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Biomedical subjects

M R Smith

Publications and source records attributed to M R Smith.

At least 181 records · Page 10Linked to original sources

Localized non-Hodgkin's lymphoma of the breast.

Chart review identified 18 patients seen at Memorial Hospital from 1970 to 1984 with primary non-Hodgkin's lymphoma localized to the breast. Sixteen involved the breast alone (Stage IE), whereas two also involved ipsilateral axillary lymph nodes (Stage IIE). None had B symptoms. Histologic subtypes included 11 diffuse histiocytic, 4 diffuse poorly differentiated, 2 diffuse mixed and one nodular mixed. Thirteen patients (72%) are alive with 55 months median follow-up (11 months-14 years). Three patients died with recurrent disease at less than 2 years, one recurred at 4 years and died 6 years after diagnosis, and one died at 30 months without clinical evidence of disease. Seven (39%) have remained continuously disease-free (11 months-11 years; median, 54 months). Of the clinical Stage I patients, 1 of 3 treated with mastectomy alone recurred in the scar, whereas 1 of 12 treated with irradiation alone recurred locally. Thus, radiation therapy alone achieved good local control, although distant relapses remain a problem in these clinically staged patients. Overall, the outcome of clinically localized non-Hodgkin's lymphoma of the breast is similar to that for localized lymphoma in other sites.

Adult↗

Cellular ras activity and tumor cell proliferation.

A monoclonal antibody able to specifically neutralize activity of the cellular proto-oncogene ras was microinjected into a variety of normal and tumor cell types in order to determine the requirement for c-ras activity during proliferation. Normal cells were always efficiently inhibited by the antibody, while most tumor cells continued to proliferate without inhibition following the injection. Tumor cells containing a mutant ras gene, however, exhibited an intermediate phenotype and were partially inhibited in proliferation by the injected anti-ras antibody. The mutant c-ras gene appears, therefore, to play a role in proliferation even of the mature tumor cell (although other gene products must also be involved). Mutations in most other tumor cells, however, fall into the class of oncogenes which promote proliferation independently of c-ras activity. In this way tumor cell proliferation is clearly distinguished from that of normal cells studied.

Animals↗

Sporulation of Clostridium cylindrosporum on a Defined, Low-Manganese Medium.

Clostridium cylindrosporum HC-1 grew and sporulated well on a defined medium. This is the first demonstration of sporulation of a purinolytic clostridium on a defined medium; manganese levels were below those considered essential for sporulation of most Bacillus species. Sporulation appeared to be initiated before exhaustion of the purine substrate.

Journal Article↗

Salt toxicosis in waterfowl in North Dakota.

About 150 waterfowl died and another 250 became weak and lethargic from suspected salt poisoning after using White Lake, a highly saline lake in Mountrail County, North Dakota. Frigid temperatures made fresh water unavailable, forcing the birds to ingest the saline waters with resultant toxic effects. Sick birds recovered when removed from the salt water and released into fresh water marshes. Brain sodium levels were higher in dead geese submitted for necropsy than in controls.

Animals↗

Human spleen contains phenotypic subsets of macrophages and dendritic cells that occupy discrete microanatomic locations.

Macrophages (M phi s) are an important component of the immune response and mediate numerous other functions. Phenotypic and functional subsets of circulating monocytes have been described, but few similar studies have analyzed M phi s in human tissues. By use of immunohistochemical techniques and a large number of monoclonal antibodies, the presence and distribution of phenotypic subpopulations of M phi s and dendritic cells in human spleen were assessed. The results of this study show that different subsets of M phi s and dendritic cells are present in the spleen and that some of these occupy discrete microanatomic locations. In the red pulp (RP) certain groups of antigens are expressed by different proportions of uniformly distributed M phi s in the cords. On the other hand, some antigens are present on M phi s that form clusters of variable size within the red pulp. M phi s in the splenic marginal zone (MZ) share some antigens with red pulp M phi s, but in addition express CR3, Mo-2, 61D3, and 63D3. These antigens are found on only a few RP M phi s. MZ cells expressing one antigen shared with RP M phi s (Leu-3a,b) and one present largely on the MZ cells (63D3) form clusters around small vessels; these structures resemble the so-called splenic ellipsoids that may play a role in the trapping of circulating antigens. Phagocytic M phi s (tingible body M phi s) of the white pulp follicular germinal centers were also shown to differ from RP and MZ cels with respect to the expression of the antigens detected by anti-FcR, Leu-M3, Mo-2, 25F9, and anti-CR3. The unique topographical and surface antigenic features of dendritic cells were confirmed by this study. Furthermore, these cells were found to share a number of antigens with RP, MZ, and white pulp M phi s, which suggests that they may be derived from a common progenitor. The presence of phenotypic subpopulations and variation in distribution among human splenic phagocytic cells and dendritic cells may be indicative of functional specialization.

Antibodies, Monoclonal↗

CA-125. Use as a tumor marker with mixed mesodermal tumors of the female genital tract.

CA-125 levels were determined in seven patients with a mixed mesodermal tumor of the ovary or endometrium. An elevated level was detected in five of six patients with metastatic or recurrent disease. Chemotherapy with cisplatin and Adriamycin (doxorubicin) resulted in a response in four patients, and the CA-125 level correlated well with the clinical status of the disease. Cisplatin/Adriamycin is an active combination in mixed mesodermal tumors and CA-125 appears to be a useful marker for following therapy.

Aged↗

Salvage therapy with whole-abdominal irradiation in patients with advanced carcinoma of the ovary previously treated by combination chemotherapy.

Whole-abdominal irradiation was delivered to 22 patients with epithelial carcinoma of the ovary who had persistent disease after chemotherapy. Seventeen patients were treated with an open whole-abdominal field and 5 with the moving-field technique. Eleven of the 22 also received a pelvic boost. Two of nine patients with microscopic disease at second look are alive and disease-free at 34 and 52 months, respectively. There were no salvages among the patient with macroscopic disease. Major complications included bowel obstruction in three patients and radiation enteritis in one patient. Whole-abdominal irradiation is not an effective salvage regimen after multiagent chemotherapy.

Abdomen↗

Reversal of transformed phenotype by monoclonal antibodies against Ha-ras p21 proteins.

The transforming activities of p21 ras proteins have been determined by micro-injection of these proteins into NIH3T3 cells. In order to facilitate functional studies on the effect of ras proteins on malignant transformation and normal cellular growth, analysis has been made with three monoclonal antibodies (YA6-172, Y13-238 and Y13-259) as originally reported by Furth et al. (J virol 43 (1982) 294). Purified immunoglobulin of Y13-259 has the highest titer of binding to bacterially synthesized p21 ras proteins. Experimental analyses indicate that only Y13-259 antibody will neutralize the transforming activity of the co-injected bacterially synthesized ras protein and the neutralization effect was blocked by co-injection of excess ras protein. In addition, micro-injection of Y13-259 immunoglobulin into transformed NIH3T3 cells (obtained by DNA transfection of NIH3T3 cells with molecularly cloned ras gene) reversed their transformed phenotypes. These results indicate that both bacterially synthesized p21 ras proteins and the natural ras proteins produced in NIH3T3 cells were neutralized by Y13-259 antibody.

Animals↗

Application of autoregressive modelling in magnetic resonance imaging to remove noise and truncation artifacts.

Magnetic resonance imaging data is conventionally reconstructed using two dimensional discrete Fourier transforms. However, there is growing interest in other types of spectral estimation which minimize noise and artifacts due to truncated data. This note presents preliminary results--showing the improvement obtainable using a modified autoregressive model, the Transient Error method.

Algorithms↗

Perception of syllable timing by prebabbling infants.

Adults hear alternating syllables with isochronous syllable onset-onset times as having a long-short, alternating rhythm when the syllables differ in initial consonant. This occurs because adults attend to syllable-internal events, called the "P centers" or "stress beats", rather than to syllable onsets. Thus they report that stress-beat aligned speech is isochronous and stress-beat aligned clicks are synchronized with the speech. The question asked here is whether, like adults, infants attend to the timing of syllable stress beats. In experiment 1, infants showed differences in time to habituate to sequences of alternating monosyllables, [bad] and [strad], having two different onset-onset times (onset- and stress-beat-timed) and two different placements of clicks on the syllables (on syllable onsets and on stress beats). Infants habituated more slowly to sequences with clicks on the stress beats than to sequences with clicks on syllable onsets and most slowly of all to stress-beat-timed speech with clicks on the stress beats. To interpret these findings, a second experiment was run using sequences only of the syllable [strad] so that speech timing measured according to onsets and stress beats was the same. Syllables had isochronous timing or a long-short alternating rhythm, corresponding to two possible ways of hearing the stress-beat-timed speech of experiment 1. In addition, two patterns of click placement were compared, uniform and syncopated, corresponding to two ways of hearing the stress-beat aligned clicks of experiment 1. The patterns of sucking times in the two experiments match exactly if stress-beat aligned speech in experiment 1 is identified with the isochronous speech of experiment 2 and the stress-beat aligned clicks of experiment 1 match with the uniformly timed clicks of experiment 2. It is inferred from this correspondence that infants perceive stress beats and stress-beat timing of syllables as adults do.

Attention↗

Improved delineation of human dopamine receptors using [18F]-N-methylspiroperidol and PET.

The brain uptake of [18F]-N-methylspiroperidol, a butyrophenone neuroleptic with high selectivity for the dopamine receptor, has been measured in three normal human volunteers using positron emission tomography for times up to 12 hr postinjection. These studies demonstrated two unique findings concerning the in vivo distribution of this neuroleptic: (a) it is tightly bound to dopamine D-2 receptors in the caudate-putamen brain regions, and (b) these regions are the only large brain structures which exhibit appreciable long-term retention. In addition, radioactivity clears rapidly from plasma, and the percentage of unchanged [18F]-N-methylspiroperidol in plasma declines rapidly. These results suggest that this compound binds irreversibly to dopamine D-2 receptors, and that there are few if any dopamine D-2 receptors in the human frontal cortex. These studies emphasize not only the importance of characterizing neurotransmitter receptors in living human brain using a ligand labeled with a positron emitting nuclide of sufficiently long half-life to allow monitoring of brain radioactivity distribution for several hours after the injection of radioligand, but also of accurately determining the amount of unchanged tracer in plasma for tracer kinetic modeling.

Adult↗

Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state.

Twenty-nine patients received intracoronary thrombolytic therapy for acute myocardial infarction 3.5 +/- 1.4 hours (mean +/- standard deviation) after the onset of pain. Ten patients received urokinase (UK) and 19 patients received streptokinase (SK). Laboratory variables of the coagulation system were measured before and immediately after therapy. When comparing patients in whom coronary artery recanalization occurred vs those in whom the artery remained occluded, those in whom recanalization was achieved had greater alterations in fibrinogen, prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products and plasminogen by thrombolytic therapy than did those in whom recanalization was not achieved (p less than 0.05 for all variables). Euglobulin lysis time showed a similar but nonsignificant trend (p = 0.114). Patients who received SK showed markedly greater alterations in coagulation parameters than did patients treated with UK (p less than 0.05 for 5 of 6 variables measured) and had a much higher incidence of successful thrombolysis (74% for SK, 20% for UK). These data indicate that the development of a systemic fibrinolytic state contributes to success when using intracoronary thrombolytic agents in acute myocardial infarction. Rather than being considered an adverse effect of therapy, a systemic lytic state may serve as a reasonable clinical goal in attempting to produce thrombolysis.

Adult↗

Non-Hodgkin's lymphoma and membranous nephropathy in mixed connective tissue disease.

A 60-year-old woman with a diagnosis of poorly differentiated lymphocytic lymphoma presented with nephrotic syndrome. Her clinical picture and serological studies were consistent with the diagnosis of mixed connective tissue disease (MCTD). Renal biopsy demonstrated the changes of membranous nephropathy by light, immunofluorescence and electron microscopy. Treatment with corticosteroids and cyclophosphamide had no effect on the proteinuria, and she demonstrated progression of renal failure. This patient demonstrates that the lymphadenopathy associated with MCTD may be of a separate malignant origin. The treatment of MCTD may not alter the course of renal disease, and renal failure may ensue in patients with MCTD.

Basement Membrane↗

Inhibition of methanogenesis and carbon metabolism in Methanosarcina sp. by cyanide.

NaCN was tested for its inhibitory effects on growth of and metabolism by Methanosarcina barkeri 227. NaCN (10 microM) inhibited catabolism of acetate methyl groups to CH4 and CO2 but did not inhibit methanogenesis from methanol, CO2, methylamine, or trimethylamine. NaCN also inhibited the assimilation of methanol or CO2 (as the sole carbon source) into cell carbon and stimulated the assimilation of acetate. These results suggest that inhibition by NaCN was a result of its action as an inhibitor of in vivo CO dehydrogenase. The results also implicate CO dehydrogenase in the oxidation of acetate but not methanol methyl groups to CO2.

Acetates↗

Methanosarcina mutant unable to produce methane or assimilate carbon from acetate.

Mutants of Methanosarcina barkeri 227 resistant to monofluoroacetate were isolated from monofluoroacetate-treated cultures. Mutant strain FAr9 was 100 times more resistant to monofluoroacetate than the wild-type strain and was deficient in carbon uptake and CH4 and CO2 production from methyl-labeled acetate. Methanol was assimilated at increased levels. Strain FAr9 was unable to shift from using methanol to using acetate for growth and exhibited increased sensitivity to growth inhibition by NaCN in methanol-containing complex medium. Unlike parent strain 227, acetate addition to methanol-containing media did not prevent NaCN inhibition. The specific activities of enzymes of exogenous acetate assimilation, CO dehydrogenase, and enzymes of the tricarboxylic acid cycle were similar for mutant and parent strain cell extracts. Mutation to monofluoroacetate resistance did not confer simultaneous resistance to 2-bromoethanesulfonate or pyruvate or alter propionate uptake. We conclude that strain FAr9 is either an acetate permeability mutant or is defective in an activation step required for the catabolism and anabolism of acetate.

Acetates↗

Nucleosome arrangement in alpha-satellite chromatin of African green monkey cells.

By analyzing the accessibility of restriction endonuclease sites in African green monkey alpha-satellite chromatin, we demonstrate the absence of a unique phase relationship between nucleosomes and alpha-satellite DNA. The data indicate a minimum of three different positions for nucleosome cores relative to the alpha-satellite sequence and suggest a random distribution in at least some regions. In addition, while we confirm published reports that staphylococcal nuclease cuts the alpha-satellite sequence in chromatin at a highly preferred site, two-dimensional gel electrophoresis of nuclear digests demonstrates that this site is preferentially cut by staphylococcal nuclease even when it is within the nucleosome core. These data indicate that staphylococcal nuclease is not useful for determining nucleosome positions on alpha-satellite DNA, and perhaps on other specific DNA sequences as well.

Animals↗