Search PubMed⌕ Search

Biomedical subjects

M Ginsberg

Publications and source records attributed to M Ginsberg.

At least 37 records · Page 2Linked to original sources
PubMed1990

Transmission of Plasmodium vivax malaria in San Diego County, California, 1986.

Between 18 June and 20 September 1986, 28 cases of Plasmodium vivax malaria were documented in Carlsbad, California, a coastal town north of San Diego. Malaria occurred in 1 local resident who had no risk factors, a second local resident who had traveled to a malarious area 9 months earlier, and 26 Mexican migrant workers (MWs). Among the 28 cases, 27 lived in a square mile marshy area where Anopheles hermsi, a newly described American species of the Anopheles maculipennis group, was known to be breeding. An investigation of MWs residing in the affected area was done to determine the extent of the outbreak and to identify risk factors for acquiring malaria. We interviewed and drew blood from 304 healthy MWs and 17 (65%) of the MWs with malaria. Fluorescent antibody titers to P. vivax greater than or equal to 1:256 occurred in 14 (82%) of the 17 MWs with malaria tested and 9 (3%) of the healthy MWs. The principal risk factor identified for contracting malaria was sleeping outside on a hillside adjacent to the marshy area. Malaria in a local resident with no malaria risk factors and the clustering in time and place of 26 cases suggest that P. vivax malaria was introduced and local transmission was sustained through several generations, producing the largest outbreak of introduced malaria in the United States since 1952.

Adolescent↗
PubMed1988

cDNA clones for human platelet GPIIb corresponding to mRNA from megakaryocytes and HEL cells. Evidence for an extensive homology to other Arg-Gly-Asp adhesion receptors.

Platelet glycoprotein (GP) IIb is one of the two subunits of the common platelet adhesion receptor, GPIIb-IIIa. The isolation, characterization and sequencing of cDNA clones encoding for the two polypeptide chains of GPIIb are described. A number of clones were isolated from lambda gt11 libraries constructed with mRNA from an erythroleukemic cell line, HEL, and human megakaryocytes. Two of these clones, lambda IIb1, from HEL cells, and lambda IIb2, from megakaryocytes, cross-hybridized and were selected for detailed analysis. The identification of these as authentic GPIIb clones was based on immunological criteria and confirmed by the presence of nucleotide sequences in each insert encoding for known protein sequences of platelet GPIIb. These clones contained inserts of 1.54 kb and 1.39 kb, respectively, with an overlapping sequence of 801 bp. The nucleotide sequence of the overlapping region was identical indicating that HEL cells produce a protein closely related, if not identical, to platelet GPIIb. The determined nucleotide sequence of two inserts included a coding sequence for 648 amino acid residues, a TAG stop codon and 185 nucleotides of 3' non-coding sequence followed by a poly(A) tail. The coding sequence contained a portion of the heavy chain, the junction between the heavy and light chains and the entire light chain including a potential transmembrane-spanning domain and a short cytoplasmic tail. When these cDNA were used to probe for GPIIb mRNA, a single mRNA species of 3.9 kb was identified in both HEL cells and human megakaryocytes. A comparison of the deduced amino acid sequence for GPIIb with those of the alpha subunit of the vitronectin and the fibronectin receptors revealed extensive homologies. These homologies further establish that GPIIb-IIIa from platelets, together with the vitronectin and the fibronectin receptors, are members of a supergene family of adhesion receptors with a recognition specificity for Arg-Gly-Asp amino acid sequences.

Amino Acid Sequence↗
PubMed1988

The localization of a platelet GpIIb-IIIa-related protein in endothelial cell adhesion structures.

Previous studies have shown that human endothelial cells (ECs) adhere to fibrinogen (fg) and fibronectin (fn) and organize their cytoskeleton on these substrata. However, the mechanism governing this chain of events is poorly known. In ECs glycoproteins immunologically and biochemically similar to the platelet membrane GpIIb-IIIa complex have been described. The functional role of this complex in ECs remains to be established. In this study we show that the antigens recognized by polyclonal antibodies raised against human platelet GpIIb-IIIa and crossreacting with the EC form have a discrete and well-organized distribution at cell adhesion structures. Indeed these antigens are located at vinculin-rich focal contacts found at the membrane insertion of microfilament bundles of the stress fiber type. They are also found at cell-to-cell contacts and, with a diffuse pattern, at the dorsal surface of ECs. GpIIb-IIIa antibodies, added to EC suspensions prior to plating, inhibit EC spreading on fg and vitronectin (vn) substrata in a concentration-dependent way. In contrast, the antibodies are very poorly active when the cells are seeded on fn-coated glass. The same antibodies, added to adherent cells, disrupt cell-to-cell contacts and cause their rounding and detachment. Overall these results indicate that EC GpIIb-IIIa complex is involved in controlling the adhesion mechanism of these cells to extracellular matrix proteins.

Antigens↗
PubMed1987

Biosynthesis and processing of platelet GPIIb-IIIa in human megakaryocytes.

Platelet membrane glycoprotein IIb-IIIa forms a calcium-dependent heterodimer and constitutes the fibrinogen receptor on stimulated platelets. GPIIb is a two-chain protein containing disulfide-linked alpha and beta subunits. GPIIIa is a single chain protein. These proteins are synthesized in the bone marrow by megakaryocytes, but the study of their synthesis has been hampered by the difficulty in obtaining enriched population of megakaryocytes in large numbers. To examine the biosynthesis and processing of GPIIb-IIIa, purified human megakaryocytes were isolated from liquid cultures of cryopreserved leukocytes stem cell concentrates from patients with chronic myelogenous leukemia. Immunoprecipitation of [35S]methionine pulse-chase-labeled cell extracts by antibodies specific for the alpha or beta subunits of GPIIb indicated that GPIIb was derived from a precursor of Mr 130,000 that contains the alpha and beta subunits. This precursor was converted to GPIIb with a half-life of 4-5 h. No precursor form of GPIIIa was detected. The glycosylation of GPIIb-IIIa was examined in megakaryocytes by metabolic labeling in the presence of tunicamycin, monensin, or treatment with endoglycosidase H. The polypeptide backbones of the GPIIb and the GPIIIa have molecular masses of 120 and 90 kD, respectively. High-mannose oligosaccharides are added to these polypeptide backbones co-translationally. The GPIIb precursor is then processed with conversion of high-mannose to complex type carbohydrates yielding the mature subunits GPIIb alpha (Mr 116,000) and GPIIb beta (Mr 25,000). No posttranslational processing of GPIIIa was detected.

Acetylglucosaminidase↗
PubMed1985

Inhibition of fibronectin binding to platelets by proteolytic fragments and synthetic peptides which support fibroblast adhesion.

To define regions within fibronectin (Fn) recognized by platelet binding sites, inhibition of Fn binding by an Fn fragment and synthetic peptides has been analyzed. A highly purified 120-kDa chymotryptic fragment, which has cell attachment activity but did not bind to insolubilized heparin or gelatin, inhibited Fn binding to platelets with an ID50 approximately 3 microM. Previous work indicates that fibroblasts attach to an 11.5-kDa subfragment of this 120-kDa fragment, and that one of four 30-residue synthetic peptides containing sequences from this region supports cell attachment. Only the peptide containing the COOH terminus of the 11.5-kDa fragment inhibited Fn binding to platelets, with an ID50 approximately 10 microM and is the peptide which supports fibroblast attachment. Of the smaller peptides studied from this sequence, all peptides containing the Arg-Gly-Asp-Ser sequence, including the tetrapeptide itself, were active in inhibiting Fn binding to platelets (ID50 values approximately 10-20 microM). The same peptides support fibroblast attachment. Those which lacked this sequence including Gly-Asp-Ser-Pro and Thr-Gly-Arg-Gly (immediately adjacent tetrapeptides) lacked both activities. Further evidence for specificity of inhibition was provided by structurally modified peptides in which substitution of a Glu for Asp abolished inhibitory activity and substitution of Lys for Arg or Ala for Gly reduced activity 6- and 8-fold, respectively. In addition, Arg-Gly-Asp-Ser-containing peptides inhibited the rate and extent of thrombin-induced platelet aggregation. These data suggest that the Arg-Gly-Asp-Ser tetrapeptide contains a recognition specificity involved in the binding of Fn to platelets and that platelets share features of this recognition specificity with fibroblasts.

Amino Acid Sequence↗
PubMed1984

Evaluation of alpha-tocopherol antioxidant activity in microsomal lipid peroxidation as detected by low-level chemiluminescence.

The significance of microsomal vitamin E in protecting against the free-radical process of lipid peroxidation was evaluated with the low-level-chemiluminescence technique in microsomal fractions from vitamin E-deficient and control rats. The induction period that normally precedes the ascorbate/ADP/Fe3+-induced lipid peroxidation was taken as reflecting the microsomal vitamin E content and was found to be 5-6-fold decreased in microsomal fractions from vitamin E-deficient rats. Supplementation of microsomal fractions from vitamin E-deficient rats with exogenous vitamin E partially restores the induction period observed in that from control rats. The decrease in chemiluminescence intensity and the increase in the induction period both correlate linearly with the amount of vitamin E added. However, the efficiency of exogenous vitamin E is about 50-fold lower than that exerted by the naturally occurring vitamin E in microsomal membranes. These observations are discussed in terms of the process of re-incorporation of vitamin E into membranes, the experimental model for lipid peroxidation selected, and the method to evaluate lipid peroxidation, namely low-level chemiluminescence.

Animals↗
PubMed1983

Moist wound healing under a vapor permeable membrane.

Ten ambulatory patients with unilateral and eight with bilateral ulcers of various etiologies were studied to determine the effects of keeping a wound bed moist under a water vapor and oxygen permeable membrane (VPM). In the bilateral group, VPM healing was compared with a debriding enzyme ointment and 10% benzoyl peroxide in the same patient. The faster healing rate with VPM was compared to the healing rate with control substances by the paired t test, with significance at less than 0.05 level. In the unilateral group two patients with ulcers to bone or joint capsule and one patient who had failed grafting healed without surgery. Two patients failed to heal with the VPM. All healing occurred in the face of gross bacterial contamination. Three patients treated with VPM developed cellulitis. Wound healing under a vapor permeable membrane occurs with an increase of the average healing rate by a factor of 2.6 when compared to control substances in ambulatory patients.

Benzoyl Peroxide↗
PubMed1983

New synthesis of a platelet-specific protein: platelet factor 4 synthesis in a megakaryocyte-enriched rabbit bone marrow culture system.

The site of synthesis of platelet-specific proteins remains to be established. With the use of short-term megakaryocyte-enriched cultures, direct evidence was obtained to show that megakaryocytes synthesize the platelet-specific protein, platelet factor 4. A megakaryocyte-enriched fraction of rabbit bone marrow for culture was obtained by centrifugal elutriation and cultured with [3H]leucine. Newly synthesized 3H-platelet factor 4 was sought by copurification with added carrier rabbit platelet factor 4, using heparin agarose affinity chromatography and immunoprecipitation with specific goat anti-rabbit platelet factor 4 antisera. SDS PAGE of the washed immunoprecipitates demonstrated a [3H]leucine-containing peak which migrated identically with purified homogeneous rabbit platelet factor 4. A second, slightly larger molecular-weight protein was identified in the gels also, suggesting that rabbit platelet factor 4 may be synthesized as a larger molecular-weight precursor in rabbit megakaryocytes. These results provide direct evidence that the platelet-specific protein, platelet factor 4, is synthesized in rabbit megakaryocytes before it is packaged into alpha-granules for release in circulating platelets.

Animals↗
PubMed1983

A multipurpose CT-guided stereotactic instrument of simple design.

The instrument is based upon a radiolucent ring fixed to the skull by four pins. This locks into a frame for CT scanning from which the x, y and z stereotactic coordinates are derived. The head ring may be locked into a compatible support on the operating table for biopsy. A similar support and localization system is used for rotational radiotherapy. With the current 14 MeV apparatus, fields as small as 2 cm in diameter are available with 90% dosage fall-off in the surrounding 1-cm shell.

Biopsy↗
PubMed1982

Controlled trial of oral acyclovir in the therapy of recurrent herpes simplex genitalis. A preliminary report.

A randomized, placebo-controlled, double-blind study was performed to evaluate the efficacy and toxicity of orally administered acyclovir in the treatment of patients with recurrent herpes simplex genitalis (HSG). A total of 107 patients from centers in Burlington, Vermont, and San Diego, California, were entered into the study within 48 hours of the onset of lesions. Patients who received acyclovir shed virus for 1.8 +/- 0.6 days (mean +/- SEM) compared with 2.8 +/- 1.2 days for those who received placebo. The duration of shedding from genital lesions of patients in the acyclovir-treated group was significantly less than from lesions of patients who received placebo (p = 0.016 by a logrank test). An analysis of the toxicity of the drug was performed in 52 of the study participants. Acyclovir was well-tolerated and no alterations were observed in measurements of bone marrow, liver, or kidney function. Orally administered acyclovir is a promising antiviral compound for the treatment of recurrent HSG.

Acyclovir↗
PubMed1982

Concanavalin A induces interactions between surface glycoproteins and the platelet cytoskeleton.

We have measured the association of platelet surface membrane proteins with Triton X-100 (Triton)-insoluble residues in platelets surface labeled with 125I. In both concanavalin A (Con A)-stimulated and resting platelets, this fraction is composed largely of polypeptides with apparent molecular weights of 45,000, 200,000, and 250,000 which comigrate with authentic actin, myosin heavy chain, and actin binding protein, respectively, as judged by PAGE in SDS. Less than 10% of the two major 125I-labeled surface glycoproteins, GPiib and GPIII, were associated with the Triton residue in resting platelets. Within 45 s after Con A addition, 80-95% of these two glycoproteins became associated with the Triton residue and the amount of sedimentable actin doubled. No cosedimentation of GPIIb and III with the cytoskeletal protein-containing Triton residue was seen when Con A was added to a Triton extract of resting cells, indicating that the sedimentation of GPIIb and III seen in Con A-stimulated platelets was not due to precipitation of the glycoproteins by Con A after detergent lysis. Treatment of Triton extracts of Con A-stimulated platelets with DNase I (deoxyribonucleate 5'-oligonucleotidido-hydrolase [EC 3.1.4.5]) inhibited the sedimentation of actin and the two surface glycoproteins in a dose-dependent manner. This inhibition of cosedimentation was not due to an effect of DNase I on Con A-glycoprotein interactions since these two glycoproteins could be quantitatively recovered by Con A-Sepharose affinity absorption in the presence of DNase I. When the Con A bound to the Triton residue was localized ultrastructurally, it was associated with cell-sized structures containing filamentous material. In intact cells, there was simultaneous immunofluorescent coredistribution of surface-bound Con A and myosin under conditions which induced a redistribution of platelet myosin. These data suggest that Con A can, in the intact platelet, induce physical interactions between certain surface glycoproteins and the internal cytoskeleton.

Actins↗
PubMed1979

Mechanisms of platelet response to monosodium urate crystals.

The mechanisms of urate-crystal-induced release of platelet constituents has been studied morphologically and biochemically. Urate crystals provoked an early energy-dependent release of the dense-body constituents serotonin, ADP, and ATP from washed platelets. Concurrently, platelet ultrastructure showed evidence of shape change, contractile wave, and aggregation. These are typical morphologic concomitants of platelet secretion. By 30 minutes' incubation, urate-induced platelet lysis occurred, as shown by loss of the cytoplasmic enzyme lactic dehydrogenase (LDH) and ultrastructurally by disruption of platelet membrane integrity. Cytochalasin B inhibited the urate-crystal-induced shape change, aggregation, and disruption of cell membranes. Platelet degranulation was not inhibited and the initial component of serotonin release was not affected. Cytochalasin B also abrogated crystal-induced LDH loss. Thus, the initial crystal-induced serotonin release does not depend on platelet lysis. It is concluded that urate-crystal--induced release of serotonin, ATP, and ADP represents an example of platelet secretion.

Adenosine Diphosphate↗
PubMed1978

Alterations in regional cerebral hemodynamics and metabolism produced by focal cerebral ischemia.

Since diffuse changes in blood flow and metabolism occur in the brain following a focal ischemic insult, changes of cerebral blood flow on the side opposite a cerebral infarction were observed. We have examined the course of the cerebral hemodynamic changes occurring in 15 patients with unilateral acute strokes. In 12 of these patients, significant blood flow changes (over 15%) occurred in the nonischemic hemisphere during the period of observation. A similar time course of change was found in the ischemic hemisphere and the flow changes in the two hemispheres appeared parallel to one another (diaschisis). Thus we have demonstrated a significant reduction in flow in the contralateral cortex following a unilateral ischemic insult. This reduction in flow was of the order of 38% from the control value which agrees quite well with the reduction in cortical glucose consumption of the order of 31%. We postulate that these changes are the hemodynamic and metabolic concomitants of diaschisis and may in part be due to a transneuronal depression of function.

Animals↗