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Biomedical subjects

N Schneider

Publications and source records attributed to N Schneider.

At least 19 recordsLinked to original sources
PubMed1999

Taxol, vincristine or nocodazole induces lethality in G1-checkpoint-defective human astrocytoma U373MG cells by triggering hyperploid progression.

In this report, we describe a novel lytic mechanism exploited by antimicrotubule drugs (AMDs) such as Taxol which are frequently used to treat multiple human cancers including breast and ovarian cancers. In cells lacking the G1-arresting capacity due to the defect in retinoblastoma or p53 gene function, AMDs trigger hyperploid progression and death. The hyperploid progression occurs via continued cell-cycle progression without cell division. Blocking hyperploid progression through hydroxyurea or ectopically expressed p27(Kip1), a G1-specific Cdk inhibitor, abrogates AMD cytotoxicity. Thus, AMDs induce lethality in G1-checkpoint-defective cells by triggering hyperploid progression. The phenomenon is reminiscent of that observed previously with bub-1 yeast mutant. The potential significance of this finding lies in that hyperploid progression-mediated death may be exploited to develop a therapy with tumor-specificity at the genetic level. As a large fraction of human cancers are mutated in p53 gene, it may have a wide therapeutic applicability.

Astrocytoma↗
PubMed1999

MR colonography: optimized enema composition.

Manganese chloride, iron glycerophosphate, and cellulose additive were assessed as base materials for use in a T1-shortening single contrast enema for magnetic resonance (MR) colonography. Contrast-to-noise ratios (CNRs) were compared to those with the standard 10 mmol/L gadolinium-based enema. On T1-weighted three-dimensional gradient-recalled-echo images, CNRs with the iron glycerophosphate enema exceeded those with the manganese- and gadolinium-based enemas. Use of an additive of 0.8% wt/wt cellulose was found to be practicable as it increased viscosity sufficiently without altering CNR. The gadolinium-based enema can be replaced with an iron glycerophosphate enema to render MR colonography less costly.

Adult↗
PubMed1998

Color and lightness constancy in different perceptual tasks.

Color and lightness constancy with respect to changing illumination was studied with three different perceptual tasks: ranking of colored papers according (1) to their lightness and (2) to their chromatic similarity in photopic, mesopic, and scotopic states of adaptation, and (3) recognition of remembered colored papers after changes of illumination in photopic vision. Constancy was found in the second task, only. Excitations of light receptors and luminance channels were computed to simulate the empirical rank orders. Results of the first task can be predicted with the hypothesis that luminance channels are activated, if lightness is asked for. Sequences arranged with respect to chromatic similarity were found independent of the illuminant spectra, even if the calculated rank orders of cone excitation were changed in the altered illumination.

Adaptation, Ocular↗
PubMed1998

Prevalence of cholelithiasis in non-diabetic haemodialysis and continuous ambulatory peritoneal dialysis patients.

Haemodialyzed (HD) patients have been found to have an increased bile cholesterol level and an increased saturation index in bile. These changes were markedly enhanced in the presence of a low-protein diet. To evaluate whether such changes influence the prevalence of cholelithiasis in patients with end-stage renal failure, real-time sonography was performed to detect the presence of gallstones (GS) in 54 HD (28 males, 26 females, mean age 52.4 +/- 15.4 years) and 39 continuous ambulatory peritoneal dialysis (CAPD; 22 males, 17 females, mean age 59.1 +/- 14.9 years) patients. No patient had diabetes. The patients' charts were reviewed for the following data: age, sex, primary renal disease, obesity (20% above ideal weight), history suggestive of gallbladder disease or previous cholecystectomy, duration of dialysis, and serum cholesterol levels. Overall, cholelithiasis was documented in 12 of 93 (12.9%) patients, 7 HD and 5 CAPD. When comparing the factors outlined above, no significant difference was found between HD and CAPD patient groups, either with or without cholelithiasis. Gallbladder disease was asymptomatic in all except 1 patient who required cholecystectomy. Using a healthy control group consisting of local age- and sex-matched inhabitants, GS were found in 8 of 134 (6%) of them (p > 0.05). We conclude that the prevalence rate of GS in our dialysis population (HD and CAPD) is similar to that of a local general population following a western-style diet, irrespective of dialysis mode.

Aged↗
PubMed1998

Insulin and body fat distribution have no direct effect on plasma leptin levels in obese Caucasian women with and without type 2 diabetes mellitus.

Leptin, a hormone produced by adipose tissue, is potentially involved in the regulation of adiposity. The effects of insulin and body fat distribution on human plasma leptin have not yet been clearly defined. The present study investigated the relationships between plasma leptin and total and regional body fat parameters measured by anthropometry and bienergetic absorptiometry associated or not with computed tomography, taking glucose metabolism into account. A cohort of 51 obese Caucasian women (23 with normal glucose tolerance, 11 with impaired glucose tolerance, and 17 with Type 2 diabetes) was analysed. All non-diabetic subjects had an oral glucose tolerance test together with plasma glucose and insulin measurements. Moreover, a subgroup of 7 diabetic subjects with failure to oral antidiabetic treatment was submitted to about 12 days of intensive subcutaneous insulin therapy. Plasma leptin was essentially dependent on total body fat mass (r = 0.83, p < 0.0001, for the whole population), but not related to adipose tissue distribution. An independent correlation between leptin adjusted on body fat mass and fasting insulinaemia (R = 0.72, p < 0.02) or C-peptide (R = 0.62, p < 0.03) was found significant only in the diabetic group. Insulin treatment was associated with a moderate and transient increase of plasma leptin. The relative variations of plasma leptin levels were strongly negatively correlated with those of free fatty acids. The present data confirm that plasma leptin is not dependent on body fat distribution and suggest an indirect effect of insulin on leptin secretion in clinical conditions.

Adipose Tissue↗
PubMed1997

A test system for leukotriene synthesis inhibitors based on the in-vitro differentiation of the human leukemic cell lines HL-60 and Mono Mac 6.

Differentiation of HL-60 cells along the granulocytic lineage by DMSO in the presence of transforming growth factor-beta and low concentrations of 1,25-dihydroxyvitamin D3 leads to the upregulation of 5-lipoxygenase activity in 100,000 g supernatants and intact cells to levels which are comparable to normal granulocytes. Similarly, differentiation of the human monocytic cell line Mono Mac 6 by 1,25-dihydroxyvitamin D3 and transforming growth factor-beta strongly upregulates the 5-lipoxygenase pathway. Here, we describe an assay system for leukotriene biosynthesis inhibitors which is based on the in-vitro differentiation of HL-60 and Mono Mac 6 cells. Different leukotriene biosynthesis inhibitors like the nonredox type inhibitor ZM 230487, the redox type inhibitor BW A4C and the FLAP inhibitor MK886 were tested and the results were compared with an assay system based on normal human granulocytes. ZM 230487, BWA4C and MK886 showed similar potencies in these cell lines as compared to normal leukocytes. Thus, the in-vitro differentiation of HL-60 and Mono Mac 6 cells provides an excellent model for the screening of drugs affecting the 5-lipoxygenase pathway.

Arachidonate 5-Lipoxygenase↗
PubMed1996

Modulation of tumor necrosis factor (TNF) receptor expression during monocytic differentiation by glucocorticoids.

OBJECTIVE AND DESIGN: Regulation of tumor necrosis factor receptors by glucocorticoids was investigated during phorbol ester-induced monocytic differentiation. MATERIALS AND TREATMENT: As model system the human monocytic cell lines U937 and THP-1, which express both types of TNF receptors (TNF-R60 and TNF-R80), were differentiated with tetradecanoyl phorbol-13-acetate (TPA, 5 x 10(-9) M) in the presence or absence of dexamethasone (10(-9) - 10(-6) M). METHODS: Expression of TNF receptors was determined at the mRNA level by Northern blot analysis and at the protein level by FACS analysis. RESULTS: During differentiation, TNF-R60 mRNA was down-regulated, whereas TNF-R80 mRNA levels were increased. Dexamethasone had no effect on TNF-R60 mRNA expression but attenuated TNF-R80 mRNA expression in both cell lines. Cell surface expression of TNF-R60 protein remained essentially unchanged during differentiation of THP-1 cells, whereas a rapid down-regulation of TNF-R80 was observed that was followed by a slow recovery. Surface expression of TNF-R80 was not affected by dexamethasone, whereas TNF-R60 expression was reduced by about 25%. CONCLUSIONS: These results indicate differential regulation of the two types of TNF receptors at the mRNA and protein level during monocytic differentiation. Glucocorticoids interfered with mRNA expression of TNF-R80 and protein expression of TNF-R60, but the rather limited effect leaves the question of its functional relevance open. In contrast to other cytokine systems, TNF receptors do not appear to be major targets of glucocorticoid action.

Cell Differentiation↗
PubMed1995

Implementing a tuberculosis control program.

Between January 1989 and December 1990, 26 patients acquired multidrug-resistant tuberculosis at our institution. Their exposures occurred when they were admitted to a ward where a patient with acid fast bacillus smear-positive pulmonary tuberculosis was also admitted. In 20 cases, the infectious patients were not isolated until the sputum smears were positive. When the outbreak was recognized in the spring of 1990, the infection control department undertook a risk assessment and instituted measures that would become the tuberculosis control program. Since then, administrative and environmental controls have been implemented, education programs are ongoing, personal protective equipment is in use, and a more aggressive employee health testing program is underway. The steps we took and the barriers we had to overcome to implement our plan are included in this article.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Evaluation of infection control measures in preventing the nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis in a New York City hospital.

OBJECTIVE: To evaluate the efficacy of Centers for Disease Control and Prevention (CDC)-recommended infection control measures implemented in response to an outbreak of multidrug-resistant (MDR) tuberculosis (TB). DESIGN: Retrospective cohort studies of acquired immunodeficiency syndrome (AIDS) patients and healthcare workers. The study period (January 1989 through September 1992) was divided into period I, before changes in infection control; period II, after aggressive use of administrative controls (eg, rapid placement of TB patients or suspected TB patients in single-patient rooms); and period III, while engineering changes were made (eg, improving ventilation in TB isolation rooms). SETTING: A New York City hospital that was the site of one of the first reported outbreaks of MDR-TB among AIDS patients in the United States. PARTICIPANTS: All AIDS patients admitted during periods I and II. Healthcare workers on nine inpatient units with TB patients and six without TB patients. RESULTS: The epidemic (38 patients) waned during period II and only one MDR-TB patient presented during period III. The MDR-TB attack rate among AIDS patients hospitalized on the same ward on the same days as an infectious MDR-TB patient was 8.8% (19 of 216) during period I, decreasing to 2.6% (5 of 193; P = 0.01) during period II. In a small group of healthcare workers with tuberculin skin test data, conversions during periods II through III were higher on wards with than without TB patients (5 of 29 versus 0 of 15; P = 0.15), although the difference was not statistically significant. CONCLUSIONS: Transmission of MDR-TB among AIDS patients decreased markedly after enforcement of readily implementable administrative measures, ending the outbreak. However, tuberculin skin-test conversions among healthcare workers may not have been prevented by these measures. CDC guidelines for prevention of nosocomial transmission of TB should be implemented fully at all US hospitals.

AIDS-Related Opportunistic Infections↗
PubMed1994

Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an emerging pathogen in immunocompromised patients.

OBJECTIVE: To describe 13 infections caused by Mycobacterium haemophilum. DESIGN: Identification of patients by microbiologic record review, followed by medical record review and a case-control study. SETTING: Seven metropolitan hospitals in New York. PATIENTS: All patients with M. haemophilum infections diagnosed between January 1989 and September 1991 and followed through September 1992. Surviving patients were enrolled in the case-control study. RESULTS: Infection with M. haemophilum causes disseminated cutaneous lesions, bacteremia, and diseases of the bones, joints, lymphatics, and the lungs. Improper culture techniques may delay laboratory diagnosis, and isolates may be identified incorrectly as other mycobacterial species. Persons with profound deficits in cell-mediated immunity have an increased risk for infection. These include persons with human immunodeficiency virus infection or lymphoma and those receiving medication to treat immunosuppression after organ transplant. Various antimycobacterial regimens have been used with apparent success to treat M. haemophilum infection. However, standards for defining antimicrobial susceptibility to the organism do not exist. CONCLUSIONS: Clinicians should consider this pathogen when evaluating an immunocompromised patient with cutaneous ulcerating lesions, joint effusions, or osteomyelitis. Microbiologists must be familiar with the fastidious growth requirements of this organism and screen appropriate specimens for mycobacteria using an acid-fast stain. If acid-fast bacilli are seen, M. haemophilum should be considered as the infecting organism as well as other mycobacteria, and appropriate media and incubation conditions should be used.

AIDS-Related Opportunistic Infections↗
PubMed1992

Prompt diagnosis of 'acute groin' conditions in infants.

Urgent sonographic examination of the groin was performed in 58 patients under the age of two years. Accurate diagnosis was done in conditions such as: incarcerated inguinal hernia, twisted undescended testis, incarcerated ovary in inguinal hernia and others. Ultrasonography facilitated decision-making and differentiation between surgical and non-surgical conditions.

Abdomen, Acute↗
PubMed1991

The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute megakaryoblastic leukemia: a Pediatric Oncology Group Study.

We report the nonrandom occurrence and frequency of the t(1;22)(p13;q13) in acute myeloid leukemia (AML) and its close association with the French-American-British M7 subtype of AML in infants (less than 1 year). This chromosomal abnormality occurred in 6 of 252 (2.4%) children and adolescents with AML (6 of 28 infants, 22%; 6 of 18 M7 AML cases overall, 33%; and 6 of 6 M7 cases in infants). Infants with AML of M7 subtype and the t(1;22) often presented with prominent abdominal masses. Two of these infants were not treated and died early. Three of four treated infants entered complete remission with therapy for AML; the remaining infant died of hemorrhage on day 8. Of the three infants who entered remission, only one remains alive and disease free at 5+ months. The other two infants relapsed in the bone marrow at 5 and 2 months from the start of therapy, respectively. We conclude that M7 AML with the t(1;22) usually presents in infants with extensive infiltration of abdominal organs by leukemic cells and may confer a poor prognosis despite intensive AML-directed treatment. Identification of this nonrandom translocation exclusively in infants with acute megakaryoblastic leukemia (AMkL) implies that it may serve as an additional diagnostic marker for this disease and links it to the pathogenesis of AMkL in infants.

Antigens, CD↗
PubMed1990

The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein.

We have analyzed t(1;14)(p32;q11) chromosome translocations from two patients with T cell acute lymphocytic leukemia. The chromosome 1 breakpoints of these patients lie within a kilobasepair of each other, and thus define a genetic locus (designated tal) involved in T cell oncogenesis. Moreover, we have identified sequences within tal that potentially encode an amphipathic helix-loop-helix motif, a DNA-binding domain found in a variety of proteins that control cell growth and differentiation. The homology domain of tal is especially related to that of lyl-1, a gene on chromosome 19 that has also been implicated in T cell oncogenesis. Hence, tal and lyl-1 encode a distinct family of helix-loop-helix proteins involved in the malignant development of lymphocytes.

Amino Acid Sequence↗
PubMed1989

[Air transportation of patients: a danger of hypoxic organ lesions?].

As illustrated by two cases, a fall in alveolar oxygen pressure at high altitude, such as during transportation by plane, can cause hypoxic pulmonary failure, especially in patients with already impaired pulmonary or circulatory functions. Arterial oxygen saturation was recorded by pulse oximetry in 14 healthy volunteers and eight patients during air transportation. Oxygen saturation decreased with reduced cabin pressure. Decreased saturation for each 100 mm Hg reduction in cabin pressure was markedly greater in the patients than the healthy volunteers. Pulmonary and circulatory status should be assessed before air transport of patients and if necessary departure delayed. Oxygen ought to be added to inspired air with appropriate supervision in all acutely ill patients. Indications for endotracheal intubation before flight should be generously defined. Continuous pulse oximetry is noninvasive and highly informative. It is urgently recommended that air ambulances be equipped with them.

Adult↗