Biomedical subjects
Publications and source records attributed to M K Bennett.
Morphometric measurements have been performed on small intestinal biopsy specimens obtained from 18 healthy adult Indian volunteers. The measurements were made using a computer aided measuring system, and results were similar to those previously reported for an adult Caucasian population.
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The magnified endoscopic appearances of the rectum are described in 12 patients with Crohn's disease with apparent rectal sparing on sigmoidoscopy. Five of them had minor abnormalities on colonoscopy but the remaining seven had a normal rectum. After the application of 0.2% methylene blue, examination using a magnifying endoscope (Olympus CF-HM) revealed characteristic 'worm-eaten' appearances in 75% of the patients regardless of the activity of their disease. Histological examination of biopsy specimens from these lesions showed marked inflammatory changes, and granulomas or microgranulomas were found in 75%. Inflammatory changes were not seen in mucosa which appeared normal on magnifying colonoscopy although microgranuloma were found in three cases. These observations confirm the focal nature of Crohn's disease and may suggest that the early lesions are mucosal and frequently contain granulomata.
Enemas of 4-amino-salicylic acid (4-ASA) have been compared with placebo enemas in a double-blind study for the treatment of distal ulcerative colitis of mild to moderate severity. 30 patients were randomised to receive enemas containing 1 g of 4-ASA or placebo, and 22 to receive 2-gram enemas of 4-ASA or placebo. For each dose of 4-ASA there was clinical and sigmoidoscopic improvement, which reached significance when all patients receiving 4-ASA enemas were compared with those receiving placebo enemas (Cochran's test: p less than 0.005). There was also a trend towards histological improvement, but this failed to reach the level of significance. These findings suggest that 4-ASA may provide a stable, inexpensive alternative to 5-ASA for the topical treatment of ulcerative colitis or for linking to carrier molecules for release in the colon.
A calcium and calmodulin-dependent protein kinase has been purified from rat brain. It was monitored during the purification by its ability to phosphorylate the synaptic vesicle-associated protein, synapsin I. A 300-fold purification was sufficient to produce kinase that is 90-95% pure as determined by scans of stained sodium dodecyl sulfate-polyacrylamide gels and has a specific activity of 2.9 mumol of 32P transferred per min/mg of protein. Thus, the kinase is a relatively abundant brain enzyme, perhaps comprising as much as 0.3% of the total brain protein. The Stokes radius (95 A) and sedimentation coefficient (16.4 S) of the kinase indicate a holoenzyme molecular weight of approximately 650,000. The holoenzyme is composed of three subunits as judged by their co-migration with kinase activity during the purification steps and co-precipitation with kinase activity by a specific anti-kinase monoclonal antibody. The three subunits have molecular weights of 50,000, 58,000, and 60,000, and have been termed alpha, beta', and beta, respectively. The alpha- and beta-subunits are distinct peptides, however, beta' may have been generated from beta by proteolysis. All three of these subunits bind calmodulin in the presence of calcium and are autophosphorylated under conditions in which the kinase is active. The subunits are present in a ratio of about 3 alpha-subunits to 1 beta/beta'-subunit. We therefore postulate that the 650,000-Da holoenzyme consists of approximately 9 alpha-subunits and 3 beta/beta'-subunits. The abundance of this calmodulin-dependent protein kinase indicates that its activation is likely to be an important biochemical response to increases in calcium ion concentration in neuronal tissue.
By three criteria, two biochemical and one immunochemical, the major postsynaptic density protein (mPSDp) is indistinguishable from the 50-kilodalton (kDa) alpha subunit of a brain calmodulin-dependent protein kinase. First, the two proteins comigrate on NaDodSO4/polyacrylamide gels. Second, iodinated tryptic peptide maps of the two are identical. Finally, a monoclonal antibody (6G9) that was raised against the protein kinase binds on immunoblots to a single 50 kDa band in crude brain homogenates and to both the alpha subunit of the purified kinase and the mPSDp from postsynaptic density fractions. The purified kinase holoenzyme also contains a 60-kDa subunit termed beta. A comparison of the peptide map of beta with the maps of 60-kDa proteins from the postsynaptic density fraction suggests that beta is present there but is not the only protein present in this molecular weight range. These results indicate that the calmodulin-dependent protein kinase is a major constituent of the postsynaptic density fraction and thus may be a component of type I postsynaptic densities.
Two patients, intubated for inoperable carcinoma of the oesophagus, recently presented with their tubes blocked by granulation tissue. This complication has not been previously reported. The tissue macroscopically resembled normal mucosa in one and recurrent tumour in the other. The presentation, aetiology, and significance of this granulation tissue is discussed.
The distribution of fibronectin (FN) and collagen type III (IIIC) have been compared in a series of epithelial neoplasms from the gastrointestinal tract and salivary gland. The difficulty of distinguishing between FN of epithelial and fibroblastic origin is emphasised and evidence is presented for the validity of this distinction. In carcinomas FN was sometimes, but not invariably, lost from epithelial cell surfaces. Both FN and IIIC were increased in reactive connective tissue stroma. It is concluded that loss of cell surface FN is unlikely to be a useful diagnostic marker for malignancy, but that the occurrence of this phenomenon in vivo as in vitro indicates that it is biologically significant.
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Twenty-nine patients with a positive antimitochondrial antibody titer greater than or equal to 1/40, who were detected during screening for other autoimmune disease, are described who had a normal serum bilirubin, alkaline phosphatase and transaminase and who had no symptoms of liver disease at presentation. Liver biopsies in 12 of the 29 fulfilled diagnostic criteria for primary biliary cirrhosis; a further 12 were consistent with primary biliary cirrhosis, but only 2 were normal. There was a high incidence of other autoantibodies and autoimmune diseases, especially thyroid antibodies and disorders. Sixteen of these patients have been followed for over 4 years since diagnosis (mean = 6 years, range = 4 to 9 years) and for a mean of 8.7 years since initial detection of the antimitochondrial antibody (range = 4 to 13). Five of 16 developed symptoms suggestive of primary biliary cirrhosis, and 11 of 16 developed elevation of alkaline phosphatase. The antimitochondrial antibody activity in these patients was in the same IgG subclasses (predominantly IgG1 and IgG3) as that seen in a group of 23 patients with clinically, biochemically and histologically advanced primary biliary cirrhosis. All showed the same abnormalities on quantitative estimation of the total IgG subclasses in serum; relative excess of IgG3 and, to a lesser extent, IgG2 was exhibited. It is concluded that, in this study, the finding of an antimitochondrial antibody titer greater than or equal to 1/40 is strongly suggestive of primary biliary cirrhosis even in the absence of symptoms and the presence of a normal alkaline phosphatase.
Forty-six patients with primary biliary cirrhosis from a single centre were studied in a randomized placebo-controlled trial to determine the effectiveness of ursodeoxycholic acid (UDCA) over a 2 year period. The two groups were well-matched at baseline. For each parameter, by calculating the difference between the median changes with time between the UDCA group and the placebo group, it was found that from entry, with respect to placebo, there were differences between median changes (MCD) favouring the UDCA group in bilirubin (MCD 5 mumol/L [95% confidence interval (CI) 1 to 12] at 1 year and 5 mumol/L (95% CI 1 to 9) at 2 years), alkaline phosphatase MCD 242 iu/L (95% CI 107 to 360) at 1 year and 268 iu/L (95% CI 146 to 424) at 2 years and aspartate aminotransferase MCD 26 iu/L (95% CI 12 to 41) at 1 year and 37 iu/L (95% CI 16 to 64) at 2 years. Within the UDCA group, there was long-term fall in alkaline phosphatase [median fall 116 iu/L (95% CI 93 to 378) at 2 years and aspartate aminotransferase [median fall 18 iu/L (95% CI 6 to 47) at 2 years; however, the major change in bilirubin was a modest rise over 2 years in the placebo group [median rise 2 mumol/L (95% CI 1 to 9)]. Changes in albumin, prothrombin ratio and immunoglobulins were generally minor and not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
pS2 is a 60 amino acid secretory polypeptide which belongs to a newly described family of trefoil-shaped growth factors. It is widely distributed throughout the gastrointestinal tract, particularly adjacent to damaged mucosa, and is also expressed by some epithelial tumours such as breast carcinoma. The aim of this study was to examine the expression of pS2 in pancreatic cancer. The presence of pS2 was analysed immunohistochemically using two antibodies, a polyclonal (pNR-2) and a monoclonal (pS2TM) in 42 cases of pancreatic adenocarcinoma and 10 cases of ampullary carcinoma. The findings were compared with chronic pancreatitis and normal pancreas. No immunostaining was seen in normal pancreas, with the exception of one area of ductular proliferation, and although 8/10 cases of chronic pancreatitis expressed pS2, it was focal and confined to the occasional duct. In contrast, a significant proportion of malignant cells in 23/42 (55%) of pancreatic adenocarcinoma and 8/10 (80%) of ampullary tumours expressed immunoreactive pS2. The finding of pS2 expression in more than 50% of pancreatic and ampullary carcinomas in contrast to the findings seen in chronic pancreatitis and normal pancreas suggests that pS2 may play an important role in the growth of these highly malignant tumours.