Biomedical subjects
Publications and source records attributed to H Holmes.
A summary of recent and proposed legislation that may affect oncologists and their patients. The report includes information about new fraud, waste, and abuse initiatives on the part of the federal government, the outlook for research funding, Medicare reimbursement, and state negotiations and legal actions against the tobacco companies.
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The object of this study was to investigate the influence of reactive oxygen intermediates (ROI), such as H2O2, on HIV-1 infection of cell cultures. The CD4+ HeLa human epithelial carcinoma cell line clone pBKTRLac was infected with HIV-1MN that had been treated with 0.01-5mM H2O2. Virus infectivity was detected by 3 methods: (a) using transactivation of LTR-linked beta-Galactosidase, (b) viral core p24 antigen enzyme-linked immunoasorbent assay (ELISA), and (c) reverse transcriptase activity assay. Treatment of HIV-1MN cell free virus particles with 0.01 mM H2O2 resulted in a significant increase in virus infection. This effect declined with increasing H2O2 concentrations from 0.05 to 0.1 mM. Further increases in H2O2 concentration up to 5 mM resulted in significant suppression in virus infection. These observations indicate that H2O2 may play a role in affecting the course of HIV infection.
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Surface-detected fluorescence spectroscopy can be used to monitor the pharmacokinetics of uptake and clearance of red-absorbing fluorophores such as zinc(II) phthalocyanine (ZnPc) in vivo. When this technique is applied to mice that have been fed on a normal chlorophyll-based diet, and particularly when measurements are performed in the abdominal region, oscillations are sometimes observed superimposed on the pharmacokinetic curve of the ZnPc. An oscillatory signal has also been observed arising from the abdominal region of control mice fed a normal diet but not injected with the ZnPc photosensitizer; this oscillatory component to the signal is reduced when mice are fed a chlorophyll-free diet. The oscillatory signal component has been attributed to fluorescence arising from chlorophyll derivatives (pheophorbide/pheophytin) contained in the rodent food, whose concentration in the measured abdominal region changes substantially with time, presumably due to digestive processes. Thus it is important to be aware of the possibility of such artifactual contributions to in vivo fluorescence pharmacokinetic measurements.
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Positively charged amino acid substitutions at positions 11 and 25 within the loop of the third variable region (V3) of HIV-1 subtype B envelope have been shown to be associated with the syncytium-inducing (SI) phenotype of the virus. The present study was designed to examine SI and NSI-associated V3 mutations in HIV-1 subtypes other than B. HIV-1 RNA was isolated from 53 virus stocks and 26 homologous plasma samples from 53 recently infected individuals from Brazil, Rwanda, Thailand, and Uganda. The C2-V3 region of the viral envelope was converted to cDNA, amplified, and sequenced. Of 53 primary virus stock samples 49 were biologically phenotyped through measurement of the syncytium-inducing capacity in MT-2 cells (to differentiate between SI and NSI phenotypes). In addition, after passage of primary isolates through PHA stimulated donor PBMC, the replication capacity was determined in U937-2, CEM, MT-2, and Jurkat-tat cell lines (to differentiate rapid/high and slow/low phenotypes). According to the sequence analysis 9 (17.0%) of the viruses belonged to subtype A, 15 (28.3%) to subtype B, 1 (1.9%) to subtype C, 13 (24.5%) to subtype D, and 15 (28.3%) to subtype E. Sequence analysis of virus RNA, obtained from 26 homologous plasma samples, confirmed the homogeneity of sequence populations in plasma compared to primary virus isolates. Of the 49 viruses tested 12 had the SI phenotype, 5 were confirmed to be rapid/high, and 4 appeared to be slow/low pattern 3 replicating. Of 49, 29 had the NSI phenotype, 24 were confirmed to be slow/low pattern 1 or 2, and 3 appeared to be slow/low pattern 3 replicating. Analysis of mutations at V3 loop amino acid positions 11 and 25 revealed that 10/12 (83.3%) of the SI viruses had SI-associated V3 mutations and that 28/29 (96.6%) of the NSI viruses lacked these mutations. V3 loop heterogeneity, length polymorphism, and a high number of positively charged amino acid substitutions were most frequently found among subtype D variants. These results indicate that both the phenotypic distinction between SI and NSI viruses and the association of biological phenotype with V3 mutations is present among HIV-1 subtypes other than B.
HIV-1 isolates were obtained from four countries within the framework of the WHO Network for HIV Isolation and Characterization. The use of standard HIV isolation procedures allowed us to compare the biological properties of 126 HIV-1 isolates spanning five genetic subtypes. In primary isolation cultures, viruses from Uganda and Brazil appeared early and replicated without delay, whereas the replication of Thai viruses was delayed by several weeks. Regardless of genetic subtype or country of origin, blood samples collected more than 2 years after seroconversion yielded virus that replicated efficiently in the primary isolation cultures. None of the isolates obtained from Thailand or Rwanda replicated in cell lines, whereas 5 of the 13 Brazilian isolates and 7 of the 11 Ugandan isolates replicated and induced syncytia in MT-2 cells. As expected for virus isolates obtained early in HIV-1 infection (within 2 years of seroconversion), all viruses from Brazil, Rwanda, and Thailand showed a slow/low replicative pattern. For the Ugandan samples, the time from seroconversion was known precisely for a few of the samples and only in one case was less than 2 years. This may explain why the five viruses that were able to replicate in all cell lines, and thus classified as rapid/high, were of Ugandan origin. Viruses able to induce syncytia in MT-2 cells, also induced syncytia in PBMC. However, 8 slow/low viruses (out of 27) gave discordant results, inducing syncytia in PBMC but not in MT-2 cells. Furthermore, using syncytium induction as a marker, changes in virus populations during early in vitro passage in PBMC could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)
The complications associated with the use of rigid internal fixation in 31 consecutive patients who had undergone a mandibulotomy for the treatment of pathology of the oral cavity or oropharynx were reviewed. Rigid fixation was accomplished with two major types of systems: compression plates and reconstruction plates. Complications occurred in 11 patients (35%) with an average of 1.7 complications per patient. Most complications were minor in nature, and were treated successfully with conservative measures. Patients who had preoperative radiotherapy were more likely to develop nonunion and osteoradionecrosis. Plate exposure was the single, most common complication, accounting for 13% of the complications. No major differences were noted in the complication rates between the two systems.
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The combination of a myocutaneous flap with a three-dimensional bendable reconstruction plate has provided satisfactory results in restoration of mandibular defects following surgical resections in irradiated patients. Twenty-eight patients were treated and prospectively evaluated. Patients requiring postoperative irradiation were excluded from this study. Two groups were identified. Group A (N = 23) required a myocutaneous flap to resurface the soft-tissue defect and group B (N = 5) was treated by primary closure. Seventy-three percent (17 of 23) of patients in group A and 60% (three of five) in group B had received presurgical irradiation but required none after surgery. To date, 64% (18) of the patients have maintained their plates for more than one year, half of these for two years or more. Another 21% (6) have had their plates in place more than six months and the remaining 14% (four) less than six months. One plate was lost in an irradiated group B patient.
This paper assesses the validity of a safety climate measure proposed by Zohar (Safety climate in industrial organizations: Theoretical and applied implications. J. Appl. Psychol. 65(1), 96-101, 1980.) on an American sample of production workers. Using LISREL, confirmatory factor analyses were carried out to test the hypothesis of similar variance-covariance structures (validation of the proposed model). The originally proposed climate model was not supported by the data. An exploratory factor analytic algorithm is then discussed as a means of refining the climate model. A smaller safety climate model was then extracted from the data, and comparisons were made for two groups of employees (accidents versus no accidents). Factorial invariance tests were conducted to test the hypotheses of similar factor patterns, equal units of measurement, equal accuracy of measurement, and equal covariance across factors, between the two groups. The results indicated that the climate structures did not differ between the two groups of interest, subsequently providing a valid and reliable climate measure across the groups. Groups were then compared on climate scores, with differences in climate perception being detected between the groups.
The ontogeny of the major intrinsic phosphoproteins in membrane fractions prepared from cerebral cortex was studied in the rat. The apparent membrane content of 4 phosphoproteins increased markedly over the period 10-15 days after birth, i.e. coinciding with the onset of synaptogenesis. Two of these proteins (molecular weights 79,000 and 86,000) were phosphorylated in cyclic AMP-dependent reactions, and two (molecular weights 50,000 and 162,000) were phosphorylated in reactions dependent on Ca2+ + cytosol extract. The apparent content of other acceptor proteins phosphorylated in analogous reactions increased more gradually from birth to adulthood. In contrast the apparent membrane content of a protein of 47,000 daltons, which was phosphorylated in a reaction requiring Ca2+ only, was relatively very high at birth and until 15 days of age, but then declined 6-fold until adulthood was reached. The relative distribution of the intrinsic phosphoproteins in several particulate fractions was also compared in 1- and 19-day-old rats. In 1-day-old animals the phosphoprotein of 47,000 daltons was found predominantly in a light membrane fraction, but at 19 days it was only just discernible in the equivalent fraction and was found instead in heavier fractions.
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Synaptic-membrane fragments from ox cerebral cortex contain basal and cyclic AMP-stimulated protein kinase(s) that transfer 32P from [gamma-32P]ATP to hydroxyl groups of serine and threonine residues in membrane-protein substrates. In the present work, labelled membrane fragments were partitioned into soluble and insoluble fractions with Triton X-100, Nonidet P. 40, sodium deoxycholate and urea, and the distribution of 32P-labelled protein in the fractions was determined by polyacrylamide-gel electrophoresis and radioautography. A high percentage of phosphorylated protein sustrates remained insoluble, including those whose phosphorylation was most highly stimulated by cyclic AMP. Whole membrane fragments and samples prepared by detergent extraction were fractionated on Sepharose 6B columns in the presence of low concentrations of sodium dodecyl sulphate and pooled fractions were analysed by polyacrylamide-gel electrophoresis and radioautography. Phosphorylated proteins were fractionated on the basis of their molecular weight, but homogeneous protein was not obtained. The results are discussed in relation to the techniques used and the results obtained in other laboratories.