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Biomedical subjects

B Hahn

Publications and source records attributed to B Hahn.

At least 37 records · Page 2Linked to original sources

Clarithromycin-resistant Helicobacter pylori in patients with duodenal ulcer in the United States.

BACKGROUND: Clarithromycin is a key component of several antimicrobial treatment regimens for Helicobacter pylori. Cure rates with clarithromycin-containing regimens are significantly decreased when resistance is present. Resistance develops by a point mutation in the ribosomal RNA of some organisms exposed to clarithromycin. We studied the prevalence of clarithromycin-resistant organisms in patients with duodenal ulcer in the United States from 1993-96. METHODS: Patients with endoscopic evidence of a duodenal ulcer were studied. Gastric biopsies were cultured for H. pylori and antimicrobial sensitivity was determined by the E-test (epsilometer agar diffusion gradient). RESULTS: In 1993-94, three of 78 patients (4%) had clarithromycin-resistant strains of H. pylori. In 1995-96, 44 of 348 patients (12.6%; p = 0.025) had resistant strains of H. pylori. Patients who had previously failed antimicrobial treatment for H. pylori accounted for much of the increase in resistant strains (25%). CONCLUSIONS: Failed therapy with clarithromycin-based regimens is a growing cause of antimicrobial resistance in H. pylori in the United States. Whereas the overall rates of primary resistance are low, the increase in secondary resistance over a short period of time is worrisome. New treatments that prevent the emergence of resistance may be important in the future.

Anti-Bacterial Agents↗

HIV type 1 subtypes, coreceptor usage, and CCR5 polymorphism.

Identification of the chemokine receptors CCR5 and CXCR4 as the major coreceptors for HIV-1 entry has greatly assisted our understanding of HIV-1 pathogenesis, transmission, and tropism. However, most of our current knowledge on coreceptor usage comes from studies using HIV-1 strains or env genes derived from the genetic subtype B predominant in North America and western Europe. In this report, the coreceptor usage of 20 primary viral isolates representative of genetic subtypes A, B, C, D, E, and group O was examined. Thirty-nine full-length CCR5 sequences from individuals of diverse geographic origins were also obtained to examine the possible effect of CCR5 polymorphism on HIV-1 subtype distribution. Our results indicate that (1) CCR5 and CXCR4 serve as the two major coreceptors for viruses belonging to HIV-1 subtypes A, B, C, D, E, and group O, whereas other chemokine receptors such as CCR2b and CCR3 play only a minor role in facilitating viral entry into stimulated PBMCs; (2) the coreceptor usage is determined by the viral phenotype rather than its genotype because all NSI strains, irrespective of their subtype classification, utilize CCR5, whereas all SI strains are able to use CXCR4; and (3) there is no geographic clustering of CCR5 polymorphism in different ethnic populations, suggesting that CCR5 diversity is not the underlying explanation for differences in the spread of different HIV-1 subtypes. Therefore, the uneven worldwide distribution of HIV-1 subtypes is more likely the result of stochastic dissemination.

Amino Acid Sequence↗

Single-dose pharmacokinetics of thalidomide in human immunodeficiency virus-infected patients.

The pharmacokinetics of thalidomide in nine human immunodeficiency virus-infected patients were studied. Single doses of thalidomide were well absorbed, with mean peak concentrations (+/- standard deviations) of 1.17 +/- 0.21 and 3.47 +/- 1.14 microg/ml in the 100- and 300-mg dosing groups, respectively, and the mean elimination half-life was approximately 6 h. Adverse effects were mild, with drowsiness being reported for seven of nine patients.

Adult↗

Sequence heterogeneity of Nef transcripts in HIV-1-infected subjects at different stages of disease.

Nef transcripts were analyzed from peripheral blood mononuclear cells of 10 HIV-1-infected subjects with 9-822 CD4+ lymphocytes/cu mm, including 4 individuals with a probable common source infection. There was no relationship between the phylogenetic position of the various nef sequences and the disease state of the person from whom they were derived. The nef open reading frame was disrupted in all three clones from only 1 subject. Functional analyses of a representative clone from each of the remaining 9 subjects showed that all nef alleles were capable of CD4 cell surface down-regulation, but only three nef alleles suppressed the induction of IL-2 transcription.

Amino Acid Sequence↗

Destroying retroviruses from within.

One strategy for neutralizing retroviral infectivity is to induce the incorporation of lethal fusion proteins, such as capsid protein-nuclease fusions, into the virion during the normal viral assembly process. Genes encoding such antiviral fusion proteins must be nontoxic to the host, lethal to the virus, and must be efficiently delivered to, and expressed in, appropriate target cells.

Antiviral Agents↗

Vpr-induced cell cycle arrest is conserved among primate lentiviruses.

We previously reported that expression of human immunodeficiency virus type 1 strain NL4-3 (HIV-1(NL4-3))vpr causes cells to arrest in the G2 phase of the cell cycle. We examined the induction of cell cycle arrest by other HIV-1 isolates and by primary lentiviruses other than HIV-1. We demonstrate that the vpr genes from tissue culture-adapted or primary isolates of HIV-1 are capable of inducing G2 arrest. In addition, we demonstrate that induction of cell cycle arrest is a conserved function of members of two other groups of primate lentiviruses, HIV-2/simian immunodeficiency virus strain sm (SIVsm)/SIVmac and SIVagm. vpr from HIV-1, HIV-2, and SIVmac induced cell cycle arrest when transfected in human (HeLa) and monkey (CV-1) cells. vpx from HIV-2 and SIVmac did not induce detectable cell cycle arrest in either cell type, and SIVagm vpx was capable of inducing arrest in CV-1 but not HeLa cells. These results indicate that induction of cell cycle perturbation is a general property of lentiviruses that infect primates. The conservation of this viral function throughout evolution suggests that it plays a key role in virus-host relationships, and elucidation of its mechanism may reveal important clues about pathology induced by primary lentiviruses.

Alleles↗

Increased envelope spike density and stability are not required for the neutralization resistance of primary human immunodeficiency viruses.

Previous observations that the gp120 envelope glycoprotein contents of some primary, clade B human immunodeficiency virus type 1 (HIV-1) isolates were higher than those of laboratory-passaged HIV-1 isolates suggested the hypothesis that increased envelope glycoprotein spike density or stability contributes to the relative neutralization resistance of the primary viruses. To test this, the structural, replicative, and neutralization properties of a panel of recombinant viruses with HIV-1 envelope glycoproteins from divergent clades were examined in an env complementation assay. In this system, although the spike density and stability of envelope glycoproteins from primary HIV-1 isolates were not greater than those from a laboratory-adapted isolate, relative resistance to neutralizing antibodies and soluble CD4 was observed for the viruses with primary envelope glycoproteins. Thus, neither high envelope glycoprotein spike density nor stability is necessary for the relative neutralization resistance of primary HIV-1 viruses.

Antigens, CD↗

No insurance, public insurance, and private insurance: do these options contribute to differences in general health?

This paper examines the validity of two of the basic assumptions made about health care insurance and health, namely that having any insurance is associated with better health and, in particular, that having public, welfare-based insurance has better health consequences for the poor than does having no insurance. These questions were addressed using data from the National Medical Expenditure Survey, a national household-based survey in 1987 of more than 36,000 people who were asked to report in detail about their medical care use and expenditures, health insurance coverage, and health and functional status. The results of the analysis indicate that being without insurance is associated with having poorer general health compared to persons with private insurance, and that the health of persons who qualify for public insurance is the poorest of any group--poorer even than those without insurance.

Adolescent↗

[PDGF-induced effect on cytosolic free calcium concentration of cultured retinal pericytes].

Although the selective loss of retinal pericytes has long been known to be one of the earliest histopathological findings in diabetic retinopathy, only limited information is available concerning their function and cell biology. Recently, it has been shown that the interaction of endothelial cells and pericytes plays an important role in the maintenance of vascular integrity. Additionally, it has been suggested that pericytes have a contractile function. Platelet-derived growth factor (PDGF), released from endothelial cells, has been shown to be a potent mitogen and vasoconstrictor. Cytosolic free calcium ([Ca2+]i) has been shown to play a key role as a second messenger for PDGF, involved in the regulation of various cellular functions, e.g. cell proliferation and vascular contractility. In order to characterize the effect of different PDGF homodimers on cultured bovine retinal pericytes, we investigated PDGF-AA- and -BB-dependent alterations in [Ca2+]i was determined with the Ca(2+)-sensitive fluorescent probe Quin-2. Basal levels were 118 +/- 30 nM. Stimulation with PDGF-BB in concentrations ranging from 5 to 20 ng/ml led to a dose-dependent increase of [Ca2+]i with an EC50 of 5.8 ng/ml. Maximum stimulation, to about 280% of basal levels, occurred after 3-4 min. In contrast, PDGF-AA was not effective. The results suggest that PDGF-BB may influence the integrity and contractility of the retinal microvasculature via modulation of the intracellular calcium homeostasis of pericytes. Additionally, it can be speculated that cultured retinal pericytes express mainly PDGF-beta-type receptors.

Animals↗

Health care utilization: the effect of extending insurance to adults on Medicaid or uninsured.

Current health care system reform proposals center on reducing the number of uninsured by extending private health insurance coverage. Discussion has also included enrolling Medicaid recipients in private programs. Much of the deliberation concerning extending coverage has centered on cost, but largely has not addressed the implications for health care utilization by these groups. If private insurance is extended to those currently uninsured as well as the Medicaid population, what impact will it have on utilization? Using data from the 1987 National Medical Expenditure Survey, the results of this analysis show that utilization would increase for the uninsured if private insurance benefits were extended, whereas utilization would decrease for those with Medicaid, however, the magnitude of the increase depends on the type of care.

Adult↗

[Growth characteristics of bovine retinal pericytes in culture].

The loss of retinal pericytes is one of the earliest changes in diabetic retinopathy. In order to study this phenomenon in vitro, an optimal isolation and cultivation system has to be established. Therefore, pericytes from bovine retinae were isolated enzymatically with 0.4% collagenase in phosphate-buffered saline and identical immunologically by positive staining with antibodies against smooth muscle alpha-actin. Routine cultivation of pericytes was performed by using DMEM supplemented with 10% fetal calf serum. Dependent on the in vitro age of cells, the effect of the following reagents on proliferative activity was determined: fetal calf serum, heparin, ECGF, ECGF+heparin, and glucose. Increasing serum concentrations stimulated the proliferation of pericytes, although the degree of stimulation was reduced with increasing in vitro age. Heparin inhibited the growth in a dose-dependent manner; the achieving 50% inhibition was extrapolated to be 25 micrograms/ml. ECGF increased pericyte proliferation significantly, with a maximum at 10 microliters/ml. In addition, ECGF reversed the inhibitory effect of heparin. Furthermore, all tested glucose concentrations (5.5-27.75 mmol/l) did not show any influence on growth rates of pericytes. The results demonstrate that routine cultivation of retinal pericytes is possible. Moreover, they indicate that enhanced blood glucose concentrations, as observed in diabetic patients, are not the only important factor in the loss of retinal pericytes.

Animals↗

Nasal secretion of the ozone scavenger uric acid.

Uric acid, an important scavenger of ozone, has been identified as the major low molecular weight antioxidant in baseline and cholinergically induced nasal secretions. The purpose of this study was to determine the specific tissue source of uric acid in airway secretions. The secretion of uric acid is increased by cholinergic stimulation and correlates closely with the secretion of lactoferrin (a nasal glandular protein), suggesting that submucosal glands are involved. Indeed, nasal turbinate tissue was found to contain uric acid. However, careful analysis of nasal turbinate tissue failed to reveal the presence of xanthine oxidase, the enzyme responsible for uric acid synthesis. These data suggest that uric acid might be taken up secondarily by glands from plasma. This possibility was strengthened by the observation that lowering the plasma urate level with probenecid concomitantly lowered urate secretion. These findings are consistent with the hypotheses that the principal source of uric acid in nasal secretions is plasma and that uric acid is taken up, concentrated, and secreted by nasal glands.

Albumins↗

[The orthodontic treatment needs of young adults. An epidemiological study of recruits].

In an epidemiological study of 370 recruits, the need for orthodontic treatment was investigated. Subjects who had previously received orthodontic treatment (n = 135) were compared with untreated subjects (n = 234). An unequivocal need for orthodontic treatment was ascertained in 50% of the recruits. Differences between previously treated subjects and untreated subjects were not Some 60% of the orthodontic measures had been carried out by an orthodontist, and 40% by a nonspecialist dentist. The results of treatment were generally unsatisfactory, although the success rate achieved by the orthodontists did appear somewhat higher than that seen with nonspecialist dentists.

Adolescent↗

Human T-lymphotropic virus type I-associated myelopathy in patients with the acquired immunodeficiency syndrome.

We describe two cases of serologically confirmed human T-lymphotropic virus type I (HTLV-I)-associated myelopathy involving North American men coinfected by the human immunodeficiency virus type 1. Our first patient suffered from a gradually progressive spastic paraparesis for 10 years prior to presenting with Kaposi's sarcoma, while our second patient developed subacutely progressive spastic paraparesis in the setting of full-blown acquired immunodeficiency syndrome. Autopsy examination of the spinal cords from these two cases revealed widespread axonal loss and demyelination principally involving the lateral columns of case no. 1 and the lateral and anterior columns of case no. 2. Vascular sclerosis and hyalinization were prominent in both cases, but in neither was there a conspicuous inflammatory component. In case no. 2, HTLV-I mRNA was not detected by in situ hybridization, but HTLV-I proviral DNA sequences were detected in this case by polymerase chain reaction. Neither case exhibited multinucleated cell (human immunodeficiency virus type 1) myelitis, vacuolar myelopathy, or evidence of HTLV-II infection by polymerase chain reaction assay.

Acquired Immunodeficiency Syndrome↗