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Biomedical subjects

S A Spector

Publications and source records attributed to S A Spector.

At least 163 records · Page 9Linked to original sources
PubMed1987

Antibody to a synthetic oligopeptide in subjects at risk for human immunodeficiency virus infection.

Detection of antibodies to human immunodeficiency virus (HIV) by enzyme-linked immunosorbent assay (ELISA) is the accepted method to screen blood products at risk to transmit infection. The presence of antibodies to HIV in 565 serum specimens from 274 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex, symptomatic and asymptomatic subjects at risk for AIDS, and controls was determined with an ELISA that incorporates synthetic peptides (designated E32/E34) representing sequences in the envelope glycoprotein gp41. Of 105 specimens from patients with AIDS or AIDS-related complex, 3 specimens that were negative by commercially licensed ELISA and immunoblot test were similarly unreactive in the E32/E34 ELISA. For homosexual men with generalized lymphadenopathy, 186 specimens were positive by the E32/E34 ELISA and 63 specimens were negative. In comparison, with the licensed ELISA, 184 of these samples were positive and 65 samples were negative. The two samples that were positive in the E32/E34 ELISA but not the commercial kit were also positive by immunoblotting. Sequential sera from one individual who apparently underwent seroconversion according to the commercial assays were all positive by E32/E34 ELISA and immunoblotting. Thus, the ELISA with synthetic peptides is an extremely sensitive and specific test of antibody response to HIV and has not yet yielded a negative result with a Western blot (immunoblot)-confirmed antibody-positive serum.

AIDS-Related Complex↗
PubMed1987

Evidence for early central nervous system involvement in the acquired immunodeficiency syndrome (AIDS) and other human immunodeficiency virus (HIV) infections. Studies with neuropsychologic testing and magnetic resonance imaging.

Although a high prevalence of central nervous system disease is seen in persons with the acquired immunodeficiency syndrome (AIDS), the natural history of brain involvement with human immunodeficiency virus (HIV) remains poorly understood. Neuropsychologic evaluations of 55 ambulatory homosexual men revealed abnormalities in 13 of 15 with AIDS, 7 of 13 [corrected] with AIDS-related complex, 7 of 16 [corrected] with HIV-seropositivity only, and 1 of 11 with HIV-seronegativity. Common neuropsychologic problems included impaired abstracting ability, learning difficulties, and slowed speed of information processing. Magnetic resonance imaging had abnormal findings in 9 of 13 patients with AIDS and 5 of 10 patients with AIDS-related complex who were available for scans. The commonest abnormalities were sulcal and ventricular enlargement and bilateral patchy areas of high signal intensity in the white matter. We postulate that central nervous system involvement by HIV may begin early in the course of AIDS and cause mild cognitive deficits in otherwise asymptomatic persons.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Model for microneurovascular muscle transplantation in the dog.

Previous studies have suggested that successful transplantation of skeletal muscle to replace previously lost function depends on the mass of the transplanted tissue. In the present experiment, the possibility that careful microneurovascular surgical technique substantially improves the chances of successful transplantation of large-sized muscle was tested using dog gracilis muscle averaging 75 gm in weight. Gracilis muscles were completely excised ipsilaterally and were implanted into their original location (orthotopic) by reattaching tendons of insertion and origin. In addition, neurorrhaphies of nerve stumps were performed along with repair of the vascular pedicle using microsurgery techniques. After approximately 1 year, orthotopic transplants weighed about 70 percent of contralateral sham-operated gracilis muscles. Although average tension output of transplants declined to about 60 percent of control values, three of the most successfully transplanted muscles produced between 73 and 88 percent of control force. A significant increase in the number of slow-twitch-oxidative fibers was correlated with a slight but significant reduction in the maximal velocity of shortening of transplanted muscles. The ability of transplants to resist fatigue when repetitively stimulated was similar to the endurance capacity of control muscles. These results suggest that microneurovascular surgery may enhance the more complete restoration of function of transplanted skeletal muscles of relatively large size.

Adenosine Triphosphatases↗
PubMed1986

Rapid viral diagnostic techniques.

The application of viral diagnosis to clinical medicine is approaching a critical period in which greater emphasis will be placed on altering patient care as a result of viral identification. Although isolation of viruses in tissue culture is the "gold standard" to which all other methods of viral identification are compared, the expense in terms of cost and technical time required as well as the time necessary for specific viral isolation has severely limited the use of viral diagnosis in clinical medicine. The concomitant development of rapid viral diagnostic procedures with the increased availability of anti-viral therapy, promises to alter how patients will be managed in the future. The greatest emphasis for rapid viral diagnosis has been placed on viral detection directly from clinical specimens since these procedures eliminate the need to cultivate the virus. Methods for direct detection of viral antigens in clinical specimens include electron microscopy and a wide range of immunologic assays. The extraction of nucleic acid directly from clinical specimens and hybridization of this DNA to specific viral probes also provides for virus identification without the need to culture the virus. Currently, many of the rapid diagnostic procedures discussed are performed only in research laboratories. Over the next several years, however, methods of antigen detection using EIA procedures and detection of viral-specific nucleic acid promise to alter how we study and diagnose viral infections.

Humans↗
PubMed1985

Rapid determination of molecular relatedness of isolates of human cytomegalovirus.

Molecular comparisons of isolates of human cytomegalovirus (CMV) with restriction enzyme digests have helped to identify patterns of CMV transmission. Current techniques, however, require extensive tissue culture passage of the virus, which limits use of these analyses. In this report, we describe a rapid, less-expensive, and equally sensitive method of comparing CMV genomes. This procedure, which we have called "junctional hybridization," uses the cloned junction fragments of CMV strain AD169 as probes that hybridize to CMV DNA restriction digests previously separated by electrophoresis and transferred to nitrocellulose filters. The procedure eliminates the need for tissue culture passage of virus beyond the primary isolation and can be used directly with DNA extracted from CMV-infected tissue. In all cases, junctional hybridization was as sensitive as currently used methods of restriction enzyme digestion analyses in identifying identical or different CMV isolates. Use of junctional hybridization should facilitate molecular analyses for study of the epidemiology of CMV infections.

Cytomegalovirus↗
PubMed1985

Inhibition of human cytomegalovirus by combined acyclovir and vidarabine.

The inhibition of human cytomegalovirus (HCMV) isolates by acyclovir (ACV) and vidarabine (ara-A) was assessed by using an infectious-center plaque-reduction assay. When fixed concentrations of 4.5 micrograms of ACV and 250 ng of ara-A per ml were compared singly and in combination, the viral inhibition resulting from the ACV-ara-A combination was synergistic for three of four HCMV clinical isolates studied and additive for one HCMV isolate. An additional four HCMV strains obtained at postmortem examination from the lungs of bone marrow transplant patients were assessed for sensitivity to ACV-ara-A by using the dose required for 50% viral inhibition (ID50) as the endpoint. The mean ID50 of ACV for the four HCMV isolates was 12.3 micrograms/ml, whereas the mean ID50 of ara-A was 3.4 micrograms/ml. When 1 microgram of ara-A per ml (which yielded a mean plaque reduction of 23.6%) was combined with ACV, a mean of 5.2 micrograms of ACV per ml was required for 50% viral inhibition. The sum of the fractional inhibitory concentrations for each of the four HCMV isolates was less than 1, indicating synergy by the ACV-ara-A combination. Although DNA synthesis in growing human embryonic lung fibroblast (HEL) cells, as determined by [3H]thymidine incorporation, was diminished to 61% of that in untreated control cells when 22.5 micrograms of ACV and 1 microgram of ara-A per ml were used, there was no additive inhibition of DNA synthesis when the two-drug combination was used. HEL cell growth remained at 97% of control cell growth at 72 h when concentrations as high as 45 micrograms of ACV combined with 1 microgram of ara-A per ml were used.

Acyclovir↗
PubMed1985

The use of DNA probes in studies of human cytomegalovirus.

Hybridization assays provide a sensitive and rapid means for studying the molecular biology of viral replication and for identifying viral nucleic acid in biological specimens. Such assays are attractive because the detection of virus does not require intact virions or concomitant viral protein synthesis, both of which may be absent in a latently infected cell or in a virus-associated tumor. For molecular and clinical studies on human cytomegalovirus (HCMV), we have cloned and characterized subgenomic EcoRI fragments representative of the entire genome of HCMV strain AD169. To study the epidemiology of HCMV infections and to identify the presence of HCMV nucleic acid in urine, blood, Kaposi's sarcoma, and other tissues, we have used various hybridization techniques, including DNA dot/slot-blot hybridization, Southern blot hybridization, and in situ cytohybridization. These studies demonstrate how cloned molecular probes can be used to study the molecular biology, pathogenesis, and treatment of viral infections.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Effects of elimination of activity on contractile and histochemical properties of rat soleus muscle.

Morphological, contractile, and histochemical properties of rat soleus muscle were studied after 2 or 4 weeks of complete elimination of neuromuscular activity. Inactivity was induced by chronic perfusion of tetrodotoxin (TTX) to the sciatic nerve. Significant reductions in muscle mass and fiber size were found after 2 or 4 weeks of disuse. Correspondingly, the percentage of dark-staining alkaline myosin ATPase fibers was increased from about 20% to 40% after 4 weeks of treatment. The capacity of soleus to generate tension when stimulated through the nerve was significantly impaired at frequencies greater than 20 Hz. Nevertheless, when the curarized muscle was stimulated directly, tension developed at frequencies above 20 Hz relative to peak tension was similar to control values. Absolute tetanic tension was significantly reduced after 2 or 4 weeks of treatment. These reductions could be only partly explained by muscle atrophy, resulting in specific tensions or approximately 55% of control after 2 or 4 weeks of treatment. Measures of the time course of the isometric twitch were found not to be reliable indicators of the contractile speed in TTX-treated soleus. Significant increases in the rate of tetanic tension development, expressed relative to peak tension, and the velocity of unloaded shortening, were seen after 4 weeks of disuse. These results reveal the extent to which virtually complete neuromuscular inactivity leads to chronic deficits in neuromuscular transmission and changes in both the net amount and quality of contractile proteins of rat soleus muscle.

Adenosine Triphosphatases↗
PubMed1985

Trophic effects on the contractile and histochemical properties of rat soleus muscle.

Contractile and histochemical properties of rat soleus muscle were studied bilaterally after 2 or 4 weeks of denervation (DEN), which eliminates activity and non-activity-related influences, and chronic application of tetrodotoxin (TTX) to the motor nerve, which produces a completely inactive innervated muscle. After 2 or 4 weeks of disuse, the percentages of slow twitch oxidative fibers in both DEN- and TTX-treated soleus were reduced significantly and to similar extents. The dynamic contractile properties of TTX-treated and denervated muscles were similar to those of control muscle after 2 weeks, but by 4 weeks, parallel increases were seen in normalized rate of tension development and maximal shortening speed of these muscles. After either period of disuse, the atrophy of TTX-treated soleus was significantly less than that of denervated muscle. Atrophy was associated with correspondingly diminished capacity of denervated or TTX-disused muscles to generate tension after 2 weeks. By 4 weeks of treatment, the reduction in tension of denervated soleus was greater than its diminished size. These results imply the existence of a non-activity-related stimulus in TTX-inactivated muscles which slows the reductions in muscle mass and specific tension observed in denervated soleus muscle. In contrast, the similarities in dynamic speed-related properties and fiber type profiles between DEN- and TTX-treated rat soleus may be explained simply by the absence of neuromuscular activity.

Adenosine Triphosphatases↗
PubMed1984

Detection of human cytomegalovirus in clinical specimens by DNA-DNA hybridization.

A diagnostic assay has been developed to detect human cytomegalovirus (HCMV) DNA in clinical specimens with 32P-labeled cloned fragments of HCMV strain AD169. The labeled probe can detect 10 pg of HCMV DNA and fails to hybridize to DNA from other herpesviruses or human DNA. The assay correctly identified 22 (92%) of 24 coded urine specimens culture positive for HCMV and 23 (88%) of 26 urine specimens culture negative for HCMV. In a prospective study of 67 buffy-coat specimens from recipients of bone marrow transplants HCMV DNA was detected in 13 (93%) of 14 culture-positive samples. Of 53 buffy-coat specimens culture negative for HCMV, 32 were hybridization negative for HCMV DNA. However, in 20 of 21 buffy-coat specimens positive for HCMV by hybridization but negative by culture there was evidence that the hybridization assay was correct and more sensitive than currently available tissue culture techniques.

Cytomegalovirus↗
PubMed1983

Transmission of cytomegalovirus among infants in hospital documented by restriction-endonuclease-digestion analyses.

Over a 4-month period, 8 infants in an intensive-care unit were identified as excreting cytomegalovirus (CMV) in their urine. 7 of the 8 viral isolates were analysed by means of restriction-endonuclease-digestion analyses for molecular relatedness. CMV isolates from 3 babies had identical DNA-fragment migration patterns, indicating that all 3 babies were infected with the same strain of CMV. Epidemiological data indicate that CMV was transmitted from 1 infant to the other 2 babies through unidentified fomites within the nursery.

Cross Infection↗
PubMed1983

Adenovirus type 7b in a children's hospital.

Between August 15 and September 15, 1980, an outbreak of infections due to adenovirus type 7b occurred at Children's Hospital and Health Center, San Diego, California. During that time, four of six patients infected with adenovirus type 7b died. All patients with hospital-acquired disease had underlying respiratory compromise. Cultures, adenoviral serology tests, and histories were obtained from 383 (93%) of the 410 hospital employees. All 11 people from whom adenovirus type 7 was cultured were nurses working in a unit with an infected patient. Seven other employees with negative cultures had a fourfold or greater rise in their adenoviral complement fixation titers. This outbreak demonstrates that adenovirus type 7 infections are capable of causing serious and potentially fatal disease in hospitalized patients and suggests that individuals with underlying respiratory diseases are especially at risk.

Adenoviridae Infections↗
PubMed1983

Inhibition of human cytomegalovirus by trifluorothymidine.

The antiviral activity of trifluorothymidine (TFT) singly and in combination with other antiviral agents against human cytomegalovirus (HCMV) was evaluated by using an infectious center plaque reduction assay. The 50% inhibitory dose of TFT against six different patient HCMV strains was 0.57 (+/- 0.24, standard deviation) microM and ranged from 0.32 to 0.97 microM. The 50% inhibitory dose for the laboratory-adapted HCMV strain, AD-169, was 2.1 microM. When TFT (0.17 microM) was combined with human fibroblast interferon (25 U/ml), the combination was additive against all four HCMV isolates evaluated. Synergism was observed when TFT (0.17 microM) was combined with phosphonoformic acid (25 microM) for all strains studied or with acyclovir (20 microM) for three of the four clinical HCMV strains tested. Each of the three antiviral agents, when combined with TFT, exhibited additive effects against strain AD-169. TFT at concentrations of 0.5, 1.7, and 3.5 microM had an increasing inhibitory effect on uninfected human embryonic lung fibroblast (HEL) cell growth over 72 h, with 16% growth inhibition at 3.5 microM after 3 days. There was no increased toxicity to growing HEL cells when the paired antiviral agent combinations were evaluated. These findings suggest that TFT may be useful singly or in combination with other antiviral agents in treating HCMV infections.

Acyclovir↗