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Biomedical subjects

M E Williams

Publications and source records attributed to M E Williams.

At least 145 records · Page 8Linked to original sources
PubMed1990

ATLL complicated by strongyloidiasis and isosporiasis: case report.

In summary, we present this as the first reported case of both isosporiasis and strongyloidiasis complicating HTLV-I-associated ATLL. Prompt diagnosis and treatment of these parasites in the immunocompromised host are necessary to prevent severe wasting and dehydration. This should also prevent the significant morbidity and mortality associated with dissemination well-described for Strongyloides, and recently seen at autopsy in a patient with isosporiasis. Recurrent infections are common with both organisms, therefore chronic suppressive therapy and prophylactic treatment prior to chemotherapy or steroid administration is warranted.

Coccidiosis↗
PubMed1989

Site-directed mutagenesis of yeast C1-tetrahydrofolate synthase: analysis of an overlapping active site in a multifunctional enzyme.

C1-tetrahydrofolate (THF) synthase is a trifunctional protein possessing the activities 10-formyl-THF synthetase, 5,10-methenyl-THF cyclohydrolase, and 5,10-methylene-THF dehydrogenase. The current model divides this protein into two functionally independent domains with dehydrogenase/cyclohydrolase activities sharing an overlapping active site on the N-terminal domain and synthetase activity associated with the C-terminal domain. Previous chemical modification studies on C1-THF synthase from the yeast Saccharomyces cerevisiae indicated at least two cysteinyl residues involved in the dehydrogenase/cyclohydrolase reactions [Appling, D. R., & Rabinowitz, J. C. (1985) Biochemistry 24, 3540-3547]. In the present work, site-directed mutagenesis of the S. cerevisiae ADE3 gene, which encodes C1-THF synthase, was used to individually change each cysteine contained within the dehydrogenase/cyclohydrolase domain (Cys-11, Cys-144, and Cys-257) to serine. The resulting proteins were overexpressed in yeast and purified for kinetic analysis. Site-specific mutations in the dehydrogenase/cyclohydrolase domain did not affect synthetase activity, consistent with the proposed domain structure. The C144S and C257S mutations result in 7- and 2-fold increases, respectively, in the dehydrogenase Km for NADP+. C144S lowers the dehydrogenase maximal velocity roughly 50% while C257S has a maximal velocity similar to that of the wild type. Cyclohydrolase catalytic activity is reduced 20-fold by the C144S mutation but increased 2-fold by the C257S mutation. Conversion of Cys-11 to serine has a negligible effect on dehydrogenase/cyclohydrolase activity. A double mutant, C144S/C257S, results in catalytic properties roughly multiplicative of the individual mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Biochemical effects of 17 beta-estradiol on UMR106 cells.

The effect of 17 beta-estradiol (E) on an osteoblast-like cell line, UMR106, was studied in vitro. The concentrations of transferrin and seven enzymes (gamma glutamyl transferase, alkaline phosphatase, acid phosphatase, lactate dehydrogenase, creatine kinase, alanine aminotransferase and aspartate aminotransferase) were measured in these cells after incubation in culture medium containing either E or the vehicle. E treatment increased five of the seven enzymes and increased the transferrin concentration in the UMR106 cells while simultaneously reducing the proliferation rates. 4-Hydroxytamoxifen, an estrogen antagonist, produced a mild estrogen agonist action on growth rates and enzyme concentrations in the UMR106 cells. When E was present simultaneously, the agonist properties of 4-hydroxytamoxifen were enhanced. These studies show that E enhanced activity of five enzymes and the transferrin content of UMR106 cells after a 2-day incubation. 4-Hydroxytamoxifen enhanced the E effect, illustrating that estrogen antagonists may manifest agonist or antagonist properties depending on the model. These results extend our previous observations showing a direct effect of E in vitro on osteoblast-like cells.

Acid Phosphatase↗
PubMed1989

Ki-1-positive cutaneous large cell lymphoma of T cell type: report of an indolent subtype.

T cell lymphomas that demonstrate skin involvement include not only mycosis fungoides and Sézary syndrome but also a wide variety of other T cell neoplasms. Whether any specific clinicopathologic associations exist for nonmycosis fungoides/Sézary syndrome cutaneous T cell lymphomas is not known, and whether they represent distinct entities or a spectrum of a similar disease process also is not known. We describe a patient with a localized cutaneous large cell lymphoma with a Ki-1-positive "aberrant" T helper/inducer phenotype. Clonal rearrangement of the T cell receptor gene was documented. Although these histologic characteristics and immunophenotype are usually associated with high-grade lymphomas, the patient appears clinically to have a much less aggressive neoplasm. The possible relationship of this overt lymphoma to lymphomatoid papulosis is discussed.

Antigens, Differentiation↗
PubMed1989

Mutations in the maize mitochondrial T-urf13 gene eliminate sensitivity to a fungal pathotoxin.

URF13, the product of the mitochondrial T-urf13 gene, confers on Texas cytoplasmic male-steril maize (Zea mays L.) a unique susceptibility to a fungal pathogen (Bipolaris maydis race T) and sensitivity to its pathotoxin. Expression of URF13 in Escherichia coli imparts pathotoxin sensitivity to the bacterium. We show by ion uptake studies in E. coli that a pathotoxin-URF13 interaction causes membrane permeability. Similarly, mitochondrial dysfunction caused by membrane permeabilization probably accounts for increased colonization of maize carrying the Texas cytoplasm by toxin-producing pathogens. Site-directed mutagenesis studies show that approximately one-quarter of the amino acids at the carboxyl end of URF13 can be eliminated without affecting toxin sensitivity. We have identified two dicyclohexylcarbodiimide (DCCD) binding sites in the URF13 protein and show that one of the sites is involved in conferring DCCD protection against the pathotoxin. Substitutional mutations at this DCCD binding site also eliminate toxin sensitivity.

Amino Acid Sequence↗
PubMed1989

Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma.

We report a case of untreated non-Hodgkin's lymphoma with histologic progression over 1 yr from a low-grade, small cleaved follicular center cell lymphoma to a high-grade, small noncleaved follicular center cell lymphoma. Both lymphomas had identical immunoglobulin (Ig) heavy-chain joining gene (JH), kappa light-chain joining gene, and bcl-2 gene rearrangements, indicating the clonal identity of the two tumors. The Ig heavy chain locus on one chromosome 14 was involved in an initial t(14; 18) translocation as shown by comigrating JH and bcl-2 rearrangements. However, the oncogene c-myc was in the germline configuration in the initial lymphoma but had one allele rearranged near the 3' end of exon I in the high-grade tumor; DNA sequence analysis was consistent with a chromosomal breakpoint at that site. The presence of the c-myc rearrangement in the high-grade tumor suggest a role for c-myc in the clonal evolution of the low-grade tumor into a more aggressive lymphoma. The coexistence of both bcl-2 gene and c-myc oncogene rearrangements in the same tumor is unusual, with only a few cases reported. Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.

Base Sequence↗
PubMed1988

Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel.

Complementary DNAs were isolated and used to deduce the primary structures of the alpha 1 and alpha 2 subunits of the dihydropyridine-sensitive, voltage-dependent calcium channel from rabbit skeletal muscle. The alpha 1 subunit, which contains putative binding sites for calcium antagonists, is a hydrophobic protein with a sequence that is consistent with multiple transmembrane domains and shows structural and sequence homology with other voltage-dependent ion channels. In contrast, the alpha 2 subunit is a hydrophilic protein without homology to other known protein sequences. Nucleic acid hybridization studies suggest that the alpha 1 and alpha 2 subunit mRNAs are expressed differentially in a tissue-specific manner and that there is a family of genes encoding additional calcium channel subtypes.

Amino Acid Sequence↗
PubMed1988

Quantifying the ease or difficulty older persons experience in opening medication containers.

To compare the difficulty experienced by older persons in using various medication containers, 50 noninstitutionalized women and men over 60 years of age were timed while opening 15 containers. Pill and liquid medication bottles with and without child-resistant closure mechanisms were tested. In addition, other types of medication packaging were evaluated, such as nitroglycerin patches. All subjects could open each of the non-child-resistant containers, though none of the child-resistant containers could be opened by all participants. For child-resistant containers, dramatic differences were observed in the proportion of subjects who could open the various designs and in the amount of time required. Subjects' comments and observations of subjects' efforts provided possible reasons for some of these differences. The results suggest that when child-resistant containers are used, consideration of the type of medication container can significantly reduce inconvenience to older persons. Containers without child-resistant mechanisms provide the best option for elderly people when access by small children is not an issue.

Activities of Daily Living↗
PubMed1988

Identification of mouse adenovirus type 1 early region 1: DNA sequence and a conserved transactivating function.

The left end of the genome of mouse adenovirus type 1 (also known as strain FL) was characterized by determination of the DNA sequence, amino acid similarities with early region proteins of primate adenoviruses, and a functional assay. Several specific DNA sequence features were similar to those found in human adenoviruses, and open reading frames from this region could encode proteins similar to human adenovirus early region 1A and early region 1B proteins. DNAs from this region were tested in transient-expression assays in human and mouse cells were found to transactivate the human adenovirus type 5 early region 3 promoter fused to the chloramphenicol acetyltransferase gene. The data indicate structural and functional homologies between mouse adenovirus type 1 early region 1 and early region 1 of primate adenoviruses.

Adenoviridae↗
PubMed1988

Maintaining health in older people with multiple chronic illnesses.

The effective management of the elderly patient who has multiple chronic conditions is an important clinical responsibility. Of special importance is an understanding and appreciation of the maintenance of function. A focus on the patient's needs and ability to function, rather than on the diseases from which he or she suffers, is more likely to improve productivity and quality of life. These goals can usually be achieved in the elderly patient without curing the underlying disease.

Activities of Daily Living↗
PubMed1987

Retrovirus infection alters growth factor responses of T lymphocytes.

A murine helper/inducer T cell clone, D10.G4, has been infected with Kirsten-murine sarcoma virus (KiSV) pseudotyped with an amphotropic murine leukemia virus. The resultant Ki-ras-expressing lines (KiSV-D10) remain dependent on exogenous factors for continued growth but display distinctly different mitotic responses to certain cytokines as compared to the uninfected parent clone. Unlike the parent D10.G4 cells, these KiSV-D10 cells can be maintained in vitro indefinitely in the presence of recombinant interleukin 2 (IL 2), and they all display a maximal proliferative response to purified or recombinant interleukin 1 (IL 1). The IL 1-induced proliferation is shown not to be dependent or secretion of the T cell autocrine growth factors IL 2 or B cell stimulatory factor-1 (BSF-1). The KiSV-D10 lines show certain differences from one another and parent D10.G4 cells in their secretory and proliferative responses to T cell receptor- and BSF-1 mediated signals. These viral oncogene-expressing T cell lines, which remain responsive to and dependent on physiologic growth factors, should prove valuable for analyzing the mechanisms of action of single oncogenes and the intracellular events in T lymphocyte activation.

Animals↗
PubMed1987

How does the team approach to outpatient geriatric evaluation compare with traditional care: a report of a randomized controlled trial.

Although team-oriented geriatric assessment clinics are growing throughout the country, little documentation exists regarding their clinical efficacy, cost-effectiveness, or impact on patient functioning and well-being. This report describes a randomized controlled clinical trial to evaluate the effectiveness of a team-oriented geriatric assessment approach compared to traditional care. One hundred-seventeen subjects 65 years of age and over, meeting eligibility criteria to target frail older persons with changing medical and social needs, were randomly assigned to receive a comprehensive geriatric assessment by a multidisciplinary team (treatment) or by one of a panel of community internists who were reimbursed according to their usual and customary fee (controls). Extensive analysis of baseline information failed to identify any significant differences between groups. Over the 1-year follow-up period, treatment participants experienced 26 hospital admissions and used 670 hospital days compared with 23 admissions and 1113 days for controls (a 39.8% difference). Annual hospital costs averaged $4297 for treatment subjects and $7018 for controls. Overall institutional costs including hospital and nursing home care revealed an average saving of $2189 per person for treatment subjects compared with controls, a 25% reduction. A small proportion of subjects accounted for this difference. No significant differences were noted in patient or caregiver satisfaction with the evaluation process, functional ability, or health status. These findings suggest that team-oriented outpatient geriatric assessment provides a promising way to deliver high-quality, satisfying care to older persons without increasing (and possibly decreasing) health care costs.

Aged↗
PubMed1987

Identifying the older person likely to require long-term care services.

The purpose of this study is to determine the accuracy of predictions in identifying older persons who subsequently require long-term care such as home services or institutionalization. Eighty-six individuals undergoing geriatric evaluation between May 1983 and April 1984 were evaluated using a series of commonplace tasks such as opening doors, stacking checkers, and copying a simple sentence. Predictions of an individual's use of long-term care services were made during the initial evaluation and were based on whether the person could complete all the manual tasks and on the amount of time required to do so. Outcomes were determined by telephone interviews by a trained social worker in Dec 1984. A statistically significant association (P less than 0.005) was observed between the predictions and actual outcomes. Analysis of variance confirmed that the mean times for each outcome were different (F = 2.6, P less than 0.05). The results suggest that timing manual performance offers a useful way to prospectively identify older persons at risk of requiring additional long-term care services.

Aged↗