Resealing of protein tyrosine kinase substrates into human erythrocytes by rapid freezing and thawing in liquid nitrogen.
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Biomedical subjects
Publications and source records attributed to C Isaacson.
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The renal histopathology of essential malignant phase hypertension in two groups of black South Africans was studied. The first, an autopsy series, consisted of material obtained in 1956-1961, a period when adequate antihypertensive therapy had not yet become generally available. The second group, a renal biopsy series, was from an era when effective antihypertensive therapy was available (1979-1989). The study showed that the clinical and histopathological changes of malignant hypertension were similar in both the pre-treatment and treatment eras. Fibrinoid necrosis was found in 92% of the autopsy sections and 44% of the biopsies. While mucinous, onion-skin and fibrotic changes of the blood vessels were commonly found, they were not invariably present and could not be considered the histopathological hallmark of malignant nephrosclerosis. It was often impossible on histological examination to distinguish malignant nephrosclerosis arising de novo from that superimposed on long-standing previous benign hypertension. Replication of internal elastic lamina, which has been considered a marker of long-standing previous benign hypertension, was a nonspecific finding and was frequently observed in young hypertensive subjects with a short clinical history. When fibrinoid necrosis is present, diagnosis of malignant nephrosclerosis can be made with confidence in black South Africans.
The nucleotide sequence of the mRNA that codes for Fab fragments from two chimpanzee monoclonal antibodies has been determined. Both antibodies have high affinity and good specificity for digoxin. Four domains from the two antibodies have been sequenced: the constant domains of the kappa and lambda light chains, the variable domain of the lambda light chain, and the CH1 domain of the IgG1 heavy chain. There are very few differences between the chimpanzee and human sequences; the nucleotide sequences differ by less than 2%.
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Autopsy material was examined from cases diagnosed as malignant nephrosclerosis in the years 1956-1961, a period when adequate antihypertensive therapy had not yet become available, a second group of malignant nephrosclerosis from the years 1970-1980, an era during which effective antihypertensive therapy was available, and a third group of essential benign nephrosclerosis, once more from the early pretreatment period (1956-1961). The observations suggest that malignant and benign hypertension may be two different diseases. Further studies will be pursued to assess whether hypertensive renal changes seen in this study are a spectrum of one disease extending from malignant nephrosclerosis de novo presenting with acute renal failure or chronic renal failure to benign hypertensive nephrosclerosis.
Liver cell dysplasia (LCD) has been recognised for many years in association with hepatocellular carcinoma (HCC). The presence of LCD relates to cirrhosis, particularly macronodular, as well as HBsAg positivity in many countries. These relationships have not previously been recognised in southern Africa. This study of LCD in 160 rural and urban black patients with proven HCC records a significant difference between the prevalence of dysplasia in rural HBsAg-positive and -negative cases: 75.6% in HBsAg+ individuals vs. 29.4% of those negative for HBsAg (P less than 0.01). Furthermore a significant relationship is reported between dysplasia and macronodular cirrhosis, LCD being observed in 62.9% of those with macronodular cirrhosis vs. 29.5% of non-cirrhotics (P less than 0.001). In addition there was evidence for a relationship between severity of dysplasia and domicile (rural greater than urban), age (being more extensive in younger patients), and ongoing viral replication (82.3% of patients showing the highest grade of dysplasia were found to be serum HBeAg+ and/or tissue HBcAg+ cf. 3.7% with absent or low-grade dysplasia). It is apparent that in southern Africa the presence of dysplasia in HBsAg+ individuals implies that HCC should be actively excluded in these patients and that they should thereafter be carefully monitored for the development of a tumour.
Human monoclonal antibodies, owing to their decreased immunogenicity, are expected to be an improvement over mouse monoclonal antibodies for in vivo therapy. Human and primate monoclonal antibodies are best produced with a human x mouse heteromyeloma. Several human chromosomes are stable in the human x (human x mouse) hybrids. Chimpanzee anti-digoxin monoclonal antibodies were prepared and characterized. Because they are structurally very similar to human antibodies, they should be well tolerated in humans. The anti-digoxin antibodies can be used for therapy of extreme overdoses or as an in vivo diagnostic tool for slight overdoses. Because the advantage of using human monoclonal antibodies is their lack of immunogenicity, preparation of the antibody must be scrupulous so as not to introduce extraneous immunogens. Analysis to ensure the purity of the preparation can be complicated by the presence of high concentrations of the antibody and the low levels of contamination that must be detected. We describe a Western blot assay for Protein A that is sensitive even in the presence of human IgG.
Cavitation is a most unusual radiological feature of Pneumocystis carinii pneumonia (PCP). Autopsy evidence of cavities in PCP is poorly documented. We describe a case of fatal PCP occurring in a patient with the acquired immune deficiency syndrome; the PCP was associated with radiological as well as autopsy evidence of large intrapulmonary cavities. These cavities are ascribed to Pneumocystis carinii infection, since other possible causes were excluded.
Malignant melanoma is common among the whites of South Africa. In the black population, the tumor is much less frequent and occurs predominantly on the lower limb--particularly the sole of the foot. This study brings to light the anomalous situation that among the Eur-African-Malay population (those of mixed ancestry), malignant melanoma has probably the lowest incidence in the world.
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Oesophageal specimens derived from 70 patients with established invasive squamous cell carcinoma of the oesophagus were histologically reviewed with special reference to the morphological manifestations of human papillomavirus (HPV) infection. Epithelial changes fulfilling the criteria for HPV infection were noted in 23 cases (33%). The presence of HPV antigens was demonstrated by immunohistochemical staining in 7 of these 23 cases. Although acceptable for routine diagnostic purposes, histological typing and immunoperoxidase staining methods are not entirely conclusive of HPV infection. Electron microscopy for detection of viral particles and a molecular hybridization technique have to be used for absolute confirmation and viral subtyping. The results of this pilot study will be used for prospective studies to determine the role of HPV infection in the aetiology of oesophageal carcinoma.
While prostatic cancer has a low frequency in rural African black men living traditionally, the disease occurs more often and is increasing in black men in the cities. Between 1982 and 1984, 101 patients with prostatic cancer were detected in Soweto, Johannesburg. Of these patients 90 had clinical stage D disease and metastasis was common. The 50 per cent mortality period of 1.6 years, while similar to that reported in some series of white patients, is considerably shorter than that noted in several others series.
Skin-lightening preparations containing hydroquinone are used extensively by black South Africans. In some instances these preparations produce severe and irreversible cutaneous damage. Clinically, the deleterious effects begin with darkening and coarsening of the skin, followed by a hyperpigmented papular condition. Histologically, there is increased basophilia of the collagen, followed by the formation of yellow fibers. These yellow fibers swell and break down to form an amorphous eosinophilic material. Electron microscopy shows that the changes arise from a breakdown of normal collagen.
A patient is presented with primary choriocarcinoma of the fallopian tube arising from a tubal pregnancy. Treatment consisted of an initial operation including adnexectomy and resection of bilateral ovarian thecalutein cysts, followed by chemotherapy. The patient delivered a healthy infant 2 years later, and is alive and well 5 years after the event.
Oesophagi of black children dying from a variety of diseases examined at autopsy showed features of chronic oesophagitis and atypical basal cell hyperplasia in a significant percentage of cases. The possible significance of this finding in relation to carcinoma of the oesophagus is discussed.
Elastosis is common in infiltrating ductal and lobular carcinomas of the breast, occurring in approximately 90% of cases. It is also well described in some benign lesions of the breast and tumours of the salivary gland. Reports of venous elastosis in association with large-bowel carcinomas are rare. We describe elastosis in single cases of prostatic, gastric, bronchiolar-alveolar and cervical carcinoma.
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Familial (hereditary) hollow visceral myopathy is a rare cause of chronic intestinal pseudo-obstruction. Fourteen black patients with the disease, 6 males and 8 females, are described. The earliest morphological lesion is an isolated smooth-muscle degeneration of the muscularis propria of the bowel, especially the colon. The pathological changes are lysis and disappearance of the muscularis propria of the bowel wall, leading to dilatation and intra-luminal stasis. progressive involvement results in large areas of defective muscularis propria. The occasional occurrence of mesenteric arteries showing medial muscular fibrosis supports the concept of a generalized primary smooth-muscle myopathy.