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Biomedical subjects

M Stein

Publications and source records attributed to M Stein.

At least 55 records · Page 3Linked to original sources

Single crystal EPR studies of the oxidized active site of [NiFe] hydrogenase from Desulfovibrio vulgaris Miyazaki F.

The Ni-A and the Ni-B forms of the [NiFe] hydrogenase from Desulfovibrio vulgaris Miyazaki F have been studied in single crystals by continuous wave and pulsed EPR spectroscopy at different temperatures (280 K, 80 K, and 10 K). For the first time, the orientation of the g-tensor axes with respect to the recently published atomic structure of the active site at 1.8 A resolution was elucidated for Ni-A and Ni-B. The determined g-tensors have a similar orientation. The configuration of the electronic ground state is proposed to be Ni(III) 3d1/z 2 for Ni-A and Ni-B. The gz principal axis is close to the Ni-S(Cys549) direction; the gx and the gy axes are approximately along the Ni-S(Cys546) and Ni-S(Cys81) bonds, respectively. It is proposed that the difference between the Ni-A and Ni-B states lies in a protonation of the bridging ligand between the Ni and the Fe.

Binding Sites↗

Prehospital stabilization of the cervical spine for penetrating injuries of the neck - is it necessary?

The purpose of this study was to assess the specific indications, benefits and risks associated with cervical spine stabilization during pre-hospital care of penetrating neck injuries. We retrospectively reviewed hospital charts and autopsy reports of 44 military casualties in Israel with a penetrating neck injury during a period of 4.5 years. A review of the literature was also carried out. In eight of 36 hospitalized casualties (22%) a life-threatening sign was diagnosed in the exposed neck - large or expanding haematoma, or subcutaneous emphysema. Surgical stabilization of the cervical spine was not performed for any of the casualties. It was concluded that life threatening complications due to penetrating neck injury are common and may be overlooked if the neck is covered by a stabilization device. It is extremely rare for a penetrating injury to result in an unstable cervical spine. New management guidelines concerning pre-hospital stabilization are suggested.

Braces↗

TIPS reduces hepatic asialoglycoprotein receptor concentration in healthy pigs.

PURPOSE: Technetium-99m-labeled diethylenetriamine pentaacetic acid galactosyl human serum albumin (TcGSA), a new agent for liver scintigraphy, is selectively attached to asialoglycoprotein receptors on liver cell membranes. A direct correlation exists between asialoglycoprotein receptor concentration, [R]o and hepatic functional reserve. The purpose of this study was to determine the effects of transjugular intrahepatic portosystemic shunting (TIPS) on hepatic asialoglycoprotein receptor concentration in pigs without liver parenchymal disease. MATERIALS AND METHODS: TIPS was performed in eight pigs with use of a single 10-mm-wide x 68-mm-long Wallstent dilated to 10 mm. TcGSA dynamic imaging studies were performed before and twice after (7 and 14 days) TIPS. To be included in the study, pigs had to have a patent TIPS at 1 week of follow-up. Liver function tests were drawn parallel to the TcGSA studies. Liver biopsies were performed at 2 weeks when the animals were killed. RESULTS: Five of the eight pigs had open shunts at 1 week and were included in the study. There was a significant (P < .0001, Student t test) difference between the mean [R]o of the pre-TIPS studies ([R]o = 1.12+/-0.04 microM) and the mean of the post-TIPS studies at 7 days ([R]o = 0.40+/-0.04 microM) and 14 days ([R]o = 0.51+/-0.06 microM, P < .01). The only blood test that was abnormal after TIPS was ammonia (mean, 129.0+/-42.7). Liver biopsies were normal. CONCLUSIONS: TIPS reduces asialoglycoprotein receptor concentration in normal pigs.

Animals↗

Xenognosin sensing in virulence: is there a phenol receptor in Agrobacterium tumefaciens?

BACKGROUND: The mechanisms of signal perception and transmission in the 'two-component' autokinase transmitters/response regulators are poorly understood, especially considering the vast number of such systems now known. Virulence induction from the tumor-inducing (Ti) plasmid of Agrobacterium tumefaciens represents one of the best understood systems with regard to the chemistry of the activating signal, and yet the existing data does not support a receptor-mediated perception event for the xenognostic phenols. RESULTS: Here we provide the first conclusive evidence that a specific receptor must be involved in xenognostic phenol perception, detail structural requirements of the xenognosins necessary for perception by this receptor, and develop a genetic strategy that demonstrates critical components of the phenol recognition system are not encoded on the Ti plasmid. CONCLUSIONS: Although the basic elements of the two-component system required for phenol-mediated induction of virulence gene expression are encoded on the Ti plasmid, they are dependent on the chromosomal background for even the very first stage of signal perception. This discovery suggests a curious evolutionary history, and also provides functional insight into the mechanisms of two-component signal detection and transmission in general.

Agrobacterium tumefaciens↗

Survey of the extent and nature of care for adults and older adults by allergy/immunology practitioners.

BACKGROUND: The proportion of older adults in the US population will increase dramatically in the near future, yet the frequency and nature of care furnished to older adults by Allergy/Immunology practitioners has not been described. OBJECTIVE: To determine the extent and nature of care being provided to adults and older adults by Allergy/Immunology practitioners. METHODS: ACAAI members and fellows were surveyed to obtain information regarding certification and training as well as their practice patterns. RESULTS: The distribution of diagnoses among patients aged 40 to 54 years were very similar to distributions found among adults age 55 to 69 years and > or = 70 years of age. Virtually all respondents indicated they provide inhalant allergen immunotherapy for patients age 40 to 54 years with asthma and/or allergic rhinitis; administration of inhalant allergen immunotherapy for asthma and allergic rhinitis was also frequently reported for adults > or = 55 years. The proportions of respondents providing venom immunotherapy for adults aged 40 to 54, 55 to 69, and > or = 70 years were 82%, 70%, and 39%, respectively. CONCLUSION: ACAAI members and fellows commonly provide care to older adults. Our survey findings highlight the need to develop strategies for successful management of Allergy/Immunology conditions specifically pertaining to older adults, including studies to determine the therapeutic utility of inhalant allergen and venom immunotherapy in this age group.

Adult↗

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease.

Aged↗

[Influence of comorbidity on the prognosis of squamous cell carcinoma in the head and neck].

BACKGROUND: The influence of comorbidity on the healing process and the prognosis of patients with carcinoma of the head and neck region undergoing surgical treatment is not clear. PATIENTS AND METHODS: In a retrospective study we examined the influence of coexistent diseases in 203 patients, hospitalized for curative surgical treatment. Findings on admission, supplemented by medical, anaesthesiological and neurological assessments, helped to form two subgroups: one of patients with minimal comorbidity (n = 135) and one with high comorbidity (n = 68). Subsequently the duration of hospitalization, incidence of complications, disease-free interval and survival was statistically compared. RESULTS: The duration of hospitalization, the incidence and degree of complications, the disease-free interval and the overall survival differed significantly, showing better results in the group with low comorbidity. CONCLUSION: Coexistent, mainly medical, diseases had a significant influence on the results of surgical treatment and prognosis of head and neck cancer.

Carcinoma, Squamous Cell↗

Expression and in vitro properties of guinea pig IL-5: comparison to human and murine orthologs.

Interleukin-5 (IL-5) is a key mediator of eosinophilic inflammation. The biological role of this cytokine in an allergic airway inflammatory response has been widely demonstrated in guinea pigs, yet the interaction of guinea pig IL-5 (gpIL-5) with its receptor has not been studied. Experiments were performed to quantitate the interaction of gpIL-5 with gpIL-5r and to compare this affinity with that of hIL-5 and mIL-5 and their cognate receptors. The cross-species affinity and agonist efficacy were evaluated to see if gpIL-5r had a restricted species reactivity (as is the case with mIL-5r) or did not distinguish between IL-5 orthologs (similar to hIL-5r). gpIL-5 was cloned using mRNA isolated from cells obtained by bronchoalveolar lavage. Recombinant gpIL-5 was expressed in T. ni insect cells and purified from spent media. Binding assays were performed using insect cells expressing hIL-5ralphabeta or gpIL-5ralphabeta1 as previously described (Cytokine, 12:858-866, 2000) or using B13 cells which express mIL-5r. The agonist potency and efficacy properties of each IL-5 ortholog were evaluated by quantitating the proliferative response of human TF-1 cells and murine B13 cells. gpIL-5 bound with high affinity to recombinant gpIL-5r as demonstrated by displacing [125I]hIL-5 (Ki = 160 pM). gpIL-5 also bound to hIL-5r with high affinity (Ki = 750 pM). hIL-5 and mIL-5 showed similar, high-affinity binding profiles to both gpIL-5r and hIL-5r. In contrast, gpIL-5 and hIL-5 did not bind to the mIL-5r as demonstrated by an inability to displace [125I]mIL-5, even at 1000-fold molar excess. These differences in affinity for IL-5r orthologs correlated with bioassay results: human TF-1 cells showed roughly comparable proliferative responses to guinea pig, human and murine IL-5 whereas murine B13 cells showed a strong preference for murine over guinea pig and human IL-5 (EC50 = 1.9, 2200 and 720 pM, respectively). Recombinant gpIL-5 binds to the gpIL-5r with high affinity, similar to that seen with the human ligand-receptor pair. gpIL-5r and hIL-5r do not distinguish between the three IL-5 orthologs whereas mIL-5r has restricted specificity for its cognate ligand.

Animals↗

Influence of the orifice inlet angle on the velocity profile across a flow convergence region by color Doppler in vitro.

The converging flow field proximal to a leaking valve is determined among other things by the orifice inlet angle formed by the leaflets. Thus, the inlet angle affects the determination of regurgitant flow rate by the flow convergence method. Based on the hypothesis of spheric isovelocity surfaces, others had postulated that a local velocity within the flow convergence should change inversely proportional to changes in the three-dimensional inlet angle. This concept would allow correction of the determination of regurgitant flow for nonplanar orifice inlet angles. We tested this concept in vitro. In a flow model, the flow convergence region proximal to different orifice plates was imaged by color Doppler: funnel-shaped, planar and tip-shaped (inverted funnels) orifice plates, with circular orifices of 2- and 7-mm diameter. Velocity profiles across the flow convergence along the flow centerline were read from the color maps. As predicted, the local velocities were inversely related to the inlet angle, but only at the 2-mm funnel orifices, this effect was inversely proportional to the three-dimensional inlet angle (i.e., in agreement with the mentioned concept). However, for any 7-mm orifice and/or inlet angle of > 180 degrees, the effect of the inlet angle was considerably less than predicted by the aforementioned concept. With increasing orifice diameter and with decreasing distance to the orifice, the effect of the orifice inlet angle was reduced. The effect of the orifice inlet angle on the flow convergence region is modulated by orifice size and the distance to the orifice. Therefore, correction of flow estimates in proportion to the three-dimensional inlet angle will lead to considerable errors in most situations of clinical relevance, namely to massive overcorrection when analyzing velocities located close to wide orifices.

Blood Flow Velocity↗

Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy.

Helminthic parasites cause widespread, persistent infections in humans. The immigration of Ethiopians to Israel (a group denoted here by "Eth."), many of them infested with helminths and in a chronic immune-activation state, enabled us to investigate the effects of such immune activation on immune responses. We studied the immune profile and immune functions of 190 Eth. and Israeli non-Eth. (Isr.) highly, partially, or non-immune-activated individuals. Immune cells from highly immune-activated individuals were defective in several signaling responses, all of which were restored gradually following anti-helminthic treatment. These cells showed poor transmembrane signaling, as seen by the phosphorylation of various tyrosine kinases and of the MAPK kinases, ERK1/2 and p38; deficient degradation of phosphorylated IkappaBalpha; increased expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), which appears to block proliferative responses in these cells; decreased beta-chemokine secretion by CD8(+) cells after stimulation; and reduced proliferation to recall antigen stimulation. Highly immune-activated individuals also showed decreased delayed-type skin hypersensitivity responses to recall antigen before deworming. These findings support the notion that chronic helminthic infections cause persistent immune activation that results in hyporesponsiveness and anergy. Such impaired immune functions may diminish the capacity of these individuals to cope with infections and to generate cellular protective immunity after vaccination.

Abatacept↗

Violence victimization after HIV infection in a US probability sample of adult patients in primary care.

OBJECTIVES: This study estimated the proportion of HIV-infected adults who have been assaulted by a partner or someone important to them since their HIV diagnosis and the extent to which they reported HIV-seropositive status as a cause of the violence. METHODS: Study participants were from a nationally representative probability sample of 2864 HIV-infected adults who were receiving medical care and were enrolled in the HIV Costs and Service Utilization Study. All interviews (91% in person, 9% by telephone) were conducted with computer-assisted personal interviewing instruments. Interviews began in January 1996 and ended 15 months later. RESULTS: Overall, 20.5% of the women, 11.5% of the men who reported having sex with men, and 7.5% of the heterosexual men reported physical harm since diagnosis, of whom nearly half reported HIV-seropositive status as a cause of violent episodes. CONCLUSIONS: HIV-related care is an appropriate setting for routine assessment of violence. Programs to cross-train staff in antiviolence agencies and HIV care facilities need to be developed for men and women with HIV infection.

Adolescent↗

A review of the epidemiology and approaches to the treatment of social anxiety disorder.

This review presents current literature on the epidemiology and treatment of social anxiety disorder (social phobia). This illness has been demonstrated to be the most common anxiety disorder with a 1-year prevalence of 7 to 8% and a lifetime prevalence of 13 to 14% in patients aged between 15 and 54 years. Social anxiety disorder can be classified into 2 subtypes, discrete and generalised. Morbidity is high with this disorder, and 70 to 80% of patients have co-morbid mental disorders. Although effective treatments are available, social anxiety disorder is under-recognised and under-treated. Treatments that have been systemically studied and have shown efficacy in patients with social anxiety disorder include pharmacotherapy (selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, reversible inhibitors of monoamine-A and benzodiazepines) and short term psychotherapies (cognitive behaviour therapy, social skills training and exposure in vivo therapy). Beta-blockers are useful in treating performance-related anxiety. Few published data are available on the treatment of social anxiety disorder with a combination of pharmacotherapy and psychotherapy. We conclude this review by discussing proposed algorithms for treating both subtypes of social anxiety disorder.

Adolescent↗

Problematic intubation in soldiers: are there predisposing factors?

Attempts by a combat medical officer to secure the airway of a multiple-injury patient in the field may frequently end in failure. The recurrence of such failures, despite Advanced Trauma Life Support training, is perplexing; therefore, we studied the prevalence of clinical criteria that could predispose active soldiers to difficult intubation. Such known anatomical features and the Mallampati classification were assessed by experts in 250 soldiers at a military outpatient clinic of the Israel Defense Forces. It was found that most soldiers had normal airways. Limitations of head and neck movement, or in opening the mouth, were not observed. Other risk factors were noted in only a small percentage of the study population. Mallampati classes I and II were noted in 40% and 31%, respectively. No statistically significant differences between young (18-21 years) and older (40-44 years) soldiers were found. It was concluded that difficult intubations among soldiers are unlikely to be associated with anatomical causes. Complicated scenarios and deficient skills of the physicians are the most important factors that contribute to in-field failures to secure airway control. Several recommendations to remedy this situation are offered.

Adolescent↗

Pediatricians and the Advanced Trauma Life Support (ATLS): time for reconsideration?

BACKGROUND: General pediatricians in Israel are actively involved in the initial evaluation, resuscitation and management of traumatized children. However, pediatric trauma care is not a part of pediatric specialty training in Israel, and the few Advanced Trauma Life Support courses per year are insufficient for most pediatricians working in accident and emergency care. OBJECTIVE: To examine the value of the course in relation to the limited resources available for such training. METHODS: A telephone survey of 115 pediatricians who had taken the course between 1990 and 1994 was conducted. The responding physicians (67%) were asked to complete a specially designed questionnaire on life-saving procedures that were taught in the course. In addition, they were asked to subjectively assess the practical utility of the course. RESULTS: Forty-three (56%) pediatricians reported that they routinely treated both adult and pediatric trauma cases. Of these, 81% performed 27 life-saving ATLS procedures. Pediatric trauma was treated by only 22 (28%), of whom 72.3% performed 18 life-saving ATLS procedures. These pediatricians ranked the courses as being "very high" to "high" in impact. CONCLUSIONS: These figures indicate that an ATLS course designed specifically for pediatricians can markedly improve pediatric trauma care. To ensure standard education and patient care, such a course should be developed and made a mandatory component of residency training. Further studies to examine the objective impact of the courses on pediatric trauma care should be carried out.

Adolescent↗

Hydroxychloroquine neuromyotoxicity.

Hydroxychloroquine (HCQ) is commonly prescribed for treatment of inflammatory arthritis. The most frequently observed serious side effect is retinal toxicity; however, case reports have described HCQ induced neuromyotoxicity. We describe a case of HCQ neuromyotoxicity and a literature review from 1965 to September 1998 using Medline and Embase. Including our patient, there are 10 reported cases of HCQ neuromyotoxicity. Muscle biopsy consistently reveals curvilinear bodies and muscle fiber atrophy with vacuolar changes. Most cases manifest as insidious onset proximal myopathy that may be associated with peripheral neuropathy and cardiac myotoxicity. Resolution of symptoms is slow after discontinuation of therapy and may be incomplete. Possible predisposing factors include Caucasian race and concomitant renal failure. Patients treated with HCQ who develop a proximal myopathy, cardiomyopathy, or neuropathy, especially in the setting of worsening renal function, should be evaluated for possible HCQ neuromyotoxicity.

Aged↗

The complex regulation of ferredoxin/thioredoxin-related genes by light and the circadian clock.

The biochemical properties of the ferredoxin/thioredoxin transduction pathway regulating the activity of key carbon-fixation enzymes through post-translational modifications are well characterized but little is known about the regulation of the different genes. In the present study, we investigated in Chlamydomonas reinhardtii the regulation of the expression of ferredoxin, thioredoxin m, ferredoxin-NADP reductase, phosphoribulokinase, as well as that of cytosolic thioredoxin h, the function of which is still largely unknown. The effects of light, the circadian clock and active cell division were investigated by northern blotting. The five genes were found to be regulated by light and the circadian clock but with different kinetics and amplitudes. This leads for the first time to the proposal that an extra-chloroplastic thioredoxin is possibly implicated in light and/or circadian-related processes. An interplay between several light-transduction pathways in controlling the expression of the genes is suggested by the expression studies and the theoretical analysis of the promoters.

Journal Article↗