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Biomedical subjects

V M Martin

Publications and source records attributed to V M Martin.

12 recordsLinked to original sources

Rearrangement and expression of immunoglobulin light chain genes can precede heavy chain expression during normal B cell development in mice.

In mouse mutants incapable of expressing mu chains, VkappaJkappa joints are detected in the CD43(+) B cell progenitors. In agreement with these earlier results, we show by a molecular single cell analysis that 4-7% of CD43(+) B cell progenitors in wild-type mice rearrange immunoglobulin (Ig)kappa genes before the assembly of a productive VHDHJH joint. Thus, mu chain expression is not a prerequisite to Igkappa light chain gene rearrangements in normal development. Overall, approximately 15% of the total CD43(+) B cell progenitor population carry Igkappa gene rearrangements in wild-type mice. Together with the results obtained in the mouse mutants, these data fit a model in which CD43(+) progenitors rearrange IgH and Igkappa loci independently, with a seven times higher frequency in the former. In addition, we show that in B cell progenitors VkappaJkappa joining rapidly initiates kappa chain expression, irrespective of the presence of a mu chain.

Animals↗

Immunomagnetic enrichment of disseminated epithelial tumor cells from peripheral blood by MACS.

Disseminated epithelial tumor cells have been detected in the bone marrow and blood of cancer patients by means of immunocytochemical or immunofluorescent staining of cytocentrifuge slides, multiparameter flow cytometry, and reverse transcriptase-polymerase chain reaction. However, it is hardly possible using such methods to detect tumor cells at a frequency below 10(-6). To increase the sensitivity of these detection techniques we have developed a new technology for the enrichment of disseminated epithelial tumor cells from hematopoietic cell samples by high-gradient magnetic cell sorting (MACS). Cells are permeabilized and fixed and carcinoma cells are magnetically labeled specifically with an anti-cytokeratin 8 monoclonal antibody (mAb) directly conjugated to superparamagnetic microbeads. Magnetically labeled cells are enriched on high-gradient magnetic columns. Tumor cells are detected in the enriched cell fraction by flow cytometry, fluorescence microscopy, or immunocytochemisty. In this study we demonstrated the method using a model system in which five to 5,000 cells from a breast cancer cell line were seeded into blood cell samples from a healthy donor containing 1.2 x 10(8) leukocytes. Tumor cells were 10,477+/-4242 (n=25)-fold magnetically enriched, and 57.7%+/-16.9% (n=33) of the initially seeded tumor cells were recovered. Applying the method to 20-40 mL blood samples from patients with advanced carcinomas of the breast, prostate, colon, rectum, or lung, we were able to detect between one and 6.8 x 10(4) cytokeratin-expressing tumor cells in 21 of 34 patients. This corresponds to frequencies of tumor cells between 6.8 x 10(-9) and 1.1 x 10(-3) among nucleated cells in the original sample. Enriched tumor cells were further analyzed for expression of tissue-specific and prognostic markers such as breast mucin glycoproteins, erbB2, and CD44v6 for additional characterization and to confirm their tumor origin. The technique described could become a valuable tool for the quantification and molecular characterization of metastatic carcinoma cells in hematopoietic tissue, and may ultimately prove useful in the diagnosis, prognosis, and monitoring of patients with carcinoma.

Adult↗

Copper--an index of erosive activity?

Using atomic absorption spectrophotometry the copper content of synovial fluid has been compared in rheumatoid and osteoarthrotic synovial fluids. Synovial fluid caeruloplasmin has been determined by single radial immunodiffusion. Both are significantly increased in the rheumatoid group. Serum copper, similarly estimated, shows a trend to greater elevation with increasing degree of rheumatoid erosion as assessed radiologically.

Arthritis, Rheumatoid↗

The effect of emboli upon intrapulmonary receptors in the cat.

The effect of successive injections (on the activity from pulmonary stretch, irritant and type J receptors) of 0.1 g aliquots of either potato starch or plastic sheres was examined in artificially ventilated, anaesthetized, open chested cats. The discharge from nineteen pulmonary stretch receptors was altered after embolisation and mean maximum changes of 10% were observed in peak frequency and spike count per respiratory cycle. The activity from twelve of fourteen irritant receptors was changed after embolisation, mainly in the form of an increase of an existing, respiratory modulated discharge. O f ten type J receptors examined, six were stimulated after embolisation to produce an erratic pattern of discharge. The response of the three groups of receptors appeared to be independent of the size of the emboli. Histological examination showed scattered emboli in capillaries and columns in arterioles, according to particle size. It is likely that all three receptor types are involved in the reflex tachypnoea induced by pulmonary embolisation, since the changes in afferent vagal discharge occurred at or before the onset of the reflex respiratory events.

Animals↗

Urinary copper excretion in rheumatoid arthritis.

The pattern of urinary copper excretion in relation to urine osmolality (as shown by series of aliquots of urine) was studied in rheumatoid patients and in control groups. Rheumatoid patients showed an abnormal copper excretion pattern compared with nonrheumatoid subjects. This was not a direct function of the raised serum copper in rheumatoid disease. Measurements based on 24-hour series of aliquots of urine (as distinct from total pooled 24-hour collections) have been shown to be a useful and sensitive method for studying copper excretion patterns.

Adult↗

Antinative DNA antibodies as a reaction to pyrazole drugs.

A case history is presented of the occurrence of a high binding capacity for native DNA in the serum of a patient on phenylbutazone. This reverted to normal on stopping the drug. The patient also had a reversible neutropenia and leucopenia, and it is suggested that the high anti-DNA binding capacity was a feature of a drug-induced lupus-like phenomenon.

Antibodies↗

A comparison of alclofenac and indomethacin in the relief of rheumatoid morning stiffness.

In a double-blind within-patient comparison of indomethacin, alclofenac and placebo taken as a single daily dose at bedtime by 29 rheumatoid out-patients, both drugs proved superior to placebo. Seventeen patients expressed a preference for indomethacin and 10 found alclofenac equal or superior in effect. The lower incidence of gastric irritation with alclofenac is confirmed and suggests its use in subjects intolerant of indomethacin.

Adult↗