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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 127 records · Page 7Linked to original sources
PubMed1995

Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid.

Pubertal mammary development in the rat is largely dependent upon GH and estrogen. We recently showed that insulin-like growth factor-I (IGF-I) can substitute for GH in inducing mammary development in male rats, suggesting that IGF-I mediates GH action. The present study investigated whether IGF-I, like GH, required estradiol (E2) to act or whether IGF-I could substitute for both GH and E2. The effects of IGF-I were tested in the presence and absence of E2. Elvax pellets containing IGF-I or des(1-3) IGF-I were implanted into right lumbar mammary glands of sexually immature, hypophysectomized, oophorectomized female rats, with control BSA-containing pellets in the contralateral glands. After 5 days, both lumbar mammary glands were removed and examined in whole mounts for mammary development by counting terminal end buds and alveolar structures. E2, administered in SILASTIC brand capsules, had no independent effect on mammary development. In the absence of E2, des(1-3) IGF-I had a small, but significant, independent effect on mammary development; native IGF-I was ineffective. The addition of E2 significantly enhanced the effects of IGF-I and des(1-3) IGF-I on mammary development, similar to that noted when E2 was given along with GH. We also studied the effects of E2 and/or hGH on mammary gland IGF-I messenger RNA (mRNA) in hypophysectomized castrated male animals. E2 alone did not increase mammary gland IGF-I mRNA concentrations, but E2 enhanced the effect of hGH on IGF-I mRNA by 4- to 6-fold. These studies indicate that IGF-I can have a small independent effect on mammary development, but like GH, E2 is required for a full effect. They also indicate that E2 is capable of synergizing with GH in the production or expression of IGF-I mRNA, and that the action of E2 on mammary development may take place at multiple sites. If locally produced IGF-I does indeed mediate the action of GH in mammary development, then although E2 is capable of enhancing the effect of GH on IGF-I mRNA, its major effect in mammary development occurs after IGF-I is produced.

Animals↗
PubMed1995

The Mini Mental State Exam as a predictor of neuropsychological functioning after cardiac surgery.

OBJECTIVE: The present longitudinal study was designed to: 1) determine the ability of the Mini Mental State Exam (MMSE) to predict neuropsychologic impairment based on neuropsychologic testing five to seven days and six weeks after cardiac surgery; and 2) to determine whether the traditional or the education-related MMSE norms are more appropriate to use for this purpose. METHOD: The day before surgery (T1), before hospital discharge (T2), and six weeks after surgery (T3), 247 subjects completed a battery of five neuropsychologic tests. Subjects also completed the Center for Epidemiological Studies Depression Scale and the Speilberger State-Trait Anxiety Inventory. Subjects completed the MMSE two to three days after surgery. RESULTS: Stepwise regression analyses revealed that the MMSE significantly predicted only a small portion of the variance in neuropsychologic test performance at T2, and to an even lesser extent at T3, over and above the demographic variables. In assessing the association between an impairment score (derived from the neuropsychologic test battery) and the MMSE, we found that the traditional MMSE cut-off score maximized specificity (number of true negatives) while the education-adjusted MMSE cut-off scores maximized sensitivity (number of true positives). CONCLUSIONS: These results suggest that although the MMSE is widely used to assess cognitive mental status, it may have limited value in identifying patients with cognitive impairment post-cardiac surgery, and special attention must be paid to the cut-off scores used in interpreting the MMSE.

Adult↗
PubMed1995

Are CD4 and Fas peptide identities of gp120 relevant to the molecular basis of AIDS pathogenesis?

The release of virions from HIV-1-infected CD4 cells, although occurring readily as a result of immune activation, does not appear to be the only mechanism mediating T-cell loss in AIDS. Three other interacting HIV-1-induced immune disorders in association with viral release (the source of gp120 molecules) may also account for the constitutive T-cell depletion and functional immune suppression: 1. gp120-induced CD4(+) cell anergy, which can be reproduced in cultures of immune activated normal T-cells in the presence of gp120 or gp120 peptide containing the SLWDQ sequence identity to the CD4 molecule; 2. overproduction of IFNalpha and gamma, 3. activation-driven apoptosis of non infected T-cells. Apoptosis of T-cells could also be: 1. induced by effector components - particularly CTL and lymphotoxins produced by helper T-cells of the anti-Fas autoimmune reaction triggered by gp120 epitopes shared with the Fas/APO-1 molecule; 2. enhanced by IFN overproduction. These molecular mechanisms stress the importance in the progression to AIDS of both the viral load and HIV-induced cytokine dysregulation, including overproduction of IFNalpha, which should be considered as targets in the development of strategies for AIDS prophylaxis and immunotherapy.

Journal Article↗
PubMed1995

Rop and Ras2, members of the Sec1 and Ras families, are localized in the outer membranes of labyrinthine channels and vesicles of Drosophila nephrocyte, the Garland cell.

The product of the ras opposite (rop) gene is an essential component of secretion processes in Drosophila. The rop gene product is homologous to the Caenorhabditis elegans UNC-18 and the rat munc-18/n-Sec1/rbSec1 proteins, implicated in the final steps of neurotransmitter exocytosis in nerve terminals, and the bovine mSec1 protein implicated in the secretion of catecholamines in chromaffin cells. The mammalian brain protein has been shown to exert its activity in the presynaptic membrane through transient interaction with syntaxin, an integral component of this membrane. rop is highly expressed in the Drosophila nervous system, where it acts as both a positive and negative modulator of neurotransmitter release. It is also expressed in specialized tissues in which intensive exocytic/endocytic cycles take place, including the garland cells, a small group of nephrocytes which take up waste materials from the hemolymph by endocytosis. rop is regulated by a bidirectional promoter shared with Ras2, a member of the R-ras/TC21 branch of the ras supergene family. Ras2 is also highly expressed in the garland cells. These cells are characterized by their labyrinthine channels, long invaginations extending from the cell membrane, and a rich population of a variety of vesicles. In this study, we analyzed the ultrastructural localization of the Rop and Ras2 proteins in the garland cell. Rop was detected in the outer membranes of the labyrinthine channels, and in the outer membranes of many vesicles located nearby the labyrinthine channels, but not in vesicles located in inner parts of the cell. Using glutathione-S-transferase-syntaxin fusion, we show that Rop is firmly bound to syntaxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Expression of two H-2K genes, syngeneic and allogeneic, as a strategy for potentiating immune recognition of tumor cells.

Metastatic clones of some tumors manifest an impaired expression of class I major histocompatibility complex (MHC) antigens. High metastatic, low immunogenic Lewis lung carcinoma clones (C57BL-H-2b origin) express low levels of the H-2Kb MHC antigen. These cells metastasize spontaneously in C57BL/6J mice. Transfection of syngeneic or allogeneic H-2K genes converted such cells to the nonmetastatic state, but did not prevent the growth of the local tumors. Transfection of two H-2K genes, syngeneic and allogeneic, into the highly metastatic clone D122, resulted in reduction of the growth rates of the transfectants and protected the mice from D122 metastases. In contrast, cells transfected with a single class I gene (syngeneic or allogeneic) gave partial protection, or did not protect the mice at all from D122 metastases. The combination of syngeneic and allogeneic genes in the same tumor cell elevated the immunogenic properties of the expressing cells and potentiated the immune response as was demonstrated by in vitro cytotoxicity analysis and by limiting dilution cytotoxicity analysis. Increased immunogenicity by double transfection may constitute an effective therapeutic modality.

Animals↗
PubMed1994

Effective anti-metastatic melanoma vaccination with tumor cells transfected with MHC genes and/or infected with Newcastle disease virus (NDV).

The therapeutic efficacy of active immunization with B16-F10.9 melanoma cells transfected with syngeneic major histocompatibility complex (MHC) class-I genes, modified by infection with Newcastle Disease virus (NDV) or modified by both treatments, was compared. B16-F10.9 tumor-bearing mice were treated at various stages of tumor growth and metastasis with irradiated, modified tumor-cell vaccines. Irradiated tumor cells and H-2Db transfectants did not stimulate anti-tumor immunity while H-2Kb transfectants and NDV-modified F10.9 cells showing low and high expression of MHC class-I genes efficiently prevented metastasis of small established tumors. NDV-modified parental-cell vaccines functioned optimally and improved overall survival by about 60%, also at early stages of metastasis establishment. A synergistic effect of H-2Kb expression and virus modification on rejection of micrometastases was observed in mice bearing advanced tumors. Postoperative vaccination of mice carrying multiple metastases with NDV-modified vaccines caused significant, but incomplete, reduction of metastatic tumor load. The therapeutic effect of NDV-modified tumor vaccines was dependent on multiple immune mechanisms. Depletion of CD8, CD4 or NK cells by in vivo treatment with monoclonal antibodies reversed the immunotherapeutic effects of the vaccine. Thus, tumor xenogenization and gene modification may act synergistically to vaccinate against advanced tumors, while single modalities can effectively vaccinate against metastasis at early stages of tumor growth.

Animals↗
PubMed1994

Chromosome painting in plants: in situ hybridization with a DNA probe from a specific microdissected chromosome arm of common wheat.

We report here on the successful painting of a specific plant chromosome within its own genome. Isochromosomes for the long arm of chromosome 5 of the wheat B genome (5BL) were microdissected from first meiotic metaphase spreads of a monoisosomic 5BL line of the common wheat Triticum aestivum cv. Chinese Spring. The dissected isochromosomes were amplified by degenerate oligonucleotide-primed PCR in a single tube reaction. The amplified DNA was used as a complex probe mixture for fluorescent in situ hybridization on first meiotic metaphase spreads of lines carrying 5BL as a distinctive marker. Hybridization signals were observed, specifically, along the entire 5BL. In some of the cells, labeling was also detected in two bivalents, presumably those of the 5B "homoeologues" (partial homologues) found in common wheat (5A and 5D). The probe also revealed discrete domains in tapetal nuclei at interphase, further supporting the probe's high specificity. These data suggest that chromosome and homoeologous group-specific sequences are more abundant in 5BL than genome-specific sequences. Chromosome-painting probes, such as the one described here for 5BL, can facilitate the study of chromosome evolution in polyploid wheat.

Base Sequence↗
PubMed1994

Identification of rat liver phosphatidylinositol synthase as a 21 kDa protein.

Substantial purification of rat liver phosphatidylinositol (PtdIns) synthase has been achieved by a combination of Hecameg extraction, heat treatment, affinity chromatography and chromatography on PBE-94. The activity chromatographs as a single peak which has an apparent molecular mass between 150 and 200 kDa on Sepharose 4B. When analysed by SDS/PAGE, two major bands are seen. The enzyme activity is correlated with a protein band of 21 kDa. A second band, at 51 kDa, is eluted from a PBE-94 column slightly ahead of the activity. Manganese is an absolute requirement for stabilization of activity in the presence of detergent. The effect of manganese is optimal at 0.5 mM; magnesium at a concentration of 10 mM is only minimally effective. Substrate Kms are 1.3 mM and 9.5 microM for inositol and CDP-diacylglycerol respectively. The activity eluting from the PBE-94 column is purified 5000-fold over the post-mitochondrial supernatant.

Animals↗
PubMed1994

CTL induction by a tumour-associated antigen octapeptide derived from a murine lung carcinoma.

Many mouse and human tumours express major histocompatibility complex (MHC) class I-associated antigens that constitute targets for syngeneic cytotoxic T lymphocytes (CTL). Genes encoding such antigens were isolated from a mouse mastocytoma and from human melanomas by genetic methods. Isolation and characterization of MHC class I-associated peptides has enabled specific anchor residues to be identified that are typical of peptides that bind to distinct class I molecules. Moreover, CTL specific to particular MHC-peptide combinations have been used to identify naturally occurring antigenic peptides in cell extracts and enabled them to be sequenced directly. Most known MHC ligands are of viral origin or are self peptides derived from normal proteins. Here we use total acid extraction and repeated fractionation to isolate and sequence Lewis lung carcinoma (3LL)-specific peptide(s), which shows sequence homology to the connexin 37 protein. Synthetic octamers based on these sequences bind to 'empty' H-2Kb molecules on RMA-S cells, sensitize RMA-S cells to lysis by specific anti-3LL CTL, and induce anti-tumour CTL. The tumour-associated peptide originates from mutated connexin 37 expressed in 3LL.

Amino Acid Sequence↗
PubMed1994

Time course analysis of the state of leukocyte adhesiveness/aggregation in patients with ischaemic heart disease.

OBJECTIVE: To determine the state of leukocyte adhesiveness/aggregation (LAA), in the peripheral blood of patients with ischaemic heart disease. METHODS: All the patients were examined during their hospitalization in the Chaim Sheba Medical Center Intensive Coronary Care Unit. The patients were divided into four diagnostic categories according to the clinical picture, electrocardiographic and echocardiographic findings, as well as enzyme levels. The white blood cell count (WBCC), the erythrocyte sedimentation (ESR) and the state of LAA were measured daily for a maximum of six days. RESULTS: The LAA in ten patients with acute anterolateral myocardial infarction, increased from 5 +/- 5% day one to 13 +/- 6% at day five; the respective values for ten patients with a diaphragmatic MI were 2 +/- 2% and 5 +/- 3% respectively. Normal LAA values were noted in ten patients with myocardial ischaemia, and no evidence for infarction, as well as in ten controls. The increases LAA correlated significantly with the erythrocyte sedimentation rate (r = 0.53, p < 0.0001), raising the possibility that fibrinogen is involved in induction and/or maintenance of an increased LAA. CONCLUSIONS: Our findings suggest that the state of LAA increases during the evolution of the infarction/inflammation process. Considering that sticky leukocytes may contribute to capillary flow retardation, the results of the present study would be relevant if optimal timing for anti-adhesive therapy is considered.

Adult↗
PubMed1994

Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury.

OBJECTIVE: To determine if a dose of aspirin exists that might inhibit thromboxane-dependent platelet function without causing gastric mucosal injury, we studied the effects of a wide range of doses of aspirin (3 mg/d to 2600 mg/d) on gastric juice prostaglandins (PGE2 and PGF2 alpha), on serum thromboxane B2, and on stomach mucosal injury as reflected by gastric juice hemoglobin and DNA concentrations. DESIGN: A randomized, placebo-controlled study. SETTING: Research laboratory at a Veterans Affairs medical center. PARTICIPANTS: 16 healthy volunteers (5 men and 11 women). INTERVENTION: In the first part of the study, volunteers received placebo; aspirin, 324 mg/d; 1300 mg/d; or 2600 mg/d for 2 days. In the second part, volunteers received placebo; aspirin, 3 mg/d; 10 mg/d; 30 mg/d; or 81 mg/d for 8 days. MEASUREMENTS: Gastric juice PGE2 and PGF2 alpha, hemoglobin and DNA concentrations; gastric juice volume and acidity; and serum salicylate and thromboxane B2 concentrations. RESULTS: In the first part, significant and similar (approximately 50%) inhibition of gastric juice prostaglandin output was observed with daily aspirin doses of 324 to 2600 mg. However, a significant increase in gastric juice hemoglobin output occurred only with 2600 mg/d. In the second part, significant inhibition (approximately 50%) of gastric PGE2 output was noted at a daily aspirin dose of 30 mg. Lower aspirin doses did not reduce PGE2 output significantly, although these doses did significantly reduce serum thromboxane B2 in a dose-related manner. CONCLUSIONS: Aspirin can significantly reduce serum thromboxane B2 at doses of 3 mg/d or 10 mg/d, which are significantly below the threshold dose for significant gastric prostaglandin inhibition and acute stomach mucosal injury.

Adult↗
PubMed1994

Age-related reductions in gastric mucosal prostaglandin levels increase susceptibility to aspirin-induced injury in rats.

BACKGROUND/AIMS: Aspirin and other nonsteroidal anti-inflammatory drugs are known to cause gastrointestinal mucosal injury in humans and animals. The present study was designed to determine the effect of aging on gastric mucosal eicosanoid formation and aspirin-induced injury in Fischer 344 rats. METHODS: In part 1 of the study, rats of three different age groups (3, 12, and 21 months) were killed after an overnight fast, and gastric mucosal formation of prostaglandins and leukotrienes was determined. In part 2, rats of various ages were killed 3 hours after receiving aspirin (100 mg/kg intragastrically) or vehicle (for controls). Gastric mucosal eicosanoid formation and gross mucosal injury were assessed. RESULTS: Gastric mucosal prostaglandin formation decreased with aging, whereas no significant changes in mucosal leukotriene formation were noted in any age groups. No gastric mucosal lesions were present in any rats treated with vehicle alone. In contrast, aspirin caused significant mucosal injury in all age groups, but significantly more mucosal lesions were noted in the older rats. CONCLUSIONS: These observations indicate that gastric mucosal prostaglandin synthesis decreases with aging in rats and that aged animals are more susceptible to aspirin-induced acute gastric mucosal injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Pathogenic disorders involved in immunosuppression and T cell depletion characterizing AIDS.

Four cardinal immune disorders interacting with each other may promote the progressive T cell depletion and immunosuppression characterizing AIDS. Immune activation of HIV-1 infected T4 cells leads to virus release and premature cell death. Both virus release with its resulting viral load and dead cells are the source of gp120 stimulus. Anergy of non-infected CD4 cells, resulting in cytokine dysregulation may be promoted by impairing the CD4-MHC interaction during CD4 cell activation either directly through the SLWDQ pentapeptide identity with the CD4 molecule and the CD4 binding region or through a gp120-induced autoimmune reaction to CD4. Overproduction of IFN alpha, the known antiproliferative and cytolytic cytokine may promote in a paracrine manner to neighbouring cells the immunosuppression generated by the lack of IL2 secretion following CD4 cell anergy. Apoptosis of activated non infected T cells could be induced by effector components of the autoimmune reaction (CTL, Lymphotoxins or Abs?) directed towards the 2 consensus gp120 sequence identity/similarity (INCTR and FYCNST) shared with the APO/Fas molecule. These two sequences are known as immunodominant sites of the gp120. Furthermore, IFN alpha overproduction may also render circulating memory T cells competent to apoptosis by upregulating the cascade of metabolic events leading to programmed cell death.

Acquired Immunodeficiency Syndrome↗