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Biomedical subjects

M Schiff

Publications and source records attributed to M Schiff.

At least 19 recordsLinked to original sources

P-element repressor autoregulation involves germ-line transcriptional repression and reduction of third intron splicing.

P cytotype is a regulatory state, characteristic of Drosophila P-strain females, in which P-element transposition is repressed. P cytotype is established maternally in the germ line but is also dependent on the presence of P elements in the zygote. One aspect of P cytotype involves transcriptional repression of the P-element promoter. Here, we show that transcriptional repression by P cytotype in the female germ line occurs by a general promoter-independent mechanism with heterologous promoters carried in P-element vectors. P-cytotype transcriptional repression results in low levels of pre-mRNA and a reduction in splicing of the P-element third intron (IVS3)-containing mRNA, thus causing an increase in the proportion of 66-kD repressor mRNA. Increased retention of IVS3 in P cytotype would result in an autoregulatory loop of 66-kD repressor production. This combination of germ-line transcriptional repression and splicing control provides a mechanism to maintain repression during the maternal inheritance of P cytotype. These findings suggest that transcriptional repression may play an additional role in the regulation of gene expression, namely allowing alteration of pre-mRNA splicing patterns.

Animals

Prostate-specific antigen obtained under optimal conditions determines extracapsular adenocarcinoma of the prostate.

OBJECTIVE: To assess the relationship of prostate-specific antigen (PSA) obtained under optimal conditions with the presence or absence of organ-confined prostate cancer following radical prostatectomy. PATIENTS AND METHODS: The medical records of 300 consecutive patients who underwent radical retropubic prostatectomy were retrospectively reviewed. Ninety-three patients were excluded who had a pre-operative PSA level potentially altered by various factors (prostate infection, manipulation or instrumentation). RESULTS: A pre-operative PSA value < 4 ng/mL accurately predicted pathologically confined disease in 42 of 51 patients (82%) which contrasted with extracapsular disease in 74 of 84 patients (88%) who had a PSA value > 10 ng/mL. One of the 53 patients with a PSA > 15 ng/mL had organ-confined disease at surgery. CONCLUSION: These data demonstrate that optimal serum PSA values correlate well with pathological stage.

Adenocarcinoma

A 12-year experience with enterovesical fistulas.

OBJECTIVES: To review our experience with enterovesical fistulas in order to determine the most accurate diagnostic studies and most effective method of treatment. METHODS: A retrospective record review of 76 patients who were diagnosed and treated for enterovesical fistulas over a 12-year period was performed. Data collection focused on presenting symptoms, urinary disease process, diagnostic studies, and methods of management. RESULTS: Diverticular disease was the primary etiologic factor in the majority of patients (59%), with colonic malignancy, granulomatous bowel disease, and radiation therapy accounting for the majority of the remainder. Cystoscopy (60%) and cystography (44%) were the most sensitive diagnostic studies. There was no statistical difference in the complication rate between groups treated with single or multistage repair. CONCLUSIONS: One-stage repair of enterovesical fistulas can be safely performed when the cause is diverticular or granulomatous bowel disease. Staged repairs may be more judicious in patients with large intervening pelvic abscesses or those in whom advanced malignancy or radiation changes are present.

Adult

Pneumocystis carinii pleural effusion. Pathogenesis and pleural fluid analysis.

We present three new cases of Pneumocystis carinii in pleural effusions of patients with AIDS, bringing the total number of reported cases to six. In our patients, diagnosis was made by visualization of Pneumocystis in pleural fluid stained with Gomori methenamine silver. LDH was greater than 400, and pleural fluid to serum LDH ratio was greater than 1.0 in all cases at time of presentation. All six reported patients have been associated with aerosolized pentamidine, and five of the six had documented underlying Pneumocystis pneumonia. The sixth patient, which we report, presented with primary pleural infection with Pneumocystis. Although we could not document underlying pneumonia, we suspect it was present. Pneumocystis pleural disease appears to be an anatomic extension of smoldering subpleural Pneumocystis pneumonia, and prognosis is not worse than with pneumonia alone.

AIDS-Related Opportunistic Infections

Juvenile nasopharyngeal angiofibroma contain an angiogenic growth factor: basic FGF.

The presence of an angiogenic protein basic fibroblast growth factor (FGF) was established in juvenile nasopharyngeal angiofibroma (JNF). Extracts of these tumors have the capacity to stimulate endothelial cell proliferation. This activity is indistinguishable from basic FGF. The biological activity contained in the extracts binds to heparin-Sepharose columns and is eluted with a characteristic 2 mol sodium chloride. The exact fraction of the biological activity corresponds to the location where an immunoreactive basic FGF can be detected by radioimmunoassay. These same fractions contain an 18,000-d molecule which is identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with an antibody to basic FGF. Indeed, immunohistochemical studies localize the growth factor to the endothelium of JNF. Although these findings do not establish that basic FGF mediates the development of this angiofibroma, they do support the possibility that the pathogenesis of JNF is associated with the presence of angiogenic factors like basic FGF. If this is the case, a comprehensive study of the etiology of JNF may lead to a better understanding of how locally produced growth factors mediate proliferative disease and how its modification might lead to better treatment on a biological basis.

Adolescent

Vaginal ultrasonographic assessment of cervical length changes during normal pregnancy.

We measured the cervical length of 166 normal, gravid patients between 8 and 37 weeks' gestation by vaginal ultrasonography. Patients were assigned to one of five groups according to gestational age at the time of the measurements. Cervical length was longest (48 mm) in group 3 (20 to 25 weeks) and significantly longer than that of groups 1 (8 to 13 weeks), 2 (14 to 19 weeks), and 5 (32 to 37 weeks). The use of vaginal ultrasonography to assess cervical length eliminates some technical problems encountered with abdominal ultrasonography. Nomogram of cervical length throughout pregnancy was established. This may aid in early diagnosis and management of preterm labor and cervical incompetence.

Cervix Uteri

Self-esteem in abused chemically dependent adolescents.

In a random sample of 500 admissions to a residential treatment center for chemically dependent adolescents. 150 cases of physical and sexual abuse had been identified. These adolescents were matched for age, race, and socioeconomic status, with two comparison groups: a group of nonabused chemically dependent adolescents and a group of nonabused, nonchemically dependent adolescents. Self-esteem was measured, utilizing the Tennessee Self-Concept Scale (TSCS), which was administered to all subjects. The abused, chemically dependent adolescents were found to demonstrate significantly lower self-esteem on all subscales when analyzed against these two comparison groups. There were negligible differences within the abused group when the TSCS scores were analyzed according to type of abuse. Aggressive/physically abused adolescents scored higher on the Physical Self subscale and the incest group scored significantly lower on the Identity subscales. These results suggest that abuse is equally devastating, regardless of the type of abuse, e.g., physical, sexual, incest, and has a long-lasting impact on self-esteem.

Adolescent

Genetic analysis of the imperfect association of H-2 haplotype with lupus-like autoimmune disease.

Unlike parental New Zealand Black (NZB) or New Zealand White (NZW) mice, (NZB x NZW)F1 mice exhibit a lupus-like disease characterized by high serum levels of IgG anti-nuclear antibodies and a fatal immune complex glomerulonephritis. Previous results from studying [(NZB x NZW)F1 x NZB] backcross mice indicated that the NZW major histocompatibility complex (MHC) or gene(s) closely linked to this locus provides the major dominant NZW genetic contribution to the F1 disease. A surprising feature of the results was the 12% frequency of discordance between the autoimmune phenotype and the presence of the NZW H-2z haplotype. In the current study, we attempted to precisely define the position of the NZW gene(s) required for lupus-like renal disease by mapping genes in individual backcross mice that are both centromeric and telomeric to the MHC and then correlating genotypes for each locus with disease. The data indicate that an adjacent NZW locus does not provide a more accurate correlation with the autoimmune phenotype compared with MHC genes themselves. Thus, the imperfect association of MHC haplotype with disease in this murine model is not explained by genetic recombination with linked genes. These data may provide insight into the mechanisms by which MHC antigens increase the probability of developing autoimmune disease and may help explain the difficulty of defining MHC relationships in human systemic lupus erythematosus.

Alleles

Acquired immunodeficiency syndrome, a complication of cardiothoracic surgery.

We identified 13 patients who contracted acquired immunodeficiency syndrome or human immunodeficiency virus-related disease after a cardiothoracic operation. The operations were performed between January 1981 and November 1984, and the diagnosis of human immunodeficiency virus-related disease was established from 26 to 54 months after operation. The survival time from diagnosis ranged from 8 days to 14 months in the 10 patients who have died. A clinical illness developed in three of the patients immediately postoperatively that was consistent with primary human immunodeficiency virus mononucleosis. The clinical features included a wide variety of opportunistic infections, but an abnormally high percentage of the patients first showed symptoms of dementia or neoplastic disease. In many patients, the diagnosis was not suspected for a prolonged period of time. On the basis of the prolonged incubation period, the incidence of this disease is likely to increase for several more years.

Acquired Immunodeficiency Syndrome

Behavioral sequelae of physical and/or sexual abuse in adolescents.

In a survey of 500 admissions to a short-term residential chemical dependency treatment center for adolescents (ages 12 to 18), 150 adolescents (30%) had been identified as victims of physical and/or sexual abuse. While the abused group had a higher incidence of prior social service and mental health intervention, extraordinarily 68% of these abuse cases had not been reported by children, family, or interviewers prior to the adolescents having entered the chemical dependency residential treatment facility. This chemically dependent, previously abused group was differentiated from a comparison group of nonabused, chemically dependent adolescents, and a second comparison group of nonabused, nonchemically dependent adolescents. Results indicated a higher incidence of acting out behavior, runaways, legal involvement and sexual promiscuity within the abused group.

Adaptation, Psychological

Injection of low-dose antigen attenuates the response to subsequent bronchoprovocative challenge.

Injection of low-dose antigen on a co-seasonal basis has been proposed as an alternative to conventional immunotherapy in allergic disorders. Few studies of efficacy have been attempted, and available data do not support the use of this technique. We evaluated the effect of low-dose antigen injection in 21 subjects with histories of asthma, after exposure to animal antigen. Each subject was injected with low-dose animal antigen, as determined by skin test end point titration, or with placebo. Twenty minutes after the injection, bronchoprovocative challenge was performed with the use of the same antigen. The provocative dose 20% (PD20), FEV1 after antigen injection, was 28.52 +/- 1.74, was compared to 6.50 +/- 1.15 after placebo injection (p less than 0.01). This experiment was repeated after pretreatment of patients with indomethacin. The protective effect of antigen injection was abolished. In a third experiment, the PD20, FEV1 for methacholine, was 10.74 breath units (BU) after antigen injection and 6.84 BU after placebo injection (PD less than 0.05). Low-dose antigen injection causes rapid reduction of bronchial sensitivity to inhaled antigen and methacholine. This effect is abolished by treatment with indomethacin.

Adult

Vascular complications in renal allografts: detection with duplex Doppler US.

Renal allografts are subject to many vascular complications. Over a 2-year period, 334 duplex Doppler ultrasonographic (US) examinations were performed in 88 renal allograft recipients. Vascular occlusion on the basis of severe vascular rejection was documented in ten patients (11.4%) for a sensitivity and specificity of 100%. Seven patients, for whom there was clinical and Doppler US evidence for renal artery stenosis, underwent angiography. A significant stenosis was confirmed and treated by angioplasty in four patients; one had an insignificant stenosis in an accessory artery, one had kinking of the renal vessels, and another had normal findings. The most reliable criteria for stenosis were a high-velocity jet exceeding 7.5 kHz and distal turbulence. One arteriovenous fistula was diagnosed by the presence of an intrarenal high-velocity jet. Duplex Doppler US is a useful, noninvasive, and portable initial procedure with which to screen patients for vascular complications of renal transplantation.

Adult

Left ventricular diastolic function in weight lifters.

Concentric left ventricular (LV) hypertrophy and asymmetric septal hypertrophy have both been described in weight lifters, but diastolic filling, which is abnormal in pathologically hypertrophied ventricles, has not been investigated in such subjects. Accordingly, pulsed Doppler examination of LV inflow, M-mode and 2-dimensional echocardiography were performed in 16 competitive weight lifters and 10 age-matched male control subjects. Peak and mean filling rates were determined in milliliters per second as the product of the cross-sectional area of the mitral anulus and the Doppler-derived peak early and mean transmitral inflow velocities, respectively. Rapid filling index was defined as peak filling rate divided by mean filling rate. Flow velocity integrals of the early and atrial diastolic filling phases were also measured. LV end-diastolic volume and ejection fraction were measured using 2-dimensional echocardiography. Weight lifters had significantly higher LV end-diastolic volume (181 +/- 50 vs 136 +/- 40 ml, p less than 0.05) and dimension (5.6 +/- 0.6 vs 5.1 +/- 0.5 cm, p less than 0.05), and posterior wall thickness (0.9 +/- 0.2 vs 0.8 +/- 0.1, p less than 0.05); however, after correction for body surface area there was no significant difference in these values. Weight lifters had significantly higher LV mass (241 +/- 70 vs 165 +/- 29, p less than 0.02) and LV mass index (114 +/- 29 vs 87 +/- 15 g/m2, p less than 0.05). There was no significant difference between the weight lifters and control subjects in rapid filling index, early to late integral ratio or ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Renal adenocarcinoma in young adults.

Survival following the diagnosis of renal adenocarcinoma in a group of young adults, twenty to forty years of age, was distinctly better than that found in adults over age forty. This disparity could not be accounted for by a larger proportion of younger patients with early stage disease, nor by a greater percentage of non-cancer deaths in the older group. Perhaps a more favorable host-tumor immunologic balance is present in younger individuals.

Adult

Opioid and neurotransmitter regulation of pituitary gonadotropin-releasing hormone (GnRH) receptors in the ovariectomized estradiol-treated rat: role of altered GnRH secretion.

An acute transient fall in the number of pituitary GnRH receptors (GnRH-R) is observed before the preovulatory gonadotropin surge in cycling rats and before the afternoon daily gonadotropin surge in ovariectomized estradiol-treated rats. In the latter model, this fall can be reproduced by administration of the opioid antagonist naloxone, whereas the opioid agonist morphine acutely increases GnRH-R. In this study we investigated the mechanisms of this opioid effect and examined the effects of other neurotransmitter substances on modulation of pituitary GnRH-R. Administration of the dopaminergic agonists bromocriptine and L-dopa or the alpha-adrenergic receptor blocker phenoxybenzamine elevated GnRH-R acutely from average basal values of 240 +/- 22 and 254 +/- 21 fmol/mg protein to maximal values of 374 +/- 49, 441 +/- 67 and 461 +/- 75 fmol/mg, respectively, whereas the alpha-adrenergic agonist clonidine transiently decreased GnRH-R to 186 +/- 19 fmol/mg. Placement of radiofrequency lesions in the mediobasal hypothalamus or pretreatment with anti-GnRH serum completely abolished the ability of both morphine and naloxone to modulate the number of GnRH-R. These data indicate that the opioid-induced modulation of pituitary GnRH-R requires an intact hypothalamus and that both dopaminergic and alpha-adrenergic neurotransmitter systems may be involved. The final step of this action probably involves acute modulation of GnRH secretion (altered frequency and/or amplitude), which results in acute transient changes in the number of pituitary GnRH-R.

Animals