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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 253 records · Page 14Linked to original sources
PubMed1997

Parental mosaicism and autosomal dominant mutations causing structural abnormalities of collagen I are frequent in families with osteogenesis imperfecta type III/IV.

Protein-chemical and molecular studies were conducted on all osteogenesis imperfecta (OI) type III/IV patients referred to our hospital during the last 15 y. Of a total of 16 OI type III/IV patients studied, 15 patients were heterozygous for a mutation in one of the two genes coding for collagen I, COL1A1 or COL1A2. Cultured fibroblasts from these 15 patients produced both normal and abnormal collagen I molecules, pointing to a dominant-negative effect of the mutation. Nine mutations had not been described previously. Parental mosaicism was demonstrated in three families. In the 16th child the causative mutation was not found. In conclusion, OI type III/IV in most patients of Western European ancestry is caused by dominant mutations in the genes for collagen I, and recurrence of OI is caused in most cases by parental gonadal mosaicism.

Adolescent↗
PubMed1997

Bicalutamide for advanced prostate cancer: the natural versus treated history of disease.

PURPOSE: To determine the therapeutic effects of bicalutamide 200 mg in patients with prostate cancers of different hormone sensitivities. METHODS: Patients with progressive prostate cancer were treated with bicalutamide 200 mg daily. Before treatment, patients' tumors were classified on the basis of prior hormone exposure and by serum testosterone levels into androgen-dependent and androgen-independent groups. Prior exposure to flutamide and response to flutamide withdrawal was also considered. Outcomes were reported independently on the basis of posttherapy changes in prostate-specific antigen (PSA), measurable disease, and radionuclide bone scans. RESULTS: Outcomes varied by prior hormone exposure as a higher proportion of patients with progression of androgen-dependent tumors showed posttherapy PSA decreases of more than 50% or more than 80%, measurable disease regression, and improvement on radionuclide bone scans than did patients with androgen-independent progression. Within the category of androgen-independent progression, clinical benefit was observed in patients who had previously progressed on flutamide, independent of the response to flutamide withdrawal. Patients who had progressed on a gonadotropin-releasing hormone (GnRH) analog alone had a low response proportion, whereas those who progressed after two or more hormone therapies did not respond. Overall, the drug was well tolerated. After progression on bicalutamide monotherapy, one third of patients with androgen-dependent progression responded to medical castration with a GnRH analog. CONCLUSION: Classifying patient tumors on the basis of prior hormone exposure permits a more precise estimate of the potential benefit of a specific hormone therapy for the individual patient. The precision is further increased by reporting the effects of a drug on each parameter of disease independently. The difference in outcomes for patients with androgen-independent progression suggests that the specific hormone therapy administered and the response to that therapy can influence the biology of the relapsing tumor and the sensitivity to subsequent therapies. The sensitivity to bicalutamide after progression on flutamide deserves further study.

Aged↗
PubMed1997

Effect of melittin on the apical membrane Na+ and Cl- conductances of frog cornea epithelium.

The transepithelial conductance increased with 10(-6) M melittin on the tear side of the frog cornea. This effect was attributed to the opening of an apical membrane Na+ conductance. However, the potency of the venom at this concentration (apical membrane fractional resistance (fRo) decreased to near zero) masked this and other effects. With 3 x 10(-7) M on the tear side, the effects were finite (fRo > 0) and reversible. With fRo > 0, the effects of melittin could be readily studied on the transport parameters of Na+, Cl-, and K+. Epithelial cells of intact bullfrog corneas were impaled with microelectrodes using an in vitro preparation. Under short-circuit current (Isc) conditions, 20 min after melittin Isc increased by 3.1 from 8.2 microA/cm2., fRo decreased by 18 from 51%; the intracellular potential, Vo, depolarized by 19.4 from -56.5 mV; and the transepithelial conductance, gv increased by 0.57 from 0.29 mS/cm2. Tenfold decreases in tear Na+ or Cl- concentrations changed the transport parameters consistent with the formation of a Na+ conductance and an increase in the apical membrane Cl- conductance by the venom. These conclusions were further supported by the minimal effect of melittin in Cl(-)-fre and, particularly, in Na(+)-free solutions. Changes in K+ concentration had no effect on transport parameters. These findings indicate that the effect of melittin at this low concentration is upon a Na+ channel protein and not due to nonspecific conductances.

Animals↗
PubMed1997

Atrial diagnostics in a tiered therapy implantable defibrillator.

Dual chamber sensing has been proposed in implantable defibrillators as an additional diagnostic modality for enhanced differentiation of ventricular and supraventricular tachycardias. A patient with different rates of wide QRS complex tachycardias is described in whom a tiered therapy implantable defibrillator with atrial sensing capability was implanted. Atrial diagnostic data in this patient enabled definitive diagnosis of his ventricular tachycardias and guided management decisions of his arrhythmia.

Defibrillators, Implantable↗
PubMed1997

Intra-abdominal lymphangiomas in children and adults. Assessment of proliferative activity.

OBJECTIVE: Intra-abdominal lymphangiomas are rare in children and even more exceptional in adults. Because these lesions occasionally progressively enlarge, we analyzed seven adult and four pediatric cases for evidence of proliferative activity. DESIGN: Immunohistochemical analysis was performed retrospectively on representative tissue sections using antibodies to the following antigens: Ki-67, proliferating cell nuclear antigen, and p53 gene product (eight cases). DNA ploidy was examined in five cases. PATIENTS: The study group consisted of seven adult women (aged 24 to 73 years), a 3.5-year-old girl, and two boys, aged 3.5 and 9 years, the last with a recurrence at age 15. The lymphangiomas ranged from 1.7 to 23 cm in maximum size. RESULTS: Ranges of percentages of cells staining for proliferating cell nuclear antigen, Ki-67, and p53 were similar between the pediatric and adult cases. Antibody to Ki-67 stained from 0.5% to 17% of the stromal and endothelial components of the lymphangiomas. Proliferating cell nuclear antigen activity was noted in 16% to 52% of lesional cells. Reactivity was noted almost exclusively in areas of inflammation and fibroplasia. For comparison, 10% to 50% of intermixed lymphocytes stained for Ki-67 and proliferating cell nuclear antigen. There was no labeling with p53. DNA content was uniformly diploid. CONCLUSIONS: The scant staining for Ki-67 in the majority of the lesions, combined with proliferative rates that were only focally elevated, suggests that lymphangiomas in children and adults are quiescent lesions whose enlargement is due to engorgement by chyle and localized secondary inflammation rather than primary tumoral growth.

Abdominal Neoplasms↗
PubMed1997

Dating aggression among high school students.

Links were examined among physical aggression toward a dating partner, parental aggression, and justification of physical aggression during an argument in a sample of 228 (122 male and 106 female) high school students. Forty-four percent of females and 16% of males reported engaging in at least one physically aggressive behavior toward a dating partner during a disagreement, with the modal form of aggression being push, grab or shove for both males and females. The probability that a male, but not a female, would aggress was significantly predicted by parental aggression and justification of aggression. Among aggressive students, the extent of males' aggression was strongly predicted by their justification of aggression; the extent of females' aggression was not predictable. Implications for prevention and intervention programs are discussed.

Adolescent↗
PubMed1996

Hyperoxia activates NF-kappaB and increases TNF-alpha and IFN-gamma gene expression in mouse pulmonary lymphocytes.

Hyperoxia-associated production of reactive oxygen species leads to neutrophil infiltration into the lungs and increased pulmonary proinflammatory cytokine expression. However, the initial events induced by hyperoxia, and leading to acute inflammatory lung injury, remain incompletely characterized. To explore this issue, we examined nuclear transcriptional regulatory factor (NF-kappaB and NF-IL-6) activation and cytokine expression in the lungs following 12 to 48 h of hyperoxia exposure. No increases in cytokine (IL-1beta, IL-6, IL-10, TGF-beta, TNF-alpha, IFN-gamma) expression nor in NF-kappaB activation were found after 12 h of hyperoxia. Following 24 h of hyperoxia, NF-kappaB activation and increased levels of TNF-alpha mRNA were present in pulmonary lymphocytes. By 48 h of hyperoxia, amounts of IFN-gamma and TNF-alpha protein as well as mRNA were increased in the lungs, and NF-kappaB continued to show activation, even though no histologic abnormalities were present. These results show that hyperoxia activates NF-kappaB in the lungs before any increase in proinflammatory cytokine protein occurs, and suggest that NF-kappaB activation may represent an initial event in the proinflammatory sequence induced by hyperoxia.

Animals↗
PubMed1996

[A follow-up study of carriers of cystic fibrosis].

The aim of the present study was to assess the long-term impact of carrier screening for cystic fibrosis. The impact of being identified as a carrier for cystic fibrosis was assessed through three questionnaires measuring the emotional responses, changes in reproductive attitudes and decisions, retention of the result, and sharing of the information about the result with relatives. The questionnaires were sent to 160 women identified as carriers between 1990 and 1992 and to 200 randomly selected women with a negative result. Carriers became surprised, anxious and worried upon receipt of their result. However, this response disappeared once the partners had been tested and found negative. No sign of residual anxiety was found among carriers who answered the third questionnaire in November 1994. Carriers freely shared the information about their result with relatives, friends, and general practitioners. Few carriers changed their reproductive plans or attitudes to abortion of a foetus with CF due to the result. No decline in fertility or change in reproductive pattern were observed among carriers after testing. The imperfect sensitivity of the carrier test caused some misunderstanding in the retention of the result. This may reflect inadequacies in the information and counselling. Psychological factors are also believed to contribute to the misunderstanding of the result. The information should be improved to avoid false reassurance.

Carrier State↗
PubMed1996

Involvement of wound-associated factors in rat brain astrocyte migratory response to axonal injury: in vitro simulation.

The poor ability of mammalian central nervous system (CNS) axons to regenerate has been attributed, in part, to astrocyte behavior after axonal injury. This behavior is manifested by the limited ability of astrocytes to migrate and thus repopulate the injury site. Here, the migratory behavior of astrocytes in response to injury of CNS axons in vivo was simulated in vitro using a scratch-wounded astrocytic monolayer and soluble substances derived from injured rat optic nerves. The soluble substances, applied to the scratch-wounded astrocytes, blocked their migration whereas some known wound-associated factors such as transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and heparin-binding epidermal growth factor in combination with insulin-like growth factor-1 (HB-EGF + IGF-1) stimulated intensive migration with consequent closure of the wound. Migration was not dominated by proliferating cells. Both bFGF and HB-EGF + IGF-1, but not TGF-beta 1, could overcome the blocking effect of the optic nerve-derived substances on astrocyte migration. The induced migration appeared to involve proteoglycans. It is suggestive that appropriate choice of growth factors at the appropriate postinjury period may compensate for the endogenous deficiency in glial supportive factors and/or presence of glial inhibitory factors in the CNS.

Animals↗
PubMed1996

First-trimester prenatal diagnosis of Crouzon syndrome.

Crouzon syndrome, one of the best known of many craniofacial syndromes, is an autosomal dominant disorder characterized by craniosynostosis, prominent eyes, and midfacial hypoplasia due to abnormal development and premature fusion of the skull. Recently mutations in the fibroblast growth factor receptor 2 gene (FGFR2) were found to cause Crouzon. We have identified the recurrent mutation C342Y in two unrelated patients with Crouzon syndrome. One patient (A) belongs to a family in which Crouzon could be followed in three generations, while the other patient (B) represents a sporadic case. The identification of the disease-causing mutation allowed first-trimester prenatal diagnosis as requested by both patients in their subsequent pregnancies. A chorionic villus biopsy was performed in the 11th gestational week of patient A's pregnancy. DNA isolated from the biopsy revealed a fetus heterozygous for the C342Y mutation, i.e., having Crouzon syndrome. The pregnancy was terminated and the molecular diagnosis was confirmed later by analysis of fetal and placental tissue. Patient B had a missed abortion before the scheduled chorionic villus biopsy was performed. Mutation analysis of the aborted fetal tissue did not show the C342Y mutation.

Base Sequence↗
PubMed1996

Genetic counselling and prenatal diagnosis of osteogenesis imperfecta caused by paternal mosaicism.

In a family with recurrent osteogenesis imperfecta (OI) caused by paternal mosaicism, prenatal diagnosis was made using restriction enzyme analysis for a mutation in COL1A2. Parental mosaicism is important to consider in genetic counselling for OI. Prenatal diagnosis of OI is available currently by means of collagen or gene analyses in the first trimester or by ultrasonography in the second trimester.

Chorionic Villi Sampling↗
PubMed1996

Guidelines for the retention, storage, and use of residual dried blood spot samples after newborn screening analysis: statement of the Council of Regional Networks for Genetic Services.

These guidelines provide scientific information for policy development by state health departments considering appropriate use of newborn screening specimens after screening tests are finished. Information was collected, debated, and formulated into a policy statement by the Newborn Screening Committee of the Council of Regional Networks for Genetic Services (CORN), a federally funded national consortium of representatives from 10 regional genetics networks. Newborn screening programs vary widely in approaches and policies concerning residual dried blood spot samples (DBS) collected for newborn screening. Recognition of the epidemiological utility of DBS samples for HIV seroprevalence surveys and a growing interest in DBSs for DNA analysis has intensified consideration of issues regarding retention, storage, and use of residual DBS samples. Potentially these samples provide a genetic material "bank" for all newborns nationwide. Their values as a resource for other uses has already been recognized by scientists, administrators, and judicial officials. Programs should promulgate rules for retention and use of residual newborn screening DBS samples based on scientifically valid information. Banking of newborn samples as sources of genetic material should be considered in light of potential benefit or harm to society.

Blood Specimen Collection↗
PubMed1996

A novel tumor-derived mediator that sensitizes cytokine-resistant tumors to tumor necrosis factor.

Therapeutic successes following treatment of murine tumors with tumor necrosis factor-alpha (TNF) have not been easily applied to clinical oncology because the concentrations of TNF required in humans induces systemic toxicity. This has led us to identify mediators which could sensitize tumors to the effects of TNF, permitting administration of lower doses and possible realization of the therapeutic potential of this cytokine. Our study reports the ability of a novel cytokine, endothelial-monocyte-activating polypeptide II (EMAP II), to sensitize initially resistant murine and human tumors to TNF-induced regression employing a murine model. Recombinant (r) EMAP II was purified from Escherichia coli transformed with a plasmid expressing mature EMAP II. The B16 melanoma, raised in C57BL/6 mice, or a human fibrosarcoma (HT-1080), grown in immunocompromised mice, was injected intratumorally with either vehicle or rEMAP II/heat-treated EMAP II (50-100 micrograms) followed by systemic TNF/heat-treated TNF (5 micrograms) and assessed for tumor volume, hemorrhage, and histologic appearance. Both the B16 melanoma and the HT-1080 human fibrosarcoma underwent thrombohemorrhagic and acute inflammatory changes concomitant with regression or significantly slowed growth after administration of intratumor EMAP II followed by systemic TNF. Omission or inactivation of either cytokine abrogated this effect. These results demonstrate that local treatment of certain tumors with EMAP II results in enhanced susceptibility to TNF-mediated induction of thrombohemorrhage and regression.

Animals↗
PubMed1996

Deletion of a Gly-Pro-Pro repeat in the pro alpha2(I) chain of procollagen I in a family with dominant osteogenesis imperfecta type IV.

We have investigated one member of a family with dominant osteogenesis imperfecta type IV through three generations. In protein-chemical studies of cultured fibroblasts derived from the proband, collagen I was overmodified, with normal processing of procollagen I, normal thermal stability, and a cyanogen bromide peptide map that suggested a C-terminal location of the structural abnormality in the collagen triple helix. Sequencing of the gene encoding the alpha2(I) chain of collagen I (COL1A2) indicated a nine base-pair deletion of nucleotides 3418-3426. When a polymerase chain reaction product containing the nucleotides in question was electrophoresed in a 12% polyacrylamide gel, two bands with a difference in size of nine base pairs could be shown. Sequencing of the molecular weight band confirmed the deletion of the nine base pairs involving codons 1003-1006 of COL1A2. The deletion introduced a SfiI restriction site that was used for confirmation of the deletion in genomic DNA from the proband. The deletion resulted in the removal of three amino acids (Gly-Pro-Pro), but this did not disrupt the Gly-X-Y sequence of the collagen triple helix, as is often the case in the more common glycine substitutions. We discuss the ways in which this deletion could result in osteogenesis imperfecta.

Adult↗
PubMed1996

Patient characteristics, safety, and benefits of same-day admission for coronary artery bypass grafting.

BACKGROUND: The move toward outpatient and same-day surgery has been phenomenal in the past several years. Efforts in this area have focused on limiting inpatient hospitalization, reducing ancillary services, and decreasing length of stay. METHODS: Two hundred seventy-six DRG 107 patients who were operated on at our institutions in 1994 and registered in The Society of Thoracic Surgeons National Cardiac Surgery Database were reviewed. There were 185 patients randomly admitted to the hospital on the day of operation and 91 patients admitted 1.78 +/- 1.94 days before. These patients were analyzed according to The Society of Thoracic Surgeons National Cardiac Surgery Database predicted risk group and expected operative mortality modules. Univariate analysis of all risk variables listed in The Society of Thoracic Surgeons National Cardiac Surgery Database were used to identify the difference between 176 elective procedure patients in the same-day admission group and 67 elective procedure patients in the non-same-day admission group. RESULTS: The same-day admission group had lower expected operative mortality (1.3% versus 2.9%), fewer female patients (17% versus 29%), younger age (62 versus 67 years), and fewer patients in the higher predicted risk group. Univariate analysis showed only age and ejection fraction variables were significantly different between the two elective groups. Comorbidities predictive of elective non-same-day admission revealed that age and New York Heart Association class IV were significant predictors. The length of stay was shorter and the total charges were less in the same-day admission group. CONCLUSIONS: There was no increase in preoperative, intraoperative, or postoperative complications in the same-day admission patients. Same-day admission was safe and cost-effective and could be carried out as a routine admission for several selected groups of patients.

Aged↗