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Biomedical subjects

R Ray

Publications and source records attributed to R Ray.

At least 217 records · Page 12Linked to original sources

Cardiovascular risk factors, premature heart disease, and all-cause mortality in a cohort of northern California women.

Large prospective studies and intervention trials have identified major risk factors for premature heart disease in men, while the Framingham Heart Disease Study has provided the leading evidence of predictors of cardiovascular disease in women. We evaluated the role of these risk factors in a 13-year follow-up study of 8935 premenopausal and 2716 postmenopausal women in the Walnut Creek Contraceptive Drug Study cohort in Northern California. Elevated cholesterol levels, high blood pressure, smoking, obesity, family history of heart disease, and diabetes were investigated for their contribution to premature death due to all causes and due to cardiovascular disease. In addition, risk factor profiles were developed separately for users and nonusers of Premarin (conjugated estrogen) in the postmenopausal cohort. The results show that the strongest predictors of cardiovascular mortality among premenopausal women were smoking, high blood pressure, and diabetes, with relative risks of 2.8, 10.5, and 11.6, respectively. A disparity between high cardiovascular risk factor prevalence and low rates of premature heart disease indicates that the high relative risks will not be accompanied by large attributable risks. Nevertheless, the study reconfirms the need for screening women for heart disease risk because life-style changes can improve cardiovascular risk factors and can potentially reduce the chance of premature death even further.

Adolescent↗

Effects of estrogen dose and smoking on lipid and lipoprotein levels in postmenopausal women.

The joint effects of conjugated estrogen use, age, body mass index, and smoking on plasma lipid and lipoprotein levels were assessed in 585 women who used oral estrogen and 1093 women who did not who participated in the Walnut Creek Contraceptive Drug Study. Whether administered daily or cyclically, conjugated estrogen was associated with reductions in low-density lipoprotein cholesterol levels and increases in high-density lipoprotein cholesterol and triglyceride levels. The adjusted mean low-density lipoprotein cholesterol concentration was 132 mg/dl for women who used conjugated estrogen in a dose greater than or equal to 1.25 mg/day; the adjusted corresponding mean concentration was 147 mg/dl for postmenopausal women who did not use estrogen. A dose-response pattern was demonstrated between conjugated estrogen and low- and high-density lipoprotein cholesterol levels. A maximum low-density lipoprotein cholesterol level reduction was reached at a dose of 1.25 mg, suggesting a saturation phenomenon. Stepwise dose-response increases in high-density lipoprotein cholesterol levels were also found with estrogen therapy, with a maximum increase of 8 to 10 mg/dl observed with the 1.25 mg dose. Estrogen-related rises in low-density lipoprotein cholesterol levels and decreases in high-density lipoprotein cholesterol levels were offset by 2 to 3 mg/dl in women who smoked. It may be concluded, therefore, that among postmenopausal women, low-risk lipoprotein profiles as assessed by low- and high-density lipoprotein cholesterol levels are found in nonsmokers whose postmenopausal hormone therapy includes the equivalent of a conjugated estrogen dose of 1.25 mg.

Cholesterol↗

Intranasal immunization of hamsters with envelope glycoproteins of human parainfluenza virus type 3.

Envelope glycoproteins of human parainfluenza virus type 3 (PIV-3) were selectively solubilized with n-octyl beta-D-glucopyranoside and reconstituted into lipid vesicles by dialysis of the detergent. The efficacy of the glycoprotein preparation as a subunit vaccine when administered to hamsters intranasally or subcutaneously was compared. Animals receiving four intranasal immunizations with 5 micrograms of the glycoprotein preparation were completely resistant to challenge infection. Only partial protection, however, was observed in animals immunized subcutaneously with the same dose of antigen. The local glycoprotein-specific IgA response was significantly higher in intranasally immunized animals and was implicated in resistance to challenge infection.

Administration, Intranasal↗

Role of individual glycoproteins of human parainfluenza virus type 3 in the induction of a protective immune response.

Affinity-purified hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of human parainfluenza virus type 3 (P13 virus) were used to investigate their role in the induction of a protective immune response following immunization of hamsters. The efficacy of immunization with the glycoprotein antigens was tested by challenge infection. Results of virus recovery from lungs and trachea demonstrated that although immunization with HN or F alone induced an antibody response to the respective glycoproteins, it did not provide a significant level of protection. However, immunization with a mixture of both purified glycoproteins induced higher virus-neutralizing activity in bronchial lavages and afforded complete protection from challenge infection. Similarly, incomplete protection was observed after passive transfer of monospecific rabbit antibody to the purified HN or F in baby hamsters. On the other hand, passive transfer of a mixture of antibodies to HN and F conferred a higher level of protection. Thus, the presence of antibody to both glycoproteins of P13 virus may be essential for protective immunity.

Animals↗

Antibiotic prophylaxis in aortic and peripheral arterial surgery in the presence of infected extremity lesions. Results of a prospective evaluation.

Over a 6-month period 124 patients submitted to aortic or infra-inguinal arterial reconstruction were alternately allocated to receive cloxacillin plus gentamicin (CX/GM) for 48 hours or cefotaxime (CTX) for 24 hours perioperatively. Evaluations during during the first month were performed by a blinded independent observer and patients were followed for between 6 and 20 months. 63 patients received CX/GM and 61 CTX; the groups were matched for sepsis risk factors. Sepsis rates were: groin and abdominal wounds, CX/GM 5.4% (7 of 129), CTX 6.2% (8 of 127); graft, CX/GM 1.5% (1 of 63), CTX 3.3% (2 of 61). The differences were not statistically significant (p greater than 0.05). Virtually all wound infections were superficial (class I) and no late infections have emerged. 56 patients had infected extremity lesions and 68 had no lesion. There was no significant difference in wound or graft sepsis rates between the 2 groups. Positive cultures of groin lymph nodes and/or aortic clot or atheroma did not predispose patients to postoperative sepsis. The organisms cultured from the extremity lesions were not found in infected wounds of abdominal surgery patients. However, species type and antibiotic susceptibility patterns suggest that the same pathogens were present in wound infections as were isolated from the extremity lesions of patients who underwent infra-inguinal surgery. Thus direct, rather than lymphatic, contamination may be the major aetiological factor. Most infecting organisms were susceptible to the antibiotic used.

Adult↗

Deposition and transfer of axonally transported phospholipids in rat sciatic nerve.

Radioactive glycerol, ethanolamine, or choline injected into the vicinity of the cell bodies of rat sciatic nerve sensory fibers is incorporated into phospholipid. Some newly synthesized ethanolamine and choline phosphoglycerides are subsequently committed to transport down the sciatic nerve axons at a rate of several hundred millimeters per day. Most labeled choline phosphoglycerides move uniformly down the axons; in contrast, the crest of moving ethanolamine phosphoglycerides is continually attenuated. These data, as well as differences in the clearance of these phospholipids distal to a nerve ligature, suggest that various classes of labeled phospholipids are differentially unloaded from the transport vector (possibly by exchange with unlabeled lipid in stationary axonal structures) during movement down the axons. The extent of unloading appears to be defined by the base moiety; both diacyl and plasmalogen species of ethanolamine phosphoglycerides exchange extensively with stationary axonal lipids, while most choline phosphoglycerides continue down the axons. Autoradiographic studies with 3H-choline and 3H-ethanolamine demonstrated that most unloaded phospholipid is initially deposited in axonal structures; some of this unloaded lipid is subsequently transferred to the axon/myelin interface (axolemma?) and then to myelin. Although transported ethanolamine phosphoglycerides exchange more extensively with lipids in stationary axonal structures than do choline phosphoglycerides, at early times more label from 3H-choline is found in myelin. A model to resolve this seeming discrepancy is proposed, wherein a differential topographic localization of phospholipid classes in the membrane of the transport vector allows for a preferential extensive exchange of transported ethanolamine phosphoglycerides with lipids in stationary axonal structures, while choline phosphoglycerides become available for rapid transfer to myelin by a process involving vesicle fusion with axolemma.

Animals↗

The protein receptor for cholerabacteriophage phi 149.

Choleraphage phi 149 receptor activity was found in the outer membrane (OM) protein of Vibrio cholerae 154. Receptor protein for phage phi 149 was separated from trypsin-treated OM on a Sephadex G-100 column. Of the three peaks obtained, phage receptor activity was noted only in peak II. SDS-PAGE showed that the Mr of the protein was 35,000. The protein was heat-labile and protease-sensitive. The specificity of this protein as choleraphage phi 149 receptor was investigated by carrying out a protection experiment by anti-protein (peak II) rabbit sera.

Bacterial Outer Membrane Proteins↗

Characterization and complete nucleotide sequence of a 5.8S ribosomal RNA gene from Plasmodium falciparum.

The 5.8S and 5S rRNA components from the FCR-3/The Gambia strain of Plasmodium falciparum have been identified and the complete nucleotide sequence of a 5.8S ribosomal RNA gene determined. Unlike the 5S rRNA species, the 5.8S is a single homogeneous population of molecules of 157 nucleotides. Comparison of its nucleotide sequence with previously reported 5.8S rRNA sequences indicates that it is homologous to these molecules, but distantly related to them. The sequence of the 5.8S rRNA coding region from the pfrib-2 recombinant of the HG13 Gambian isolate of P. falciparum is identical.

Animals↗

Mithramycin selectively inhibits transcription of G-C containing DNA.

Mithramycin induces a reversible inhibition of cellular RNA synthesis without affecting DNA synthesis. The authors have shown this drug induces myeloid differentiation of HL-60 promyelocytic leukemia cells and is an effective agent in certain patients with chronic granulocytic leukemia. In order to investigate the mechanism by which this drug inhibits RNA synthesis we have compared the effect of mithramycin on RNA synthesis by whole cells, isolated nuclei, and RNA synthesis by isolated E. coli RNA polymerase and eukaryotic RNA polymerase II. Exposure of HL-60 cells to mithramycin at concentrations of 4.6 X 10(-7) m or higher for 48 hours causes an almost immediate inhibition of RNA synthesis (up to 85% at 4 hours) with only modest cytotoxicity at these concentrations. Endogenous RNA synthesis by isolated nuclei can be inhibited by mithramycin only at high concentrations (greater than 10(-5) m), suggesting that mithramycin primarily may inhibit initiation, rather than elongation. Mithramycin inhibits in vitro transcription of salmon sperm DNA by E. coli RNA polymerase at DNA:drug ratios similar to those required for RNA synthesis inhibition in whole cells. Similar DNA binding studies with synthetic oligonucleotides demonstrate that mithramycin is a potent inhibitor of transcription of Poly dG.dC by E. coli RNA polymerase but has no effect on transcription of Poly dA.dT. The rapid inhibition of whole cell and isolated RNA polymerase transcription, and the relative insensitivity of isolated nuclei, suggest mithramycin may interact with specific DNA sequences in order to inhibit the initiation of RNA synthesis in intact cells.

Base Composition↗

Glycoproteins of human parainfluenza virus type 3: affinity purification, antigenic characterization and reconstitution into lipid vesicles.

Monoclonal antibodies to the envelope glycoproteins, HN and F, of human parainfluenza virus type 3 were coupled to a Sepharose 4B matrix and used for affinity purification of the viral glycoproteins. The purity of the glycoproteins was demonstrated by SDS-PAGE followed by fluorography or silver staining. The antigenicity of the glycoproteins was determined by immunization of rabbits; polyclonal rabbit antisera demonstrated inhibition of functional activities of the virus glycoproteins. The F glycoprotein, when reconstituted into lipid vesicles, showed distinct spike-like projections similar to those of intact virions.

Animals↗

Photoaffinity labeling of the rat plasma vitamin D binding protein with [26,27-3H]-25-hydroxyvitamin D3 3 beta-[N-(4-azido-2-nitrophenyl)glycinate].

It is well recognized that the vitamin D binding protein (DBP) is important for the transport of vitamin D, 25-hydroxyvitamin D (25-OH-D), and its metabolites. In an attempt to better understand the molecular-binding properties of this ubiquitous protein, we designed and synthesized a photoaffinity analogue of 25-OH-D3 and its radiolabeled counterpart. This analogue, 25-hydroxyvitamin D3 3 beta-[N-(4-azido-2-nitrophenyl)glycinate] (25-OH-D3-ANG), was recognized by the rat DBP and was about 10 times less active than 25-OH-D3 in terms of binding. Incubation of [3H]25-OH-D3 or [3H]25-OH-D3-ANG with rat DBP revealed that both compounds were specifically bound to a protein with a sedimentation coefficient of 4.1 S. Each was displaced with a 500-fold excess of 25-OH-D3. When [3H]25-OH-D3-ANG was exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3, there was no displacement of tritium from the 4.1S peak. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of [3H]25-OH-D3-ANG exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3 revealed one major band with a molecular weight of 52 000. These data provide strong evidence that [3H]25-OH-D3-ANG was covalently linked to the rat DBP. This photoaffinity probe should provide a valuable tool for the analysis of the binding site on this transport protein.

Affinity Labels↗

Inhibition of acetylcholinesterase from electric eel by (-)-and (+)-physostigmine and related compounds.

Unnatural (+)-physostigmine (2) inhibited acetylcholinesterase (AChE) from electric eel considerably less than natural (-)-physostigmine (1), but 2 may because of its possible lower toxicity still be an interesting anticholinesterase agent. (-)-Eseroline (3), a major metabolite of (-)-physostigmine (1) and a potent narcotic analgetic, and its unnatural (+)-antipode (4), were both poor inhibitors of the enzyme. (-)-Dihydrosecophysostigmine (5), a ring-open analog of (-)-physostigmine was less, but (-)-N-methylphysostigmine (6) much more potent than the natural alkaloid. The availability of compounds related to (-)- and (+)-physostigmine by improved chemical synthesis suggests that further structural variation may well lead to other biologically interesting AChE inhibitors.

Acetylcholinesterase↗

Smoking as a risk factor for recurrence of sudden cardiac arrest.

We obtained information about cessation of smoking in 310 survivors of out-of-hospital cardiac arrest who had been habitual cigarette smokers at the time of their arrest. Patients with coronary heart disease were stratified according to mortality risk on the basis of recognized criteria. The expected first-year rate of recurrent arrest ranged from 2 to 40 percent among the strata. Life-table analyses showed that reformed smokers had a lower incidence of recurrent arrest than patients who continued to smoke (19 vs. 27 percent at three years; P = 0.038 by one-sided test adjusted across strata). This effect occurred to varying degrees in all but the highest risk stratum. No differences in survival were observed for mortality due to other causes. It is possible that continued smoking in these patients led to acceleration of an ongoing atherosclerotic process, but the differences in early survival suggest that smoking may also act in the short term to enhance vulnerability to cardiac arrest.

Coronary Disease↗

Monoclonal antibodies reveal extensive antigenic differences between the hemagglutinin-neuraminidase glycoproteins of human and bovine parainfluenza 3 viruses.

A panel of twenty monoclonal antibodies to the hemagglutinin-neuraminidase (HN) glycoprotein of human parainfluenza 3 (PI3) virus has been obtained and tentatively classified into four different groups based on reactivity in hemagglutination inhibition (HI), neuraminidase inhibition (NI), and plaque neutralization (NT) tests. The antibodies were tested for cross-reactivity with bovine PI3 virus, Sendai virus, and simian virus 5 (SV5). Only two of these antibodies showed similar reactivities with human and bovine PI3 viruses in HI and NT tests; a few other antibodies showed low levels of reactivity with the heterologous viruses in HI tests. A competitive binding assay further suggested that the two cross-reactive antibodies are directed against the same domain of the HN molecule. Therefore, the HN glycoproteins of human and bovine PI3 viruses appear to be antigenically dissimilar, although they share at least one common epitope.

Antibodies, Monoclonal↗