Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.

Morphometric analysis of the endocrine and exocrine pancreas was done on immunoperoxidase stained post-mortem tissue from 15 Type 2 diabetic and 10 age-matched control subjects. Thirteen of the 15 Type 2 diabetic patients had islet amyloid deposits (mean, 6.5% islet area) in the corpus (body, tail and anterior part of the head) but not in the caput (the "pancreatic polypeptide rich" part of the head) whereas none was seen in control subjects. In the corpus in diabetic subjects, the pancreatic area density of B-cells was decreased by 24% (p = 0.005) and A-cells increased by 58% (p less than 0.001) compared with control subjects. The mean A/B-cell ratio increased in the corpus from 0.27 in control subjects to 0.57 in Type 2 diabetic patients. Positive immunoreactivity for the amyloid constituent peptide, Diabetes Associated Peptide, was demonstrated in islet amyloid of diabetic subjects and in B-cells of control and diabetic subjects. The increase in A-cells may contribute to the hyperglucagonaemia and hyperglycaemia of Type 2 diabetes. The impaired insulin secretion in Type 2 diabetes may be due to a decrease in B-cells and to disruption of the islet structure by amyloid. Exocrine fat was similar in the control and diabetic subjects with both groups having more in the corpus than the caput. Diabetic subjects had increased exocrine fibrosis in the corpus region (p less than 0.001), but not in the caput. Exocrine fibrosis may be secondary to disordered islet cell function.

The Sda antigen in the human kidney and colon.

The range of concentration of the Sda blood group antigen has been determined in the human adult kidney and colon. No Sda antigen was found in 2% of kidneys. Immunofluorescent studies of the kidney showed that Sda is present in the distal convoluted tubules and collecting ducts and occurs in the same location as Tamm-Horsfall protein. No Sda antigen was detected in about 2% of colons. In an additional 6%, no antigen was detected in saline extracts but was present in an insoluble form. In the colon, Sda is sited on the brush borders of the epithelial cells and in the goblet cells. No Tamm-Horsfall protein was identified in the colon.

Prognostic factors in non-Hodgkin's lymphoma: the importance of symptomatic stage as an adjunct to the Kiel histopathological classification.

A prospective study of prognostic factors for patients with non-Hodgkin's lymphoma was carried out based on the Kiel histopathological classification. Other presentation features assessed for prognostic value included clinical features, haematological and biochemical findings, and immunochemical findings. The most powerful factors that emerged were the presence or absence of systemic symptoms and the histopathological grade of malignancy of the lymphoma (whether low or high grade). These 2 factors were largely independent. Clinical Stage I disease also carried a good prognosis, but beyond this, staging gave little further prognostic information. Nine of the group of 15 patients with Stage I high grade lymphoma have achieved prolonged disease-free survival after local therapy only. After allowing for histopathology and symptom assessment in patients with Stage II-IV disease, other factors, with the exception of C-reactive protein levels, were of minor importance.

Islet changes induced by hyperglycemia in rats. Effect of insulin or chlorpropamide therapy.

To investigate the effect of hyperglycemia on normal islets, rats were made diabetic by a 95% partial pancreatectomy and treated with insulin, saline, or chlorpropamide for 3 mo. Histologic examination and morphometry of the residual pancreas showed islet enlargement and fibrosis that correlated with the mean lasting plasma glucose during the experimental period. Treatment of diabetes with insulin prevented the islet disorganization. The B-cell area per islet remained constant and was not affected by hyperglycemia. Chlorpropamide had little effect on the fasting plasma glucose or islet structure, and no "beta cytotrophic" effect was seen. Chronic hyperglycemia induces islet damage that may affect residual B-cell function in diabetes.

Cytological diagnosis of lymphoma in serous effusions.

A consecutive series is presented of 100 cases of malignant lymphoma in which a correlation could be made between the histological findings and the cytology of pleural or peritoneal fluid or both. Using the Kiel classification, 80 cases could be given a histological label, while 20 remain unclassified. In those cases in which lymphoma cells were identifiable in the serous fluid, their morphology was studied and was found in general to correlate well with the cell-type expected from the histology. It is not claimed that the type of lymphoma can be reliably diagnosed from the cytology of pleural or peritoneal fluid, but an opinion can be provided as to the grade (high or low), and in some cases it is also possible to give an indication of the cell-type involved.

Light chain isotype-associated suppression of normal plasma cell numbers in patients with multiple myeloma: Medical Research Council's Working Party for Leukaemia in Adults and the Oxford Lymphoma Group.

The number of plasma cells in the lamina propria of the gut has been assessed in patients with multiple myeloma and other B-cell neoplasms. The total number of these plasma cells was reduced in most patients with myelomatosis and one-third of patients with lymphoplasmacytoid tumours. This reduction was not, however, seen in patients with other neoplasms of B-cell origin, although hypogammaglobulinaemia was common to all groups of patients. The depletion of gut plasma cell numbers was not uniform in myelomatosis patients. They showed selective loss of plasma cells with the same light chain isotype as that produced by the neoplastic clone.

Peripheral neuropathy and benign IgG paraproteinaemia.

Three patients with peripheral neuropathy and an associated benign IgG paraproteinaemia are described. No direct immunological evidence for an aetiological role of the paraprotein was found, and the implications of this are discussed.

Atypical multicentric reticulohistiocytosis with paraproteinemia.

Two women had multiple subcutaneous nodules that showed features of multicentric reticulohistiocytosis (MR). Neither had joint symptoms. Both had a raised erythrocyte sedimentation rate, an immunoglobulin G paraproteinemia, and raised levels of nonhepatic serum alkaline phosphatase. The skin lesions have been followed up, using light and electron microscopy, immunoperoxidase, and histochemical methods. The material in the giant cells stained positively for gamma heavy chain determinants: the light chain type in each case was that of the paraprotein. An attempt to reproduce the skin lesions in one patient by intradermal injection of her paraprotein failed.