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Biomedical subjects

R Fine

Publications and source records attributed to R Fine.

At least 37 records · Page 2Linked to original sources
PubMed1991

The impact of diuretic therapy on reported sexual function.

BACKGROUND: --Thiazide diuretics are the most commonly prescribed antihypertensive agent in the treatment of hypertension. No studies to date have isolated conclusively the effect of diuretic therapy on patient quality of life, and particularly on sexual dysfunction. METHODS: --We carried out a randomized placebo-controlled trial of the effect of thiazide diuretics on quality of life in mildly hypertensive men between the ages of 35 and 70 years. After a 1-month washout period off diuretic therapy, the men were randomized to a 2-month trial of a thiazide treatment or placebo. At the end of the trial, 176 men completed a confidential self-administered questionnaire assessing aspects of social performance, general well-being, and emotional and physiologic states. RESULTS: --Patients taking diuretics reported significantly greater sexual dysfunction than control subjects, including decreased libido, difficulty in gaining and maintaining an erection, and difficulty with ejaculation. Multivariate analysis suggested that the findings were not mediated by low serum potassium levels or by low blood pressure. Sexual dysfunction was noted more often in the confidential self-report questionnaire than in response to direct questions from clinicians. We found no differences between diuretic and placebo groups in measures of mood, general sense of well-being, ability to work, alertness, and social/recreational activities. CONCLUSIONS: --Thiazide diuretic use is associated with male sexual dysfunction but does not appear to adversely affect other aspects of quality of life.

Adult↗
PubMed1990

Phase I and pharmacokinetic study of arabinofuranosyl-5-azacytosine (fazarabine, NSC 281272).

A Phase I clinical trial of 1-beta-D-arabinofuranosyl-5-azacytosine (ara-AC or fazarabine) given as a 72-h continuous infusion on a 21-day cycle was conducted in 27 adult patients with refractory cancer. The major toxicity was reversible granulocytopenia and thrombocytopenia. Dose-limiting toxicity was observed at a dose rate of 1.96 mg/m2/h in which Grade IV leukopenia (WBC less than 1,000/mm3) occurred in 4 of 11 patients and Grade IV thrombocytopenia (platelets less than 25,000/mm3) occurred in 3 of 11 patients. Plasma steady-state levels ranged from 0.13 to 0.6 microM for doses of 1.25 to 5.94 mg/m2/h. Mean total body clearance was 647 ml/min/m2. Minor clinical responses were seen in one patient with testicular cancer, one patient with colon cancer, one patient with breast cancer, and one patient with acute nonlymphocytic leukemia. Another patient with adenocarcinoma of unknown primary had stable disease during 13 cycles of therapy. Based on the results of this study, the recommended dose for Phase II studies of 1-beta-D-arabinofuranosyl-5-azacytosine administered as a 72-h continuous infusion is 2.0 mg/m2/h (48 mg/m2/day).

Adult↗
PubMed1990

Characterization of the role of melanoma growth stimulatory activity (MGSA) in the growth of normal melanocytes, nevocytes, and malignant melanocytes.

Melanoma growth stimulatory activity (MGSA) was originally described as an endogenous growth factor for human melanoma cells. To test the hypothesis that an MGSA autocrine loop is responsible for the partial freedom from growth control observed in nevocytes and melanoma cells, MGSA growth response and MGSA mRNA/protein levels were examined in these cells compared with normal melanocytes. As a single agent, or in combination with other factors, MGSA stimulated the growth of normal human epidermal melanocytes as well as other growth promoters for melanocytes. Nevocytes were not as responsive to exogenous MGSA as melanocytes. MGSA mRNA was minimal or not detected in cultured normal melanocytes, although the protein was present when the cells were cultured in the presence of serum/growth factors and absent when serum/growth factors were omitted. In contrast, MGSA mRNA was constitutively expressed in the absence of exogenous growth factors in cultures established from benign intradermal and dysplastic nevi and melanoma lesions in different stages of tumor progression. Nevus cultures contained immunoreactive MGSA protein in the presence of serum but were negative or only faintly positive in the absence of serum. Melanoma cell lines were positive for MGSA protein in both the presence and the absence of serum. Thus, continued expression of both MGSA mRNA and MGSA protein in the absence of exogenous hormones or serum factors may correlate with partial freedom from growth control exhibited by malignant melanocytes.

Blotting, Northern↗
PubMed1989

Gallstone disease. The clinical manifestations of infectious stones.

Gallstones from 82 patients were examined under a scanning electron microscope for evidence of bacteria, and the findings were compared with the clinical manifestations of the disease. Bacteria were present in 68% of pigment stones and the pigment portions of 80% of composite stones. These gallstones were referred to as infectious stones. No bacteria were found in cholesterol gallstones. Acute cholangitis was diagnosed in 52% of patients with infectious stones and in 18% of patients with noninfectious stones. Over half of the patients with noninfectious stones presented with mild symptoms. Infectious stones were more often associated with a previous common duct exploration, an urgent operation, infected bile, a common duct procedure, and complications. These data show that gallstone disease is more virulent in patients whose gallstones contain bacteria.

Acute Disease↗
PubMed1988

Flow cytometry crossmatching for kidney transplantation.

1. Overall, positive FCXM reactions were associated with graft losses in regrafts but not in primary transplants. 2. In transplants involving older female or CVA donors, a positive FCXM appeared to be deleterious in both first transplants and regrafts. If the donor were a younger male and not a CVA victim, only FCXM positive regrafts had low graft survival rates. 3. We presented a 3-color technique allowing the differentiation of antibody reactions against T cells, B cells, and monocytes. Another method allows the simultaneous evaluation of both IgG and IgM reactions against T cells. Using these kinds of methods may make better identification of antibodies that may be harmful to a transplant allograft possible.

Antilymphocyte Serum↗
PubMed1987

Computer simulations of the diffusion of a substrate to an active site of an enzyme.

Computer simulations of the diffusion of a substrate to an enzyme active site were performed. They included the detailed shape of the protein and an accurate description of its electrostatic potential. Application of the method to the diffusion of the superoxide anion to the protein superoxide dismutase revealed that the electric field of the enzyme enhances the association rate of the anion by a factor of 30 or more. Calculated changes in the association rate as a function of ionic strength and amino acid modification paralleled the observed behavior. Design principles of superoxide dismutase are considered with respect to insights provided by the simulations. A possible means of enhancing the enzyme turnover rate through site-directed mutagenesis is proposed.

Binding Sites↗
PubMed1987

The flow cytometry crossmatch in kidney transplantation.

1. Positive FCXM reactions were associated with sensitization in transplants with negative cytotoxic crossmatches. Recipients of regrafts, females, particularly those with previous pregnancies, and recipients with historical cytotoxic antibody reactivity were more likely to have FCXM detectable antibodies. 2. Primary nonfunction grafts were associated with a positive FCXM, but predominantly in those transplants involving female, older, or nontrauma donors. Nearly 40% of the FCXM positive transplants of these organs did not function during the first month posttransplant 3. Low 3-month graft survival rates were associated with a positive FCXM reaction, but once again this was seen with female, older, and nontrauma donor transplants. In addition, approximately 40% of FCXM positive transplants involving older or nontrauma donors that did survive had poor graft function at 3 months.

Antilymphocyte Serum↗
PubMed1986

Focusing of electric fields in the active site of Cu-Zn superoxide dismutase: effects of ionic strength and amino-acid modification.

In this paper we report the implementation of a finite-difference algorithm which solves the linearized Poisson-Boltzmann equation for molecules of arbitrary shape and charge distribution and which includes the screening effects of electrolytes. The microcoding of the algorithm on an ST-100 array processor allows us to obtain electrostatic potential maps in and around a protein, including the effects of ionic strength, in about 30 minutes. We have applied the algorithm to a dimer of the protein Cu-Zn superoxide dismutase (SOD) and compared our results to those obtained from uniform dielectric models based on coulombic potentials. We find that both the shape of the protein-solvent boundary and the ionic strength of the solvent have a profound effect on the potentials in the solvent. For the case of SOD, the cluster of positive charge at the bottom of the active site channel produces a strongly enhanced positive potential due to the focusing of field lines in the channel-a result that cannot be obtained with any uniform dielectric model. The remainder of the protein is surrounded by a weak negative potential. The electrostatic potential of the enzyme seems designed to provide a large cross-sectional area for productive collisions. Based on the ionic strength dependence of the size of the positive potential region emanating from the active site and the repulsive negative potential barrier surrounding the protein, we are able to suggest an explanation for the ionic strength dependence of the activity of the native and chemically modified forms of the enzyme.

Amino Acids↗
PubMed1986

Growth factor and cytogenetic abnormalities in cultured nevi and malignant melanomas.

It has been proposed that benign nevi that fail to differentiate normally may undergo stepwise growth and morphologic changes resulting in progression toward dysplastic nevi, which in some cases progress into malignant melanoma. In this study, we sought to determine the relationship between production of endogenous growth factors and the appearance of chromosomal abnormalities in cultured nevi and melanomas. Newly established cultures from 8 nevi with benign histology and 6 malignant melanomas, and 2 malignant melanoma cell lines were studied. Assays for mitogenic growth factors were based on stimulation of [3H]thymidine incorporation into DNA in Hs0294 malignant melanoma cells, produced by serum-free conditioned medium from nevus or melanoma cultures. Karyotypes were examined in cultures of an equivalent passage. Three of the 8 nevus cultures were mitogen-negative and displayed normal karyotypes; one nevus culture was mitogen-positive and had a normal karyotype, although the biopsied tissue demonstrated histologic evidence of benign melanocytic proliferation; one was mitogen-negative initially, but had an extra chromosome 8 in 2 of 50 cells; 3 were mitogen-positive and chromosomally abnormal. Each of the cultures in this latter group exhibited reciprocal translocation (rcpt) as the only identifiable abnormality [rcpt(6;15), rcpt(10;15), rcpt(15;20)], or a constitutional rcpt(4;5). Thus, there was direct correlation between growth factor production and chromosome abnormality in 6 of 8 benign nevus cultures. In the newly established melanoma cultures there was also concordance between growth factor and chromosomal status; conditioned media from 4 of 6 were mitogen-positive by at least one assay, and all 4 of the mitogen-positive cultures had chromosomally abnormal cell populations. Of the 2 melanoma cultures negative for growth factors, one was also negative for chromosome abnormality; the other had chromosomal change consisting of increased polyploidy. Both melanoma cell lines had abnormal karyotypes and were mitogen-positive. Though numerous chromosome changes were noted in the karyotypically abnormal melanoma cells, 6 of the 8 cultures exhibited abnormalities in chromosomes 1, 6, and/or 7. These data suggest that steps in the progression from benign nevi toward dysplastic nevi or malignant melanoma include: proliferation resulting from altered production of endogenous mitogenic growth factors; and development of specific chromosomal abnormalities.

Cells, Cultured↗
PubMed1985

On the calculation of electrostatic interactions in proteins.

In this paper we present a classical treatment of electrostatic interactions in proteins. The protein is treated as a region of low dielectric constant with spherical charges embedded within it, surrounded by an aqueous solvent of high dielectric constant, which may contain a simple electrolyte. The complete analysis includes the effects of solvent screening, polarization forces, and self energies, which are related to solvation energies. Formulae, and sample calculations of forces and energies, are given for the special case of a spherical protein. Our analysis and model calculations point out that any consistent treatment of electrostatic interactions in proteins should account for the following. Solvent polarization is an important factor in the calculation of pairwise electrostatic interactions. Solvent polarization substantially affects both electrostatic energies and forces acting upon charges. No simple expression for the effective dielectric constant, Deff, can generally be valid, since Deff is a sensitive function of position. Solvent screening of pairwise interactions involving dipolar groups is less effective than the screening of charges. In fact for many interactions involving dipoles, solvent screening can be essentially ignored. The self energy of charges makes a large contribution to the total electrostatic energy of a protein. This must be compensated by specific interactions with other groups in the protein. Strategies for applying our analysis to proteins whose structures are known are discussed.

Electricity↗
PubMed1985

Studies on the elastolytic activity of chymotrypsin.

Chymotrypsin can completely solubilize insoluble [3H]-labeled ligamentum nuchae elastin. At similar enzyme levels, trypsin solubilizes only 5% of the elastin substrate whereas pancreatic elastase completely solubilizes the elastin at one-tenth the concentration required for chymotrypsin solubilization. The elastolytic activity of chymotrypsin is dependent on Ca+2, is enhanced by SDS, and is inhibited by NaCl at concentrations above 10 mM. The elastolytic activity of chymotrypsin is also inhibited by TPCK, a chymotrypsin specific inhibitor, but not by TLCK, a trypsin specific inhibitor. Neither TPCK nor TLCK abolish the elastolytic activity of pancreatic elastase. The sizes of [3H]elastin fragments produced by the elastolytic activity of chymotrypsin are similar to those produced by pancreatic elastase, and larger than those produced by trypsin.

Animals↗