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Biomedical subjects

M E Williams

Publications and source records attributed to M E Williams.

At least 127 records · Page 7Linked to original sources
PubMed1991

Multifactor stimulation of megakaryocytopoiesis: effects of interleukin 6.

We have previously demonstrated that interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) stimulate various aspects of megakaryocytopoiesis. We have investigated the capacity of interleukin 6 (IL-6) to stimulate megakaryocyte colony formation from both normal Balb/C marrow and light-density marrow extensively depleted of adherent, pre-B, B and T cells. Human recombinant IL-6 (167 ng/ml) stimulated megakaryocyte colony formation from normal marrow (8.6 +/- 1 megakaryocyte colony-forming units [CFU-meg]/10(5) cells) as compared to control (1.5 +/- 4 CFU-meg/10(5) cells) in 16 determinations (p less than 0.01). IL-6 (167 ng/ml) also stimulated CFU-meg formation from depleted marrow (control, 10.8 +/- 4 CFU-meg/10(5) cells versus IL-6, 68 +/- 19 CFU-meg/10(5) cells in 12 determinations, p less than 0.01). IL-6 synergistically augmented IL-3-induced colony formation (139% IL-3 control, 120% calculated IL-3 plus IL-6 control, n = 11, p less than 0.01) in normal marrow and showed an additive effect in depleted marrow (133% IL-3 control, p less than 0.01, 114% of IL-3 plus IL-6, value not significant [NS] at 0.05 level). Studies with recombinant murine IL-6 gave similar results. There was an increasing level of megakaryocyte colony-stimulating activity from G-CSF (16,667 U/ml, 2.47 +/- 0.6 CFU-meg/10(5) cells, n = 17), to IL-6 (167 ng/ml, 8.47 +/- 0.96 CFU-meg/10(5) cells, n = 19), to GM-CSF (52 U/ml, 23 +/- 4 CFU-meg/10(5) cells, n = 14), to IL-3 (167 U/ml, 48 +/- 5 CFU-meg/10(5) cells, n = 20) as compared to media-stimulated marrow (range 1.29-1.86 CFU-meg/10(5) cells). A similar hierarchy was seen with depleted marrow. Combinations of factors (including IL-3, GM-CSF, G-CSF, and IL-6) tested against normal unseparated murine marrow did not further augment CFU-meg numbers over IL-3 plus IL-6 but did increase colony size. These data suggest that IL-6 is an important megakaryocyte regulator, that at least four growth factors interact synergistically or additively to regulate megakaryocytopoiesis, and that combinations of growth factors, possibly in physical association, might be critical in stimulating megakaryocyte stem cells.

Animals↗
PubMed1991

Endocrine crises. Hyperkalemia.

Clinical disorders causing hyperkalemia require a basic understanding of normal K homeostasis, which consists of external and internal K balances. The kidney is predominant in maintaining the external balance of K, and a number of mechanisms exist to provide a renal adaptation to defend against K excess. Likewise, several factors are known to modulate internal K balance--i.e., its distribution within the body. Some of these factors may provide defense against hyperkalemia before the kidneys have time to adapt. Potassium retention by the kidney causes hyperkalemia when renal failure is advanced, or earlier in the face of impaired tubular function in a variety of disorders. Hyperkalemia out of proportion to loss of renal function also occurs in the syndrome of hyporeninemic hypoaldosteronism. Drug-induced hyperkalemia is increasingly common and usually is caused by nonsteroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, cyclosporine, or K-sparing diuretics. Clinical disorders of internal K imbalance include diabetes mellitus, systemic acidosis, and use of beta-blockers. Hyperkalemia is usually asymptomatic, but the danger of cardiac arrest or arrhythmia in severe hyperkalemia forces prompt clinical attention. Available treatment choices include agents that antagonize the effect of K on membrane potentials, redistribute it internally into cells, and remove it altogether from the body. The diagnostic work-up can then proceed, first by distinguishing renal and extrarenal causes, then by examining the roles of specific factors outlined in the section on normal K homeostasis.

Aged↗
PubMed1990

Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus.

Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC). These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas. DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements. All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin. None of the specimens had detectable CB, bcl-2, or c-myc rearrangements. However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus. Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements. This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases. Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas.

Blotting, Southern↗
PubMed1990

Primary structure of the gamma subunit of the DHP-sensitive calcium channel from skeletal muscle.

Affinity-purified, polyclonal antibodies to the gamma subunit of the dihydropyridine (DHP)-sensitive, voltage-dependent calcium channel have been used to isolate complementary DNAs to the rabbit skeletal muscle protein from an expression library. The deduced primary structure indicates that the gamma subunit is a 25,058-dalton protein that contains four transmembrane domains and two N-linked glycosylation sites, consistent with biochemical analyses showing that the gamma subunit is a glycosylated hydrophobic protein. Nucleic acid hybridization studies indicate that there is a 1200-nucleotide transcript in skeletal muscle but not in brain or heart. The gamma subunit may play a role in assembly, modulation, or the structure of the skeletal muscle calcium channel.

Amino Acid Sequence↗
PubMed1990

Anti-CD3 antibody induces unresponsiveness to IL-2 in Th1 clones but not in Th2 clones.

Culture of murine T cells with immobilized (platebound) anti-CD3 antibody results in autocrine growth factor secretion in both Th1 (IL-2 producing) and Th2 (IL-4 producing) cells. Using a panel of murine T cell clones, we demonstrate that the IL-2-induced proliferation of Th1 clones is dramatically inhibited by immobilized anti-CD3 antibody, whereas that of Th2 clones is not. This unresponsiveness of Th1 clones to IL-2 is not due to decreases in IL-2R expression. Supernatants from Th1 or Th2 cell cultures fail to alter the effects of anti-CD3 on the two types of clones, suggesting that unresponsiveness induced in Th1 clones or the lack thereof in Th2 clones is not mediated by a stable cytokine(s). Accessory cells enhance the proliferation of Th1 cells exposed to low concentrations of anti-CD3, but the unresponsiveness induced by high concentrations of anti-CD3 is not prevented by accessory cells. Finally, soluble anti-CD4 antibody prevents the induction of the unresponsive state even at high concentrations of anti-CD3. These experiments demonstrate that two subsets of cloned CD4+ T cells differ in their responses to anti-CD3, and that CD4 molecules may play a critical role in regulating the outcome of receptor-mediated stimulation.

Animals↗
PubMed1990

Differential expression of two related organ-specific genes in pea.

We have screened a pea genomic library using a cDNA probe derived from pea shoot RNA. From this screen, we isolated two closely related genes, designated as S2 and P4. An intriguing property of these two genes is the presence in their coding region of a repeated sequence that is conserved between them in sequence but not in the number of the repeating units. The predicted amino acid sequence suggests that these proteins could be exported and glycosylated. 3' S1 analysis reveals that one of the genes, S2, is expressed highly in stem, as expected from previous work. However, mRNA derived from the other gene, P4, is not detectable in stem tissue, but is present in tissue derived from pea pods. The 5' upstream sequence of S2 and P4 are 94% identical up to position -121, suggesting that sequences upstream of -121 are responsible for organ-specific expression of the two genes.

Amino Acid Sequence↗
PubMed1990

Career development in academic medicine.

Clinical academic medicine desperately needs the continued infusion of talented young academicians, but many young faculty are not pursuing strategies that optimize their chances for academic survival. Many junior faculty are overburdened with clinical demands and do not have a well-focused research agenda. Such situations will hinder the full development of many talented young persons. In order to optimize chances for success, young faculty should clearly define their goals, carefully negotiate the terms of their employment, practice sound principles of time management, identify a mentor, and develop a focused research agenda.

Attitude of Health Personnel↗
PubMed1990

Detection of B- and T-cells in paraffin-embedded tissue sections. Diagnostic utility of commercially obtained 4KB5 and UCHL-1.

Although many recent studies have begun exploring the diagnostic utility of anti-B- and anti-T-cell antibodies that work on paraffin-embedded tissue sections, the most optimal panel to use remains uncertain. In addition, many of the published reports have used antibodies obtained before their commercial formulation and distribution. For these reasons, B5-fixed paraffin-embedded tissue samples from 174 reactive or neoplastic lymphoid and hematopoietic proliferations were immunostained with the commercially obtained antibodies 4KB5, UCHL-1, and, in selected cases, L26. In reactive nodes, 4KB5 stained B-cell areas and UCHL-1 T-cell areas. Seventy-nine percent of the B-cell neoplasms were 4KB5 positive, and only 2% were UCHL-1 positive. Two cases of myeloma were 4KB5 and UCHL-1 negative. The 4KB5-negative B-cell lymphomas (ML-B) were all L-26 positive. UCHL-1 stained 78% of the T-cell lymphomas (ML-T), and 4KB5 stained 14%. In the five 4KB5-positive putative T-cell lymphomas, immunoglobulin and T-cell receptor gene rearrangement studies were performed. In Hodgkin's disease (HD), Reed-Sternberg (RS) cells were UCHL-1 negative in 75% of cases and occasionally positive in 25%. Definite 4KB5 positivity of RS cells was identified in both cases of lymphocyte predominant HD and in one case of nodular sclerosing HD with monomorphic large cell areas. With the exception of 1 of 15 acute nonlymphocytic leukemias that was UCHL-1 positive, all acute leukemias were 4KB5 and UCHL-1 negative. In summary, commercially obtained 4KB5 and UCHL-1 form a useful but not absolutely specific or sensitive paraffin section immunoperoxidase panel for the categorization of B- and T-cell lymphoid neoplasms. Addition of L26 appears to add to the sensitivity and specificity of the panel. Definite immunophenotypic distinction of HD from non-Hodgkin's lymphomas, particularly of T-cell type, often was not possible.

Antibodies, Monoclonal↗
PubMed1990

Fine-needle aspiration of non-Hodgkin's lymphoma. Southern blot analysis for antigen receptor, bcl-2, and c-myc gene rearrangements.

To determine the utility of Southern blot analysis for fine-needle aspiration samples, the authors prospectively analyzed immunoglobulin, T-cell receptor, c-myc, and bcl-2 gene rearrangements in 27 cases of known or suspected lymphoma. Adequate DNA for analysis was obtained from 20 of 27 cases (74%), including 18 of 22 (82%) with non-Hodgkin's lymphoma (NHL). Patients whose tumors showed sclerosis, cellular degeneration, or necrosis yielded inadequate DNA. Of the 18 NHLs with successful Southern blot studies, 17 tumors had a B-cell lineage and one was an adult T-cell leukemia/lymphoma; clonal integration of the human T-cell leukemia virus I (HTLV-I) genome was present in the latter case. Four cases had bcl-2 rearrangements and two had c-myc rearrangements. One patient with follicular small cleaved cell NHL that evolved to a small noncleaved cell NHL had coexisting bcl-2 and c-myc rearrangement in the aspiration specimen of the high-grade NHL, suggesting sequential bcl-2 and c-myc activation during the tumor's progression. Southern blot analysis is a useful technique for establishing tumor cell lineage, clonality, and the presence of oncogene rearrangements in fine-needle aspiration specimens of NHL.

Adult↗
PubMed1990

The emerging relationship between academic health centers and continuing care retirement communities.

A survey of the 96 member-institutions of the Association of Academic Health Centers was conducted by the authors during the 1988-89 academic year to determine the number and types of contractual ties with continuing-care retirement communities (CCRCs). Of the 88 academic health centers that responded, 24% had an existing relationship with a CCRC; 26% were in the process of developing such a relationship; 7% had considered but decided against such a relationship; and 43% had not considered developing such a relationship. The authors document a rapid increase in the number of such relationships in the latter half of the 1980s and suggest that this trend is comparable to the increase in formal relationships with nursing homes begun by academic health centers in the early 1980s. Issues raised by those institutions that responded are presented, levels of possible involvement with a CCRC are described, and the contractual agreement between the University of North Carolina School of Medicine's Program on Aging and a local CCRC is presented as an example of the benefits that can be gained from such a relationship.

Academic Medical Centers↗
PubMed1990

Timed manual performance in a community elderly population.

The extent of functional disability measured by performance of a series of simple manual tasks was determined in 1,286 elderly people, aged 66 to 98, who resided in central North Carolina. Missing data left 1,106 subjects for analysis. Poor manual performance was defined by either of two criteria: (1) inability to complete all the test items, or (2) taking longer than 350 seconds to complete the test. Using the first criterion, 113 persons (10.2%) were poor performers. When the two writing items were omitted from the analysis, 28 persons (2.4%) were in the poor performance group. Of the 993 persons who completed all items, 59 persons (5.9%) performed poorly. Using both criteria, the extent of functional disability was 16.1%; excluding the writing items, the extent of poor performance was 8.3%. Compared to those who performed well, those who performed poorly were older, poorer, less educated, more likely to be black, and less healthy. Because manual ability correlates highly with functional dependency and identifies those at risk for increased care needs, the magnitude of manual dysfunction noted in this survey has important implications for care providers and policy-makers.

Activities of Daily Living↗
PubMed1990

What practicing physicians in North Carolina rate as their most challenging geriatric medicine concerns.

We recently surveyed a random sample of 500 physicians in family practice, general practice, and internal medicine in North Carolina, to discover their most challenging geriatric concerns. Using a three-stage survey technique, respondents were asked to answer two open-ended questions about the most challenging geriatric problems they face and what specific geriatric content areas would attract their participation in an educational program. They were then asked to rank 34 topics on which they would like more information. A total of 242 responses were received for a 55% response rate (63 of the 500 were undeliverable). Responses indicated that physicians are more concerned with management than diagnosis and revealed considerable evidence of empathy and concern. The top three topics had to do with the management of dementia, multiple problems, and depression. Approximately 25% of physicians consider problems of financing health care as among the most challenging problems.

Adult↗
PubMed1990

The physician's role in nursing home care: an overview.

Providing effective, high-quality care in the nursing home is an important medical responsibility. Physicians must have knowledge of the nursing home environment, medical problems common in nursing home patients, and basic aspects of care required in the elderly. While the medical director of a nursing home must set and maintain the standard of care, attending physicians need to understand the clinically relevant differences between young and old people, be skilled in geriatric assessment, prescribe medications knowledgeably and with restraint, respond promptly to changes in the patient's status, and carefully document medical observations and care plans.

Aged↗
PubMed1990

Monomorphic lymphomas arising in patients with Hodgkin's disease. Correlation of morphologic, immunophenotypic, and molecular genetic findings in 12 cases.

Patients with Hodgkin's Disease (HD) occasionally develop monomorphic lymphomas in which mononuclear cells, usually large in size, grow in sheets, and in which there are few reacting cells or classic Reed-Sternberg (RS) cells. Twelve patients of this type were reviewed to determine the nature of the monomorphic growth. Paraffin-embedded tissue sections from the original diagnostic HD and the monomorphic growths were stained for Leu-M1 (CD15), leukocyte common antigen (LCA, CD45), pan B-cell markers LN1, LN2, and L26, and pan T-cell marker UCHL1 (CD45R) reactive in paraffin-embedded tissues. Cases were included only if the original diagnostic material had the classic histopathologic features of HD, if there was a separate monomorphic growth (in place or time), and if sufficient materials from both phases were available for study. Original diagnoses of HD included nodular sclerosing (NS; 8 cases); lymphocyte predominant (LP; 2 cases); mixed cellularity (MC; 1 case); and lymphocyte depleted (LD: 1 case) types. RS cells in the eight cases of NS HD and one case of MC HD were generally Leu-M1 and LN2 positive, and L26, LN1, UCHL1, and LCA negative. RS cells in one case of NS HD were LCA positive in addition to Leu-M1, LN1, and LN2. Two cases of NS HD showed L26 positive RS cells. Conversely, RS cells and lymphocytic-histiocytic (L and H) variants in the cases of LP HD were Leu-M1 and LN2 negative, and LCA and LN1 positive. The one case of LD HD possessed RS cells that were negative for Leu-M1, but positive for LCA, L26, LN1, and LN2. In seven cases (4 NS, 2 LP, 1 LD) the monomorphic growths possessed a B-cell phenotype (LCA, L26, and LN1 positive; Leu-M1 and UCHL1 negative). In the remaining cases (4 NS, 1 MC), the monomorphic growths were Leu-M1 positive, and displayed phenotypes similar to the RS cells of the original NS HD. Southern blot analysis was performed on the monomorphic components of five cases and showed some form of immunoglobulin gene rearrangement in each (4 cases: rearranged heavy chain-joining region gene; 1 case: rearranged Mu chain-constant region gene). Two of these cases expressed L26 and LN1 in the monomorphic phases. Despite apparent immunoglobulin gene rearrangement, one case expressed T-cell antigens Leu-4 (CD3) and Leu-1 (CD5), in addition to Leu-M1 (CD15).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗