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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 379 records · Page 21Linked to original sources
PubMed1996

Combined diphtheria, tetanus, pertussis, and Haemophilus influenzae type b vaccines for primary immunisation.

A total of 146 infants were immunised at ages 2, 3, and 4 months with a combined diphtheria, tetanus, pertussis (DTP)--Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) vaccine (Pasteur Merieux) to assess the antibody response and adverse events associated with immunisation. Adverse events, including fever, were recorded by parents in a diary for three days following each injection. Blood was taken before the first immunisation and four weeks after the third immunisation to assess antibody response. Data were compared with those from historical controls who had received DTP and PRP-T vaccines by separate injection. The combined vaccine was well tolerated. Rates of local and general reactions were similar to those reported for infants immunised by separate injection. All infants achieved protective antibody titres (> 0.01 IU/ml) for diphtheria and tetanus; 98% acquired Hib (PRP) antibody > 0.15 microgram/ml and 82.5% > 1.0 microgram/ml. Pertussis antibody titres (pertussis toxin, filamentous haemagglutinin, total agglutinins, and agglutinins 2 and 3) showed appreciable rise following immunisation. DTP and PRP-T vaccines provide similar antibody responses and adverse effects whether mixed in the same syringe or administered by separate injection. The vaccines could be combined for use in the United Kingdom primary immunisation schedule.

Antibody Formation↗
PubMed1996

Increased prevalence of septal cavitation in a nonschizophrenic sample: an MRI study of HIV-infected individuals.

Analyses of MRI scans of 26 asymptomatic HIV-infected individuals (HIV+) and 10 HIV-seronegative psychiatric control subjects (HIV-) revealed an incidental finding: 50% of the HIV+ subjects had discernible cleft in the septum pellucidum (cavum septi pellucidi; CSP), compared to only 20% of the HIV- control subjects. HIV+ subjects with CSP were more likely to complain of sensory changes and performed more poorly on specific neuropsychological tests when compared with HIV+ subjects without CSP. These findings suggest that elevated rates of CSP are not limited to the schizophrenic population. CSP may be a marker of premorbid events that increase the vulnerability to cognitive and perhaps behavioral sequelae of neurologic disease or injury.

Adult↗
PubMed1996

Intrathyroidal T cell accumulation in Graves' disease: delineation of mechanisms based on in situ T cell receptor analysis.

We have explored the pattern of T cell clonal and nonclonal expansion within the thyroid glands of 7 patients with surgically treated hyperthyroid Graves' disease. Radiolabeled RT-PCRs were performed with 18 V alpha and 21 V beta oligonucleotides as forward primers and 32 P-labeled constant (C) region oligonucleotides as reverse primers, giving 273 experiments in all. Peripheral blood mononuclear cells showed CDR3 banding patterns involving at least 6-12 distinct bands per V gene family. However, 2 distinct banding patterns were seen with intrathyroidal T cell samples. The first was a limited number of bands (< 6), representing within V gene family restriction, seen in 38/153 (25%) PCR positive samples. The second was the presence of markedly enhanced bands representing either clonal expansion or accumulation of T cells using the same V gene with the same CDR3 length and observed in 15/153 (10%) of samples. Further examination of the enhanced bands by sequencing of gel-selected PCR-amplified V gene products showed the presence of both T cell clonal expansion, as evidenced by similar CDR3 sequences, and in a few samples, heterogenous T cell populations, as evidenced by differing CDR3 sequences, yet all sharing the same V gene family. These data support the hypothesis that the human intrathyroidal T cell population in Graves' disease was selected by two distinct mechanisms. The first was associated with the TcR V gene invariant product and represented by nonclonal accumulation of T cells sharing the same V gene. The second mechanism responsible for T cell accumulation was specific antigen recognition by the human T cell receptor CDR3 region and was represented by clonally expanding T cells.

Amino Acid Sequence↗
PubMed1996

Diurnal rhythm of the muscular performance of elbow flexors during isometric contractions.

The influence of time of day on elbow flexion torque was studied. Thirteen physical education students, 7 males and 6 females, made maximal and submaximal isometric contractions at 90 degrees of elbow flexors using a dynamometer. The torque developed was measured on each contraction. The myoelectric activity of the biceps muscle was also measured at the same time by surface electromyography (EMG) and quantified from the root mean square (RMS) activity. Torque and surface EMGs were measured at 6:00, 9:00, 12:00, 15:00, 18:00, 21:00, and 24:00 h over the same day. Oral temperature before each test session was measured on each occasion after a 30-min rest period. We observed a diurnal rhythm in elbow flexor torque with an acrophase at 18:00 h and a bathyphase at 6:00 h, in phase with the diurnal rhythm in oral temperature. However, the diurnal rhythm of temperature did not appear to have any influence on the torque. Links between neuromuscular efficiency and RMS/torque ratio were evaluated by measuring muscle activity along with torque. We also assessed variations in the level of maximal activity of the muscle under maximal voluntary contraction. Neuromuscular efficiency fluctuated during the day, with maximal and minimal efficiency at 18:00 h and 9:00 h, respectively, whereas activation level was maximal at 18:00 h and minimal at 9:00 h. The diurnal rhythm of torque was accounted for by variations in both central nervous system command and the contractile state of the muscle.

Adult↗
PubMed1996

Soluble adhesion molecules in renal transplantation.

Serum levels of sICAM-1 and sVCAM-1 adhesion molecules as well as TNF cytokine were measured in 50 kidney transplant recipients [14 patients with stable graft function, 18 patients with acute rejection, 10 patients with CsA toxicity, 6 patients with ATN, and 2 patients with cytomegalovirus (CMV) disease] during the first 3 postoperative weeks. All the patients studied showed, on the first posttransplant day, elevated serum levels of sICAM-1 (260 +/- 53 ng/mL). Interestingly, all the patients with good graft function presented thereafter a reduction of sICAM-1 serum levels close to the normal values (185.2 +/- 40 ng/mL). In contrast, the group of patients with acute allograft rejection showed significantly increased serum levels of sICAM-1 (371.5 +/- 86 ng/mL; p < 0.001), 3-4 days before diagnosis of acute rejection. Although sVCAM-1 levels were increased in both acute graft rejection (2263 +/- 106) and CsA toxicity (1650 +/- 315) patients, such increase was not significant among either group of patients when the group with CsA toxicity was compared with either ATN (1320 +/- 204) or stable renal function (1089 +/- 167). No statistical differences in the levels of TNF were demonstrated between the different groups of patients studied. Our findings demonstrate that quantitative determination of serum sICAM-1 may be of predictive clinical value in transplanted patients with acute renal allograft rejection.

Cyclosporine↗
PubMed1996

Fludarabine in resistant or relapsing B-cell chronic lymphocytic leukemia: the Spanish Group experience.

Fludarabine produces high response rates in patients with B-cell chronic lymphocytic leukemia (CLL). Nevertheless, response to fludarabine of patients with previously treated CLL varies from 17% to 74% (0% to 38% CR). In 68 patients with heavily pretreated and advanced CLL, an overall response rate to fludarabine of 28% (4% CR) was observed. Response correlated with sensitivity of the disease to previous treatments (relapsing vs. refractory disease) (62% vs. 20%; p = 0.005) and, albeit not significantly, with the number of cycles of fludarabine (>3 vs. < or = 3) that patients could receive (36% vs. 15%; p = NS). Responding patients had a longer survival (median, not reached) than those not responding (median, 11 months) (p = 0.03). Severe toxicity was observed in some cases. It is concluded that fludarabine is a highly useful agent in CLL. However, in order to improve its effectiveness and decrease its toxicity, fludarabine should be given as soon as a lack of response to front-line therapy is observed and before the disease becomes completely resistant to therapy.

Anemia, Hemolytic, Autoimmune↗
PubMed1996

Vascular endothelial growth factor stimulates protein kinase C-dependent phospholipase D activity in endothelial cells.

Many tumors produce vascular endothelial growth factor (VEGF), a paracrine factor acting selectively on endothelial cells. VEGF has many effects on cultured endothelial cells and mediates angiogenesis and enhanced vascular permeability in vivo. The endothelial signal transduction pathways of VEGF represent novel targets for cancer therapy because they are readily accessible to systemically administered drugs. We have examined VEGF-stimulated signals generated in HUVEC to identify potential targets for therapeutic intervention. The transphosphatidylation reaction has been used to monitor phospholipase D (PLD) activity; total inositol phosphates have been measured after prelabeling of cells with [3H]myoinositol; and intracellular free calcium has been measured using Fura-2 fluorescence. After HUVEC-stimulation with VEGF, there is an early influx of calcium (maximal by 100 seconds) followed by activation of PLD (half maximal by 100 seconds, EC50 70 pm). The PLD activity was inhibited by reducing extracellular calcium (150 nM, 50% inhibition), exposure to 12-O-tetradecanoylphorbol 13 acetate (200 nM, 24 hours, 100% inhibition), Roche 31,8220 (10 microM, 15 minutes, 72% inhibition), or genestein (100 microM, 30 minutes, 56% inhibition), which suggests a dependence on both protein kinase C and tyrosine phosphorylation. Activation of phospholipase C-catalyzed hydrolysis of phosphatidylinositol-4,5-bisphosphate was inferred from the production of inositol phosphates, although this response was slower (half maximal by 3 minutes). The phospholipase C activity was also dependent on influx of calcium and was partially inhibited by low (150 nM) extracellular calcium. PLD may be involved in mediating a number of endothelial responses to tumor-secreted VEGF, notably cytoskeleton-dependent effects such as the cell migration involved in angiogenesis. This signal transduction pathway could represent an accessible and vulnerable target for cancer therapeutic intervention and has the novelty of being located within normal cells rather than tumor cells.

Calcium↗
PubMed1996

Changing approach to gastroenteropancreatic tumours. Case report of a gastrinoma metastasis localized by somatostatin-receptor scintigraphy.

A 60-year-old female with a history of chronic pancreatitis and previous pancreaticojejunostomy has been submitted to distal gastric resection for recurrent perforating ulcers. A carcinoid tumour was identified in the surgical specimen. Hypergastrinaemia was subsequently diagnosed and tumour localization was carried out by a new scintigraphic technique with 111In-Pentetreotide. The tumour was found to be a metastasis confined to a peripancreatic lymph node. Surgery was successful, and 6 months later the patient is still eugastrinaemic. The different imaging methods for the identification of gastrinomas are discussed together with the current therapeutic options.

Duodenal Neoplasms↗
PubMed1996

[Multinucleated cell angiohistiocytoma. Report of 6 cases].

Multinucleate cell angiohistiocytoma is a recently described entity. It is a benign vascular proliferation. Clinically, it is characterized by violaceous red papules, often mimicking Kaposi's sarcoma. Acral sites and face were the commonest sites. The six patient's age was between 41 and 64 years and sex ratio was equal. Microscopic features were an increased number of blood vessels together with mononucleated and multinucleated histiocyte-like cells with scalloped borders. Staining of mononucleated cells with CD68, anti vimentin and anti factor XIIIa antibodies emphasized a fibrohistiocytic origin. Loss of factor XIIIa expression in multinucleate cells gets clue to think that these cells are dedifferenciated.

Adult↗
PubMed1995

Identification and site-directed mutagenesis of the primary (2A/2B) cleavage site of the hepatitis A virus polyprotein: functional impact on the infectivity of HAV RNA transcripts.

The junction between 2A and 2B proteins of the hepatitis A virus (HAV) polyprotein is processed by the virus-encoded 3C protease to liberate the precursor for capsid proteins, but details of this cleavage remain poorly defined. We identified the location of this primary cleavage by a novel approach involving expression of HAV polypeptides in eukaryotic cells via recombinant vaccinia viruses. A substrate polyprotein spanning the putative HAV 2A/2B site was fused at its C-terminus to a poliovirus VP1 reporter sequence. This substrate was cleaved efficiently in trans by protease 3C derived from another recombinant vaccinia virus expressing a 3C precursor protein. N-terminal sequencing of the 2B-poliovirus VP1 fusion product identified the site of cleavage as the Gln836/Ala837 dipeptide, 144 residues upstream of the originally predicted site. Two mutations were introduced at the P1 position of the 2A/2B site. Gln836-->Asn, and Gln836-->Arg. Asn substitution at the P1 residue reduced the efficiency of cleavage in the vaccinia expression system and resulted in a small replication focus phenotype of virus rescued from infectious HAV RNA transcripts. Arg substitution abolished cleavage and was lethal to HAV replication. In addition to identifying the site of the primary HAV polyprotein cleavage, these results shed light on the in vivo specificities of the HAV 3C protease.

3C Viral Proteases↗
PubMed1995

Discrete cortical regions associated with knowledge of color and knowledge of action.

The areas of the brain that mediate knowledge about objects were investigated by measuring changes in regional cerebral blood flow (rCBF) using positron emission tomography (PET). Subjects generated words denoting colors and actions associated with static, achromatic line drawings of objects in one experiment, and with the written names of objects in a second experiment. In both studies, generation of color words selectively activated a region in the ventral temporal lobe just anterior to the area involved in the perception of color, whereas generation of action words activated a region in the middle temporal gyrus just anterior to the area involved in the perception of motion. These data suggest that object knowledge is organized as a distributed system in which the attributes of an object are stored close to the regions of the cortex that mediate perception of those attributes.

Adult↗
PubMed1995

Purification and characterization of novel plasma membrane phosphatidate phosphohydrolase from rat liver.

An N-ethylmaleimide-insensitive phosphatidate phosphohydrolase, which also hydrolyzes lysophosphatidate, was isolated from the plasma membranes of rat liver. The specific activity of an anionic form of the enzyme (53 kDa, pI < 4) was increased 2700-fold. A cationic form of enzyme (51 kDa, pI = 9) was purified to homogeneity, but the -fold purification was low because the activity of the highly purified enzyme was unstable. Immunoprecipitating antibodies raised against the homogeneous protein confirmed the identity of the cationic protein as the phosphohydrolase and were used to identify the anionic enzyme. Both forms are integral membrane glycoproteins that were converted to 28-kDa proteins upon treatment with N-glycanase F. Treatment of the anionic form with neuraminidase allowed it to be purified in the same manner as the cationic enzyme and yielded an immunoreactive protein with a molecular mass identical to the cationic protein. Thus, the two ionic forms most likely represent different sialated states of protein. An immunoreactive 51-53-kDa protein was detected in rat liver, heart, kidney, skeletal muscle, testis, and brain. Little immunoreactive 51-53-kDa protein was detected in rat thymus, spleen, adipose, or lung tissue. This work provides the tools for determining the regulation and function of the phosphatidate phosphohydrolase in signal transduction and cell activation.

Animals↗
PubMed1995

The natural protein kinase C alpha mutant is present in human thyroid neoplasms.

An altered protein expression of Ca(2+)-dependent protein kinase C (PKC) isoforms and a point mutation in the PKC alpha cDNA (position 908 of the nucleotide sequence, position 294 of the amino acid sequence, substitution of an aspartic acid by a glycine) have been previously described in a subpopulation of human pituitary tumors. In this work, we screened 16 thyroid tissue samples (four follicular adenomas, five colloid adenomas, three papillary carcinomas, one follicular carcinoma and three normal tissues adjacent to the tumors) for the presence of the PKC alpha point mutation and for PKC alpha, beta 1, beta 2, epsilon and delta protein expression. Screening for the presence of the PKC alpha mutant was performed by a subcloning technic. The polymerase chain reaction products were generated using reverse-transcribed cDNAs, subcloned and sequenced (10 clones were routinely sequenced). The PKC alpha point mutation at position 908 of the cDNA sequence was found in four out of the nine adenomas and in the follicular carcinoma. It was neither detected in the papillary carcinomas nor in the adjacent normal tissues (one was the adjacent normal tissue of the follicular carcinoma; in this sample, genomic DNA and cDNA were used to look for the presence of the mutant), demonstrating the somatic nature of this mutant. Western blot analysis of PKC isoforms showed that the expression of all isoforms was higher in the thyroid neoplasms as compared with their adjacent normal tissue (n = 3). It was also higher in the samples containing the PKC mutant (two follicular adenomas, two colloid adenomas and the follicular carcinoma) as compared with the tumors where it was not detected (three papillary carcinomas and five adenomas). Samples could be ordered according to their increasing PKC expression as follows: normal adjacent tissue < follicular adenomas without PKC alpha mutant < or = papillary carcinoma < follicular adenomas with PKC mutant < follicular carcinoma with PKC mutant. In conclusion, the discovery of the PKC alpha mutant in thyroid neoplasms demonstrates that this mutant is not particular to human pituitary tumors where it was originally detected. It is a somatic mutation and its presence is concomitant with high levels of all of the PKC isoforms analysed. The presence of the PKC mutant in thyroid neoplasms raises the question of its importance in thyroid tumorigenesis.

Adenocarcinoma, Follicular↗