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Biomedical subjects

R Grubb

Publications and source records attributed to R Grubb.

At least 19 recordsLinked to original sources
PubMed1992

Herpesvirus serology, aberrant specific immunoglobulin G2 and G3 subclass patterns and Gm allotypes in individuals with low levels of IgG3.

One objective of this study was to determine whether IgG3-deficient individuals have an increased frequency of reactivated herpesvirus infections. Serum titres to Epstein-Barr virus (EBV) and human herpesvirus-6 were examined in 10 healthy and in 10 symptomatic persons with serum IgG3 < 0.1 g/l. Atypical titres were found in 16% of the IgG3-deficient individuals. Reactivations of these viruses thus do not seem common in IgG3 deficiency. Antigen-specific IgG responses were also determined. A lowered frequency of IgG3 to an EBV-derived peptide was found only in symptomatic, IgG3-deficient individuals. Levels of IgG2 to a bacterial polysaccharide were lowered in the same group, despite normal serum levels of total IgG2. A functional IgG2 deficiency may contribute to symptoms in IgG3 deficiency. The G3(g) allotype, known to be associated with low total IgG3, dominated in IgG3-deficient persons (13/17) independently of presence or absence of symptoms. A linkage of G3(g) to the G2(n) negative allotype, associated with low IgG2, was equally common irrespective of symptoms. G3(g) and absence of G2(n) seem to be one prerequisite for most of IgG3 deficiency combined with low specific IgG2.

Antibodies, Viral↗
PubMed1991

Immunogenetic markers as probes for polymorphism, gene regulation and gene transfer in man--the Gm system in perspective.

The genetic markers of immunoglobulins (Ig) demonstrable by immunological methods have shown their usefulness as genetic probes. The study of these allotypes originally proved that Ig production is under conventional genetic control and also established that allelic exclusion is valid for the key molecules of the immune response. The codons responsible for the G1m(a) marker and their position in the human genome are precisely known. This knowledge implies that Gm typing may be used as a convenient and reliable means of following the fate of IgG constant gene segments. Anti-Gm's are common in rheumatoid arthritis. They appear early in the disease and may persist throughout life. The stimulus for their appearance has not yet been established. The anti-Gm's in the allegedly autoimmune disease rheumatoid arthritis are commonly and apparently paradoxically specific for Gm gene products of other persons. Another apparent paradox brought to light by Ig allotype research is the occasional appearance of non-nominal allotypes in contradiction to Mendelian laws. It is proposed that a plausible explanation for these two paradoxes is Ig gene transfer between individuals with viral vectors. Reasons for this proposal and some possible consequences of gene transfer in a polymorphic species are delineated. Immunogenetics and DNA technology in combination provide powerful tools to elucidate the fate of genes. A method allowing the assignment of G1m(a+) and G1m(a-) at the gene level by polymerase chain reaction analysis has recently been established and is briefly described.

Codon↗
PubMed1991

The clinical application of neurogenic motor evoked potentials to monitor spinal cord function during surgery.

The purpose of this study was to report results from 300 cases (177 children, 123 adults) administered somatosensory and neurogenic motor evoked potentials during surgery. Of these 300 cases, there were 16 cases of spinal fractures, 16 neurosurgical cases, 28 vascular cases, and 240 cases of elective posterior spinal deformity requiring instrumentation. Results indicated that somatosensory evoked potentials, especially cortical components, demonstrated greater variability than neurogenic motor evoked potentials. Variability was attributed to anesthesia and unknown factors. Neurogenic motor evoked potentials proved to be a more valid indicator of postoperative motor status than somatosensory evoked potentials. Based on their anatomic substrates and results from this study, it was recommended that somatosensory evoked potentials and neurogenic motor evoked potentials be used to monitor spinal cord function during surgery that would place that structure at risk.

Adolescent↗
PubMed1991

Determination of allotypes G1m(f) and G1m(z) at the genomic level by subclass-specific amplification of DNA and use of allele-specific probes.

Two oligonucleotide primers were used for selective enzymatic amplification of a DNA segment encoding a major portion of the first constant region domain (CH1) of the human IgG1 heavy chain. The selective amplification was confirmed by use of subclass-specific oligonucleotide probes. Two 15-mer oligonucleotides, hybridizing with the alleles for the allotypes G1m(f) and (z), respectively, could then be used for determination at the genomic level of these two truly allelic allotypes. Serum and DNA samples from 12 individuals, one of them with a considerable amount of anti-Gm(f) antibodies, were used for allotype assignment by classical serological methods and by the new method operating at the genomic level. The resulting classifications agreed completely, demonstrating the reliability of the new method.

Alleles↗
PubMed1991

Alloimmunization to human immunoglobulin genetic markers is frequent in early rheumatoid arthritis.

HLA and Gm allotypes of 99 consecutive Swedish patients with rheumatoid arthritis were determined. Ninety-two of the 198 haplotypes contained DR4, a significant increase. The patients' sera from 3 different occasions were studied for anti-immunoglobulin profile as judged by 6 selected anti-Rh coats, 4 of them being monoclonal anti-Ds restricted as to allotype. Ninety-two of the patients were reactive with a polyclonal anti-Rh Ri as against 10 with the monoclonal carrying the G1m(f) allotype. Antibodies to Ig coats carrying defined allotypes were more frequently observed in patients not carrying the allotype in question than in those individuals possessing it. The difference was significant or highly significant as regards presence/absence of G1m(a), G3m(b) and G3m(g), respectively. Anti-G1m(a) and anti-G3m(g) cooccurred in 17 of the patients. Results consistent with presence/absence of particular anti-immunoglobulins at the 3 examinations were observed in 74 of the patients. Gm allotypes or antiallotypes were not statistically related with DR4 status. In conclusion, alloimmunization to Gm markers frequently occurs in early rheumatoid arthritis.

Adult↗
PubMed1990

Distribution of Gm allotypes in juvenile chronic arthritis.

The immunoglobulin allotypes G1m(a), G1m(x), G2m(n), G3m(b) and Km(1) were determined in 76 Swedish patients with juvenile chronic arthritis (JCA). Eight of the patients had the systemic form of the disease. 37 belonged to the polyarticular and 31 to the oligoarticular subset. The frequency of the G1ma(x), G3m-b haplotype was significantly increased in the polyarticular subset but not in the oligoarticular subset, compared with the normal population (p less than 0.01). The polyarticular subset also differed from the oligoarticular subset with increased frequency (p less than 0.01) and higher levels (p less than 0.01) of IgM rheumatoid factor and a lower rate of remission (p less than 0.05). The few JCA patients in the systemic subset showed similar features as the polyarticular patients. The frequencies of G2m(n) and Km(1) did not deviate from the expected in any of the JCA subsets.

Adolescent↗
PubMed1990

Assignment of allotypes G1m(a+) and G1m(a-) at the genomic level by polymerase chain reaction analysis.

A method of assignment of the human immunoglobulin allotypes G1m(a+) and G1m(a-) without the use of serological reagents is described. It is based upon oligonucleotide-directed enzymatic amplification of genomic segments encoding CH3 of gamma chains, followed by dot-blot hybridization of radioactively labelled oligonucleotides to the amplified DNA. The method was used to classify the immunoglobulin allotypes of 11 persons, six G1m(a+) and five G1m(a-), and the resultant classification agreed completely with that of classical serological typing.

Amino Acid Sequence↗
PubMed1989

Determination of homozygosity or heterozygosity for the G2m(n) allotype by a monoclonal, precipitating antibody.

Monoclonal antibody SH 21 was found to be a good anti-IgG2m(n) reagent both for the conventional typing (HA inhibition) and for precipitation in polyethylene glycol containing gel. Antibody SH 21, together with monoclonal antibody HP 6014 (anti-IgG2), was used for the discrimination between G2m(+n) homozygotes and heterozygotes in a double diffusion assay, where the two antibodies and a serum sample were placed in corners of a triangle. In the case of a homozygote SH 21 was able to stop the diffusion of IgG2 to a precipitation line, but some IgG2 of a heterozygote was able to diffuse beyond the precipitate, forming a crossed precipitation pattern. The validity of the typing was checked with serum samples from 54 families. All the 33 'obligatory heterozygotes' (G2m(+n) parent(s) of a G2m(-n) child, or the other way round) exhibited the crossed precipitate. The frequency of the G2mn allele in a Finnish population of 297 unrelated adults was 0.409.

Alleles↗
PubMed1989

On the origin of antibodies to immunoglobulin genetic markers in rheumatoid arthritis. An outline of a novel concept of the nature of rheumatoid arthritis--transduction in man.

Anti-Gm's in rheumatoid arthritis patients detect products of the Mendelian genes G1ma, G1mx, G3mb, G3mc, G3mg, G3mst. Commonly, these anti-Gm's are specific for other individuals immunoglobulin allotypes. Reasons are given for the contention that such anti-Gm's in patients with rheumatoid arthritis are indicative of the expression of nonnominal allotypes, the genes for which have been transferred from one individual to another by means of a B cell virus. This process - akin to transduction and occurring after the tolerance induction period - may lead to a chimaeric state of the B cell compartment in rheumatoid arthritis patients. Special features of Ig gene regulation in normal B cell progression are allelic exclusion and the excision-expulsion-rejoining of DNA segments. Perturbation of B cell regulation by external genomes may be favoured by allelic exclusion. The DNA excision-rejoining processes may have consequences for concomitant (viral) nucleic acid assembly, particularly for viruses sharing nucleotide sequences with the Ig switch regions.

Antibodies, Anti-Idiotypic↗
PubMed1989

Immunoglobulin allotypes are normally distributed in Swedish AIDS patients.

Immunoglobulin allotypes G1m(a), G1m(x), G3m(b) and Km(1) were determined in 83 Swedish AIDS patients. Twenty of the patients had Kaposi's sarcoma and 29 had Pneumocystis carinii pneumonia. The distribution of the Gm and Km allotypes did not significantly differ between these different disease categories and the general Swedish population.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Incidence of anti-human Ig with restricted specificity in Japanese, Kuwaiti, and Swedish patients with rheumatoid arthritis.

Assuming that anti-allotypic anti-Ig in rheumatoid arthritis is stimulated by the individual's allotype, it would be reasonable to expect a higher incidence of anti-G1m(a) in individuals carrying G1m(a). There is marked divergence among various populations in allotype frequencies. G1m(a) allotype and the prevalence of anti-Ig reactive with G1m(a) Ig were determined in 18 Kuwaiti, 23 Japanese, and 41 Swedish rheumatoid arthritis patients. An inverse relationship was observed between the frequency distribution of allotype G1m(a) and anti-allotype; thus, the stimulus for the anti-allotype is not the patient's own allotype.

Antibodies, Anti-Idiotypic↗
PubMed1988

The Gm system. Anti-Gm's: characteristics in rheumatoid arthritis; experimental induction without resort to allotype; frequent occurrence in mononucleosis.

UNLABELLED: Gm system: Some RFs specifically detect Mendelian markers of human Ig, originally proving that Ig production is gene controlled. The genetic marker systems of human Ig with 17 Gm, 2 Am, 3 Km and 1 Em markers are briefly described. Examples of the usefulness of the Gm system in medicine, immunology and molecular biology are mentioned. CONCLUSIONS: 1. Some RFs have been essential tools in elucidating genetic control mechanisms in Ig production. 2. Knowledge of the Gm system is extensive. Anti-Gm's: High-titered anti-Gm's are common in R.A. The anti-allotypes in R.A. are markedly restricted as to their specificity. They are usually not directed against the individuals own Gm markers. Anti-human-immunoglobulins were observed in 12 of 18 sera from patients with mononucleosis. The majority of these anti-immunoglobulins were inhibitable by native human Ig and showed restricted specificity. CONCLUSIONS: 1. There is a strong stimulus for production of particular anti-Gm's in a majority of R.A. cases. 2. Notions of an autoimmune origin for many anti-Gm's in R.A. are not in obvious agreement with experimental observations. 3. Anti-human-Ig's with restricted specificity are commonly induced in mononucleosis.

Antibodies↗
PubMed1987

Failure of doxycycline treatment in aquarium-associated Mycobacterium marinum infections.

Two cases of aquarium-associated Mycobacterium marinum infections are described. Neither was cured by the initial therapy consisting of surgical excision followed by doxycycline treatment. Both strains of M. marinum were shown to be resistant to doxycycline. In one patient the lesions were subsequently healed with cotrimoxazole. The other patient, a 12-year-old girl with sporotrichoid spread of the lesions on the lower arm, failed to respond satisfactorily to a combination of rifampicin and ethambutol despite favourable effect in vitro of both drugs. Nine months after the initial treatment, the infection was finally cured with renewed surgery followed by additional chemotherapy with rifampicin and ethambutol. No signs of immunological disorder could be detected in the patient. Increased awareness of the possibility of tetracycline resistance of M. marinum is advocated. A combination of adequate chemotherapy and surgical intervention may be required at least in complicated cases.

Adult↗
PubMed1986

Correlation between deficiency of immunoglobulin subclass G3 and Gm allotype.

Gm allotypes were investigated in 63 Swedes: 46 females and 17 males, in whom serum IgG3 was below 0.35 g/l. Both monoclonal antibodies and polyclonal antisera were used for the quantification. Concentrations of the other IgG subclasses were within the age-related normal ranges. The distribution of the IgG1 genetic markers G1m(a,x,f) differed markedly from that observed in normal Swedes (p less than 0.001). Thus G1m(a) was present in 60 subjects as compared to an expected 36, and phenotype G1m(-f) in 34 subjects as against an expected 8. The mean IgG3 concentration was numerically lower in the G1m(-f) group than in the G1m(+f) cohort, and individuals with IgG3 levels 0.10 g/l were more frequent in the G1m(-f) group. Among Caucasians, G3mg is in linkage disequilibrium with G1ma and our interpretations is that the haplotype G1ma;ax G2m-n G3mg is markedly increased in individuals with IgG3 deficiency.

Dysgammaglobulinemia↗
PubMed1986

Familial occurrence of cervical cancer, stages 0-IV.

All patients hospitalized in 1982 at the Department of Gynecology in Malmö because of malignancy of the cervix uteri attended an interview study concerning the presence of cervical cancer among their nearest relatives. In addition, these patients were questioned concerning earlier gonorrheal infection. The blood group was determined as also was the secretory status and Gm allotype. As a control group the families of the male consorts were used. Cervical cancer was found significantly more often in mothers of the patients (7.9%) than in the consorts' mothers (1.0%). Sisters, aged 20 or over, of the patients had cervical cancer significantly more often (7.5%) than sisters of the consorts (1.1%). Moreover, cervical cancer in mothers and/or sisters was found in 15.6% of the patients. In cases of invasive cancer or previously operated CIS, this figure was 17.5%. The patients did not differ significantly from the normal population regarding blood group or secretory status. A somewhat lower, although non-significant, frequency of Gm(1) allotype was found in patients with invasive cancer, compared with patients with CIS. Patients with a positive family history of cancer had more often had gonorrhea (24%) than patients with a negative family history (18%). The study indicates a multifactorial etiology for cervical cancer.

Adult↗
PubMed1986

Burkitt lymphoma and genetic markers of immunoglobulin.

The Ig allotype G3m (c3) was numerically more frequent among 70 Kenyan Burkitt lymphoma (BL) cases than in 70 Kenyans with other tumors of the neck (0.02 greater than p greater than 0.01). The distribution of allotypes G1m (a, x) and G3m (b5) did not differ between 50 Caucasian BL cases and blood donors.

Antibodies, Neoplasm↗