Showing papers in "International Journal of Clinical & Laboratory Research in 1994"
TL;DR: The pre-clinical data which have led to the use of Taxol in man, the main clinical results thus far obtained, the toxicities associated with its use, current ongoing trials and future clinical directions of this promising agent are addressed.
Abstract: Taxol (paclitaxel), an anti-microtubule agent extracted from the needles and bark of the Pacific yew tree Taxus brevifolia, has shown a remarkable anti-neoplastic effect in human cancer in phase I studies and early phase II and III trials thus far conducted. This has been reported primarily in advanced ovarian and breast cancer, although significant activity has also been documented in small-cell and non-small-cell lung cancer, head and neck cancers, and with lower activity in metastatic melanoma. The clinical utilization of Taxol had been previously somewhat restricted by its limited availability, a limitation that has recently been overcome by combined efforts of pharmaceutical, agricultural, and governmental agencies. In this review we shall address the pre-clinical data which have led to the use of Taxol in man, the main clinical results thus far obtained, the toxicities associated with its use, current ongoing trials and future clinical directions of this promising agent.
89 citations
TL;DR: It is demonstrated that simvastatin lowered both low-density lipoprotein-cholesterol and Apo B plasma levels and plasma and platelet levels of CoQ10, and that CoQ 10 prevent both plasma and Platelet CoQ20 reduction, without affecting the hypocholesterolemic effect of simvASTatin.
Abstract: Ubiquinone is a carrier of the mitochondrial respiratory chain which regulates oxidative phosphorylation: it also acts as a membrane stabilizer preventing lipid peroxidation. In man the quinone ring originates from tyrosine, while the formation of the polyisoprenoid lateral chain starts from acetyl CoA and proceeds through mevalonate and isopentenylpyrophosphate; this biosynthetic pathway is the same as the cholesterol one. We therefore performed this study to evaluate whether statins (hypocholesterolemic drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase) modify blood levels of ubiquinone. Thirty unrelated outpatients with primary hypercholesterolemia (IIa phenotype) were treated with 20 mg of simvastatin for a 3-month period (group S) or with 20 mg of simvastatin plus 100 mg CoQ10 (group US). The following parameters were evaluated at time 0, and at 45 and 90 days: total plasma cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, Apo A1, Apo B and CoQ10 in plasma and in platelets. In the S group, there was a marked decrease in total cholesterol low-density lipoprotein-cholesterol and in plasma CoQ10 levels from 1.08 mg/dl to 0.80 mg/dl. In contrast, in the US group we observed a significant increase of plasma CoQ10 (from 1.20 to 1.48 mg/dl) while the hypocholesterolemic effect was similar to that observed in the S group. Platelet CoQ10 also decreased in the S group (from 104 to 90 ng/mg) and increased in the US group (from 95 to 145 ng/mg).(ABSTRACT TRUNCATED AT 250 WORDS)
70 citations
TL;DR: There was a decrease of protein S activity throughout pregnancy, although protein S antigen did not follow this trend, and the percentage of activated platelets was within the normal reference range, even in late pregnancy.
Abstract: Nineteen pregnant women with uncomplicated pregnancies were studied during the first, second, and third trimesters. We measured the following hemostatic parameters: prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, protein C, protein S, platelet number and volume. Platelet function was examined by a cytofluorimetric method, using an anti-GPM-140 antibody which is directed against a platelet α granule membrane protein. Activated platelets were expressed as a percentage of the GMP-140-positive platelets over total platelets. Fibrinogen levels showed a steady increase during pregnancy; conversely prothrombin time, activated partial thromboplastin time, protein C, and antithrombin III showed no significant modifications and remained within the reference range. There was a decrease of protein S activity throughout pregnancy, although protein S antigen did not follow this trend. The decrease occurred early in pregnancy and persisted during the second and third trimesters, reaching a stable plateau. We observed no platelet volume change or activation: the percentage of activated platelets was within the normal reference range, even in late pregnancy.
68 citations
TL;DR: Because small low-density lipoprotein appears to be a common trait in the general population, more than one of these atherogenic mechanisms may be operating simulataneously to increase risk of coronary heart disease.
Abstract: Data from case-control and cross-sectional studies uniformly demonstrate an association between small, dense low-density lipoprotein and risk of coronary heart disease. This relationship may be attributable to the association of small, dense low-density lipoprotein with other atherogenic lipoproteins, the presence of the insulin resistance syndrome in subjects with small low-density lipoprotein, and/or the increased oxidative susceptibility of small, dense low-density lipoprotein particles. Furthermore, because small low-density lipoprotein appears to be a common trait in the general population, more than one of these atherogenic mechanisms may be operating simulataneously to increase risk of coronary heart disease.
49 citations
TL;DR: In this article, one hundred sixty-one refractory epileptic patients (46 with partial epilepsy) were treated with intravenous immunoglobulins in a controlled double-blind/dose finding clinical trial; patients were followed for 6 months.
Abstract: Sixty-one refractory epileptic patients (46 with partial epilepsy) were treated with intravenous immunoglobulins in a controlled double-blind/dose finding clinical trial; 18 (7 females, mean age 18.5 years) received placebo, while 14 (3 females, mean age 26.2 years, 2 excluded), 14 (4 females, mean age 24.6 years, 1 excluded) and 15 (5 females, mean age 24.4 years) patients received 100, 250 and 400 mg/kg per infusion of intravenous immunoglobulins, respectively. Seven perfusions were scheduled, four the Ist week, and thereafter one during the 2nd, 3rd and 6th week. The patients were followed for 6 months. An optional infusion was given at the end of the study. A comparison of the mean number of seizures per day was made between the baseline (4 weeks before the first infusion) and the 6th month after the first infusion. Patients were considered responders if they had a decrease of at least 50% in daily seizure frequency at the end of the study compared with the baseline. We did not find severe adverse events. One patient had to stop infusions for possible related side effects (vomiting). When all patients were analyzed together, we found a positive trend in favor of intravenous immunoglobulin treatment, but this was not significant (P = 0.095). There was no relationship between dose and efficacy (P = 0.31). When the largest group with partial epilepsy was analyzed separately, we noted 19 responders in the test group, compared with 2 in the placebo. These results were significant (P = 0.041) and remained significant in the subgroup of partial epilepsy with secondarily generalized seizures (30 patients, P = 0.049). The results were not significant after the 3rd month. There was an insignificant correlation between a better therapeutic response and a lower IgA serum level (P = 0.07) or a more severe daily seizure frequency (P = 0.06). The mechanisms of action of intravenous immunoglobulins in epilepsy still remain hypothetical.
48 citations
TL;DR: Understanding of structural domains involved in catalysis, heparin, lipid binding, and enzyme-cofactor interaction as well as the mechanism of action of LPL as an acylglycerol hydrolase has been greatly enhanced.
Abstract: Lipoprotein lipase (LPL) plays a central role in the hydrolysis of circulating triglycerides present in chylomicrons, and very low density lipoproteins. The active form of the enzyme is a non-covalent homodimer which contains multiple functional domains required for normal hydrolytic activity including a catalytic domain, as well as sites involved in co-factor, heparin and lipid binding. Recent studies involving site-directed mutagenesis, the elucidation of the three dimensional crystallographic structure of different lipases, as well as analysis of the molecular defects that result in the expression of the familial chylomicronemia syndrome have provided new insights into the structure-function relationship of LPL. As a result, our understanding of structural domains involved in catalysis, heparin, lipid binding, and enzyme-cofactor interaction as well as the mechanism of action of LPL as an acylglycerol hydrolase has been greatly enhanced.
39 citations
TL;DR: It is found that the treatment was well tolerated after 12 months of therapy and was associated with a substantial increase in the number and function of CD4+ T cells, suggesting the need for a controlled, double-blind clinical trial.
Abstract: We have investigated the effects of combination therapy with thymosin alpha 1 and natural human lymphoblastoid interferon-alpha in human immunodeficiency virus infection and have shown that in vitro this combination treatment: (1) synergistically stimulated the cytotoxic activity against natural killer-sensitive target cells of lymphocytes collected from human immunodeficiency virus-infected donors and (2) did not interfere with the antiviral activity of zidovudine. We thus studied the effects of combination therapy with thymosin alpha 1, interferon-alpha and zidovudine in patients with CD4+ lymphocytes ranging from 200 to 500/mm3 in a randomized non-blinded study and found that the treatment was well tolerated after 12 months of therapy and was associated with a substantial increase in the number and function of CD4+ T cells. A similar effect was not observed in human immunodeficiency virus patients treated with zidovudine alone or associated with single agents. These data suggest the need for a controlled, double-blind clinical trial, recently initiated with the approval and the support of the Italian Ministry of Health.
35 citations
TL;DR: Less known are hemostatic changes induced by exercise training programs: a few data are available on the effects on platelets and coagulation, whereas studies performed on fibrinolysis show a decrease in plasminogen activator inhibitor-1 levels at rest and an increase in fibralelytic capacity after training.
Abstract: A number of hemostatic changes involving platelets, coagulation and fibrinolysis have been reported after acute physical exercise. Results have sometimes been controversial, due to differences in subjects investigated, type of exercise and methods used for hemostatic evaluation. On the whole, physical exercise has been shown to induce: (1) increases in platelet number and activity, (2) activation of coagulation leading to a slight but significant thrombin generation and (3) activation of fibrinolysis. These changes are short lasting. Less known are hemostatic changes induced by exercise training programs: a few data are available on the effects on platelets and coagulation, whereas studies performed on fibrinolysis show a decrease in plasminogen activator inhibitor-1 levels at rest and an increase in fibrinolytic capacity after training.
32 citations
TL;DR: It is suggested that hepatocellular carcinoma develops in liver with severe impairment of cellular antioxidant systems, since, in patients with liver metastases from different cancers, despite low selenium concentrations, cellular scavenger enzymes have normal activities.
Abstract: To investigate the role of oxygen free radicals in hepatocellular carcinoma we assayed tissue scavenger enzymes (superoxide dismutase and selenium-dependent glutathione peroxidase) in liver homogenate, plasma concentrations of vitamins A and E and the serum selenium level from 19 control patients, 23 cases of hepatocellular carcinoma and 18 cases of metastases to liver from different carcinomas. In hepatocellular carcinoma tissue the enzyme activities were all significantly lower than in control liver and in metastases-bearing liver; the enzyme activities of the latter tissues were not different from control liver. In contrast, normal liver adjacent to the hepatocellular carcinoma had decreased activity of superoxide dismutase. Serum selenium concentrations were significantly decreased in patients with hepatocellular carcinoma and those with liver metastases, while vitamin A was significantly decreased only in the former. These findings suggest that hepatocellular carcinoma develops in liver with severe impairment of cellular antioxidant systems, since, in patients with liver metastases from different cancers, despite low selenium concentrations, cellular scavenger enzymes have normal activities.
31 citations
TL;DR: The data indicate that CAP, Allercoat and RAST are satisfactory techniques for specific IgE determination, either for inhalants or for food allergens; CAP, however, offers the highest sensitivity without loss of specificity.
Abstract: Three immunoenzymatic techniques for specific IgE detection (Pharmacia CAP System, Kallestad Allercoat System, Neo Abello Hamlet-IgE) and the classical Phadebas RAST were compared using 34 sera from patients with a clinical diagnosis of allergic disease and 19 sera from healthy non-atopic controls IgE antibodies to 9 aeroallergens and 6 food antigens were assessed and 399 tests were run with each method All techniques showed a high specificity (92%–100%) and satisfactory efficiency (82%–98%), while the sensitivity for RAST, CAP, Allercoat and Hamlet was 89%, 91%, 83% and 53%, respectively, with the lowest values for food allergens There was a good overall correlation of the four techniques, except when the Hamlet method was compared with the other methods for food-specific IgE detection (correlation coefficient <03) These data indicate that CAP, Allercoat and RAST are satisfactory techniques for specific IgE determination, either for inhalants or for food allergens; CAP, however, offers the highest sensitivity without loss of specificity
28 citations
TL;DR: Natural killer cells were found to express a clonally distributed ability to recognize HLA class I alleles, and the selection of new monoclonal antibodies directed against members of a novel family of natural killer specific p58 molecules allowed the identification of the putative natural killer receptors for different MHC class I allele.
Abstract: Recent data have substantially modified our view of natural killer cells. Although maturation of natural killer cells occurs in the absence of a functional thymus, we have shown that clonogenic precursors capable of differentiating into mature CD3−16+56+ natural killer cells exist in CD3−4−8−16− populations isolated from human thymus. Analysis of peripheral bloodderived natural killer clones showed that they can lyse normal cells (e.g., phytohemagglutinin-induced blasts) isolated from some individuals. Importantly, natural killer clones isolated from single individuals displayed different patterns of cytolytic activity against a panel of normal allogeneic cells. These data suggested the existence of a natural killer cell repertoire. A number of observations have revealed that the expression of given HLA class I alleles protects target cells from lysis by different groups of natural killer clones. Evidence has been gained by genetic analysis of the determinants responsible for susceptibility/resistance to lysis by natural killer clones together with analysis, as target cells, of HLA-defective variants or HLA transfectants. Thus, natural killer cells were found to express a clonally distributed ability to recognize HLA class I alleles. The selection of new monoclonal antibodies directed against members of a novel family of natural killer specific p58 molecules allowed the identification of the putative natural killer receptors for different MHC class I alleles. Firstly, a correlation was established between the expression of given p58 molecules (e.g., EB6 and GL183) and the class I alleles recognized. Secondly, anti-p58 monoclonal antibodies restored the natural killer-mediated lysis of class I-protected cells. A similar effect was obtained by inducing modulation of p58 surface molecules with anti-p58 monoclonal antibodies. The implications of these receptor/ligand interactions in the physiopathological behavior of natural killer cells are discussed.
TL;DR: In conclusion, fibroblasts were found to regulate MC survival and differetion, whereas MCs were shown to affect the biochemical properties of fibroblast properties, which can lead to fibrosis.
Abstract: Mast cell (MC) fibroblast interactions may have a role in health and disease. We analyzed the relationships between these cells by utilizing our in vitro model in which mucosal (MMC) and connective tissue (CTMC) type MC were cocultured long-term with different fibroblasts. Mouse 3T3 fibroblasts were used to provide a normal iicroenvironment for MC, while fibroblasts derived from mouse with chronic graft-versushost disease (cGVHD) provided a fibrotic one. We found that both 3T3 and cGVHD fibroblasts maintain CTMC viability, phenotype and functional activity. When MMC were cocultured with 3T3 or cGVHD fibroblasts, they changed their phenotype towards that of CTMC. On the other hand, MCs were found to affect fibroblast properties. Coculture of MMC on 3T3 monolayers was shown to increase Forsmann antigen production and collagen synthesis and stimulate fibroblast proliferation. Resting CTMC or CTMC activated by anaphylactic stimuli induced 3T3 and cGVHD fibroblasts to proliferate more. In addition, CTMC activation increased collagen production by 3T3 fibroblasts. In conclusion, fibroblasts were found to regulate MC survival and differetion, whereas MCs were shown to affect the biochemical properties of fibroblasts, which can lead to fibrosis.
TL;DR: This review focuses on interleukin-1 as a cytokine of strategic importance to the outcome of disease, particularly inflammatory and infectious diseases.
Abstract: During inflammation, injury, immunological challenge or infection, interleukin-1 appears to mediate, in part, the pathogenesis, of disease. Most studies on interleukin-1 are derived from experiments in which bacterial products, such as endotoxins from Gram-negative bacteria or exotoxins from Gram-positive organisms, are used to stimulate macrophagic cells. In general, several cytokines are induced by microbes to their products. Although cytokines are thought to play a role in the outcome of disease, only a few have been directly implicated as mediators of the pathogenic mechanisms of the host. Studies on specific inhibition of interleukin-1 activity have employed interleukin-1 receptor antagonist, interleukin-1 receptors blocking antibodies or soluble interleukin-1 receptors. Experiments in vitro, in animal models of disease and in human subjects have shed considerable light on a critical role for interleukin-1 in the pathogenesis of disease. This review focuses on interleukin-1 as a cytokine of strategic importance to the outcome of disease, particularly inflammatory and infectious diseases.
TL;DR: “Superantigens” have in common an extremely potent stimulatory activity for CD4+, CD8+, and some γδ+ T lymphocytes, and are recognized as important factors in the pathogenicity of the producing pathogens, inducing shock and immunosuppression.
Abstract: “Superantigens” have in common an extremely potent stimulatory activity for CD4+, CD8+, and some γδ+ T lymphocytes. Superantigens use a unique mechanism: they crosslink variable parts of the T cell receptor with MHC class II molecules on accessory or target cells. The interaction site on the T cell receptor is the variable part of the β-chain (Vβ). There are several reasons why these molecules have aroused such tremendous interest in recent years. First, they have provided key information on tolerance mechanisms, both on the deletion of T cells in the thymus and on the induction of peripheral tolerance by anergy and apoptosis. Second, of all polyclonal T cell stimulators they are the ones that most closely mimic the recognition of specific antigen. Finally, they have been recognized as important factors in the pathogenicity of the producing pathogens, inducing shock and immunosuppression. Moreover, it has been postulated that superantigens could be involved in the pathogenesis of certain human diseases.
TL;DR: The ability of interleukin-1, tumor necrosis factor and interleucin-6 to modulate the secretion of the late complement components by HepG2 cells, a human hepatoma-derived cell line known to produce several complement proteins, was evaluated.
Abstract: Liver cells can be induced by interleukin-1, tumor necrosis factor and interleukin-6 to secrete higher amounts of complement components. Information, so far available only for the early components, indicates that these cytokines exhibit different effects on various complement proteins. For instance, they promote the biosynthesis of C3 and B but have no effect on that of C4 and C2. These observations led us to evaluate the ability of interleukin-1, tumor necrosis factor and interleukin-6 to modulate the secretion of the late complement components by HepG2 cells, a human hepatoma-derived cell line known to produce several complement proteins. The amount of complement components in the culture supernatant was evaluated by a sensitive enzyme-linked immunosorbent assay revealing picogram levels of these proteins. The HepG2 cells were found to secrete a substantial amount of C3 (approximately 1μg/106 cells), easily detectable C5 (approximately 150 ng/106 cells) and C8 (approximately 10 ng/106 cells) and a low amount of C6 (approximately 0.5 ng/106 cells), whereas the levels of both C7 and C9 could not be measured. The addition of interleukin-1, tumor necrosis factor and interleukin-6 to the cell culture resulted in an enhanced secretion of C8, whereas that of C5 was only marginally increased. None of these cytokines had a clear effect on the secretion of C6 nor induced the production of C7 and C9. The magnitude of increased levels of C3 and C8 in the culture medium was related to the cytokine used, since interleukin-6 induced a more substantial response of C8 than interleukin-1, and, conversely, interleukin-1 was more effective than interleukin-6 in enhancing the secretion of C3. No clear differences were found in the amount of the various components secreted in response to tumor necrosis factor.
TL;DR: The risk of Down's syndrome pregnancies can be estimated by quantitation of maternal serum markers, namely α-fetoprotein, unconjugated estriol and human chorionic gonadotropin (triple test) by comparison with similar studies performed in other laboratories.
Abstract: The risk of Down's syndrome pregnancies can be estimated by quantitation of maternal serum markers, namely α-fetoprotein, unconjugated estriol and human chorionic gonadotropin (triple test). A prospective study of 2892 pregnant women (median age 33.5 years) is reported. The detection rate of Down's syndrome pregnancies was 80% (confidence intervals 45%–100%) when a risk of 1∶380 or greater was considered “screen positive”; the false positive rate was 13.3% (confidence intervals 12.0%–14.5%). The importance of the accurate assessment of gestational age and the time of blood sampling are emphasized. Our findings are compared with similar studies performed in other laboratories.
TL;DR: The heterogeneity of the vascular mechanisms involved in vascular dementia—namely hypoperfusion—might be a factor that can be positively influenced by targeted therapeutic intervention.
Abstract: Vascular dementia accounts for approximately 20% of all cases of dementia and for about 50% in subjects over 80 years. Thromboembolism with multiple cerebral infarcts was considered to be almost the only pathogenetic pathway of vascular dementia, with multi-infarct dementia as its clinical manifestation. However, there is a great heterogeneity of vascular dementia syndromes and pathological subtypes, as documented by the number of pathogenetic mechanisms now known to underlie the clinical picture. They include thromboembolism and extracerebral and cerebral factors. Among the extracerebral factors are ischemic hypoxic dementia (i.e., dementia due to hypoperfusion), vasculitis, hyperviscosity and abnormalities of hemostasis. Among the cerebral factors are lipohyalinosis, cerebral amyloid angiopathy, disruption of the blood-brain barrier and altered regulation of cerebral blood flow. Therefore, the approach to vascular dementia should take the heterogeneity into account. In this context, the importance of non-infarct type should be considered; subcortical white matter disorder seems to be a noteworthy common pathway of vascular dementia produced by various vascular mechanisms. Finally, the heterogeneity of the vascular mechanisms involved in vascular dementia--namely hypoperfusion--might be a factor that can be positively influenced by targeted therapeutic intervention.
TL;DR: The method is specific, sensitive, rapid, and capable of detecting human papillomavirus-6,−11,−16,−18, and −33 in cervical biopsy specimens.
Abstract: We describe use of a polymerase chain reaction in conjunction with a DNA enzyme immunoassay for the simultaneous detection of multiple types of human papillomavirus in a single microtiter plate The method is specific, sensitive, rapid, and capable of detecting human papillomavirus-6,−11,−16,−18, and −33 in cervical biopsy specimens
TL;DR: Therapy of acute leukemia may be improved by a more accurate assessment of the effects of treatment on tumor burden and by anticipating relapse with greater precision, and the initial results of studies correlating minimal residual disease and clinical outcome are discussed.
Abstract: Therapy of acute leukemia may be improved by a more accurate assessment of the effects of treatment on tumor burden and by anticipating relapse with greater precision. The sensitivity limit of assessing residual disease by morphology is usually 5%. Several alternative approaches are available to study minimal residual disease, defined as the presence of leukemic cells not detectable by morphology. These include studies of chromosomal abnormalities by conventional karyotyping, flow cytometry, in situ hybridization and polymerase chain reaction (PCR), investigation of gene rearrangements by Southern blotting and PCR, and immunological methods. Some of these techniques enable the detection of 1 leukemic cells among 10 000 or more normal cells. In the following, the advantages and limitations of sensitive methods for detecting small numbers of leukemic cells are reviewed. The rationale for monitoring residual disease in acute leukemia and the initial results of studies correlating minimal residual disease and clinical outcome are discussed.
TL;DR: En enzyme-linked immunosorbent assays to detect antibodies of IgG, IgA, and IgM classes reactive with pyruvate dehydrogenase showed high sensitivity and specificity for primary biliary cirrhosis when evaluated in 28 patients withPrimary biliary Cirrhosis, 59 disease controls, and 214 healthy persons.
Abstract: Autoantibodies to the recently described mitochondrial autoantigen, pyruvate dehydrogenase, have been shown to be specific for primary biliary cirrhosis. In the present study we describe enzyme-linked immunosorbent assays to detect antibodies of IgG, IgA, and IgM classes reactive with pyruvate dehydrogenase. These assays showed high sensitivity (95%) and specificity (100%) for primary biliary cirrhosis when evaluated in 28 patients with primary biliary cirrhosis, 59 disease controls, and 214 healthy persons. Quantitation of these autoantibodies by calculating the areas under the sera titration curves of 10 primary biliary cirrhosis patients indicated that an increase in IgA antibodies to pyruvate dehydrogenase is related to more rapid disease progression.
TL;DR: Good peritoneal lavage seemed to be as effective as any combination of antibiotic treatment in the treatment of experimental septic peritonitis, whether alone or in combination.
Abstract: This study was undertaken to evaluate the efficacy of different combinations of antimicrobial agents in the treatment of experimental septic peritonitis. Two hundred rabbits, divided into ten groups of 20 rabbits each, were used. Septic peritonitis was provoked in two stages: treatment of animals by mechanical lavage or antibiotics was performed during the first stage; blood cultures, isolation and identification of aerobic and anaerobic bacteria in the peritoneal cavity were performed during the second stage. The parameters assessed were survival and, in the second phase, the formation of peritoneal abscesses. The most significant finding was noted in the first phase, where diffuse peritonitis took place, with a very high mortality rate due to bacteremia and sepsis. In both blood and pus from the peritoneal cavity cultures in all groups,Escherichia coli, Klebsiella pneumoniae andProteus mirabilis (among the aerobes) andBacteroides fragilis, Clostridium sp. andPeptostreptococcus sp. (among anaerobes) were the predominant pathogens identified. High mortality rates appeared to be due to the aerobic microbes, particularlyEscherichia coli, whereas abscess formation was related to the anaerobes, particularlyBacteroides fragilis. All antibiotics tested were effective, whether alone or in combination. Metronidazole, however, was the most effective in the reduction of intra-abdominal abscesses. The lowest mortality rate was observed in animals injected with piperacillin and a combination of cefoxitin and an aminoglycoside with metronidazole. Finally, good peritoneal lavage seemed to be as effective as any combination of antibiotic treatment.
TL;DR: Variation in the envelope proteins of hepatitis B virus has been described in vaccinees and in patients receiving monoclonal and polyclonal antibody therapy and has clinical relevance, in particular with regard to vaccine failure and diagnostic difficulties.
Abstract: The envelope proteins of hepatitis B virus are highly conserved. They are involved in viral attachment to hepatocytes, virion assembly and secretion and induction of humoral and T-cell immune responses. The major neutralisation epitope is located within the S protein and is conformation dependent, probably due to the formation of disulphide bridges. Variation in the envelope proteins of hepatitis B virus has been described in vaccinees and in patients receiving monoclonal and polyclonal antibody therapy. Thes arise through point mutations in the surface gene and appear to be selected by the immune response. The emergence of such variants has clinical relevance, in particular with regard to vaccine failure and diagnostic difficulties.
TL;DR: Analysis of the fine specificity of the two Ab3 immune sera suggest they share idiotopes with HP2/6 and contain antibodies reacting with CD4 antigen, and anti-idiotypic antibodies F16-14D6 and F 16-16D7 behave as “network antigen” for human CD4; idiotope-triggered antibody cascade may have a role in changing the specificities of antibody.
Abstract: Of 1019 hybridomas generated from a BALB/c mouse immunized with the syngeneic anti-CD4 monoclonal antibody HP2/6, 3 were found to secrete anti-idiotypic antibodies. Detailed analysis of anti-idiotypic monoclonal antibodies F16-10F6, F16-14D6 and F16-16D7 showed they recognize idiotope(s) not expressed by any of the anti-CD4 monoclonal antibodies tested, including those which inhibit the binding of HP2/6 to CD4 antigen. The idiotope recognized by the three anti-idiotypic antibodies are within (or closely related to) the antigen combining site of the immunizing antibody and distinct and spatially distant from the idiotope defined by monoclonal antibody F11-2302 which was previously shown to be outside the antigen combining site of HP2/6. Although F16-14D6 and F16-16D7 are indistinguishable in isotype, binding titer to idiotopes, fine specificity on a panel of monoclonal antibodies, relation to the combining site and competitive binding, it is likely that they are structurally different and recognize two distinct combining site-related idiotopes on HP2/6, as they display different spectrotypes and induce antianti-idiotypic (Ab3) immune sera with different specificities. Analysis of the fine specificity of the two Ab3 immune sera suggest they share idiotopes with HP2/6 and contain antibodies reacting with CD4 antigen. Among the latter, those induced with F16-14D6 display a different CD4 epitope specificity than HP2/6. Hence, anti-idiotypic antibodies F16-14D6 and F16-16D7 behave as “network antigen” for human CD4; idiotope-triggered antibody cascade may have a role in changing the specificities of antibody.
TL;DR: The ganglioside pattern in the meningosarcoma was different from the previously reported pattern in meningiomas of different histological origin, showing a higher concentration of GD3, indicating that the so-called b pathway of gangLioside biosynthesis was the preferred one in this type of tumor.
Abstract: In a sample of meningosarcoma, obtained at the time of surgery, the amount of total gangliosides and phospholipids was examined, together with the cholesterol content and the distribution of different ganglioside and phospholipid species. The phosphatidylinositol, phosphatidylinositol-4-phosphate, phosphatidylinositol-4, 5-bisphosphate and phosphatidylcholine fatty acid composition was also analyzed. The ganglioside pattern in the meningosarcoma was different from the previously reported pattern in meningiomas of different histological origin, showing a higher concentration of GD3, indicating that the so-called b pathway of ganglioside biosynthesis was the preferred one in this type of tumor; moreover the percentage content of polysialylated gangliosides was very low. Cholesterol and phospholipid content was lower than in meningiomas; the phosphatidylcholine increase and the sphingomyelin decrease would indicate a lower membrane microviscosity, a characteristic of tumor cells. Phosphoinositide and phosphatidylcholine fatty acid analysis revealed a considerable amount of docosahexaenoic acid. This abnormal presence of this fatty acid could lead to the production, after receptor stimulation, of a diacylglycerol containing docosahexaenoic acid, which, in turn, could be responsible for an altered activation pattern of protein kinase C, in this way promoting carcinogenesis.
TL;DR: It is concluded that prolonged treatment with high doses of corticosteroids, which have a depressive effect on metabolism, was responsible for the obesity of patients with acute lymphoblastic leukemia.
Abstract: We studied the hormonal pattern of nine patients with acute lymphoblastic leukemia. The patients were treated with standard therapeutic regimens. They were overweight by a mean of 52% at the end of the consolidation treatment, and this persisted after a followup of 2 years. The only endocrine alteration observed was a moderate decrease in serum testosterone levels in male patients. The other parameters studied were in the normal range. We conclude that prolonged treatment with high doses of corticosteroids, which have a depressive effect on metabolism, was responsible for the obesity.
TL;DR: It is postulated that the drug, by reducing the peripheral vascular resistance seen during hypoxia, could increase renal blood flow, thus improving the renal oxygen supply and partially restoring the imbalance between gas supply and demand, which drives erythropoietin formation.
Abstract: The present study was undertaken to assess the effect of prazosin, a selective postsynaptic α1-adrenergic receptor blocking agent, on normoxic and hypoxic mice, in order to evaluate experimentally its use in the treatment of the excessive erythrocytosis that characterizes chronic mountain sickness. The drug, injected intraperitoneally to adult mice at a dose of 400 μg/kg per day, induced a significant depression of the rate or eryhtropoiesis, as measured by red blood cell59iron uptake, with a decrease in the hematocrit from the 3rd day. The drug also inhibited the oxygen-dependent secretion of erythropoietin (estimated by the plasma immunoreactive hormone concentration) in hypoxemic mice when injected between 0 and 2 h after initiation of the hypoxic stimulation. When injected daily into mice exposed to intermittent hypobaric hypoxia, prazosin limited the degree of polycythemia or induced a sustained decrease in the hematocrit when polycythemia was already present due to previous exposure. It is postulated that the drug, by reducing the peripheral vascular resistance seen during hypoxia, could increase renal blood flow, thus improving the renal oxygen supply and partially restoring the imbalance between gas supply and demand, which drives erythropoietin formation.
TL;DR: Some of the findings should probably be considered as non-specific and all protocols and data critically reviewed before a firm conclusion be made.
Abstract: Despite the several papers that have appeared in the literature or have been communicated at scientific meetings, the detection of hepatitis C virus RNA by in situ hybridization seems a difficult goal to achieve. There have been conflicting reports on the type and proportion of hepatitis C virus-infected cells, the intracellular distribution of viral RNA and the topographical association with cell damage. As a consequence, some of the findings should probably be considered as non-specific and all protocols and data critically reviewed before a firm conclusion be made.
TL;DR: The findings raise the possiblity that FN might be implicated in some of the clinical symptoms of multiple myeloma, as it is shown to inhibit thrombin and collagen-induced platelet aggregation under physiological conditions of pH and ionic strength.
Abstract: Fibronectin (FN) has an active role in the immune response, interacting with a number of different cells and components. It has been implicated in the formation of cryoprecipitates in rheumatic diseases and is present in tissues where under pathological conditions immune complexes are deposited. Under physiological conditions of pH and ionic strength both heavy and light chain of all multiple myeloma and normal IgG show affinity to FN. FN binds to both B and T cells and is shown to inhibit thrombin and collagen-induced platelet aggregation. We have found elevated levels of FN in the plasma of multiple myeloma patients tested compared to a group of normal subjects. Even though the level of FN did not correlate with the level of the paraprotein, our findings raise the possibility that FN might be implicated in some of the clinical symptoms of multiple myeloma.
TL;DR: The role of cytomegalovirus as a co-factor of the progression towards immunodeficiency in subjects infected with the human immunodficiency virus type 1 needs to be elucidated with more extensive clinical studies and the application of new molecular biology techniques.
Abstract: Cytomegalovirus has been suggested as a co-factor of disease progression in patients with human immunodeficiency virus type 1 infection. Cytomegalovirus infection is highly prevalent among populations at risk of human immunodeficiency virus 1 infection, and has been associated with both an increased susceptibility to infection and a more rapid course of the disease towards immunodeficiency. Cytomegalovirus can have a direct immunosuppressive effect (through infection of immune cells) and can enhance the replication of human immunodeficiency virus (through the transactivation of the genic immunodeficiency virus expression, the stimulation of cytokine production, and the increase in Fc receptor expression on target cells). The role of cytomegalovirus as a co-factor of the progression towards immunodeficiency in subjects infected with the human immunodeficiency virus type 1 needs to be elucidated with more extensive clinical studies and the application of new molecular biology techniques.