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Biomedical subjects

N Levy

Publications and source records attributed to N Levy.

At least 91 records · Page 5Linked to original sources

Interleukin 6 induces DNA binding activity of AP1 in M1 myeloblastic cells but not in a growth resistant cell derivative.

The effects that three different growth inhibitory cytokines exert on expression and function of members of the Jun family were studied in this work. M1 myeloblastic cells were chosen for this purpose because of their high growth sensitivity to interleukin 6 (IL-6), transforming growth factor beta 1 and alpha- and beta-interferons. It is reported here that IL-6 elevated the junB and c-jun mRNA levels and induced the formation of a novel DNA-protein complex with high sequence specificity to 12-O-tetradecanoylphorbol-13-acetate response element (TRE) oligonucleotides. This IL-6 induced TRE binding complex was abolished by anti-Jun specific antibodies and was efficiently competed by an oligonucleotide that comprises the mouse homologue of a previously described human c-myc negative DNA element. It persisted in cells for at least 48 h after IL-6 treatment and failed to be induced by alpha- and beta-interferons or by transforming growth factor beta 1, which affected differently the pattern of jun mRNA expression. To further explore regulatory and functional aspects of this induced TRE binding activity, an IL-6 resistant M1 clone was isolated and further analyzed. This clone carried a postreceptor deficiency that abrogated completely the growth inhibitory responses to IL-6 but did not interfere with the induction of two differentiation related cell surface markers. Interestingly, the IL-6 resistant clone had lost two molecular responses to IL-6, induction of TRE binding activity and suppression of the c-myc gene. The data correlate the IL-6 induced AP1 activity with the suppression of c-myc and growth inhibition.

Animals↗

Utility of serum interleukin-6 for diagnosis of invasive bacterial disease in children.

STUDY OBJECTIVE: To evaluate measurement of interleukin-6 as a diagnostic test for the presence and severity of invasive bacterial disease. DESIGN: Prospective measurement of interleukin-6 in children with signs of sepsis. (Controls, retrospective from serum bank.) SETTING: Emergency department of an urban children's hospital. PARTICIPANTS: Twenty children with clinical signs of sepsis and 50 other febrile infants and toddlers with negative blood cultures. RESULTS: Eleven of the 20 patients had bacteriologically documented infections: four with meningitis and two with bacteremia caused by Neisseria meningitidis, three with meningitis caused by Haemophilus influenzae type b, and one each with meningitis and bacteremia caused by Streptococcus pneumoniae. Ten of these 11 had detectable interleukin-6. The geometric mean interleukin-6 level in these culture-positive patients was 407 pg/mL (95% confidence interval, 108 to 1,545); all three children with levels of more than 300 pg/mL developed septic shock, and one died. One of nine culture-negative patients with clinical signs of sepsis had detectable serum interleukin-6 (166 pg/mL), but none of 50 other febrile children without occult bacteremia did. The detection of interleukin-6 had a sensitivity of 91% and a specificity of 98% for invasive bacterial disease. CONCLUSION: High levels of interleukin-6 occur in children with septic shock, and the presence of interleukin-6 in serum is predictive for the isolation of bacteria from blood and/or spinal fluid.

Bacteremia↗

Hepatitis C virus is detected in a monocyte/macrophage subpopulation of peripheral blood mononuclear cells of infected patients.

Hepatitis C virus (HCV) is the primary agent of posttransfusion non-A, non-B hepatitis. HCV RNA was detected in peripheral blood mononuclear cells (PBMC) by polymerase chain reaction in 17 of 24 HCV-infected patients with chronic hepatitis with or without cirrhosis. One of 5 patients whose PBMC contained HCV RNA also had negative-stranded HCV RNA in the PBMC. In 3 of 11 patients whose PBMC contained HCV RNA, flow cytometry with a murine monoclonal antibody to HCV core epitope revealed cytoplasmic staining of peripheral blood monocytes. The monocyte surface and the peripheral blood lymphocytes did not stain for HCV core epitopes. No correlation could be made between the presence of HCV RNA or antigen in PBMC and any serologic markers of HCV infection. These results indicate that monocyte uptake of HCV by either phagocytosis or infection may be part of the pathophysiology of this chronic disease.

Adult↗

Cellular immunity in interstitial cystitis.

It has been suggested that interstitial cystitis is an autoimmune disease. The evidence for this hypothesis, based on studies of humoral immune factors, has been contradictory. We assessed the immune response in interstitial cystitis by evaluating lymphocyte populations in the peripheral blood and bladder tissue of interstitial cystitis patients. The lymphocyte phenotypes in peripheral blood were entirely normal, including the CD4 (cluster designation nomenclature) and CD8 subsets, and the CD4:CD8 ratio. Bladder lamina propria showed a predominance of CD4 over CD8 lymphocytes in interstitial and other forms of cystitis. Bladder epithelium showed a similar pattern in bacterial or mechanical cystitis but specimens from patients with interstitial cystitis had a predominance of CD8 cells. The findings of normal lymphocyte populations in the peripheral blood are not supportive of an autoimmune mechanism in the disease. The findings in bladder tissue show that the urothelium is not involved in the inflammatory reaction, as is the lamina propria, and they would suggest, therefore, that the initiating factor does not originate from the bladder lumen. The CD8 predominance in the urothelium along with a CD4 predominance in the lamina propria may form a characteristic pattern for the diagnosis of interstitial cystitis and merits further study.

Adult↗

Acquired immune dysfunction in cats with experimentally induced feline immunodeficiency virus infection: comparison of short-term and long-term infections.

Specific pathogen-free domestic cats with experimentally induced feline immunodeficiency virus (FIV) infections of short duration (less than or equal to 10 months) exhibited depressed total leukocyte and neutrophil numbers and a marginally decreased lymphocyte proliferative response to pokeweed mitogen (PWM), while cats with infections of more lengthy duration (greater than or equal to 25 months) exhibited normal leukocyte and neutrophil numbers but a dramatic loss of responsiveness to both PWM and concanavalin A (Con A). Cats with short-term infections exhibited a decrease in the percentage of CD4+ lymphocytes in peripheral blood and a corresponding depression of the CD4+:CD8+ ratio. Cats with long-term infections exhibited a similar but more profound perturbation of the CD4+ lymphocyte subset that also included a decrease in the absolute number of CD4+ cells. The decreased responsiveness to Con A and PWM in cats infected long term paralleled the decline in CD4+ cell counts, and the duration of infection was directly correlated with the decrease in the percentage of CD4+ cells. These data provide evidence supporting the hypothesis that FIV is the cause of an immune dysfunction in cats, with distinct similarities to that produced by human immunodeficiency virus (HIV) in people.

Acquired Immunodeficiency Syndrome↗

Chronic functional gastrointestinal symptoms in Holocaust survivors.

In Nazi-occupied Europe (1939-1945), Jews were submitted to extreme mental and physical hardships (the Holocaust). This study was designed to investigate the impact of the severe protracted suffering on the development of chronic functional gastrointestinal symptoms. Thus, we studied 623 consecutive patients of Eastern European origin who had been admitted for nongastrointestinal complaints. They filled out detailed questionnaires, and were divided into the following two groups: A) Holocaust survivors [237 subjects who had been for at least 6 months in either German concentration/extermination camps (95 subjects), ghetto and/or underground movements (65 subjects), labor camps not directly supervised by Germans (79 subjects)], and B) a control group (384 subjects from the same demographic background, who had not been exposed to Nazi persecutions). The symptoms investigated were the following: abdominal pain, irregular bowel habits, diarrhea, constipation, abdominal distension, heartburn, flatulence, anorexia, nausea, vomiting, mucus in stool, tenesmus, and aerophagia. Patients were defined as having functional symptoms after these had been present for at least 5 yr and relevant organic disease had been excluded. The prevalence, duration of suffering, and frequency of appearance of most symptoms were significantly higher in the group of Holocaust survivors. This study supports the clinical observations that severe and protracted suffering contributes to the development of chronic functional gastrointestinal symptomatology.

Aged↗

Brucellosis as a cause of severe colitis.

A 16-yr-old girl presented with osteomyelitis and massive rectal bleeding. Colonoscopy revealed severe nonspecific colitis. Multiple laboratory investigations failed to disclose the etiology of either the bone or colon infections. Empiric treatment with corticosteroids and sulfasalazine resulted in only transient improvement. One month after discharge, her original symptoms recurred. Blood and pus cultures at this time yielded Brucella melitensis. After tetracycline treatment, the patient recovered. At 1-yr follow-up, she was found completely asymptomatic. Although osteomyelitis is a well-known manifestation of brucellosis, colitis related to this agent has so far not been described.

Adolescent↗

Immunologic abnormalities in pathogen-free cats experimentally infected with feline immunodeficiency virus.

Blood mononuclear cells from 47 cats experimentally infected with feline immunodeficiency virus (FIV) were examined by using monoclonal antibodies directed against feline CD4 and CD8 homologs, a pan-T-cell antigen, and cell surface immunoglobulin. Significant inversion of the CD4+/CD8+ T-cell ratio was observed only in cats that were infected for 18 months or more. This inversion was associated with a decrease in the absolute numbers of CD4+ T cells and a concomitant increase in CD8+ cells. However, the total numbers of circulating T and B cells were not significantly reduced. Cats infected with FIV for 24 to 28 months also had significantly elevated levels of serum immunoglobulin G (IgG), but normal levels of IgA and IgM. The long-term decline in CD4+ T cells and hypergammaglobulinemia observed in FIV-infected cats resemble the abnormalities occurring in humans after human immunodeficiency virus infection.

Animals↗

Feline leukemia virus infection as a potentiating cofactor for the primary and secondary stages of experimentally induced feline immunodeficiency virus infection.

Preexistent feline leukemia virus (FeLV) infection greatly potentiated the severity of the transient primary and chronic secondary stages of feline immunodeficiency virus (FIV) infection. Of 10 FeLV-FIV carrier cats, 5 died of experimentally induced FIV infection, compared with 2 deaths in 10 cats infected only with FeLV and 1 death in 7 cats infected only with FIV. FIV-infected cats with preexistent FeLV infections developed severe depression, anorexia, fever, diarrhea, dehydration, weight loss, and leukopenia 4 to 6 weeks after infection and were moribund within 2 weeks of the onset of signs, whereas cats infected only with FIV developed much milder self-limiting gross and hematologic abnormalities. Pathologic findings in dually infected cats that died were similar to those observed previously in cats dying from uncomplicated primary FIV infection but were much more widespread and severe. Coinfection of asymptomatic FeLV carrier cats with FIV did not increase the levels of FeLV p27 antigen present in their blood over that seen in cats infected with FeLV alone. The amount of proviral FIV DNA was much higher, however, in dually infected cats than in cats infected only with FIV; there was a greater expression of FIV DNA in lymphoid tissues, where the genome was normally detected, and in nonlymphoid tissues, where FIV DNA was not usually found. Dually infedted cats that recovered from the primary stage of FIV infection remained more leukopenic than cats infected with FIV or FeLV alone, and their CD4+/CD8+ T-lymphocyte ratios were inverted. One of these cats developed what was considered to be an opportunistic infection. It was concluded, therefore, that a preexistent FeLV infection in some way enhanced the expression and spread of FIV in the body and increased the severity of both the resulting transient primary and chronic secondary stages of FIV infection. This study also demonstrated the usefulness of the FIV model in studying the role of incidental infectious diseases as cofactors for immunodeficiency-causing lentiviruses.

Animals↗

Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial.

A controlled double-blind trial was carried out to assess the effect of the early introduction of combined corticosteroid and beta-adrenergic drugs for the treatment of acute asthma in infants and toddlers. Seventy-four emergency room patients (aged 7 to 54 months) who were treated for acute asthma were studied. Treatment included, in addition to salbutamol inhalations, a single dose of intramuscular methylprednisolone (4 mg/kg) or normal saline as placebo. The patients were reevaluated 3 hours after initiation of treatment. At that time, patients were either admitted or discharged based on a clinical decision. Only 8 (20%) of 39 patients treated with steroids were admitted, compared with 15 (43%) of 35 in the placebo group (P less than .05). Sequential analysis of 33 pairs, matched by age and severity of symptoms, revealed statistically significant reduced admission rates in patients treated with steroids. In the younger patients (6 to 24 months), admission rate was significantly lower for those treated with steroids (18%) as compared with those treated without steroids (50%) (P less than .05). In the older group (24 to 54 months), the trend was similar but not statistically significant: 23% vs 31% in the steroid and placebo groups, respectively. These data indicate that corticosteroid treatment combined with an adrenergic agent, given early during an acute asthmatic episode, significantly reduces the hospital admission rate of infants and toddlers.

Acute Disease↗

Overt gastrointestinal bleeding in the course of chronic low-dose aspirin administration for secondary prevention of arterial occlusive disease.

We describe 13 patients who developed erosive gastritis with overt gastrointestinal bleeding while receiving 75-250 mg nonbuffered aspirin per day for the secondary prevention of cardiac or cerebrovascular events. The bleeding occurred despite good initial tolerance to aspirin for several months or years. All patients were elderly and had severe atherosclerotic cardiovascular disease. Our data suggest that, contrary to common belief, very low doses of nonbuffered aspirin are attendant with clinically apparent gastrointestinal complications.

Aged↗