Improvement in allograft survival of islets of Langerhans by pretreatment with deoxyguanosine.

In vitro pretreatment of isolated islets of Langerhans prior to transplantation with deoxyguanosine (dGuo) was found to be effective in improving the survival in fully allogeneic diabetic rats (Wistar----PVG). Post transplant immunosuppression was not used. Islets pretreated with various concentrations of dGuo, 1, 1.35, 1.5 and 2 microM dGuo per islet showed a graft survival of 9, 36, 9 and 14% respectively.

Prolongation of allograft survival in diabetic rats treated with cyclosporine by deoxyguanosine pretreatment of pancreatic islets of Langerhans.

In vitro pretreatment of islets of Langerhans with deoxyguanosine (dGuo) has been shown to be effective for the prolongation of islet allograft survival in rats. [This study evaluates the effect of pretreatment of islets with dGuo transplanted into CsA-treated recipients.] Transplantation of dGuo-treated islets from Wistar rats into diabetic hooded (PVG) rats resulted in 36% graft survival without immunosuppression (dGuo-group) and 89% islet survival after a short course of cyclosporine was used in recipients (dGuo + CsA group). In contrast, transplantation of untreated islets into rats without immunosuppression (controls) and with CsA (CsA group) immunosuppression resulted in 0 and 56% survival, respectively. The differences in graft survival between dGuo versus control group (P less than 0.001), (dGuo + CsA) versus control group (P less than 0.0001), and CsA versus control group (P less than 0.002) are statistically significant. Donor-strain skin-graft challenge failed to induce rejection of transplanted normoglycemic rats in (dGuo) and (dGuo + CsA) groups. The results indicate that a state of immunologic unresponsiveness may have been induced in the recipients of dGuo-treated islets, and further treatment with CsA synergistically prolongs islet survival in fully mismatched rats.

Collagen of the dystrophic hamster diaphragm.

The collagen content of the diaphragm was measured in normal and dystrophic hamsters aged 130 and 270 days. The diaphragm collagen content was greater in dystrophic hamsters than in control hamsters of the same age. The effect was greater in the older hamsters whether the collagen content was expressed in terms of the percentage of dry weight, in relation to surface area, or as total collagen. This increase was apparently at the expense of muscle tissue and may be a major factor contributing to respiratory muscle weakness as dystrophy advances.

Primary gastrointestinal non-Hodgkin's lymphoma: a study of 35 patients.

In a retrospective study of 35 patients (29 men, 6 women) with primary non-Hodgkin's lymphomas of the gastrointestinal tract, 13 of the tumours were located in the stomach, 21 in the small bowel and one in the colon. Various radiological findings were detected, and the majority of tumours (23) had high grade histology. Three patients had immunoproliferative small intestinal disease. Only tumours in stages I and II were included in the study, and the majority (25) were in stage IIA. All patients except one had undergone resection of the neoplasm. This was followed by combined chemotherapy in 25 patients, and chemotherapy followed by radiotherapy in three cases. There were two (5.7%) hospital mortalities. Two- and 5-year survival rates were better in those patients with low stage and low grade tumours. The overall 5-year survival rate was 38%.

Transplantation of islets of Langerhans isolated by Trowell's T8 medium in outbred rats: effect of cyclosporine.

This study was carried out to investigate the efficacy of cyclosporine to prolong islets isolated by collagenase in Trowell's T8 medium and Ficoll gradient separation. Our results demonstrate that a short course of cyclosporine is effective in minimizing rejection of transplanted islets in outbred rats.

Differential immunohistochemical localization of cytokeratins and collagen types I and III in experimentally-induced cirrhosis.

Liver cirrhosis was induced in male Wistar rats by subcutaneous injection (1 ml of 30 g/l) of an aqueous solution of thioacetamide. Using the indirect immunoperoxidase technique, high molecular weight keratins were localized in bile ducts and ductules. Low molecular weight cytokeratins were present in regenerating hepatocytes in active cirrhosis; bile ducts were unstained. These results suggest that cytokeratin staining may be useful in distinguishing bile duct epithelium and hepatocytes in hepatobiliary diseases. Anticollagen type III antibody stained hepatocytes and thin connective tissue fibres, while anticollagen type I antibody stained thicker fibres and some sinusoidal cells but not hepatocytes. Collagens were usually undetectable in normal liver cells. It is suggested, therefore, that hepatocytes may play a major role in collagen type III production which precedes the deposition of collagen type I. By contrast, collagen type I may be produced by fibroblasts and some cells along sinusoids (e.g. perisinusoidal fat-storing cells) after liver injury.

Structural changes in glomeruli and proteinuria in streptozotocin diabetic rats.

In streptozotocin induced diabetes in rats, excretion of urinary protein fractions were studied in relation to structural changes in the renal glomeruli, using light and transmission electron microscopy. After six weeks of induced diabetes only beta 1 and beta 2 plasma globulins were significantly elevated. The amount of excreted proteins and degree of glomerular changes were not proportional. In the initial stages (1-2 weeks) glomerular structural changes were very mild and were accompanied by significantly elevated proteinuria. This progressed (4-8 weeks) to moderate to prominent structural changes with intermittent proteinuria except for the fractions beta 1 & beta 2 which were elevated throughout the duration of the experiment. The amount of proteinuria was not proportional to changes in the plasma protein levels. The following conclusions may be made: 1) The mild early glomerular abnormalities seem to be mainly due to acute metabolic disturbances. 2) An early indication of diabetic nephropathy is provided not only by albuminuria, but may also be an elevated excretion of beta-globulin fractions. 3) Decrease of albuminuria in the later stages of diabetes may be related to the deposition of albumin as a basement membrane-like material in the mesangium.

Takayasu's arteritis and nephrotic syndrome in a patient with crossed renal ectopia.

A male patient with nephrotic syndrome, crossed renal ectopia, and extensive Takayasu's arteritis (TA), involving one of the renal arteries, is described. Renal histology showed amyloidosis. After reviewing the literature and considering the finding of raised serum amyloid protein A levels, it was concluded that TA had probably caused the amyloidosis. The crossed renal ectopia must have been a purely coincidental finding.

Immunohistochemistry of cytokeratin proteins in squamous and transitional cell lesions of the urinary tract.

Expression of low and high molecular weight cytokeratin proteins was investigated immunohistochemically in a variety of transitional and squamous epithelial lesions of the urinary tract with and without schistosomiasis. The monoclonal antibodies used were CAM 5.2 and NCL5D3 for low, PK 63 and 121 for high, and MAK 6 for a broad range of intermediate molecular weight cytokeratins. On staining with CAM 5.2 and NCL5D3, urothelial hyperplasias (n = 12) and grades 1 (n = 5) and 2 (n = 10) papillary transitional cell carcinomas showed labelling patterns quite distinct from carcinoma in situ (n = 4) and non-papillary grades 2 (n = 6) and 3 tumours (n = 3). Among squamous lesions only focal positivity was obtained in 14 of 22 moderate to poorly differentiated squamous cell carcinomas. By contrast, PK 63 and 121 stained squamous lesions exclusively. MAK 6 stained the whole range of urothelial and squamous lesions with the exception of squamous metaplasias. Polyclonal antikeratin adequately labelled spindle cell areas of high grade tumours. The distinctive staining patterns given by these or similar antibodies may help in the identification of squamous metaplasia and in diagnosing tumours of the urothelium.

Enzyme immunoassay of prostatic acid phosphatase after prostatic examination. Correlation with prostate size and immunopathology.

Variation in serum prostatic acid phosphatase (PAP) after prostatic digital examination was studied in 22 patients, 18 with benign prostatic hyperplasia (BPH), and 4 with prostatic carcinoma. Serum PAP was determined by enzyme immunoassay (EIA) and compared with standard enzymatic assay (EA). Prostatic tissue from transurethral resection (TUR) was subjected to routine pathologic examination and stained for PAP. PAP level increased above reference range and up to several-fold in 12 of 22 patients (54.5%) by EIA and in 22.7 percent by EA. The increase in PAP correlated positively with the prostate size estimated by digital palpation (R = 0.82, P less than 0.001). There was no definite correlation between the histologic parameters studied and the increase in PAP. No day-to-day variation in PAP level was detected in 8 other patients when samples were taken at 7 AM for three successive days. For proper comparison of PAP value, we suggest that sampling time should be fixed and specimens should be taken before prostatic manipulation.

Hepatitis B core and surface antigens and delta agent in chronic liver disease in Kuwait.

Hepatitis B surface antigen was detected immunohistochemically in 25 out of 85 liver biopsies (29.4%) of chronic liver disease. Core antigen was also demonstrated in 9 of the 25 Hepatitis HBs Ag positive biopsies (36%). Delta agent however, was found in only one case of HBs positive chronic active hepatitis. The number of hepatocytes staining positively for HBc antigen was greater in those biopsies with the strongest staining for HBs antigen. The only case of chronic active hepatitis positive for delta agent showed that the positive staining was confined to the nuclei of few hepatocytes. The routine histology showed chronic active hepatitis with a moderate degree of inflammation. The present results confirm our previous reports that almost one third of chronic liver disease in Kuwait is associated with hepatitis B infection. Previous serological studies suggest that delta agent infection is also common; however, the present study suggest that delta agent may be a transient, and not a major, contributing factor in the progression of liver disease.

Expression of chorionic gonadotropin by schistosomiasis-associated squamous carcinomas of bladder.

Of 22 consecutive cases of squamous cell carcinomas of the urinary bladder, 4 expressed the beta subunit of human chorionic gonadotropin as demonstrated by immunohistochemistry. The significance of this finding is compared to similar observations made in urothelial carcinomas by others and its value as a possible marker in diagnosing and monitoring the progress of these tumors is discussed.

Schistosomiasis-associated squamous lesions of the bladder. Expression of low molecular weight cytokeratin proteins.

The monoclonal antibody CAM 5.2 was used to investigate the expression of lower molecular weight cytokeratin proteins immunocytochemically in conventionally processed samples of schistosoma-associated squamous metaplasias and carcinomas of the urinary bladder. The antibody did not differentiate between squamous metaplasias and well differentiated squamous carcinomas, though it did focally label moderate to poorly differentiated tumours. The results suggest that squamous carcinomas of the bladder in this setting differ fundamentally from such tumours at other sites in their patterns of cytokeratin protein expression.

Immunohistochemical localization of collagens and fibronectin in human breast neoplasms.

Forty four specimens from neoplastic, hyperplastic and normal human breast tissues were studied for localization of collagens and fibronectin. Affinity purified antihuman type I, III and IV collagens and antifibronectins were utilized by the indirect immunoperoxidase technique on fixed and paraffin-embedded sections. 86% of the cell cytoplasm of infiltrating ductal and 83% of the lobular cancers were positively stained for collagen type I and III. Collagen type IV, however, was detected in 100% of infiltrating ductal and 83% of lobular carcinomas. Focal cytoplasmic staining is a predominant feature for all antigens in the intraduct carcinoma while a diffuse pattern is encountered in the infiltrating types. Intact basement membranes in various lesions always stained for type IV collagen and showed variable staining for type III collagen and fibronectin. Epithelia of normal, benign, hyperplastic breast and most medullary carcinoma were negative for the three collagen types. Our results are in favour of the view that infiltrating breast carcinoma cells produce inappropriately the majority of collagens and inconsistently other proteins such as fibronectin.

Expression of connective tissue stromal elements in human cholangiocarcinomas. An immunohistochemical and ultrastructural study.

The results of the study of ten cholangiocarcinomas from intrahepatic or extrahepatic origins are reported. Using both light microscopic immunohistochemistry and transmission electron microscopy the scirrhous stroma of the tumour showed clear evidence for the production of its collagenous, elastic and possibly other fibrillar elements by the neoplastic cells. Our findings refute the view that the occasional spindle cells (i.e. fibroblasts, myofibroblasts or even smooth muscle cells) could play a major role in the production of such a voluminous amount of the various connective tissue elements. Therefore, it seems reasonable to suggest that the scirrhous stroma of cholangiocarcinomas is produced by the malignant cells similar to those of the breast, oesophagus, stomach and ureter.

Patterns of stromal elements in an implanted ureteric transitional cell carcinoma. An immunohistochemical and ultrastructural study.

The results of the study of three implanted ureteric tumors from a primary transitional cell carcinoma of the renal pelvis are reported. Using both light microscopic immunohistochemistry and transmission electron microscopy, the stroma of the tumor showed consistent evidence for the production of at least its collagenous component by the neoplastic cells. Our findings argue with the notion that occasional fibroblasts and other cells of mesenchymal origin could play a major role in this phenomenon. Therefore, it seems plausible to suggest that what is happening in these tumors is similar to the behavior of malignant cells in scirrhous 'infiltrating' carcinoma of the breast and other sites.