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Biomedical subjects

N Schneider

Publications and source records attributed to N Schneider.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

The chromosome translocation (11;14)(p13;q11) associated with T-cell acute lymphocytic leukemia: an 11p13 breakpoint cluster region.

The translocation (11;14)(p13;q11) was observed in karyotypes of leukemic cells from a 3-year-old boy with T-cell acute lymphocytic leukemia (T-ALL). Since this translocation is a recurrent marker of T-ALL, we undertook to investigate its mode of formation and role in leukemogenesis. The cytogenetic breakpoint on chromosome 14 occurs in 14q11, the same band wherein lies the T-cell receptor alpha/delta chain gene; and Southern hybridization analysis of peripheral blood and bone marrow DNA uncovered a tumor-specific rearrangement in the D delta-J delta region of this locus. DNA encompassing the rearrangement was isolated by molecular cloning, and further analysis revealed it to be the t(11;14)(p13;q11) junction. Nucleotide sequence determination of the junction indicates that the 14q11 breakpoint occurs immediately adjacent to the D delta 2 gene segment. Hence, the translocation arose as an aberrant rearrangement between the downstream recombination signal of D delta 2 and a pseudo recombination signal adjacent to the chromosome 11 breakpoint. Finally, comparison of the breakpoint in band 11p13 with those of other translocations (11;14)(p13;q11) identified a breakpoint cluster region of approximately 1.2 kilobase-pairs (kb), alterations of which may promote the development of T-ALL.

Base Sequence↗

Hospitalized schizophrenic patient views about seclusion.

Twenty-six of 100 consecutively admitted schizophrenic or schizoaffective patients required seclusion during their hospital stays. Seclusion episodes usually involved involuntarily committed, severely ill patients and occurred early in their hospitalizations. The recollections of the personal seclusion experiences of 17 patients were generally factually accurate, except for a tendency to play down disruptive aggressive behavior on their part. Patients described seclusion as a painful experience associated with feelings of helplessness, fear, sadness, and anger. However, patients also stated that seclusion rooms were necessary on inpatient psychiatric units and that the rooms were used for the control of disruptive aggressive patient behaviors. This study highlights not only the need for staff to clarify for patients what behavior has led to seclusion and what behavior will lead to release, but also the need for staff to acknowledge patients' distress at the experience.

Adult↗

Drop in heart rate following smoking cessation may be permanent.

Data are reported on the heart rates of nine smokers who underwent 5 weeks of abstinence. There was an initial fall of 9.1 beats per min from 79 to 69.9 beats per min on the 1st day, with no significant change thereafter. The average heart rates after 2, 3, 4 and 5 weeks were 69.1, 69.1, 71.7 and 69.9 beats per min, respectively. Heart rate after 5 weeks was still significantly below baseline. The results indicate that the drop in heart rate which occurs open smoking abstinence is either a permanent change, or if it is a temporary withdrawal effect lasts longer than 5 weeks. If it is a permanent change then it may not make sense to consider drop in heart rate as part of a withdrawal syndrome; it could merely reflect absence of nicotine's stimulant action.

Adult↗