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Biomedical subjects

R Martin

Publications and source records attributed to R Martin.

At least 451 records · Page 25Linked to original sources

Active polysomes in the axoplasm of the squid giant axon.

Axons and axon terminals are widely believed to lack the capacity to synthesize proteins, relying instead on the delivery of proteins made in the perikaryon. In agreement with this view, axoplasmic proteins synthesized by the isolated giant axon of the squid are believed to derive entirely from periaxonal glial cells. However, squid axoplasm is known to contain the requisite components of an extra-mitochondrial protein synthetic system, including protein factors, tRNAs, rRNAs, and a heterogeneous family of mRNAs. Hence, the giant axon could, in principle, maintain an endogenous protein synthetic capacity. Here, we report that the squid giant axon also contains active polysomes and mRNA, which hybridizes to a riboprobe encoding murine neurofilament protein. Taken together, these findings provide direct evidence that proteins (including the putative neuron-specific neurofilament protein) are also synthesized de novo in the axonal compartment.

Animals↗

Cloning of the two essential yeast genes, PRP6 and PRP9, and their rapid mapping, disruption and partial sequencing using a linker insertion strategy.

In the yeast Saccharomyces cerevisiae, some thermosensitive (ts) mutants have been shown to be impaired in pre-mRNA splicing (prp mutants). From a yeast genomic library, we have isolated plasmids that complement prp6 or prp9 ts mutations. These plasmids also complement the ts growth defect of additional independent mutants identified as new prp6 and prp9 ts alleles, indicating that the cloned DNAs encode PRP6 and PRP9 genes, respectively. Here, we describe the restriction maps of these loci which are localized on chromosome II and IV, respectively. The limits of open reading frames (ORFs) within the cloned inserts have been determined using a linker insertion strategy combined with the ts complementation assay. Double-strand DNA sequencing was also performed directly on the yeast expression vector from the inserted linkers. Gene disruption experiments demonstrate that both genes are essential for viability.

Base Sequence↗

Immunoglobulin G subclass preference of intrathecally produced HIV-specific oligoclonal antibodies.

Cerebrospinal fluid (CSF) and serum samples from 16 HIV-seropositive subjects were examined by ELISA and isoelectric focusing for the presence of HIV-specific immunoglobulin G (IgG) subclass antibodies. Autochthonous synthesis of IgG in the CSF was demonstrated in 11 patients. Intrathecally synthesized antibodies specific for individual HIV structural proteins were largely restricted to IgG1 (10 of 11 patients). One patient revealed additional local synthesis of IgG2 antibodies related to HIV-p15. In another patient locally produced antibodies specific for HIV consisted entirely of IgG4. In this patient amounts of locally produced antibodies were too low to be detected by routine procedures (calculation from an evaluation graph). No local synthesis of HIV-related IgG3 was demonstrated in any patient. Further studies will be needed to show whether determination of IgG-subclass-restricted antibodies to HIV is of prognostic value.

Adult↗

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma.

In patients with metastatic malignant melanoma the distribution patterns of radiolabelled lymphokine-activated killer (LAK) cells were investigated. Peripheral mononuclear cells (PMC) were isolated from six patients. LAK cells were generated by culturing PMC in complete medium containing 1000 U interleukin (IL)-2/ml and labelled with indium 111 before retransfer. We obtained scans at 2.5, 24, 48 or 96 h after injection with a high resolution gamma-camera. Intravenously injected LAK cells distributed to the lungs, liver, spleen and bone marrow. External tumour detection of known lymph node and bone metastases was successful in four. It failed in one patient with a solitary lung metastasis and in another patient with subcutaneous metastases. Our results suggest that LAK cells show tumour homing, providing a direct interaction between tumour and cytotoxic cells. We conclude that PMC seem to retain their ability to migrate after IL-2 stimulation and 111In-labeling. This technique may be helpful for kinetics studies or external detection of metastases in patients with malignant melanoma.

Adult↗

Haemodynamic interactions of muscle relaxants and sufentanil in coronary artery surgery.

The haemodynamic interactions between sufentanil (S) and muscle relaxants (MR) were studied in 40 ASA physical status III or IV patients (four groups of ten) scheduled for coronary artery bypass grafting (ABG). Group I received pancuronium (P) 0.08 mg.kg-1, Group II received vecuronium (V) 0.1 mg.kg-1, Group III received atracurium (A) 0.5 mg.kg-1 and Group IV metocurine 0.1 mg.kg-1 plus pancuronium 0.02 mg.kg-1 (M-P). Sufentanil, 20 micrograms.kg-1 was administered before sternotomy, 10 micrograms.kg-1 being injected before tracheal intubation and 10 micrograms.kg-1 afterwards. Heart rate (HR), ECG leadII and V5, systolic, diastolic and mean arterial and pulmonary blood pressures, central venous pressure (CVP) and pulmonary capillary wedge pressure (W) were measured and recorded at the time of seven strategic events between the pre-induction of anaesthesia period and sternotomy. Cardiac output (CO) and systemic vascular resistances (SVR) were also measured before induction of anaesthesia and after the administration of S 10 micrograms.kg-1 plus the MR. The HR decreased from baseline values in the post-tracheal intubation period in all groups except in P group. The mean arterial pressure also decreased significantly in all groups except in the P group. The CO did not change from baseline values but SVR decreased in all groups. There was no evidence of new myocardial ischaemia according to the ECG monitoring and there was no significant difference in the HR changes between patients who had or who had not received beta-blockers in any group. We conclude that within the present study conditions and design, HR and blood pressure changed least with pancuronium.

Adrenergic beta-Antagonists↗

Controlling system uncertainty in sport and work.

An applied psychological framework for coping with performance uncertainty in sport and work systems is presented. The theme of personal control serves to integrate ideas prevalent in industrial and organisational psychology, the stress literature and labour process theory. These commonly focus on the promotion of tacit knowledge and learned resourcefulness in individual performers. Finally, data from an empirical evaluation of a development training programme to facilitate self-regulation skills in professional athletes are briefly highlighted.

Journal Article↗

Interferon-gamma secretion by in vivo activated cytotoxic T lymphocytes from the blood and cerebrospinal fluid during mumps meningitis.

Functional studies of cerebrospinal fluid T lymphocytes during acute viral infections of the nervous system are rare. Recently, we had the opportunity to investigate the requirements for interferon-gamma (IFN-gamma) production of human in vivo activated (primary) cytotoxic T lymphocytes (CTL) generated during acute viral meningitis. Two HLA-B7-restricted, CD4-, CD8+ CTL clones from cerebrospinal fluid of one patient with mumps meningitis were studied. Although lytic activity was restricted by HLA-B7, the clones produced similar amounts of IFN-gamma when stimulated with HLA-matched and mismatched mumps virus-infected target cells. In addition, peripheral blood mononuclear cells of infected patients secreted significant amounts of IFN-gamma when incubated with autologous or allogeneic (HLA-A/B-mismatched) mumps virus-infected target cells. T cells capable of lytic activity and IFN-gamma secretion could only be isolated from venous blood during the initial phase of the infection. We suggest that the ability of human in vivo activated CTL to secrete INF-gamma early during the course of inflammation and in a HLA-unrestricted fashion is important for the elimination of viruses invading the central nervous system.

Child, Preschool↗

Intermittent fetal tachycardia and fetal hydrops.

A case is reported where fetal hydrops was noted 10 days after an initial observation of intermittent fetal tachycardia at 31 weeks. A diagnosis of supraventricular tachycardia was made and a successful conversion to sinus rhythm was achieved with maternally administered flecainide, with subsequent resolution of the hydrops. The fetus required no further treatment in pregnancy or at follow up. The mother suffered no side effects of the treatment.

Adult↗

Postmitotic reassembly of the cell nucleus in whole cells: an electron-spectroscopic study.

By electron-spectroscopic imaging it is possible to visualize selectively the distribution of phosphorus-rich structures such as nucleosomes, ribosomes or other ribonucleoprotein particles. Using this method we re-examined assembly of the nucleus in telophase of dividing onion root cells and human HeLa cells. Our observations disagree considerably with conclusions drawn from work with cell-free systems. We consistently observed reassembly of nuclear envelope cisternae from vesicles in the cytoplasm without direct contact with chromatin. The preassembled envelope cisternae then enclosed the telophase chromosome mass, contacting the chromatin in some tracts, but also trapping cytoplasmic material such as ribosomes between chromosomes and envelope. Until a late stage in telophase the re-forming nuclear envelope left large gaps between the nuclear and the cytoplasmic compartments. Exclusion of cytoplasmic material from the re-assembling nucleus was facilitated by prenucleolar material, which accumulated in the deep furrows of the chromosomes and interchromosomal spaces. This material expanded considerably while the envelope was still open, in this way displacing cytoplasm non-selectively from the future nucleus. The model we propose for reassembly of the nucleus in whole cells does not postulate contact with and complete enclosure of chromosomes by the re-forming envelope, and suggests a decisive role for expanding prenucleolar material in the process of nucleocytoplasmic compartmentalization.

Cell Nucleolus↗

Campylobacter intestinal carriage among stray and pet dogs.

The natural distribution of thermotolerant Campylobacter sp. in dogs (150 stray animals and 64 pets) was studied. Campylobacters were more frequently isolated (p < 0.01) from stray dogs (51.3%) rather than from pet dogs (21.9%). All the biotypes described by Lior for C. jejuni and C. coli were found among stray animals, whereas only C. jejuni biotypes I and II and C. coli biotype II were found among pet dogs. The need for more studies related to the role of environmental sanitary conditions in the spreading of Campylobacter species is noted.

Animals↗

[Clinical-diagnostic significance of steroid hormone receptor determinations].

The determination of steroid hormone receptors obtained an increasing significance in the last years. It has contributed to the explanation of the mechanism of hormone regulation in the organism. The test allows an additional indication, exceeding the histological differentiation, both in breast and endometrial cancer with regard to prognosis of the patient and of success of an adjuvant or curative hormone therapy, especially in progredient cases. The receptor test can be decisive for the strategy of therapy. The test allows a better indication of the expected success of therapy for different types of leukemia and malignant lymphoma, too. But the success of a pure glucocorticoid therapy is often temporarily restricted because of the spontaneous occurrence of steroid resistant receptor mutants.

Breast Neoplasms↗

[Degree of DNA ploidy and steroid hormone receptors as prognostic factors in endometrial carcinoma].

In a prospective investigation the concentration of DNA (ploidy) and of steroid hormone receptors (ER and PgR, resp.) were studied in endometrial carcinoma and related to each other, to established morphological prognostic criteria (stage, typing, grading, relative invasion of myometrium), and to the clinical progress of disease, respectively. The microscopic spectrophotometric analysis of DNA showed diploid main lines in 2/3 of investigated endometrial carcinoma. It could be demonstrated a relationship between heteroploidy, decreased mean concentrations of ER and PgR, unfavourable prognostic factors (stage II-IV, G3, myometrial invasion of greater than 2/3) and clinical progress of disease. The mean value of ER and PgR was higher in diploid carcinoma than in heteroploid ones. Significant differences were found both in the relation of the PgR concentration to different tumor stages (stage I vs. II-IV) and of the concentration to the different types of ploidy. Exceeding the histological differentiation, the determination of DNA and ER/PgR receptors can results in additional prognostic informations for a scientific proved, adjuvant or curative strategy of therapy after the operation.

Carcinoma↗

[Electron microscopic evidence of aluminum in lysosomes of kidney cells by electron energy loss spectroscopy].

Aluminium effects have increasing attention in long term dialysis of kidney patients and in a number of cerebral diseases. At present, however, there are still many open points concerning its localization and actions in the cell. If using electron spectroscopic imaging (ESI), aluminium could be directly demonstrated in the lysosomes of the kidney cells of uraemic rats experimentally loaded with aluminium. These findings were corroborated by means of electron energy loss spectroscopy (EELS).

Aluminum↗

HLA-DR2a is the dominant restriction molecule for the cytotoxic T cell response to myelin basic protein in DR2Dw2 individuals.

The HLA-DR2 restriction of the T cell response to myelin basic protein (MBP) was studied using murine L cells transfected with DRalpha and either DR2a or DR2b beta-chain cDNA. DR2a and DR2b represent the two isotypic DRbeta chains expressed in DR2Dw2 haplotypes. Eleven MBP-specific cytolytic T cell lines derived from patients with multiple sclerosis were isolated. Two of these cell lines recognized MBP-pulsed DR2-expressing L cell transfectants and four of them could only recognize the L cells if the adhesion molecule ICAM-1 was expressed in addition to HLA-DR2. Five of the six lines were restricted by HLA-DR2a; one line recognized Ag in conjunction with DR2b, but only if ICAM-1 was coexpressed. The remaining five lines did not lyse MBP-pulsed L cells. The ability of the DR2b molecules on transfected cells to stimulate T cells was confirmed with DR2b-allospecific T cell clones. Although five MBP-specific lines were restricted by DR2a, they recognized different parts of the MBP molecule, as demonstrated by the presentation of shorter peptides. Thus, our results suggest that DR2a is a dominant restriction molecule in MBP-specific responses by DR2+ MS patients. The results also indicate that the reported heterogeneity in MBP epitopes recognized by DR2-restricted T cells, may not be due to the use of different restriction elements but rather to the binding of different MBP peptides to DR2a molecules.

Animals↗

Melanoma-inhibiting activity inhibits cell proliferation by prolongation of the S-phase and arrest of cells in the G2 compartment.

Autocrine-secreted melanoma tumor growth-inhibiting activity (MIA, approximately Mr 8000) was isolated from supernatants of a malignant melanoma cell line HTZ-19 dM, established from a central nervous system-melanoma metastasis. Cell cycle kinetic analysis performed with bromodeoxyuridine/Hoechst flow cytometry revealed a MIA-sensitive period at the G0/G1 to S traverse; MIA mediated prolongation of the S-phase and increased arrest of cells in the G2 compartment. Growth inhibition by MIA is cell-density dependent; maximal effect is seen at low densities, and the effect may be partially antagonized by whole serum. MIA may cause growth stimulation at high cell densities and low MIA concentrations. The effect of MIA on different histological neuroectodermal cell types was compared by the same methodology: proliferation of a second malignant melanoma was inhibited, and no effect was observed with an ependymoma; 2 glioblastomas were slightly stimulated. Effects on human fibroblast-like cell strains were inconsistent. The mechanism of MIA is discussed in relation to other endogenous autocrine growth inhibitors.

Cell Count↗

Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals.

Myelin basic protein (MBP) is a candidate Ag for the autoimmune process believed to be involved in the pathogenesis of multiple sclerosis (MS). To investigate the fine specificity and HLA restriction of human MBP-specific CTL, long term T cell lines (TCL) were established from 22 MS patients and 16 healthy individuals by repeated antigenic restimulation. By using this approach, MBP-specific cytotoxic TCL were generated from 81% of the lines from MS patients and 69% of those from controls. TCL from both groups expressed the CD3+, CD4+, CD8- phenotype and secreted substantial amounts of IFN-gamma. By using large enzymatic and small synthetic peptides of MBP, TCL were primarily specific for the C-terminal part of the molecule and to a lesser extent for the N-terminal portion. Two regions of the molecule, MBP peptide 87-106 and MBP peptide 154-172, were recognized by the majority of the polyspecific lines and by four and three of 14 monospecific TCL, respectively. These highly immunogenic regions are of interest because they include sequences encephalitogenic in other species. The HLA restriction of each line was determined by using antibody blocking as well as various target cells including EBV-transformed B cells, homozygous typing cells, and fibroblasts transfected with cDNA for DR-alpha and DR-beta genes. All TCL were restricted by HLA-DR Ag. Several HLA-DR molecules restricted multiple cathepsin D-derived and synthetic MBP peptides, including the regions of peptides 87-106 and 154-172 which, respectively, were recognized in conjunction with four and three HLA-DR types. Three of these HLA-DR types are overrepresented in MS patients in different geographic regions. Together, these findings suggest that the MBP-specific cytotoxic T cell response, although not sufficient for disease, may be important for the pathogenesis of MS.

Amino Acid Sequence↗