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Biomedical subjects

S Rath

Publications and source records attributed to S Rath.

At least 73 records · Page 4Linked to original sources

Immunization with live versus killed Salmonella typhimurium leads to the generation of an IFN-gamma-dominant versus an IL-4-dominant immune response.

The mechanisms responsible for differential commitment of effector T cells to the production of either the IL-4/5/10 group or to the IL-2/IFN-gamma group of lymphokines during an immune response have not yet been clearly elucidated. We have used Salmonella typhimurium as a model murine bacterial parasite in BALB/c mice for live-cell versus killed-cell immunization and looked at the immune response in terms of delayed type hypersensitivity (DTH), IgG subclass distribution in the serum antibody response, and antigen-specific T cell proliferation and lymphokine secretion. The results indicate that the two forms of immunogen induce qualitatively different immune responses. Intraperitoneal immunization with live bacteria induces an IFN-gamma-dominant immune response associated with a strong DTH reaction and relatively higher levels of specific antibodies belonging to the IFN-gamma-dependent IgG2a isotype rather than the IL-4-dependent IgG1 isotype. Immunization with heat-killed bacteria gives rise to an IL-4-dominated response that shows excellent proliferative capacities in vitro, with lower levels of DTH responses and comparatively high levels of specific antibodies of the IgG1 isotype. IL-2 production in the responses generated by the two modes of immunization, however, is not preferentially associated with IFN-gamma production, unlike the reported profiles of long-lived murine T cell clones in vitro.

Animals↗

Evaluation of a new mechanical atherectomy system (TRAC) in normal canine coronary arteries. Transluminal Rotary Atherectomy System.

BACKGROUND: The feasibility and safety of a new mechanical atherectomy device, the Transluminal Rotary Atherectomy System (TRAC), for coronary application was examined in vivo in eight dogs. The system operates over a standard balloon coronary guide wire and excises and removes the atherosclerotic material in a single application. METHODS: The TRAC was introduced percutaneously using routine cardiac catheterization technique in four open-chest dogs (acute experiments) and in four closed-chest dogs (chronic experiments). RESULTS: Coronary angiography at the end of the procedure and 1-3 days later demonstrated normal coronary arteries without evidence of dissection, perforation, spasm, or thrombus formation. Macroscopic examination revealed perivascular bleeding along the treated coronary arteries in two out of eight dogs. Microscopic examination of these arteries demonstrated minimal endothelial peeling. Histology of the other coronary arteries demonstrated normal intact blood vessels without evidence for thrombus formation. CONCLUSIONS: These results demonstrate that it is feasible and relatively safe to introduce and operate the new TRAC mechanical atherectomy system in the normal coronary arteries of a beating dog heart.

Animals↗

The Bard Rotary Atherectomy System (BRAS): initial experience in patients with peripheral vascular disease.

Sixteen patients with a mean age of 65.4 +/- 9.8 years and suffering from peripheral vascular disease underwent peripheral atherectomy using a new mechanical device--the BARD Rotary Atherectomy System (BRAS). The BRAS is an "over the wire" system that consists of a spiral guidewire and a handheld motor drive unit, which rotates at 1,500 rpm. Prior to the procedure angiography demonstrated the presence of 18 obstructions (1 tibial, 2 popliteal, 15 superficial femoral arteries) with a mean stenosis of 95.7 +/- 8%. Successful atherectomy was achieved in 16 of 18 lesions and resulted in an 89% immediate success rate and a significant (P less than 0.01) reduction of stenosis to 37.8 +/- 12.5%. There were no significant complications. The excised and removed material embedded over the spiral guidewire demonstrated the presence of fibrotic tissue, fatty lesions, and calcium deposits. Medial or adventitial layers were not present in the removed atherosclerotic material. Mean ABI was significantly (P less than 0.01) increased from 0.38 +/- 0.17 to 0.55 +/- 0.21 following atherectomy. Angiographic follow-up obtained in ten patients 8.8 +/- 5.2 months following the procedure demonstrated restenosis in six of those ten patients. The ABI at this time remained unchanged. These results demonstrated that the new BRAS mechanical atherectomy system is feasible and safe for recanalization of severely stenosed arteries in patients with peripheral vascular disease.

Aged↗

Balloon aortic valvuloplasty in the elderly: useful when there is no alternative.

Of 63 elderly patients with calcific aortic stenosis in whom balloon aortic valvuloplasty was performed, 26 treated with the new technique of Cribier and Letac are the subject of this report. Patients were referred for the procedure because they were at high surgical risk, or were not candidates for surgery. Seven matched patients who fit the criteria for balloon valvuloplasty but refused the valvuloplasty procedure served as controls. Aortic gradient decreased from 78 +/- 27 mm Hg to 35 +/- 20 mm Hg and aortic valve area increased from 0.47 +/- 0.16 cm2 to 0.83 +/- 0.38 cm2 (P < 0.0001). Symptomatic improvement was immediately obtained in each patient. Complications were rare, with only one patient needing vascular repair for femoral artery occlusion. Three patients died during the initial hospitalization (none during the procedure). Valvuloplasty patients were followed for a mean period of 9.6 +/- 9.4 months. Three months survival was 87%, 6 months survival was 76%, and 12 months survival was 61%. Four of seven patients in the control group (57%) died within 3 months after initial referral. Balloon aortic valvuloplasty is a useful treatment in elderly patients who are poor surgical candidates. It may have a positive influence on short-term survival.

Actuarial Analysis↗

Monoclonal antibody detection of a major self peptide. MHC class II complex.

MHC class I and class II molecules transport foreign and self peptides to the cell surface and present them to T lymphocytes. Detection of these peptide:MHC complexes has thus far been limited to analysis of the response of a T cell. Previously, we showed that a mAb, Y-Ae, reacts with 10 to 15% of class II molecules on peripheral B lymphocytes and on cells in the thymus medulla but not thymus cortex in mice that express both I-Ab and I-Eb molecules. Elsewhere, we show that Y-Ae detects a self E alpha peptide bound to I-Ab molecules. Data presented here suggest that the antibody binds over the peptide binding groove of class II molecules, and, like a TCR, appears to recognize both the self peptide and polymorphic class II residues. In addition to B lymphocytes, the Y-Ae determinant is expressed at comparable levels on other APC, including macrophages and dendritic cells. Finally, the antibody does not react with invariant chain-associated class II complexes, thus providing direct evidence that invariant chain:class II complexes and peptide:class II complexes are mutually exclusive. These data provide further evidence that immunologic self is of limited complexity, and have important implications for T cell selection, self tolerance, and autoreactivity.

Animals↗

T and B cell receptors discriminate major histocompatibility complex class II conformations influenced by the invariant chain.

Direct recognition of major histocompatibility complex (MHC) molecules may occur when T cells are positively selected in the thymus and also during recognition of non-self MHC molecules. Since peptide recognition and binding of particular monoclonal antibodies is strongly influenced by the invariant chain (Ii) of the class II molecule, we have asked whether Ii also affects recognition of non-self MHC molecules by T cells. We find that Ii binding alters MHC class II conformation as detected by a monoclonal antibody, and that this alteration is retained in cell surface MHC class II molecules after Ii dissociates. This altered conformation also affects recognition by allogeneic T cells. Normal T cells and T cell clones preferentially recognize MHC class II molecules that have been associated with Ii, suggesting that thymic selection may be influenced by MHC conformation independently of specific peptide binding.

Animals↗

On the complexity of self.

Self peptides bound to self major histocompatibility complex (MHC) molecules have been implicated both in positive and in negative selection of T cells during intrathymic development. We report here that the novel MHC-restricted monoclonal antibody Y-Ae detects the MHC class II bound form of a major self peptide. Y-Ae binds approximately 12% of the relevant MHC class II molecules on self antigen presenting cells. The peptide detected by Y-Ae is one of several major peptides eluted from the MHC molecule. These data suggest that self peptides presented by self MHC class II molecules at densities sufficient to signal a CD4 T cell are of very limited complexity. Furthermore, as Y-Ae stains antigen presenting cells that mediate negative selection but not thymic cortical epithelial cells that drive positive selection, differential expression of self peptide:self MHC class II complexes may be a key feature of intrathymic selection.

Amino Acid Sequence↗

Control of T cell responses to staphylococcal enterotoxins by stimulator cell MHC class II polymorphism.

The bacterial toxic mitogens or superantigens are a family of related proteins that elicit potent T cell proliferative responses. These responses require APC that express MHC class II proteins, but they are not MHC restricted and they do not depend on a processing step, presumably because these mitogens bind directly to MHC class II molecules. These mitogens stimulate T cells by interacting in an unknown way with the portion of the TCR encoded by certain V beta gene segments. In this paper, we explore the importance of MHC class II polymorphism in T cell responses to staphylococcal enterotoxins. We find that certain MHC molecules present SEB to V beta 8-bearing T cells far better than others. These data suggest that one route of host defence against bacterial toxic mitogens may be to alter MHC class II molecules so that stimulation is inhibited.

Animals↗

B cell abnormalities induced by a mu Ig transgene extend to L chain isotype usage.

We have analyzed the phenotype of B cell populations from mice transgenic for a rearranged Ig mu H chain gene. We find a decrease in the number of B cells in the spleens of these mice. Transgenic B cells have decreased surface levels of both IgM and IgD. The circulating IgM in these mice is 3- to 10-fold enriched in lambda L chains, compared with that in non-transgenic mice. Analysis of IgM-producing hybridomas, from transgenic mice that express the transgene at high levels, demonstrates that this higher lambda frequency is observed in transgene-nonexpressing as well as transgene-expressing hybridomas. A partial loss of L chain isotype exclusion is also noted in these hybridomas, and a significant proportion of primary B cells expressing both kappa and lambda L chains on their surface can be demonstrated. These findings suggest an ability of the transgenic Ig H chain to affect events in B cell ontogeny beyond the H chain locus. Our results support a quantitative model of exclusion for both the H chain alleles and the L chain isotypes.

Animals↗

Management of the Galeazzi fracture.

Fifty-one adults with Galeazzi fractures were treated by operation and the results compared in cases treated early, late and after inadequate initial treatment. We conclude that in cases treated up to 10 weeks after injury, immobilisation with the forearm in full supination in an above elbow cast helps to maintain stability of the inferior radioulnar joint. The distal end of the ulna should only be excised after 6 months, and if the symptoms warrant it. In patients who were inadequately treated initially, the distal end of the ulna should be excised at the time of the operation on the radius, but a poor result is the inevitable outcome. Union, or nonunion of the ulnar styloid did not affect the end result.

Adolescent↗

Selectivity of distal reinnervation of regenerating mixed motor and sensory nerve fibres across muscle grafts in rats.

This study investigated target specificity during axonal regeneration of a mixed motor and sensory nerve towards respective targets. The femoral nerves in rats were divided and allowed to grow across a 6 mm gap interposed with frozen and thawed muscle grafts towards their distal motor and sensory nerve stumps. Fourteen weeks later the number of motoneurons projecting axons into the motor and sensory branches were determined by retrograde axonal tracing using horse-radish peroxidase. There were significantly higher numbers of motoneurons (p = 0.0034) projecting into the motor nerve than the sensory nerve. Efferent axons of a mixed nerve selectivity grew into motor branches when allowed to regenerate across a 6 mm gap interposed with muscle grafts. It is possible that a deliberately created 'structured gap' during repair of mixed nerves could improve axonal matching by allowing expression of neurotropism.

Animals↗

Silastic implant arthroplasty for post-traumatic stiffness of the finger joints.

In the years 1981 to 1987, 50 patients had 59 replacements of the finger joints. Of these, 41 patients with 49 joint operations were reviewed, with follow-up ranging from two to eight years (average 32 months). About 80% of these patients were satisfied that silastic implant arthroplasty had relieved their pain and stiffness and improved function of the finger and hand. They were satisfied that this procedure was preferable to amputation or fusion. Success or failure was assessed not only on the range of movement of the joint being replaced, but on relief of pain, correction of deformity, stability and overall finger function. The seven patients regarded as failures are analysed in detail.

Adolescent↗

Lack of topographical specificity in sensory nerve regeneration through muscle grafts in rats.

Regenerating sensory axons of each receptor class make new connections with similar denervated receptors. This study investigates to what extent these axons return to their original receptive field. The lateral cutaneous nerves of the thigh in rats were divided and allowed to regenerate across a 6 mm. gap interposed with frozen and thawed muscle graft towards their original distal nerve stump and a "foreign" sensory nerve, the saphenous nerve. 16 weeks later, myelinated axon counts of 26 pairs of distal nerves showed no preferential growth towards the original receptive field. Lack of topographic specificity during sensory nerve regeneration may explain the faulty localisation of sensation after nerve repair in clinical practice. Following sensory nerve regeneration, the somatosensory cortex receives accurate afferent information but from disparate skin sites; this probably alters the relationship of overlapping sensory fields and may be the cause of distorted pattern recognition.

Animals↗

Exclusive expression of MHC class II proteins on CD45+ cells in pancreatic islets of NOD mice.

The expression of MHC class II molecules on beta-cells of the pancreatic islet has been proposed to play a role in the genesis of insulin-dependent diabetes mellitus in the NOD mouse. We investigated this by immunofluorescent double labeling of islet cells with anti-MHC and anti-CD45 to identify cells of hematopoietic origin. MHC class I expression increased with age on CD45- islet cells. MHC class II expression was not observed on CD45- islet cells at any age; the only cells in the islet that were MHC class II positive were also CD45+. This indicates that all MHC class II-positive cells in the islet are lymphoid cells that infiltrate the islet, whereas the islet endocrine cells express no MHC class II molecules. However, an increase in MHC class I expression occurred on beta-cells, and this may play a role in immunopathogenesis.

Animals↗

Pregnancy after myocardial infarction: are we playing safe?

The safety of pregnancy after myocardial infarction remains a significant dilemma for both the obstetrician and the cardiologist. Only 20 cases of pregnancy after myocardial infarction have been reported. To clarify this problem, we add our experience of four such cases in which conception occurred 9 months to 9 years after myocardial infarction with no previous consultation. Each woman had an uneventful pregnancy with no cardiac or obstetric complications related to the myocardial infarction. All patients were under the strict supervision of an obstetrician and a cardiologist during pregnancy in our conjoined antepartum-cardiologic clinic. The mode of delivery in all patients was related to the obstetric indications. Our experience and the accumulated experience in the literature demonstrate good prognosis for patients who conceive after myocardial infarction.

Adult↗