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Biomedical subjects

A Wunderlich

Publications and source records attributed to A Wunderlich.

31 records · Page 2Linked to original sources
PubMed1997

Alopecia areata but not androgenetic alopecia is characterized by a restricted and oligoclonal T-cell receptor-repertoire among infiltrating lymphocytes.

Although the etiology of alopecia areata is still unknown, evidence has accumulated to support an autoimmune pathogenesis for this disease. To evaluate the role of T cells in alopecia areata the T-cell receptor VB-repertoire was investigated in lesional skin and blood of 5 patients by means of a semiquantitative technique based on the reverse transcriptase polymerase chain reaction. Three patients with androgenetic alopecia served as controls. Amplification products were screened for clonality by temperature gradient gel electrophoresis. Four of 5 patients with alopecia areata exhibited a lesional T-cell receptor-repertoire characterized by an almost exclusive utilization of variable regions beta 2, 4, and 13. Temperature gradient gel electrophoresis revealed the oligoclonal constitution of the infiltrate. The restricted nature of the lesional T-lymphocytic infiltrate in alopecia areata strongly suggests that an antigen-specific T-cell response plays an important role in the pathogenesis of this disease.

Adult↗
PubMed1996

[Virtual cystoscopy based on spiral CT data].

Simulation of three-dimensional cystoscopy based on helical CT scan data in real-time in patients with tumours of the urinary bladder. In three patients with histologically confirmed carcinoma of the urinary bladder, a helical CT scan with double detector technology was carried out preoperatively. A native scan was first performed, followed by an examination in the early contrast medium enhanced phase. After adequate contrasting of the urinary bladder (30 minutes latency), further images were acquired. These data were transferred to a separate graphic computer workstation and reconstructed. The results were then compared with the cystoscopic and pathohistological findings. All tumours of the urinary bladder identified at fiberoptic cystoscopy were also visualised by virtual cystoscopy. The best reconstruction results were obtained from data acquired after the 30-minute latency period. Virtual cystoscopy represents an interesting option in helical CT scanning, which is able to visualise polypoid tumours of the urinary bladder. Its clinical relevance, however, must be demonstrated in studies with a larger number of patients examined.

Aged↗
PubMed1995

HIV gp120-specific cell-mediated immune responses in mice after oral immunization with recombinant Salmonella.

Salmonella is of great interest as a potential human immunodeficiency virus vaccine vector because of its ability to elicit potent mucosal and systemic immune responses when administered orally. To determine whether such a vaccine could elicit an immune response in mice, plasmids expressing HIV gp120-LAI were introduced into attenuated S. typhimurium. Three serial doses of 10(10) recombinant organisms were administered orally to BALB/c mice at 2-week intervals. Immunized mice but not control mice demonstrated proliferative T cell responses to gp120-LAI, comparable in magnitude to the proliferative responses to Salmonella antigens. Immunized mice had detectable serum and intestinal Salmonella-specific IgA and serum Salmonella-specific IgG. However, no gp120-specific antibody was detected in either serum or intestinal washes. These results indicate that live recombinant Salmonella-based vaccine constructs can induce HIV-specific cellular immune responses in vivo.

AIDS Vaccines↗
PubMed1987

Encystation and expression of cyst antigens by Giardia lamblia in vitro.

The cyst form of Giardia lamblia is responsible for transmission of giardiasis, a common waterborne intestinal disease. In these studies, encystation of Giardia lamblia in vitro was demonstrated by morphologic, immunologic, and biochemical criteria. In the suckling mouse model, the jejunum was shown to be a major site of encystation of the parasite. Small intestinal factors were therefore tested as stimuli of encystation. An antiserum that reacted with cysts, but not with cultured trophozoites was raised in rabbits and used as a sensitive probe for differentiation in vitro. Cultured trophozoites that were exposed to bile salts showed a more than 20-fold increase in the number of oval, refractile cells that reacted strongly with anticyst antibodies, and in the expression of major cyst antigens. Exposure to primary bile salts resulted in higher levels of encystation than exposure to secondary bile salts. These studies will aid in understanding the differentiation of an important protozoan pathogen.

Animals↗
PubMed1985

Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies.

Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells. The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the J5 mutant of Escherichia coli, which is deficient in O antigenic side chains. This deficiency exposes the core oligosaccharide, common to LPS of all Gram-negative bacteria. The mAbs cross-reacted strongly with endotoxins from a wide range of unrelated species of Gram-negative bacteria. The mAbs also gave strong protection against LPS in the dermal Shwartzman reaction and against lethal Gram-negative bacteremia in mice. These findings indicate that monoclonal IgM against LPS endotoxin can neutralize its toxicity in vivo and might be valuable for treatment of patients with Gram-negative bacteremia. Analysis of one of the hybridoma clones, A6(H4C5), showed that the IgM mAb is directed against the covalently bound lipid A, which represents the most conservative and least variable structural element of LPS.

Animals↗
PubMed1983

Immunity to pasteurellosis in compromised rabbits.

Pasteurellosis in the rabbit inoculated with a malignant variant of Shope fibroma virus (SFV-MV) is presented as a model for the study of immunosuppression and immunoprophylaxis in pasteurellosis. The rabbits, before the inoculation, were healthy carriers of Pasteurella multocida. They were intradermally inoculated with SFV-MV, and 3 to 6 days later, a primary tumor appeared at the site of inoculation. By postinoculation day (PID) 7 or 8, the rabbits had snuffles, conjunctivitis, and tumor metastases; death occurred on PID 10 to 14. Rabbits given the nonmalignant Patuxent strain of SFV developed local primary tumors, but not pasteurellosis nor metastases. In SFV-MV-inoculated rabbits, there was decreased responsiveness of spleen lymphocytes to B and T cell mitogens by day 6, and of spleen and peripheral blood lymphocytes by day 10. In addition, SFV-MV antigen was detected (by immunofluorescence) in mononuclear phagocytes in all major organs and in epithelial cells of the conjunctiva and nasal mucosa. Both nasal and conjunctival epithelia showed squamous metaplasia as well. These changes did not appear in SFV-infected rabbits. With SFV-MV-inoculated rabbits, we obtained partial protection against pasteurellosis by immunization with heat-killed P multocida or a cross-protective core lipopolysaccharide mutant of Escherichia coli (J5). Rabbits were immunized before the inoculation with SFV-MV which precipitated "spontaneous" pasteurellosis due to impaired defenses. Rabbits immunized with J5 or P multocida had less severe conjunctivitis and snuffles than nonimmunized controls, indicating that immunization with the J5 mutant may be useful as prophylaxis against pasteurellosis in compromised hosts.

Animals↗
PubMed1977

Role of urinary solutes in natural immunity to gonorrhea.

Natural resistance of the male urethra to gonococci has not been explained by classical immune mechanisms but could result from antibacterial properties of urine. Accordingly, we measured survival in midmorning urine of 10(7) F-62 T2 gonococci per ml by serial dilutions and plate counts. Fifteen killer urines from eight people all killed greater than 3 logs (average, 5.3), and 13 of 15 were sterilized. Fourteen nonkiller (inhibitor) urines from seven subjects allowed no growth. Killer urines were more acidic (pH 5.4 versus 6.4) and more concentrated (861 versus 717 mosmol/kg) than nonkillers. Upon addition of hydrogen ion, urea, and sodium chloride to urines and broth, pH proved to be the major killing factor, but urea and NaCl were also bactericidal. Susceptibility to urine bactericidal power did not vary with colony type (T2 versus T4) or strain (F-62 versus two fresh isolates). Killing was rapid (0.5 to 3 h) and not bacteriolytic. Escherichia coli multiplied 10-fold in urines that inhibited growth of gonococci. Thus, the bacteriostatic effect of urine may explain why gonococci do not infect the bladder and kidney during gonorrhea. The bactericidal properties of urine may contribute to resistance against gonococcal urethritis.

Bacteriolysis↗
PubMedDate not supplied

Diffusion-weighted MRI: detection of cerebral ischemia before and after carotid thromboendarterectomy.

PURPOSE: Conventional postoperative evaluation of patients following carotid thromboendarterectomy (TEA) consists of a clinical neurologic examination to assess neurologic deficits, color duplex ultrasound to document the surgically reestablished patency of the carotid artery, and CT for exclusion of postoperative ischemic infarctions. Recent studies prove that diffusion-weighted MRI is more sensitive in the detection of fresh insults than conventional MRI and CT. The objective of the study was to ascertain the incidence of clinically asymptomatic peri-and postoperative ischemic infarctions visualized at MRI. METHOD: We included 52 patients in the study. Fifty-one patients (31 men, 20 women; average age 68 years) underwent cranial MR examination including a diffusion-weighted sequence at 24 h prior to carotid TEA and again 24 h following the procedure. One patient did not agree to participate. RESULTS: In 29 of 51 patients (56%), neither the pre-nor the postoperative MR scans showed any diffusion abnormalities. In 16 patients (31%), however, preoperative MRI detected fresh ischemic insults. In nine patients (17.6%), the size of the insult resulted in surgery being postponed for 4 weeks. In six patients (11.8%), postoperative MRI returned findings of fresh disturbances of diffusion suggestive of ischemia that were not visualized on preoperative scans. Discrete neurologic deficits were observed in only two (3.9%) of these patients. Deficits were transient and disappeared within 72 h. CONCLUSION: Our findings underscore MRI's capacity for visualizing perioperative ischemic events. Moreover, MRI provides evidence of clinically asymptomatic embolisms that occur perioperatively.

Acute Disease↗
PubMedDate not supplied

Antisense p53 oligonucleotides inhibit proliferation and induce chemosensitivity in follicular thyroid cancer cells.

BACKGROUND: The potential of MTp53 knockout by oligodesoxyribonucleotide phosphothioates (ODNs) to affect proliferation, apoptosis and chemosensitivity in undifferentiated thyroid cancer (UTC) cells with a recessive MTp53 mutation was evaluated. MATERIALS AND METHODS: Transient transfections with ODNs complementary to p53 and control ODN (HIV-RT) were carried out in FTC 133 cells. In vitro proliferation was evaluated by cell counting of 10 random fields and by the MTT assay. A single pulse of 100 microg/ml Cytarabine was added to each well and the cells were incubated for an additional day. Chemosensitivity was calculated as the ratio of apoptotic and necrotic cells versus viable cells by flow cytometry (FACS). RESULTS: Transfection of UTC cells with ODN decreased the cell number by up to 70% (p < 0.002). The proliferation rate also decreased up to 35% (p < 0.03), without inducing apoptosis. ODNs rendered FTC cells sensitive to treatment with Cytarabine, inducing apoptosis in 35% of cells, as compared to 17% of cells transfected with the reverse transcriptase gene of HIV (ODN-HIV) and less than 10% of non-transfected cells (p < 0.05). CONCLUSION: Transient MTp53 knockout with ODNs complementary to p53 nucleotide sequences inhibited proliferation and increased chemosensitivity in the UTC cell line FTC133.

Adenocarcinoma, Follicular↗