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Biomedical subjects

A Pasi

Publications and source records attributed to A Pasi.

At least 19 recordsLinked to original sources
PubMed2001

Family study of non-responsiveness to hepatitis B vaccine confirms the importance of HLA class III C4A locus.

Non-responsiveness to hepatitis B virus (HBV) vaccine in adults is strongly associated with HLA-C4AQ0,DRB1*0301,DQB1*02 haplotype. This association was also demonstrated in neonates who failed to mount a humoral response to challenge with HBV vaccine. About 4% of vaccinated newborns do not reach a protective antibody level (> or =10 mIU/ml) at seroconversion and 0.4% is a non-responder even after receiving a fourth dose of vaccine (true non-responders (TNR)); while 3.6% achieved an antibody level > or =10 mIU/ml (slow responders (SR)) only when reboostered with the fourth dose. In the present study we extend the vaccination and HLA typing to 91 family members of probands to understand better the possible parent-to-child transmission of this trait. A transmission disequilibrium test (TDT), performed in 27 families, showed that the C4AQ0 allele was almost always transmitted to probands, both TNRs and SRs. Although not statistically significant, the highest LOD score was obtained with C4A locus: 1.58. These results suggest the presence of a region regulating immune response against HBV vaccination near to or coincident with the C4A locus.

Alleles↗
PubMed2000

Humoral response to recombinant hepatitis B virus vaccine at birth: role of HLA and beyond.

From 1991 to 1998 we vaccinated 4835 neonates against hepatitis B virus (HBV) and monitored their humoral response to the recombinant vaccine. In a sample of 184 of these babies we studied the association between HLA class I and II genomic polymorphisms and humoral response to the vaccine and the association between the response and immune-mediated diseases. A subgroup of 96 babies also underwent HLA class III (C4A and C4B) typing. Four levels of humoral response were identified, each with a peculiar MHC restriction. Different HLA products seem to act as agonists (C4AQ0 and HLA-DQB1(*)02) or antagonists (C4AQ0, HLA-DQB1(*)02, and HLA-DRB1(*)11, DQB1(*)0301) in lowering humoral response to HBV vaccine. The group of responders was characterized more for lacking "nonresponder" alleles than for having specific "responder" ones. Tolerance to HBV peptides may have clinical implications, possibly being a marker for babies with a genetic risk of immunopathologies. In fact, many of the poor responders carried from two to four HLA-DQ alpha beta heterodimers predisposing to insulin-dependent diabetes mellitus and celiac disease. Two true nonresponders suffered from allergies and two slow responders had transient episodes of hyperglycemia.

Alleles↗
PubMed1997

Fulminant liver failure in association with the emetic toxin of Bacillus cereus.

BACKGROUND: A 17-year-old boy and his father had acute gastroenteritis after eating spaghetti and pesto that had been prepared four days earlier. Within two days, fulminant liver failure and rhabdomyolysis developed in the boy and he died. The father had hyperbilirubinemia and rhabdomyolysis but recovered. We investigated the cause of these illnesses. METHODS: Bacteria were isolated and characterized by conventional methods, and bacterial toxins were quantified by immunoassays and cell-culture techniques. The effect of the isolated toxin on the rates of oxidation of various substrates was analyzed in rat-liver mitochondria. RESULTS: Autopsy of the boy's liver revealed diffuse microvesicular steatosis and midzonal necrosis that suggested impaired beta-oxidation of liver mitochondria due to a mitochondrial toxin. There was no evidence of ingestion of heavy metals, halogenated compounds, hepatotoxic drugs, or staphylococcal enterotoxin. However, high concentrations of Bacillus cereus emetic toxin were found in both the residue from the pan used to reheat the food and the boy's liver and bile. B. cereus was cultured from the intestinal contents and the pan residue. The emetic toxin isolated from the B. cereus cultures was found to be a mitochondrial toxin. CONCLUSIONS: Fulminant liver failure developed after the ingestion of food contaminated with the B. cereus emetic toxin. The toxin inhibits hepatic mitochondrial fatty-acid oxidation, indicating that it caused liver failure in this patient.

Adolescent↗
PubMed1997

Characterization of nephropathy induced by immunization with high molecular weight dextran.

BACKGROUND: Injection of DEAE dextran into Lewis rats can produce proteinuria and has been reported as a model of IgA nephropathy. METHODS: Cationic diethyl aminoethyl (DEAE) dextran of molecular weight 500 kDa was injected into male Lewis rats. After a pre-immunization period of 3 weeks, the animals were divided into two groups: group 1 (n = 14) received daily i.v, injections of 3.5 mg of antigen, group 2 (n = 14) was injected with 1.5 mg three times per week for a total period of 6 weeks. I.v. treatment was initiated with gradually increasing doses of DEAE dextran in both groups for 1 week, after which the maintenance dose was reached. RESULTS: We observed the appearance of proteinuria in a nephrotic range after 5 weeks of i.v. injections in group 1 (urinary excretion: 332 +/- 83 mg/24 h, controls: 53 +/- 14 mg/24 h). In group 2, the proteinuria was almost equal to protein excretion of healthy rats of the same weight (67 +/- 20 mg/24 h). The serum and urine creatinine were normal. By light microscopy of kidney biopsies, the presence of focal and segmental proliferation of mesangial cells after 6 weeks of i.v. injections was identified. Immunohistochemistry revealed no deposition of IgA, IgM, IgG, or C3. Using anti-ED1 antibodies, there was no evidence of interstitial infiltration of monocytes/macrophages after 6 weeks of i.v. injections. Staining for proliferating cell nuclear antigen (PCNA) did not show the presence of proliferating cells either in glomeruli or in the interstitium. Staining with FITC-WGA lectin revealed focal and segmental loss of the negative charge in the capillary wall. By electron microscopy there was deposition of dextran in the basal membrane and segmental and focal damage of the podocyte foot processes. As the chemokine RANTES may be involved in glomerular injury, we examined the kidneys of proteinuric and non-proteinuric rats for the presence of RANTES. By indirect immunofluorescence only the proteinuric rats showed RANTES deposition in the mesangium. CONCLUSIONS: Injection of rats with DEAE dextran leads to dose-dependent proteinuria without deposition of immune complexes but with podocyte damage. This is associated with local expression of the chemokine RANTES which may play a role in proteinuria of glomerular disease.

Animals↗
PubMed1997

[Drug addiction--origin, development and pharmacological intervention].

The present essay on drug addiction deals, under the escort of empirical knowledges emanating from medico-legal toxicology, mainly with the behavioural, neurobiological, forensic and pharmacotherapeutical aspects of drug seeking and taking behaviour. The article emphasizes the idea that treatment of drug dependence [including that of the associated diseases and complications] should be performed according to the specific pharmacological and toxicological properties of the drugs involved. Furthermore, the treatment of drug dependence should be carried out in agreement with the individual needs of the patient, and in concordance with the multiple factors involved in the development and maintenance of drug addiction.

Acupuncture Therapy↗
PubMed1994

A novel hypothesis: specific oncogenes and tumor suppression genes are involved in the expression of the proopiomelanocortin gene by small cell lung cancer.

The endogenous opioid beta-endorphin, a derivative of proopiomelanocortin, stimulates the growth of cloned human small cell lung carcinoma. The present hypothesis states that mutations of the retinoblastoma gene (a tumor suppressor gene) associated to the malignant transformation of bronchial cells would trigger a cascade of biomolecular events leading to 'de novo' proopiomelanocortin expression in small cell lung carcinoma.

ACTH Syndrome, Ectopic↗
PubMed1993

Classifying cytostatics on the basis of their angiocidal and angiostatic effects.

This study describes the effects of ten clinically used cytostatics [bleomycin (BLM), cytarabine (Ara-C), cyclophosphamide (CTX), doxorubicin (DOX), etoposide (VP-16), 5-fluorouracil (5-FU), methotrexate (MTX), mitoxantrone (MXN), vincristine (VCR), and vinblastine (VLB)] on the chorioallantoic membrane vessels--especially on vessel counts--and on the weight of the chicken embryo. A significant reduction of vessel counts (VC) due both to angiocidal and an angiostatic action, was induced by DOX, MXN, VP-16, VCR, and VLB. 5-FU and BLM induced only a (weak) angiostatic effect. MTX, Ara-C, and CTX were neither angiocidal nor angiostatic. The classification of cytostatics presented here might have implications for their use in the clinical treatment of malignant tumors.

Allantois↗
PubMed1993

beta-Casomorphin-immunoreactivity in the brain stem of the human infant.

Using a peptide extraction procedure, reversed phase high performance liquid chromatography, and a radioimmunoassay that utilized an antibody raised specifically against human beta-casomorphin-8 (BC8), BC-immunoreactivity (BCIR) was detected in rostrocaudally increasing levels in nineteen microscopically distinct and functionally relevant areas of mesencephalon, pons cerebri, and medulla oblongata of eight infants. On the basis of the methodology used, it can be concluded, that the BCIR present in their brain stem was due to BC8 and/or to some of its congeners. Data in the literature together with those of this study indicate that beta-casomorphins could be transported by specific mechanisms from the blood into the brain stem and that they could play a role in the central regulation of various physiological phenomena.

Blood-Brain Barrier↗
PubMed1992

Behavioral and enzymatic interactions between benzyl alcohol and ethanol.

Acute IP injection of benzyl alcohol but not benzaldehyde (0.5 g/kg) caused aversion to voluntary drinking of 5% ethanol solution by male rats with preference to ethanol. Benzyl alcohol noncompetitively inhibited hepatic alcohol dehydrogenase of rats maintained for a short term on 5% ethanol compared to control. The results suggest an adverse interaction between benzyl alcohol and ethanol underlying the observed aversion to ethanol.

Alcohol Dehydrogenase↗
PubMed1992

Beta-endorphin: regional levels profile in the brain of the human infant.

Immunoradiometrical determinations of beta-endorphin (beta-EP) levels in 29 discrete brain regions from a series of victims of "Sudden Infant Death Syndrome" yielded a uniformly low levels profile in various areas of telencephalon, thalamus, pons, cerebellum and medulla oblongata. This low levels profile was interrupted by intermediate and high beta-EP levels in the midbrain and in two diencephalic zones. This study provides, for the first time, a comprehensive, neurochemically determined regional profile of beta-EP levels in the brain of the human infant.

Brain Chemistry↗
PubMed1992

A novel two-site enzyme immunoassay for the sensitive detection of beta-endorphin in specific human brain stem regions.

On the line of experiences previously made in the development of a two-site immunoradiometric assay (TS-IRMA), we generated, in the present study, a novel, sequential, noncompetitive two-site immunoenzymometric assay (TS-IEMA) for the determination of the non-acetylated form of human beta-endorphin (beta h-EP). At variance with other assays reported in the literature, but in analogy to the TS-IRMA, the TS-IEMA does not require previous separation of beta h-EP. The TS-IEMA detects beta h-EP in central nervous tissues at a very low detection limit, and to a high degree of reproducibility, precision, sensitivity, and accuracy. The newly developed assay was then used to determine beta h-EP levels in the tissues of distinct brainstem regions. Tissues were collected, by the Palkovits's punching technique, from a series of victims of "Sudden Infant Death Syndrome" and of miscellaneous infections. The TS-IEMA, combined with the punching technique, has revealed, in the measure of its application in the present study, an unprecedented high degree of resolution of the neurochemical architecture of beta h-EP in the human infantile brainstem.

Brain Stem↗
PubMed1991

Angiogenesis: modulation with opioids.

1. The effect of beta-endorphin (beta-EP) and morphine sulfate (MS), in presence and absence of naloxone (NX), on chicken chorioallantoic membrane was studied as a function of blood vessel proliferation. 2. A 50% reduction in blood vessel proliferation occurred by 10 micrograms of beta-EP or by 5 micrograms of MS per egg compared to controls. 3. An individual dose, i.e. 5 micrograms of beta-EP, did not significantly inhibit blood vessel counts after initial 24 hr period of the drug application when given alone compared to inhibition occurring with combined use of NX. 4. NX (1 microgram) did not significantly reverse the angiostatic effects of MS (10 micrograms) or of beta-EP (5 micrograms). 5. The observed modulation of angiogenesis by opioids suggests involvement of beta-EP and MS in the proliferation of vascular endothelial cells. 6. This may be due to an effect of beta-EP and MS on cell-mediated immunity factors such as interferons, interleukins and prostaglandin E2.

Animals↗
PubMed1991

Opioid receptor proteins in human brain. Detection with monoclonal anti-idiotypic antibodies.

In order to identify opioid receptor proteins, we first ascertained the presence of mu-receptors in membranes of the human cerebral frontal cortex, using binding studies performed with sufentanil. Sufentanil binding was reversed by naloxone and prevented by an anti-idiotypic opioid receptor-specific antibody. This antibody was bound specifically by proteins (molecular weights of 66 and 68 Kda) detected in frontal cortex membrane preparations by sodium dodecyl sulphate-polyacrylamide-gel electrophoresis in combination with western blot analysis. Binding of the same antibody was achieved in dot blots of homologous cerebral and cerebellar cortex preparations.

Antibodies, Anti-Idiotypic↗
PubMed1991

Beta-endorphin-like immunoreactivity: assessment of blood levels in patients with tumors of different origin.

Beta-endorphin-like immunoreactivity (beta-ELIR) blood levels in control subjects and in patients with different carcinoma and non-Hodgkin's lymphoma tumor types, were found within the same range, with the exception of one carcinoma type. This pertained to a group of patients with small cell lung cancer who had a significantly higher median beta-ELIR level compared to controls. This finding, and the fact that proopiomelanocortin expression is enhanced in tissues of this cancer type, suggest that the latter might secrete elevated beta-ELIR amounts into the blood of the affected patients.

Female↗
PubMed1989

Beta-endorphin in the brainstem and the cerebellum of the human infant: regional levels' profile assessed with immunoaffinity chromatography and solid phase radioimmunoassay.

The regional levels' profile of human beta-endorphin (beta h-EP) was studied in the brainstem and the cerebellum of 16 infant victims of "Sudden Infant Death Syndrome" and other death causes. An immunoaffinity chromatography procedure based on a monoclonal antibody directed specifically against the N-terminus of beta-EP was used to extract this peptide from the tissue samples. Beta-EP was then assessed quantitatively by means of a very sensitive solid phase radioimmunoassay (using a polyclonal antibody specific for the C-terminus of beta-EP) developed especially for the study presented here.

Brain Stem↗