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Biomedical subjects

T Martin

Publications and source records attributed to T Martin.

At least 145 records · Page 8Linked to original sources
PubMed1996

Developmental toxicity of Exell, a surfactant mixture, in rats and rabbits.

A surfactant mixture (C.A.S No. 104559-06-2), is used in combination with foliar-acting herbicides to improve herbicidal performance by increasing plant uptake. It was administered by gavage as an aqueous solution to groups of 25 assumed pregnant Crl:CD BR rats from days 7-16 of gestation at daily dosage levels of 0, 3, 8, 20 or 50 mg/kg body weight. The dams were euthanized on Day 22 of gestation and the offspring were weighed and examined for external, visceral, and skeletal alterations. The surfactant mixture was maternally toxic at levels of 20 mg/kg/day and above as evidenced by reduced maternal weight gain and by an increased incidence of lung noise (wheezing and/or rattling) and sneezing. In addition, maternal food consumption was reduced in the high dosage group. There was no evidence of developmental toxicity at any dosage level. In the rabbit study, groups of 20 artificially inseminated adult Hra:(NZW)SPF rabbits were similarly dosed from Days 6-18 of gestation at daily dosage levels of 0, 12, 35, or 100 mg/kg body weight. The dose were euthanized on Day 29 of gestation and the offspring were weighed and examined for external, visceral, and skeletal alterations. Dosages of 35 and 100 mg/kg/day resulted in reduced maternal body weight gain, food consumption and fetal body weight. Thus, in the rat, the maternal and developmental no-observed-adverse-effect levels (NOAELs) were 8 mg/kg/day and greater than 50 mg/kg/day, respectively. In the rabbit, the maternal and developmental NOAELs were 12 mg/kg/day. This surfactant mixture was, therefore, not demonstrated to be uniquely toxic to either the rat or rabbit conceptus.

Abnormalities, Drug-Induced↗
PubMed1996

Simultaneous radiochemotherapy with paclitaxel in non-small cell lung cancer: a clinical phase I study.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most active single agents available for the treatment of non-small cell lung cancer (NSCLC), with reported response rates of 21% to 24%. Its observed radiosensitizing effect is attributed to its interruption of cell development at the G2/M phase of the cell cycle, when cells are most sensitive to the killing effects of ionizing radiation. This phase I study of paclitaxel and simultaneous radiation therapy in patients with previously untreated, locally advanced inoperable stage IIIA/B NSCLC was designed to determine the maximum tolerated paclitaxel dose, to define the safety and toxicity of this combined modality, and to obtain preliminary data on its activity. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week, in shrinking-field technique, for a total dose of 59.4 Gy) and concomitant chemotherapy with a 3-hour infusion of paclitaxel once weekly on day 1, initially at a dose of 45 mg/m2, for 3 weeks. This dose remained constant during study levels 1 to 3, with the number of weeks of treatment increasing to 5 and 7 at levels 2 and 3, respectively. At dose level 4, the paclitaxel dose was increased to 55 mg/m2 over 7 weeks. Of 22 NSCLC patients who entered the study, 18 are evaluable for toxicity and response. Responses included one complete and 10 partial remissions; the other seven patients had minimal improvement. The therapy was well tolerated; no severe adverse events were associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment for NSCLC. The maximum tolerated paclitaxel dose has not yet been reached, and dose escalation is planned.

Adult↗
PubMed1996

Paclitaxel and simultaneous radiation in locally advanced stage IIIA/B non-small cell lung cancer: a clinical phase I study.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most active single agents for the treatment of non-small cell lung cancer, with response rates of 21% to 24%. We present a phase I study with paclitaxel and simultaneous radiation in previously untreated, locally advanced, inoperable, stage IIIA/B non-small cell lung cancer. The aims of the study were to determine the maximum tolerated dose, define the safety and toxicity, and obtain preliminary data about the activity of the combined modality. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week for 6.5 weeks, for a total dose of 59.4 Gy) and concomitant chemotherapy with paclitaxel 45 mg/m2 days 1, 8, and 15 in level 1; days 1, 8, 15, 22, and 29 in level 2; and days 1, 8, 15, 22, 29, 36, and 43 in level 3. The paclitaxel dosage was increased to 55 mg/m2 on days 1, 8, 15, 22, 29, 36, and 43 in level 4. Paclitaxel was administered as a 3-hour continuous intravenous infusion. Dexamethasone, clemastine, and ranitidine were given for hypersensitivity prophylaxis. Twenty-two patients (18 men and four women) entered the study; their median age was 66.5 years (age range, 38 to 74 years). Disease stage was IIIA in six of 22 patients and stage IIIB in 16. Six patients were treated at level 1, five at level 2, five at level 3, and six at level 4. There were 18 patients evaluable for toxicity and response. Side effects generally were moderate during the treatment period. One patient withdrew by request after the first course, one patient died of tumor bleeding after five courses, one patient died of progressive disease (lymphangiosis carcinomatosa of both lungs) after the sixth course, and one patient is too early for evaluation. Among the 18 patients evaluable for response, there were one complete and 10 partial remissions; seven patients reached a minor response. It is concluded that the therapy was well tolerated in these patients. Importantly, no severe adverse events were observed that could be associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment of non-small cell lung cancer. The maximum tolerated dose has not yet been reached, and dose escalation is planned.

Adult↗
PubMed1995

Heavy chain variable region, light chain variable region, and heavy chain CDR3 influences on the mono- and polyreactivity and on the affinity of human monoclonal rheumatoid factors.

Monoreactive high affinity pathologic autoantibodies were supposed previously to derive through somatic mutation from polyreactive low affinity autoantibodies that are encoded by a small set of unmutated V region genes in fetal and neonatal B cells. However, recent data exploring the physiologically expressed Ab repertoire and the importance of the stochastically generated heavy chain CDR3 (H-CDR3) in autoreactivity suggest that this scheme is incomplete. Here we analyzed via gene-swapping experiments and site-directed mutagenesis the relative contributions of the mutations in the light chain variable region (VL) and the heavy chain variable region (VH) domains and of the H-CDR3 in the autoreactivity of two IgM rheumatoid factors (RF), one a polyreactive low affinity Ab, the other a monoreactive high affinity Ab. These two RFs derived from the same V kappa III (humkv325) and VH1 (51p1) genes, but differed from each other by a few mutations and by the structure of the H-CDR3. The analysis of the reactivity patterns of different combinations of wild-type and in vitro engineered hybrid gene products clearly demonstrates the main influence of the H-CDR3 in the autoAb activity profiles. The results directly demonstrate the previously proposed hypothesis, namely, that the H-CDR3 plays a critical role in distinguishing poly- from monospecific RF. However, the data also indicate that self polyreactivity is a very fragile property and is dependent upon the primary structure of the VH segment.

Amino Acid Sequence↗
PubMed1995

Direct sequencing of PCR amplified pig PrP genes.

The protein coding regions of the PrP genes of six pigs were sequenced directly from PCR-amplified genomic DNA. All six sequences were identical. The gene encodes a protein of 257 amino acids and shows an overall similarity of 77 to 88% with the PrP sequences from other mammalian species. The significance of amino acids unique to the pig PrP are discussed.

Amino Acid Sequence↗
PubMed1995

Monoclonal IgM rheumatoid factor secreted by CD5-negative B cells during mixed cryoglobulinemia. Evidence for somatic mutations and intraclonal diversity of the expressed VH region gene.

Mixed cryoglobulinemia is usually considered to be a nonmalignant human B cell proliferation that produces a monoclonal IgM rheumatoid factor (RF). Important immunologic similarities and differences were described between the monoclonal B cells during mixed cryoglobulinemia and during malignant chronic lymphocytic leukemia (CLL):high frequency of the same VH and V kappa gene usage by both types of monoclonal B cells producing IgM with RF activity, apparent intraclonal homogeneity, but different expression of the pan T cell CD5 Ag. The description of an unusual CD5-negative B cell CLL case secreting a mutated IgM RF led the authors to suggest that the usage of non-mutated germline Ig genes is a property of cells derived from the CD5 lineage or stage of differentiation, rather than an intrinsic property of CLL or of IgM RF-producing cells in general. Because mixed cryoglobulinemia cells are usually CD5-negative, it was of interest to test for the existence of mutations in the VH and V kappa regions, as well as for the intraclonal homogeneity of the expressed Ig genes. In this study, we used the PCR technique to analyze the monoclonal rheumatoid factor (mRF) V genes from a patient with mixed cryoglobulinemia. We show that the CD5-negative monoclonal B cells express a slightly mutated V kappa 3 gene, but a more mutated VH1 gene whose genomic counterpart was shown to be the 51p1 germline gene. The sequence analysis of several independent clones shows some degree of intraclonal diversity, suggesting the existence of a clonal filiation. These results are discussed in terms of the origin of the monoclonal B cell during mixed cryoglobulinemia and CLL.

Antibodies, Monoclonal↗
PubMed1995

Association of intermediate uveitis with HLA-A28: definition of a new systemic syndrome?

BACKGROUND: Endogenous posterior uveitis (PU) can be associated with systemic diseases, and certain forms have strong association with HLA antigens. Much less is known regarding intermediate uveitis (IU). The purpose of this study was to determine whether IU is associated with the HLA system and whether it can be associated with systemic symptoms. METHODS: In 179 consecutive patients consulting for uveitis, a detailed history was obtained and a physical examination performed. HLA typing for 71 HLA-A, B, DR and DQ antigens, laboratory tests, and radiography of the chest, sinuses, and sacroiliac joints were systematically performed. RESULTS: Thirty-two patients (18%) had IU; 51 (28.5%) had PU and constituted our internal control group. Nine of the patients with IU (28%) had the HLA-A28 antigen, compared with 8.1% of a healthy control population and 8.6% of the patients with PU (P < 0.001). An associated disease was found in four patients with IU (12.5%) (none was HLA-A28) and in 45% of the patients with PU (P < 0.01). Some 67% of HLA-A28 patients with IU had arthralgias affecting the knee(s), compared with 17% of non-HLA-A28 patients and 18% of patients with PU (P < 0.05 and P < 0.01 respectively); 55% had gonalgias and hypocomplementemia compared with 9% and 2% respectively (P < 0.01 and P < 0.001). CONCLUSIONS: IU is significantly associated with HLA-A28; patients having this antigen may represent a subset of the disease characterized by an increased prevalence of arthralgias and hypocomplementemia.

Adolescent↗
PubMed1995

Corynebacterium diphtheriae osteomyelitis in an immunocompetent child: a case report.

UNLABELLED: Septic osteomyelitis of the hip in a previously healthy child is described. A weakly toxigenic Corynebacterium diphtheriae strain was isolated from the bone aspirate. The results of the treatment were rapidly satisfactory, after surgical drainage and antibiotic therapy with pristinamycin. CONCLUSION: This case report shows that C. diphtheriae has not disappeared in the developed world and can be responsible of systemic infections.

Child, Preschool↗
PubMed1995

[Treatment of lupus glomerulonephritis with intravenous cyclophosphamide].

The treatment of severe lupus nephritis remains problematic. We have analysed retrospectively 17 patients with corticoresistant lupus nephritis treated with pulse cyclophosphamide. Single monthly doses (500 mg/m2) were given by intravenous infusion with a mean of 10.4 infusions per patient (3 to 18). A comparison of parameters at entry and at the end of the treatment revealed an improvement in proteinuria (4.8 vs 1.9 g/24 h; p < 0.013) whereas mean serum creatinine level and SLAM (Systemic Lupus Activity Measure) remained stable. The results were identical at follow up (mean: 14.5 months). Most of the therapeutic effect was achieved as soon as the 6th pulse. Further treatment was beneficial for four patients only. None of the studied parameters (serum creatinine level, renal biopsy, SLAM) was predictive of a response to an extended course of pulse cyclophosphamide. The infusions were definitively stopped in one patient and delayed in two others because of serious adverse effects. The data indicate that, in mean term, monthly intravenous cyclophosphamide was associated with a substantial amelioration of 24 hours urinary protein level. An amelioration of the renal function was however, uncommon.

Adult↗
PubMed1995

Peripheral vascular complications of aortic dissection.

BACKGROUND: The incidence and management of peripheral vascular complications of aortic dissection is unsettled. PATIENTS AND METHODS: Peripheral vascular complications of spontaneous aortic dissection were examined in a 5-year retrospective review. Patients who had peripheral vascular complications were categorized as group A; those without as group B. RESULTS: Thirty-eight major vessels were affected in 18 patients. No patient underwent a peripheral vascular procedure for complications of the carotid, subclavian, celiac, mesenteric, or renal arteries. Three patients underwent femorofemoral bypass for acute iliofemoral occlusion due to dissection. A fourth patient had repair of an iliac aneurysm that developed as a complication of chronic dissection. The mortality rate was 17% for group A, 9% for group B, and 10% overall. Following repair of the aortic dissection, the majority of the peripheral vascular complications resolved. CONCLUSIONS: Peripheral revascularization is infrequently required in aortic dissection following primary dissection repair.

Adult↗
PubMed1995

Detection of Rhizobium meliloti cells in field soil and nodules by polymerase chain reaction.

A genetically marked Rhizobium meliloti strain, R692, was prepared by insertion of a 1.7-kb DNA segment from Tn903 between the nifHDK and fixABC genes in the nod megaplasmid. This DNA was used as a marker, detectable by polymerase chain reaction (PCR), for the specific identification of bacteria in soil samples and alfalfa nodules. This detection technique was tested by applying different titres of the marked strain to field plots seeded with alfalfa. Samples of soil and nodules were assayed for the presence of the marker DNA fragment by PCR using primers specific to the marker sequence. The experiments revealed that the bacteria could be detected directly in soil containing about 10(3)-10(4) bacteria/g, but greater sensitivity was prevented by potent PCR inhibitors present in the samples. The titre of the bacteria in the soil decreased rapidly after inoculation, dropping about 10-fold per week. Tests of vertical location of the bacteria in soil cores showed that the bacteria were initially dispersed to a depth of 18 cm, and subsequently retained viability in the top 2-8 cm. As few as 10 marked R. meliloti per gram of soil resulted in its establishment at detectable levels in nodules. Application of about 10(4)-10(5) bacteria/g soil was sufficient to give the maximum number of nodules per plant and resulted in 70-90% occupancy by the marked strain. Limited movement of the inoculant was detected by analysis of nodules from plants adjacent to the sites where the bacteria were applied, probably by movement in water. The experiments demonstrated the advantages of PCR for the monitoring of marked microorganisms in the environment.

Base Sequence↗
PubMed1995

Acquisition of a conditioned reflex in New Zealand white rabbits from three sources.

In studies of learning using rabbits, there has been standardization of behavioural procedures across laboratories. Less attention has been paid to variation that may arise from genetic differences and/or differences in rearing conditions. The present experiment revealed that acquisition of a conditioned reflex can be affected dramatically by such differences. Specifically, the acquisition of a conditioned reflex in New Zealand White (NZW) rabbits from 3 different suppliers was compared. All rabbits received behavioural training in which a tone or a light signalled an electrotactile stimulation of the trigeminal nerve near the rabbits' right eye. This tactile stimulus reliably elicited an eyeblink. Repeated presentations of the auditory and visual signals followed by the tactile stimulus yielded the acquisition of a conditioned response (CR), namely closure of the eyelids during the warning period provided by the signal stimuli. Two of the groups showed steady CR acquisition at a rate that matched previous results in other laboratories as well as in the senior author's laboratory. However, the third group of rabbits showed very slow acquisition, and some rabbits failed to show any CR acquisition.

Animal Husbandry↗
PubMed1995

Presence of D-aspartate and D-glutamate in tumor proteins.

Over 50 years ago Kögl and Erxleben reported that tumor proteins contain appreciable amounts of D-amino acids. This postulate remained highly controversial for several years, during which time several researchers either supported or refuted the hypothesis. We have analyzed several sets of tumors and normal control tissues for the presence of D-aspartate (D-Asp) and D-glutamate (D-Glu). Most tumors contain less D-Asp than the control tissues, whereas nearly half of the tumors contain 1.6 to 5.4 times more D-Glu than the controls. The tumors averaged 0.72% D-Asp and 0.61% D-Glu compared to 0.94% D-Asp and 0.35% D-Glu in the control tissues. However, within the limits of experimental error, there is no significant difference in the level of these D-amino acids between the tumors and normal tissues.

Aspartic Acid↗
PubMed1994

Renal epithelial cells rapidly bind and internalize calcium oxalate monohydrate crystals.

Renal tubular fluid is supersaturated with calcium and oxalate ions, which can nucleate to form crystals of calcium oxalate monohydrate (COM), the most abundant constituent of kidney stones. However, the mechanisms by which nascent crystals are retained in the nephron and then grow into kidney stones are unclear. An interaction of COM crystals with the surface of renal epithelial cells could be a critical initiating event in nephrolithiasis. To investigate this possibility we used cultures of monkey kidney epithelial cells (BSC-1 line) as a model system and found that [14C]COM crystals bound to the cell surface within seconds. Scanning electron microscopy revealed that crystals bind first to apical microvilli, which subsequently migrate over the crystalline surface. When visualized by transmission electron microscopy, intracellular crystals were located within vesicles. Cytoskeletal responses to crystal uptake were sought by immunofluorescence microscopy, which revealed concentration of F-actin at sites of crystal contact as well as a generalized reorganization of the intermediate filament network containing cytokeratin 8. Uptake of COM crystals did not adversely affect renal epithelial cell growth, and internalized crystals were apparently distributed to daughter cells during division. Rapid adherence of COM crystals to the apical surface of tubular epithelial cells could promote crystal retention in the kidney. Elucidation of factors that regulate this process may provide insight into the pathogenesis of nephrolithiasis.

Animals↗