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Biomedical subjects

A Barzilai

Publications and source records attributed to A Barzilai.

At least 91 records · Page 5Linked to original sources

The proto-oncogene Bcl-2 inhibits cellular toxicity of dopamine: possible implications for Parkinson's disease.

It is currently believed that excessive oxidant stress induced by metabolism of dopamine (DA), plays a major role in the pathogenesis of the selective nigrostriatal neuronal loss in Parkinson's disease. We recently showed that the neurotransmitter DA, in physiological concentrations, is capable of initiating apoptosis in cultured, post-mitotic sympathetic neurons. Bcl-2 is a proto-oncogene that blocks apoptosis. We now report that Bcl-2 is a powerful inhibitor of DA toxicity in PC-12 pheochromocytoma cells. We induced stable expression of Bcl-2 in PC-12 cells by transfection with recombinant pCMV5 expression vector, containing mouse bcl-2 (coding-sequence) cDNA. Cells expressing Bcl-2 manifested marked resistance to otherwise lethal (300 uM) in vitroconcentrations of DA. This protective effect was reflected in the trypan-blue test of cell survival, 3 H-thymidine incorporation and inhibition of the characteristic apoptotic morphologic alterations in scanning electron microscopic studies. Bcl-2 and associated control systems of apoptosis may have an important physiological role in restraining the apop-tosis-triggering potential of DA in nigrostriatal neurons. This novel field of research may yield insights into the pathogenesis of Parkinson's disease and lead to development of novel therapeutic approaches.

Journal Article↗

Biochemical and temporal analysis of events associated with apoptosis induced by lowering the extracellular potassium concentration in mouse cerebellar granule neurons.

We analyzed biochemically and temporally the molecular events that occur in the programmed cell death of mouse cerebellar granule neurons deprived of high potassium levels. An hour after switching the neurons to a low extracellular K+ concentration ([K+]o), a significant part of the genomic DNA was already cleaved to high-molecular-weight fragments. This phenomenon was intensified with the progression of the death process. Addition of cycloheximide to the neurons 4 h after high [K+]o deprivation resulted in no cell loss and complete recovery of the damaged DNA. DNA margination and nuclear fragmentation as assessed by 4,6-diaminodiphenyl-2-phenylindole staining were observable in a few cells beginning approximately 4 h after the removal of high [K+]o and developed to nuclear condensation 4 h later. Six hours after high [K+]o deprivation, the DNA was fragmented into oligonucleosome-sized fragments. Within 6 h after removal of the extracellular K+, 50% of the neurons were committed to die and lost their ability to be rescued by readministration of 25 mM [K+]o. Similar to high [K+]o deprivation, inhibition of RNA or protein synthesis failed to halt neuronal degeneration of a similar percentage of cells 6 h after the onset of the death process. Mitochondrial function steadily decreased after [K+]o removal. An approximately 40% decrease in RNA and protein synthesis was detected by 6 h of [K+]o removal during the period of cell death commitment; rates continued to decline gradually thereafter. The temporal characteristics of the DNA damage and recovery, DNA cleavage to oligonucleosome-sized fragments, and the reduction in mitochondrial activity-events that occurred within the critical time-may indicate that these processes have an important part in the mechanism that committed the neurons to die.

Adenosine Triphosphate↗

Two waves of cyclin B and proliferating cell nuclear antigen expression during dopamine-triggered neuronal apoptosis.

The neurotransmitter dopamine is capable of inducing apoptosis in postmitotic sympathetic neurons via its oxidative metabolites. To detect genes whose expression is transcriptionally regulated during the early stages of dopamine-triggered apoptosis, we applied the differential display method to cultured sympathetic neurons. One of the up-regulated genes was identified as cyclin B2, which exhibited two waves of induction and destruction, both at the mRNA and protein levels, resembling the sequential oscillations typical of two successive mitotic events in proliferating cells. The time window between the two waves was characterized by a change in expression of other cell-cycle stage-specific genes, and oscillations in proliferating cell nuclear antigen and alterations in cyclin A were observed. Cyclin D1 and cyclin-dependent kinases were undetected and no sign of active DNA synthesis could be observed, indicating that activation of cell-cycle components is incomplete. In comparison with a normal cell cycle, temporal expression profile of these mediators was unsynchronized. Whereas the first wave of cell-cycle changes occurred prior to the commitment of the cells to the death process and could be tolerated by the cells, the second wave of changes coincided with the death commitment point. Our findings indicate that inappropriate and incomplete activation of some cell cycle-related genes in postmitotic neurons occurs during dopamine-triggered neuronal apoptosis.

Animals↗

Stethoscopes and otoscopes--a potential vector of infection?

OBJECTIVES: We aimed to determine whether stethoscopes and otoscopes used in community paediatric clinics harboured pathogenic micro-organisms, and, if so, which measures could prevent this. METHODS: Fifty-five stethoscopes belonging to paediatric physicians working in 12 community clinics were sampled for bacterial cultures by two methods: (i) direct impression of the diaphragm and bell section of each stethoscope for 5 seconds onto blood agar plates and a mannitol-salt-agar plate; (ii) swabbing the entire surface of the diaphragm of the stethoscope with a sterile cotton-tipped applicator. Forty-two otoscopes from the same physicians were sampled by rubbing the handles of the otoscopes with cotton-tipped swabs. The plates were incubated at 37 degrees C for 48 hours and examined for colony growth at 24 and 48 hours of incubation. Culture results were recorded as mean numbers of colony-forming units (CFUs). Eight additional stethoscope diaphragms were chosen at random at the participating clinics and cultured as described above. They were then wiped with alcohol swabs (isopropyl alcohol 70%), allowed to air dry for approximately 10 minutes and cultured a second time. RESULTS: All the stethoscopes and 90% of the otoscope handles were colonized by microorganisms. Staphylococci were isolated from 85.4% of the stethoscopes and 83.3% of the otoscopes, with 54.5% and 45.2% respectively being S. Aureus. Methicillin-resistant S. aureus were found in four each of the stethoscopes (7.3%) and otoscopes (9.5%). Cleaning with alcohol reduced the colony count by an average of 96.3%. CONCLUSIONS: Fomites can harbour potentially pathogenic bacteria, and with the increasing trend for children with more complex medical problems to be managed in an ambulatory setting, often by physicians who also work in hospitals, there is a real risk of spreading potentially serious infections to such patients. Simple cleansing with alcohol effectively eliminates the bacterial contamination of the fomites, and should be encouraged.

Community Health Centers↗

Aesthetic results and patient satisfaction with immediate breast reconstruction using tissue expansion: a follow-up study.

Immediate breast reconstruction with the tissue expander is now established as an accepted procedure after mastectomy, and large series have been published concerning the technique and its complications. Unfortunately, only scarce information is available regarding the long-term aesthetic results and patient satisfaction achieved by immediate reconstruction using tissue expansion. In this study, we reviewed 52 patients who had undergone immediate breast reconstruction using the tissue expander with a follow-up of at least 1 year after completion of the reconstruction. We developed an objective assessment of patient satisfaction, aesthetic results, and the factors affecting them. The results show remarkable concordance of assessment by patient, surgeon, and independent observer: All gave good scores for aesthetic appearance (6.4 to 7.4 on a scale of 1 to 10). A total of 92.3 percent of patients rated their satisfaction as good to excellent. Symmetry was the main parameter influencing the patients' score, while the surgeon's score also was affected by the quality of the inframammary fold and capsular contracture. Breast size, chemotherapy, complications, time interval, and additional procedures had no relation to either scoring or patient satisfaction.

Breast Neoplasms↗

Fixed drug eruption of the penis due to hydroxyzine hydrochloride.

OBJECTIVE: To report four cases of fixed drug eruption induced by hydroxyzine hydrochloride (Otarex, Teva, Israel). CASE SUMMARY: Four children with restlessness who were treated with hydroxyzine hydrochloride developed fixed drug eruption of the penis. Drug discontinuation was followed by complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration inhibiting factor (MIF) assay with hydroxyzine hydrochloride was positive. DISCUSSION: The pathogenesis of fixed drug eruption and the role of macrophage MIF assay in diagnosis is discussed. CONCLUSIONS: A fixed drug eruption induced by hydroxyzine hydrochloride is possible, but is a rare phenomenon.

Animals↗

Urine samples from disposable diapers: an accurate method for urine cultures.

BACKGROUND: The method of collection of the urine sample is of paramount importance in making a diagnosis of urinary tract infection in infants and children. Squeezing urine out of disposable diapers can provide a urine sample that can be used to detect chemical abnormalities as well as a specimen suitable for microscopic examination. To date there have been no reported studies on the use of this technique for urine culture as compared with samples collected by suprapubic aspiration and catheterization. METHODS: Urine was obtained from 38 infants aged under 2 years who presented with fever with no obvious cause. All infants had urine collected either by catheterization or suprapubic aspiration and by extraction from a disposable diaper. The urine samples were cultured using standard bacteriologic techniques. RESULTS: Five infants had a urinary tract infection, as shown by a pure growth of more than 10(5) colonies/mL of a single species of bacterium. In all the cases the same result was obtained from both the diaper urine sample and the sample obtained by suprapubic aspiration or catheter. In 31 infants the urine samples collected by both techniques (diaper and catheter or suprapubic aspiration) were negative, and in only 2 infants did the diaper specimen yield a positive result, while the urine obtained by suprapubic aspiration or catheter was sterile. CONCLUSIONS: Urine obtained from a disposable diaper can provide a valid sample for diagnosing urinary tract infection. The technique is simple, and can be carried out readily in ambulatory settings with minimal equipment and expense.

Disposable Equipment↗

Striae in adolescents mistaken for physical abuse.

Physiological striae are common in adolescence, occurring in the lumbar and gluteal regions, the upper thighs, breast, lower abdomen, and back. The lesions may be mistaken for nonaccidental injury, that is, physical abuse. We present four cases of adolescents with lesions thought to be due to physical abuse. Three of these cases were revealed during a school screening program for scoliosis; of the 2600 adolescents screened, aged 12 to 16 years, 168 were found to have striae. One case was found by a family physician when a young boy presented with low back pain. Since striae may be mistakenly ascribed to physical abuse, it is important for family physicians, nurses, and pediatricians to be familiar with this benign condition.

Adolescent↗

[Immediate breast reconstruction with transverse abdominal myocutaneous flap].

Mastectomy in 16 consecutive patients with carcinoma of the breast was immediately followed by reconstruction with a transverse abdominal, myocutaneous flap. Surgery was performed simultaneously by a team of general surgeons and a team of plastic surgeons. The final cosmetic result was considered very good by most patients. Complications were only minor and were treated conservatively. We consider breast reconstruction by this method, after mastectomy for breast carcinoma, to be the method of choice.

Breast Neoplasms↗

Necrobiotic xanthogranuloma with paraproteinemia.

Necrobiotic xanthogranuloma (NXG) is a rare skin disease mimicking necrobiosis lipoidica diabeticorum clinically and histologically. However, its association with paraproteinemia, and the evolution of hematologic malignancies in some cases, established NXG as a separate clinicopathologic entity. A typical case with indolent course is described.

Aged↗

[Carcinoma of the appendix--rare but important].

Villous adenoma of the vermiform appendix is very rare; the treatment of choice is appendectomy. We report a 72-year-old woman with a villous adenoma and a single focus of invasive, colonic adenocarcinoma. This finding required changes in diagnostic procedures and treatment, and altered the prognosis. The purpose of this report is to increase awareness of this phenomenon and to indicate correct management.

Adenocarcinoma↗

Dopamine-induced programmed cell death in mouse thymocytes.

Exposure of mouse thymocytes to dopamine caused apoptosis (programmed cell death). This was manifested by cellular condensation and membrane damage shown by flow cytometry measurements and scanning electron microscopic study. Dopamine also affected thymocytic nuclei and their genomic DNA integrity. Most of the DNA molecules accumulated in a subdiploid peak in flow cytometry analysis, indicating DNA fragmentation to small particles. DNA analysis showed the typical pattern of 'DNA ladder' caused by internucleosomal DNA cleavage. X-ray microanalysis of the cellular elements of dopamine-treated cells showed elevation of sodium (Na), chloride (Cl) and calcium (Ca) peaks, accompanied by reduction in phosphate (P) concentrations. Comparison of the potassium (K) and P concentrations showed significant differences between the two major death processes: necrosis (induced by exposure to sodium azide (NaN3)) and apoptosis (induced by dopamine). High concentrations of K indicated cell viability while reductions in P and elevations in Ca levels were found to be typical of apoptotic cell death. The antioxidant dithiothreitol (DTT) suppressed dopamine-induced apoptosis in thymocytes, suggesting that its toxicity may be mediated via generation of reactive oxygen radicals. Our study suggests that under certain circumstances, dopamine and/or its metabolites, may induce a process of apoptotic cell death of the dopamine-producing cells in the substantia nigra. Increased accessibility of dopamine to the nigral cell nucleus or inability to scavenge excess free radicals generated from dopamine oxidation triggering programmed cell death, may cause the progressive nigral degeneration in Parkinson's disease.

Animals↗

Hepatitis E virus infection in hemophiliacs.

Israel is endemic for hepatitis E virus (HEV), the causative agent of enteric non-A, non-B hepatitis. Transmission is via the feco-oral route but the possibility of transmission through blood transfusion has been raised. This question was addressed by examining sera from 188 hemophilic patients in Israel, screening was performed with an enzyme immunoassay (EIA) for antibody against hepatitis E virus (anti-HEV) and confirmed with a neutralization test. Sixteen patients (9%) were seropositive for anti-HEV. A statistically significant difference was not found between the seroprevalence in this group and that of a healthy Israeli control population, matched for sex and age. The anti-HEV-seropositive hemophiliacs had the same seroprevalence of antibodies to hepatitis B and C virus and to HIV and the same number of cases with chronic hepatitis as among the anti-HEV-seronegative patients. The seroprevalence of antibodies to hepatitis A virus (anti-HAV) was, on the other hand, higher in the anti-HEV-seropositive group. This study indicates that HEV is not transmitted by cryoprecipitate or lyophilized factor concentrates. High prevalence of coinfection with hepatitis A supports our conclusion that HEV infection in Israeli hemophiliacs was due mainly to feco-oral transmission.

Adolescent↗