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Biomedical subjects

D Stein

Publications and source records attributed to D Stein.

At least 55 records · Page 3Linked to original sources
PubMed2000

Investigating the function of follicular subpopulations during Drosophila oogenesis through hormone-dependent enhancer-targeted cell ablation.

Although it is known that the establishment of polarity during Drosophila oogenesis is initiated by signalling from the oocyte to the overlying follicle cells, much less is understood about the role of specific follicular subpopulations. One powerful approach for addressing this question, toxigenic cell ablation of specific subpopulations, has not previously been applicable to studying follicular subpopulations because many of the genes and Gal4 enhancer trap insertions that are expressed in the ovary are also expressed at earlier times in development. To overcome this problem, we have utilized a fusion protein between Gal4 and the human estrogen receptor to achieve hormone-dependent, tissue-specific gene expression of UAS-linked transgenes in flies. We used this system to study the role of the polar subpopulations of follicle cells during oogenesis by expressing within them a modified form of diphtheria toxin that causes cell death. Our results confirmed previous functions ascribed to these cells, and also demonstrated a previously undescribed role for the border cells in facilitating the migration of the anterior Fasciclin III-expressing polar pair cells to the edge of the oocyte.

Animals↗
PubMed1999

Prognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma.

PURPOSE: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium (103Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma. METHODS AND MATERIALS: One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) >15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal <4 ng/ml). RESULTS: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14). CONCLUSION: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients.

Acid Phosphatase↗
PubMed1999

The site of general anesthesia and cytochrome P450 monooxygenases: occupation of the enzyme heme pocket by xenon and nitrous oxide.

In previous studies, cytochrome P450 monooxygenases were shown to be appropriately sensitive to structurally diverse compounds varying widely in anesthetic potencies and to increasing carbon-number series of straight chain primary and secondary alcohols and rigid cyclic alcohols. We now report that xenon and nitrous oxide, at one atmosphere, occupy the P450 heme cavity and competitively inhibit catalytic activity. The heme enzymes appear to be the most relevant model of the site of general anesthesia, thus far identified.

Anesthetics, General↗
PubMed1999

New directions in treatment research of anorexia and bulimia nervosa.

Although considerable progress has been made in the understanding and treatment of anorexia and bulimia nervosa, a substantial proportion of people with these disorders have a limited response to treatment. Treatment strategies used in eating disorders have tended to be adopted from therapies that were devised to treat other psychiatric illnesses. Recent studies suggest that eating disorders are independently transmitted familial liabilities with a unique pathophysiology. These new findings raise the possibility that an improved understanding of the pathogenesis of eating disorders will generate more specific and effective psychotherapies and pharmacologic interventions.

Anorexia Nervosa↗
PubMed1999

Familial aggregation of eating disorders: results from a controlled family study of bulimia nervosa.

OBJECTIVE: While familial aggregation of bulimia nervosa (BN) is known to occur, the extent to which aggregation of a broader spectrum of eating disorders (ED) occurs in the families of individuals with BN is less certain. METHOD: Direct interviews and blind best-estimate diagnostic procedures were used to assess lifetime histories of EDs among first-degree relatives (n = 177) of probands with BN (n = 47) and first-degree relatives (n = 190) of non-ED control probands (n = 44). RESULTS: Forty-three percent of sisters and 26% of mothers of BN probands had a lifetime ED diagnosis, with eating disorder not otherwise specified (ED-NOS) diagnoses being most common. These rates were significantly higher than among sisters (5%) and mothers (5%) of controls. Few male relatives of either cohort had an ED. CONCLUSIONS: Diagnostic assessment using contemporary family-epidemiology methodology revealed very strong familial aggregation of a broad spectrum of EDs among female relatives of women with BN.

Bulimia↗
PubMed1999

A trial of L-deprenyl for the treatment of neuroleptic-induced parkinsonism.

This study examined the potential of L-Deprenyl, a selective monoamine oxidase-B (MAO-B) inhibitor, for the treatment of neuroleptic-induced parkinsonism (NIP). Thirty-one consecutive schizophrenic or schizophreniform patients were treated with haloperidol in a flexible dose design. Nineteen of them developed NIP and were administered adjunctive L-Deprenyl 10 mg/d for six weeks in an open fixed-dose design. One patient had to be withdrawn from the study because of exacerbation of the NIP. Severity of NIP was mild to moderate throughout the whole study period in all other cases. Five patients were considered to require biperiden 2-4 mg/d in addition to L-Deprenyl after two weeks of treatment, although they did not differ from the other 13 patients in any of the variables studied. A significant improvement in NIP was found in both groups of patients, with no psychotic exacerbation or a change in the dosage of haloperidol. These findings suggest that selective MAO-B inhibitors may be effective in some patients with mild to moderate NIP.

Adult↗
PubMed1999

Panic disorder following torture by suffocation is associated with predominantly respiratory symptoms.

BACKGROUND: We previously reported that in panic disorder a history of near-suffocation is associated with predominantly respiratory panic attacks. It might be hypothesized that the near-suffocation experienced in certain kinds of torture is also associated with the development of predominantly respiratory panic attacks. METHODS: A sample of patients who had experienced torture (N = 14) was drawn from an Anxiety Disorders Clinic in South Africa. Subjects were questioned about symptoms of panic disorder, posttraumatic stress disorder and depression. RESULTS: Patients with a history of torture by suffocation were more likely than other patients to complain of predominantly respiratory symptoms during panic attacks. These patients also demonstrated higher levels of depressive symptoms. CONCLUSIONS: While various interpretations of the data can be made, it is possible that torture by suffocation is associated with a specific symptomatic profile. Were such an association to be replicated, this would perhaps support the suffocation alarm hypothesis of panic disorder and provide evidence that specific environmental factors play a role in the development of this alarm.

Adult↗
PubMed1999

Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.

Basic fibroblast growth factor (bFGF, FGF-2), a classical transforming factor, mitogen, and survival factor in multiple cell types, and has a paradoxic role in mammary epithelial cell transformation and proliferation. We have also demonstrated that recombinant FGF-2 uncharacteristically promotes cell death in MCF-7 human breast cancer cells. In this study, we investigated the effects of FGF-2 overexpression on survival in the same MCF-7 cells. In eight breast cancer cell lines and two nontransformed mammary epithelial cell lines, we demonstrated that high levels of Bcl-2 are only expressed in cells with undetectable levels of FGF-2 on western blot. In retrovirally transduced MCF-7 cells expressing both cytoplasm- and nucleus-localizing FGF-2 species and ones expressing only cytoplasm-localizing FGF-2 species, Bcl-2 levels were strongly decreased at both the mRNA and protein levels. Immunoprecipitation of Bax demonstrated a decreased association of Bax with Bcl-2 in these cells. Levels of Bax did not correlate with expression of FGF-2 in the 10 cell lines or in MCF-7 cells. The clonogenic potential of MCF-7 cells in tissue culture was decreased by the expression of FGF-2 and was additively suppressed by the chemotherapeutic agents etoposide and 5-fluorouracil in a dose and time dependent manner. MCF-7 cells overexpressing FGF-2 had a greater rate of programmed cell death at baseline and in response to etoposide and 5-fluorouracil in a TUNEL assay by immunofluorescent microphotography and by flow cytometric quantitation. The pro-apoptotic effect of FGF-2 overexpression on the chemosensitivity of these cells was confirmed by quantitative morphologic determination. These data demonstrate that the expression of FGF-2 downregulates Bcl-2 and promotes programmed cell death in MCF-7 human breast cancer cells.

Antimetabolites, Antineoplastic↗
PubMed1999

Unequal pronuclear size--a powerful predictor of embryonic chromosome anomalies.

PURPOSE: Our purpose was to evaluate whether pronuclei of unequal size, observed in 13.7% of zygotes evaluated after in vitro fertilization (IVF), are predictive of chromosome anomalies in the developing embryo. METHODS: Five ploidy of 38 embryos grown from zygotes with unequal-sized pronuclei was assessed by fluorescent in situ hybridization (FISH). Twenty-six embryos developed after intracytoplasmic injection of sperm (ICSI) and 12 embryos were derived from conventional IVF. RESULTS: Chromosome anomalies were documented in the ICSI and IVF groups in 88.5 and 50% of cases, respectively. CONCLUSIONS: We suggest that FISH should be employed to examine the ploidy of zygotes with unequal pronuclei, prior to embryo transfer.

Adult↗
PubMed1999

Autistic subjects with comorbid epilepsy: a possible association with viral infections.

This study evaluates the comorbidity of epilepsy as a variable supporting a viral hypothesis in Autism. Data covering a 30-year period (1960-1989), including general population live births, autistic births, and incidence of viral encephalitis and viral meningitis, were collected for Israel. 290 autistic births were evaluated. The annual birth pattern of subjects with comorbid epilepsy fit the seasonality of viral meningitis. These findings support the role of viral C.N.S. infections in the causality of this disorder.

Adolescent↗
PubMed1999

The safety and efficacy of granulocyte-macrophage colony-stimulating factor (Sargramostim) added to indinavir- or ritonavir-based antiretroviral therapy: a randomized double-blind, placebo-controlled trial.

Sargramostim is a yeast-derived, recombinant human granulocyte-macrophage colony-stimulating factor with therapeutic potential in human immunodeficiency virus (HIV) infection. Its safety and activity when used in combination with protease inhibitors were evaluated in a randomized, double-blind trial in which 20 HIV-infected subjects on stable antiretroviral regimens, including indinavir or ritonavir, received sargramostim or placebo 3 times a week for 8 weeks. Analysis of HIV virus load excluded any 0. 5 log10 increase due to sargramostim (95% confidence interval, -0.68 to 0.44). Sargramostim was well tolerated, and inflammatory cytokines and surrogate markers of disease progression, such as serum levels of interleukin-10 and soluble tumor necrosis factor receptors types Iota and IotaIota, remained stable in subjects receiving sargramostim. Sargramostim treatment was associated with a trend toward decreased HIV RNA (>0.5 log10) and increased CD4+ cell count (>30%). These results became statistically significant only when subjects with baseline virus loads within the limits of detection or baseline CD4 cell count >50 were analyzed. No difference in indinavir pharmacokinetics was observed before or after sargramostim therapy.

Adult↗
PubMed1999

Psychopathological characteristics of recovered bulimics who have a history of physical or sexual abuse.

We sought to clarify the influence of a history of sexual or physical abuse on a variety of psychopathologies in subjects with bulimia nervosa (BN). To avoid confounding effects, the presence of a history of sexual or physical abuse, lifetime axis I disorders, and personality disorders were assessed through direct structured interviews in 44 subjects recovered from BN for at least 1 year. Twenty abused subjects (45%) were significantly more likely than 24 subjects without abuse to have severe general psychopathology and eating disturbance. Compared with nonabused subjects, abused subjects showed a trend toward more frequent lifetime diagnoses of posttraumatic stress disorder and substance dependence. These results suggest that abusive experiences may be associated with some psychopathology of BN, particularly related to anxiety, substance abuse, and more severe core eating disorder pathology.

Adolescent↗
PubMed1999

High serum and cerebrospinal fluid Ca/Mg ratio in recently hospitalized acutely depressed patients.

Calcium (Ca) and magnesium (Mg) are involved in many processes related to depression. Evaluations of serum and plasma Ca and Mg levels in depressive disorders do not show consistent results. The few studies that examined their cerebrospinal fluid (CSF) levels tended to find no differences between depressed patients and controls. Because both hypercalcemia and hypomagnesemia are associated with depression, and as Mg may function as a Ca antagonist, it is suggested that the relationship between these cations could be different in depressed patients and controls. We examined CSF and serum Ca and Mg in acutely depressed patients diagnosed as having major depressive disorder or being in a depressive episode of bipolar disorder. Controls were subjects undergoing lumbar puncture as part of an evaluation for headache or suspected meningitis and found to demonstrate no physical or mental disorder. Serum and CSF Ca/Mg ratios were found to be elevated in the depressed patients compared with the controls. A retrospective analysis of previous trials assessing serum/plasma or CSF Ca and Mg does not seem to refute the findings of this study. We further discuss our findings in their relation to the acuteness of the depressive disorders.

Acute Disease↗
PubMed1999

Indinavir-induced nephropathy.

We report the case of a 38-year-old male who developed renal insufficiency while on the protease inhibitor, indinavir. This patient had an increase in serum creatinine over a period of approximately one year, along with persistently abnormal urinalysis. A renal biopsy was performed and showed marked tubular crystal deposition. The indinavir was discontinued, and after two months the patient's serum creatinine and urinalysis returned to normal. To our knowledge this is the second case of indinavir associated nephropathy.

Adult↗
PubMed1999

The subjective experience of problem irresolvability and suicidal behavior: dynamics and measurement.

This article presents the dynamics and measurement of a relatively unstudied concept in children's and adolescents' suicidal behavior: the subjective experience of problem irresolvability (SEPI). This concept relates to the youngsters' sense of lack of control due to being pressured to resolve irresolvable problems within the family circle. The first study describes the construction and factor analysis of the SEPI scale as well as its relationship to suicidal tendencies, perceived parental care, and self-esteem. The second study presents a repeated factor analysis and the association between the SEPI scale and suicidal tendencies, hopelessness, depression, anxiety, and commitment to parents. The results suggest that the scale has a 4-factor structure with sound psychometric properties that distinguish successfully between suicidal adolescents on the one hand, and psychiatric and normal adolescents on the other. The SEPI was also found to be associated with the various studied variables.

Adolescent↗
PubMed1999

Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced agranulocytosis in jewish Israeli schizophrenic patients.

The atypical antipsychotic agent clozapine is known to be effective in schizophrenic patients refractory to other medications; however, it induces agranulocytosis in approximately 1-2%. In Jews, this complication is associated with the haplotype HLA B38,DR4,DQ3. The aim of the present study was to determine which human leukocyte antigen (HLA) antigens are involved in clozapine-induced agranulocytosis. We performed HLA typing in 88 Jewish Israeli schizophrenic patients and in 127 ethnically matched healthy individuals. Thirty-eight patients responsive to standard antipsychotic medications were treated with haloperidol, and 50 refractory patients received clozapine. A trend was noted for elevated rates of HLA B38 among control individuals and clozapine-treated patients of Ashkenazi origin compared to individuals of non-Ashkenazi origin, but the findings failed to reach statistical significance. No association was found between HLA class I antigens and the response to haloperidol or clozapine. Neutropenia developed in two clozapine-treated patients and agranulocytosis in one. Two of these three patients were of Ashkenazi origin, and both demonstrated the HLA B38 phenotype. Although the findings did not reach a statistical significance because of the small number of patients, they may support an association between clozapine-induced neutropenia/agranulocytosis and Ashkenazi origin and the HLA B38 phenotype. The rate of agranulocytosis in our sample (2%) is similar to the usual cumulative risk of agranulocytosis but in contrast to its high frequency among Jewish American patients. One possible explanation for this difference is the high rate of Ashkenazi patients in the American sample and the preponderance of non-Ashkenazi patients in our population.

Adolescent↗