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Biomedical subjects

M Frosch

Publications and source records attributed to M Frosch.

156 records · Page 9Linked to original sources
PubMed1986

Antibodies to the capsular polysaccharide of Neisseria meningitidis group B or E. coli K1 bind to the brains of infant rats in vitro but not in vivo.

The binding of monoclonal and polyclonal IgG antibodies specific to the capsular polysaccharide of Neisseria meningitidis group B and E. coli K1 was tested to the cross-reacting polysialosyl structures previously shown to be present in the brain of infant rats (Lancet 1983; ii: 355-7). Strong immunofluorescence was obtained after in vitro incubation of the brains of 1 to 13 days old rats with the antibodies whereas the brains of adult rats remained negative. The number of antibody-binding structures decreased as a function of age, being highest at the age of 1 to 5 days. However, when the same antibodies were injected intraperitoneally into the infant rat, or into the mother rat 2 days before parturition, no binding of antibodies to the infant rat brain tissue was observed.

Animals↗
PubMed1985

NZB mouse system for production of monoclonal antibodies to weak bacterial antigens: isolation of an IgG antibody to the polysaccharide capsules of Escherichia coli K1 and group B meningococci.

A system for the production of monoclonal antibodies, particularly of the IgG type, against weakly immunogenic bacterial polysaccharide antigens is described. This system, which is based on the autoimmune NZB mouse strain, has been used to produce a monoclonal IgG2a antibody against the meningococcus group B and Escherichia coli K1 polysaccharides, identical homopolymers of alpha (2----8)-linked units of N-acetylneuraminic acid that are extremely poor immunogens. Comparison of the humoral immune responses of normal BALB/c mice and autoimmune NZB mice to hyperimmunization with group A, B, and C meningococci showed that, although both strains mounted a weak meningococcal B polysaccharide-specific IgM response, only the NZB strain mounted an IgG response. Similarly, NZB mice mounted a stronger IgG response to the more immunogenic group C meningococcal polysaccharide than did BALB/c mice, although this difference was less pronounced than that observed with meningococcal B polysaccharide. No difference between the two strains of mice was demonstrable with the strongly antigenic group A meningococcal polysaccharide. These results indicate that the NZB system may be generally useful for the production of monoclonal antibodies against weakly antigenic bacterial determinants.

Animals↗
PubMed1977

[Quantitative digital dermatoglyphic parameters--their distribution in families].

112 mother-child-father tercettes have been examined for several quantitative dermatoglyphic parameters (total ridge count--TRC--, radial and ulnar differrences, index of pattern type [KEITER]). The distribution of pattern among children has been compared to those of their parents. In the majority of cases within the empirical distribution of the children extreme values outside of the variation range of the parents were observed. This is in contrast to the formal genetic model of additive polygeny (HOLT). These findings have been interpreted as manifestation of TRC-heterogeneity suggesting a modifying action of radial and ulnar ridge differences. The parent-child correlation for the radio-ulnar differences and the index of pattern type were lower than that for the TRC. The interpretation of unexpected differences in quantitative dermatoglyphic parameters of children in relation to the variation of their parents has to be discussed very carefully. Due to the small number of material a correlation between the isolated position of the children in TRC to mother-child-differences in serological markers could not be excluded in this study.

Adult↗
PubMed1976

Independent effects of IgG and complement upon human polymorphonuclear leukocyte function.

Particle ingestion by polymorphonuclear leukocytes (PMN) is promoted by cell surface recognition and binding of fragments of the third component of complement (C3) and Fc regions of certain immunoglobulin (IgG) molecules. In order to determine the influence of these specific ligandsurface membrane interactions upon other PMN functions, we have employed nonphagocytosable particles (serum-treated Sepharose beads) coated with fragments of C3 and/or IgG, and have investigated whether these provide a sufficient stimulus for the metabolic changes and degranulation that ordinarly accompany phagocytosis by PMN. Sepharose 4B activates complement in fresh normal serum and consequently is coated with fragments of C3 (confirmed by immunoelectrophoretic evidence of factor B and C3 conversion and by immunofluorescence). Adsorbed IgG could be removed from serum-treated Sepharose by boiling in 2 M NaCl without significantly influencing bound complement. We have found that normal human PMN recognize and adhere to Sepharose beads coated with fragments of C3 and consequently are stimulated to increase their oxidative metabolism (measured as superoxide anion generation). This PMN response occurred in the absence of IgG but could be amplified if this immunoglobulin was also present on the bead surfaces. Both adherence and metabolic stimulation could be blocked by treatment of the beads with F(ab)2 anti-C3. In contrast to metabolic stimulation, degranulation (selective extracellular release of lysosomal constituents) was observed only when PMN encountered both C3 fragments and IgG on the beads. This response could be blocked by treating beads with either F(ab)2 anti-C3 or F(ab)2 anti-IgG. These results indicate that cell surface stimulation of PMN is not an "all or none" phenomenon and that certain vital functions of these cells may be mediated or modulated independently by immunoglobulins and complement.

Cell Adhesion↗
PubMedDate not supplied

The contrasting mechanisms of serum resistance of Neisseria gonorrhoeae and group B Neisseria meningitidis.

Neisseria gonorrhoeae and Neisseria meningitidis have evolved intricate mechanisms to evade complement-mediated killing. Sialylation of gonococcal lipooligosaccharide (LOS) results in conversion of previously serum sensitive strains to unstable serum resistance, which is mediated by factor H binding. Porin (Por) is also instrumental in mediating stable serum resistance in gonococci. The 5th loop of certain gonococcal PorlAs binds factor H, which efficiently inactivates C3b to iC3b. Factor H glycan residues may be essential for factor H binding to certain Por1A strains. Por1A strains can also regulate the classical pathway by binding to C4b-binding protein (C4bp) probably via the 1st loop of the Por molecule. Certain serum resistant Por1 B strains can also regulate complement by binding C4bp through a loop other than loop 1. Purified C4b can inhibit binding of C4bp to Por 1B, but not Por1A, suggesting different binding sites on C4bp for the two Por types. Unlike serum resistant gonococci, resistant meningococci have abundant C3b on their surface, which is only partially processed to iC3b. The main mechanism of complement evasion by group B meningococci is inhibition of membrane attack complex (MAC) insertion by their polysaccharide capsule. LOS structure may act in concert with capsule to prevent MAC insertion. Meningococcal strains with Class 3 Por preferentially bind factor H, suggesting Class 3 Por acts as a receptor for factor H.

Blood Bactericidal Activity↗
PubMedDate not supplied

Selective cell loss in Edinger-Westphal in asymptomatic elders and Alzheimer's patients.

Exaggerated pupillary response to a low concentration of cholinergic antagonists has been suggested as an early marker for Alzheimer's Disease (AD). To examine the anatomic basis of this phenomenon, we determined possible neuropathological changes in the Edinger-Westphal (EW) nucleus, a midbrain neural center with a significant functional role in the control of pupil size. Stereologically determined neuronal numbers within the EW were counted in individuals with pathologically confirmed AD, control cases with no AD-type pathology, and subjects with AD pathology not meeting diagnostic criteria for AD. The EW of AD patients displayed a marked and striking neuronal loss when compared with controls. In contrast, the number of neurons in the somatic portion of the nucleus of the third cranial nerve (NCNIII) remained intact. The EW in brains from clinically normal individuals with evidence of early AD-type pathology also displayed a significant and selective loss of neurons. The magnitude of EW neuronal loss in the latter group was smaller than that observed in AD. These findings suggest that pupillary hypersensitivity in AD may be caused by abnormalities in the EW. Neuronal loss and pathology within the EW in a subpopulation of clinically silent controls with pathologic findings consistent with early-stage AD constitutes a possible explanation for the reported exaggerated pupil response in some normal elderly subjects.

Aged↗
PubMedDate not supplied

[Sinus histiocytosis with massive lymphadenopathy with complete occlusion of the superior and inferior vena cava].

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disease of the lymph nodes, still of unknown origin. We are reporting the case of a 16 year old boy with SHML which occurred in 1983. Investigations showed a massive lymphadenopathy of the mediastinal and abdominal nodes, causing displacement and compression of surrounding tissue. The patient further developed a blockage of the vena cava superior and inferior, leading to numerous collateral circulation routes in the upper and lower extremities. The etiology of the venous blockage is still disputed. It is possible that they are the result of compression of the major veins. Alternatively, the cause could lie in the disruption of the coagulation system. Finally and more likely, the problem could be the result of fibrosis developing through the healing process.

Adolescent↗
PubMedDate not supplied

Myeloid related proteins MRP8/MRP14 may predict disease flares in juvenile idiopathic arthritis.

OBJECTIVE: An unsolved problem in juvenile idiopathic arthritis (JIA) is to identify patients at special risk for relapse. It is important to adjust anti-inflammatory and immunosuppressive therapy to the children's actual disease activity especially in times of remission. Our aim was to analyze if the serum levels of MRP8/MRP14 are reliable predictive markers for the risk of relapse in clinically inactive juvenile idiopathic arthritis. METHODS: Serum concentrations of MRP8/MRP14 were determined by ELISA and correlated with laboratory and clinical parameters for disease activity in patients with JIA. 29 patients with changing disease activity were followed up for a mean time of 2.9 years. Two groups of patients--one before relapse (mean 3.7 months) but without clinical signs of disease reactivation, and one in remission for 12 further months--were compared. RESULTS: MRP8/MRP14 serum levels in patients before relapses were significantly higher than the levels in patients in stable remission for one year (662 ng/ml versus 395 ng/ml; p < 0.05). Using a cut-off for MRP8/MRP14 of 450 ng/ml the likelihood ratio for relapse was 3.7 (positive predictive value 80%), while no differences were found for C-reactive protein and erythrocyte sedimentation rate between the two groups. CONCLUSION: MRP8/MRP14 correlate with individual disease activity in patients with JIA. Our data suggest that local disease activity may be present even months before flares become clinically apparent. Serum levels of MRP8/MRP14 can give a hint as to clinically occult disease activity, in this way helping to adjust therapy in times of low disease activity.

Adolescent↗
PubMedDate not supplied

Steal syndrome after kidney transplantation caused by A-V fistula at the thigh.

The cases of two low-weight children are reported, who became dialysis patients at the age of 2.5 and 5.5 years, respectively, and were hemodialyzed by way of a bovine artgraft A-V fistula at the thigh. One year later, both patients were successfully transplanted with a cadaveric kidney. Immunosuppression was carried out in the first 3 weeks with prednisone, azathioprine and ciclosporin, later on with prednisone and ciclosporin. The first patient (A-V fistula at the right thigh) was transplanted on the right fossa iliaca. After an acute rejection episode 11 days after kidney transplantation, successfully treated by prednisolone pulse therapy, there was another episode similar to rejection after 5 weeks. This episode was complicated by a hypertensive crisis with convulsion. Again bolus injections of prednisolone were performed, but kidney function declined rapidly. Diagnostics (perfusion scintigraphy with Tc-DTPA, digital substraction angiography) demonstrated hypoperfusion of the graft, caused by a steal syndrome due to the A-V fistula in the groin. Ligation of the fistula resulted in rapid improvement of renal function and decrease in blood pressure occurred. The second patient was transplanted on the fossa iliaca contralaterally of the A-V fistula in the groin. Twenty-one days after kidney transplantation we saw a rejection episode accompanied by cytomegalovirus (CMV) infection. After bolus injection of prednisolone and CMV-antibody treatment in the beginning, stabilization of kidney function was seen. But the following week we experienced an unexplainable deterioration of graft function followed by progressive acute renal failure. Again, a steal syndrome due to the contralateral A-V fistula could be demonstrated. After ligation of the A-V fistula renal function normalized within 14 days. Currently graft function is satisfactory in both patients.

Arteriovenous Shunt, Surgical↗
PubMedDate not supplied

Evaluation of ELISA to detect Chlamydia trachomatis antigen in urine samples from arthritis patients.

OBJECTIVE: To determine whether examination of urine samples using ELISA allows the detection of asymptomatic C. trachomatis infection in arthritis patients. METHODS: The in vitro sensitivity of IDEIA Chlamydia ELISA to detect C. trachomatis in urine samples was determined by the investigation of serial dilutions of chlamydial elementary bodies. In a clinical study, urine samples from 402 consecutive arthritis patients (182 men and 220 women) in a tertiary care rheumatology clinic were examined for asymptomatic chlamydial infection by ELISA and the results were compared to culture and direct immunofluorescence assay (DFA, MicroTrak) of urogenital swabs. RESULTS: The in vitro sensitivity of ELISA for detecting purified elementary bodies of C. trachomatis serovar K in urine was 60 infection forming units. Twenty-three of 402 arthritis patients (6%) had asymptomatic chlamydial infection as shown by DFA and culture from urogenital smears. The ELISA method identified only 3 of 17 swab-positive patients among 271 patients when urine specimens were collected during the clinical visit, while the assay detected all 6 swab-positive patients among 131 patients when first-voided early morning urine specimens were used (p < 0.001). CONCLUSION: It is mandatory to examine only first voided early morning urine samples if ELISA is used instead of DFA or culture from urogenital swabs to detect asymptomatic chlamydial infection in arthritis patients.

Adolescent↗