Biomedical subjects
Publications and source records attributed to T Martin.
The author in this article tries to find out the other aspect of human rights as it is felt by the subordinate staff of an Indian prison. He tried to put the problem on headings like 'human rights in prisons', 'human rights and prison staff', 'the problem of subordinate prison staff' and concludes with human rights education and prison staff.
Native Clostridium botulinum gene coding for type A neurotoxin has been used to construct recombinant derivatives coding separately for L and H polypeptide chains of the toxin. The gene derivatives have been cloned into an expression vector pET28b in E. coli BL21 (DE3) cells. The recombinant L and H proteins seem to be the major individual proteins after IPTG induction of the recombinant cells. Each of the proteins has been accumulated only in inclusion bodies. The recombinant L chain (but not H chain) has been successfully resolubilized. Each of the proteins contains six His residues on the N terminus which allows purification on Ni-agarose columns with high yield. No toxic effect has been observed for both L and H chains after injection of 10 micrograms of recombinant preparations purified from inclusion bodies. Moreover, the injection resulted in an increase in the titer of specific antibodies which protected mice from 1 DLM of type A native botulinum neurotoxin. Hence, the recombinant neurotoxin protein derivatives which are present in E. coli inclusion bodies can be a source of material for producing diagnostic and therapeutic sera against type A botulinum neurotoxin.
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Plasmid-based (naked DNA) genetic vaccines are now entering clinical trials to test their safety and efficacy in healthy human volunteers. A safety concern unique to this new class of vaccines is the potential risk of deleterious integration into host cell genomic DNA following direct intramuscular injection. To address this issue experimentally, a preclinical safety study was conducted in mice to determine the structural nature of plasmid DNA sequences persisting in total muscle DNA at both 30 and 60 days following a single intramuscular injection of a plasmid expressing the Plasmodium falciparum circumsporozoite protein. In a protocol described for the first time, total DNA was extracted from muscle tissue and was subsequently linearized with a restriction endonuclease to enable agarose gel size fractionation of all extrachromosomal plasmid DNAs from high molecular weight mouse genomic DNA. Using PCR assays to quantitate plasmid-specific sequences, it was found that the amount of plasmid DNA persisting in muscle tissue varied but averaged about 10 fg per microgram of genomic DNA (in the range of 1500 copies per 150,000 genomes). In two of four separate experimental injections of mouse muscle, PCR assays of genomic DNA fractions indicated that agarose gel purification removed plasmid DNA down to a level of < or =3 copies per 150,000 mouse genomes. In the two other experimental samples, 3-30 copies of plasmid DNA remained associated with purified genomic DNA. The time following injection (i.e., 30 or 60 days) was not a factor in the number of copies of plasmid associating with genomic DNA and it was not possible to conclude if such sequences were covalently linked to genomic DNA or simply adventitiously associated with the genomic DNA. However, if an assumption is made that the highest level plasmid DNA found associated with genomic DNA (i.e., 30 copies) represented covalently integrated plasmid inserts and that each insert resulted in a mutational event, the calculated rate of mutation would be 3000 times less than the spontaneous mutation rate for mammalian genomes. This level of integration, if it should occur, was not considered to pose a significant safety concern.
AIDS-associated primary central nervous system lymphomas are late events that have an extremely poor prognosis. Despite different hypotheses, the brain localization of these B cell lymphomas remains an enigma. To better define the cell origin of the lymphomas and the possible role of the B cell receptor (BCR) in the brain localization and/or in the oncogenic transformation, we analyzed the V region genes of the Ig heavy chain expressed by lymphoma cells in five randomly selected patients. After amplifying the rearranged VHDJH DNA by PCR, cloning, and sequencing of the amplified products, we observed that: 1) of the five lymphomas analyzed, four were clearly monoclonal; 2) there was no preferential use of one peculiar VH family or one peculiar segment of gene; 3) the mutation analysis showed that an Ag-driven process occurred in at least two cases, probably before the oncogenic event; and 4) there was no intraclonal variability, suggesting that the hypermutation mechanism is no longer efficient in these lymphoma B cells. Taken together, our results suggest that distinct Ags could be recognized by the BCR of the lymphoma cells in different patients and that, if the Ags are responsible for the brain localization of these B cells bearing mutated BCR, other factors must be involved in B cell transformations in primary central nervous system lymphoma.
Intraoperative radiotherapy (IORT) is a new concept in the treatment of recurrent and primary advanced colorectal tumors. Between October 1994 and December 1997 27 patients (primary tumor: 8, first recurrent tumor: 12, second recurrent tumor: 7) received IORT (32 applications). Chemotherapy and percutaneous radiotherapy had already been given to all patients with advanced and recurrent colorectal tumors. The intraoperative irradiation was performed through HDR iridium afterloading. A flexible flab--individually adapted to the "tumor bed"--was used as applicator. The contact dose ranged from 10 to 15 Gy. The mean operation time (rectum resection: 5, rectum amputation: 14, debulking: 8) increased by 30 min on average. Eight patients had postoperative complications: perianal wound infections (3), sacrovesical fistulas (3), leakage of anastomosis (1) and neural ureter dysfunction (1). To date--on average 17.1 months (range: 3-33) after operation--13 patients are free of tumor recurrence or show stable disease. Ten patients--all of them had macroscopic residual tumor--have local tumor progression combined with good quality of life. Only 4 patients died (acute kidney failure, stroke, marasmus, systemic progression). The afterloading flab technique represents a technically simple, minimally harmful procedure in the therapy of colorectal tumor. Even when IORT with electrons is not feasible or the patients have already been irradiated, a higher radiation dose is possible. Given the demonstrated rate of local tumor recurrence, the afterloading flab technique seems to be a valuable treatment alternative to extended, high-risk resections. Long-term follow-ups will be necessary.
We have developed a new interstitial HDR brachytherapy technique for the treatment of prostate cancer using CT based 3D planning after transrectal implantation of four non-parallel needles. CT based needle reconstruction, target definition, evaluation and documentation, including DVHs and 3D imaging, is a feasible, safe and well tolerated treatment concept.
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Rheumatoid arthritis is a common and debilitating autoimmune disease whose cause and mechanism remain a mystery. We recently described a T cell receptor transgenic mouse model that spontaneously develops a disease with most of the clinical, histological, and immunological features of rheumatoid arthritis in humans. Disease development in K/BxN mice is initiated by systemic T cell self-reactivity; it requires T cells, as expected, but B cells are also needed, more surprisingly. Here, we have identified the role of B cells as the secretion of arthritogenic immunoglobulins. We suggest that a similar scenario may unfold in some other arthritis models and in human patients, beginning with pervasive T cell autoreactivity and ending in immunoglobulin-provoked joint destruction.
BACKGROUND: Previous studies on semantic priming have suggested that schizophrenic patients with language disturbances demonstrate enhanced semantic and indirect semantic priming effects relative to controls. However, the interpretation of semantic priming studies in schizophrenic patients is obscured by methological problems and several artefacts (such as length of illness). We, therefore, used a psychometric high-risk approach to test whether healthy subjects reporting language disturbances resembling those of schizophrenics (as measured by the Frankfurt Complaint Questionnaire subscale 'language') display increased priming effects. In addition, the Schizotypal Personality Questionnaire was used to cover symptoms of schizotypal personality. Enhanced priming was expected to occur under conditions favouring automatic processes. METHODS: One hundred and sixty healthy subjects performed a lexical decision semantic priming task containing two different stimulus onset asynchronicities (200 ms and 700 ms) with two experimental conditions (semantic priming and indirect semantic priming) each. RESULTS: Analyses of variance revealed that the Frankfurt Complaint Questionnaire-' language' high scorers significantly differed from low scorers in three of the four priming conditions indicating increased automatic spreading activation. No significant results were obtained for the Schizotypal Personality Questionnaire total and subscales scores. CONCLUSIONS: In line with Maher and Spitzer it is suggested that increased automatic spreading activation underlies schizophrenia-typical language disturbances which in our study cannot be attributed to confounding variables such as different reaction time baselines, medication or length of illness. Finally, results confirm that the psychometric high-risk approach is an important tool for investigating issues relevant to schizophrenia.
Psychogeriatrics and especially psychiatric services in nursing and old-age homes are sorely lacking in research. Four years ago we developed and implemented a model for service delivery for old-age homes within our hospitals' catchment area. In the first year of operation 48 of 373 residents (13%) were evaluated and treated by a psychogeriatrician. The aim of the present study was to evaluate outcome of these patients three years later. All patients and medical records were re-assessed. During the three-year period 16/48 subjects (33.3%) passed away; of these half were previously diagnosed as suffering from a major depressive episode. None of the subjects who died had attempted suicide. Following a preliminary diagnosis of affective spectrum disorder, 4/48 patients (8.3%) were re-diagnosed at follow up as suffering from dementia. Full or partial remission of the original symptomatology was achieved in 18/32 surviving subjects (50.7%); mostly depressed or anxious patients. We conclude that although mortality rate among elderly psychiatric patients is high persistent interventions lead to successful remission in the majority of patients.
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A single injection of Escherichia coli lipopolysaccharide (LPS; intraperitoneally [i.p.] and intravenously [i.v.]) reliably induces peripheral nerve disturbances in the hindlimbs of inbred Australian albino Wistar (AaW) rats. In the series of experiments presented here, we aimed to characterize this syndrome by examining electrophysiologic, immunologic, and immunochemical features. The LPS-induced neurologic sequelae in AaW rats were transient, at least partly reversible by drug treatment, and were not associated with any detectable neuropathologic findings by light microscopy. Neurologic sequelae were prevented by administration of dexamethasone and by pretreatment with the macrophage inhibitor gadolinium chloride, suggesting that they were caused by LPS-induced activation of peripheral macrophages. Sequelae were associated with early decreases in compound muscle-action potential amplitudes, indicating impaired functioning of either proximal sciatic nerve axons and/or neuromuscular synapses. Spinal somatosensory-evoked potential latencies also were increased, indicating impaired somatosensory function at the sciatic nerve, dorsal roots, spinal cord, and/or postsynaptic interneurons, although the precise location of impairment could not be delineated. Similarities between this syndrome and immune-mediated polyneuropathies in humans are discussed.
Research indicates that 8.5% of all patients undergoing surgical procedures for more than 3 hours develop pressure ulcers. In some types of surgery, incidence rates in excess of 25% have been reported. An 11-month study was conducted on the safety and efficacy of an experimental alternating air device in comparison with a tertiary care facility's conventional practice. A series of 217 patients undergoing surgical procedures scheduled for a minimum of 3 hours were enrolled. No ulcers developed in the experimental group and 11 ulcers developed in seven patients in the control group (8.75% incidence rate). Of the 11 ulcers, one was Stage I, four were Stage II, and six were unstageable secondary to eschar. The difference between the groups is significant at the P = 0.005 level. Individuals who developed ulcers had a length of stay approximately 7 days longer than the hospital average for comparable patients who did not develop ulcers.
Terminal deoxynucleotidyl transferase (TdT) enzyme activity in lymphocytes generates diversity in the Ag receptor repertoires by adding template-independent N nucleotides and disrupting homology-directed rearrangements. The importance of this diversity in vivo and the significance of the suppression of TdT during fetal life remain uncertain. Previous studies have shown that in TdT knockout mice (TdT(0)) 1) the T cell repertoire is less peptide oriented; and 2) natural autoantibody, particularly anti-DNA autoantibodies, are less polyreactive, and their mean affinities are reduced. Consequently, the suppression of TdT during early T/B cell ontogeny may participate in controlling autoimmunity. To study the impact of TdT suppression in autoimmune-prone mice, we introduced the TdT null mutation into the (NZB x NZW)F1 (B/W) mouse strain. We show that TdT deficiency significantly reduces the incidence of autoimmune nephritis and prolongs survival compared with those in control mice. Surprisingly, the long-term survivor TdT(0) mice produced amounts of anti-ADN and anti-histone autoantibodies similar to those of their TdT+ littermates. However, these TdT(0) mice showed no evidence of renal inflammation, and the immune deposits were restricted to the mesangium, whereas basal membrane deposits were clearly correlated with overt renal disease. The present study supports the idea that the absence of TdT enzyme activity in lymphocytes protects mice against autoimmunity and could offer a therapeutic approach to autoimmune diseases. Moreover, our results may help to unravel the mechanisms of lupus nephritis.