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Biomedical subjects

H Gur

Publications and source records attributed to H Gur.

At least 19 recordsLinked to original sources
PubMed2001

Polyarteritis nodosa in patients with Familial Mediterranean Fever (FMF): a concomitant disease or a feature of FMF?

BACKGROUND: Familial Mediterranean Fever (FMF) is caused by mutations in the gene encoding pyrin and is characterized by self-limited, recurrent attacks of fever and serositis. Vasculitis has been increasingly reported in FMF. A study evaluating the prognosis in FMF and polyarteritis nodosa (PAN) patients has not been reported previously. OBJECTIVES: To determine the special characteristics and the prognosis of PAN in FMF patients. METHODS: A questionnaire was used for the present survey. The setting was 7 referral centers from Turkey and Israel. Seventeen patients who were diagnosed with FMF and who developed PAN were included. PAN was diagnosed in those who met the Chapel Hill consensus criteria for microscopic polyarteritis or classic PAN. The clinical features of these 17 patients and the outcomes of their vasculitis were analyzed. RESULTS: The age at diagnosis of PAN in these FMF patients ranged from 3.5 to 37 years. All patients had constitutional symptoms, elevated acute phase reactants, and myalgia at the time PAN was diagnosed. The diagnosis of PAN was confirmed by renal angiography in 8 patients, by renal biopsy in 6 patients, and by muscle and/or nodule biopsies in 6 patients. A number of patients had definite features of both classic PAN and microscopic polyarteritis. CONCLUSIONS: When compared with other PAN patients, those with FMF tended to have a younger age at PAN onset, more frequent perirenal hematomas, and an overall better prognosis. The cases with overlapping features of microscopic and classic PAN pose a problem for the current classification of vasculitis. We suggest that the clinical representation of PAN in FMF patients has certain characteristics and may be a feature of FMF per se.

Adolescent↗
PubMed2001

Pulmonary-renal syndrome in systemic sclerosis.

BACKGROUND AND OBJECTIVE: Renal failure, pulmonary hypertension, and interstitial lung disease are major causes of morbidity and mortality in systemic sclerosis (SSc). However, the concomitant occurrence of pulmonary hemorrhage associated with acute renal failure in SSc has been rarely described. The present study is the first analysis of pulmonary-renal syndrome in SSc. PATIENT AND METHODS: We present a 44-year-old woman with SSc who died of a fulminant course of acute renal failure associated with diffuse alveolar hemorrhage. We termed this uncommon and fatal complication of SSc scleroderma-pulmonary-renal syndrome (SPRS). A search of the English-written literature yielded reports of 10 additional similar cases. These patients, together with our present case, form the basis of the present analysis. RESULTS: The average age of the patients with SPRS was 46 years. The majority of the patients (80%) were women, and most had diffuse SSc. SPRS occurred an average of 6.4 years after disease onset and was associated with prior fibrosing alveolitis and/or D-penicillamine treatment. Interestingly, normotensive renal failure seems to characterize the scleroderma patients, because 9 of 11 (82%) had normal blood pressure. SPRS bears a poor prognosis: all of the 11 patients (100%) died within 12 months of admission. However, only 60% of the 5 patients for whom we have treatment data received corticosteroids. CONCLUSIONS: Pulmonary-renal syndrome is a rare but fatal complication of SSc. Because the treatment data are scarce and the prognosis is poor, aggressive treatment with pulse corticosteroids, cyclophosphamide, and possibly plasmapheresis is suggested.

Acute Kidney Injury↗
PubMed2000

Delivery of cytokines by liposomes: hematopoietic and immunomodulatory activity of interleukin-2 encapsulated in conventional liposomes and in long-circulating liposomes.

Although liposomal delivery of interleukin-2 (IL-2) and other cytokines improves their pharmacokinetics and biologic activity in vivo, there are no comparative functional studies of various liposomal formulations as cytokine carriers. In the present investigation, recombinant human IL-2 was encapsulated in two formulations of large (mean diameter 0.75-1.5 microns) multilamellar vesicles (MLV, referred to as conventional liposomes) or in small (mean diameter, 60 nm), unilamellar, long-circulating liposomes (referred to as sterically stabilized liposomes, SSL). The biologic activity of the liposomal formulations and of free IL-2 was tested in parallel in vitro and in mice. The main observations were as follows: (a) All the liposomal IL-2 (Lip-IL-2) formulations were more efficient than soluble IL-2 in stimulating spleen cell proliferation and lymphokine-activated killer (LAK) cell activation in vitro, particularly at low cytokine doses (1-100 CU/mL). (b) After i.v. injection, the circulation time of MLV-IL-2 and SSL-IL-2 was 7 and 17 times greater, respectively, than that of soluble IL-2. (c) In comparison with IL-2, all Lip-IL-2 formulations caused a marked increase in the leukocyte levels in blood, spleen, and peritoneal exudate, especially in those of myeloid origin (neutrophils, eosinophils, immature granulocytes, and macrophages). (d) Although SSL-IL-2 exhibited the longest circulation time, MLV-IL-2 was more potent in elevating leukocyte levels and in triggering LAK cell activity in vivo. (e) The route of Lip-IL-2 administration greatly affected the immunomodulatory activity in the various compartments. (f) MLV-IL-2 proved to be a much more efficient immunoadjuvant than free IL-2 for influenza subunit vaccines as well as for tumor cell vaccines. These findings lend support to our previous studies in which we demonstrated the superior immunomodulatory activity of liposomal IL-2, and suggest that cytokine pharmacokinetics, biodistribution, and pharmacodynamics are markedly influence both by liposomal formulation and route of administration.

Adjuvants, Immunologic↗
PubMed2000

Systemic vasculitis presenting as a tumorlike lesion. Four case reports and an analysis of 79 reported cases.

Systemic vasculitis might present as a tumorlike lesion that initially could misdirect the correct diagnosis and the appropriate medical treatment. The aim of the present study is to summarize all reported cases of tumorlike presentation in systemic vasculitides, in order to have comprehensive data on the characteristics of this unusual phenomenon. We report 4 cases of systemic vasculitis presenting as a tumorlike lesion. In addition, we performed a MEDLINE search of all English-language papers published from 1966 to 1999, looking for vasculitis presenting as tumorlike lesion. Details were included concerning vasculitis classification, specific characteristics, location of the "tumor," the presence or absence of systemic involvement, and whether surgery was performed before diagnosis. Seventy-nine cases of vasculitis presenting as a tumorlike lesion were found in the literature, in addition to the 4 new cases described. The average age of the reported cases was 50.5 +/- 15.8 years, and 51% were female. In 82% of the cases the "tumor" was associated with constitutional symptoms and elevated erythrocyte sedimentation rate (ESR). The most common vasculitis categories with tumorlike presentation were Wegener granulomatosis (WG; 28 cases) and giant cell arteritis (GCA; 17 cases). In almost half the patients, surgery was performed before diagnosis. All patients with GCA presented with either a breast or an ovarian tumor. The most common location of a tumorlike lesion was the breast (22%), followed by central nervous system lesions (16%). Other frequent locations were the ovary (10%), caused exclusively by GCA and polyarteritis nodosa (PAN), and the male genitourinary system, almost all caused by PAN. Including vasculitis in the differential diagnosis of a tumorlike lesion might lead to an earlier diagnosis and consequently to prompt and appropriate treatment, avoiding needless operations. Constitutional symptoms and elevated ESR should alert clinicians to the possible diagnosis of vasculitis rather than a tumor. The association of GCA with ovarian pseudotumor is distinct and has not been emphasized before. We therefore suggest that GCA should be included in the list of differential diagnosis of an ovarian or breast tumor in an elderly woman, particularly when systemic symptoms and parameters of inflammation are present.

Adult↗
PubMed2000

Aspergillus niger endocarditis in an immunocompetent patient: an unusual course.

Aspergillus is an opportunistic nosocomial fungus generally associated with a high mortality rate. A niger has been rarely associated with infection, and most cases have occurred in patients who have recently undergone heart surgery or in immunocompromised patients. We present a case of an immunocompetent patient with A niger endocarditis which illustrates the difficulties in diagnosis and the possible insidious course of fungal endocarditis.

Aspergillosis↗
PubMed2000

Aortic aneurysm and dissection are not associated with an increased risk for giant cell arteritis/ polymyalgia rheumatica.

It has recently been claimed that giant cell arteritis (GCA) is associated with a markedly increased risk of aortic aneurysm formation or rupture. In the present study, the opposite approach was taken, by looking for the incidence of GCA and polymyalgia rheumatica (PMR) in patients with aortic aneurysm, aortic dissection, or both (AA/D). The records of 315 consecutive patients admitted with the diagnosis of AA/D were reviewed. In addition, follow up information was obtained in 82 patients by examination in the outpatient clinic. After careful examination and assessment of clinical and laboratory data, it was found that none of the 82 patients who survived hospitalisation and were available for examination had GCA or PMR. Moreover, review of the retrospective data available from hospital records of the total consecutive 315 patients with AA/D failed to find any patient with a diagnosis of GCA/PMR. In conclusion, the present study did not find an increased prevalence of GCA/PMR among a cohort of Israeli patients with AA/D. Therefore, it is suggested that a thorough investigation aiming to diagnose GCA/PMR is not cost effective in most of the elderly patients presenting with AA/D.

Aortic Dissection↗
PubMed1999

Induction of donor-type chimerism and transplantation tolerance across major histocompatibility barriers in sublethally irradiated mice by Sca-1(+)Lin(-) bone marrow progenitor cells: synergism with non-alloreactive (host x donor)F(1) T cells.

Induction of transplantation tolerance by means of bone marrow (BM) transplantation could become a reality if it was possible to achieve engraftment of hematopoietic stem cells under nonlethal preparatory cytoreduction of the recipient. To that end, BM facilitating cells, veto cells, or other tolerance-inducing cells, have been extensively studied. In the present study, we show that BM cells within the Sca-1(+)Lin(-) cell fraction, previously shown to be enriched for early hematopoietic progenitors, are capable of reducing specifically antidonor CTL-p frequency in vitro and in vivo, and of inducing split chimerism in sublethally 7-Gy-irradiated recipient mice across major histocompatibility complex barriers. The immune tolerance induced by the Sca-1(+)Lin(-) cells was also associated with specific tolerance toward donor-type skin grafts. The minimal number of cells required to overcome the host immunity remaining after 7 Gy total body irradiation is very large and, therefore, it may be very difficult to harvest sufficient cells for patients. This challenge was further addressed in our study by demonstrating that non-alloreactive (host x donor)F(1) T cells, previously shown to enhance T-cell-depleted BM allografts in lethally irradiated mice, synergize with Sca-1(+)Lin(-) cells in their capacity to overcome the major transplantation barrier presented by the sublethal mouse model.

Animals↗
PubMed1999

Experimental autoimmune encephalomyelitis induced in B6.C-H-2bm12 mice by myelin oligodendrocyte glycoprotein: effect of MHC class II mutation on immunodominant epitope selection and fine epitope specificity of encephalitogenic T cells.

The effect of the bm12 mutation on susceptibility to MOG-induced EAE, TCR repertoire and fine epitope specificity of the encephalitogenic T-cells, was assessed. prMOG35-55 was encephalitogenic for H-2bm12 and H-2b mice. Despite only minor differences in TCRVbeta expression and fine epitope specificity, H-2bm12/ and H-2b/prMOG35-55-specific T-cells failed to recognize Ab/prMOG35-55 and Abm12/prMOG35-55, respectively. rhMOG-induced EAE was milder in H-2bm12 mice, possibly as a result of co-dominant responses to prMOG35-55 and to the non-encephalitogenic pMOG94-116, rather than a single dominant response to prMOG35-55 in H-2b mice.

Amino Acid Sequence↗
PubMed1999

The cytoplasmic and the transmembrane domains are not sufficient for class I MHC signal transduction.

Class I MHC molecules deliver activation signals to T cells. To analyze the role of the cytoplasmic and the transmembrane (TM) domains of class I MHC molecules in T cell activation, Jurkat cells were transfected with genes for truncated class I MHC molecules which had only four intracytoplasmic amino acids and no potential phosphorylation sites or native molecules or both. Cross-linking either the native or the truncated molecules induced IL-2 production even under limiting stimulation conditions of low engagement of the stimulating mAb. Moreover, direct comparison of transfected truncated and native class I MHC molecules expressed on the same cell revealed significant stimulation induced by cross-linking the truncated molecules, despite low expression. In addition, truncated class I MHC molecules were as able to synergize with CD3, CD2, or CD28 initiated IL-2 production as native molecules. In further experiments, hybrid constructs made of the extracellular portion of the murine CD8 alpha chain and of the TM and the intracytoplasmic domains of H-2Kk class I MHC molecule were transfected into Jurkat T cells. The expression of the transfected hybrid molecules was comparable to that of the native HLA-B7 molecules. Cross-linking the intact monomorphic HLA-A,B,C epitope or the polymorphic HLA-B7 epitope induced IL-2 production upon costimulation with PMA. In contrast, cross-linking the hybrid molecules generated neither an increase in intracellular calcium concentration ([Ca2+]i) nor stimulated IL-2 production. By contrast, cross-linking intact murine class I MHC molecules induced [Ca2+]i, signal and IL-2 production in transfected Jurkat cells. The data therefore indicate that unlike many other signaling molecules, signaling via class I MHC molecules does not involve the cytoplasmic and the TM portions of the molecule, but rather class I MHC signal transduction is likely to be mediated by the extracellular domain of the molecule.

Animals↗
PubMed1999

Effect of the bm12 class II mutation on proliferative and cytokine responses of encephalitogenic T cells in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis.

The bm12 mutation in the class II I-A(b)molecule can profoundly influence experimental autoimmune disease, enhancing the development of systemic lupus erythematosus-like syndromes in NZB.H-2(bm12)mice or, conversely, abolishing the susceptibility of C57BL/6J (H-2(b)) mice to the induction of experimental autoimmune myasthenia gravis. We have studied the effect of this mutation on experimental autoimmune encephalomyelitis (EAE), induced in H-2(b)mice by myelin oligodendrocyte glycoprotein (MOG), and recently showed that MOG 35-55 peptide (pMOG 35-55), which represents the immunodominant encephalitogenic region for H-2(b)mice, is also a strong encephalitogen for H-2(bm12)mice. Nevertheless, although the differences in fine epitope specificity and TCR-Vbeta gene usage between encephalitogenic pMOG 35-55-specific T cells from H-2(b)and H-2(bm12)mice were subtle, H-2(bm12)and H-2(b)antigen presenting cells failed to effectively cross-present pMOG 35-55 non-syngeneically to I-A(b)/pMOG 33-55- and I-A(bm12)/pMOG 35-55-specific T cells, respectively. In the present study, we show that the abrogation of the response to pMOG 35-55 by the Th1 encephalitogenic pMOG 35-55-specific T cells upon non-syngeneic cross-presentation is neither due to a cytokine shift to a Th2 pattern, nor a result of anergy induction. Therefore, we suggest that presentation of pMOG 35-55 to I-A(b)/pMOG 35-55-specific T cells via the bm12 class II MHC molecule resulted in ineffective stimulation, similar to a weak agonistic effect.

Animals↗
PubMed1999

Polyarteritis nodosa: a report from Israel.

BACKGROUND: The clinical manifestations and outcome of all adult patients with polyarteritis nodosa (PAN), allocated during a 15-year period in the largest medical center in Israel, were examined. METHODS: A retrospective analysis of patients with PAN who fulfilled the American College of Rheumatology (ACR) 1990 Classification Criteria and were either biopsy- or angiography-proven. RESULTS: Nine patients were included in the report. The clinical and laboratory manifestations were similar to those in previous studies. All patients were treated with combinations of cyclophosphamide and corticosteroids. There were two (22%) deaths, 2 and 5 months after initiation of treatment in patients who probably had microscopic polyangiitis (MPA) rather than classical PAN. Considering the patients with a complete follow-up, 71% had a complete and long-term remission. Moreover, by exclusion of the two patients with probable MPA who died, all of the five patients with classical PAN were alive and well as of this writing. Two patients (22%) had a long history, since childhood, of familial Mediterranean fever (FMF). CONCLUSIONS: The clinical presentation and course of PAN in Israeli patients is comparable with reports elsewhere. However, a distinction should be made between PAN and MPA. The present report emphasizes the good long-term prognosis of patients with typical PAN who are treated adequately. In addition, a possible association of PAN with FMF in Israeli patients is suggested.

Adult↗
PubMed1999

Rheumatologic features of hematologic disorders.

This review focuses on the various rheumatologic manifestations of hematologic diseases and is based on the English literature published over the past year. Interrelationships between leukemia, lymphoma, POEMS syndrome, multiple myeloma, hemophilia, and rheumatic manifestations are discussed. Other less common associated conditions dealt with include the RS3PE syndrome, large granular lymphocyte syndrome, and interferon-related arthritis. Finally, therapeutic measures, such as bone marrow transplantation and the use of granulocyte colony-stimulating factor, are reviewed.

Antineoplastic Agents↗
PubMed1999

The epidermotropic mycosis fungoides associated alpha1beta1 integrin (VLA-1, CD49a/CD29) is primarily a collagen IV receptor on malignant T cells.

Several of the beta1 integrin receptors [very late antigen (VLA) molecules] for extracellular matrix (ECM) proteins are expressed by malignant T cells in cutaneous T-cell lymphoma (CTCL). We evaluated the function of VLA-1, a beta1 integrin specifically expressed in epidermotropic mycosis fungoides (MF), in CD4+ leukemic T cells Jurkat line). We found that Jurkat cells adhere significantly to collagens only after their activation with phorbol 12-myristate 13-acetate (PMA). However, the adhesion to collagen IV (but not to collagen I) of Jurkat cells selected for expressing increased levels of VLA-1 (with unchanged levels of VLA-2, the second collagen integrin receptor) was significantly enhanced relative to that of "VLA-1 low" cells. Monoclonal antibody (mAb) 1B3.1, directed against the collagen binding domain of VLA-1, inhibited adhesion to collagen IV and to collagen I by 36.67%+/-5.25% and 18%+/-4.32%, respectively (p<0.05), whereas the inhibition by anti-VLA-2 mAb PIE6 was comparable on both collagens (25%+/-7.48% and 36.3%+/-0.94%, respectively; p<0.09). Immuno-histochemical studies of skin biopsies from 10 untreated MF patients showed that in all cases at least 10% of the lymphocytes residing in the epidermis are VLA-1+VLA-2-. While not directly applicable to MF, the demonstrated functions of VLA-1 in leukemic Jurkat cells, together with its expression in MF skin, suggest a role for VLA-1 integrins in epidermotropism in a small proportion of leukemic MF cells.

Antigens, CD↗
PubMed1999

Efficacy and safety of intravenous amiodarone in recent-onset atrial fibrillation: experience in patients admitted to a general internal medicine department.

We examined the efficacy and safety of intravenous amiodarone in 20 unselected patients with recent-onset atrial fibrillation who were admitted to a general internal medicine department during a 6-month period. The treatment protocol included a loading dose of 1200 mg intravenous amiodarone in 24 hours, after which amiodarone treatment was continued orally. Eleven of the 20 patients (55%) converted to sinus rhythm within 48 hours of intravenous amiodarone treatment and were discharged in sinus rhythm, while 9/20 (45%) patients failed to convert during hospitalisation. Six patients (30%) failed to convert to sinus rhythm even after one further month of oral treatment. There was one death and a high frequency (25%) of thrombophlebitis during hospitalisation. The in-hospital non-convertors had a significantly lower ejection fraction and initial low ventricular response rate than the convertors. In conclusion, the acute conversion rate by intravenous amiodarone was at best modest. It is suggested that intravenous amiodarone is probably more effective in patients with rapid recent-onset atrial fibrillation and good left ventricular function.

Aged↗