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Biomedical subjects

M Galli

Publications and source records attributed to M Galli.

At least 19 recordsLinked to original sources

Kaolin clotting time and dilute Russell's viper venom time distinguish between prothrombin-dependent and beta 2-glycoprotein I-dependent antiphospholipid antibodies.

Antiphospholipid (aPL) antibodies include anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies. LA antibodies recognize the complex of lipid-bound (human) prothrombin, in this way inhibiting the phospholipid-dependent coagulation reactions, whereas aCL antibodies are directed towards beta 2-glycoprotein I (beta 2-GPI) bound to an anionic lipid surface. According to their behavior in coagulation reactions, we have divided aCL antibodies into two groups: aCL-type A, which inhibit the phospholipid-dependent coagulation reactions because they enhance the binding of beta 2-GPI to the procoagulant phospholipid surface; and aCL-type B antibodies, which are devoid of anticoagulant properties. We report the distinctive laboratory and clinical profiles of 25 patients with well-characterized, phospholipid-dependent inhibitor of coagulation. Fourteen patients had LA antibodies (aCL-type B were concomitantly present in 10 cases, while in the other four, aCL titer was normal), and the other 11 had aCL-type A antibodies. The laboratory evaluation of the two groups showed the dilute Russell viper venom time (dRVVT) to be the most abnormal coagulation test in the aCL-type A-positive group, whereas the kaolin clotting time (KCT) was the most abnormal assay in the LA-positive group. In fact, the ratios of the coagulation times of patient plasma over normal pooled plasma (mean +/- standard deviation) for LA versus aCL-type A antibodies were 1.48 +/- 0.27 versus 2.20 +/- 0.42, P = .0001, and 2.22 +/- 0.42 versus 1.50 +/- 0.42, P = .0003, for the dRVVT and KCT, respectively. No differences were observed either in the ratios of the activated partial thromboplastin times and the prothrombin times or the plasma levels of beta 2-GPI and prothrombin. Conversely, aCL titers were significantly higher in aCL-type A-positive patients (147 +/- 44 U) than in the LA-positive group (61 +/- 55 U; P = .0003). We ruled out the possibility that platelet contamination of plasma could account for the observed coagulation profiles, as the two patterns were reproduced in platelet-free plasma. In addition, we performed clotting tests in plasma in the presence of phospholipids and calcium after addition of factor IXa or factor Xa. The assay performed with factor Xa was more sensitive to the presence of aCL-type A antibodies, while the assay performed with factor IXa was preferentially sensitive to LA-containing plasmas, supporting the earlier findings with the dRVVT and KCT assays.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Balloon expandable stent implantation after iatrogenic arterial dissection of the left subclavian artery.

A patient undergoing attempted angioplasty of a left internal mammary artery graft to left anterior descending coronary artery developed an iatrogenic dissection of the left subclavian artery, with symptoms of left arm claudication. A balloon expandable stent was inserted with an excellent angiographic result. The patient has remained free of symptoms or signs of decreased arm flow, with a patent subclavian artery demonstrated on angiography 8 months later. The excellent early-to-moderate term clinical and angiographic results support the efficacy of this technical approach.

Angioplasty, Balloon

Monoclonal antibodies against native ovarian tumor cells: specificity and characterization of the antigen. A preliminary report.

Monoclonal antibodies were prepared against native human ovarian carcinoma cells derived from the ascitic fluid of a patient (BH). One antibody, HC7R7, was selected on the basis of its binding to tumor BH cells, to other ovarian tumor cell lines (CAOV-3 and GZL-8), but not to the patient's fibroblasts. One hundred cell smears from ascitic and pleural effusions of tumor-suspected patients were immunostained with HC7R7. All serous ovarian carcinomas and half of the breast carcinomas stained positive with HC7R7; cells from noncancer ovarian aspirates were negative. Mesothelial cells were also stained with HC7R7. A correlation was noted between HC7R7 and OC-125 staining of ovarian tumor cells but not between HC7R7 and c-neu staining of breast tumor paraffin sections. The location of HC7R7-positive material in ovarian tumor cell lines (CAOV-3 and GZL-8) differed from that in the breast tumor cell line (MCF-7). CAOV-3 and GZL-8 showed membrane binding while, in MCF-7, not fully identified intracellular organelles were stained. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis and immunoblots from membrane and cytosol fractions of GZL-8 and MCF-7 showed HC7R7 binding to three protein bands in the membrane fraction and to three other bands in the cytosol, all in the 29- to 68-kDa range. Two of the bands were glycoproteins. The only band that was different in the GZL-8 and MCF-7 cells was a 43-kDa glycoprotein, which was more pronounced in the MCF-7 cells. The possible significance of the new HC7R7 antibodies for detection and survey of ovarian malignancies is discussed.

Aged

Activation of human lymphocytes by a monoclonal antibody to B lymphoblastoid cells; molecular mass and distribution of binding protein.

A novel monoclonal antibody (BAT) to the B-lymphoblastoid cell line activates murine lymphocytes and exhibits a striking antitumor activity in mice. In order to evaluate the potential use of this antibody against human cancer, we have investigated its immuno-stimulatory properties on human peripheral blood lymphocytes (PBL). Our findings demonstrate that BAT mAb induces proliferation and cytotoxicity in human PBL against natural-killer-cell-sensitive and natural-killer-cell-resistant tumor cell lines. Interleukin-2 at a low concentration synergizes with BAT mAb in eliciting these effects. BAT mAb binds to human peripheral T cells as revealed by a double-labelling technique using anti-CD3 and BAT mAb. The molecular mass of the antigen recognized by BAT mAb was 48-50 kDa under reducing and non-reducing conditions. This study provides a basis for future experiments to evaluate the use of BAT mAb in the immunotherapy of cancer.

Adjuvants, Immunologic

Frequent detection of antibodies against HTLV antigens in patients with AIDS-related non-Hodgkin lymphoma.

We studied the prevalence of anti-HTLV-I/II antibodies in 22 patients with AIDS-related non-Hodgkin lymphoma (NHL), 453 HIV-1-infected patients without lymphoma (194 of whom were diagnosed as having AIDS), and 6 HIV-1-positive and 75 HIV-1-negative patients with Hodgkin lymphoma. The frequency of serological reactivity against HTLV antigens was significantly higher in the AIDS patients with lymphoma than in those without (8 of 22, 36.4% vs. 20 of 194, 10.3%-p = 0.0027). One of the HIV-1-positive and none of the HIV-1-negative patients with Hodgkin lymphoma showed anti-HTLV-I/II reactivity. Four of the eight seropositive NHL patients showed antibodies directed against HTLV-II recombinant antigens when tested for serological discrimination in a Western blot assay. A PCR study of PBMCs from the only patient with NHL still alive at the time of the study showed HTLV-II-specific sequences in the genomic DNA. These data suggest that HTLV-II or a closely homologous retrovirus infects a high proportion of patients with AIDS-associated NHL.

Adult

High prevalence of human T cell lymphotropic virus type II infection in patients affected by human immunodeficiency virus type 1--associated predominantly sensory polyneuropathy.

The etiopathogenesis of peripheral neuropathy (PN) that frequently affects human immunodeficiency virus (HIV) type 1-positive patients remains undefined. Forty-seven HIV-1-positive patients with PN (8 with inflammatory demyelinating polyneuropathy and 39 with predominantly sensory polyneuropathy [PSP]) and 266 controls with symptomatic HIV-1 infection without PN were screened for antibodies to human T cell lymphotropic virus (HTLV) types I and II. The prevalence of antibodies to HTLV-II was significantly higher in patients with PSP than in controls (30.8% vs. 8.3%; P < .001). All seropositive patients with PN had HTLV-II DNA in their peripheral blood mononuclear cells by polymerase chain reaction (PCR) analysis. PCR analysis of tissues from 1 patient with PSP who died during the study showed HTLV-II proviral sequences in the femoral nerve and basal nuclei. These results support the hypothesis that HTLV-II represents an etiologic factor in the pathogenesis of a considerable proportion of PSP in patients infected with HIV-1.

Acquired Immunodeficiency Syndrome

A simple method for estimating the skeletal uptake of diphosphonates.

It is possible to obtain an estimate of the bone uptake of diphosphonates after 3 h (BU) on the basis of the difference between the dose administered and the sum of the component eliminated in the urine plus the component present in the extra-osseous volume of distribution. The results of this simple method have been compared in 15 patients using whole body retention at 24 h (determined by means of a complete urine collection) and the ratio of plasma concentrations of 51Cr-EDTA/99Tcm-HMDP after 3 h (DPS). Both DPS and BU can be used on a practical basis, and therefore be used routinely with scintigraphy. The added advantage is that, for BU, the use of a second radiopharmaceutical is avoided.

Adult

In vitro anti-HIV-1 antibody production in subjects in different stages of HIV-1 infection.

We evaluated the in vitro antibody production from peripheral blood mononuclear cells (PBMC) against HIV-1 proteins in infected adults. Fifty-four HIV-1 infected patients (four recent seroconverters, 15 asymptomatics with a CD4 count higher than 500/microliters, 27 asymptomatics with a CD4 count between 200 and 500/microliters and eight symptomatic patients) were tested. PBMC were incubated in the presence or absence of 1% pokeweed mitogen (PWM) at 37 degrees C for 8 days. Western blot assay, p24 antigen ELISA and anti-p24 antibody ELISA were performed on serum and culture supernatants. Spontaneous production of anti-env antibody in culture supernatants was evidenced in all subjects. All the positive supernatants for anti-core antibodies (18/54) were derived from asymptomatic patients. PBMC from recent seroconverters and from symptomatic patients did not produce any anti-core antibody. Antibody production decreased after stimulation with PWM. The concentration of p24 antigen did not significantly increase in p24 positive supernatants following acidification (P = 0.1), suggesting that the inability to detect p24 antibody was not due to the anti-p24 antibody complexed to p24 antigen in culture supernatants. In vitro production of anti-p24 antibodies was significantly more frequent in asymptomatic subjects with high CD4+ cell counts (P = 0.02) and was absent in recent seroconverters. This last finding suggests that during the initial phases of the infection, anti-p24 antibody production may be restricted to cells residing in lymphoid organs. In addition, the lower percentage of anti-core antibody in people with low CD4+ cell counts is not merely a consequence of the binding of the antibody to an increased amount of antigen, but probably reflects an impaired production or a sequestration of producing cells in lymphoid tissue during the late stages of the infection.

Acquired Immunodeficiency Syndrome

Percutaneous balloon pericardiotomy for malignant pericardial tamponade.

Recurrent pericardial effusion or tamponade can complicate malignant disease. The medical approach with pharmacologic agents has a high recurrence rate. Balloon pericardiotomy (BP) may provide a less invasive alternative to surgery. We performed BP in ten high-risk patients with malignant pericardial tamponade (MPT). BP was performed with aseptic technique under fluoroscopic and echocardiographic guidance. We used a percutaneous subxiphoid approach. A 20- to 25-mm-wide and 4-cm-long balloon was introduced over a stiff guide wire, positioned across the parietal pericardium, and manually inflated until the waisting disappeared. Echocardiographic study and chest radiograph were taken before, immediately after the procedure, and during follow-up. The procedure was successful and well tolerated in all patients. There were no immediate or late complications. No patients developed recurrence of pericardial effusion at up to 10 months' follow-up. In conclusion, BP can be performed in patients with MPT with high rate of procedural success. It may become the preferred treatment to avoid a more invasive procedure in these critically ill patients.

Adult

The AIDS epidemic.

AIDS epidemic began about 15 years ago; since then, the number of new cases have increased over time. By the end of 1994, 1,025,073 AIDS cases had been reported to the WHO, with a 20% increase in the number of cases since December 1993. As is now evident that the majority of cases occur in developing countries, under-diagnosis, under-reporting and delays in reporting explain the big difference existing between reported and estimated AIDS cases, giving a 4.5 million cumulative AIDS cases worldwide, as of late 1994. In the industrialized countries, the spread of HIV infection began in the late 1970's or early 1980's among homosexual men and IVDU's. Heterosexual transmission was, at first, very limited, though recent data has shown an increase in its diffusion. On the contrary, in Sub-Saharan Africa and the Caribbean, transmission was almost exclusively heterosexual. High rates of infection among young women led to a corresponding increase of perinatal transmission, infecting more than 1.5 million children since the beginning of the pandemic. The estimated number of HIV infections worldwide, as of late 1994, is of 17 millions. Thus, even if some evidence indicates a possible decline of the pandemic in industrialized countries over the next few years, probably because heterosexual transmission was less common, developing countries appear to present an increasing number of HIV infections in young people and, consequently, in children. The real impact of such an epidemic is stressed by the fact that HIV is becoming the leading cause of death among, young people, both in industrialized and developing countries.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

The role of upper limb somatosensory evoked potentials in the management of cervical spondylotic myelopathy: preliminary data.

We studied upper limb somatosensory evoked potentials (SEPs) in 11 patients with MRI and clinical evidence of cervical spondylotic myelopathy (CSM), before and after cervical open-door laminoplasty. SEP studies before surgery revealed two main types of abnormality, the first characterized by the isolated loss of the spinal N13 response, reflecting the dysfunction of dorsal horn cervical cells in 4 patients. The second combined abnormalities of both spinal N13 and scalp far-field P14 potential, suggesting the involvement of both dorsal horn cells and dorsal columns at the cervical level in 7 patients. After surgery, N13 recovered in 9 patients, while P14 abnormalities remained unchanged. Clinical recovery, evaluated by means of the Japanese Orthopaedic Association (JOA) disability scale, was accompanied by SEP improvement. Moreover, this improvement was more pronounced in patients with isolated loss of the N13 than in patients with combined abnormalities of the N13 and scalp P14 response. Our data strongly suggest that upper limb SEPs can be useful in monitoring the effectiveness of surgery, as well as in selecting before surgery patients who are likely to have a better postsurgical outcome.

Adult

Evidence of residual ischaemia: real danger or myth?

The extent and severity of residual myocardial ischaemia are well-known as major determinants of mortality after myocardial infarction, and non-invasive assessment of these parameters still plays a critical role in the management of patients. Most of the published data on this topic derive from observations collected before the widespread use of thrombolysis. The results of large multicentre trials assessing the most appropriate therapies after thrombolysis have shown that the more conservative strategy of reserving catheterization and revascularization for patients with recurrent spontaneous or induced ischaemia may be the best approach. Sophisticated techniques to detect more accurately the residual ischaemic burden after infarction have been suggested that would have a major impact on clinical decision making and on the cost of health care. The relative influence of residual ischaemic on the prognosis after myocardial infarction, however, has recently been questioned. The relative risk associated with residual ischaemia seems to be low compared with other predictors of mortality. The progression of coronary artery disease is variable and highly unpredictable, and this may be a major limitation of our ability to predict further ischaemic events.

Clinical Trials as Topic

Anticoagulant activity of beta 2-glycoprotein I is potentiated by a distinct subgroup of anticardiolipin antibodies.

Plasmas of 16 patients positive for both IgG anticardiolipin (aCL) antibodies and lupus anticoagulant (LA) antibodies were subjected to adsorption with liposomes containing cardiolipin. In 5 of these plasmas both the anticardiolipin and the anticoagulant activities were co-sedimented with the liposomes in a dose-dependent manner, whereas in the remaining cases only the anticardiolipin activity could be removed by the liposomes, leaving the anticoagulant activity (LA) in the supernatant plasma. aCL antibodies purified from the first 5 plasmas were defined as aCL-type A, while the term aCL-type B was used for antibodies in the other 11 plasmas, from which 2 were selected for this study. Prolongation of the dRVVT was produced by affinity-purified aCL-type A antibodies in plasma of human as well as animal (bovine, rat and goat) origin. aCL-type B antibodies were found to be devoid of anticoagulant activity, while the corresponding supernatants containing LA IgG produced prolongation of the dRVVT only in human plasma. These anticoagulant activities of aCL-type A and of LA IgG's were subsequently evaluated in human plasma depleted of beta 2-glycoprotein I (beta 2-GPI), a protein which was previously shown to be essential in the binding of aCL antibodies to anionic phospholipids. Prolongation of the dRVVT by aCL-type A antibodies was abolished using beta 2-GPI deficient plasma, but could be restored upon addition of beta 2-GPI. In contrast, LA IgG caused prolongation of the dRVVT irrespective of the presence or absence of beta 2-GPI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Determination of glutamic acid decarboxylase activity and inhibition by an H2O2-sensing glutamic acid oxidase biosensor.

The catalytic activity of the enzyme L-glutamic acid decarboxylase (GAD) is determined by an amperometric method based on a recently developed glutamate-selective biosensor. The biosensor is composed of an amperometric H2O2 electrode and a biocatalytic membrane containing the enzyme glutamic acid oxidase (GAO). The biosensor allows the direct and continuous measurement of GA levels by monitoring the H2O2 produced at the electrode interface as a coproduct of the GAO-catalyzed GA oxidation to alpha-ketoglutaric acid. Since GA is transformed to gamma-aminobutyric acid and CO2 under the catalytic activity of GAD, the rate of GA consumption in solution, monitored by the GAO biosensor, represents a reliable measure of GAD catalytic activity. Additional experiments performed in the presence of different concentrations of the GAD inhibitor valproic acid have shown the suitability of the proposed approach for the study of GAD inhibitors also. Discussion of the main experimental characteristics of this new analytical method is given in terms of sensitivity, reproducibility, and reliability of the experimental results and ease, time, and cost of operation.

Amino Acid Oxidoreductases