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Biomedical subjects

B Cohen

Publications and source records attributed to B Cohen.

At least 37 records · Page 2Linked to original sources

Engraftment syndrome: a common cause for rash and fever following autologous hematopoietic stem cell transplantation for multiple sclerosis.

Autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated as a therapy for patients with progressive multiple sclerosis (MS) at risk of debilitating neurological impairment. While preliminary results from a few studies have been reported, little is known about toxicities or outcome of HSCT for MS. We report a relatively frequent triad of non-infectious fever, rash and fatigue or lassitude that may also be associated with pruritus, pulmonary symptoms, and eosinophilia and frequently occurs around engraftment. This syndrome occurred in 26% of our series of patients (5/19) undergoing HSCT for multiple sclerosis. The engraftment syndrome is usually self-limited but may require intervention with systemic corticosteroids.

Adult↗

Causes of morbilliform rash in a highly immunised English population.

AIMS: To determine the causes of morbilliform rash and fever in a population with high vaccination coverage for measles and rubella. METHODS: Comprehensive laboratory investigation additional to routine oral fluid testing of children presenting to primary care physicians in East Anglia, England. RESULTS: Laboratory confirmation of infection was obtained in 93 (48%) of 195 children: parvovirus B19 in 34 (17%); group A streptococcus in 30 (15%); human herpesvirus type 6 in 11 (6%); enterovirus in nine (5%); adenovirus in seven (4%); and group C streptococcus in six (3%) (four individuals tested positive for two agents). None had measles or rubella. CONCLUSIONS: Oral fluid testing to cover infections additional to measles and rubella aids clinical management and is likely to maintain uptake of testing, which is essential for measles and rubella surveillance in highly immunised low incidence populations.

Adenoviridae Infections↗

Smoking behaviours and attitudes among male restaurant workers in Boston's Chinatown: a pilot study.

OBJECTIVE: Asian American immigrants experience high rates of cigarette smoking. A community based survey was conducted to understand the smoking behaviours, knowledge, and attitudes of restaurant workers in Boston's Chinatown. DESIGN: Cross sectional survey in Chinese of a convenience sample of 54 restaurant workers recruited through extensive outreach activities. RESULTS: All 54 of the workers were male immigrants. 45 (83.3%) reported smoking cigarettes regularly, and the remaining nine were former smokers. 36 of the smokers (80.0%) started smoking before entering the USA. The workers were aware that cigarettes are addictive (98.1%), cause lung cancer (79.6%), and lead to heart disease (64.8%). However, a substantial number reported that smoking was relaxing (75.9%) and enhanced concentration (66.7%). Nearly half believed low tar and low nicotine cigarettes to be safer than standard brands. The vast majority of workers believed that smoking was not socially acceptable for women. Smokers reported they received information on quitting most commonly from friends (60%), newspapers (53.5%), and television (44.4%). The restaurant workers most often saw advertising against smoking in Chinese newspapers (63%). CONCLUSION: Despite high rates of smoking, Chinese American restaurant workers were generally aware of the health risks and were interested in quitting. Community based research can set the stage for targeted public health efforts to reduce smoking in immigrant communities.

Adult↗

Comparison between caloric and canal impulse rotatory test.

It has been suggested that the rotatory test using videosnystagmoscopy can also be applied for identification of vestibular canal paresis. In this study, we test this hypothesis by comparing the results of a canal impulse rotatory test with those of the caloric test using the method described by Freyss. Our study indicates that only in 38% of all tested patients, the same results between the two tests have been obtained. Furthermore, which the group with abnormal findings is observed separately, in 24% patients only these two test methods lead to the same results. Consequently, the canal impulse rotatory test cannot replace the caloric test.

Caloric Tests↗

Comparison between caloric and canal impulse rotatory test.

It has been suggested that the rotatory test using videonystagmoscopy can also be applied for identification of vestibular canal paresis. In this study, we test this hypothesis by comparing the results of a canal impulse rotatory test with those of the caloric test using the method described by Freyss. Our study indicates that only in 38% of all tested patients, the same results between the two tests have been obtained. Furthermore, when the group with abnormal findings is observed separately, in 24% patients only these two test methods lead to the same results. Consequently, the canal impulse rotatory test cannot replace the caloric test.

Caloric Tests↗

Application of FTIR microscopy for the characterization of malignancy: H-ras transfected murine fibroblasts as an example.

Recently, microscopic FTIR is widely used in the field of biology and medicine. FTIR can detect biomolecular changes in the cells and tissues responsible for various disorders. In this report, we characterize the H-ras transfected fibroblasts and its normal control using microscopic FTIR. The intensity of the normal fibroblasts was higher than that of H-ras transfected fibroblasts. Our studies showed significant differences occur in the concentration of vital metabolites upon transformation. The DNA and carbohydrates level decreased in the transformed cells compared to the controls. A linear correlation could be found between the levels of carbohydrates and phosphate, while the RNA/DNA ratio varied inversely with glucose/phosphate levels.

3T3 Cells↗

Fluorescence spectroscopy for detection of malignancy: H-ras overexpressing fibroblasts as a model.

Autofluorescence from intracellular chromophores upon illumination of cells by monochromatic light has been studied towards the development of novel noninvasive and sensitive technology for the early detection of cancer. To investigate the relationship between biochemical and morphological changes underlying malignant disease and resulting fluorescence spectra, an in vitro model system of a paired normal and malignant murine fibroblasts cell lines, differing in cancer-associated H-ras expression was employed. A comparison of fluorescence excitation and emission spectra of proliferative cells revealed that fluorescence intensity of malignant cells was significantly less than that of normal cells upon excitation at 290 nm. Fluorescence of both cell lines decreased with decreasing cell concentration, but at each concentration, normal cells had higher fluorescence intensity than malignant cells. Similar differences between the cell lines were observed when brought to quiescence or at stationary phase. Results suggested that the chromophore contributing most significantly to these spectra is tryptophan and its moieties in proteins. This model system demonstrates the specific contribution of H-ras to subcellular chromophores, resulting in a significant difference in their autofluorescence intensity, and implies the potential use of the technique for cancer detection. This model system is potent for analysis of the contribution of other oncogenes and their combinations towards spectral detection of cancer.

3T3 Cells↗

CSF antiretroviral drug penetrance and the treatment of HIV-associated psychomotor slowing.

The authors evaluated whether highly active antiretroviral therapy (HAART) with multiple CSF-penetrating drugs results in greater improvement in HIV-associated psychomotor slowing than HAART with a single CSF-penetrating drug. Both groups had improvement in CD4 count, plasma viral load, as well as two tests of psychomotor speed. Comparing the two groups, there were no differences in the mean change for CD4 count, viral load, or any of the neuropsychological tests. Multiple and single CSF-penetrating HAART may be equivalent for treating HIV-associated psychomotor slowing.

Adult↗

MMR vaccine in HIV-infected children -- potential hazards?

Although given routinely as prophylaxis against wild-type measles to HIV-infected children, the live attenuated measles component of the MMR triple vaccine also possesses potential for disease. We document a case of measles proven to be caused by vaccine strain in a HIV-infected child here in the UK and discuss the clinical and immunological aspects. We also consider the new guidelines for MMR vaccination in HIV-infected children adopted last year in the USA.

Antiretroviral Therapy, Highly Active↗

An overview of the immune system.

We are continually exposed to organisms that are inhaled, swallowed, or inhabit our skin and mucous membranes. Whether these organisms penetrate and cause disease is a result of both the pathogenicity of the organism (the virulence factors at its disposal) and the integrity of host defence mechanisms. The immune system is an interactive network of lymphoid organs, cells, humoral factors, and cytokines. The essential function of the immune system in host defence is best illustrated when it goes wrong; underactivity resulting in the severe infections and tumours of immunodeficiency, overactivity in allergic and autoimmune disease. In this review we have covered the normal function of the immune system in recognising, repelling, and eradicating pathogens and other foreign molecules.

B-Lymphocytes↗

Regulation of p53 stability and p53-dependent apoptosis by NADH quinone oxidoreductase 1.

The tumor suppressor gene wild-type p53 encodes a labile protein that accumulates in cells after different stress signals and can cause either growth arrest or apoptosis. One of the p53 target genes, p53-inducible gene 3 (PIG3), encodes a protein with significant homology to oxidoreductases, enzymes involved in cellular responses to oxidative stress and irradiation. This fact raised the possibility that cellular oxidation-reduction events controlled by such enzymes also may regulate the level of p53. Here we show that NADH quinone oxidoreductase 1 (NQO1) regulates p53 stability. The NQO1 inhibitor dicoumarol caused a reduction in the level of both endogenous and gamma-irradiation-induced p53 in HCT116 human colon carcinoma cells. This reduction was prevented by the proteasome inhibitors MG132 and lactacystin, suggesting enhanced p53 degradation in the presence of dicoumarol. Dicoumarol-induced degradation of p53 also was prevented in the presence of simian virus 40 large T antigen, which is known to bind and to stabilize p53. Cells overexpressing NQO1 were resistant to dicoumarol, and this finding indicates the direct involvement of NQO1 in p53 stabilization. NQO1 inhibition induced p53 degradation and blocked wild-type p53-mediated apoptosis in gamma-irradiated normal thymocytes and in M1 myeloid leukemic cells that overexpress wild-type p53. Dicoumarol also reduced the level of p53 in its mutant form in M1 cells. The results indicate that NQO1 plays an important role in regulating p53 functions by inhibiting its degradation.

Animals↗

HIV-associated neurologic disease incidence changes:: Multicenter AIDS Cohort Study, 1990-1998.

This study examined the temporal trends in the incidence rates of HIV dementia, cryptococcal meningitis, toxoplasmosis, progressive multifocal leukoencephalopathy, and CNS lymphoma from January 1990 to December 1998 in the Multicenter AIDS Cohort Study. The incidence rates for HIV dementia, cryptococcal meningitis, and lymphoma decreased following the introduction of highly active antiretroviral therapy (HAART). The proportion of new cases of HIV dementia with a CD4 count in a higher range (i.e., 201 to 350) since 1996 may be increasing.

AIDS Dementia Complex↗

Leptin induces angiopoietin-2 expression in adipose tissues.

Adipose tissues consisting of adipocytes, microvasculature, and stroma are completely ablated upon over-expression of leptin in rats. This tissue regression is mediated by enhanced lipid beta-oxidation, adipocyte dedifferentiation, and apoptosis. To further characterize this phenomenon, we studied the possible effect of leptin on the adipose microvasculature. Tissue microvasculature is maintained by the interplay between positive and negative signals mediated by factors including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, angiopoietin-1 (Ang-1), and Ang-2. Expression of the negative signal Ang-2 was reported in fetal tissues and in the adult ovary, which undergoes vascular remodeling or regression. We demonstrate that leptin induces the expression of Ang-2 in adipose tissue without a concomitant increase in VEGF. Induction of Ang-2 occurred in an autocrine manner, as demonstrated in cultured adipocytes but not in several other cell types. This tissue-specific induction of Ang-2 coincided with initiation of apoptosis in adipose endothelial cells. We propose that induction of Ang-2 by leptin in adipose cells is one of the events leading to adipose tissue regression.

3T3 Cells↗

Diagnosis of human parvovirus B19 infections by detection of epitope-type-specific VP2 IgG.

In the B19 VP2 molecule an immunodominant heptapeptide epitope has been detected, recently for which IgG antibodies are synthesized exclusively in the acute phase of B19 infection. Using this acute-phase-specific epitope (KYVTGIN) a 2(nd)-generation epitope-type EIA was developed, which compares serum IgG activity for native VP2 capsids exhibiting conformational VP2 epitopes with IgG activity for the KYVTGIN epitope. In this study the diagnostic performance (clinical sensitivity and specificity) of the 1st and 2nd-generation epitope-type EIAs and of a peptide-based EIA utilising as antigen the KYVTGIN epitope alone was assessed in comparison with various high-quality IgM- and IgG- based B19 assays. Serum samples from 489 patients with B19-related symptoms and asymptomatic controls from three countries were studied. Among 323 patients with B19-IgG, 20% were diagnosed as acute infection, 73% had past immunity and 7% were not classified due to contradictory results among the different assays. The unclassified samples were explored for viral strain diversity by PCR and DNA sequencing but all sequences obtained were B19-like with variance of only a few per cent. The 2nd-generation epitope-type EIA had a diagnostic sensitivity of 98% and a diagnostic specificity of 94%. In combination with conventional approaches, the epitope-type assays increase greatly the accuracy of B19 serodiagnosis.

Acute Disease↗

Interaction of the body, head, and eyes during walking and turning.

Body, head, and eye movements were measured in five subjects during straight walking and while turning corners. The purpose was to determine how well the head and eyes followed the linear trajectory of the body in space and whether head orientation followed changes in the gravito-inertial acceleration vector (GIA). Head and body movements were measured with a video-based motion analysis system and horizontal, vertical, and torsional eye movements with video-oculography. During straight walking, there was lateral body motion at the stride frequency, which was at half the frequency of stepping. The GIA oscillated about the direction of heading, according to the acceleration and deceleration associated with heel strike and toe flexion, and the body yawed in concert with stepping. Despite the linear and rotatory motions of the head and body, the head pointed along the forward motion of the body during straight walking. The head pitch/roll component appeared to compensate for vertical and horizontal acceleration of the head rather than orienting to the tilt of the GIA or anticipating it. When turning corners, subjects walked on a 50-cm radius over two steps or on a 200-cm radius in five to seven steps. Maximum centripetal accelerations in sharp turns were ca.0.4 g, which tilted the GIA ca.21 degrees with regard to the heading. This was anticipated by a roll tilt of the head of up to 8 degrees. The eyes rolled 1-1.5 degrees and moved down into the direction of linear acceleration during the tilts of the GIA. Yaw head deviations moved smoothly through the turn, anticipating the shift in lateral body trajectory by as much as 25 degrees. The trunk did not anticipate the change in trajectory. Thus, in contrast to straight walking, the tilt axes of the head and the GIA tended to align during turns. Gaze was stable in space during the slow phases and jumped forward in saccades along the trajectory, leading it by larger angles when the angular velocity of turning was greater. The anticipatory roll head movements during turning are likely to be utilized to overcome inertial forces that would destabilize balance during turning. The data show that compensatory eye, head, and body movements stabilize gaze during straight walking, while orienting mechanisms direct the eyes, head, and body to tilts of the GIA in space during turning.

Acceleration↗

Ocular counterrolling induced by centrifugation during orbital space flight.

During the 1998 Neurolab mission (STS-90), four astronauts were exposed to interaural centripetal accelerations (Gy centrifugation) of 0.5 g and 1 g during rotation on a centrifuge, both on Earth and during orbital space flight. Subjects were oriented either left-ear out or right-ear out, facing or back to motion. Binocular eye movements were measured in three dimensions using a video technique. On Earth, tangential centrifugation that produces 1 g of interaural linear acceleration combines with gravity to tilt the gravitoinertial acceleration (GIA) vector 45 degrees in the roll plane relative to the head vertical, generating a summed vector of 1.4 g. Before flight, this elicited mean ocular counterrolling (OCR) of 5.7 degrees. Due to the relative absence of gravity during flight, there was no linear acceleration along the dorsoventral axis of the head. As a result, during in-flight centrifugation, gravitoinertial acceleration was strictly aligned with the centripetal acceleration along the interaural axis. There was a small but significant decrease (mean 10%) in the magnitude of OCR in space (5.1 degrees). The magnitude of OCR during postflight 1 g centrifugation was not significantly different from preflight OCR (5.9 degrees). Findings were similar for 0.5 g centrifugation, but the OCR magnitude was approximately 60% of that induced by centrifugation at 1 g. OCR during pre- and postflight static tilt was not significantly different and was always less than OCR elicited by centrifugation of Earth for an equivalent interaural linear acceleration. In contrast, there was no difference between the OCR generated by in-flight centrifugation and by static tilt on Earth at equivalent interaural linear accelerations. These data support the following conclusions: (1) OCR is generated predominantly in response to interaural linear acceleration; (2) the increased OCR during centrifugation on Earth is a response to the head dorsoventral 1 g linear acceleration component, which was absent in microgravity. The dorsoventral linear acceleration could have activated either the otoliths or body-tilt receptors that responded to the larger GIA magnitude (1.4 g), to generate the increased OCR during centrifugation on Earth. A striking finding was that magnitude of OCR was maintained throughout and after flight. This is in contrast to most previous postflight OCR studies, which have generally registered decreases in OCR. We postulate that intermittent exposure to artificial gravity, in the form of the centripetal acceleration experienced during centrifugation, acted as a countermeasure to deconditioning of this otolith-ocular orienting reflex during the 16-day mission.

Acceleration↗