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S Schwartz

Publications and source records attributed to S Schwartz.

At least 127 records · Page 7Linked to original sources
PubMed1999

Molecular cytogenetics of a de novo interstitial deletion of chromosome arm 6q in a developmentally normal girl.

Using fluorescence in situ hybridization and microsatellite analysis, we have characterized a de novo interstitial deletion on the long arm of chromosome 6 [46,XX,del(6) (q23.3q24.2)] in a developmentally normal girl with very mild phenotypic abnormalities. The deletion was paternal in origin and was between markers WI-5023 and D6S1042. The size of the deletion was estimated to be approximately 4-5 Mb. The normal phenotype in this patient might be the result of imprinting of paternal copies of genes located in the segment 6q23. 3-q24.2. Alternatively, the genes located in the segment 6q23.3-q24. 2 might not be subject to dosage effects and therefore the haploinsufficiency of genes in this segment might not have phenotypic consequences.

Child, Preschool↗
PubMed1999

Molecular cytogenetic studies of a serially transplanted primary prostatic carcinoma xenograft (CWR22) and four relapsed tumors.

BACKGROUND: Established cell lines or xenografts from prostatic carcinoma have been infrequently studied cytogenetically. CWR22 and CWR22-R are xenografts that are unique in offering one strongly androgen-dependent and several relapsed strains of a human prostate cancer that can be investigated in the laboratory. We report on the cytogenetic characterization of the hormone-dependent CWR22, and the relapsed CWR22-R serially transplanted xenografts, in our laboratory. METHODS: We utilized a suspension harvest of the xenograft tissue to optimize our yield for metaphase chromosome studies and analyzed the hormone-dependent CWR22 and four relapsed CWR22-R xenografts. These studies were accomplished using standard G-banded analysis and fluorescence in situ hybridization (FISH). A variety of DNA probes including alpha-satellite DNA probes, and chromosomal libraries, were utilized for the FISH analysis. RESULTS: Utilizing both standard cytogenetic analysis and FISH studies we have more precisely defined the CWR22 xenograft: 49,XY,+i(1)(q10),-2, der(4)t(2;4)(p21;q33), +7,+8,+12[7]/50,XY,idem, +der(2)t(2;4)(p21;q33)del(2)(q13q33)[13]. Four relapsed xenografts, CWR22R-2152, CWR22R-2524, CWR22R-2274, and CWR22R-2272 were also studied. Each of these lines demonstrated a different karyotype. CONCLUSIONS: The CWR22 karyotype offers the simplest reported karyotype for a prostate cancer tissue culture cell line or xenograft; this makes CWR22 an attractive candidate for studies of genetic changes associated with the relapse of prostate cancer treated with androgen withdrawal. Four separate, serially transplanted, relapsed CWR22-R xenografts were detected, each with a separate karyotype.

Androgens↗
PubMed1999

Prognostic value of immunohistochemical expression of the c-erbB-2 oncoprotein in metastasic prostate cancer.

It is well established that the activation of proto-oncogenes could trigger uncontrolled cell growth and cancer development. Although this correlation has already been evidenced in several human tumors, no conclusive studies have related oncogene activation with the development of prostatic neoplasia. Nevertheless, some reports suggest that c-erbB-2, which is a prognostic marker in breast cancer, could be implicated in the development of prostatic adenocarcinoma. We have studied the expression of the c-erbB-2 oncoprotein in primary prostatic tissue in a series of 70 patients with metastasic disease, by means of immunohistochemistry. The NCL-B 11 anti-c-erbB-2 monoclonal antibody was used, and the immunoreactivity was quantified by image analysis. The overall rate of prostatic-tissue sections presenting positive c-erbB-2 immunostaining was 64.3%. No significant relation was observed between histological grade and c-erbB-2 over-expression or severity of the disease, based on the extent of metastases. The average specific survival in patients with c-erbB-2 over-expression was 33 months, while it was 54 in patients with c-erbB-2 negativity; p < 0. 034. These results, as well as the logistic-regression analysis, suggest that expression of c-erbB-2 oncoprotein would be considered as an independent prognostic factor of metastatic prostate cancer. Moreover, it could discriminate between the prognosis of patients with Gleason score 2 to 7 and those with score 8 to 10. Our results suggest that the expression of c-erbB-2 oncoprotein in primary prostatic tissue could have a prognostic value in patients with metastatic prostate cancer. Int. J. Cancer (Pred. Oncol.) 84:421-425, 1999.

Adenocarcinoma↗
PubMed1999

Use of cyproheptadine to control urine spraying in a castrated male domestic cat.

A 10-year-old castrated male domestic cat was admitted to the hospital because of lifelong urine spraying of vertical surfaces. A diagnosis of territorial urine marking was made. Laboratory analytes for urine analysis, hemogram, serum biochemical analysis, and serum thyroxine concentration were within reference ranges, and testosterone concentration was consistent with the reference range of castrated male cats. Treatment included behavior modification and the administration of cyproheptadine, which resulted in the immediate arrest of undesirable urine marking. Cyproheptadine administration was adjusted to determine the lowest dosage that effectively maintained the cat's consistent use of the litter box. Cyproheptadine administration was recommended for at least 1 year before any attempt to withdraw its use. A follow-up phone call to the owner 8 months after the beginning of treatment revealed that the cat continued to have remission of inappropriate urination. Cyproheptadine, an antihistamine prescribed for its orexigenic effects in cats, has antiandrogenic effects in other species. Information in this report indicates that cyproheptadine is effective in the control of urine spraying even in castrated cats.

Animals↗
PubMed1999

Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype.

The majority of tumors from hereditary nonpolyposis colorectal cancer families and a subset of unselected gastrointestinal and endometrial tumors exhibit a microsatellite mutator phenotype (MMP) that leads to the accumulation of hundreds of thousands of clonal mutations in simple repeat sequences. The mutated genes with positive or negative roles in cell growth or survival in aneuploid gastrointestinal cancer (e.g., APC, K-ras, and p53) are less frequently mutated in near-diploid MMP gastrointestinal tumors. These tumors accumulate mutations in other genes, such as DNA mismatch repair hMSH3 and hMSH6, transforming growth factor-beta type II receptor, and BAX. All these genes carry, within their coding sequences, mononucleotide repeats that are preferred targets for the MMP. Endometrial carcinoma is the most common type of extracolonic neoplasia in the hereditary nonpolyposis colorectal cancer syndrome, but the spectrum of its target cancer genes is not well characterized. Here, we report that endometrial cancer of the MMP also accumulates mutations in genes that are typically mutated in gastrointestinal cancer of the mutator pathway, including BAX (55%), hMSH3 (28%), and hMSH6 (17%). We also report the detection of frameshift mutations in caspase-5, a member of the caspase family of proteases that has an (A)10 repeat within its coding region, in MMP tumors of the endometrium, colon, and stomach (28, 62, and 44%, respectively). We therefore suggest caspase-5 as a new target gene in the microsatellite mutator pathway for cancer.

Caspases↗
PubMed1999

Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial.

We performed a prospective, randomized, multicenter trial to evaluate the effectiveness of prophylactic inhalations with aerosolized amphotericin B (aeroAmB) to reduce the incidence of invasive aspergillus (IA) infections in patients after chemotherapy or autologous bone marrow transplantation and an expected duration of neutropenia of at least 10 days. From March 1993 until April 1996, 382 patients with leukemias, relapsed high-grade non-Hodgkin lymphomas, or solid tumors were randomized with a 13:10 ratio to receive either prophylactic aeroAmB inhalations at a dose of 10 mg twice daily or no inhalation prophylaxis in an unblinded fashion. The incidence of proven, probable, or possible IA infections was 10 of 227 (4%) in patients who received prophylactic aeroAmB. This did not differ significantly from the 11 of 155 (7%) incidence in patients who received no inhalation prophylaxis (P =.37). Moreover, no differences in the overall mortality (13% v 10%; P =.37) or in the infection-related mortality (8% v 7%; P =.79) were found. In contrast to other nonrandomized trials, we observed no benefit from prophylactic aeroAmB inhalations, but the overall incidence of IA infections was low.

Administration, Inhalation↗
PubMed1999

Declining HIV/AIDS mortality in New York City.

BACKGROUND: New York City has only 3% of the U.S. population but has reported nearly 16% of all AIDS cases. METHODS: This is an observational study using the New York City vital events and AIDS case surveillance registries to describe trends in HIV/AIDS mortality from 1983 through June 30, 1998. RESULTS: Annual HIV/AIDS deaths increased steadily until stabilizing at 7046 in 1995, declined 29% to 4998 in 1996, and declined 47% to 2625 in 1997. Comparing data from 1997 with those from 1995, declines occurred in all demographic groups and in all major HIV transmission categories: 74% in men who have sex with men, 68% in injecting drug users, and 64% in heterosexuals. In the first 6 months of 1998, declines were smaller than they had been in previous 6-month intervals in all demographic groups except Hispanic males and those between 35 and 44 years of age. From 1995 to the first 6 months of 1998, the number of people living with AIDS in New York City increased 22% (from 32,692 to 39,976). CONCLUSIONS: The precipitous 63% decline in HIV/AIDS deaths from 1995 to 1997 occurred at the same time that more effective antiretroviral therapies became widely available. The slowing in the mortality decline observed in 1998, however, suggests that although these new therapies may have a profound effect at the population level, deaths due to AIDS will continue.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Use of cyproheptadine to control urine spraying and masturbation in a cat.

A 5-year-old male domestic longhair cat was examined because of urine spraying and masturbation. The cat had sprayed urine from the time it was acquired as a stray 4 years earlier. The cat was cryptorchid, and at 1 year of age, the scrotal testicle was removed. The cryptorchid testicle was surgically removed several months later; however, urine spraying and masturbation persisted. A diagnosis of territorial marking and separation anxiety was made. Serum testosterone concentration was within the reference range for sexually intact male cats. Treatment included behavior modification and administration of cyproheptadine (2 mg, p.o., q 12 h), which has been shown to have antiandrogenic effects in other species. Frequency of urine marking and masturbation decreased, along with serum testosterone concentration. The cat continued to do well as long as medication was given consistently. Eventually, the cat underwent a laparotomy for removal of remnant testicular tissues but was then lost to follow-up.

Animals↗
PubMed1999

Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma.

We report on a 7-year-old boy with mosaic variegated aneuploidy (MVA) who developed embryonal rhabdomyosarcoma of the soft palate. This patient is the 11th case report of MVA and represents further documentation of the true existence of this rare mitotic mutant. Clinical findings share similarities to those previously described patients including microcephaly and growth retardation as the two most common abnormalities. Notably, mental retardation is not universally present. Results of serial cytogenetic analyses performed on somatic and neoplastic tissues are reviewed and compared with those of other previously reported patients. We postulate that mosaic variegated aneuploidy is causally related to the development of rhabdomyosarcoma in our patient. This is the first report of a patient with MVA who developed cancer and suggests that these patients may be at risk for malignancy and require long-term follow-up and cancer surveillance.

Adolescent↗
PubMed1999

The identification of monoclonality in human aberrant crypt foci.

Malignant neoplasms, including colon cancers, are thought to arise from a single initiated progenitor cell. Aberrant crypt foci (ACF) are putative precursors of at least some colon cancers. The pattern of X chromosomal inactivation, which is identified by the differential methylation of a site near a polymorphic CAG repeat in the androgen receptor gene, was used to determine the clonality status of 11 ACF from eight female patients. Ten of 11 ACF were found to be monoclonal aberrations. The eleventh ACF appeared monoclonal, but nonrandom inactivation of the X chromosome was also seen in normal crypts from this patient. These results clearly demonstrate that: (a) a high percentage of ACF lesions are neoplastic rather than hyperplastic; and (b) ACF are the earliest identified neoplastic lesions in the colon.

Chromosome Aberrations↗
PubMed1999

A new mutation in the regulatory domain of the myophosphorylase gene affecting protein dimer contact.

We have identified a novel missense mutation in the myophosphorylase gene in a Spanish patient with McArdle's disease. The patient was homozygous for a T-to-C transition at codon 115 (L115P) in exon 3, which changed an encoded leucine (CUG) to a proline (CCG). This is the first mutation to be described in exon 3 and in a protein domain related to dimer contact. These data further emphasize the importance of private mutations in McArdle's disease, some of which are associated with specific ethnic groups.

Glycogen Phosphorylase, Muscle Form↗
PubMed1999

Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2beta predict immune-mediated (Type 1) diabetes in relatives.

We report here our prospective study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2beta autoantibodies (ICA, IAA, GAD65A, IA-2A and IA-2betaA), on the first available serum samples. The latter three autoantibodies were however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year risk=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year risk=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2beta A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant beta-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing.

Adolescent↗
PubMed1999

Virus-receptor interactions of human parainfluenza viruses types 1, 2 and 3.

Human parainfluenza viruses types 1, 2 and 3 (HPF 1, 2 and 3) are important pathogens in children. While these viruses share common structures and replication strategies, they target different parts of the respiratory tract; the most common outcomes of infection with HPF3 are bronchiolitis and pneumonia, while HPF 1 and 2 are associated with croup. While the HPF3 fusion protein (F) is critical for membrane fusion, our previous work revealed that the receptor binding hemagglutinin-neuraminidase (HN) is also essential to the fusion process; interaction between HN and its sialic acid-containing receptor on cell surfaces is required for HPF3 mediated cell fusion. Using our understanding of HPF3 HN's functions in the cell-binding and viral entry process, we are investigating the ways in which these processes differ in HPF 1 and 2, in part by manipulating receptor availability. Three experimental treatments were used to compare the HN-receptor interaction of HPF 1, 2 and 3: infection at high multiplicity of infection (m.o.i.); bacterial neuraminidase treatment of cells infected at low m.o.i.; and viral neuraminidase treatment of cells infected at low m.o.i. (using Newcastle disease virus [NDV] neuraminidase or UV irradiated HPF3 as sources of neuraminidase). In cells infected with HPF3, we have shown that infection with high m.o.i. blocks fusion, by removing sialic acid receptors for the viral HN. However, in cells infected with HPF 1 and 2, infection with high m.o.i. did not block fusion; the fusion increases with increasing m.o.i. In cells infected with HPF 1 and 2, neither bacterial nor NDV neuraminidase blocked cell fusion, using amounts of neuraminidase that completely block fusion of HPF3 infected cells. However, when inactivated HPF3 was used as a source of viral neuraminidase, the treatment inhibited fusion of cells infected with HPF 1 and 2 as well as 3. The differences found between these viruses in terms of their interaction with the cell, ability to modulate cell-cell fusion and response to exogenous neuraminidases of various specificities, may reflect salient differences in biological properties of the three viruses.

Animals↗
PubMed1999

Insomnia and heart disease: a review of epidemiologic studies.

Since the discovery and successful treatment of sleep apnea, researchers seem to believe that the association between sleep disturbance and coronary heart disease (CHD) has been explained. To determine whether subjective nighttime sleep complaints (trouble sleeping, trouble falling asleep, trouble staying asleep), exclusive of apnea, predicted myocardial infarction and other coronary events, a MEDLINE search was conducted for articles published between January 1976 through August 1997. Ten studies with an explicit measure of association between an insomniac complaint and CHD were identified. Reported risk ratios for various sleep complaints and CHD events ranged from 1.0 for waking too early and CHD death in an elderly North Carolina community to 8.0 for the highest versus lowest quintile of a sleep scale in Finnish men. Higher quality studies showed risk ratios of 1.47-3.90 between trouble falling asleep and coronary events after adjusting for age and various coronary risk factors (combined effect=1.7, p<0.0001). While alternative explanations such as medication use still need to be ruled out, we theorize that a subjective insomniac complaint either may be part of a larger syndrome that includes poor health and depression, or it may be related to continual stressors, reduced slow-wave sleep, and autonomic dysfunction, which increase the risk of heart problems.

Confounding Factors, Epidemiologic↗
PubMed1999

Silicone oil in the repair of pediatric complex retinal detachments: a prospective, observational, multicenter study.

OBJECTIVE: To report anatomic and visual acuity outcomes, as well as complications, after using 1000-centistoke silicone oil as a retinal tamponade for the treatment of complex retinal detachments in a pediatric population. DESIGN: A prospective, observational, multicenter study. PARTICIPANTS: The study cohort consisted of 205 patients 16 years of age or younger (211 eyes) treated at community and university-based ophthalmology clinics for complex retinal detachments associated with trauma, proliferative vitreoretinopathy (PVR), giant retinal tear (GRT), or retinopathy of prematurity (ROP). INTERVENTION: Vitrectomy surgery for complex retinal detachment with 1000-centistoke silicone oil as the retinal tamponade. MAIN OUTCOME MEASURES: Anatomic outcomes include complete retinal attachment and macular attachment. Visual acuity outcomes include ambulatory vision (> or = 4/200) and preservation of preoperative visual acuity. Complications include rates of secondary intraocular pressure (IOP) elevation (> or = 30 mmHg), hypotony (< or = 5 mmHg), corneal opacification (including band keratopathy, corneal edema, and corneal abrasions), oil emulsification, and cataract. All outcome measures were assessed 6, 12, and 24 months after surgery and at last examination. RESULTS: At the 6-month examination, the retina was completely attached in 43 (57%) of 76 eyes in the trauma group, 24 (63%) of 38 PVR eyes, 23 (68%) of 34 GRT eyes, and 6 (33%) of 18 ROP eyes. The macula was attached in 60 (79%), 33 (87%), 26 (76%), and 8 (44%) eyes, respectively. Ambulatory vision was achieved in 19 (25%) eyes in the trauma group, 18 (47%) PVR eyes, 19 (56%) GRT eyes, and 4 (22%) ROP eyes. Visual acuity was preserved in 53 (70%), 26 (68%), 28 (82%), and 9 (50%) eyes, respectively. The corresponding rates of complications for traumatic, PVR, GRT, and ROP eyes were: elevated IOP-3 (4%) of 76, 1 (3%) of 38, 1 (3%) of 34, and 0 (0%) of 18; hypotony--9 (12%), 3 (8%), 2 (6%), and 2 (11%); corneal opacity--25 (33%), 8 (21%), 15 (44%), and 5 (28%); emulsification--4 (5%), 1 (3%), 3 (9%), and 1 (6%); and cataract in phakic eyes--1 (33%) of 3, 2 (67%) of 3, 2 (50%) of 4, and 1 (33%) of 3. CONCLUSIONS: Retinal reattachment and preserved visual acuity were achieved in the majority of eyes using vitrectomy and silicone oil retinal tamponade. Complete retinal and macular attachment was achieved less frequently in ROP eyes than in eyes in the other diagnostic groups. Use of 1000-centistoke silicone oil can be considered in the management of pediatric complex retinal detachments associated with multiple etiologies.

Adolescent↗
PubMed1999

Inflammation does not decrease intraluminal pH in chronic inflammatory bowel disease.

Intestinal inflammation may influence intraluminal pH. Profiles of the gastrointestinal pH were evaluated in 15 patients with active Crohn's disease of the ileocecal area. In addition, five patients with moderate (1) or severe (4) ulcerative colitis were studied. Fifteen healthy subjects served as controls. Intraluminal pH of the different parts of the gastrointestinal tract was measured by a free-floating pH-sensitive telemetering capsule. A metal sphere was attached to the capsule for exact localization by a metal detector. Physiological patterns of pH were maintained throughout the gastrointestinal tract including the inflamed segments. Median pH in the terminal ileum of the patients with Crohn's disease was 7.5 vs. 7.7 and in the rectum in ulcerative colitis 7.8 vs. 7.2 in the controls. In conclusion, intraluminal pH is not decreased by inflammatory changes in Crohn's disease and ulcerative colitis, allowing eudragit-coated pH-controlled-release formulations of mesalazine to dissolve in diseased areas also.

Acid-Base Equilibrium↗
PubMed1999

CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Altered growth and function of synoviocytes, the intimal cells which line joint cavities and tendon sheaths, occur in a number of skeletal diseases. Hyperplasia of synoviocytes is found in both rheumatoid arthritis and osteoarthritis, despite differences in the underlying aetiologies of the two disorders. We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome. Using a positional-candidate approach, we identified mutations in a gene (CACP) encoding a secreted proteoglycan as the cause of CACP. The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins. In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium. The similarity of CACP sequence to that of other protein families and the expression of CACP in non-skeletal tissues suggest it may have diverse biological activities.

Amino Acid Sequence↗