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Biomedical subjects

M J Stone

Publications and source records attributed to M J Stone.

126 records · Page 7Linked to original sources

Gated blood pool imaging following 99mTc stannous pyrophosphate imaging.

Cardiac patients who have undergone 99mTc-stannous pyrophosphate (99mTc-PYP) myocardial imaging can be injected 24 hours later with 99mTc-pertechnetate (99mTc04) to assess left ventricular function. Reduction of 99mTc04 by tin remaining in the blood following the stannous pyrophosphate injection causes labeling of the red cells by 99mTc04 and the creation of a vascular tracer suitable for electrocardiographically gated imaging.

Animals↗

The clinical spectrum of light chain myeloma. A study of 35 patients with special reference to the occurrence of amyloidosis.

During a 40 month interval, 35 patients were seen with a plasma cell dyscrasia in which the only detectable monoclonal immunoglobulin abnormality consisted of excess production of either type kappa or type lambda light chains (Bence Jones protein). This group constituted 17.3 per cent of the total number of patients with plasma cell dyscrasias and 25.7 per cent of the patients with myeloma identified during the same period. Variable initial clinical presentation, the absence of a typical monoclonal serum spike and the unreliability of commonly used urine protein tests made recognition of the disorder difficult in many patients. Sulfosalicylic acid and p-toluene sulfonic acid proved valuable in screening for ueine protein. Definition of "proteinuria" by quantitative, electrophoretic and immunochemical studies was essential for diagnosis. Bence Jones proteinemia was present in 80 per cent of the patients; panhypogammaglobulinemia and lytic bone lesions were demonstrable in more than 60 per cent. Although no specific morphologic abnormality of marrow plasma cells was evident by light microscopy, the absence of rouleau on peripheral blood smear was a helpful diagnostic clue. Although patients with lambda light chains presented with more Bence Jones proteinuria, this did not correlate with the severity of initial renal functional impairment or with survival when compared to patients with kappa light chains. No other clinical or laboratory observation differentiated the groups with kappa light chains from those with lambda light chains. Amyloid was identified in seven patients. Their course was dominated by the features of primary systemic amyloidosis instead of the usual findings of classic myeloma. Patients with amyloidosis had lower initial serum albumin levels, fewer lytic bone lesions and reduced survival compared to patients without amyloidosis.

Acute Kidney Injury↗

Radioimmunoassay of myoglobin in human serum. Results in patients with acute myocardial infarction.

A radioimmunoassay has been developed for the measurement of serum myoglobin in order to evaluate the time-course and frequency of myoglobinemia in patients with acute myocardial infarction. The method can detect as little as 0.5 ng of myoglobin and is not affected by hemolysis or storage of serum at -- 20 degrees C. Myoglobin was detected in all of 92 sera from normal adults and ranged between 6 and 85 ng/ml. Levels were markedly elevated in sera from 18 of 20 patients with acute myocardial infarction when samples were obtained within 12 h after hospital admission, the mean concentration being 380+/-53 ng/ml. Wehn the initial sample was drawn between 12 and 24 h after admission in another group of 20 patients with acute myocardial infarcts, the mean serum myoglobin concentration was 195+/-47 ng/ml, and 11 of these individuals had normal levels. Serial determinations performed on nine patients with acute infarction demonstrated that maximum myoglobin levels occurred within the first 8-12 h after admission and fell rapidly toward normal thereafter. The serum concentration of myoglobin in 21 additional patients admitted with chest pain but without acute myocardial infarction was 41+/-6 ng/ml. Radioimmunoassay of serum myoglobin appears to be useful and sensitive test for the early detection of myocardial infarction.

Acute Disease↗

Studies on the specificity of autoantibodies produced in systemic graft-vs-host disease.

Anti-erythrocyte antibodies were found in serum and on RBC of F-1 hybrid hamsters afflicted with systemic graft-vs-host (GVH) disease. These antibodies were shown to be reactive with antigenic determinants unique to hamster erythrocytes compared to heterologous erythrocytes and to non-erythrocytic hamster tissues. They fulfilled the criteria for true autoantibodies by failing to discriminate strain specificities among the domestically maintained isogenic hamster lines that were tested. It is suggested that the excessive production of these antibodies results from the allogeneic effect by which donor T-lymphocytes attack host B lymphocytes and stimulate heretofore quiescent self-reactive clones. Moreover,it is proposed that these autoantibodies can function as enhancing antibodies and subvert continued progression of GVH disease. In this regard, they resemble antibodies directed at allogeneic transplantation antigens that have been shown to attenuate and abort GVH processes.

Adsorption↗

Why are secondary metabolites (natural products) biosynthesized?

We adopt the definition of a natural product as a substance that has no known role in the internal economy of the producing organism. The literature abounds with conflicting views for the existence of such natural products. We propose that all such structures serve the producing organisms by improving their survival fitness. We argue that this conclusion is necessitated by the fact that natural products are normally complex structures, whose biosynthesis is programmed by many kilobases of DNA. If it were otherwise, the pressures of Darwinian natural selection would have precluded the expenditure of so much metabolic energy in their construction and the development of such complexity. We further conclude that a natural product improves the producer's survival fitness by acting at specific receptors in competing organisms. Current studies of natural products interacting with receptors support this view, in terms of both the sophistication of the molecule/molecule recognition and the mechanistic details of physiological action. By the application of Occam's razor and general weaknesses of other hypotheses, these other hypotheses are rejected. It is a consequence of our proposal that natural product/receptor interactions of sophistication comparable to enzyme/substrate interactions will be commonplace. Additionally, structures that are candidates to interact with known receptors (e.g., double helical DNA) can on occasion be suggested by inspection of the structures. A range of evidence to support the general conclusions is presented.

Anti-Bacterial Agents↗

Lymphocyte phenotyping by fluorescence microscopy and flow cytometry: results in homosexual men and heterosexual controls.

Absolute numbers of peripheral blood T3, T4 and T8 positive cells from 15 homosexual men and concurrent controls were determined by fluorescence microscopy (FM) and by a fluorescence-activated cell sorter (FACS). A significant difference in the number of positive cells was observed between FM and FACS in the control group for all three monoclonal antibodies and for the T4/T8 ratio. FACS methodology yielded a lower number of T4 positive cells and a lower T4/T8 ratio in the homosexual subjects. Two homosexual men had normal T4/T8 ratios by FM but were found to have low ratios by FACS. The reasons for the disparate results obtained by the two methods are unclear, but such findings are important to bear in mind when evaluating male homosexuals for immunologic abnormalities.

Acquired Immunodeficiency Syndrome↗

Heterotransplantation of human multiple myeloma cell lines in severe combined immunodeficiency (SCID) mice.

Human multiple myeloma (MM) xenografts have been difficult to establish in athymic mice. We examined the feasibility of establishing human MM xenograft growth in SCID mice following subcutaneous (sc) injection of 1-2 x 10(7) cells from the human plasma cell dyscrasia (PCD) cell lines RPMI 8226 and ARH-77. SC tumors emerged in 67% (6/9) of RPMI 8226- and 6 of 6 ARH-77-injected mice after a latency period of 9-54 days, and reached 19-35 mm in diameter before the mice were sacrificed. RPMI 8226 and ARH-77 primary tumor DNA hybridized positively with the human genome probe Alul-(Blur8), confirming successful engraftment of the human MM cell lines. The RPMI 8226 xenografts comprised predominantly of plasmacytoid cells that expressed the relevant cytoplasmic immunoglobulin (cIg) light chain isotype. Xenografted RPMI 8226 cells also expressed CD10 (CALLA; 44% reactive cells), CD38 (OKTIO; 69%), CD5 (49%), and reacted with the MM monoclonal antibody MM4 (39%). Human MM growth appeared to be localized subcutaneously for both RPMI 8226 and ARH-77 xenografts. There were no detectable metastatic foci in kidney, brain, heart, or bone marrow. Whereas diffuse plasma cell infiltrates were observed in spleen, GI tract, and lung biopsies of tumor-bearing mice, these infiltrates were of host origin according to immunophenotyping and DNA analyses. Neither the originating RPMI 8226 line nor its SCID mouse xenograft expressed Epstein Barr virus (EBV) genome sequences. These observations indicate that both EBV- (RPMI 8226) and EBV+ (ARH-77) cell lines can be successfully propagated in SCID mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗