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D Schwartz

Publications and source records attributed to D Schwartz.

At least 163 records · Page 9Linked to original sources

Role of the GRO family of chemokines in monocyte adhesion to MM-LDL-stimulated endothelium.

We have previously shown that treatment of endothelial cells with minimally modified LDL (MM-LDL) induces the binding of monocytes to unknown endothelial receptor molecules. We now report that a member of the GRO family of chemokines plays a role in MM-LDL-induced monocyte binding. A cDNA library made from rabbit aortic endothelial cells (RAEC) treated with MM-LDL was expression screened for molecules inducing binding of a human monocyte cell line (THP-1). A cDNA was isolated with 75% homology to GRO. GRO mRNA levels were significantly elevated after exposure of RAEC or human aortic endothelial cells (HAEC) to MM-LDL. HAEC treated with MM-LDL displayed an increase in a surface-associated protein that bound to antibody against GRO despite low levels of GRO in the medium. Antibody to GRO significantly inhibited the binding of monocytes to MM-LDL-treated RAEC and HAEC. The increase in GRO expression and monocyte binding were reduced by incubating MM-LDL-treated endothelial cells with heparin (in a method that releases heparan sulfate bound molecules from the cell surface). These results suggest that GRO related chemokines are bound to the surface of MM-LDL-treated endothelial cells and may contribute to the monocyte adhesion induced by MM-LDL.

Amino Acid Sequence↗

Comparison of in vivo and in vitro prostaglandin E2 production by squamous cell carcinoma of the head and neck.

Prostaglandin E2 has been identified as an immunosuppressive factor in patients with squamous cell carcinoma of the head and neck. Spontaneous prostaglandin E2 production by 21 cancer cell lines, which were obtained from 17 patients with squamous cell carcinoma of the head and neck, was determined by radioimmunoassay. In comparison with normal keratinocyte cultures, prostaglandin E2 production by cancer cell lines was significantly decreased (p < 0.0001). Prostaglandin E2 levels demonstrated no correlation to the site, stage, or histopathologic differentiation of the tumor. In a separate group of 17 patients with squamous cell carcinoma of the head and neck, tumor cells were isolated from fresh tumor specimens, and 24-hour PGE2 production in vitro was assayed. No correlation was found with tumor site, stage, or 2-year disease-free survival. Although prostaglandin E2 may have biologic significance in vivo in patients with squamous cell carcinoma of the head and neck, these findings suggest that measurements of tumor cell-derived prostaglandin E2 are not predictive of biologic behavior.

Aged↗

Role of nitric oxide in glycerol-induced acute renal failure in rats.

EDRF results from the metabolism of L-arginine. N-omega-nitro-L-arginine is a nitric oxide synthase inhibitor (L-arginine competitive inhibitor). Acute renal failure was induced by i.m glycerol (50%) 5 ml/kg bw. L-arginine: 3 mg/kg bw/min for 60 min before and 60 min after glycerol administration. L-arginine inhibitor (150 micrograms/kg bw/min for 120 min). Cin, Cpah and FENa% were measured immediately or 24 h after glycerol (mean of three periods of 20 min). A second series of similar experiments was done in dehydrated (16 h) rats with a high dose of glycerol (50% solution, 10 ml/kg bw). L-arginine ameliorates the severity of ARF immediately after glycerol administration and enhances the recovery of glycerol-induced ARF. The L-arginine inhibitor resulted in a more severe ARF. Urinary cGMP decreased significantly after glycerol administration. It is concluded that nitric oxide has an important pathogenetic role in the glycerol induced ARF.

Acute Kidney Injury↗

Does wild-type p53 play a role in normal cell differentiation?

Inactivation of the p53 tumor suppressor gene plays a major role in malignant transformation. The central question in this issue is concerned with the understanding of the function of p53 in normal cells and its deregulation in cancer cells. Several in vitro and in vivo experimental models have indicated that induction of cells to undergo differentiation involve up-regulation in the expression of the p53. In the case of B cell differentiation, p53 was found to be involved in several steps of the differentiation pathway. The conclusion that p53 plays a role in normal development and differentiation in vivo is substantiated by the observation that p53 is expressed during embryonic development and is detected at low levels in a number of organs of adult mice. Accentuated levels of p53 in testes of adult mice, suggests that p53 plays a role in the meiotic process of spermatogenesis. B cell differentiation and spermatogenesis are biological pathways which normally involve DNA reshuffling and rearrangements. In accordance with the notion that p53 is associated with DNA repair it is tempting to speculate that at least in these physiological pathways p53 functions as a master gene that controls genome integrity.

Animals↗

Further delineation of the ear, patella, short stature syndrome (Meier-Gorlin syndrome).

Two daughters of phenotypically normal parents are described with severe proportional dwarfism with microcephaly, peculiar craniofacial anomalies, microtia, absent patellae, joint hyperextensibility, and other anomalies. Intrafamilial variability is minimal. This combination of anomalies has many similarities to the six cases previously described with the Ear, Patellae, Short stature syndrome (Meier-Gorlin syndrome), which is distinguished by the triad of microtia, absent patellae and growth retardation. Autosomal recessive inheritance is strongly suggested by the presence of two pairs of affected siblings and the equal sex ratio.

Child, Preschool↗

Spinal stenosis.

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Aged↗

Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome.

Transgenic mice which carry hybrid p53 promoter-chloramphenicol acetyltransferase (CAT) transgenes were found to express CAT enzymatic activity predominantly in the testes. Endogenous levels of p53 mRNA and protein were lower than in the nontransgenic control mice. The various p53 promoter-CAT transgenic mice exhibited in their testes multinucleated giant cells, a degenerative syndrome resulting presumably from the inability of the tetraploid primary spermatocytes to complete meiotic division. The giant-cell degenerative syndrome was also observed in some genetic strains of homozygous p53 null mice. In view of the hypothesis that p53 plays a role in DNA repair mechanisms, it is tempting to speculate that the physiological function of p53 that is specifically expressed in the meiotic pachytene phase of spermatogenesis is to allow adequate time for the DNA reshuffling and repair events which occur at this phase to be properly completed. Primary spermatocytes which have reduced p53 levels are probably impaired with respect to DNA repair, thus leading to the development of genetically defective giant cells that do not mature.

Animals↗

Poor survival of black patients in carcinoma of the endometrium.

PURPOSE: To compare the prognostic factors and survivals of black and white patients with endometrial carcinoma. METHODS AND MATERIALS: A retrospective study was undertaken of a total of 290 patients with endometrial carcinoma who were treated similarly at the Health Science Center at Brooklyn and Kings County Hospital Center from 1975 and 1990. One hundred and thirty-six of 290 (47.2%) were black and 135/290 (46.9%) were white. Well-known prognostic factors affecting endometrial carcinoma were studied in black and white group of patients. Their overall survival and comparison of survival in each prognostic group were also estimated using multi-variate analysis. RESULTS: Fifty-four percent of white patients had Stage I disease, compared to 45.9% in black patients. In Stage II, 51.6% were white and 48.4% were black, and in Stage III, 88.89% were black and 11.1% were white patients (p = 0.034). Fifty six percent Grade 1 patients were white and 44% were black. In Grade 2, 53.3% were white and 46.7% were black and in Grade 3 disease, 70.5% were black and 29.5% were white (p = 0.008). Up to the inner third of myometrial invasion had occurred in 60.6% of white patients and 39.4% in black patients. The middle third of the myometrium was invaded in 60.7% of white patients, and 39.3% of black patients. Thirty-seven percent of outer third of myometrial invasion was found in white patients and 63% in black patients (p = 0.038). Seventy-two percent of positive lymph nodes were found in black patients and 28.0% in white patients (p = 0.01). Sixty-one percent of patients with positive peritoneal cytology were black as compared to 38.7% in white patients (p = 0.017). The overall ten-year corrected survival for white and black patients was 72% and 40%, respectively (p = 0.0003). Survivals comparisons, when stratified by race and each prognostic group, showed statistically significant overall survival differences in favor of white patients. CONCLUSION: Black patients with endometrial carcinoma have poor survival. Low socio-economic status (SES) would not explain these findings. More research is required to determine the cause of poor survival in black patients with endometrial carcinoma.

Adult↗

Endometrial carcinoma. Influence of prognostic factors on radiation management.

The earliest intracavitary radium treatment for uterine cancer was reported in 1908. Refinements reported during the next 20 years, using an intrauterine tube and colpostats or radium capsules, established a treatment philosophy of preoperatively irradiating uterine and parauterine tissues. Thus, preoperative intracavitary irradiation became entrenched as therapy for all endometrial cancers for the better part of four decades. In the 1950s and 1960s, the ability of external irradiation to eradicate cancer in regional lymphatic vessels prompted the use of pelvic field irradiation in Stage II and III and recurrent disease. The results of surgical exploratory studies in the 1970s established more refined criteria for preoperative or postoperative external pelvic irradiation in high-grade infiltrating Stage I cancers. In the 1980s, it became apparent that, for tumors with lymphovascular invasion, clear cell, and serous papillary histologic types, the disease spread to the upper abdomen and the paraaortic nodes might benefit from extended field and/or whole abdominal irradiation, with or without systemic bolus or concomitant continuous-infusion chemotherapy. In the 1980s, a subset of patients was identified with high-grade lymphovascular invasion clear cell and papillary serous histologic types or with positive peritoneal cytologic findings who were at high risk of failing in the paraaortic nodes and/or the upper abdomen for whom extended field or whole abdominal irradiation have been advocated. Given the fraction and dose limitation for a large abdominal field, the addition of systemic concomitant bolus or continuous infusion of chemotherapy currently is proposed to improve the control of intraabdominal failure in these high-risk patients.

Combined Modality Therapy↗

Testicular tissue-specific expression of the p53 suppressor gene.

The hybrid transgene approach was adapted to study the physiological pathway(s) in which the p53 suppressor gene is involved. p53 promoter-CAT transgenic mice were found to express enzymatic CAT activity predominantly in the testes. In situ hybridization indicated that expression of the transgene as well as the endogenous p53 agreed with the typical wave and cycle patterns of spermatogenesis. p53 promoter-CAT transgenic mice expressed in the testes reduced levels of endogenous p53 mRNA that correlated with the copy number of the mouse or human transgene. The spatial and cyclical expression of the p53 gene which is confined to the primary spermatocytes in the seminiferous tubuli suggested that p53 may play a role in the meiotic process of spermatogenesis in vivo.

Animals↗

Quantitative determination of pentane in exhaled air correlates with colonic inflammation in the rat colitis model.

Oxygen radicals play a key role in inflammation and inflammatory tissue damage. Quantitative determination of pentane, a hydrocarbon generated by membrane lipid peroxidation initiated by oxygen radicals, in expired air has been used as a noninvasive determinant or index of inflammation in various conditions. Herein we report the first examination of the relationship between exhaled pentane and colonic inflammation in a rodent model of colitis. Colitis was induced in rats (n = 33) using the trinitrobenzene-sulfonic acid (TNB) model of colitis. Exhaled air was collected in a closed chamber on randomly selected animals on days 1, 2, 4, 7, 11, 13, 15, 20, and 25 post-TNB treatment, and pentane was assayed by means of gas chromatography. Gross and microscopic evidence of inflammation was compared with exhaled pentane levels. Pentane levels varied from 0.0 to 14.6 nmol/l of air and were significantly increased in TNB-treated rats compared with control rats only on days 7 to 15 after treatment (P < 0.05). Gross inspection showed severe colonic inflammation through the first week (mean score = 4.7 out of a possible 5), persistent inflammation on days 7 to 15 (3.2), and healing and fibrosis from the end of week two until day 25 (1.9 to 0). Histologic evaluation confirmed a progression of inflammation from acute ulceration to chronic inflammation to fibrosis and scarring. We have demonstrated that pentane exhalation is increased after the induction of colonic inflammation, with a seven-day lag time, and returns rapidly to normal as acute inflammation resolves. This suggests that pentane exhalation can be used as a noninvasive measure of colonic inflammation in rodent models of colitis and perhaps clinically in humans.

Air↗

Rectal manometry, computed tomography, and functional results of anal atresia surgery.

Children with anal atresia often have compromised function. This is especially common with the anatomic "high lesion." Twenty-five patients have been studied using clinical evaluation, computed tomography (CT), and manometry to make an objective evaluation. The patients were an average of 9.6 years old; the male-to-female ratio was 3:2. Thirty-three percent had acceptable bowel function as defined by a continence score of 1 or 2. Only two (11%) had an abnormal sacrum. The mean rectal pressure was 20 cm H2O and 5 patients (23%) had a normal rectal relaxation reflex. Thirty percent had CT scans that demonstrated an intact external sphincter and puborectalis. In comparing the objective criteria and clinical results no technique could predict continence. CT demonstrated no significant group (P = .046 to .659) and manometry demonstrated no significant group (P = .082 to .752). We found no objective criteria that could evaluate the patient's clinical result or dictate therapy.

Adolescent↗

Immunoglobulin secretion by the normal and the infected newborn infant.

The development of quantitative single-cell immunoassays has provided a novel opportunity to demonstrate the isotype-specific immunoglobulin responses in normal and infected neonates. The reverse enzyme-linked immunospot assay was used to determine the number of immunoglobulin-secreting cells (IgSCs) in peripheral blood. Baseline numbers of IgSCs were established in 69 uninfected term and preterm infants within 5 days of birth; values above the 99th percentile were considered elevated. The IgSCs were also measured in 266 infants with proved or suspected infections or congenital anomalies. A subset of newborn infants was retested weekly. Few IgSCs (mostly IgMSCs) were detected within 5 days of birth in uninfected neonates, but by 1 month 77% had increased numbers of IgSCs, primarily IgASCs. Sixty-three (24%) of 266 study infants had increased IgSCs on initial sampling (predominantly IgMSCs); these included infants as immature as 25 to 27 weeks of gestational age; elevations in IgSCs were most frequent in infants with intrauterine infections. Increased numbers of IgSCs were uncommon in infants with early-onset sepsis in the first 5 days but were frequent by the second week, consistent with acquisition of infection near the time of delivery. We conclude that the presence of elevated numbers of IgSCs soon after birth may be a useful surrogate marker of untreated intrauterine infection. The development of predominantly IgASCs in the first month of life suggests postnatal exposure to common mucosal antigens.

Antibody-Producing Cells↗

Plasmid profiles and antimicrobial susceptibility of Campylobacter jejuni isolated from Israeli children with diarrhea.

Thirty Campylobacter jejuni (C. jejuni) strains isolated from stools of Israeli children with enteritis were tested for sensitivity to eight antimicrobial agents (MIC) and the presence of plasmids. It was found that all the isolates were sensitive to ciprofloxacin, ofloxacin, furazolidone and erythromycin. Of the 30 strains tested, 21 (70%) were found to be tetracycline-resistant, a relatively high resistance rate as compared with data from other countries and previous reports from Israel. Plasmids were detected in 17 out of 30 C. jejuni isolates (55.6%). A total of nine different plasmid profiles could be distinguished; six profiles were represented by one strain each. Of the 21 tetracycline-resistant strains, plasmids were found in 17 isolates (80%) carrying from 1-2 to 5 plasmids of various sizes. No plasmids were found in tetracycline-sensitive strains, with the exception of one isolate which contained a 24.4 MDa plasmid and was co-trimoxazole-resistant. Our studies indicate a relatively high percentage of tetracycline-resistant C. jejuni isolates in the Tel Aviv area. In 80% of these strains, various plasmid profiles were detected.

Amoxicillin↗

Self- and spouse ratings of anger and hostility as predictors of coronary heart disease.

Self- and spouse ratings of anger and hostility were examined as predictors of coronary heart disease (CHD) in 185 cardiac patients. Patients completed the Multidimensional Anger Inventory (MAI) and the Marlowe-Crowne Social Desirability (MCSD) Scale; the MAI (rewritten to 3rd person) was completed by patients' spouses or by a peer. Thallium scans were used to measure CHD status. Results showed that patient-rated MAI scores were inversely correlated with MCSD. There were no gender differences for patient-rated MAI scores, but spouse ratings showed gender effects for Anger-Arousal and Hostile Outlook: Women rated their husband higher than men rated their wife. Patients with positive thallium scans were no different from those without CHD on patient-rated MAI scores; however, spouse ratings indicated that those with CHD had higher Hostile Outlook and Anger-In scores. After accounting for the effects of traditional CHD risk factors, only spouse-rated hostility contributed significant incremental variance to the prediction of CHD status.

Adult↗

Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma.

Neonates born to women with reactive serologic tests for syphilis were studied; the total of 116 included 18 who were symptomatic, 60 asymptomatic but possibly infected, and 38 asymptomatic and probably uninfected. The fluorescent treponemal antibody-absorption (FTA-ABS) 19S IgM test and an IgM capture ELISA for Treponema pallidum, both treponema-specific assays, and the reverse enzyme-linked immunospot (RELISPOT), which detects immunoglobulin-secreting cells and is a nonspecific indicator of infection, were evaluated. Sensitivities among symptomatic neonates were 88% (IgM ELISA), 73% (FTA-ABS), and 78% (RELISPOT). Specificities ranged from 97% to 100%. A major problem has been the inability to identify which asymptomatic but possibly infected neonate is really uninfected. Among 41 such babies who had all three tests done, 93% were negative by all assays, suggesting they were uninfected or recently infected. Strategies to accurately identify the truly uninfected asymptomatic newborn would prevent the unnecessary hospitalization of all at-risk infants, resulting in improved quality of care and reduced costs.

Adult↗