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Biomedical subjects

M Blank

Publications and source records attributed to M Blank.

At least 163 records · Page 9Linked to original sources
PubMed1995

Induction of tolerance to experimental anti-phospholipid syndrome (APS) by syngeneic bone marrow cell transplantation.

Previously, we have shown the ability to induce experimental autoimmune conditions (e.g. SLE, APLS, Wegener's granulomatosis) following active immunization with the pathogenic autoantibody emulsified in adjuvant. The mice first develop anti-autoantibodies (Ab2: anti-id) and eventually generate anti-anti-autoantibodies (Ab3: anti-anti-id) which carry the same antigen binding characteristic as the autoantibody (Ab1). The appearance of the specific autoantibodies in mice sera was associated with the emergence of the compatible laboratory and with the clinical findings characteristic to the respective autoimmune disease. The effects of syngeneic bone marrow transplantation (BMT) on experimental anti-phospholipid syndrome (APS) were investigated. BALB/c mice were immunized with anti-cardiolipin monoclonal antibody (MoAb) named CAM and developed elevated serum titres of anti-phospholipid Abs accompanied by prolonged activated partial thromboplastin time, thrombocytopenia and a high percentage of fetal resorptions. These mice were then lethally irradiated and transfused with bone marrow (BM) cells (T cell depleted) from syngeneic naive mice. The titres of antiphospholipid antibodies were reduced in the recipients. The decrease in titre of autoantibodies was found to be related to depletion of antibody forming cells in vivo, associated with reduced proliferative response of lymph node cells to anti-cardiolipin MoAbs. The recipients showed improvement in clinical parameters following syngeneic BMT. The same recipients developed specific unresponsiveness to a second challenge with the anticardiolipin MoAb (CAM), but developed experimental systemic lupus erythematosus upon immunization with a monoclonal anti-DNA antibody. We conclude that acute myeloablative immunosuppression combined with syngeneic bone marrow transplantation may induce a state of tolerance to the pathogenic autoantibodies in mice with experimental APLS. Our results suggest that a similar approach may be useful in treating life-threatening autoimmune syndromes (e.g. catastrophic APLS) in clinical practice.

Animals↗
PubMed1995

Distribution of HLA and haplotypes of Colombian and Jamaican black populations.

To investigate the genetic background of the black populations of Colombia and Jamaica, we determined HLA types of 78 Colombian and 98 Jamaican blacks from 2 different socioeconomic groups (Jamaican #1 and Jamaican #2) and estimated the frequencies of HLA genes and haplotypes. A phylogenetic tree based on the HLA gene frequencies revealed that Jamaican #1 and Jamaican #2 were distinct from each other, Jamaican #1 being closely related to the Colombian blacks and the Jamaican #2 being closely related to Senegalese and Zairean populations. Three-locus HLA haplotypes of Colombian and Jamaican #1 blacks were an admixture between Africans and Caucasians or South American Indians, while Jamaican #2 blacks were relatively homogeneous and appeared to conserve African lineages. The major five-locus HLA haplotypes were not shared among Colombian, Jamaican #1 and Jamaican #2 blacks. These results indicated that the black populations of Colombia and Jamaican were originated from African blacks and admixed variably with Caucasians and South American Indians to make genetic subpopulations in Colombia and Jamaica.

Black People↗
PubMed1995

Antiphospholipid syndrome and the idiotypic network.

To study whether monoclonal anticardiolipin antibodies (aCL), derived from patients with antiphospholipid syndrome (APS), have similar pathogenic potential, we have employed an experimental model of antiphospholipid syndrome. Monoclonal aCL were produced by the combined method of EBV transformation and somatic cell hybridization of lymphocytes, derived from patients with APS. The monoclonal aCL were used to immunize mice at the footpads and the mice were followed for serological and clinical manifestations of APS. The monoclonal antibody EY2C9, was found to bind weakly to cardiolipin and other phospholipids (i.e. phosphatidyl-serine, phosphatidyl-ethanolamine and phosphatidyl-inositol). The antibody TM1B9, although derived from a patient with SLE and with secondary APS, did not react with phospholipids. Immunization of naive BALB/c mice with EY2C9 was followed by production of sustained high titers of antiphospholipid antibodies associated with prolonged activated partial thromboplastin time (APTT) (46.8 +/- 5.0 s vs. 22.4 +/- 1.7 s, in the non-immunized mice). Mice immunized with TM1B9 had a more moderate titer of antiphospholipid antibodies and did not show prolonged APTT. The pregnant mice, that were immunized with EY2C9, had increased fetal resorption rate (the equivalent of fetal loss in the human) of 36.8 +/- 10% (vs. 2 +/- 4% in mice immunized with TM1B9). Our results confirm that monoclonal aCL, derived from a patient with APS, can have a pathogenic potential, dysregulating the idiotypic network and leading to the development of characteristic signs of APS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The presence of antiphospholipid antibodies in acute myocardial infarction.

This study was undertaken to determine if there is an association between increased titers of five different antiphospholipid antibodies (aPLA) in young patients' sera and the occurrence of acute myocardial infarction (AMI). Antibodies to anticardiolipin (aCL), anti-phosphatidylserine (aPS), antiphosphatidylinositol (aPI), anti-phosphatidylcholine (aPC), and anti-phosphatidylethanol amine (aPEA) were measured in 214 patients (102 patients, 102 healthy controls and 10 patients with antiphospholipid syndrome). These antibodies were measured twice (within 4h of onset of acute myocardial ischemic chest pain and 3 months after the myocardial infarction) by enzyme linked immunosorbent assay (ELISA). Elevated titers of four different aPLA were detected in 6.9% of all patients with AMI on hospitalization. Titers of aPLA in AMI were elevated in the younger age group < 50 years old (P < 0.001) and in men only (not statistically significant). No correlation was found between the presence of aPLA and cardiovascular risk factors (smoking, hypertension, diabetes mellitus and hyper-cholesterolemia). Three of the seven patients with increased titers of aPLA did not have any other cardiovascular risk factors. The titers of aPLA were within normal range 3 months after AMI. Evidence of significantly elevated titers of different aPLA at the early stage of AMI suggests that these autoantibodies are present before the AMI and are not secondary to them. The disappearance of the elevated aPLA 3 months after AMI may be due to an absorption effect or possibly a cyclic phenomenon similarly found in other autoimmune diseases. aPLA may be an additional risk factor for AMI, and should especially be considered in a patient of the younger age group without apparent cardiovascular risk factors.

Adult↗
PubMed1995

De facto mental health services in the rural south.

Health care reform efforts highlighted the continuing scarcity of mental health services for the rural poor. Most mental health services are provided in the general medical sector, a concept first described by Regier and colleagues in 1978 as the de facto mental health service system, rather than through formal mental health specialist services. The de facto system combines specialty mental health services with general medical services such as primary care and nursing home care, ministers and counselors, self-help groups, families, and friends. The nature of the de facto system in rural areas with large minority populations remains largely unknown due to minimal available data. This article examines the availability, accessibility, and use of mental health services in the rural South and the applicability of the de facto model to rural areas. The critical need for data necessary to inform changes in health care relative to rural mental health service delivery is emphasized.

Adult↗
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

[Reactive hyperemia after arterial occlusion: comparison of infrared telethermography and laser Doppler flowmetry].

Before, during and after arterial occlusion we measured Laser-Doppler Flux (LDF) and skin temperature using Infrared-Thermographie (IRT) in 40 healthy adults (20 female, 20 male). In the region of the hypothenar eminence of the left hand LDF and skin temperature showed significantly higher values in male compared with female subjects prior to occlusion (p < 0.01 resp. p < 0.05). After arterial occlusion for 120 seconds LDF showed a significant overshoot of 71.3% (+/- 39.5%) above baseline. During this phase of hyperemia skin temperature rose from 33.5 to 34.8 degrees C (p < 0.0001). This reaction was similar in men and in women. Changes in skin temperature were slower and more prolonged compared with the rapid changes of LDF. The absolute temperatures were significantly higher when we used IRT compared with temperatures measured by resistance thermometry. Both methods showed a close correlation (p < 0.0001, r = 0.891). Using the IRT technique a large number of skin temperatures can be measured simultaneously and temperature changes can be detected and visualized by colour thermograms. Postocclusive cutaneous hyperemia induces similar responses in LDF parameters and in skin temperatures. IRT therefore could be used as an additional tool for the assessment of physiological and pathological functions of the cutaneous microcirculation.

Adolescent↗
PubMed1994

Expression of MUC2-mucin in colorectal adenomas and carcinomas of different histological types.

The expression of mucin MUC2 was investigated in normal colonic tissue, in colonic adenomas and in carcinomas of the mucinous and non-mucinous type. The latter were subdivided into carcinomas originating from the adenoma-carcinoma sequence (ACS) and de novo (DN) carcinomas. The expression was assayed by immunohistochemistry with the monoclonal anti-MUC2 antibody CCP58 and by mRNA semiquantitation. MUC2 protein epitope CCP58 was strongly expressed in 21% of normal colonic tissues, in 40% of villous and in 48% of tubular adenomas. Mucinous carcinomas exhibited strong expression in 72%, ACS carcinomas in 21% and DN adenocarcinomas in none of the tumors investigated. Compared with the adjacent non-malignant tissue (transitional mucosa), CCP58 epitope expression in the tumor was higher in 74% of mucinous carcinomas, but equal or lower in 69% of ACS carcinomas and in 100% of de novo carcinomas. The alterations of MUC2 expression detected by immunohistochemistry in adenocarcinomas were confirmed on mRNA level. These data indicate that the MUC2 expression pattern is different in the 3 carcinoma types investigated. MUC2 over-expression occurs in the adenomatous tissue. It is always maintained in mucinous carcinomas, but frequently decreased in non-mucinous ACS carcinomas. DN carcinomas are most frequently associated with decreased expression of MUC2.

Adenocarcinoma, Mucinous↗
PubMed1994

Protein aggregation reactions: surface free energy model.

The energetics of protein reactions can be evaluated in terms of the surface free-energy model, an approach that estimates changes in the surface free energy of proteins from changes in the area and the charge density of the protein-water interface. This approach has given insight into the reactions of proteins in solution as well as in membranes (receptors and voltage-gated channels). The model highlights the importance of pH and thermal changes in aggregation reactions. It also enables a correct interpretation of the Hill equation describing co-operative reactions, since the Hill coefficient is related to a Gibbs surface excess that varies with the degree of reaction.

Chemical Phenomena↗
PubMed1994

Induction of tissue factor-like activity in monocytes by anti-cardiolipin antibodies.

Anti-cardiolipin Abs (ACLA) are present in the sera of patients with antiphospholipid syndrome (APLS) and are associated with high incidence of thromboembolic phenomena, fetal loss, thrombocytopenia, and prolongation of the phospholipid-dependent coagulation assays (lupus anticoagulant). Recently, it has been shown that APLS can be induced experimentally by using ACLA. However, the pathophysiology of thrombus formation in this syndrome is unknown. Monocytes generate a potent procoagulant activity (PCA) after stimulation with various substances. Increased PCA has been found in monocytes from patients with diseases that are associated with high incidence of thromboembolic phenomena. In the present study, we report that the monoclonal ACLA that were shown previously by us to induce APLS stimulate mononuclear cells to generate a potent PCA. The PCA resembled tissue factor (TF) in that it accelerated clotting through the extrinsic coagulation pathway, was abolished by phospholipase C, and was inhibited by anti-TF mAbs. The induction of TF-like activity by ACLA in monocytes was dose- and time-dependent. It was induced in monocytes and monocytic cell lines, but not in lymphoid or myeloid cells, and did not require T lymphocytes for expression. The generation of PCA was dependent on protein synthesis inasmuch as it was prevented by adding puromycin to the system and was not affected by cytarabine. The TF-like activity that is induced by ACLA in monocytes may activate coagulation and thereby play a major role in the pathogenesis of thrombus formation in APLS.

Adult↗
PubMed1994

Suppression of experimental antiphospholipid syndrome and systemic lupus erythematosus in mice by anti-CD4 monoclonal antibodies.

OBJECTIVE: To investigate whether anti-CD4 antibodies can suppress experimental antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) induced by an anti-DNA monoclonal antibody (MAb). METHODS: BALB/c mice were treated with anti-CD4 MAb either before or 2 months after induction of experimental APS and SLE. Control mice were treated with rat IgG or phosphate buffered saline. Serologic and clinical manifestations of the disease were determined. RESULTS: Treatment of mice with anti-CD4 before or 2 months after disease induction prevented the development of experimental APS and SLE. The treated mice did not develop leukopenia or proteinuria, and had fewer episodes of fetal resorption. Similarly, the treated mice did not develop elevated erythrocyte sedimentation rate, prolonged activated partial thromboplastin time, or thrombocytopenia, and had significantly lower levels of antibodies to double-stranded DNA, histones, MIV-7, cardiolipin, and phosphatidylserine. Levels of CD4+ cells in the lymph nodes declined temporarily after the treatment and then returned to normal. CONCLUSION: Anti-CD4 antibodies can prevent experimental APS and SLE. These results may suggest a role for anti-CD4 treatment in human autoimmune diseases.

Animals↗
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↗
PubMed1994

Antimitochondrial (pyruvate dehydrogenase) antibodies in leprosy.

Sera from 69 patients with leprosy but without liver involvement were assayed for the presence of mitochondrial pyruvate dehydrogenase (PDH)-specific autoantibodies by enzyme-linked immunoabsorbent assay (ELISA), immunoblotting using PDH as an antigen and by enzymatic inhibition test. Twenty-seven of the leprosy serum samples (39.1%) were found to react with PDH by ELISA. However, unlike sera from primary biliary cirrhosis (PBC) patients, none of these were able to inhibit the PDH enzymatic activity. By immunoblotting, it was found that only 2 of the 27 positive sera recognized the 74-kD protein of the PDH complex, which is recognized by sera of most PBC patients. The antimitochondrial antibodies in lepra most probably recognize different epitopes than those in PBC. These findings may indicate that anti-PDH autoantibodies in patients with leprosy may arise by polyclonal B cell stimulation and may represent natural anti-PDH autoantibodies.

Autoantibodies↗
PubMed1994

Geographic independence of HTLV-I and HTLV-II foci in the Andes highland, the Atlantic coast, and the Orinoco of Colombia.

To clarify the ethnic specificity of human T cell leukemia virus type I (HTLV-I) and type II (HTLV-II) carriers among Colombian native Indians, we investigated the geographic distribution of HTLV-I and HTLV-II seroprevalence among the isolated ethnic groups of Mongoloid origin in the Andes highlands and the Atlantic coast of Colombia. HTLV-I carriers were found in 1.6% (1/62 samples) of Inga, 8.5% (5/59) of Kamsa, and 0% (0/55) of Cumbal Indians who live in the Andes highlands at 3000 m above sea level. On the other hand, HTLV-II carriers were found in 4.1% (5/123) of Wayuu Indians, who live in the Guajira region of the Atlantic coast of Colombia at a distance of 1000 km from the Andes highlands. This ethnic specificity of HTLV-II was similarly observed among Guahibo Indians in the Orinoco. The seroprevalence of HTLV-I and HTLV-II was mutually exclusive among Inga, Kamsa, and Wayuu Indians. These results suggest that HTLV-I and HTLV-II may have evolved among Mongoloid populations and been independently transmitted among two different lineages of Colombian native Indians, Andes highlanders and Atlantic coast lowlanders.

Adolescent↗
PubMed1994

Suppression of experimental systemic lupus erythematosus (SLE) with specific anti-idiotypic antibody-saporin conjugate.

The importance of the idiotypic network is represented in experimental SLE induced by active immunization of naive mice with an anti-DNA idiotype (Ab1) emulsified in adjuvant. The mice after 4 months of incubation generate Ab3 having anti-DNA activity. In addition, the mice develop other serological markers for SLE associated with clinical and histopathological manifestations characteristic of the disease. To confirm further the etiological role of the idiotype in this experimental model, the mice were treated with specific anti-idiotypic antibodies (anti-Id) which were also conjugated to a toxin-saporin (Immunotoxin (IT)). Pretreatment of hybridoma cell line producing the anti-anti-Id (anti-DNA = (Ab3)) for 48 h with the anti-Id MoAb (Ab2) reduced the production of anti-DNA by 58%, while pretreatment with the IT resulted in 86% decrease in anti-DNA secretion (saporin alone had only 12% effect). The anti-Id MoAb had no effect on the production of immunoglobulin by an unrelated cell line. In vivo treatment of mice with experimental SLE led to a significant decrease in titres of serum autoantibodies, with diminished clinical manifestations. The results were more remarkable when the IT was employed. These suppressive effects were specific, since an anti-Id treatment of experimental anti-phospholipid syndrome was of no avail. The anti-Id effect was mediated via a reduction in specific anti-DNA antibody-forming cells, and lasted only while anti-Id injections were given. Discontinuation of the anti-Id injection was followed by a rise in titres of anti-DNA antibodies. No immunological escape of new anti-DNA Ids was noted. Our results point to the importance of pathogenic idiotypes in SLE and to the specific potential of implementing anti-idiotypic therapy, enhanced by the conjugation of the anti-Id to an immunotoxin, in particular one with low spontaneous toxicity.

Animals↗
PubMed1994

Pathogenic natural anti-cardiolipin antibodies: the experience from monoclonal gammopathy.

Anti-cardiolipin antibodies (ACA) were detected in 19% of sera from patients with monoclonal gammopathies (MG). ACA were purified from the sera of patients with MG. One of the IgG-ACA was found to be monospecific with high affinity for cardiolipin, and to carry a pathogenic ACA Id (1.10). Active immunization of naive BALB/c mice with the purified IgG-ACA was followed by production in the mice of sustained high titres of ACA, associated with prolonged activated partial thromboplastin time (APTT) (61 +/- 14s versus 31 +/- 2s in control mice; P < 0.001) and thrombocytopenia (468,000 +/- 224,000/mm3 versus 994,000 +/- 92,000/mm3 in controls; P < 0.001). The titres of other autoantibodies (e.g. anti-DNA, anti-histones), although being high after immunization, decreased rapidly and were undetected after 1 month following the boost injection. The mice immunized with the IgG-ACA exhibited low fecundity (36% of mice became pregnant versus 62% observed in the group immunized with control IgG). The pregnant mice had increased resorption rate (the equivalent of fetal loss in the human) of 52 +/- 8% (versus 5 +/- 4% in the control group). The mean (+/- s.d.) embryo and placental weights in mice with anti-phospholipid syndrome (APLS) were significantly lower compared with the mice injected with control IgG (682 +/- 304 mg and 102 +/- 12 mg versus 1303 +/- 105 mg and 145 +/- 8 mg, respectively; P < 0.001). Serum monoclonal immunoglobulins having autoantibody activity may be regarded as an expansion of clones producing natural autoantibodies. Our results confirm the pathogenic role of natural ACA in the pathogenesis of the anti-phospholipid syndrome.

Adult↗