Biomedical subjects
Publications and source records attributed to H T Cook.
A case is described of a 25-year-old male who developed angiolymphoid hyperplasia with eosinophilia involving the tissue over the left parotid gland and subsequently involving the right lacrimal gland with proptosis. Treatment was by excision.
The authors have used a sensitive alkaline phosphatase-anti-alkaline-phosphatase immunohistochemical method to examine 28 human pulmonary carcinomas for the presence of renin. Immunoreactive renin was found in 23 (82%) cases. Specific staining was always associated with small vessels in the stroma of the tumor or in adjacent areas of inflamed fibrous tissue. Within vessels, renin was localized in the cytoplasm of medial cells. Adenocarcinoma exhibited the most consistent staining (11/12 cases), and this appeared to be independent of the degree of tumor differentiation. Immunoreactive renin was also detected in squamous cell (7/8 cases), undifferentiated large cell (4/4 cases), and small cell undifferentiated carcinoma (1/1 cases), but the number of vessels and intensity of staining were usually less than seen in adenocarcinoma. Staining was not found in the bronchioloalveolar variant of adenocarcinoma (0/3 cases). By means of immunoaffinity chromatography with monoclonal antibodies (MAbs) raised to kidney renin, both active and inactive renin were extracted from homogenates of surgical specimens. The molecular weight of both forms of renin was approximately 59,000 daltons.
Between January 1982 and May 1986 279 biopsy specimens from 82 patients with acquired immune deficiency syndrome (AIDS) were examined. A wide variety of infectious conditions were diagnosed, the commonest being Pneumocystis pneumonia (n = 36), cytomegalovirus (n = 21), a variety of fungi (n = 8), mycobacteria (n = 7). Kaposi's sarcoma was the commonest tumour (n = 40), and there were two cases of extranodal lymphoma. Striking features were the unusual sites of disease and the occasional paucity of organisms.
One hundred and twenty consecutive bronchoscopic examinations were carried out on 80 patients with acquired immune deficiency syndrome (AIDS) between January 1982 and December 1986. Ninety one paired biopsy and cytology specimens from 72 of these patients were analysed. There was no significant difference between biopsy and cytology in diagnosing Pneumocystis carinii pneumonia (0.95 greater than p greater than 0.1). In 10 cases P carinii pneumonia was diagnosed by biopsy but not cytology and in seven cases by cytology but not biopsy. Nineteen patients had multiple infections or Kaposi's sarcoma. Biopsy was more useful than cytology in the diagnosis of other infections (n = 20) and Kaposi's sarcoma (n = 2) with positive cytological correlation in only three of the infections. Biopsy and cytology together have a diagnostic yield of 78.3%. We conclude that all patients presenting with respiratory disease who have, or are in a high risk group for, AIDS should be examined by bronchoscopy at an early stage with both cytology and biopsy.
The production of the lipoxygenase metabolite of arachidonic acid, leukotriene B4 (LTB4) by normal rat glomeruli has been studied. Isolated glomeruli from saline-perfused rat kidneys were incubated in Kreb's buffer for 15 min at 37 degrees C. The concentrations of LTB4 and other eicosanoids in cell-free supernatants were determined by direct radioimmunoassays (RIA). Mean basal syntheses of eicosanoids were: thromboxane B2 (TXB2) 0.77 +/- 0.13, prostaglandin (PG) E2 0.40 +/- 0.05, 6-keto-PGF1 alpha 0.38 +/- 0.06 ng/mg glomerular protein (mean +/- SEM n = 8). In these assays immunoreactive LTB4 synthesis was 0.12 +/- 0.02 ng/mg. In samples incubated with BW755C, 50 micrograms/ml, an inhibitor of arachidonate metabolism via both the cyclo-oxygenase and lipoxygenase pathways, there was more than 80% inhibition of the synthesis of TXB2, PGE2 and 6-keto-PGF1 alpha. However, immunoreactive LTB4 was only reduced by 44%, suggesting the presence of other materials which cross-react in the RIA. The presence of authentic LTB4 in the supernatants was confirmed after extraction and high-pressure liquid chromatography (HPLC). This material represented 25% of the original material detected by RIA. Although the physiological role of LTB4 in the normal state is unknown, its chemotactic activity may be of great significance during glomerular inflammation.
Inflammatory cell populations in glomerulonephritis (GN) are not well characterized. A method is reported for isolating leukocytes from glomeruli. GN was induced in rats by perfusing left kidneys (LKs) with cationized human IgG followed by intravenous rat anti-human IgG serum. Acute GN developed in LKs with proteinuria, deposition of human and rat IgG and C3, leukocyte infiltration, and capillary wall electron-dense deposits. Glomeruli (GL) isolated at 24 hours were digested with collagenase, trypsin, and DNase, and the resulting cells were as follows (mean +/- SEM): LK, 354 +/- 25/GL; RK, 214 +/- 32/GL. Cells were labeled with monoclonal antibody MRCOX1 (anti-rat leukocyte common [LC] antigen) followed by FITC F(ab')2 rabbit anti-mouse Ig: LK, 170 +/- 11 leukocytes/GL;RK, 8 +/- 2 leukocytes/GL (P less than 0.001). Isolated cells were sorted by flow cytometry to 98% pure LC+ cells with greater than 80% viability (Giemsa staining: 86% mononuclear cells, 14% neutrophils); the ultrastructure was that of maturing macrophages and neutrophils. This method quantitates leukocyte infiltration and provides leukocytes from nephritic glomeruli suitable for in vitro studies.
An experiment is presented which shows that colonic primary tumours cluster around a previously constructed anastomosis and that the choice of suture materials (but not the technique of their insertion) can influence this. In a rodent model where dimethylhydrazine was administered 2 months after surgery, anastomotic tumours were most often seen when wire sutures--as used in the staples of anastomotic stapling guns--had been employed (10 out of 16 large bowel tumours were anastomotic as compared with 2 of 12 in a silk sutured group, P = 0.019). An explanation may be that wire sutures persist much longer than silk (in the experiment, 10 months after insertion, 4 per cent of silk sutures were still present, 15 per cent of wire, P less than 0.01). This was translated into a greater degree of scarring at the anastomosis, being most severe in the presence of persisting sutures. Of the 12 anastomotic tumours found in both groups, 7 (58 per cent) were in the minority (17-26 per cent) who had persisting sutures and the remaining 5 in the 47 who had none. Techniques of suturing (needle always passed from the serosa in; needle from mucosa out--the latter in such a way that mucosal cells could be displaced into the bowel wall where it was supposed that they might be more susceptible to subsequent carcinogenesis) did not affect tumour yield. We suggest that non-absorbable sutures, and especially stainless steel wire, should not be used when constructing an anastomosis after large bowel cancer surgery.
Eicosanoid synthesis was studied in a model of in situ glomerulonephritis (gn) in the rat. Unilateral gn was induced by perfusion of left kidneys with 200 micrograms cationized human IgG followed by intravenous (i.v.) autologous anti-human IgG antiserum. Rats developed proteinuria in the first 24 hours and hypercellular gn with leukocyte infiltration in the left kidney. Synthesis of thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and 6-ketoprostaglandin F 1 alpha(6-keto-PGF 1 alpha) was measured at 6, 12, 18 and 24 hours in isolated glomeruli by radioimmunoassay. In nephritic glomeruli there was a nine-fold rise in TXB2 at six hours (5.35 ng/mg glomerular protein) when compared to control (0.6 ng/mg). TXB2 was still elevated at 24 hours (2.7 +/- 1 ng/mg; control 0.7 +/- 0.2 ng/mg). There were no consistent changes in PGE2 or 6-keto-PGF 1 alpha. No changes were found in right kidneys of nephritic or control rats. Treatment of nephritic rats with a selective thromboxane synthetase inhibitor, dazmegrel (20 mg/kg 8 hourly intraperitoneally), suppressed glomerular TXB2 at 24 hours. TXB2 was also inhibited in right (non-nephritic) kidneys and serum. Dazmegrel did not inhibit proteinuria or glomerular hypercellularity. We conclude there is a major increase in glomerular TXB2 in this model which does not play an essential role in the development of proteinuria or cellular infiltration.
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We studied the effect of modulators of tetrahydrobiopterin (BH4) synthesis on the production of nitrite by glomeruli from rats with immune complex-mediated glomerular inflammation. Glomeruli were isolated 24 h after induction of accelerated nephrotoxic nephritis and cultured at 2,000/ml for 48 h. Lipopolysaccharide dose dependently increased ex vivo nitrite production. 2,4-Diamino-6-hydroxypyrimidine (DAHP), an inhibitor of the de novo synthetic pathway of BH4, inhibited nitrite production by up to 50% and this effect was reversed by sepiapterin, a substrate for the salvage pathway of BH4 synthesis. Sepiapterin alone increased nitrite generation indicating that BH4 is rate limiting. Inhibition of both pathways with DAHP and methotrexate led to 80% inhibition of nitrite. Pharmacological inhibition of BH4 synthesis may be a useful mechanism to reduce nitric oxide synthesis in immune complex inflammation.