Inhibition of human benzylamine oxidase (BzAO) by analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

A sensitive assay for human plasma BzAO, involving the conversion of 14C-benzylamine to 14C-benzaldehyde, was developed. MPTP and several of its analogues were found to be competitive inhibitors of the enzyme. Ki values for the MPTP analogues in the presence of human plasma BzAO were determined. The analogues had a different rank order of inhibition of human plasma BzAO compared with the rank order of inhibition of bovine plasma BzAO found previously. MPTP and 1-methyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP), which are potent nigrostriatal toxins, were weak inhibitors of human plasma BzAO.     

Suppression of canine antral gastrin secretion by urine

Distention of the gastric antrum with an alkaline fluid normally results in the secretion of gastrin. Following gastrocystoplasty in humans, however, hypergastrinemia has not been observed. We explored the possibility that a component of urine may suppress antral gastrin activity in the dog. Partial cystectomy and antral transposition to the bladder (ATB) was performed in five animals and antral transposition to the colon (ATC) was performed in five other dogs to serve as a hypergastrinemic controls. At four and eight weeks after surgery the mean serum gastrin levels in the ATC dogs were significantly greater than the mean preoperative levels (p less than 0.05). In contrast, at four and eight weeks after surgery the mean serum gastrin levels in the ATB animals were significantly less than the mean preoperative levels (p less than 0.05). The antral G-cell density as determined by immunohistochemical study at eight weeks after surgery was greater than normal in the ATC dogs but less than normal in the ATB dogs; but the differences did not achieve statistical significance. In another series of experiments using four other dogs a 4% aqueous peptone solution and a 4% peptone solution in concentrated dog urine were instilled into exteriorized antral pouches. The mean serum gastrin levels at 60 and 90 minutes after instillation of the former were significantly increased (p less than 0.05), but there was little or no change after instillation of the latter. Urine, or a component of urine, appears to suppress canine antral gastrin secretion and may explain the absence of hypergastrinemia following gastrocystoplasty in humans.     

Inefficient delivery of yeast cells as an explanation for reduced plating efficiency of Candida albicans.

The plating efficiency for fungal yeast cells is usually less than that expected from microscopic counts, and a number of explanations for this phenomenon have been proposed. The present study was undertaken to explore possible reasons for reduced plating efficiency of Candida albicans. Explanations that we evaluated and found unlikely included: ineffectiveness of different culture media and/or incubation temperatures for growing colonies, insufficient area of the plate available for expression of individual colonies, production of microcolonies, and inaccurate counting of the organisms in the inoculum. An assay for delivery of the inoculum into tissue culture plate wells indicated that reduced delivery of the organisms accounted for lower than expected plating efficiency. C. albicans yeast cells grown under low glucose conditions and expected to have reduced adhesiveness were found to have higher values for both delivery and plating efficiency in our assays. In summary, our results indicate that reduced plating efficiency for C. albicans under the conditions used for these experiments is best explained by the loss of some yeast cells during preparation of the inocula or delivery of the yeast cells onto the plates.     

Fasciolopslasis--a re-emerging infection in Azamgarh (Uttar Pradesh)

Fasciolopsiasis is endemic in the far east. In India, there have been a few reports of the infection, prior to the 1990's. We report two cases from Azamgarh district of Uttar Pradesh. Both the cases were from nearby villages where water chestnuts are cultivated. These may be a source of infection. Pigs are commonly observed in these areas and and may be the source of ova. The only missing link is the finding of infected snails. Presence of at least three cases (one reported earlier) in the area indicates the potential for the infection to re-emerge. Further epidemiological studies are needed to analyse the various ecological factors of transmission. Fasciolopsiasis is endemic in China, Taiwan, Vietnam and Thailand. In India, (Fascilopsis buski) infections in man have been reported earlier from Assam, Maharashtra, Tamil Nadu and parts of Uttar Pradesh. However, to the best of our knowledge, no such reports have been made since 1990's. We herewith report two recent cases from district Azamgarh, Uttar Pradesh (U.P.), India. Factors, such as cultivation of water chestnuts, presence of snails as intermediate hosts and pigs as definitive host in this geographical area seem to be suggestive of an endemic focus and thus needs further epidemiological survey for preventive and control measures, at the earliest.     

Enteric pathogens and their isolation at a cancer hospital in Pakistan

Diarrhoeal diseases remain a major cause of mortality and morbidity in developing countries. However, due to lack of funds, supply problems and some inexperience, some laboratories have difficulty identifying a causative agent in stool samples. In the year following the opening of the Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Pakistan, the microbiology department had not isolated a single enteric pathogen. From January 1996, new culture techniques were introduced, with a resulting increase (10%) in identification of these pathogens. In addition, the introduction of formol-ether concentration made a significant contribution to the number of intestinal parasites seen. This report demonstrates how simple microbiology methods made a difference to the running of the department and, ultimately, to the patients.     

The GAA triplet-repeat sequence in Friedreich ataxia shows a high level of somatic instability in vivo,with a significant predilection for large contractions

Friedreich ataxia is commonly caused by large expansions of a GAA triplet-repeat (GAA-TR) sequence in the first intron of the FRDA gene. We used small-pool PCR to analyze somatic variability among 7190 individual FRDA molecules from peripheral blood DNA of subjects carrying 12 different expanded alleles, ranging in size from 241 to 1105 triplets. Expanded alleles showed a length-dependent increase in somatic variability, with mutation loads ranging from 47% to 78%. We noted a strong contraction bias among long alleles (>500 triplets), which showed a 4-fold higher frequency of large contractions versus expansions. Some contractions were very large; of all somatic mutations scored, approximately 5% involved contractions of >50% of the original allele length, and 0.29% involved complete reversion to the normal/premutation length (< or =60 triplets). These observations contrast sharply with the strong expansion bias seen in expanded CTG triplet repeats in myotonic dystrophy. No somatic variability was detected in >6000 individual FRDA molecules analyzed from 15 normal alleles (8-25 triplets). A premutation allele with 44 uninterrupted GAA repeats was found to be unstable, ranging in size from 6 to 113 triplets, thus establishing the threshold for somatic instability between 26 and 44 GAA triplets. Analysis of an additional 7850 FRDA molecules from serially passaged lymphoblastoid cell lines carrying nine expanded alleles (132-933 triplets) showed very low mutation loads, ranging from 0% to 6.2%. Our data indicate that expanded GAA-TR alleles in Friedreich ataxia are highly mutable and have a natural tendency to contract in vivo, and that these properties depend on multiple factors, including DNA sequence, triplet-repeat length and unknown cell-type-specific factors.     

Management of Isolated Blunt Duodenal Injury

Five cases of duodenal injuries were treated in our hospital between January 1, 1975 and June 18, 1979. They belonged to the Class II and early Class III of duodenal injuries. They were treated with simple closure of the perforation in a single or double layer with external drainage. Only in one case were gastrojejunostomy and bilateral vagotomy added because the patient had a history of ulcer disease. The delay in operative treatment ranged between five and 48 hours. All responded well to the surgical treatment. In the instance of the longest operative delay, a purulent drainage occurred and it responded promptly to a selective antibiotic therapy. The average hospitalization stay was nine days for the patients operated upon early, whereas it was 15 days for the two delayed cases. No mortality was recorded.     

Effects of topical administration of levocabastine on psychomotor and cognitive function.

The possible central nervous system effects of topical administration of levocabastine, a new H1-antagonist, were investigated in a double-blind, placebo-controlled, crossover study using a battery of objective and subjective tests. These were carried out in 12 volunteers up to five hours postapplication. Neither the recommended (0.5 mg/mL) nor the four times higher (2.0 mg/mL) concentration level was found to be distinguishable from placebo, while the verum (triprolidine 10 mg) was significantly worse, on both objective and subjective measures.     

Protease of adenovirus type 2: partial characterization.

An adenovirus-associated protease activity specific for the cleavage of core polypeptide PVII to polypeptide VII was identified and its properties were studied using an in vitro assay system. All temperature-sensitive (ts) mutants examined failed to induce protease activity at 39°. Activity was restored in revertants. The protease activity was completely inhibited by 1 mM tosylamide phenylethylchloromethyl ketone while phenylmethylsulfonylfluoride and tosyl-lysinechloromethyl ketone at 1 mM reduced enzyme activity to 36 and 10% of control, respectively. By contrast ethylenediamine tetraacetic acid had no effect. Optimum enzyme activity was observed at neutral pH. Enzyme activity was stable up to, but not beyond, 45°. Polypeptide PVII was cleaved whether it was in the soluble form, bound form, heat-, or acid-precipitated form. Wild-type young virions contain endogenous protease activity while the virions produced at 39° by tsl-infected cells do not. The PVII contained in these tsl-39 virions, however, may be processed by exogenous WT enzyme after the particles have been frozen-thawed several times. These results suggest that the adenovirus-associated protease is a chymotrypsin-like, nonmetalo, neutral protease.