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Biomedical subjects

A O Williams

Publications and source records attributed to A O Williams.

At least 19 recordsLinked to original sources

Pathology of spontaneous and oncogene transformed rat liver epithelial cells and derived tumours in nude mice.

The histological and ultrastructural features of oncogene transformed rat liver epithelial (RLE) cells in culture and spontaneously transformed RLE cells were studied. The tumours produced in nude mice by all the transformed cells were either moderately well differentiated carcinomas or sarcomatous tumours. Epithelial tumours were produced in the RLE cells after transduction of both v-raf and v-myc oncogenes whereas sarcomatous tumours were produced after transduction of v-raf alone. These data suggested that transformation of RLE cells with a single oncogene, v-raf, produced malignant tumours which were consistent with sarcomas while a combination of two oncogenes, v-raf and v-myc, produced an epithelial tumour, consistent with a carcinoma. The effects of these oncogenes on RLE cells indicate that they were able to differentiate and were capable of producing two morphologically distinct tumour types. The possible role of v-myc in switching the sarcomatous lineage to an epithelial tumour lineage is considered to be significant and worthy of further studies. The epithelial tumour produced in RLE cells by combination of v-raf and v-myc is consistent with an embryonal type of hepatoblastoma. The trabecular type of liver cell carcinoma which resulted from spontaneous transformation of RLE cells illustrates the inherent potential of the RLE cell to undergo malignant change and strongly suggests that the RLE cells may be the precursor cells in the development of hepatocellular carcinoma in the rat.

Animals

Leishmaniasis in a domestic goat in Kenya.

The pathological and electron-microscopic features of the first case of autochthonous leishmaniasis affecting a domestic goat in Kenya are described. They are similar to what have been described in man and other animals. Using a short amino-acid sequence common to all the species of leishmania as primers for kDNA synthesis, the intervening sequence of 120 bases was amplified in the goat's tissues by polymerase chain reaction (PCR). The leishmania kinetoplast DNA sequence was detected in all the different infected tissues of the goat examined. The sensitivity and specificity of this assay are discussed. The result of the assay used was consistent with the parasite being either L. major or L. aethiopica as the infecting agent. The isoenzyme studies were consistent with L. aethiopica as the strain responsible for this goat's infection. The control of leishmaniasis and its vector must take into account the potential role of animal reservoirs in the environment. Even though Kenya and other East African countries are endemic for kala-azar, the presence of kala-azar in goats is of considerable veterinary public health importance in Africa. Efforts must not be spared to identify and detect other possible animal reservoirs in the subregion. Using DNA amplification techniques, which are sensitive and specific, such as the one described in this paper, sera and other biological fluids and tissues from different animal species should be utilized for detecting additional reservoirs for leishmania parasites particularly in known endemic areas of the world.

Animals

Dimethylnitrosamine metabolism: I. In vitro activation of dimethylnitrosamine to mutagenic substance(s) by hepatic and renal tissues from three inbred strains of mice.

The potential of hepatic and renal homogenates from three inbred strains of mice (BALB/c, C57BL and DBA) to activate dimethylnitrosamine (DMN) was investigated. Microsomal enzyme (S-9) preparations of liver and kidney from mature and immature mice were used in the Ames Salmonella mutagenicity assay. No age or sex-related differences in the formation of active mutagenic DMN Metabolites by liver microsomal enzymes were observed within any of the three inbred strains. In contrast, mature male kidney S-9 fractions from all three strains had a significantly greater potential to activate DMN than mature female and immature animals. Testosterone treatment resulted in no apparent changes in the ability of hepatic tissue to biotransform DMN to its mutagenic metabolites among age and sex classes. However, after testosterone treatment, renal microsomal fractions from mature female mice of all three strains did not differ significantly from their male counterparts in their ability to transform DMN to mutagenic metabolites.

Age Factors

Dimethylnitrosamine metabolism: II. In vitro activation of dimethylnitrosamine by hepatic and renal tissues from crosses among BALB/c, DBA and C57BL mice.

Crosses among BALB/c, C57BL and DBA mice were performed to investigate the genetic mechanisms involved in metabolism of DMN by renal and hepatic tissues. Liver S-9 fractions from parental strain DBA had the greatest potential to activate DMN and liver fractions from parental strain BALB/c had the lowest. No age or sex-related differences were observed within strain. Crossing of either C57BL or DBA to BALB/c mice resulted in F1 hybrids with liver microsomal enzymes that gave results similar to the BALB/c parental strain. There were no sex or age differences within crossbred strains in the potential of liver to activate DMN. In contrast male DBA and C57BL parental mice renal S-9 fractions did not differ significantly from each other but did differ significantly from male BALB/c renal fractions and from female and immature animals of all strains. Crossing of either DBA or C57BL mice with BALB/c mice resulted in male F1 hybrids whose renal S-9 fractions did not differ significantly from males of the parental BALB/c strain. In all instances, male renal S-9 fractions had a significantly greater potential to activate DMN than female or immature animals. F1 DBA X C57BL hybrids had renal S-9 fractions that did not differ significantly from the parental strains. These data suggest that the gene(s) for low DMN metabolism of BALB/c mice are apparently dominant over the genes from both DBA and C57BL. The exact genetic or physiological mechanism needs further elucidation.

Animals

Tardive dyskinesia in schizophrenics under 60 years of age.

Ninety-one schizophrenics (mean age 34 years) were examined for tardive dyskinesia (TD) during chronic neuroleptic treatment. Dyskinesia was found in 23 (25.3%). The only variable that showed an association with TD was the current doses of neuroleptics: in none of the TD patients did the dose of fluphenazine decanoate (or equivalent) exceed 45 mg/week, whereas it was higher in 23 of the 68 without TD (p less than 0.01). When these 23 "high-dose" patients were disregarded, the TD group differed significantly from the 45 dose-matched non-TD subjects in that it had more common anticholinergic drugs, more common parkinsonian symptoms, and less instances of good remission (p less than 0.05 in each case). There was no association between TD and other considered variables (drug history, age, sex, clinical characteristics, size of the lateral brain ventricles, neurological "soft" signs, cognitive impairment). The results illustrate a relationship between TD prevalence and current doses of neuroleptics and indicate that differences in doses between the groups with and without TD may obscure associations between dyskinesia and other factors.

Adult

The epidemiology of deliberate self-harm. The Ibadan experience.

In a 6-month prospective study of the three main general hospitals in Ibadan, Nigeria, 39 cases of deliberate self-harm were reported out of a total 23,859 subjects attending the sections of hospital studied. Thirty (76.9%) were under 30 years of age and 36 (86.3%) were under 34 years of age. The male to female ratio was 1.4.1: more than half of the population (51.3%) were students and 25.6%, manual workers. The methods used were mainly ingestion of chemicals (24 patients) and psychotropic drugs (11 patients). Disturbed interpersonal relationships, especially with parents, were mainly found to have motivated the acts. The implications of these findings are discussed.

Adult

Recent developments in the care, treatment, and rehabilitation of the chronic mentally ill in Nigeria.

Nigeria, with a population estimated at 80 million, has fewer than 100 psychiatrists and psychologists and only 20 psychiatric facilities. Most chronic mental patients are cared for by their relatives, by traditional healers, or by religious healers affiliated with the new Christian churches, which have proliferated in recent years. Lack of organized social welfare services makes the family the only consistent source of social support for the mentally ill; patients who lose contact with their families often become homeless wanderers. Although the majority of the mentally ill in Nigeria are cared for outside the mental health system, recent developments, such as the establishment of mobile clinics and village-based psychiatric units, show great potential for advancing the treatment of chronic mental illness in Nigeria.

Chronic Disease

Schizophrenia with good and poor outcome. I: Early clinical features, response to neuroleptics and signs of organic dysfunction.

Seventy-seven patients with diagnosis of schizophrenia (62) or schizoaffective disorder (15) were studied 2-20 years since onset of illness, when in a stable condition. The investigation included clinical assessment, measurement of plasma concentrations of neuroleptics and prolactin, computed tomography brain scan, neuropsychological and neurological examination. Outcome of illness was classified according to the presence of chronic psychiatric symptoms and social impairment, and response to neuroleptics according to the effect of treatment in the most recent psychotic episode. Neither outcome nor response to neuroleptics was related to duration of illness. The groups with good and poor outcome differed in premorbid adjustment, age at onset and symptoms of the initial episode, but not in drug bio-availability or prolactin response. Large cerebral ventricles and cognitive impairment, but not neurological 'soft' signs, were associated with unfavourable outcome. The three measures of organicity were not inter-related. No clinical differences were found between chronic patients with and without signs of organic dysfunction. The findings suggest that schizophrenia with good and unfavourable outcome may be separate sub-types. However, the role of organic factors in the latter group remains unclear.

Adult

Schizophrenia with good and poor outcome. II: Cerebral ventricular size and its clinical significance.

Computer tomography brain scans were carried out on 40 patients with schizophrenia or schizo-affective disorder of 2-20 years duration. Ventricular-brain ratio (VBR) was significantly greater than that of the control group. In six patients the VBR exceeded the control mean + 2 s.d. Among the 13 whose VBR was more than 1 s.d. above the control mean, none had schizo-affective disorder, all but one had chronic illness, and patients with negative symptoms and those with premorbid schizoid traits were over-represented. VBR was unrelated to medical history, age, duration of illness, or neuroleptic treatment. It was not associated with neurological 'soft' signs or cognitive deficit. Among chronic patients, clinical features showed no association with ventricular size. The findings suggest that large ventricles may be related to a sub-type of chronic schizophrenia rather than to its particular clinical features.

Adult

Schizophrenia with good and poor outcome. III: Neurological 'soft' signs, cognitive impairment and their clinical significance.

Fifty-six patients with RDC schizophrenia (42) or schizoaffective disorder (14), of two to 20 years' duration, were assessed for neurological 'soft' signs and cognitive impairment when in a stable condition--the 'outcome'. Neurological dysfunction (46% of 50 examined patients) was associated with a history of developmental abnormalities, but was unrelated to outcome, psychiatric symptoms, or treatment. Deficits in particular cognitive fields were related to two independent factors: overall severity of residual psychiatric disorder (outcome) and neurological dysfunction. There was no relationship between the size of the lateral brain ventricles on CT scan and either 'soft' signs or cognitive impairment. The findings do not provide evidence for an association between the presence of organic brain disorder (as indicated by the joint occurrence of neurological dysfunction and cognitive impairment) and either poor outcome or particular symptoms of schizophrenia.

Adult

Cancer of the prostate and aging: an autopsy study in black men from Washington, DC, and selected African cities.

Age-related changes of arteries, veins, glands, and stroma in the prostate of black men from Washington, DC, and from Ibadan, Nigeria, and Accra, Ghana, West AFrica, were studied in a total of 795 consecutive, unselected prostate specimens removed at autopsy during a 7-year period (1973-1980). Except for age group 80 and over, aging changes in the prostate were more severe in all age groups in black men from Washington, DC, than in black men from Ibadan and Accra (P less than 0.01). However, when the intensity of age-dependent alterations was compared in either US or African black men with carcinoma and with no carcinoma, no significant differences were found. These findings do not support the idea that the aging process per se increases susceptibility to cancer.

Adult

Blood hormone profiles in prostate cancer patients in high-risk and low-risk populations.

Epidemiologic data reveal that the incidence rate of prostate gland carcinoma among the black population in the United States (US) is several times higher than among Nigerians. A collaborative study between the two countries was undertaken, and blood hormone (testosterone [T], dihydrotestosterone [DHT], estrone [E1], estradiol [E2], and prolactin [P1]), total acid phosphatase (TP), and prostatic acid phosphatase (PAP) profiles in the two population groups were compared. In the US groups (patients and controls) there were significantly higher levels of T (P less than 0.01) and E1 (P less than 0.05) compared with the Nigerians. Also, the US patients had significantly higher levels of T (P less than 0.05) and E1 (P less than 0.01) compared with their matched controls. In the Nigerians T but not E1 levels were significantly lower (P less than 0.05) in patients compared with controls. DHT, E2, and P1 were not significantly different in patients and controls between and within the populations. Nigerian patients had higher levels (P less than 0.001) of TP and PAP compared with US patients. It is concluded that differences in blood hormone profiles in the two population groups are based on factors other than the genetic makeup of the populations.

Acid Phosphatase

Extrahepatic portal hypertension due to congenital obstruction of the portal vein and associated gross hepatic lobulation.

A 10-233k old girl presented with splenomegaly and recurrent hematemesis from esophageal varices. Splenoportography revealed a dilated extrahepatic portion of the portal vein with nonvisualization of its intrahepatic tributaries. The child died following an episode of hematemesis and was found to have a dilated portal vein which ended blindly. In addition, there was abnormal lobulation of the inferior surface of the liver which was not cirrhotic. The portal vascular anomaly, which presumably was responsible for the portal hypertension, was probably due to failure of communication between the embryonic vitelline veins or to atresia of the portal vein secondary to pressure from the abnormal hepatic lobulation in utero. It would appear that congenital factors may be significant in the etiology and pathogenesis of some cases of extrahepatic portal hypertension in early life and recognition of such developmental anomalies is of importantance in management.

Female

Jaundice associated with lobar pneumonia. A clinical, laboratory and histological study.

Twenty-eight patients with jaundice associated with lobar pneumonia have been studied. The epidemiological and clinical features were compared with 70 patients with lobar pneumonia without jaundice. Jaundice was associated with a predominance of males, a high incidence of right lower lobe consolidation and hepatic tenderness. Although the jaundiced patients remained pyrexial for longer it was not associated with a poor prognosis. There was no evidence of immunological deficiency although pneumococcal polysaccharide antigenaemia was commoner in jaundiced patients. Laboratory investigations showed evidence of haemolysis in the majority of jaundiced patients and the cause of this was found to be G6PD deficiency. Starch-yel electrophoresis demonstrated that the phenotype was A- in deficient patients. Hepatic function tests were unhelpful. Light and electron microscopical changes consistent with haemolysis were present in liver biopsies from G6PD deficient patients although hepatocellular damage and cholestasis were also present.

Adolescent