Biomedical subjects
Publications and source records attributed to A Kane.
We reported four cases of Takayasu's arteritis cases. Hypertension in only one arm was found in three of them. The other one were a reversed coarctation of the aorta. Diagnosis was made by clinical examination, vascular Doppler Echography, and, in one case, arteriography. Thus, were examined the etiology of this disease, it might probably due to tuberculosis, the outcome and therapy problems at the occlusive stage.
We reported six patients with Marfan's syndrome, studied retrospectively from May 1990 to April 1992 in the department of Cardiology in Dakar. Morphological, cardiovascular, skeletal and ocular abnormalities have been reviewed. All the patients had been evaluated by echocardiography. Prevalence of Marfan's syndrome among congenital heart diseases during this period was 4.8%. The mean age was 27.6 years. The mean height was 1.80 m (range 1.38-2.02 m) for a mean weight of 62.8 kg. All the patients had dolichostenomely and arachnodactyly. Kyphosis or scoliosis was present in 5 cases. Chest deformities (pectus carinatum and excavatum) were present in 5 cases. 5 patients had hyperextensible joints. 5 patients had ocular abnormalities. Cardiac pathology was found in 5: mitral prolapse with insufficiency in 2; mitral prolapse with aortic dystrophy in 2; and isolated dilatation of ascending aorta in an other. One patient with diffuse Marfan's syndrome died of cardiac failure. Our study confirm polymorphic manifestations of Marfan's syndrome and the frequency of cardiac abnormalities which are the major determinants of life-prognosis in these patients. Echocardiography is very useful as a noninvasive method for defining the extent of cardiovascular involvement and following its course, for more appropriate treatment.
Ochratoxin A (OTA) is a mycotoxin which has been implicated in Balkan endemic nephropathy, a disease characterized by a high incidence of urinary tract tumors. It induces DNA single-strand breaks and has been shown to be carcinogenic in two rodent species. For a better understanding of the OTA genotoxic effect, OTA-DNA adduct formation and disappearance has been measured using the 32P-post-labelling method after oral administration of 2.5 mg/kg of OTA to mice. In kidney, liver and spleen, several modified nucleotides were clearly detected in DNA, 24 h after administration of OTA, but their level varied significantly in a tissue and time dependent manner over a 16-day period. Total DNA adducts reached a maximum at 48 h when 103, 42 and 2.2 adducts per 10(9) nucleotides were found respectively in kidney, liver and spleen, indicating that kidney is the main target of the genotoxicity and likely carcinogenicity of OTA. The major adduct differed between kidney and liver. All adducts disappeared in liver and spleen 5 days after compound administration, whereas some adducts persisted for at least 16 days in the kidney. Some adducts were organ specific. The finding that the adducts are not quantitatively and qualitatively the same in the three organs examined is likely due to differences of metabolism in these organs, leading to different ultimate carcinogens and may also result from differences in the efficiency of repair processes.
Cell fusing agent (CFA) is an RNA virus originally isolated from a line of Aedes aegypti mosquito cells. Although our characterization of the virus many years ago showed that it resembled the flaviviruses, there was no detectable serological cross-reaction with members of the genus flavivirus. Furthermore, unlike the well-studied members of the genus flavivirus, CFA did not replicate in any of several vertebrate cell lines tested. We have now determined the nucleotide sequence of the CFA genome. Comparison of the predicted amino acid sequence of the CFA polyprotein with viral protein sequences in Genbank, has made it apparent that CFA should now be assigned to the family Flaviviridae, genus flavivirus. The homology between CFA proteins and those of other flaviviruses was highest for NS5 (45%) and NS3 (34%). Little homology was found for the structural proteins. Thus, CFA is only distantly related to the other flaviviruses for which there is sequence information; nevertheless, with respect to their hydrophobicity plots, the CFA polyprotein and the polyproteins of other flaviviruses are remarkably similar. We suggest that CFA is an insect virus, which was present in the embryos from which the Ae. aegypti cell line was established. Thus, CFA seems to be the first member of the family Flaviviridae, genus flavivirus, to be identified as an insect virus.
The authors report a rare observation of left intraventricular thrombus in a 39 years old senegalese man with a dilated non-obstructive cardiomyopathy. With the echocardiographic follow-up, it was possible to follow the regression of the clot. Echocardiographic diagnosis and evolutive problems of such left intraventricular thrombus are reviewed.
The authors report five cases of mycetomas with an original localization, cranio-encephalic and vertebro medullary. Four times it concerned a dorsal or cervical mycetoma with deep enlargement responsible for compression of the spinal cord. In the 5th case, scalp infection reached the dura mater. All patients have got histopathological diagnosis. Therapeutic difficulties are evocated about these singular localizations in a pathology for which greater amputation stands as the rule.
When our stock of standard Sindbis virus (SVSTD) is assayed by plaque formation on Aedes albopictus mosquito cells, about 1-2% of the plaques appear much clearer and sharper than the majority of the plaques. One of these clear plaques was picked, grown into a viral stock (SVCP), and used to prepare viral cDNA. Making use of the infectious Sindbis virus plasmid, Toto 1101 (Rice et al., 1987), we mapped the causal mutation for the clear plaque phenotype to a region between nt 7334 and 7716, and by sequencing of the viral RNA identified a mutation at nucleotide 7592. This mutation lies in the junction region of the viral genome, specifically at nucleotide -6, with reference to the initiation site for 26 S RNA synthesis. In SVCP-infected mosquito cells, but not in SVCP-infected chick cells, the ratio of subgenomic 26 S to 49 S (genomic) RNA synthesis was decreased relative to that observed in SVSTD infected cells. In terms of amino acid coding, the SVCP mutation is silent.
A retrospective study covering 1984-88 showed that urogenital diseases were the third most frequent cause of death in Senegal. The purpose of our study was to see whether ochratoxin A is involved in the etiology of these nephropathies. A total of 166 samples of eight principal types of food and feed consumed in this country were obtained randomly at markets in Dakar and Kaolack and analysed for ochratoxin A using the method of analysis of the Association of Official Analytical Chemists. Only cowpea (Vigna unguiculata), from a legume widely distributed in Senegal, was contaminated (16% of samples), at an average level of 34 micrograms/kg. All other samples were free of ochratoxin A, indicating that it is not directly correlated with the renal diseases observed. Aflatoxin B1 was detected in almost all of the samples, and a competition between moulds producing the two toxins is suggested.
Bloodless laparotomy (BL) is defined as an opened exploration of the abdominal cavity that yields negative results, i.e., "provides no information as to the cause of the clinical and paraclinical symptoms responsible for prompting the surgical investigation". The authors report a retrospective study spanning January 1975 to December 1989, on the incidence of and mortality associated with emergent BL in patients with acute abdominal syndrome, with the intent of reducing its frequency. Over this period, 24 BL occurred in 3480 emergent laparotomies, i.e., 0.63%. These involved 7 men, 5 women, 5 boys and 7 girls, aged 4 to 52 years (mean age = 19.5 years). Indications for surgery were based on clinical signs, as well as on laboratory findings such as chest X-ray and plain radiography and needle-puncture of the abdomen. Surgical data indicated:liver cirrhosis--3 cases; mesenteric adenopathy--3 cases; intestinal parasitosis--1 case; bilateral adnescitis--1 case; polycystic ovaries--1 case; wall abscess--1 case; unexplained pain--14 cases. The mortality rate was 2/24. Use of other paraclinical investigations, namely ultrasonography, laparoscopy and peritoneal lavage, and of computer science methods after a prior clinical examination initiated by history-taking, might help reduce the rate of BLs, which are non-devoid of mortality.
The iatrogenic aetiology of urethral stricture appears to be increasing in frequency. Transurethral catheterization and endourethral manipulation are the principal aetiologic factors. Prevention is based essentially upon a greater respect of the urethra when an endoscopic exploration is necessary and the use of suprapubic catheterization whenever bladder drainage is necessary.
A case of systemic sclerodermy mainly affecting the lungs is presented. For a long time the diagnostic was incorrect. The case is all the more interesting since the patient had worked in iron mines and unproved pneumoconiosis had been diagnosed. Treatment basically with corticotherapy and oxygenotherapy, with D-penicillamine added, produced a satisfactory outcome to the attack and definite improvements in the cutaneous lesions.
Ochratoxin B (OTB), the dechloro-analogue of ochratoxin A (OTA), was studied separately and in combination with OTA on the aminoacylation of phenylalanine tRNA (tRNAPhe) catalysed by mice liver phenylalanyl-tRNA synthetase. OTB was neither a significant inhibitor of the reaction nor an antagonist of OTA. OTB was also assayed for its possible antagonistic effect on the in vivo protein synthesis inhibition caused by OTA in hepatoma tissue culture cells. No prevention of OTA inhibition could be found for OTB. It rather showed a slight additional inhibitory activity when mixed (100-180 microM) with low concentrations of OTA (40-60 microM). In conclusion, these results are not in favor of an antagonistic effect of OTB with respect to OTA action, at least on the level of cellular protein synthesis.
The distribution and elimination of [3H]ochratoxin A (OTA) from stomach content and tissue, intestine content and tissue, liver, bile, serum and urine of Swiss male mice which had received a single low dose of OTA by intubation was followed as a function of time. The profiles of radioactivity do not show a smooth decline after the absorption period, but an oscillating pattern with rapid declines followed by increases which favour the assumption of an enterohepatic circulation. Between 28% and 68% of conjugated OTA together with OTA cleavage products were found in bile giving evidence for biliary excretion of OTA and its metabolites in mice. When given i.m. to mice [3H]OTA is already found after 30 min in bile and intestine contents and its elimination patterns show several peaks confirming the biliary excretion and the enterohepatic circulation. Cholestyramine, which is known to prevent the enterohepatic circulation of drugs and toxins, changes the profile of elimination of OTA which no longer presents the cyclic pattern. This result is also in favour of an enterohepatic circulation of OTA. When phenylalanine is given together with OTA by oral gavage the toxicokinetics of the mycotoxin change completely in the different body fluids, in stomach and intestine content and tissues. Phenylalanine seems to facilitate the gastric absorption of OTA and the gastro-intestinal transit. It increases also its early excretion into urine and bile. However, its elimination pattern no longer shows the oscillating pattern. Thus phenylalanine seems to inhibit the intestinal reabsorption of OTA conjugates.
The activities of 5 enzymes in urine and renal tubules were measured after administration to male Wistar rats of small doses of ochratoxin A (145 micrograms/kg per day for 8-12 weeks, corresponding to 2 ppm in the feed) by intubation. These doses are in the range of natural contaminations found in food and feed. The enzymes examined were gamma-glutamyl transferase (gamma-GT), alkaline phosphatase (ALP), leucine aminopeptidase (LAP), lactate dehydrogenase (LDH), and N-acetyl-beta-D-glucosaminidase (NAG). The doses employed caused increased enzymuria and lower activities of tubular enzymes after 1 week of feeding. This suggests tubular injury. The change of the enzyme activities in the urine and in the tubules appeared in a cyclic way (degeneration and regeneration). Phenylalanine (20 ppm) partially prevented this action of ochratoxin A. The p-[14C]aminohippurate accumulation was inhibited by 60% in the second week but returned to almost normal level 6 weeks after the beginning of the treatment, suggesting an adaptation of the organism or a substitution of damaged cells.
Protein, RNA, and DNA synthesis, and enzyme (gamma GT, LDH, LAP, A1-P, NAG) activities were assayed in Madin Darby Canine Kidney cells (MDCK) treated by ochratoxin A, a mycotoxin known to be nephrotoxic in animal and man. Both cellular macromolecules syntheses and enzymatic activities are inhibited by OTA in a dose-dependent manner after 24 h incubation. The protection by 100 microM additional phenylalanine is optimal when MDCK cells were pretreated 4 h before the poisoning by OTA. When OTA 25 microM and phenylalanine 100 microM were added simultaneously the prevention of toxic effects is evident, but not complete in spite of the respective intracellular concentrations of OTA 2.22 microM and phenylalanine 2.4 microM which are normally not in favor of a strong inhibition by OTA, except if one admits that MDCK cells are really very sensitive to OTA.
The distribution of a single low dose of [3H]-ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [3H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased. After a 12-week feeding experiment, with doses of 288.8 micrograms/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA.
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Ochratoxin A, a natural contaminant of feed and food, has been shown to induce experimental liver and kidney tumours. In vitro experiments on mice spleen cells showed evidence of DNA single-strand breaks induced by ochratoxin A. We measured single-strand breaks in the DNA of spleen, liver and kidney of ochratoxin A-treated animals. Ochratoxin A induced DNA damage in vivo. This damage reversed with time. The appearance and extent of the damage varied in different tissues. Except for spleen our data correlate with the tumours induced by ochratoxin in mouse liver and kidney. With regard to the spleen, there has been no report to date of experimental leukemia induced by ochratoxin A. Thus our results indicate that this possibility has to be considered.