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Biomedical subjects

J Rotta

Publications and source records attributed to J Rotta.

At least 19 recordsLinked to original sources
PubMed1997

Mosaicism in pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a spondylo-epi-metaphyseal dysplasia characterized by disproportionate short stature, generalized ligamentous laxity, and precocious osteoarthritis. PSACH is caused by mutations in the cartilage oligomeric matrix protein (COMP) gene, which codes for a noncollagenous protein expressed in the territorial matrix of chondrocytes. Autosomal dominant inheritance has been demonstrated in many families; however, autosomal recessive inheritance has been suggested in some severe familial cases. Alternatively, germline/somatic mosaicism has been proposed and is credible, since it has been shown that dominantly inherited and sporadic cases of PSACH are caused by the same genetic defect. Here, we present evidence demonstrating somatic mosaicism in two PSACH families that were originally considered to represent autosomal recessive inheritance. The results of this study suggest that autosomal recessive inheritance is unlikely and all cases of PSACH should be studied for mutations in COMP.

Achondroplasia↗
PubMed1996

Natural history study of pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a well-characterized autosomal dominant dwarfing condition. A great deal of information is available about orthopedic complications, but little is known about extraskeletal complications in adulthood. This study was undertaken to delineate the natural history of PSACH at all ages. Seventy-nine individuals responded to an extensive questionnaire that included information about deformities, operations, general health, chronic diseases, and reproduction. PSACH individuals were ascertained through the University of Texas Medical Genetics patient population, a genetic linkage study, and the social organization, Little People of America. The results show that PSACH individuals with a family history do not have a distinct or more severe phenotype than new mutation cases. There were not differences in the number of orthopedic complications, operations, or number of offspring between these two groups. Less than half of affected adults reported having total hip replacement surgery, which was less common than previously reported. Extraskeletal complications were generally uncommon. There were four cases of cancers in 41 individuals queried. Premature osteoarthritis was the major health problem for PSACH individuals. PSACH individuals are generally healthy but have problems associated with debilitating osteoarthritis.

Adult↗
PubMed1992

Group A streptococcal strains in Kuwait: a nine-year prospective study of prevalence and associations.

During a period of 9 years (December, 1980, through November, 1989), 407 Group A streptococcal strains were isolated from 294 children with acute rheumatic fever and 303 of their family contacts, 234 children with acute post-streptococcal glomerulonephritis and 242 of their family contacts and 219 children with uncomplicated Group A streptococcal pharyngitis. Of the 407 strains 216 (53%) were M and/or serum opacity factor typable, 143 (35%) were only T typable and 48 (12%) were nontypable. Throughout the period of study the M12 and M1 were the most prevalent strains; however, important changes among the prevalent strains were observed. Although the study started in 1980 the serotypes M18, M81, M3, M15 and M58 made their first appearance 7 to 9 years later. These findings show the value of long term studies in detecting the changes in the prevalence of streptococcal strains in the community. M18 was isolated from three children with nephritis but not from children with rheumatic fever; this association has not been reported before. M12 was isolated from 26% of the nephritic children and their families vs. 7% from the rheumatic children and their families (P less than 0.05) vs. 17% from children with uncomplicated streptococcal pharyngitis. M49 was isolated from 7% of the nephritic children and their families vs. none from rheumatic children and their families vs. 1.4% from children with uncomplicated streptococcal pharyngitis. These findings support the concept of nephritogenicity of some streptococcal strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Human heart sarcolemmal sheath antibodies in children with non-suppurative sequelae of group A streptococcal infections: a follow up study.

The kinetics of the human heart sarcolemmal sheath antibody were studied in children with acute rheumatic fever who had no carditis, children with acute rheumatic fever who had carditis and developed rheumatic heart disease, and in children with acute poststreptococcal glomerulonephritis. The children with rheumatic fever and those who developed valvular heart disease were given continuous secondary antistreptococcal prophylaxis. The titre of antibody at onset was significantly higher than that of the controls in children with acute rheumatic fever and carditis and in children with acute poststreptococcal nephritis. The difference in the antibody titre between children with rheumatic fever who had no carditis and controls was not statistically significant. After a mean follow up of three years, however, a high titre was only maintained in children with rheumatic fever who developed valvular heart disease.

Acute Disease↗
PubMed1989

Prospective study of pharyngitis: clinical diagnosis and microbiological profile.

A prospective study of pharyngitis was carried out in the general population of twenty-two thousand in a small country town, over a period of ten weeks in the fall of 1984. It has been confirmed that, as in the past clinical diagnosis "streptococcal" and "nonstreptococcal" pharyngitis without microbiological examination is still highly inaccurate. From the clinical and microbiological parameters, the incidence in the period of follow-up was calculated as 7.2 and 12.0 cases per 100 population per year for streptococcal and nonstreptococcal pharyngitis, respectively. These data document the health importance of this disease which is frequently underestimated. The M (by M or OF antigens) typability accounted for 62% of group A strains isolated, the prevailing types being M 1 and M 12. Comparison of M and OF typability of field strains immediately after isolation and three weeks later proved the superiority of an early typing. The accurate identification of prevailing types is essential for the prospect of streptococcal vaccine. In streptococcal pharyngitis cases treated with penicillin, the increase of antistreptolysin O and antideoxyribonuclease B titres was recorded in very few instances during a three week period after the onset of the disease. The examination of patients with nonstreptococcal pharyngitis aimed at detecting the role of some viruses or of M. pneumoniae proved that the etiology by these agents was practically nil in the cases concerned at this particular period of time. This finding suggests focusing interest on a possible role of other pathogens. The morbidity rates of pharyngitis, and the clinical as well as the microbiological data resulting from the study make it urgent to pay further attention to this infection and to attempt to elucidate the missing points in the etiology and diagnosis of this disease which belongs to the bacterial infections most frequently seen in man in economically developed countries.

Antibodies, Bacterial↗
PubMed1988

The effects of peptidoglycan, a pyrogenic constituent of gram-positive microorganisms, on the pharmacokinetics of rifampicin.

Pharmacokinetics of rifampicin (20 mg/kg orally or i.v.) was determined in calves and rabbits. Seven days later a model pyrogen was administered i.v. to the same animals and 1 hr later the rifampicin administration was repeated. The pharmacokinetic analysis of oral rifampicin was performed using a one-compartment open model with absorption. Intravenously administered rifampicin was analysed by a two-compartment intravascular model. Injection of peptidoglycan in pyrogenic doses led to a significant increase of orally applied rifampicin serum levels in both animal species. The i.v. administration of rifampicin had the same parameters in the control and peptidoglycan experiments. Daily pretreatment of rabbits with small doses of peptidoglycan induced tolerance to the pyrogenic effect. In tolerant animals we did not observe any changes of rifampicin serum levels. Elevated temperature alone was not responsible for observed pharmacokinetic changes leading to the increase of bioavailability of oral rifampicin since another pyrogenic substance (endotoxin) had an opposite effect on pharmacokinetics of previously tested drugs.

Administration, Oral↗
PubMed1987

Gonadal mosaicism in pseudoachondroplasia.

We report on a family in which a brother and sister have pseudoachondroplasia and normal parents. The brother married a normal woman, and they have 2 daughters; one of them has typical changes of pseudoachondroplasia, the other is normal. The most likely explanation in this family is gonadal (germinal cell) mosaicism in one of the grandparents. Other reports of possible autosomal recessive pseudoachondroplasia are reviewed. It is likely that gonadal mosaicism is responsible for a small percentage of cases with what appears to be a new mutation for pseudoachondroplasia.

Achondroplasia↗
PubMed1987

Multicentre evaluation of a direct coagglutination test for group A streptococci.

A coagglutination test for detection of group A streptococci in throat samples was evaluated in a multicentre study and found to be about 95% sensitive when applied to swabs taken from symptomatic patients which yielded more than 100 colonies per plate on culture. The sensitivity of the test dropped significantly when it was applied to swabs giving fewer than 100 colonies on culture. The specificity of the test was high regardless of colony count on conventional media.

Acute Disease↗
PubMed1987

Blood-platelets-damaging activity of some synthetic Streptococcus peptidoglycan subunits and analogues.

A series of 25 synthetic subunits or analogues of streptococcal peptidoglycan was tested for their ability to damage rabbit blood platelets. The morphological changes of the platelets were studied on an ultrastructural level. Minimal subunit structure able to produce a complete lysis of the platelets was found to be muramyldipeptide (MDP). Comparable lysis of platelets was also caused by muramyltetrapeptide and MDP containing D-Ala instead of L-Ala. The lytic effect was dose-dependent and was exhibited rather after high doses of the substances used (up to 500 micrograms/ml). For the lytic reaction, the configuration of C3 and C4 in the muramyl residue of MDP was essential. Many substances produced only degranulation without lysis of the platelets and some of them did not influence the platelet ultrastructure at all. The paper presents some structure-to-function relationships of the compounds and shows that the platelet-damaging activity of peptidoglycan may be related to certain portions of the peptidoglycan molecule. This activity should be tested when the immunomodulatory substances derived from the bacterial peptidoglycan are searched for.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Streptococcal diseases worldwide: present status and prospects.

Infections caused by streptococci pathogenic for man are some of the most common bacterial diseases in temperate zones and occur very frequently in tropical and subtropical countries. The highest morbidity occurs from infections caused by group A streptococci; these infections can lead to rheumatic fever and acute glomerulonephritis. The incidence of rheumatic fever and the prevalence of rheumatic heart disease are several times higher in tropical countries than temperate countries.Recent developments in fundamental and applied research are throwing light on various aspects of the problem, e.g., the rapid (non-culture) identification of group A streptococcal infection. Analyses of the chemical structure of the M-protein molecule of group A streptococcus and of the biological properties of the epitopes of the M-protein have provided encouraging results. Furthermore, synthetic analogues of the protective immunodominant polypeptides of the M-protein have been prepared. The prospect of a streptococcal vaccine for preventing group A streptococcal diseases is thus more realistic.The control of infections caused by group B streptococci is important for the health of neonates. The identification of the chemical structure of the major group B streptococcal types may lead to development of a vaccine in the future. An alternative approach would entail the use of anti-group-B immunoglobulins, but a number of questions have to be answered before the new control measures can be introduced. The streptococci causing bacterial pneumonia, subacute bacterial endocarditis and possibly dental caries have been widely studied and promising advances have been made towards the introduction of better control of the diseases caused by these pathogens.

Humans↗
PubMed1986

The concurrent associations of group A streptococcal serotypes in children with acute rheumatic fever or pharyngitis-associated glomerulonephritis and their families in Kuwait.

A group of 146 children with acute rheumatic fever and 256 members from their families, and a group of 125 children with post-streptococcal glomerulonephritis and 199 family members, together with a group of 145 children with non-complicated group A streptococcal pharyngitis were examined over a period of three years. The purpose of the study was to explore the concurrent association and distribution of group A streptococcal serotypes among the three groups. Strains isolated from the children with non-complicated group A streptococcal pharyngitis represented the prevalent strains of group streptococci in the childhood community during the period of study. Rheumatic fever was encountered in a non epidemic situation. As expected, the recovery of group A streptococci was low. The strains however belonged mainly to two patterns, namely type M1 and M non-typable strains. Nephritis was pharyngitis-associated and occured also sporadically throughout the year. Types M12 and 49 accounted for the majority of the isolates. Type M12 accounted for 34.4% of the group A isolates from family members of children with nephritis and was totally absent in family members of children with rheumatic fever (p less than 0.001). The T pattern 8/25/Imp. 19 accounted for 40% of the group A isolates from family members of rheumatic patients compared to 3.3% from family members of nephritis patients (p less than 0.005). Data from this study show that the group A streptococcal serotypes, concurrently isolated from children with acute rheumatic fever and their families are disparately different from those of children with pharyngitis-associated glomerulonephritis and their families in the same population. These findings support the concept of "nephritogenicity" and "rheumatogenicity" and indicated the important role of the biological characteristics of the streptococcal serotypes in the aetiology of acute rheumatic fever and acute poststreptococcal glomerulonephritis.

Acute Disease↗
PubMed1986

Streptococcal group A polysaccharide antibodies assayed by an ELISA determination of antibodies in rabbit hyperimmune sera; normal levels in man and comparison with levels in patients with rheumatic fever and with poststreptococcal glomerulonephritis.

An enzyme-linked immunosorbent assay (ELISA) was adapted to measure antibodies to streptococcal group A polysaccharide. The components of the reaction were studied, including the concentration of the polysaccharide antigen, the suppression of non-specific reactions, optimal conjugate binding conditions and the most suitable plates. The specificity of this test was documented by studies using immune sera and polysaccharide antigens of various groups of beta-hemolytic streptococci. In addition dynamics of the antibody response in animals as well as in man were investigated. The upper limit of normal level of this antibody in normal healthy persons was determined by this technique. We found that 80% of patients with rheumatic fever and acute glomerulonephritis showed an elevation of the group A polysaccharide antibody titer. Determination of this antibody response by the ELISA technique is clinically useful in evaluation patients with the nonsuppurative sequelae of group A streptococcal infections.

Adolescent↗
PubMed1985

Biological activity of synthetic subunits of streptococcus peptidoglycan. III. Relationship of subunit and analogue structure to adjuvant activity in cell-mediated immunity.

Each of a series of synthetic peptidoglycan subunits and subunit analogues was injected in combination with streptococcus type M24 antigen extract. The substances tested were: (8a) N-acetylmuramyldipeptide (MDP) and the following derivatives thereof: MDP modified in positions C3 and C4, or with L-alanine substituted by L-2-aminobutyric acid or with the peptide chain prolonged (by three lysines or a polylysine); (b) some synthetically prepared peptides: a hexapeptide, a tridecapeptide and an octadecapeptide. Configurations in positions C3 and C4 were found essential for the adjuvant effect. Adjuvant activity, though somewhat lower than in MDP, was pronounced in the analogue containing the L-2-aminobutyryl residue. Surprisingly, potent adjuvant effect was displayed by the hexapeptide; prolongation of the peptidic chain was not effective. The use of a polymeric carrier for MDP increased the adjuvant effect. Contrary to expectation, streptococcal antigens used with immunoadjuvant materials showed that induced delayed hypersensitivity was type related.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Biological activity of synthetic subunits of Streptococcus peptidoglycan. II. Relation of peptidoglycan subunits and analogues to fever effect and induction of tolerance.

A series of synthetic subunits and analogues of streptococcal peptidoglycan was prepared and used in fever and tolerance experiments on rabbits. The lengthening of the chain of the peptide moiety of peptidoglycan did not result in pyrogenic activity, except for hexapeptide. Attachment of the muramyl residue rendered the peptides pyrogenic. The activity of such materials varied in degree and was rather in an indirect relation to peptide chain length. A change in the configuration of C4-OH or C3-OR in the muramyl residue resulted in a profound decrease in pyrogenicity. No inhibitory effect of N-acetylmuramyl-D-alanyl-D-isoglutamine on muramyldipeptide (MDP) pyrogenicity could be demonstrated. Repeated administration of MDP resulted in the induction of tolerance to the pyrogenicity of this substance in rabbits. These animals were not tolerant to the pyrogenicity of peptidoglycan. Nontolerance was also observed in reciprocal experiments with these materials as well as in trials with hexapeptide and peptidoglycan given in either order. The data are consistent with the assumption that peptidoglycan contains more than one biologically active subunit. There is a structure-to-function relationship. The knowledge of the biological effects of the synthetic analogues is essential for the prospect of their use under model or human conditions.

Acetylmuramyl-Alanyl-Isoglutamine↗