Prevalence of Crohn's disease in Israel.
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Biomedical subjects
Publications and source records attributed to S Weitzman.
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Metyrosine 1.5 g daily for days decreased 24-h urine metanephrine concentration by about 60% in a patient with multiple catecholamine-secreting paragangliomas. Despite the considerable inhibition of catecholamine synthesis, this patient exhibited stress-induced sympathetic overactivity, indicated by increases in arterial pressure and serum catecholamine and urine metanephrine concentrations. It is concluded that metyrosine should be introduced early to the preoperative regimen. In this way, optimal inhibitory effect on catecholamine synthesis can be obtained and maintained for a sufficient time to allow catecholamine stores to become as close to normal as possible. Attainment of the optimal therapeutic effect is not clearly defined, but would seem to be best gauged by a combination of clinical tests of sympathetic responses and of suppression of urinary excretion of metanephrines or VMA.
A mouse myeloma cell line, 45.6.3, produces an IgG2b immunoglobulin (Ig) with 2 carbohydrate attachment sites on the heavy chains. One site is in the CH2 domain and the other in the VH region. The oligosaccharides at each site have different structures. The ratio of radioactive glucosamine incorporated in the VH compared with the CH2 oligosaccharide is approximately 1 to 3. In an attempt to understand this observation further, variant cell lines derived from 45.6.3 were isolated and their Ig were characterized. A ricin-resistant line, R4R1.5, has the same 2 attachment sites as the wild type, but the ratio of radioactive glucosamine in VH compared with CH2 was 1:1 and not 1:3 as in the wild type. This alteration is most probably due to cellular factors, since the Ig protein is unchanged. The M3.11 cell line produces an Ig with a polypeptide deletion involving the CH3 domain. In this Ig, a 3rd carbohydrate attachment site can be demonstrated. The percentage of radioactivity glucosamine in the CH2 domain compared with the total Ig is about 25% instead of 75% as in the wild type. These results suggest that the extent of glycosylation of different sites on Ig can be affected by both cellular factors and structural changes in the Ig protein.
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A healthy young man developed acute anterior myelitis resembling the "polio syndrome." He had visited an area (the Gulf of Suez) in which West Nile fever is endemic prior to his illness. The course of his febrile illness, the spinal fluid findings, and complement fixation antibody titers established the diagnosis of West Nile fever. Meningoencephalitis is a serious, and previously the only known, complication of this usually benign febrile illness. This is the first report, to our knowledge, of another neurological complication, namely acute anterior myelitis.
The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in 16 cerebrospinal fluid samples from eight patients with bacterial meningitis due to several different organisms was determined. An age- and sex-matched control group of 12 patients with a variety of acute, noninfectious systemic and neurological diseases was also examined. To quantitate the amount of cAMP, a new, improved radioimmunoassay was used with the ability to measure 2.5 X 10(-15) mol of cAMP. The mean concentration of cAMP in the cerebrospinal fluid from patients with meningitis was 0.05 nM, and from patients in the control group it was 1.18 nM. The difference between these two values is statistically significant. The decreased cAMP concentration in the cerebrospinal fluid from patients with bacterial meningitis did not seem to be secondary to metabolism by bacteria or leukocytes, increased enzymatic degradation within the cerebrospinal fluid, or an artifact introduced by the collection and storage procedure. Since the concentration of cAMP in the cerebrospinal fluid is normally found to be within narrow limits and probably reflects intracellular cAMP levels, the results described in this study suggest that interference with cAMP metabolism in central nervous system tissue occurs in bacterial meningitis. This finding seems to be independent of the causative organism and might explain the pathogenesis of selected, neurological manifestations of this disease.
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The number of lymphocytes with mobile receptors for concanavalin A (Con A) on their surface membrane (forming visible caps after the addition of fluorescein-conjugated Con A) was determined in the peripheral blood of 53 patients with Hodgkin disease. Of 29 individuals studied prior to treatment, the level of capped cells was found to be below the normal range in 9 of 13 in stages I and IIA, 6 of 8 in stage IIIA, and all 8 in stages IIIB and IV. Even among patients in remission 2 yr after successful treatment the level was below the lower normal limit in 9 of 16. The number was also reduced in 7 of 8 individuals with recurrent lymphoma. The level of lymphocytes that cap with Con A may prove to be a more sensitive measure of active Hodgkin disease than the total peripheral lymphocyte count or the level of T cells. This lymphocyte parameter merits further study as a correlate in vitro of cellular immunity.
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Of 14 splenectomized patients with Hodgkin's disease who were treated with total nodal irradiation and combination chemotherapy (MOPP), fulminant sepsis developed in three (21.4 per cent) while they were in remission; two died within hours. Similar cases were not observed in a larger group of 146 patients with Hodgkin's disease (including 104 splenectomized patients who were treated less intensely). Our experience indicates the need for caution when asplenic persons are aggressively treated with both radiation and drugs.
Two mutant cell lines derived from the MPC-11 mouse myeloma synthesize immunoglobulin with abnormal heavy chains and normal light chains. The defective heavy chains have molecular weights of 38,000-42,000 (M3.11) and 50,000 daltons (ICR 11.19) as compared to 55,000 daltons of the wild-type. The glycosylation of the defective heavy chains demostrated several unusual features: first, 30-50% of the M3.11 heavy chain contained no carbonydrate, while 100% of the wildtype and ICR 11.19 heavy chains were glycosylated; second, the glycopeptides of the M3.11 heavy chains revealed an altered gel filtration pattern when compared with the wild-type; and third, digestion with an endoglycosidase indicated that the heterogeneity of the wild-type and M3.11 glycopeptides involved structural changes in the core region of the oligosaccharide. Examination of two other glycoproteins (the major histocompatibility complex antigens) in these cell lines showed that in M3.11, the H-2D but not the H-2K product was abnormally glycosylated and contained a smaller glycopeptide. However, in a subclone of M3.11 that had lost the ability to produce immunoglobulin heavy chains, the H-2D glycopeptide had returned to wild-type size. We concluded from these studies that the defective M3.11 immunoglobulin heavy chain interfered both with its own glycosylation and the glycosylation of another protein, H-2D.
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Multiple myeloma raises a number of puzzling questions about the production of immunoglobulins and the malignant transformation of lymphoid cells. Some of these questions can be approached by studying mouse plasmacytomas and by genetic and biochemical studies of mouse myeloma cells in culture. The synthesis, assembly, glycosylation, and secretion of immunoglobulin has been analyzed in detail using the mouse myeloma system. The development of a technique that detects variants in clones of cultured mouse myeloma cells has led to the demonstration of a unique genetic instability in these cells. Based on these results a model is presented to explain the high frequency of ligh-chain producing (Bence Jones) myelomas in patients. Finally, mutant cell lines have been recovered which produce defective immunoglobulins similar to those found in heavy-chain disease and some other lymphoproliferative disorders.