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Biomedical subjects

S Karpatkin

Publications and source records attributed to S Karpatkin.

At least 109 records · Page 6Linked to original sources
PubMed1981

Immune thrombocytopenia in children.

Idiopathic thrombocytopenic purpura in the adult has a clearly established autoimmune etiology; IgG antiplatelet antibody is demonstrable on the patient's platelets and is frequently present in the serum. Platelet IgG is correlated inversely with the platelet count. In the acute childhood form of the disease, serum antibody is usually absent but increased IgG is present on the platelets, thus suggesting the immune nature of the childhood disease. The spleen acts as a significant source of antiplatelet antibody as well as the major reticulo-endothelial site for destruction of antibody-coated platelets. The majority of children with idiopathic (autoimmune) thrombocytopenia recover completely and have normal platelet counts within 6 months of diagnosis. Some patients recover after a longer period of time. Ten to 15 percent have a chronic form of the disease which is indistinguishable from the adult disease; splenectomy benefits approximately 70% of these patients.

Adrenal Cortex Hormones↗
PubMed1981

Easy bruising, thrombocytopenia, and elevated platelet immunoglobulin G in Graves' disease and Hashimoto's thyroiditis.

Platelet IgG levels, count, and function and easy bruising or bleeding were studied in 25 patients with Graves' disease and 12 with Hashimoto's thyroiditis (normal value for platelet IgG 10.7 +/- 4.5 ng [SD]/10(6) platelets). Eight of 22 patients with Graves' disease and normal platelet counts had elevated platelet IgG averaging 38 +/- 4.0 ng (SEM) (range, 24 to 60). Four of 10 patients with Hashimoto's thyroiditis and normal platelet counts ahd elevated platelet IgG averaging 45 +/- 7.2 ng (range, 27 to 66). Five patients with thrombocytopenia had platelet counts averaging 53000 +/- 12000/microL (SEM) and elevated platelet IgG averaging 154 +/- 40 ng (range, 27 to 300). Twelve of 15 patients with a history of easy bruising or bleeding had elevated platelet IgG compared to five of 22 without easy bruising (p < 0.001). Four of six with elevated platelet IgG had one or more abnormal in-vitro platelet aggregation measurements (particularly with epinephrine) compared to none of six with normal platelet IgG levels (p = 0.03). We conclude that elevated platelet IgG is associated with easy bruising and thrombocytopenia in about half of patients with Graves' disease or Hashimoto's thyroiditis.

Blood Coagulation Disorders↗
PubMed1981

Role of platelets in tumor cell metastases.

Platelets may have a role in the development of animal tumor metastases. Ultrastructural studies in vivo have shown arrested tumor emboli surrounded by platelets. Several tumor cell lines induce thrombocytopenia in vivo. Certain tumor cells aggregate platelets in vitro. Correlations exist between the ability of some tumor cells to aggregate platelets in vitro and their metastatic potential in vivo. Antiplatelet agents have impaired or altered the spread of certain tumor metastases. It is suggested that platelets have a role in the sequestration, adherence, and penetration of tumor cells through the blood vessel endothelial cell barrier, thus preventing their rapid clearance from the circulation and allowing extravascular formation of nests of cells. Antiplatelet agents, particularly prostaglandins, may prove useful in preventing experimental animal metastases when administered before the inoculation of tumor cells. Their potential in human malignancy, where the patient presents with an established tumor, remains to be established.

Animals↗
PubMed1981

Inhibition of the platelet-aggregating activity of two human adenocarcinomas of the colon and an anaplastic murine tumor with a specific thrombin inhibitor, dansylarginine N-(3-ethyl-1,5-pentanediyl)amide.

Platelets are required for certain experimental metastases. Several lines of animal tumor cells aggregate platelets in vitro and in vivo. Previous studies with one of these lines, an SV40-transformed 3T3 mouse fibroblast (SV3T3) have revealed that the platelet-aggregating material is an extractable membrane-associated sialolipoprotein which requires divalent cation, complement, and a heat-stable plasma component for activity. Little information is available on the interaction of human tumors with platelets. We now report on the ability of two human adenocarcinomas of the colon (LoVo and HCT-8) and an anaplastic mouse tumor (Hut-20) to aggregate platelets by a different mechanism, the generation of thrombin. These spontaneous cell lines aggregate human or rabbit platelet-rich plasma after a 1- to 2-min lag period. This is often followed by a visible clot. Unlike SV3T3 cells, aggregation by LoVo, HCT-8, and Hut-20 cells is not inhibited by neuraminidase, trypsin, or cobra venom factor. These three cell lines markedly shorten the recalcification time of citrated plasma, whereas SV3T3 cells do not. Phospholipase A2 treatment inhibits the shortening of the recalcification time for the three tumors; this parallels its inhibitory effect on platelet aggregation. LoVo, HCT-8, and Hut-20 cells generate thrombin via the "tissue factor" coagulation pathway (using coagulation factor-deficient substrates). Dansylarginine-N-(3-ethyl-1,5-pentanediyl)amide, a highly specific, potent antithrombin antagonist, inhibits LoVo-, HCT-8-, and Hut-20-induced platelet aggregation at 4 to 15 microM, whereas its effect on SV3T3 cells is negligible. If platelets are required for certain human tumor metastases, dansylarginine-N-(3-ethyl-1, 5-pentanediyl)amide, or other antithrombin agents, may prove to be valuable therapeutic agents.

Adenocarcinoma↗
PubMed1980

Correlation between spontaneous metastatic potential, platelet-aggregating activity of cell surface extracts, and cell surface sialylation in 10 metastatic-variant derivatives of a rat renal sarcoma cell line.

Several properties of 10 cell lines derived from the polyoma-induced PW20 Wistar-Furth rat renal sarcoma have been examined, including the ability of the tumor cells to metastasize spontaneously from subcutaneous sites in syngeneic hosts, the platelet-aggregating activity of material extracted by urea from the surface of cultured cells, the sialic acid content of the platelet-aggregating material, and the degree of sialylation of cell surface glycoconjugates in cultured cells. A correlation has been observed among all of these parameters. The results suggest a possible link between the degree of cell surface sialylation of tumor cells, their ability to aggregate platelets, and their ability to metastasize.

Acetylgalactosamine↗
PubMed1980

Platelets and microtubules. Effect of colchicine and D2O on platelet aggregation and release induced by calcium ionophore A23187.

We examined the role of microtubules in platelet aggregation and secretion (release reaction) induced by the calcium ionophore A23187 (0.8-5 muM). At these concentrations, platelet aggregation was preceded by a lag period of approximately 1 min. Colchicine (an agent that disrupts microtubule assembly-disassembly) was shown to bind to platelet microtubules by employing [(3)H]colchicine at a concentration that is specific for microtubules in other tissues (10 nM). Colchicine prolonged the lag period, inhibited the secondary wave of platelet aggregation, and inhibited the release reaction (release of [(14)C]serotonin). Platelets were next incubated with 20-60% D(2)O, an agent that stabilizes microtubules. D(2)O overcame colchicine-induced inhibition of the lag period, aggregation, and release. D(2)O alone enhanced platelet aggregation by 59+/-14% (SEM) and shortened the lag period by 43+/-10%. We conclude that functioning microtubules are required for platelet aggregation and release, and that microtubules of platelet preparations are functioning submaximally.

Adenosine Diphosphate↗
PubMed1980

Autoimmune thrombocytopenic purpura.

Adult autoimmune throbocytopenic purpura (ATP) is a platelet disorder that develops in certain individuals with a genetic as well as sex (female) predisposition following an environment event (?viral). This results in the production of an IgG antiplatelet antibody capable of reacting with the host's platelets, as well as crossing the placenta. This leads to the rapid clearance and destruction of opsonized platelets by the reticuloendothelial system, particularly the spleen, by greater than tenfold the normal rate. Bound platelet IgG correlates with disease severity, whereas serum antiplatelet IgG does not. It has not been rigorously established whether bound platelet IgG is directed against a platelet antigen or represents an immune complex bound to the platelet Fc receptor. Nevertheless, several lines of evidence suggest that antiplatelet IgG binds directly to a platelet antigen(s). Megakaryocyte number, volume, and mass are increased commensurate with increased platelet turnover. Platelets of increased size, megathrombocytes, are noted on peripheral smear or via platelet volume distribution analysis. Megathrombocyte number is proporationate to megakarocyte number and to platelet turnover. Megathrombocyte diameter is inversely proportional to platelet survival. Antiplatelet antibody is also associated with qualitative platelet functional defects, which are indistinguishable from those noted with thrombopathia (i.e., apparent platelet release defect). Antibody-induced functional defects are probably more common than quantitative thrombocytopenic defects and may represent a significant portion of those women with the "easy bruising" syndrome and normal platelet count. Adults who develop ATP generally develop the chronic variety, which remains permanently with the patient. Treatment should be directed towards maintaining the patient free of purpura, not restoring the platelet count to normal. This can generally be accomplished with a platelet count of > 40,000/cu mm with patients having this disorder. Approximately 50% of patients respond to steroids by a significant elevation of platelet count and improvement of purpura. However, cessation of therapy results in eventual relapse if the disease is of the chronic variety. Splenectomy is successful in approximately 65-75% of patients, resulting in a restoration of the platelet count to normal or safe levels by removing a major source of platelet destruction as well as antibody production; platelet survival improves. At least 50% of patients "in remission" following steroids or splenectomy generally have a compensated thrombocytolytic state in which increased platelet production keeps up with increased platelet destruction. Antiplatelet IgG can often be found in the serum of these patients. Patients refractory to steroids and/or splenectomy present with a serious therapeutic problem. Immunosuppressive therapy is effective in approximately one-third of refractory patients, but often relapses occur, requiring maintenance therapy with potentially mutagenic drugs...

Adult↗
PubMed1980

Plasma requirement for the aggregation of rabbit platelets by an aggregating material derived from SV40-transformed 3T3 fibroblasts.

Certain tumors require platelets for metastases, and many of these aggregate platelets in vitro. We have studied their in vitro interaction by extracting a PAM from SV40-transformed 3T3 fibroblasts. The preparation is enriched with membrane vesicles and requires an intact sedimentable sialolipoprotein for activity. PAM aggregates platelets after a lag period (J Lab Clin Med 93:332, 1979) and requires plasma as a cofactor(s). Two plasma components have been identified with the use of PRP or GFP. The first component shortens the platelet aggregation lag period after preincubation of PAM with plasma at 37 degrees C for 10 min prior to its addition to PRP or GFP and is labile to heating at 56 degrees C for 30 min. However, the activated PAM (formed by incubation with plasma at 37 degrees C) is stable at 56 degrees C for 30 min. This labile factor appears to be a component(s) of the complement alternative pathway, since it is inactivated by treatment of plasma with cobra venom or zymosan; and guinea pig PRP deficient in C' 4 can be aggregated by PAM. The second component is a plasma factor that is stable to heating at 56 degrees C. Activated PAM can be sedimented at 100,000 x g. The sediment, when suspended in Veronal buffer, pH 7.4, does not aggregate GFP, however, addition of plasma heated at 56 degrees C restores the platelet aggregation response. Thus a material extracted from SV40 3T3 fibroblasts aggregates platelets in vitro in the presence of two factors: (1) a component(s) of the alternative complement pathway that activates PAM and shortens the platelet aggregation lag period and (2) a heat-stable factor that is required for activated PAM to aggregate platelets.

Animals↗
PubMed1980

Heavy-chain subclass of round antiplatelet IgG in autoimmune thrombocytopenic purpura.

The gamma heavy-chain subclass of bound antiplatelet antibody was examined in six patients with autoimmune thrombocytopenic purpura (ATP) by a solid-phase radioimmunoassay. Monospecific antisera for gamma G1, gamma G2, gamma G3, and gamma G4 subclasses were employed in a "sandwich" technique, utilizing the binding of 126I-staphylococcal protein A. We have previously reported that serum antiplatelet antibody was restricted to be gamma G3 subclass in ATP. In contrast, all 4 IgG subclasses were found bound to platelets of ATP patients in the same distribution as that present in normal serum. It is suggested that the differences noted between serum antiplatelet IgG and platelet-bound IgG may represent different mechanisms of platelet injury.

Animals↗
PubMed1980

Asialo platelets enhance thrombopoiesis.

Because the terminal sialic acid of several glycoproteins regulates their intravascular half-life, and because asialo platelets have a shortened survival, we postulated that asialo platelets might affect the basal rate of thrombopoiesis. Thrombopoiesis was measured by the incorporation of intravenous 75Se-selenomethionine (a cohort label) into circulating rabbit platelets. Each animal acted as its own control. In one control group, saline was injected intravenously once daily for two days. 75Se-selenomethionine was then injected, 15 microCi/kgm on day 2 and platelets harvested on day 5 for measurement of specific activity (S.A.), cpm/10(7) platelets. The animals were allowed to rest for two weeks, and the experiment repeated. The ratio of the second SA over the first SA was utilized as the stimulation index. When saline was injected the second time, the stimulation index was 1.22 +/- 0.07 (SEM) in eight animals. Asialo platelets were prepared by incubating washed platelets with neuraminidase, 2 units/ml for 60 min. Injection of 2-4 X 10(9) asialo platelets/kgm (the second time) resulted in a stim. index of 2.08 +/- 0.23 (P less than 0.001) in 11 animals. Similar results were obtained with 1 mM DFP and neuraminidase (12 animals). Negative results were obtained when 11 rabbits were injected with a comparable number of untreated washed platelets, stim. index 1.07 +/- 0.13; when 10 rabbits were injected with sonicated asialo platelets, stim. index 1.10 +/- 0.12; or when four rabbits were injected with platelets treated with chymotrypsin, 3 mg/ml for 45 min, stim. index 0.80 +/- 0.04. We conclude that asialo intact platelets stimulate megakaryocytes to produce more platelets. It is suggested that the basal stimulus to thrombopoiesis may be regulated by desialidated older platelets.

Animals↗
PubMed1979

Humoral factor that specifically regulates prothrombin (factor II) levels (coagulopoietin-II).

Prothrombin (Factor II) was decreased in rabbits by injection of a goat antiserum to prothrombin. When plasma from these rabbits was injected into normal animals, circulating prothrombin increased in the recipients, suggesting transfer of a humoral regulating factor ("coagulopoietin-II"). This coagulopoietin-II resisted boiling for 20 min. On Sephadex G-50 gel filtration, it remained in the retained volume, suggesting a molecular weight of less than 30,000. In an in vitro liver system, prothrombin increased in the incubation medium in the presence of coagulopoietin-II.

Animals↗
PubMed1979

Association of HLA-DRw2 with autoimmune thrombocytopenic purpura.

Peripheral blood lymphocytes from 38 patients with autoimmune thrombocytopenic purpura (AITP) were tested for HLA-A, -B, and -C alloantigens. Isolated B lymphocytes from 20 of these patients were tested for HLA-DRw (Ia) alloantigens. The profile of HLA alloantigens in the patients with AITP was significantly different from that of a matched control population. The most significant finding was the presence of the HLA-DRw2 alloantigen in 75% of patients as compared with 23% in the control population, P less than 0.001, relative risk 10.0 (A relative risk of 1 would indicate no association between the presence of the antigen and the disease.) The co-occurrence of either A3 and B7 (known to be in linkage disequilibrium with DRw2) or A26 and Bw38 was significantly increased as compared with the control population (P less than 0.001). Of the patients positive for DRw2, 47% had the association A26 and Bw38 as compared with the control population association incidence of 21% (P less than 0.1). Thus, in the patient population, A26-Bw38 appears to be a haplotype that is in linkage disequilibrium with DRw2 (as presumably is the case with A3-B7). These data indicate that a predisposition to AITP is inherited with a DRw2 gene of the major histocompatibility system.

Autoimmune Diseases↗