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Biomedical subjects

I Goldberg

Publications and source records attributed to I Goldberg.

At least 145 records · Page 8Linked to original sources
PubMed1995

The fumR gene encoding fumarase in the filamentous fungus Rhizopus oryzae: cloning, structure and expression.

The filamentous fungus Rhizopus oryzae (Ro) is known for its ability to overproduce and accumulate high levels of fumaric acid (FA) under stress conditions. In order to study the molecular mechanisms involved in the increased biosynthesis of FA, the gene (designated fumR) encoding Ro fumarase was cloned and analysed for its structure and expression. Nucleotide (nt) sequence and comparison of the fumR product with fumarases from various sources established that fumR contains nine introns and encodes a deduced product of 494 amino acids (aa), related to class-II fumarases. A fumarase protein of 50 kDa was immuno-detected in crude Ro extracts. Primer extension experiments mapped the 5' end of the fumR RNA 159 nt upstream from the putative translation start codon. Both primer extension and Northern analysis showed the existence of one transcript of fumR. The level of fumR RNA increased in cells producing FA under stress conditions (high carbon and low nitrogen levels in the medium), suggesting that transcriptional regulation of fumR might be involved in the overproduction and accumulation of FA by Ro cells under stress conditions. The possibility that additional mechanisms are responsible for this phenomenon is discussed.

Amino Acid Sequence↗
PubMed1995

Bromocriptine immunomodulation of experimental SLE and primary antiphospholipid syndrome via induction of nonspecific T suppressor cells.

Bromocriptine (BRC) is a dopamine agonist that suppresses the secretion of prolactin by the pituitary gland and is known to have immunomodulating properties. In the present study, we investigated the effect of BRC on the development of two autoimmune experimental models: (i) systemic lupus erythematosus (SLE), induced by injection of a human anti-dsDNA monoclonal antibody (MIV-7); (ii) primary anti-phospholipid syndrome (PAPS), induced by injection of a mouse anticardiolipin monoclonal antibody (CAM). BRC had a suppressive effect on in vivo autoantibody production, as well as on the appearance of other manifestations of the respective disease. The BRC activity seems to be nonspecific, since the same effect was demonstrated in mice with lupus and with PAPS. These data were supported by the in vitro nonspecific effect of CD8 cells induced in vivo by bromocriptine, on specific lymph node cell proliferation in the presence of the pathogenic monoclonal antibodies (MIV-7 or CAM, respectively), and on the response to an irrelevant autoantigen, myelin basic protein. These data were complemented by the nonspecific suppressive effect by the T-suppressor factor, produced by the CD8 cells, on specific thymidine uptake by lymph node cells from experimental SLE or PAPS in the presence of the immunizing mAb. Injection of CD8 cells from BRC-treated mice with SLE or PAPS abolished the disease development in the lupus and PAPS experimental models. The data suggest a possible novel role of bromocriptine in downregulating autoimmune phenomena through induction of natural nonspecific CD8+ suppressor cells.

Animals↗
PubMed1995

The SMC proteins and the coming of age of the chromosome scaffold hypothesis.

The mechanism of chromosome condensation is one of the classic mysteries of mitosis. A number of years ago, it was suggested that nonhistone proteins of the chromosome scaffold fraction might help chromosomes to condense, possibly by constructing a framework for the condensed structure. Recent results have shown that topoisomerase II and the SMC proteins, two abundant members of the scaffold fraction, are required for chromosome condensation and segregation during mitosis. Topoisomerase II is a well-characterized enzyme. In contrast, nothing is yet known about the function of the SMC proteins. We summarize evidence suggesting that these proteins may be enzymes whose activity is somehow involved in the establishment and maintenance of mitotic chromosome morphology.

Animals↗
PubMed1995

Flash and pattern electroretinogram changes with optic atrophy and glaucoma.

We investigated recent reports that, contrary to common belief, glaucoma can affect flash as well as pattern electroretinograms. An extensive flash and pattern electroretinogram test protocol was used in a large sample of glaucoma patients and age-matched controls who were either visually normal or had other optic nerve diseases. All electroretinogram parameters were reduced and delayed in normal people > 55 years of age. The effect did not increase in later decades. In patients aged < or = 55 years, flash electroretinograms showed mild reductions and delays from optic atrophy alone. Glaucomatous ERG changes were larger and increased with disease severity. Pattern electroretinograms and oscillatory potentials were almost equally reduced in optic atrophy and all degrees of glaucoma. Mildly affected patients > 55 years of age had similar electroretinogram change to age-matched normals in most conditions. Advanced glaucoma patients showed similar differences from normal irrespective of age. This suggests that direct diagnostic application of these results to older patients will be difficult, that the ERG changes in glaucoma cannot be attributed simply to optic atrophy and that additional widespread outer retinal damage occurs in glaucoma.

Age Factors↗
PubMed1995

Sodwanones G, H, and I, new cytotoxic triterpenes from a marine sponge.

Three cytotoxic triterpenes, sodwanones G [5], H [6], and I [7], have been isolated from a marine sponge. The three structures were determined by interpretation of nmr spectra, and in the case of 5, also on the basis of the X-ray diffraction analysis. The X-ray diffraction analysis of two other earlier reported sodwanones, E [3] and F [4] is also discussed. The cytotoxic activity against several cancer cell lines, has been tested. IC50 values between 20 and 0.02 microM were obtained. Compounds 5 and 6 were 10- and 500-fold, respectively, more cytotoxic to A-549 cells than to any of the other cell lines tested (HT-29, MEL-28, P-388).

Animals↗
PubMed1995

Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine.

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocyte growth and contractility in vitro. This study was designed to investigate the effect of exogenous IGF-II on regional myocardial function at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anaesthetized pigs by affigel blue beads, embolizing microvessels of the left anterior descending coronary artery distribution. In the experimental group (n = 6), IGF-II (0.12 microgram.kg-1 in two animals and 0.6 microgram.kg-1 in four) was incorporated into the beads and delivered by them to the infarct area. Myocardial function was followed echocardiographically, and the excised heart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to an echocardiographic segmental wall motion score (mean +/- SEM), was similar between the two groups at baseline, but at 4 weeks post-infarction was significantly (P = 0.008) reduced in the control group (0.58 +/- 0.38 vs 3.42 +/- 0.84), in contrast to nearly baseline values in the experimental group (0.58 +/- 0.33 vs 1.17 +/- 0.42, P = 0.41). Cardiac performance in injured segments was significantly better after myocardial injury in the experimental group (P = 0.04). Tissue samples from both groups (4 weeks post-infarction), stained with haematoxylin and eosin demonstrated peri-infarct myocyte hypertrophy, corresponding to regions selectively stained by an antibody for CD56, which highlights growing cardiac myocytes. By image analysis semi-quantification, staining for CD56 was significantly (P = 0.04) higher in the peri-infarct region of the experimental group, as compared with controls (106.5 +/- 2.8 vs 92 +/- 4.4 gray level units). Microvessels stained for von-Willebrand factor were similar in number in both groups (P = 0.8), as were mesenchymal cells stained for vimentin (P = 0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area ameliorates regional cardiac function in the pig, perhaps by inducing peri-infarct myocyte growth.

Animals↗
PubMed1995

Betaxolol eye drops. A clinical trial of safety and efficacy.

OBJECTIVE: To study the cardiopulmonary safety and ocular hypotensive efficacy of topical betaxolol hydrochloride 0.5% (a selective beta-1 blocker) in patients with unacceptably elevated intraocular pressure (IOP) and respiratory dysfunction. METHODS: Thirty-one patients with poor control of elevated IOP were selected on the basis of coexistent respiratory disease which could be exacerbated by beta-antagonist administration and/or who had past adverse reactions to topical timolol. Using an open-label design, the ophthalmic, cardiovascular and pulmonary parameters of these patients were measured before betaxolol therapy, for four hours immediately after the first administration of the drug, and after one, four and 12 weeks of therapy. The screening and 12-week examinations included a bronchial challenge with methacholine, a non-specific bronchoconstricting agent. RESULTS: IOP reduction was significant at all time points measured after first instillation of betaxolol, with a mean maximum fall of 8.4 (SD, 3.2) mmHg (95% Cl -9.545 to -7.261) from a baseline mean IOP of 23.9 (SD, 3.8) mmHg. Over 12 weeks of therapy, the mean reduction from baseline in IOP was 3.9 (SD, 2.6) mmHg (95% Cl -4.908 to -2.988). After first instillation of betaxolol, mean arterial pressure (MAP) fell transiently to a mean maximum fall of 3.9 (SD, 9.3) mmHg (95% Cl -7.159 to -0.582), from a mean baseline MAP of 107.7 (SD, 9.4) mmHg. Heart rate did not change. There were no changes in any of the respiratory parameters measured: forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. Over 12 weeks of betaxolol therapy, there were no changes in any of the above systemic parameters and no change in mean bronchial reactivity as measured by methacholine challenge. Of the 31 patients, who included 13 patients with previous intolerance to timolol (a non-selective beta-antagonist), only one showed intolerance to betaxolol. CONCLUSIONS: Betaxolol appears to be an effective and well tolerated ocular hypotensive agent in a typical glaucoma population, which includes many patients with cardiopulmonary disease. Individual intolerance to betaxolol will continue to occur and care is always required when patients with cardiac or respiratory dysfunction are exposed to any beta-antagonist.

Aged↗
PubMed1995

Abrogation of experimental systemic lupus erythematosus and primary antiphospholipid syndrome with intravenous gamma globulin.

OBJECTIVE: To evaluate the effect of intravenous gamma globulin (IVGG) treatment on the immunological and clinical manifestations of experimental systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: BALB/c mice were actively immunized with anti-DNA (MIV-7) monoclonal antibodies (Mab) or anticardiolipin (aCL, CAM) Mab, to induce experimental SLE and primary APS, respectively. Eight weeks after immunization the mice were treated for 6 weeks with IVGG (whole molecule), F(ab')2, or Fc fragments. The following studies were carried out: autoantibody profile (ELISA), clinical manifestations including erythrocyte sedimentation rate (ESR), white blood cell and platelet count, immunoglobulin deposits in the kidneys, and fetal resorptions. The presence of antiidiotypic activity to anti-DNA and aCL antibodies in the IVGG was determined by inhibition studies employing the F(ab')2 as inhibitor. RESULTS: Following treatment with IVGG or IVGG F(ab')2, a complete clinical remission, manifested as normal ESR and leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated partial thromboplastin time, and fetal resorption rate in the mice with experimental primary APS was achieved. Autoantibody titers in the mice decreased to within normal levels. Treatment with Fc fragments had no effect upon those variables. Inhibition studies pointed to the presence of antiidiotypic activity to anti-dsDAN and aCL antibodies in the IVGG preparation. CONCLUSION: Treatment with IVGG can lead to clinical and immunological remission in mice with experimental SLE and primary APS. This effect may be carried out through manipulation of the idiotypic network and neutralization of pathogenic autoantibodies. Our results may justify the use of IVGG in patients with SLE and/or APS.

Animals↗
PubMed1995

C3, C4, factor B and HLA-DR alpha mRNA expression in renal biopsy specimens from patients with IgA nephropathy.

The deposition of complement in the kidney mesangium is a constant finding associated with renal injury in IgA nephropathy, even though IgA does not bind complement. We have previously reported that complement gene expression in the kidney increases concurrently with the progression of immune complex disease in murine lupus nephritis. We have now studied the expression of C3, C4, factor B and HLA-DR alpha mRNA by in situ hybridization in renal biopsy specimens of patients with IgA nephropathy and compared these findings to those in patients with other immune-mediated diseases of the kidney, hereditary nephritis and normal kidney. In IgA nephropathy, C3 and factor B mRNA were expressed in the renal tubular epithelial cells, while no expression of either C3 or factor B mRNA was apparent in the glomerulus. Specimens from patients with other immune-mediated forms of chronic glomerulonephritis also showed a similar pattern of expression of C3 and factor B mRNA only in the tubules, but not in the glomerules. However, C3 and factor B mRNA were not found in normal kidney tissue or biopsy specimens from patients with hereditary nephritis. C4 mRNA was expressed in the tubular epithelial cells in all specimens examined, indicating that C4 mRNA is constitutively expressed in the human kidney. In IgA nephropathy HLA-DR alpha mRNA was observed in the interstitium, but not the tubules or glomerular cells. In contrast, HLA-DR alpha mRNA was present in the glomerulus and scattered in the interstitium in other immune-mediated kidney diseases. There was no expression of HLA-DR alpha mRNA in hereditary nephritis or normal kidney. Our findings, which reflect the immunopathogenic events in vivo, provide new insights as to the interpretation of the molecular immunology of this immune complex disease.

Adolescent↗
PubMed1995

Induction of Goodpasture antibodies to noncollagenous domain (NC1) of type IV collagen in mice by idiotypic manipulation.

The characteristic pathogenic autoantibodies in Goodpasture's syndrome (GPS) are directed to the noncollagenous domain (NC1) of basement membrane type IV collagen. To examine whether immunization with anti-NC1 antibodies could lead to GPS-like pathology, naive BALB/c mice were immunized intradermally with a mouse IgG anti-NC1 monoclonal antibody or IgG serum fraction derived from patients with GPS. Mice immunized with normal mouse or human IgG and nonimmunized mice served as controls. Anti-NC1 antibodies of IgG isotype were detected in the sera of mice injected with anti-NC1 antibodies, but not in the sera of control mice. The presence of circulating anti-NC1 antibodies coincided in some of the mice erythrocyturia or proteinuria and pathological changes in the kidneys. No pathologic alterations were seen in the control mice. The results show that specific idiotypic manipulation can induce anti-NC1 antibodies and pathological changes resembling human GPS.

Animals↗
PubMed1994

Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth.

Magnetic resonance imaging at high spatial resolution and histochemical staining were applied to monitor the influence of tamoxifen versus estrogen on the growth, endothelial density, and extent of necrosis in tumors of MCF7 human breast cancer cells implanted in nude mice. Concomitantly with tamoxifen growth arrest, a highly significant decrease, by more than 2-fold, in the endothelial density of viable tumor regions had occurred, together with a significant increase in the extent of necrosis. The results suggest that the antiestrogenic activity of tamoxifen in breast cancer, which results in enhanced necrosis and tumor regression, is due to the inhibition of angiogenesis and of endothelial growth, thus reducing vascularization and impairing tumor perfusion.

Animals↗
PubMed1994

[Tendon interposition arthroplasty vs Kessler silicone prosthesis for basal joint arthritis of the thumb].

Of 86 patients with osteoarthrosis of the trapeziometacarpal or pantrapezial joint operated on during 1978-1988, 52 cases (14 males, 38 females) were reviewed. 32 had undergone interposition of the flexor carpi radialis tendon and 18 Kessler's silicone prosthesis technique. 2 had silicone prosthesis replacement in 1 hand and tendon interposition in the other. The average age of all patients was 65.5 years (range 56-74). Average follow-up was 7.0 years for the 32 after the interposition procedure (range 8-14), and 10.5 years (range 8-14) after prosthesis implantation. A greater proportion of those after tendon interposition reported alleviation of pain. There was no statistically significant difference between the groups with regard to patient satisfaction, need for job change, range of abduction and opposition, grip and pinch power, thumb length and ability in activities of daily living. Tendon interposition arthroplasty is simple and relatively inexpensive compared to silicone prosthesis insertion, which has inherent complications, such as breakage of the prosthesis and synovitis. Tendon interposition has therefore been our standard procedure since 1988.

Aged↗
PubMed1994

Role of scatter factor in the pathogenesis of AIDS-related Kaposi sarcoma.

Kaposi sarcoma (KS) is a complex multicellular neoplasm that is commonly associated with AIDS. The pathogenesis of KS is not well understood. KS tumor cells grow poorly in vitro and require medium conditioned by retrovirus-infected T lymphocytes. We observed that conditioned medium (CM) from type II human T-cell leukemia virus (HTLV-II)-infected T cells (HTLV-II CM) induces conversion of endothelial cells (ECs) to a KS tumor cell-like phenotype. ECs grown in HTLV-II CM acquired a spindle-shaped morphology, the ability to express factor XIIIa and other KS cell markers, and a cytokine production profile similar to that of KS cells. We found that HTLV-II CM contains large quantities of scatter factor (SF), an angiogenic cytokine that stimulates cell motility. SF induced ECs to become spindle-shaped and express factor XIIIa. Moreover, SF was found to be a mitogen for KS cells in vitro and was identified within KS lesions in vivo. SF mRNA was present in KS cells in vitro, and antibodies against SF inhibited the growth of KS cells. The receptor for SF, the c-met protein, was expressed by ECs, dermal dendrocytes, and KS tumor cells in vitro and in vivo. HTLV-II CM was highly angiogenic in vivo, which was blocked by antibodies against SF. Based on these findings, we suggest that SF plays a role in the initiation and maintenance of KS lesions.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Immunization with anticardiolipin cofactor (beta-2-glycoprotein I) induces experimental antiphospholipid syndrome in naive mice.

Beta-2-GPI is a 50 kDa glycoprotein which is known to be a serum co-factor, with a role in determining the binding of pathogenic anticardiolipin antibodies to phospholipids. Immunization of naive mice with beta-2-GPI resulted in elevated levels of antibodies directed against negatively charged phospholipids (cardiolipin, phosphotidylserine, phosphatidylinositol). The presence of increased titres of antiphospholipid antibodies in the sera of the mice was later followed by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, and when the mice were mated, by a high percentage of fetal resorptions in the uterus. These data point to the ability of beta-2-GPI to induce pathogenic anti-cardiolipin antibodies following active immunization.

Animals↗
PubMed1993

[Thumb reconstruction with microsurgical wrap-around neurovascular flap from big toe].

A 27-year-old man had his right dominant thumb amputated, together with skin from the dorsal area of the first metacarpal. Reconstruction was performed using a neurovascular flap taken from his right big toe. It consisted of skin and two-thirds of the distal phalanx, including the nail bed and digital plantar nerves. The vascular pedicle of the flap was formed by branches of the dorsalis pedis artery and the greater saphenous vein. The flap was wrapped around a bony scaffold formed by an iliac bone graft and inserted into the thumb. The revascularization of the flap was performed by connecting the end of the dorsalis pedis artery to the side of the radial artery, and the end of the greater saphenous vein to the end of cephalic vein. Reinnervation was achieved by connecting the plantar digital nerves to the stumps of the digital nerves of the thumb. 1 year later, the patient expressed full satisfaction with the appearance and good function of his reconstructed thumb.

Adult↗
PubMed1993

Cloning, expression, and characterization of a synthetic analog to the bioadhesive precursor protein of the sea mussel Mytilus edulis.

Repetitious gene cassettes that encode the consensus decapeptide repeat of Mytilus edulis bioadhesive protein were designed, constructed, and expressed in Escherichia coli. The bioadhesive precursor (BP) with a relative molecular mass of 25,000 was expressed from one 600-bp gene at levels approaching 60% of total cell protein in strains employing T7 RNA polymerase for induction and carrying a repetitious gene comprised of a 30-bp unit repeat that accounts for E. coli codon bias. BP forms intracellular inclusions and yet methionine was processed from the N-terminus of the purified protein, as shown by amino acid composition and N-terminal sequencing, to give an authentic consensus precursor protein.

Amino Acid Sequence↗