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Biomedical subjects

R Gertner

Publications and source records attributed to R Gertner.

At least 19 recordsLinked to original sources
PubMed2000

Distinct requirements for IFNs and STAT1 in NK cell function.

NK cell functions were examined in mice with a targeted mutation of the STAT1 gene, an essential mediator of IFN signaling. Mice deficient in STAT1 displayed impaired basal NK cytolytic activity in vitro and were unable to reject transplanted tumors in vivo, despite the presence of normal numbers of NK cells. IL-12 enhanced NK-mediated cytolysis, but poly(I:C) did not, and a similar phenotype occurred in mice lacking IFNalpha receptors. Molecules involved in activation and lytic function of NK cells (granzyme A, granzyme B, perforin, DAP10, and DAP12) were expressed at comparable levels in both wild-type and STAT1(-/-) mice, and serine esterase activity necessary for CTL function was normal, showing that the lytic machinery was intact. NK cells with normal cytolytic activity could be derived from STAT1(-/-) bone marrow progenitors in response to IL-15 in vitro, and enhanced NK lytic activity and normal levels of IFN-gamma were produced in response to IL-12 treatment in vivo. Despite these normal responses to cytokines, STAT1(-/-) mice could not reject the NK-sensitive tumor RMA-S, even following IL-12 treatment in vivo. Whereas in vitro NK cytolysis was also reduced in mice lacking both type I and type II IFN receptors, these mice resisted tumor challenge. These results demonstrate that both IFN-alpha and IFN-gamma are required to maintain NK cell function and define a STAT1-dependent but partially IFN-independent pathway required for NK-mediated antitumor activity.

Adaptor Proteins, Signal Transducing↗
PubMed2000

STAT1 affects lymphocyte survival and proliferation partially independent of its role downstream of IFN-gamma.

Lymphocytes derived from mice deficient in STAT1 showed reduced apoptosis and enhanced proliferation in vitro. To understand the involvement of STAT1 in the observed reduction in apoptosis, we examined the levels of caspase and bcl-2 family genes that are involved in cell survival and/or apoptosis. The levels of caspase 1 and 11, two enzymes involved in both cytokine protein processing and induction of apoptosis, were reduced in STAT1-/- cells compared with wild-type. However, the levels of bcl-2 genes were comparable in both mice. STAT1-/- cells also displayed an enhanced proliferation following TCR stimulation. This hyperproliferation could not be ascribed completely to the loss of IFN-gamma-mediated antiproliferation. First, similar phenotypes were also observed in fibroblasts and pre-B cells derived from STAT1-/- mice, which do not produce IFN-gamma. Second, comparisons with cells lacking the gene for IFN-gamma or with cells treated with neutralizing Abs to IFN-gamma only partially mimicked the STAT1-/- phenotype. Interestingly, the kinetics of degradation of p27kip1, a CDK inhibitor, following TCR ligation were faster, and, concomitantly, the up-regulation of CDK2 kinase activity and protein levels were increased in stimulated T cells of STAT1-/- mice relative to those of wild-type mice. Furthermore, STAT1-/- animals were more susceptible to carcinogen-induced thymic tumors, a possible consequence of altered T cell growth and/or survival. These results demonstrate an essential role for STAT1 for lymphocyte survival and proliferation that is only partially dependent on IFN-gamma signaling.

Animals↗
PubMed1999

FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway.

Several genetic forms of human dwarfism have been linked to activating mutations in FGF receptor 3, indicating that FGF signaling has a critical role in chondrocyte maturation and skeletal development. However, the mechanisms through which FGFs affect chondrocyte proliferation and differentiation remain poorly understood. We show here that activation of FGF signaling inhibits chondrocyte proliferation both in a rat chondrosarcoma (RCS) cell line and in primary murine chondrocytes. FGF treatment of RCS cells induces phosphorylation of STAT-1, its translocation to the nucleus, and an increase in the expression of the cell-cycle inhibitor p21WAF1/CIP1. We have used primary chondrocytes from STAT-1 knock-out mice to provide genetic evidence that STAT-1 function is required for the FGF mediated growth inhibition. Furthermore, FGF treatment of metatarsal rudiments from wild-type and STAT-1(-/-) murine embryos produces a drastic impairment of chondrocyte proliferation and bone development in wild-type, but not in STAT-1(-/-) rudiments. We propose that STAT-1 mediated down regulation of chondrocyte proliferation by FGF signaling is an homeostatic mechanism which ensures harmonious bone development and morphogenesis.

3T3 Cells↗
PubMed1998

The role of interferon in influenza virus tissue tropism.

We have studied the pathogenesis of influenza virus infection in mice that are unable to respond to type I or II interferons due to a targeted disruption of the STAT1 gene. STAT1-/- animals are 100-fold more sensitive to lethal infection with influenza A/WSN/33 virus than are their wild-type (WT) counterparts. Virus replicated only in the lungs of WT animals following intranasal (i.n.) virus inoculation, while STAT1-/- mice developed a fulminant systemic influenza virus infection following either i.n. or intraperitoneal inoculation. We investigated the mechanism underlying this altered virus tropism by comparing levels of virus replication in fibroblast cell lines and murine embryonic fibroblasts derived from WT mice, STAT-/- mice, and mice lacking gamma interferon (IFNgamma-/- mice) or the IFN-alpha receptor (IFNalphaR-/- mice). Influenza A/WSN/33 virus replicates to high titers in STAT1-/- or IFNalphaR-/- fibroblasts, while cells derived from WT or IFNgamma-/- animals are resistant to influenza virus infection. Immunofluorescence studies using WT fibroblast cell lines demonstrated that only a small subpopulation of WT cells can be infected and that in the few infected WT cells, virus replication is aborted at an early, nuclear phase. In all organs examined except the lung, influenza A WSN/33 virus infection is apparently prevented by an intact type I interferon response. Our results demonstrate that type I interferon plays an important role in determining the pathogenicity and tissue restriction of influenza A/WSN/33 virus in vivo and in vitro.

Administration, Intranasal↗
PubMed1997

Immune complex glomerulonephritis in patients coinfected with human immunodeficiency virus and hepatitis C virus.

Human immunodeficiency virus-associated nephropathy (HIVAN), characterized by heavy proteinuria, rapidly progressive renal failure, "collapsing" glomerulopathy, and tubulointerstitial abnormalities, is the most common finding in HIV-infected patients undergoing a renal biopsy and predominantly affects blacks. We describe the clinical features and renal pathologic findings of 12 intravenous drug users (IVDUs) coinfected with HIV and hepatitis C virus (HCV) who were selected for renal biopsy because they presented with features different from typical HIVAN, including hypertension, microscopic hematuria, and cryoglobulinemia. There were seven black and five Hispanic patients. Eleven patients had immune complex glomerulonephritis (ICGN); one had glomerulosclerosis with immune complex deposits. Ten individuals had evidence of past hepatitis B viral infection, but none had persistent hepatitis B surface antigenemia. No other underlying cause for immune complex glomerulonephritis was identified. Renal biopsy showed membranoproliferative glomerulonephritis in five patients, mesangial proliferative glomerulonephritis in five, membranous nephropathy in one, and "collapsing" glomerulopathy with immune complex deposits in one. Hepatitis C virus RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in the renal tissue and/or serum of nine of the 11 patients tested, and also in the renal biopsy tissue of four of eight patients with clinical and pathologic features of typical HIVAN without immunofluorescence evidence of immune complex deposits. One patient presented with renal failure, five patients developed end-stage renal disease (ESRD) requiring hemodialysis (mean time, 6.5 months), and six had stable renal function after a mean follow-up of 29.1 months (range, 2 to 72 months). Liver function abnormalities were present in seven of the 12 individuals, including four of the six patients who developed renal failure. These findings indicate that in some patients coinfected with HIV and HCV, the development of ICGN may dominate the clinical course of the disease. The occurrence of ICGN among black patients at risk for HIVAN may be related to the relatively high prevalence of HCV infection among IVDUs in this group.

AIDS-Associated Nephropathy↗
PubMed1993

Squamous cell carcinoma of the nasal septum mucosa.

Primary squamous cell carcinomas of the nasal septum constitute only 9% of all malignant tumors of the nasal cavity. We present 16 cases occurring during a 14-year period. As the initial signs of these carcinomas are no different from non-neoplastic disease, a high index of suspicion is necessary in order to correctly diagnose these lesions. It seems to us that when the diagnosis of nasal septum carcinoma is established, the best method of treatment is wide surgical excision and immediate repair of the defect by a split-skin graft.

Adult↗
PubMed1992

Late development of lateral sinus vein thrombosis.

The incidence of lateral sinus vein thrombosis has been reduced by the use of antibiotics, but it is still a major complication of middle ear disease. Patients without active acute or chronic middle ear infection, however, develop this deadly complication. CT scan is helpful in diagnosis, but mostly the final diagnosis is made by surgical exploration. A case of a 23-year-old patient who developed lateral sinus vein thrombosis without an active middle ear disease is presented. The pertinent literature is discussed.

Adult↗
PubMed1991

Unusual complication of an ingested foreign body.

Migration of a foreign body from the mouth and throat to the subcutaneous tissue of the neck is very rare. We present a case of a migrating foreign body (a piece of straw) from the floor of the mouth to the neck. To our knowledge, this is the second case reported in the English literature.

Abscess↗
PubMed1991

Incidence and treatment of deviation of nasal septum in newborns.

Four thousand and ninety consecutive newborns were investigated for nasal septal deviations over a two-year period in the Bnai Zion Medical Center, Haifa. An incidence of 0.93% of anterior nasal septal cartilaginous dislocation was found. No statistically significant correlation was observed between the newborns' weight and the nasal deformities. Definite correlation between the type of delivery and the nasal deformity was noted, however. The importance of early treatment during the first three days after birth is stressed. The infants were followed for a three-year period and no evidence of recurring septal deformity was noted. Birth trauma was first reported by Metzenbaum in 1929 as being a causative factor in nasal septal dislocation. Since then, it has been reported by other authors. Deviated nasal septum in the newborn is said to occur due to various intrauterine and transnatal pressures operating on the fetus. In 1963, Klaff reported 12 cases of septal dislocation in newborns and went on to describe the causative factors and methods of treatment. Gray investigated septal deformities in 2,380 infants at birth and found anterior cartilage deformity in 4%. He put forward a maxillary moulding theory of transmitted pressure during pregnancy or birth in an attempt to explain septal deformities in the newborn. Hartikainen et al. screened 4,724 newborns for congenital nasal deformities and found a 1.9% incidence of anterior septal dislocation. In this study no evidence of birth trauma as the cause of congenital nasal deformities was found and it was proposed that the majority of dislocations originated during intrauterine life. Collo reported correction of 19 birth traumatic nasal septal deviations by manual manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1991

Treatment of perennial allergic rhinitis with ascorbic acid solution.

The object of our study was to assess the therapeutic effects of Ascorbic Acid (AA) solution in patients suffering from perennial allergic rhinitis. Sixty patients were included in a two week randomized study. Synthetic AA Solution was found to decrease symptoms in 74% of patients, parallely there was a decrease of the pH of nasal secretion to normal limits.

Administration, Intranasal↗
PubMed1988

Liposarcoma of the larynx.

Liposarcomas of the larynx are very rare. Only nine cases appear to have been recorded in the English literature. An additional case of liposarcoma of the larynx occurring in a young patient is reported and the relevant literature discussed.

Adult↗
PubMed1988

Carbon-carbon middle ear prosthesis: a preliminary clinical human trial report.

In a variety of structural forms, carbon-carbon possesses certain properties that render it suitable for implantation in the human body. Twenty-four patients underwent tympanoplasty in which carbon-carbon was used as an alloplastic material for reconstructing the ossicular chain; these patients were followed for a period of 9 to 15 months. The good anatomic and hearing results of our clinical trial led us to suggest the carbon-carbon prosthesis as an alternative alloplastic material to be used in tympanoplasties.

Adolescent↗
PubMed1987

Treatment of perennial allergic rhinitis by sodium cromoglycate plus 0.025 per cent xylometazoline (a double-blind study).

The object of this double-blind study was to assess the therapeutic effects of a combination of two per cent sodium cromoglycate and 0.025 per cent xylometazoline compared with a matched placebo. Forty patients were included in the two-week study. The treatment was found to be rapidly effective taking only a day to control symptoms in almost 80 per cent of the patients in the group receiving active treatment. No evidence of rebound effects due to the decongestant was observed during the study.

Adolescent↗
PubMed1986

Rhabdomyoma of the larynx.

Since 1897 a total of 37 cases of extracardiac rhabdomyomas of the fetal type have been reported in the literature. Only two of these were localized in the larynx. We report an additional case of extracardiac rhabdomyoma localized in the larynx, and the pertinent literature is discussed. Although rare, its existence should be kept in mind in the differential diagnosis of laryngeal tumours.

Aged↗
PubMed1986

Auditory brain stem evoked potentials in patients suffering from peripheral facial nerve palsy and diabetes mellitus.

Forty-two patients affected by acute idiopathic peripheral facial palsy (AIPFP) underwent auditory brainstem evoked potential (ABEP) investigation in order to further our understanding of the nature of facial palsy. Twenty-two of these patients suffered from diabetes mellitus. Our results indicate that the AIPFP of the diabetic person may be considered as a preliminary sign of diabetic peripheral neuropathy.

Adult↗