentrations, the areas under the serum concentration-time curves, and cumulative 6-day urinary digoxin excretion after the oral ingestion of 0.5 mg of the cardiac glycoside in tablet form. Neomycin also prolonged the mean time at which peak serum digoxin levels were attained by 1.7 to 3 hr. The inhibition of digoxin absorption was also seen: (1) when the antibiotic was given 3 or 6 hr before the cardiac glycoside, (2) with digoxin tablets of varying dissolution rate, (3) when digoxin or neomycin solutions were used instead of tablets, and (4) in a patient who had had a total gastrectomy. When neomycin was administered with maintenance doses of digoxin, steady state serum digoxin concentrations were significantly reduced. When neomycin was given after a 9-day period of digitalization, the terminal serum digoxin half-life was not significantly shortened. Single doses of neomycin did not interfere with the extent of absorption of d-xylose. In vitro, neomycin did not affect the movement of digoxin across dialysis membranes, nor did it precipitate digoxin out of human bile or intestinal fluid. Neomycin thus clearly depresses the rate and extent of digoxin absorption in man. The mechanism of this effect remains to be established.


The influence of hypercalcemia on basal and cholecystokinin-stimulated pancreatic, gallbladder, and gastric functions in man.

Hypercalcemia produced in normal volunteers by intravenous infusions of CaCl2 increased outputs of pancreatic enzyme and gastric acid. Further, hypercalcemia enhanced cholecystokinin (CCK)-stimulated pancreatic enzyme secretion and gallbladder contraction. Our results suggest that hypercalcemia affects pancreatic, gallbladder, and gastric functions as well as their responses to exogenous CCK.


Effect of gastrin on pancreatic enzyme secretion and gallbladder emptying in man.

This study was designed to assess the effect of unsulfated synthetic human little gastrin (HG-17-I) on pancreatic secretion and gallbladder emptying in man. During continuous gastric and duodenal aspiration, 6 male subjects were given, on different days, either HG-17-I (7, 20, 60, 180 AND 540 PMOL KG-1 HR-1), chlecystokinin (0.1, 0.3, and 0.9 UKg hr-1) or 238 pmol kg-1 (500 ng kg-1) of HG-17-I as a rapid intravenous injection. Trypsin output and bilirubin output increased significantly (P less than 0.05) above basal levels during the infusion of both peptides. During HG-17-I infusion the highest trypsin output (2.08 +/- 0.22 Karmen U per 10 min) and bilirubin output (4.66 +/- 0.61 mg per 10 min) occurred during the 60 pmol kg-1 hr-1 dose, whereas highest acid output occurred during the 540 pmol kg-1 hr-1 dose. Rapid intravenous injection of HG-17-I produced a prompt and significant rise in trypsin, bilirubin, bicarbonate, and acid outputs. It is concluded that HG-17-I produced significant pancreatic enzyme secretion and gallbladder emptying at doses that are submaximal for acid secretion, suggesting that this may be a physiological effect of gastrin.


Epithelial cell loss in remaining intestine after small bowel resection in the rat.

It is known that after small bowel resection, mucosal hyperplasia and increased cell turnover occur in the remaining intestine, particularly the ileum. At the end of their life span, epithelial cells are extruded into the bowel lumen. Comparative estimates of this cell loss may be obtained by collecting the DNA from a perfused gut segment. Male Sprague-Dawley rats underwent resection of 50 cm of proximal or distal small intestine or sham operation. One and six months after surgery, 50 cm of the remaining proximal or distal remnant were perfused with saline in vivo and the perfusate DNA was assayed. The DNA recovered from the perfusate of the distal remnant was at least twice as much as that from sham control segments. This was associated with comparable increases in mucosal weight, DNA, and protein concentration per centimeter of distal remnant. No significant changes were found in perfusate DNA recovered from proximal remnants. This correlated with minimal, if any, changes in mucosal weight, DNA, or protein concentration per centimeter of these remnants. Increased desquamation of epithelial cells may reflect the hyperplasia of intestinal mucosa after bowel resection. Recovery of intraluminal DNA may prove useful as an index of intestinal adaptation.


The effect of gastrointestinal hormones on the gastric microcirculation.

The purpose of the present study was to evaluate the effects of several gastrointestinal hormones on the gastric submucosal arterioles using an in vivo microscopy technique. Alteration in diameter of submucosal arterioles, 40 to 90 mu in diameter, in response to infusion of different agents into the celiac axis, was measured in the anesthetized cat. Pentagastrin, the octapeptide of cholecystokinin, natural secretin, and histamine produced arteriolar dilation. Only with histamine and the octapeptide of cholecystokinin did this occur with doses that might be considered physiological. Synthetic secretin had no vasodilator activity, suggesting the presence of a contaminating agent in natural secretin. Glucagon had no effect on the submucosal arterioles. In addition, the effect of glucagon on the smaller (10 to 30 mu) terminal and subterminal submucosal arterioles was studied in the rat by in vivo microscopy. Again no effect was observed with glucagon, but norepinephrine in small doses produced vasoconstriction.


A randomized trial of percutaneous transhepatic cholangiography with the Chiba needle versus endoscopic retrograde cholangiography for bile duct visualization in jaundice.

Sixty consecutive patients, who were deeply jaundiced or in whom intravenous cholangiography had failed, were randomized to retrograde endoscopic cholangiography or percutaneous transheptic cholangiograhy with the "skinny" Chiba needle technique. Twenty-eight patients were assigned to retrograde cholangiography, which succeeded in 17 (65%). Percutaneous cholangiography was successful in 16 (50%) of the remaining 32 patients. When patients in whom the first procedure was unsuccessful were reinvestigated by the alternative technique, retrograde cholangiograms were obtained in 13 (81%) of 16, and percutaneous cholangiograms in 8 (73%) of 11. Thus, one or the other technique was successful in 54 (90%) of 60 patients. When the results were analyzed separately for extrahepatic (29 patients) or intrahepatic (31 patients) cholestasis, percutaneous cholangiography was successful in 95% of patients with extrahepatic cholestasis but in only 25% with intrahepatic cholestasis. Endoscopic retrograde cholangiography successded in 63% of patients with extrahepatic and 76% with intrahepatic causes of cholestasis. Complications occurred only in patients with extrahepatic cholestasis. Cholangitis and septicemia occurred in 1 patient after retrograde cholangiography and in 2 after the percutaneous technique. An intraperitoneal bile leak occurred in one other patient after percutaneous cholangiography. Percutaneous cholangiography with the narrow needle is a simple, inexpensive, and reliable method for demonstrating the biliary system and is usually successful when an extrahepatic cause of cholestasis is present. The occurrence of serious complications in patients with extrahepatic cholestasis, despite prophylactic antibiotics, makes provision for early surgery mandatory after both techniques.


Responses to treatment can differentiate chronic active liver disease with cholangitic features from the primary biliary cirrhosis syndrome.

Of 125 patients fulfilling preestablished criteria for severe chronic active liver disease (CALD) and enrolled in a prospective trial of treatment, 15 (12%) presented with morphological features of liver biopsy consistent with the diagnosis of both CALD and primary biliary cirrhosis (PBC) syndrome. Customary clinical, biochemical, and immunoserological studies failed to distinguish fully between these conditions. By contrast, early response to treatment with prednisone and/or azathioprine identified two different groups of patients. Five patients failed to respond, whereas 10 improved and this was followed by resolution of all clinical, biochemical, and morphological evidence of disease activity. Analysis of the initial chemical findings and cumulative bile duct counts from multiple biopsies correlated failure to respond with biochemical and morphological features more consistent with PBC than CALD. Responses to treatment can therefore be utilized when indicated for differentiating CALD with cholangitic features from PBC.


Lymphocyte cytotoxicity and inhibition studied with autologous liver cells: observations in chronic active liver disease and the primary biliary cirrhosis syndrome.

A method is described for determining the cytotoxicity of normal and autologous lymphocytes for 51Cr-labeled isolated parenchymal liver cells in a low aggressor to target cell ratio. Results were compared from patients with chronic active liver disease (CALD), chronic persistent hepatitis (CPH), miscellaneous liver diseases, or primary biliary cirrhosis (PBC). In 53% of CALD patients, lymphocytes showed greater cytotoxicity for hepatic cells than did normal allogenic lymphocytes, but in 32% there was significantly less 51Cr release than normal; in the remainder, results were in the normal range. Lymphocyte cytotoxicity was greater in patients with disease of short duration and less in those treated with corticosteroids. In untreated CALD, decreased 51Cr release was associated with the presence of plasma factor(s) inhibiting phytohemagglutinin (PHA)-induced transformation of normal lymphocytes. Lymphocytes from approximately 50% of the patients with PBC exhibited cytotoxicity for hepatic cells but 25% showed less 51Cr release than controls and the remaining patients had results in the normal range. Lymphocyte cytotoxicity was also greater during the earlier stage of PBC. In contrast to CALD, decreased 51Cr release was not associated with the presence of plasma factor(s) inhibiting PHA-induced transformation of normal lymphocytes. Our findings support the hypothesis of in vivo lymphocyte-mediated liver cell damage in CALD and PBC, suggesting a potentially important role for lymphocyte suppression in the pathogenesis of both diseases.


Effects of anticopper therapy on hepatocellular mitochondria in patients with Wilson's disease: an ultrastructural and stereological study.

Liver biopsy specimens from 7 patients with Wilson's disease (hepatolenticular degeneration), obtained before and after 3 to 5 years of D-penicillamine therapy, were studied by electron microscopy and stereology. The characteristic mitochondrial abnormalities encountered in the hepatocytes of untreated patients were less pronounced or disappeared after treatment in 5 of the 7 patients. Simultaneously, relative mitochondrial volume, surface density of the external mitochondrial membranes, and the number of these profiles per unit area increased, whereas abnormal elevations SGOT and SGPT returned to normal levels.


The effect of loss of gallbladder function on biliary lipid composition in subjects with cholesterol gallstones.

The effect on biliary lipid and bile acid composition was assessed during the development of gallbladder nonfunction in 5 subjects with asymptomatic cholesterol cholelithiasis. There was a significant increase in the relative proportion of bile salt but a decrease in that of cholesterol in bile after development of gallbladder nonfunction which persisted after recovery from cholecystectomy. These findings were associated with a decrease in cholesterol crystals in bile sediment and an increase in the proportion of secondary bile acids after cholangiographic evidence of gallbladder nonfunction. Percentage cholesterol saturation of bile reverted to normal after development of gallbladder nonfunction which persisted after recovery from cholecystectomy.


The effect of sodium taurocholate on biliary iodipamide excretion in the dog.

The effect of sodium taurocholate in stepwise increasing infusion rates, 0.3 to 9.6 mumoles per min per kg, on the biliary excretion rate of iodipamide was investigated in 6 dogs (10 experiments) with complete bile diversion under general anesthesia. Iodipamide was administered intravenously with an initial priming dose of 33 mumoles per kg followed by a constant infusion of 1.3 mumoles per min per kg. Although the bile flow continuously increased with an increasing taurocholate dose, the iodipamide excretion rate reached a plateau with a 0.6 mumoles per min per kg of taurcholate infusion, which was 20% higher than with the lowest taurocholate dose. With a taurocholate dose over 2.4 mumoles per min per kg, a significant decrease in the iodipamide rate was found, amounting to 22% of its maximum value with the largest taurocholate dose. The bile iodipamide concentration was already at its maximum with the lowest taurocholate dose, and it decreased with an increasing taurocholate dose. Since the bile iodipamide concentration is probably the most important determinant in clinical cholangiography, low bile salt plasma levels should result in the best radiographic visualization of the biliary tree.


Acute intermittent porphyria with relapsing acute pancreatitis and unconjugated hyperbilirubinemia without overt hemolysis.

A 36-year-old woman was admitted to hospital with a first attack of acute intermittent porphyria. At the same time increased serum levels of amylase and lipase as well as an increased amylase clearance to creatinine clearance ratio were observed, permitting the diagnosis of acute pancreatitis. The etiology of the latter could not be determined. In addition, elevation of indirect bilirubin without evidence of hemolysis was observed Gilbert's syndrome was suspected. 40 weeks after the first episode, a second attack of identical abdominal pain was noted, with elevation of pancreatic enzymes in the serum. There is evidence that acute intermittent porphyria and acute relapsing pancreatitis may have some etiological connection in this patient.


Effect of Amadori-type sugar derivatives of poly-L-lysine of platelet aggregation.

Fully substituted Amadori-type sugar derivative of Sigma type V-A poly-L-lysine does not induce platelet aggregation, but inhibits 30% of the platelet aggregation induced by collagen.


Further studies of the interaction between ristocetin and fibrinogen.

Fibrinogen (FG) precipitation by ristocetin is enhanced by lowering the temperature to 4 degrees C. The  precipitate has similar properties to an acquired cryofibrinogen being resolubilised on rewarming to 37 degrees C, and the process of precipitation and resolubilsation can be repeated indefinitely by lowering and raising the temperature. Other plasma proteins are also precipitated by ristocetin, but to a lesser degree than FG. This property appears to have no relation to ristocetin's ability to aggregate platelets in the presence of von Willebrand's factor, since platelet aggregation by ristocetin is inhibited by lowering the temperature.


The appearance of schistocytes in the peripheral blood in correlation to the degree of disseminated intravascular coagulation. An experimental study in rats.

The infusion of thrombin in rats induced a disseminated intravascular coagulation (DIC) with haemolysis and schistocytosis. The number of schistocytes was found to be correlated to fibrinogen catabolism, plasma haemoglobin level and to the extent of fibrin deposition in the renal glomeruli in the early phase only. Later, no correlation could be observed, indicating a time-dependent behaviour of schistocytosis. The results suggest that a large number of schistocytes in blood smear is suspicious for DIC. These studies also support the concept that fibrin depositions in the blood vessels could play a role in the production of red cell fragmentation by mechanical destruction.


Haemostasis in the microvasculature of the rabbit mesentery, effects of some pharmacological agents of current interest in haemostasis and thrombosis.

A study has been performed to evaluate the effect on haemostatic plug formation in the rabbit mesenteric microcirculation of some principally different pharmacological substances of current interest in thrombosis research. It seems as if agents which have a potential value in the prophylaxis of venous thrombosis also modify haemostasis in our experimental model.


Inhibition of platelet aggregation by acetylsalicylic acid and other inhibitors.

Effects on platelet aggregation were examined of acetylsalicylic acid (ASA), indomethacin and a number of other agents including dipyridamole, phenylbutazone and sulfinpyrazone under standardized conditions. The Born turbidometric method of measuring platelet aggregation was used with collagen as the stimulus for aggregation. ASA and indomethacin were shown to be among the most potent inhibitors of aggregation, being active at minimal effective concentrations of 1-3 mug/ml using a 10 min time of pre-incubation with the platelet-rich plasma (degree of aggregation inhibition was time dependent). Most of the other agents tested were also active in vitro and both prostaglandin E1 and adenosine were more potent than ASA or indomethacin. However, these agents were shown not to exert significant inhibitory effects when administered orally to rats (dose 10 and 30 mg/kg). ASA proved to be effective in doses as low as 3 mg/kg, and indomethacin in doses as low as 1 mg/kg orally. The inhibitory effects of ASA on aggregation remained for several days after a single oral dose, whereas the effects of indomethacin disappeared within 24 h.


National surveillance of vectors and animal reservoirs.

In carrying out the national surveillance of vectors and animal reservoirs in Czechoslovakia the theory of the natural focus infections has been taken into account. In order to achieve a successful surveillance, besides studying the distribution of vectors and vertebrate hosts, the greatest emphasis has been put on the compilation of important data concerning their ecology, ethology and phenology. The author refers to some of the practical rsults of the national surveillance programme in Czechoslovakia.


Leptospiral antibodies in domestic animals in Tyrol.

Results are presented of a serological examination of 1,547 domestic animals (cattle, pig, sheep, horse, goat, dog, cat) from 9 Tyrolian districts (Austria), performed in order to disclose the incidence of leptospirosis. Completely significant titres were domonstrated by means of the MAL test in the serotypes icterohaemorrhagiae or copenhageni, sorex-jalna, bratislava, sejroe and saxkoebing. In addition, antibodies were confirmed against L. bataviae, L. pomona, L. tarassovi and L. bulgarica, but the titres were insignificant. Of the animals examined, 7.2% gave positive reactions in titres of 1: 800 and above (for dogs and cats 1: 100 and more); positive reactions were obtained from 8.8% of cattle serum, 6.8% of pig-, 1.1% of sheep-, 3.3% of dog-, 18.2% of cat serum. A positive reaction was obtained with the serum of one out of the 9 horses examined, the sera of the two goats examined were negative. he percentage of positivity in animals from the individual districts ranged from 1.0 to 17.0, and variations were found also in the distribution of serotypes in the individual districts. The results indicate that the percentage of positivity in domestic animals from Tyrol decreases as the altitude of the localities increases.


Circular DNA and cardiolipin in hydrogenosomes, microbody-like organelles of trichomonads.

Circular molecules of DNA approximately 3 mum in length were revealed by electron microscopy in deproteinized extracts prepared from purified hydrogenosomal fraction of a protozoan Tritrichomonae foetus. This fraction contained also cardiolipin amounting to approximately 14.4% of its total phospholipids, as detected by thin-layer chromatography and quantitative phosphorus measurement. These characteristics extend a number of biochemical properties of hydrogenosome shared also by mitochondria and by prokaryotic cells.


Polymorphism of larvae of the genus Aploparaksis Clerc, 1903 (Hymenolepididae).

The larvae of 12 cestode species of the genus Aploparaksis have been studied. In order to confirm the determination, the definitive hosts, birds, were experimentally infected with 5 species and the intermediate hosts, oligochaetes, with 6 species of cestodes. A great variability was observed in the morphology of tail appendix of cysticercoids belonging to five types of larvae. It is assumed that the polymorphism of larvae of the genus Aploparaksis results from the morphological adaptation to the development under arctic conditions.


Studies on species specificity of proteins in Ascaris lumbricoides and Ascaris suum.

The separate identity of A. lumbricoides and A. suum was confirmed by means of the disc electrophoresis method in that differences were established in the protein profile of somatic and ribosomal proteins. In addition differences were found in the representation of lipoproteins, glycoproteins, and in the activity of LDH, SDH, peroxidase, esterase and alkalic phosphatase.


Acanthophthirius kolenatii, a new species, and some new records of fur-mites (Acarina: Myobiidae and Labidocarpidae) from Armenia.

A description of the female of a new species, Acanthophthirius kolenatii sp.n., is given. The species is very closely related to A. poppei (Trouessart, 1895) and A. etheldredae Perkins, 1925 and has been collected from Pipistrellus kuhli (Kuhl) in the Armenian S.S.R. The species Pteracarus pipistrellius pipistrellius (Radford, 1938) and Alabidocarpus calcaratus calcaratus Lawrence, 1952 are recorded from the territory of Armenia for the first time.


To the knowledge of fauna of synanthropic flies of the Nepal Himalya.

A material of flies collected in two localities (altitude of 3900 and 4500 m) in the Barun Khola Valley (East Nepal) was studied, representing the early spring aspect of the species composition of flies. Of the total number of 2309 fly specimens 99.3% represented two species of the genus Paregle (P. aterrima, P. sp.); both are autochthonous high altitude hemisynanthrophic forms. The remainining 0.7% represent 9 species, most of which are more or less eurytopic species of palearctic or holoarctic distribution (Calliphora vicina, C. vomitoria, Meoneura flavifacies, Scatophaga stercoraria, Hydrotea hirticeps, Orthellia caesarian, Paregle danieli, Anthomyiidae g. sp. 1, g. sp. 2).


Gyrodactylus konovalovi sp. n. (Gyrodactylidae: Monogenoidea) from Phoxinus lagowskii Dybowski.

A new species of the genus Gyrodactylus, G. konovalovi, from the fins, gills and skin of Phoxinus lagowskii Dybowski is described. The specimens were found for the first time in the Mongolian People's Republic by Ergens and Dulmaa (1967) and were erroneously determined as D. macronychus Malmberg, 1957.


Are the mites of the genus Tarsonemus really parasites of man?

Mites of the genus Tarsonemus were found in several preparations of human skin samples. It was revealed that the mites got into the preparations from insufficiently cleaned coverslips. Similar previous reports are discussed on this occasion.


Managing problem behaviors of elderly patients.

Professional as well as nonprofessional staff who work with the elderly in nursing homes must be reminded repeatedly that most problem behaviors are symptoms of such underlying problems as unresolved conflicts, the loss of normal, appropriate life roles, and the anticipation of illness and death. The author describes how those problems are reflected in such "senile" behaviors as incoherence, incontinence, ritualism, and inappropriate sexual behaviors. She believes the concept of personality regression under stress is a useful framework for helping staff understand and manage such behaviors. She illustrates how nonprofessional staff can help patients achieve a more satisfactory adjustment by using certain behavior modification techniques, by roleplaying, and by identifying feelings responsible for porblem behaviors and helping patients ventilate them.


The adult development program: an educational approach to the delivery of mental health services.

The adult development program is an intensive, shortterm program for individuals who want to change their behavior. It is based on an educational model; participants, who are called students, set their own behavior-change goals, and a multidisciplinary staff teach them techniques for reaching those goals. The program curriculum consists of about 20 seminars and workshops, which give the students an opportunity to learn and to practice new behaviors. Students pay fees that vary from $40 to $500 per month depending on the number of classes they take. Approximately 1750 students have participated in the program since it began six years ago.


Responsibility therapy in community psychiatry.

The author describes a day treatment program using responsibility therapy, a form of behaviorism based on the principles of Alcoholics Anonymous. Mental illness is conceptualized as an addiction or bad habit to be corrected through definition of the client's problems, values, and therapeutic objectives. The program, which is operated by the county, requires high client motivation and the involvement of significant others. About 100 clients enter the program each year; more than half are referrals from the county probation department. A recent study showed that the program is serving the most disabled group of clients as least as effectively as the other county services.


Origins of a Jungian-oriented therapeutic community for schizophrenic patients.

The author believes that rapid hospital turnover of psychiatric patients and heavy reliance on psychotropic drugs often interfere with recovery, especially for many psychotic patients who need a retreat where they might be helped to heal themselves. He describes the origins and operation of a Jungian-oriented therapeutic community for schizophrenic patients in a Veterans Administration hospital, the community is based parly on his earlier work with therapeutic communities and his belief that clear lines of authority must be maintained as well as his experiences with videotherapy and art therapy. The community relies heavily on art therapy in which patients are encouraged to make abstract paintings of their delusions, visions, hallucinations, dreams, and fantasies and to interpret the paintings themselves.


The development of a program for treating obesity.

During its first three years of operation a health center in California developed a program for treating obesity. It was originally called a weight-control class and had an educational orientation. The first series of classes lasted 12 weeks and subsequent series lasted six weeks. After four series, attendance had dropped drastically and the class leaders were ready to discontinue the program. Health center staff encouraged them to continue, and during the next series they made several changes that made the program more successful. The program was called a health and weight class and included patients who were not obese. The leaders restricted the class to adult women, drew up a specific diet plan, and set a weight-loss goal of two pounds a week.


Breaking a cycle of hospitalization through the psychiatric house call.

The authors discuss a case in which family therapy administered in a home setting helped to break a cycle of psychiatric hospitalization that had continued for ten years. Their patient had adopted a persistent behavioral pattern involving protective magic rituals and consultations with spirits as a defense against other problems in her family relationships. With regular visits from the therapists and cooperation from each member of the family, the patient's symptoms were ameliorated and the family situation greatly improved after eight months. The authors believe that because they worked with the entire family as a system, were able to recognize sociocultural factors that had not been dealt with in the patient's hospitalizations, and were able to stimulate communication among family members in a home setting, they were able to see more immediate results and thus were able to break the costly cycle of repeated hospitalizations.


Mental health care and treatment: will health planning make a difference?

The National Health Planning and Resources Development Act of 1974 establishes a five-tiered system for health planning that begins with the Secretary of Health, Education, and Welfare and reaches the local level through areawide health systems agencies. The author describes the implications of the law for mental health services, focusing particularly on its impact at the local level. He describes the functions of the health systems agencies, points out limitations in their authority, and emphasizes that cooperation of community organizations and agencies is essential if they are to be effective in improving health and mental health care and treatment.


Consumer-professional collaboration for evaluation in neighborhood mental health programs.

Neighborhood mental health programs are challenged with the scientific and fiscal necessity of evaluating their services. Since most such programs are joint endeavors of neighborhood residents (usually a consumer board) and nonneighborhood professionals, such evaluative efforts require the sanction and collaboration of both groups to be maximally effective. However, the authors point out that collaboration is often strained by lack of trust and conflicts of interest. Study design may fail to consider neighborhood values, with the result that the provision of services is impeded, consumers are frightened or coerced, the role of paraprofessionals is threatened, and the consumer board's responsibilities to the neighborhood are ignored. The authors discuss those four issues and suggest ways of resolving them.


A model for interagency cooperation in the provision of mental health services to youths.

In 1971 the Chedoke-McMaster center initiated an assessment and placement program for emotionally disturbed preadolescents in the Hamilton, Ontario, area. That project was used as the springboard for a cooperative venture with other health and social service agencies dealing with children. At the heart of the collaborative project is a multidisciplinary team, composed of representatives from the various participating agencies, that is responsible for all clinical decision-making regarding the need for impatient assessment and placement in residential treatment programs. The team also participates in the planning for discharge and aftercare. The other two components of the project are a short-term inpatient cottage assessment unit and several long-term residential treatment programs.


The parent-therapist program: an innovative approach to treating emotionally disturbed children.

The authors describe the parent-therapist program, an innovative alternative to residential treatment for emotionally disturbed children. In the program, which is based on the extended family model, couples not only provide a residential milieu for a child placed with them, but also are trained to be therapists who can deal with specific emotional and behavioral problems. The parent-therapists work together in three treatment teams, each consisting of five couples. Education and supervision are ongoing. A total of 27 children have been treated in the program since it got under way in May 1972. Clinical impressions indicate that the children have made substantial gains in developing social and interpersonal skills and in their academic acievement.


The management and mismanagement of a suicidal patient.

The author begins with the premise that the actions of therapists and hospital staff can contribute to the likelihood that a suicidal patient will eventually take his life. He recounts a case history of a depressed 51-year-old man who was hospitalized following a suicide attempt and delineates eight "mistakes" that contributed to the patient's eventual suicide and that are common occurrences in dealing with a suicidal patient. He believes that if more therapists and mental health professionals share mistakes and experiences of this kind with each other, such errors might be minimized or even prevented.


Psychiatric treatment in jail: an experiment in health-care delivery.

The author discusses the source of referral, psychiatric diagnosis, and treatment of 539 inmates who were referred for psychiatric treatment in two metropolitan jails. Almost one-third of the patients were evaluated within 24 hours of their being booked into jail. Manifestly disordered and violent behavior accounted for 50 per cent of the referrals; almost half the patients were diagnosed as schizophrenic or manic. The author emphasizes the importance of a close working relationship with the custody staff to facilitate identifying inmates who need psychiatric treatment.


The association of blood groups, ABH secretion, haptoglobins and hemoglobins with filariasis.

Results on 605 patients and 597 controls carefully matched in relation to sex, age, marital status and profession are reported. A higher frequency of nonsecretors, as well as an excess of B and lack of A2 were observed among the filarial patients. Since these differences do not occur in other series, however, their significance is doubtful.


The occurrence of consanguineous marriages in Hungary.

The occurrence of first cousin couples was 2.90/00 in Hungary involving three different population samples (about 2,000, 1,000 and 2,000 women after delivery in the capital, two cities, and a city with agricultural characteristics, respectively).


An autosomal glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) polymorphism in human saliva.

Glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) from human saliva has been demonstrated by the zymogram technique. Three phenotypes were found. Family and population studies suggested that these phenotypes are the products of an autosomal locus with two alleles Sgd-1 and Sgd-2.


Atypical serum cholinesterase in the Netherlands.

Pseudocholinesterase was examined in 322 samples from unrelated, healthy blood donors. In 14 cases heterozygosity was found, i.e. the frequency of the allele for atypical cholinesterase amounts to 0.022. A comparison is made with other European populations.


Inbreeding among some Brahman populations of Tamil Nadu.

A statewide survey of four endogamous Brahman populations of Tamil Nadu reveals a low level of inbreeding in three of them. In the fourth population, the Thengalai, the level is higher, but not as high as in other social castes. The Tamil Brahmans rank next to the Telugu and the Kanarese Brahmans in this respect. Uncle-niece marriages also occur as in Telugu-speaking populations, and these exceed in the two Ayyangar populations in comparison to the Ayyar. A decline of first-cousin marriages and an increase of uncle-niece marriages are detected in the first two living generations in each population.


Heterogeneity of congenital retinal non-attachment, falciform folds and retinal dysplasia. A guide to genetic counselling.

The heritable falciform folds and congenital retinal non-attachment reported in the literature are here divided into monosymptomatic and complex types. Of the former, autosomal dominant and recessive disorders are known. The complex types comprise several syndromes, both autosomal recessive and X-linked. Retinal dysplasia is sometimes seen in histological sections from these affections, but it is an unspecific histological reaction, and not a disease sui generis. Attention is drawn to the syndrome with microcephaly, microphthalmia and falciform detachment which, though previously described, has not so far been delineated. It is hypothesized that hydrocephaly and congenital retinal non-attachment with or without microphthalmia and persistent hyperplastic primary vitreous constitute yet another 'new' syndrome, mainly seen in females.


Saliva acid phosphatases: genetic studies.

Acid phosphatases from human saliva have been demonstrated by the zymogram technique. Six phenotypes were found. Family and population studies suggested that the phenotypes are the product of two loci, Sap-A with three alleles A, A' and O, and Sap-B with two alleles B and O.


Gene frequencies and linkage data on EsD in man.

Gene frequencies of the esterase D system were estimated in a sample of 1,392 unrelated adults living in Copenhagen; the results were EsD1 = 0.896 and EsD2 = 0.104. No genetic linkage could be demonstrated between this system and a series of autosomal makers.


Separation of six bovine complement components and one inactivator (1, 2).

Six components (C1, C5, C6, C7, C8 and C9) of bovine complement and one inactivator (C3 in) could be separated from bovine serum. Bovine C1 was separated by precipitation at low molarity (0.03 M of relative salt concentration) other components by DEAE-cellulose chromatography using 0.005 M sodium phosphate buffer, pH 7.5, as a base for solvents having the relative salt concentration adjusted by addition of NaCl from 0.03 to 0.3 M. The separated bovine complement components could be tested using intermediates formed from sheep erythrocytes, rabbit hemolysin, guinea pig C1 and remaining human complement components. C2, C3 and C4 of bovine origin remained undetected either because of incompatibility with the intermediates used or interference of inhibitors or inactivators.


Cephacetrile--application of pharmacokinetic data to dosage determination.

This pharmacokinetic investigation was based on the determination of serum and urinary levles of cephacetrile in 50 subjects given single intramuscular or intravenous doses of 0.5 or 1 gm of the antibiotic; 30 normal subjects, 10 patients with renal insufficiency, and 10 patients with chronic nephritis undergoing maintenance haemodialysis were included in this study. In normal subjects, mean serum half-life was 1.09 hours (Ke = 0.6337) after intramuscular injection of 0.5 gm cephacetrile, 1.31 hours (Ke = 0.5276) after intramuscular injection of 1 gm, and 0.89 hours (Ke = 0.7806) after intravenous injection of 1 gm. Absorption half-life was 0.45 hours after intramuscular injection of 1 gm cephacetrile. The urinary elimination of cephacetrile over the first 6 hours after injection was on the average 72.7% of the administered dose. After intravenous injection of 1 gm of the antibiotic, the plasma clearance of cephacetrile was 407 ml/min., and its renal clearance 313 ml/min. A linear correlation was found between the values of overall elimination rate constant (Ke) and creatinine clearance in the subjects under investigation (Ke = 0.0080 + 0.0061 ClCr). The established pharmacokinetic characteristics were used to calculate the maintenance and loading doses as well as the intervals between injections adjusted to creatinine clearance. These data constitute true dosage schemes adapted to the particular case of each patient according to his kidney function.


Analgesia, plasma levels, and dosage of propoxyphene.

It can be shown that both the mean plasma levels observed and the mean analgesic scores (effectiveness) are related to the dose of an orally effective analgesic agent, although wide individual variations exist. Based on the pharmacokinetic characteristics of propoxyphene, it can be predicted and confirmed that equilibrium (or steady state) plasma levels will be achieved after about six doses when administered on a q. 6h. schedule. Similar predictions indicate that an initial loading dose of 2 to 2 1/2 times the maintenance dose will produce more promptly plasma levels within or close to the equilibrium levels.


Absorption and excretion of a new antidepressive (SQ 10,996) in humans.

A single oral dose of 10 mg of SQ 10,996-14C was absorbed slowly by 3 normal male volunteers, with peak plasma concentrations achieved 6 hr after ingestion; the plasma half-life was about 38.5 hr. On average, 82.3 +/- 3.5% of the radioactivity present in the 2 hr plasma sample was bound to plasma proteins. These volunteers excreted an average of 31 and 52% of the dose in the urine and feces, respectively. All subjects excreted minor amounts of 14CO2 in the expired air. No unchanged SQ 10,996-14C was found in the urine. Three unidentified metabolites were excreted in urine. SQ 10,996-14C was excreted in the feces only as unchanged drug, suggesting that the drug is incompletely absorbed. The volunteers tolerated the drug well and experienced no adverse effects.


The frequency of adverse drug reactions as dependent upon age, sex and duration of hospitalization.

In 1972, 171 (18, 7%) of 914 patients showed evidence of an adverse drug reaction (ADR) in a prospective study of the division of internal medicine in a regional teaching hospital (Zieglerspital, Bern). The following factors correlated positively with frequency of ADR: 1. The duration of hospital stay. 2. The age between 60 and 80 years. 3. Female sex. 4. Previous ADR. The fact that most of the ADR occur within the first three weeks of a hospital stay, combined with point 1, suggests early ADR having some predictive value for duration of hospital stay. Statistical data of type, severity, duration and pathogenesis of ADR are given. The drugs involved are mentioned.


EPFFECT OF PROPRanolol on plasma renin level and angiotensin sensitivity in man.

The effect of 160 mg oral propranolol daily for a week on angiotensin sensitivity and plasma renin activity has been studied in ten patients with Kaplan's test and by determining renin with the radioimmunoassay. Propranolol was found to increase angiotensin activity and to reduce the plasma renin level. The results are compared with the respective effects of other antihypertensive drugs tested under identical conditions.


The antidiuretic action of 1-deamino-8-D-arginine vasopressin (DDAVP) in man.

1. After administration of a new vasopressin analogue (DDAVP), a marked and prolonged antidiuresis occurred in 10 patients with pituitary diabetes insipidus. 2. The antidiuretic effects of single intravenous doses of 0.04--24 mug DDAVP and single intranasal doses of 5--320 mug DDAVP were investigated. Time curves of the antidiuretic responses expressed in changes of urine osmolality (Uosm) and free water clearance per 100 ml GFR (CH2O X 100/GFR) are described. 3. Maximal "peak" response was obtained after an intravenous dose of 1 mug within the first 12 hrs (Uosm was 7--800 mOsm/KgH2O). Further increase of dosage resulted only in prolongation of duration of action (up to 48 hrs) and peak ("plateau") effect (up to 24 hrs). 4. There was a linear relationship between the log dose and log osmolality of urine collected in the second 12 hours after administration of single intravenous and intranasal doses of DDAVP. 5. Comparison of the effects of 1 mug lysine-vasopressin and 1 mug DDAVP revealed only slight differences in peak effects, but extreme differences in duration of action. 6. It is concluded that in the evaluation of a synthetic vasopressin analogue the maximal antidiuretic ability and the prolongation of action have to be analysed separately.


Significance of daily rhythm for the interpretation of functional diagnostic procedures.

For the first time, the reaction of the cardiovascular system during day and night in young people was examined. We were mostly interested in the influence of the nervous system and any autonomic mechanism. We examined 20 subjects at 4-hour intervals on the ergometer (active exercise) and on the tilt-table (passive exercise) to find out the rhythm in the circulatory regulation. The test person was kept in vertical position on the tilt-table for 10 minutes. On the ergometer he had to perform a work-load of 100 Watt for 10 minutes. We measured pulse rate and blood pressure; we introduced new terms for the evaluation. "Orthostatic Index" and "Performance Index" will be further explained. The results were: A minimum in the orthostatic stability around 1 p.m. and 1--5 am, and a performance maximum at 1 p.m. and 5 p.m. Further details will be reported.


Methods of measuring physical fitness.

Clinical pharmacology is in need of standarized test-methods for guaranteeing objective controls of therapeutic efficacy. In the field of cardiology, test methods had been created for electrocardiographic and special cardiologic examinations by Kaltenbach, Korkmann et al. For objectivating the therapeutic success in hypertension and orthostatic tolerancy, some regimens had been made and published in their journal, according to the test methods of Kirchhoff. This report is to discuss the criteria which show an assessment for the range and the limit of efficacy of functional circles and circular systems determining the efficiency.


Clinical bioavaiability of nitrofurantoin--a case of bioinequivalence.

In a crossover study of the bioavailability of marketed nitrofurantoin tablets, there were significant differences in the urinary excretion of nitrofurantoin suggestive of bioavailability problems with this drug. Standard in vitro assessments of dissolution rate and disintegration time were not correlated with bioavailability and failed to detect 3 to 18 fold differences in the amount of nitrofurantoin absorbed. In fact, four lots, made by the same manufacturer had almost identical in vitro measurements (dissolution rate; distinegration time), yet two of these lots were only 6.6 and 26% as available as the reference nitrofurantoin product, and two others were comparatively available. The need for the development of an in vitro - in vivo correlation for control of lot to lot uniformity has clearly been demonstrated for nitrofurantoin. Such correlations must include tests other than those presently required.


Continuous measurement of vascular diameters via television microscopy.

In the past 10 years, microcirculation studies have emphasized quantitative measurements of microvascular diameters to characterize in vivo small vessel responses to experimental forcings such as hemorrhage, anesthesia, and hypoxia. We have developed an instrument to obtain continuous diameter measurements of a small artery and vein (40-200 mu) via closed-circuit television microscopy. The outputs are analog voltages proportional to the vessel diameters. Video processing is limited to two image areas termed "windows," which are defined by markers on the monitor and positioned over separate vertically aligned vessels. Each vessel, which appears darker than the surrounding tissue, is located by comparing the video signal to a reference voltage that adapts to changes in the relative contrast within the window. In the presence of a vessel, a ramp voltage is generated, the peak value of which is proportional to the vessel diameter. These peaks are averaged over the 15-video lines of the window and over several video frames to reduce noise sensitivity. In order to accommodate preparation movement such as skeletal muscle contraction, window position and width automatically adapt to changes in vessel position and width. Visual verification of system performance is provided by clamping the video signal to white on that portion of the image which the instrument identifies as vessel.


Time delay effects in the estimation of pulmonary diffusing capacity.

Steady state estimates of the pulmonary diffusing capacity for carbon monoxide require measurement of the uptake and the average partial pressure of CO in the lung. The expired alveolar sample obtained by different experimental methods and/or breathing patterns rarely represents the actural average alveolar partial pressure. This error in choosing the correct alveolar sample arises in the sampling time chosen by the experimental method. The time (TAV) at which the correct alveolar sample (FAV) is obtained occurs one-half of a breathing period after the effective inspiration time. If TAV and the sample time chosen by the experimental method are known then the measured diffusing capacity can be corrected to the actual diffusing capacity.


Ultrasonic blood flow measurements: transcutaneous compared with implanted cuff.

Experiments were undertaken in our laboratory to establish relationships between flow parameters calculated from implanted ultrasonic cuff signals and those obtained with a transcutaneous probe. Analog signals were received from crystals surgically implanted on the right carotid, right femoral, and abdominal aorta of a mature male beagle dog. Near these locations, transcutaneous measurements were made using a prescribed technique. From these ultrasonic signals, the following time dependent flow parameters were calculated: spatial velocities, velocity profiles, diameters, flows, and velocity frequency distributions. Using these measurements, a comparison between the implanted cuff and transcutaneous probe was made. In addition to high reproductibility, results confirm a strong correlation between the two techniques; consequently, the validity of the less traumatic transcutaneous method is substantiated.


[Hemangioperocytoma in the infant. A histogenetic study].

Two children with hemangiopericytomas are reported-one with a congenital tumor, the second hemangiopericytoma was noticed during the first trimenon. Histologically there was no obvious difference to the hemangiopericytomas in adults. Tumor immaturity should not be seen as a nondifferentiation but as an embryonal immaturity. In analogy to other reticulo-histiocytic proliferations, reticular fibers, shown by silver impregnation, can be demonstrated in both cases. The silver stain should not be over-rated in its diagnostic and prognostic significance.


[Technical experience with 8-methoxypsoralen photochemotherapy in common psoriasis].

Photochemotherapy with 8-MOP und UV-A is a modality to treat psoriasis vulgaris successfully. Technical experiences with three types of machines, a horizontal box with Sylvania fluorescent lamps, a stand-up box, and a hand-foot-box with Osram fluorescent lamps are reported. Oral and topical 8-MOP applications are compared for these three types of boxes. Disadvantages of the oral or topical 8-MOP applications are compiled. Oral 8-MOP is superior to the topical treatment in both the stand-up and the horizontal box. The following technical features are discussed: Minimal phototoxic dose, photopigmentation index, radiation-dose, time increments during treatment, maintenance therapy, and UV-A meters.


[Ito's syndrome (incontinentia pigmenti achromians)].

Ito's syndrome is a distinct entity characterized by bilateral systematized linear depigmentations denominated by Ito as "incontinentia pigmentiachromians". The syndrome includes a variety of anomalies predominantly affecting the central nervous system, the eyes, and the muscular-skeletal-system. The patient described in this paper was a 26 year old man suffering from a sever scoliosis. This anomaly had not been mentioned in previous case reports.


[Atypical Kaposi's disease].

To demonstrate that Kaposi's sarcoma may initially take several different courses, a case is presented and the literature reviewed.


Alborixin, a new antibiotic ionophore: isolation, structure, physical and chemical properties.

Alborixin, a polycyclic polyether ionophorous antibiotic, active against Gram-positive bacteria and fungi, was isolated from cultures of a strain of Streptomyces albus. The isolation, structure and physiochemical properties of this antibiotic are reported. Some derivatives have been prepared and their structures and properties are also described in this paper.


U-43,120; a new antitumor antibiotic. I. Production, biological activity, microbiological assay and taxonomy of the producing microorganism.

A new antitumor antibiotic, U-43,120 was discovered. It is produced by fermentation of a new species of Streptomyces, designated Streptomyces paulus DIETZ sp. n. Its antimicrobial activity is limited to bacteria. A microbiological assay with Bacillus subtilis was developed that can be detect concentrations of 1 approximately 2 mug/ml of the drug in fermentation liquors. U-43,120 was active in vivo against P-388 leukemia in mice.


Samarosporin, a new peptide antibiotic. I. Fermentation, isolation ahd characterization.

A new antibiotic, samarosporin, was isolated in a crystalline state from a mycelial extract of a strain of Samarospora species (an ascomycete). Samarosporin is a neutral cyclopeptide and has a molecular formula of C72H111N15O19. Samarosporin shows a broad antimicrobial activity against various test microorganisms.


Structure of a new isoflavone from fungi and Streptomyces inhibiting dopa decarboxylase.

A new dopa decarboxylase inhibiting isoflavone has been isolated from culture filtrates of fungi and streptomyces and shown to be 3',4',5,7-tetrahydroxy-8-methoxyisoflavone.


Biosynthesis of formycin. Incorporation and distribution of labeled compounds into formycin.

1. Two carbons, carbon-2 and one of carbons-3 to -5, of lysine seemed likely to be incorporated into one of carbon of the chromophore moiety of formycin. 2. From the results of radioisotopic studies with glutamate, gamma-amino-n-butyrate or organic acids related to tricarboxylic acid cycle, the important role of glutamate in the biosynthesis of formycin was strongly suggested. 3. The incorporation of nitrogen(s) of lysine into three nitrogens, including two nitrogens of pyrazole ring, of formycin was suggested by mass spectroscopy. 4. Ribose was estimated as a direct precursor moiety of formycin, whereas the biosynthesis of ribose was shown to occur via the pathway other than hexose monophosphate shunt or glucuronate pathway. 5. In replacement culture, the salvage synthesis of formycin from its chromophore moiety was not observed and it was also evident that the chromophore moiety or pyrazofurin (pyrazomycin) inhibited the biosynthesis of formycin.


Formation of 3-methylthioacrylic acid from methionine by Streptomyces lincolnensis. Isolation of a peroxidase.

Cultures of Streptomyces lincolnensis accumulated 3-methylthioacrylic acid in amounts directly related to the concentration of methionine in the medium. The metabolite was labeled by L-(methyl-14C) but not by DL-(carboxyl-14C) methionine, indicating biosynthesis from the amino acid with loss of the carboxyl group. S. lincolnensis mycelium contained sufficient peroxidase activity to catalyse oxidative decarboxylation of L-methionine to 3-methylthiopropionamide as the initial step of a biosynthetic sequence. The enzyme, partially purified by ammonium sulfate precipitation, chromatography on a DEAE-cellulose column ang gel filtration, had a molecular weight of approximately 350,000, a pH optimum of 6.0, with o-dianisidine as electron donor and a Km value of 7.5 x 10(-4) M with respect to hydrogen peroxide. Cultures of S. lincolnensis supplemented with 3-(methyl-14C) methylthiopropionic acid gave labeled 3-methylthioacrylic acid. However, 3-(methyl-14C) methylthiopropionamide did not label the metabolite, suggesting that the first intermediate in the pathway may be the keto acid, which is then oxidatively decarboxylated to 3-methylthiopropionic acid.


CGP 9000: a new orally active, broad-spectrum cephalosporin.

CGP 9000, (7-[D-2-amino-2-(1,4-cyclohexadienyl)-acetamido]-3-methoxy-3-cephem-4-carboxylic acid), is a new broad-spectrum cephalosporin antibiotic. Its antibacterial activity in vitro (MIC) is similar, but its bactericidal efficacy superior to that of cephalexin and cephradine. Upon oral administration to mice infected with various bacteria, CGP 9000 is, in general, 2 to 7 times more effective than either cephalexin or cephradine.


In vitro anti-mycoplasmal activity of amphotericin B methyl ester.

The polyene macrolide antibiotic amphotericin B (AB) and its chemically modified derivative amphotericin B methyl ester (AME) were tested for in vitro activity against Acholeplasma laidlawii, Spiroplasma citri and Mycoplasma gallisepticum. Both polyene macrolide preparations demonstrated anti-mycoplasmal activity. However, AME was mycoplasmacidal toward all three strains of mycoplasma at levels which previous studies have indicated would be permissible for most cell culture systems, whereas the levels of AB required for similar activity would be physiologically intolerable for tissue culture cells. In addition, AME was 100 fold more active than AB toward A. laidlawii, 10 fold more active than AB toward S. citri and demonstrated equivalent activity as AB toward M gallisepticum. The in vitro anti-mycoplasmal activity of AME and AB was directly correlated with polyene macrolide antibiotic levels and the number of treated mycoplasma.


Studies on luciferase from Photobacterium phosphoreum. VIII. FMN-H2O2 initiated bioluminescence and the thermodynamics of the elementary steps of the luciferase reaction.

Bacterial luciferase from Photobacterium phosohoreum was found to produce bioluminescence on reaction with FMN and H2O2 in the presence of aldehyde. This luminescence is presumably produced by the same X1 intermediate as that found in FMNH2-O2 initiated luminescence. From the ratio of the light intensities of the FMN-H2O2 initiated reactions, we calculated the association constant of the reaction, luciferase+FMN+H2O2in equilibriumX1, and estimated its temperature dependence. From these results we calculated the thermodynamic parameters of the reaction, luciferase+FMNH2+O2in equilibriumX1. We found that the free energy level of X1 is only 3.2 kcal below that of fr-e FMN and H2O2. We also estimated the thermodynamic parameters of other steps of the luminescent reaction. The values obtained showed that the formation of X1 from luciferase, FMNH2 and O2 involves a positive entropy change, but the intermediate is in a state stabilized against decomposition. Results also suggest a considerable degree of electronic rearrangement on formation of the excited-state molecule from the X1-aldehyde complex.


Thermodynamic characteristics of the adsorption of sulfanilamide, phenol, and n-butanol on bio-gel beads.

The thermodynamic properties of the adsorption of sulfanilamide, phenol and n-butanol on Bio-Gel beads have been studied. Bio-Gel was chosen as the adsorbent as it possesses both hydrophobic and hydrophilic sites on its surface. Adsorption of the former two adsorbates was found to be exothermic, and the relevant thermodynamic parameters at 20 degrees are in the ranges: deltaH degrees = -2.7 to -5.4 kcal/mole; deltaF degrees = -6.0 to -7.6 kcal/mole; deltaS degrees = +7.7 to +11.6 e.u. In the presence of urea, adsorption of sulfanilamide and phenol was partially disrupted. This, together with the large entropy gain of the process, indicates that both hydrogen bonding and hydrophobic bonding contribute cooperatively to the adsorption. On the contrary, adsorption of n-butanol, which was not susceptible to urea, was an endothermic process with the parameters, deltaH degrees = +5.8kcal/mole, deltaF degrees = -1.8 kcal/mole, and deltaS = +26.1 E.U. at 20 degrees. These data conform to the thermodynamic properties of hydrophobic bond formation. Finally, possible implications of these data in the structural assembly of lipoprotein molecules are discussed.


Snake venom proteinase inhibitors. III. Isolation of five polypeptide inhibitors from the venoms of Hemachatus haemachatus (Ringhal's corbra) and Naja nivea (Cape cobra) and the complete amino acid sequences of two of them.

Five proteinase inhibitors which all inhibit the activity of bovine trypsin [EC 3.4.21.4] were isolated from African Elapid venoms of Hemachatus haemachatus (HHV, Ringhal's cobra) and Naja nivea (NNV, Cape cobra). All the inhibitors were essentially homogeneous by polyacrylamide gel electrophoresis in the presence or absence of sodium dodecylsulfate. Amino acid analysis and terminal analysis also supported their chemical homogeneities, except for one of the two inhibitors from Hemachatus haemachatus venom. The isolated inhibitors had a molecular weight of about 6,500, consisting of 52 to 57 amino acid residues, and they were all devoid of tryptophan. However, their amino acid compositions differed from each other. One of the three inhibitors isolated from Naja nivea venom, designated NNV inhibitor Ia, was unique, in that 4 half-cystinyl residues per mole fof the polypeptide were present, whereas all the others contained six residues. Of the isolated proteinase inhibitors, the complete amino acid sequences of two major inhibitors were established by manual and automatic Edman degradations and standard enzymatic techniques. Each of the inhibitors, designated HHV inhibitor II and NNV inhibitor II, consisted of 57 amino acid with arginine and glycine at the NH2- and COOH-termini, respectively. Both contained six half-cystines in disulfide linkages, and their overall amino acid sequences were similar, showing 91% homology. The two inhibitors differed in sequence by only five amino acid replacements, Asp-3 to Arg; Tyr-17 to Arg; Leu-25 to Arg; Gln-32 to Glu; and Arg-52 to His, in the 57 residue peptide chain. Comparing the amino acid sequences of these two cobra venom inhibitors with those of Russell's viper venom inhibitor II and bovine pancreatic trypsin inhibitor (BPTI), about 50% homology was found in their sequences. The 6 half-cystinyl residues of these inhibitors were in the same linear positions. Moreover, the regions which are structurally and functionally important in the well-known BPTI molecule were found with extremely high sequence homology in the cobra venom inhibitors. These findings strongly suggest that the cobra venom inhibitors as well as Russell's viper inhibitor II have very similar conformations to that established for BPTI.