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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 667 records · Page 37Linked to original sources

[Acute effects of extracorporeal LDL cholesterol and fibrinogen elimination on blood rheology and microcirculation].

Long-term intermittent heparin-induced extracorporeal low-density lipoprotein (LDL)-cholesterol precipitation was performed in three men - aged 32, 52 and 56 years - with severe familial hypercholesterolaemia and angiographically demonstrated coronary heart disease. This significantly lowered by 65-70% their LDL-cholesterol concentration and by 48-54% their fibrinogen concentration. Fibrinogen elimination reduced plasma viscosity by 13-14% and clearly raised the transcutaneously measured partial pressure of oxygen by 33-50%. Clinically the improved microcirculation achieved a decrease in angina symptoms: the walking distance of the 52-year-old man increased from about 100 m to 4000 m, the daily need of glyceryl trinitrate falling from an average of 12 to 4 aerosol doses.

Adult↗

Client cognitive responses to counselor paradoxical and nonparadoxical directives.

Client cognitive responses to counselor paradoxical and nonparadoxical directives were examined. It was predicted (a) that clients who received paradoxical symptom prescriptions would display a greater negativity toward the counselor and counseling than those who received nonparadoxical directives; and (b) that clients who received no rationale for the paradoxical directives would display a greater negativity than those who received a rationale. Thirty clients who had reported performance anxiety received one 45-minute counseling interview. Ten clients received paradoxical directives with a rationale, 10 received paradoxical directives with no rationale, and 10 received nonparadoxical directives. Results showed no significant differences in either client in-session negativity or out-of-session implementation of directives between the paradoxical and nonparadoxical conditions and between the rationale and no rationale paradoxical conditions. Possible implications of the findings are discussed.

Adaptation, Psychological↗

Polyclonal IgM anti-GM1 ganglioside antibody in patients with motor neuron disease and variants.

Recent studies reported the presence of anti-ganglioside antibodies in occasional patients with motor neuron disease. We found polyclonal serum IgM anti-GM1 antibodies by an anti-GM1 enzyme-linked immunosorbent assay (ELISA) in 9 (19%) of 48 patients with motor neuron disease. A comparable frequency of IgM anti-GM1 antibodies was found in 4 (10%) of 40 sera from patients with other neurological disease. Three (17%) of 18 sera from the patients with motor neuron disease and 2 (17%) of 12 sera from patients with other neurological diseases had anti-GM1 immunostaining as shown by thin layer chromatography immunoblot. One patient with a lower motor neuron variant of motor neuron disease or motor axonopathy without multifocal conduction block had a markedly elevated polyclonal IgM anti-GM1 ELISA titer (greater than 1:64,000) with prominent immunostaining of GM1, moderate immunostaining of GM2, and weak and inconsistent immunostaining of GD1b by thin layer chromatography immunoblot. Treatment with prednisone resulted in clinical improvement despite increasing anti-GM1 antibody titers. These data indicate that patients with motor neuron disease have measurable levels of anti-ganglioside antibodies as frequently as patients with other neurological diseases. This contrasts with a small subgroup of patients with a lower motor neuron variant of motor neuron disease or motor axonopathy who have markedly elevated levels of serum anti-ganglioside antibodies and a clinical syndrome that is treatable with immunosuppression.

Amyotrophic Lateral Sclerosis↗

Frequency of the cystic fibrosis delta F508 mutation in a large sample of the French population.

We have determined the frequency of the cystic fibrosis (CF) delta F508 mutation in a large sample of CF patients originating from different areas of France, including the greater Paris, Brittany, Alsace, Lorraine and Rhône-Alpes regions. A total of 422 CF chromosomes were studied, and the defect was found to account for 75% of the mutant alleles. In the course of the survey, a rare nucleotide sequence polymorphism leading to an isoleucine to valine substitution at position 506 of the CF transmembrane conductance regulator protein has been characterized in an unaffected individual. Our data enable the evaluation of the probabilities that a chromosome negative for the delta F508 mutation carriers another CF defect.

Cystic Fibrosis↗

Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis.

The cystic fibrosis (CF) gene was recently identified as a gene spanning 250 kilobases (kbp) and coding for a 1480 amino acid protein, cystic fibrosis transmembrane conductance regulator (CFTR). Approximately 70% of CF mutations involve a three-base-pair deletion in CFTR exon 10, resulting in the loss of a phenylalanine at position 508 in the gene product (delta F508). In order to screen for other molecular defects, we have used a strategy based on denaturing gradient gel electrophoresis (DGGE) of polymerase chain reaction (PCR)-amplified gene segments. This method, which permits rapid detection of any sequence change in a given DNA stretch, was used successfully to analyse 61 non-delta F508 CF chromosomes from French CF patients. A study of CFTR exons 10, 11, 14a, 15 and 20 detected three mutations located in exons 14a, 15 and 20, along with several nucleotide sequence polymorphisms. These nucleotide changes were identified by direct sequencing of PCR fragments displaying altered electrophoretic behaviour, together with some of the polymorphisms and mutations previously characterized by others. The strategy presented here constitutes a valuable tool for the development of carrier testing for individuals or couples with a family history of cystic fibrosis, and will contribute to deciphering the functionally important regions of the CFTR gene.

Cystic Fibrosis↗

The effects of gamma-interferon on human peripheral blood monocyte/macrophage-mediated bone particle degradation.

gamma-Interferon (IFN-gamma) has recently been demonstrated to inhibit the ability of mononuclear phagocytes to degrade bone particles. We have further addressed the specificity, potency and mechanism of this activity using human recombinant IFN-gamma. Adherent peripheral blood mononuclear leukocytes from normal human volunteers were cultured with washed, sieved (less than or equal to 75 microns) 45Ca-labelled rat bone particles for 3 days, after which bone particle degradation (7.1 +/- 1.6%, n = 11) was calculated from the fraction of 45Ca released into the medium. As little as 5 U/ml IFN-gamma significantly suppressed bone particle degradation and 50 U/ml was associated with consistent marked suppression (74.0 +/- 3.5% inhibition, P less than 0.001, n = 11). IFN-gamma was not suppressive if added to cells 24 h or more after exposure to bone particles. Addition of indomethacin (10 microM) did not reverse the effect of IFN-gamma, suggesting that it was not prostaglandin-mediated. In addition, 1,25(OH)2D3 (10 nM) did not remove the inhibitory effect of IFN-gamma. Contact of mononuclear phagocytes with bone particles and secretion of soluble factors from these cells have both been demonstrated to play a role in their ability to degrade bone particles. IFN-gamma (50 U/ml) inhibited monocyte/macrophage interaction with another unopsonized surface, i.e., one micron fluorescent latex particles, decreasing the number of internalized particles from 12.6 +/- 2.9 per cell to 5.9 +/- 1.4 per cell (P less than 0.01, n = 15), as measured using flow cytometry. However, binding of bone particles by the cells was not diminished by IFN-gamma. Exogenous alpha-interferon and human recombinant IL-1 beta, TNF-alpha, and lymphotoxin did not alter bone particle degradation. In addition, endogenous IL-1 beta release from human monocyte/macrophages exposed to bone particles was negligible and unaffected by IFN-gamma. We conclude that IFN-gamma is a potent and specific inhibitor of monocyte/macrophage-mediated bone particle degradation, and that this activity does not appear to be due to effects on the ability of monocytes to bind bone particles or to release IL-1 in response to the particles.

Animals↗

Ambulatory medical care for the elderly in Switzerland.

Data from a study on ambulatory medical care in two Swiss cantons are used to describe the characteristics of consultations delivered to patients 65 years old and over. The differences with younger patients are presented. The elderly generally suffer from different diseases, and their problems are often chronic. Primary care concerns three-quarters of visits. Medical problems are very frequent and important among this population. It is important to know their specific needs in order to adapt medical practice to them and to be aware of the complexity of the aging process in industrialized societies.

Aged↗

High progesterone receptor concentration in a variant of the ZR-75-1 human breast cancer cell line adapted to growth in oestrogen free conditions.

Culture of ZR-75-1 human breast cancer cells for 5 days in the absence of oestrogens (phenol red-free medium supplemented with dextran coated charcoal stripped 5% fetal calf serum) resulted in a slowing of growth rate and loss of progesterone receptors. Oestradiol at 10(-9) M markedly stimulated growth and progesterone receptor synthesis over a 5-day period. While medroxyprogesterone acetate (10(-10) to 10(-6) M) inhibited growth of ZR-75-1 cells growing in complete medium, in the short-term absence of oestrogens low concentrations were growth stimulatory. Cells deprived of oestrogens for 5 days retained sensitivity to growth inhibition by 4-hydroxy tamoxifen. ZR-75-1 cells were also adapted to growth in the absence of oestrogens over a 5-month period. These cells (ZR-PR-LT) failed to express binding sites characteristic of the type 1 oestrogen receptor but progesterone receptor expression was at a level normally associated with oestrogen induction. Adapted cells were growth inhibited by oestradiol, 4-hydroxy tamoxifen and medroxyprogesterone acetate, but despite elevated progesterone receptor expression the progestin was only marginally more inhibitory than in the parent line. Our data indicate a poor quantitative relationship between response to progestins in vitro and progesterone receptor concentration and support previous findings that acquisition of an oestrogen independent phenotype does not necessarily result in resistance to anti-oestrogens.

Antineoplastic Agents↗

Expression and function of mutant Ia antigen in transgenic mice.

Cell surface expression of Ia antigens requires the assembly of alpha and beta heterodimers. We have produced a double transgenic mouse with a wild form Ak alpha gene and a mutant Ak beta (Ak beta MB) gene with d-allele substitution at positions 63 and 65-67. Initial studies indicated that the Ak alpha and Ak beta MB transgenes are not expressed on the surface of lymphoid cells of the transgenic mice. However, when spleen cells were stimulated with LPS prior to FACS analyses, Ak/Ak MB assembly and subsequent surface expression was induced. The tail skins from transgenic founder mice were rejected by the parental mice indicating a role for the mutant antigen on the allograft. In addition, the Ak transgenic mice on H-2q/q background can partially delete V beta 6+ T cells, suggesting the presence of the transgene product in the thymus.

Animals↗

Localization of ATP Sulfurylase and O-Acetylserine(thiol)lyase in Spinach Leaves.

The intracellular compartmentation of ATP sulfurylase and O-acetylserine(thiol)lyase in spinach (Spinacia oleracea L.) leaves has been investigated by isolation of organelles and fractionation of protoplasts. ATP sulfurylase is located predominantly in the chloroplasts, but is also present in the cytosol. No evidence was found for ATP sulfurylase activity in the mitochondria. Two forms of ATP sulfurylase were separated by anion-exchange chromatography. The more abundant form is present in the chloroplasts, the second is cytosolic. O-Acetylserine(thiol)lyase activity is located primarily in the chloroplasts and cytosol, but is also present in the mitochondria. Three forms of O-acetylserine(thiol)lyase were separated by anion-exchange chromatography, and each was found to be specific to one intracellular compartment. The cytosolic ATP sulfurylase may not be active in vivo due to the unfavorable equilibrium constant of the reaction, and the presence of micromolar concentrations of inorganic pyrophosphate in the cytosol, therefore its role remains unknown. It is suggested that the plant cell may be unable to transport cysteine between the different compartments, so that the cysteine required for protein synthesis must be synthesized in situ, hence the presence of O-acetylserine(thiol)lyase in the three compartments where proteins are synthesized.

Journal Article↗

Methadone treatment in medical private practice: outcome according to the number of courses followed.

In the Swiss Canton of Vaud, methadone treatment is mostly provided by the private medical practitioners. 562 opioid dependent persons followed at least one course of treatment between 1976 and 1986; at that time, 209 of them had completed a first course, 118 a second one and 31 a third one. Evolution of the persons was observed from the end of their last course to the end of the study. Outcome was evaluated according to the rank of the last course. Whatever its rank, each course resulted in about 17% of stable abstainers and 6% of chronic opioid-dependent persons. In contrast, the risks to start a new course, to be imprisoned and to enter into a therapeutic community showed a clear gradient with the rank of the course: they were about 38%, 27% and 10% respectively one year after a first or a second course, and rose to 43%, 38% and 28% one year after a third course.

Adult↗

Neuropeptides in hypertension: role of neuropeptide Y and calcitonin gene related peptide.

1. The effect of neuropeptide Y (NPY) on cardiovascular function at three levels of the noradrenergic axis where the peptide is known to co-exist with noradrenaline (NA) and or adrenaline (A) was studied in normotensive Sprague-Dawley (SD), Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). 2. In the perfused mesenteric arterial bed, NPY and the structurally similar peptide intestinal polypeptide (PYY) decreased the periarterial nerve stimulation induced release of NA and potentiated the increase in perfusion pressure to nerve stimulation or exogenously applied agonists (e.g. angiotensin, vasopressin, phenylephrine). In contrast to NPY and PYY, C-terminal NPY fragments inhibited NA release and produced a parallel decrease in perfusion pressure thus supporting the concept of Y1 (post) and Y2 (pre) NPY receptors. 3. In the mesenteric artery of SHR the prejunctional inhibitory effect of NPY was attenuated while the postjunctional response was enhanced. 4. Following intrathecal (Int) injection of NPY, there was a decrease in blood pressure, total peripheral resistance (predominantly by a decrease in mesenteric vascular resistance) and renal nerve activity. The depressor effect of Int NPY was attenuated in the SHR. 5. Unilateral injections of NPY into the posterior hypothalamic nucleus increased blood pressure, hindquarter and renal vascular resistance and renal nerve activity. The pressor effect was enhanced in the SHR. 6. Periarterial nerve stimulation of the perfused mesenteric artery produced a frequency dependent vasodilation in beds pretreated with guanethidine and precontracted with methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The rights of man and animal experimentation.

Since emotions give contradictory signals about animal experimentation in medical science, man's relationship to animals must be based upon reason. Thomas Aquinas argues that man is essentially different from animals because man's intellectual processes show evidence of an abstract mechanism not possessed by animals. Man's rights arise in association with this essential difference. The consequence is that only man possesses true rights by Aquinas's definition; animals have them only by analogy. However, cruelty to animals is illicit and they should be protected, principally not because they have rights, but because he who is cruel to animals is more likely to be cruel to his fellowman. If there is a need for animal experimentation in science for the good of man, this approach gives philosophical justification for experimentation, since man's well-being must come before that of animals because of his unique possession of rights. However, those experiments should be carried out in the kindest way possible, to promote kindness towards man. To see man as solely part of a biological continuum in competition for rights with those beings close to him biologically, detracts from man's dignity.

Animal Experimentation↗