Search PubMed⌕ Search

Biomedical subjects

S Rath

Publications and source records attributed to S Rath.

At least 55 records · Page 3Linked to original sources
PubMed1996

Analysis of T-cell hybridomas with an unusual MHC class II-dependent ligand specificity.

We have characterized two unusual T-cell hybridomas, 1E3 and 3B8, from H-2k mice immunized with I-Ab-transfected L cells (H-2k), that are stimulated by L cells transfected with I-Ab, I-Ak or I-Eb, but not by non-transfected L cells. These hybridomas could not be stimulated by spleen cells from H-2i3, H-2k, H-2b or H-2d mice. Monoclonal anti-I-A antibodies did not block their responses, suggesting that mouse major histocompatibility complex (MHC) class II molecules may be peptide donors rather than restriction elements for them. The stimulation of these hybridomas by fibroblast targets was not blocked by an anti-H-2kk, Dk-specific monoclonal antibody. Lipopolysaccharide (LPS)-activated splenic and peritoneal exudate cells from H-2k, H-2d, H-2i3, H-2b as well as beta 2-microglobulin-deficient, TAP-1-deficient and I-A alpha-deficient H-2b mice stimulated these hybridomas. LPS could also activate a macrophage cell line, but not a B-cell line, to become stimulatory for 1E3. A rat antiserum against untransfected L cells specifically and significantly blocked the response of 1E3. Thus, 1E3 may recognize a conserved murine MHC class II peptide loaded in a TAP-1-independent fashion on a non-classical, monomorphic, beta 2-microglobulin-independent restriction element.

Animals↗
PubMed1996

Absence of coronary calcification on double-helical CT scans: predictor of angiographically normal coronary arteries in elderly women?

PURPOSE: To test the hypothesis that angiographically normal coronary arteries in elderly women are identifiable by the absence of coronary calcification on double-helical computed tomographic (CT) scans. MATERIALS AND METHODS: Forty-eight consecutive women (age range, 60-76 years) underwent coronary angiography for chest pain evaluation, as well as double-helical CT. Thirty women (mean age, 65 years +/- 5) had coronary artery disease (CAD), defined as any angiographic disease, and 18 women (mean age, 66 years +/- 4) had angiographically normal coronary arteries. RESULTS: Women with angiographically normal coronary arteries had lower coronary calcification scores than those of patients with CAD: 5.7 +/- 11 versus 580 +/- 634, respectively (P = .0004). Seven women with angiographically normal coronary arteries demonstrated mild coronary calcification (score < 50). Of the 11 women without coronary calcification, none had CAD. Thus, the absence of coronary calcification on double-helical CT scans in elderly women was predictive of angiographically normal coronary arteries with 61% sensitivity, 100% specificity, and 85% accuracy. CONCLUSION: Double-helical CT is an accurate, noninvasive modality for diagnosing angiographically normal coronary arteries in elderly symptomatic women.

Aged↗
PubMed1996

Suprascapular nerve entrapment: experience with 28 cases.

Suprascapular nerve entrapment (SNE) in the suprascapular notch is a rare entity that must be considered in the differential diagnosis of radicular pain, as well as that of shoulder discomfort. Over a period of 10 years (1985-1995), the authors treated 28 cases of SNE in 27 patients by surgical decompression of the nerve. One patient underwent operation bilaterally within 5 years. Five patients presented with a history of trauma to the shoulder region. In three patients, a ganglion cyst was the origin of the nerve lesion. In 16 patients, the nerve problem was primarily related to athletic activities. Eight of these patients were professional volleyball players. In the remaining three patients, there was no relationship between the nerve lesion and trauma or athletic activities. Twenty-one patients (22 cases) complained of pain located over the suprascapular notch. Seventeen patients had paresis and atrophy of both the supraspinatus (SS) and infraspinatus (IS) muscles. In 10 patients only the IS muscle was involved. One patient exhibited a sensory deficit over the posterior portion of the shoulder. Electromyography was performed in all cases. The mean follow-up period in the 25 cases (24 patients) that could be evaluated was 20.8 months (range 3-70 months). Nineteen of 22 cases with preoperative pain could be evaluated. Sixteen of these patients were completely free of pain after surgery and three patients found their pain had improved. Motor function in the SS muscle improved in 86.7% and motor function in the IS muscle in 70.8% of cases. Atrophy of the SS muscle resolved in 80.7% and atrophy of the IS muscle in 50% of cases. Surgical treatment of SNE is indicated after failed conservative treatment and in cases of atrophy of the SS and IS muscles. The authors recommend the posterior approach, which minimizes risks and complications and produces good postoperative results.

Adolescent↗
PubMed1996

[Cavernoma. Indications for surgical removal and outcome].

Between July 1990 and October 1994 26 patients were operated on for 26 intracranial and 2 intraorbital cavernous hemangiomas. We found seizures in 62% of our patients, focal neurological deficits and unspecific complains (like headache or dizziness) in 19% each. The average follow-up period was 12 months, 24 patients could be included in this study. 12/14 patients of the seizure group improved, 10/14 reported a complete relieve of their epilepsy. All 5 patients with focal deficits improved, among them 2 with no residual deficit. Finally 3/5 patients with unspecific complains improved, 2/5 remained unchanged. The functional morbidity was 4% (one slight aphasic syndrome), we did not have any mortality. Therefore we conclude that a neurosurgical treatment is indicated in any case of cavernous hemangioma with focal deficits or intractable epilepsy. The operation should also be considered in patients with supressed seizures by anti-convulsants, if the malformation is not located in an eloquent area. Due to the risk of spontaneous bleeding (comparable to incidental aneurysms), the indication for a neurosurgical treatment mainly depends on the location of the cavernoma in cases of its accidental discovery.

Adolescent↗
PubMed1995

Q wave and Non-Q wave myocardial infarction after thrombolysis.

OBJECTIVES: We studied the clinical outcome of Q wave and non-Q wave infarction after thrombolytic therapy. BACKGROUND: Controversy exists over the clinical significance of Q waves after thrombolysis. METHODS: We studied postthrombolytic angiographic results and short- and long-term clinical outcome in 150 patients with acute myocardial infarction classified as Q wave and non-Q wave on the 24-h and discharge electrocardiograms (ECGs). The results from the two groups were then compared. RESULTS: Eighty percent of patients had a Q wave and 20% a non-Q wave infarction on the 24-h ECG. The latter patients had lower peak creatine kinase (CK) levels (p < 0.001), but the two groups did not differ significantly otherwise. In 18 patients with a Q wave infarction on the 24-h ECG, pathologic Q waves disappeared. However, in seven patients with a non-Q wave infarction on the 24-h ECG, pathologic Q waves appeared throughout the hospital period. Q wave regression was associated with lower peak CK levels (p < 0.001) and an improvement in left ventricular ejection fraction (p < 0.01). Thus, only 72% of patients had a Q wave and 28% a non-Q wave infarction on the discharge ECG. Patients with a non-Q wave infarction on the discharge ECG had higher patency of the infarct-related artery (p < 0.04), lower mean peak CK levels (p < 0.0001), a higher ejection fraction (p = 0.001) and a lower incidence of heart failure (p = 0.06) than patients with a Q wave infarction on the discharge ECG. Although the 2-year incidence of reinfarction and revascularization was higher in patients with a non-Q wave infarction on the discharge ECG (p < 0.05), 2-year mortality was lower (p = 0.08). CONCLUSIONS: Although the early postthrombolytic distinction between Q wave and non-Q wave infarction conveys no significant information, during the hospital period, non-Q wave infarction is associated with a smaller infarct area, improved left ventricular function and lower mortality.

Aged↗
PubMed1995

Induction of tolerance in freshly isolated alloreactive T cells by activated T cell stimulators is not due to the absence of CD28-B7 interaction.

Human T cells express MHC class II molecules on activation, and this makes them potential APCs for responder CD4 T cells. We have shown earlier that MHC class II-expressing human T cell APCs induce specific tolerance in freshly isolated alloreactive responder CD4 T cells. In this study, we show that this induction of tolerance does not depend on the expression of a specific coreceptor on the stimulator T cell APCs, because both CD4 and CD8 T cell stimulators efficiently induce tolerance. Such a tolerant cell population responds significantly better to IL-2 than unprimed cells, indicating the physical presence of T cells expressing higher levels of IL-2 receptors. The addition of exogenous IL-2 during priming with activated T cell APCs effectively blocks the induction of tolerance and permits successful priming of alloreactive responder cells. We have investigated the possible role of the CD28/CTLA4-B7 family interaction in this model of induction of T cell anergy in T-T interactions. The freshly activated T cell APCs used in this study express CTLA4-binding ligand(s). Furthermore, cross-linking CD28 on responder T cells does not enable activated T cell APCs to elicit a primary proliferative alloresponse, nor does it prevent the induction of tolerance in responder T cells. The CD28/CTLA4-B7 family interaction is thus unlikely to be involved in the induction of T cell anergy by T cell APCs.

Antigen Presentation↗
PubMed1995

Modulation of immunogenicity and antigenicity of proteins by maleylation to target scavenger receptors on macrophages.

We have maleylated proteins to target macrophage-specific scavenger receptors and have used this system to study changes in the epitopes and immunogenicity of such proteins. We show that maleylation of diphtheria toxoid (DT) induces targeting to macrophage scavenger receptors and enhances its immunogenicity. DT does not evoke detectable serum Ab responses upon injection as soluble protein. However, maleylated DT (mDT) does generate a significant Ab response. Furthermore, immunization with soluble mDT leads to a better T cell proliferative response in vitro than immunization with DT can generate, thereby demonstrating that maleylation leads to enhanced T cell immunogenicity in vivo. We also find that maleylation disrupts the native B cell epitopes of DT and creates new epitopes, because antisera to DT and mDT do not cross-react. At least some of the new epitopes generated are maleylation specific, because antisera against various maleylated proteins do cross-react. In contrast, maleylation does not significantly modify the repertoire of T cell epitopes generated from DT, because T cells generated by either DT or mDT immunization are cross-reactive, and both DT and mDT can stimulate T cells that are specific for single synthetic DT peptide. Maleylated proteins are better presented in vitro than are their native counterparts, and this enhancement of presentation is blocked by unrelated maleylated proteins. These results suggest that Ags targeted to scavenger receptors on macrophages by maleylation are better presented to T cells and are immunogenic in vivo without adjuvant.

Animals↗
PubMed1995

Analysis of immunization route-related variation in the immune response to heat-killed Salmonella typhimurium in mice.

In examinations of the factors regulating the quality and quantity of the immune response to Salmonella typhimurium, we have shown previously that live and heat-killed preparations of S. typhimurium can induce gamma interferon-dominant and interleukin-4-dominant immune responses, respectively, upon intraperitoneal (i.p.) immunization of BALB/c mice. Using this system to investigate the role of the route of immunization in the immune response, we show in the present study that i.p. immunization with heat-killed S. typhimurium generates a quantitatively better immune response than does intradermal (i.d.) immunization. The quantitative differences observed between the i.p. and i.d. routes are apparent in the amount of S. typhimurium-specific antibodies produced, the extent of responses in T-cell proliferation assays, and the quantities of lymphokines generated. However, the ratios of immunoglobulin (Ig) isotypes [IgG1/IgG2a] are comparable and the relative dominance of interleukin-4 over gamma interferon is seen in both i.p.- and i.d.-immunized mice, suggesting that the predominant T-cell effector pathways triggered are not qualitatively dependent on the route of immunization. An examination of the antigenic profile recognised by the B-cell and T-cell responses in i.p.- versus i.d.-immunized mice shows that while the Western immunoblot patterns recognized by serum antibodies from the two groups of mice were not significantly different, T cells from i.p.-immunized mice recognized a broader spectrum of antigens in an immunoblot assay than did those from i.d.-immunized mice. These data suggest that there may be a significant difference in the antigen-processing ability of peritoneal and dermal antigen-presenting cells for complex antigenic formulations such as bacterial vaccines.

Animals↗
PubMed1995

Calcification of coronary arteries: detection and quantification with double-helix CT.

PURPOSE: To evaluate the accuracy of double-helix computed tomography (CT) in coronary artery calcification detection and quantification. MATERIALS AND METHODS: One hundred sixty patients with coronary disease (135 men, 25 women; age range, 45-62 years), of whom 138 had obstructive (stenosis of > 50% of diameter; n = 129) or mild (< 50% stenosis; n = 9) coronary artery disease (CAD) and 22 had normal coronary arteries (per angiographic findings), and 56 age-matched healthy control subjects underwent double-helix CT. RESULTS: Double-helix CT findings indicated that calcification was significantly more prevalent in patients with CAD (> 83%) than in patients with normal coronary arteries (27%) or in healthy control subjects (34%; P < .01). Sensitivity in detecting obstructive CAD was high (91%); however, specificity was low (52%) because of calcification in nonobstructive lesions. Comparison of double-helix CT and angiographic findings indicated that double-helix CT was 84% accurate with positive and negative predictive values of 89% and 59%, respectively. CONCLUSION: Double-helix CT is a useful noninvasive method for detection and quantification of coronary artery calcification.

Adult↗
PubMed1995

Antimony oxidation states in antileishmanial drugs.

Chemical methods specific for the determination of the levels of trivalent antimony (Sb+3) and pentavalent antimony (Sb+5) were used to investigate proprietary formulas used to treat leishmaniasis. Trivalent antimony was determined by differential pulse polarography, whereas Sb+5 was determined by iodine titration. Proprietary formulas based on N-meglumine antimoniate (Glucantime) were analyzed in detail. The results showed Sb+3 in all ampules of Glucantime. In formulations said to contain either 85 or 100 mg of Sb+5/ml, we found both forms of antimony. The amount of Sb+3 ranged from 10.5 to 15.8% (10.06-18.96 mg of Sb/ml). These findings raise issues on product stability and standardization and may help to clarify resistance to antimonial drugs and the reducing effect of tissue on Sb+5.

Antimony↗
PubMed1995

[Meralgia paraesthetica and its surgical treatment].

Compression neuropathy of the lateral femoral cutaneous nerve (meralgia paresthetica) leads to pain and dysesthesia in the anterolateral thigh. Over a period of 23 1/2 years, 29 patients (33 procedures) were operated on after failure of conservative treatment: 18 patients (20 procedures) underwent neurolysis of the nerve, and in 11 the nerve was transected. The 33 procedures were necessary because 1 patient had bilateral meralgia paresthetica and there were 3 recurrences with persisting pain. The average follow-up was 32 months after neurolysis and 87 months after transection. Complete or partial pain relief was found in 72% after decompression and in 82% after transection of the nerve.

Adult↗
PubMed1994

Ligation of CD45 on B cells can facilitate production of secondary Ig isotypes.

The possibility that isotype switching in B cells may be affected by engagement of the CD45 molecule on B cells has been investigated in microcultures containing limiting numbers of B cells and nonlimiting numbers of both alloreactive Th cells and purified dendritic cells (DC). Addition of Abs to the B cell-specific isoform, B220, to the microcultures leads to an increase in the proportion of B cell clones that secrete secondary Ig isotypes. In the presence of anti-CD45 Ab, microculture wells show a 39% frequency of secondary isotypes (560/1440) compared with a 11% frequency in control microcultures (89/780). Cross-linking appears to enhance this effect. Even in cultures of B cells and DC without T cells, addition of anti-B220 induces isotype switching in a significant number of microwells. Cross-linking and capping B220 molecules results in co-capping of surface Ig and MHC class II molecules. The results suggest that signal transduction through the CD45 molecule may affect pathways involved in isotype switching.

Animals↗
PubMed1994

Induction of tolerance in freshly isolated alloreactive CD4+ T cells by activated T cell stimulators.

Activated human T cells express major histocompatibility complex class II proteins, and their potential to present antigens to T cell clones has been documented extensively. The effect of such TT presentation on responder T cell clones has been shown to be the induction of tolerance, sometimes accompanied by activation. To investigate whether freshly isolated responder T cells are also susceptible to such induction of tolerance by activated T cells functioning as antigen-presenting cells (APC), we have used the capability of unprimed ex vivo T cells to respond in a proliferation assay in vitro to alloligands on professional APC. We show that purified human T cells ex vivo, when exposed to alloligand on activated T cells for primary allorecognition in vitro, fail to mount a proliferative response. Priming of responder CD4+ T cells with alloligand expressed on activated T cells results in the induction of nonresponsiveness to a subsequent challenge by competent allo-APC. This ability of activated, HLA-DR+ T cells to induce nonresponsiveness to subsequent challenge in bulk CD4+ T cell populations ex vivo has interesting implications for infections involving T cells such as human immunodeficiency virus.

Antigen-Presenting Cells↗
PubMed1994

Early T wave inversion after thrombolytic therapy predicts better coronary perfusion: clinical and angiographic study.

OBJECTIVES: This study was undertaken to test the hypothesis that early inversion of T waves after thrombolytic therapy for acute myocardial infarction predicts patency of the infarct-related artery with high Thrombolysis in Myocardial Infarction (TIMI) perfusion flow and better in-hospital outcome. BACKGROUND: Although numerous studies have demonstrated a strong association between early resolution of ST segment elevation after acute myocardial infarction and successful thrombolysis, little is known about early changes in T waves after thrombolytic therapy. METHODS: Ninety-four consecutive patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) were studied with admission and predischarge radionuclide ventriculography and with coronary angiography within 72 h of admission. Patient stratification was based on the presence or absence of early (within 24 h) T wave inversion. RESULTS: Early T wave inversion was associated with a higher patency rate of the infarct-related artery (90% vs. 65%, p < 0.02) and less severe residual stenosis ([mean +/- SD] 73 +/- 27 vs. 83 +/- 22, p = 0.06), and when only TIMI perfusion grade 3 was considered, the difference was even greater (77% vs. 41%, p < 0.001). Patients with early inversion of T waves had a lower peak creatine kinase value ([mean +/- SD] 678 +/- 480 vs. 1,076 +/- 620, p < 0.01), and although a similar percent of patients with and without early T wave inversion had a normal ejection fraction (> or = 55%) on admission, a higher percent of patients with early inversion had a normal ejection fraction at hospital discharge (71% vs. 44%, p < 0.03). Early T wave inversion anticipated a more benign in-hospital clinical course with a lower incidence of adverse cardiac events (10% vs. 33%, p < 0.02). CONCLUSIONS: Early inversion of T waves in patients with acute myocardial infarction treated with thrombolytic therapy suggests patency of the infarct-related artery, better perfusion grade and left ventricular function and a more benign in-hospital course.

Coronary Angiography↗
PubMed1993

Murine CD8+ T suppressors against mycobacterial 65-kDa antigen compete for IL-2 and show lack of major histocompatibility complex-imposed restriction specificity in antigen recognition.

The mechanism of antigen-specific suppression and reasons for aberrant major histocompatibility complex (MHC) class II restriction mediated by CD8+ T cells was investigated in a previously reported murine model of immunosuppression, generated by intraperitoneal priming with Mycobacterium vaccae. Both the CD4+ T helper cells (Th) and CD8+ T suppressor cell (Ts) of M. vaccae-primed mice recognized the 65-kDa antigen of the bacillus, presented by I-A and I-E, respectively. The CD8+ Ts could inhibit non-antigen-specific proliferation of primed CD4+ T cells induced by the exogenously added interleukin (IL)-2 (concanavalin A-stimulated culture supernatant). For inhibition, the Ts had to be activated by the 65-kDa antigen. The degree of inhibition was dependent upon the amount of added IL-2 and the relative numbers of primed CD8+ and CD4+ T cells. On incubation with antigen-presenting cells, and the 65-kDa antigen, the primed CD8+ T cells absorbed IL-2 as efficiently as primed CD4+ T cells. Based on this, it was concluded that the primed CD8+ T cells induced suppression by competition for IL-2. Employing the same model, the MHC restriction of recognition of the suppressor epitope of the 65-kDa antigen by the CD8+ Ts was investigated. The epitopes presented by diverse MHC class II molecules, such as self I-A, I-E and even allogeneic I-E were similar, because they were recognized by the same population of primed CD8+ Ts. Further, immunization of C57BL/6 mice with Ltk-cells expressing H-2 DkKk alloantigens, stimulated CD8+ T cells capable of recognizing M.vaccae 65-kDa antigen. Based on these data, it was proposed that recognition of the suppressor epitope of the 65-kDa antigen by the primed CD8+ Ts exhibits lack of restriction specificity imposed by MHC diversity.

Animals↗
PubMed1993

Revision procedures for complications of surgery for osteoarthritis of the carpometacarpal joint of the thumb.

Between the years 1980 to 1987, 17 patients had revision procedures for complications of surgery for osteoarthritis of the carpometacarpal joint of the thumb. 12 followed silastic implant arthroplasty, four trapeziectomy and one arthrodesis. The failed silastic arthroplasties were treated by removal of the implant, and soft tissue arthroplasty in eight, revision with another implant in three and intermetacarpal bone grafting in one. Patients with metacarpo-scaphoid arthritis after trapeziectomy were treated by silastic implant arthroplasty in three and fusion in one. Nine of the 17 revision procedures (53%) had good, three (18%) fair and five (29%) poor results respectively.

Adult↗