Search PubMed⌕ Search

Biomedical subjects

T Martin

Publications and source records attributed to T Martin.

At least 19 recordsLinked to original sources
PubMed1992

Evidence for somatic selection of natural autoantibodies.

Natural autoantibodies are primarily immunoglobulin M (IgM) antibodies that bind to a variety of self-antigens, including self-IgG. Accounting for a large proportion of the early B cell repertoire, such polyspecific autoantibodies are speculated to contribute to the homeostasis and/or competence of the primary humoral immune system. Recent studies indicate that the leukemia cells from most patients with chronic lymphocytic leukemia (CLL) also express such IgM autoantibodies. Similarly, the leukemia cells from many CLL patients react with murine monoclonal antibodies (mAbs) specific for crossreactive idiotypes (CRIs) associated with human IgM autoantibodies. In particular, leukemic cells frequently react with G6, a mAb specific for an Ig heavy chain (H chain)-associated CRI, and/or with 17.109, a mAb that defines a kappa light chain (L chain)-associated CRI. Generated against IgM rheumatoid factor (RF) paraproteins, G6 and 17.109 each recognize a major CRI that is present in many IgM RF paraproteins. Furthermore, over 90% of the IgM paraproteins found to bear both H and L chain-associated CRIs also are found to have RF activity. Molecular characterization of these CRIs demonstrates that each is a serologic marker for expression of a highly conserved Ig V gene. As such, the frequent production of IgM polyspecific autoantibodies in CLL simply may reflect the frequent use of such highly conserved autoantibody-encoding Ig V genes with little or no somatic mutation. To test this hypothesis, we generated murine transfectomas to pair the 17.109-reactive kappa L chain of SMI, a 17.109/G6-reactive CLL population, with the Ig H chain of SMI or other G6-reactive leukemia cells or tonsillar lymphocytes. Cotransfection of vectors encoding the Ig H and L chains of SMI generated transfectomas that produce IgM kappa RF autoantibodies reactive with human IgG1 and IgG4. In contrast to G6/17.109-reactive IgM kappa RF Waldenstrom's paraproteins, the SMI IgM kappa also reacts with several other self-antigens, including myoglobin, actin, and ssDNA. However, cotransfection of the SMI L chain with a vector encoding any one of 10 different G6-reactive Ig H chains generated transfectomas that produce IgM kappa antibodies without detectable polyspecific autoantibody activity. These results indicate that polyspecific antiself-reactivity of G6/17.019-reactive Ig is dependent on the somatically generated Ig third complementarity determining region. Collectively, these studies imply that selection may be responsible for the frequent expression of polyspecific autoantibodies in CLL and early B cell ontogeny.

Amino Acid Sequence↗
PubMed1992

Molecular analysis of the V kappa III-J kappa junctional diversity of polyclonal rheumatoid factors during rheumatoid arthritis frequently reveals N addition.

Much interest was stirred in recent years by the evidence that rheumatoid factors (RF) variable regions are encoded by a restricted set of V genes, with little or no somatic mutations, that are often overexpressed in the fetal repertoire. This is reminiscent of what has been observed for natural autoantibodies. However, these data come from studies of monoclonal RF (mRF) isolated from patients with lymphoproliferative disorders who usually do not present autoimmune symptoms. The molecular characterization of RF during autoimmune diseases such as rheumatoid arthritis (RA) has been hampered for some time because of their polyclonality; recently using the polymerase chain reaction method, we have demonstrated that RF kappa variable regions from a patient with RA were encoded by V kappa III genes known to code for mRF but that these genes had undergone somatic mutations with a pattern suggesting an antigen-driven maturation. Because an important role of the light chain third complementarity-determining region (CDR3) in anti-IgG reactivity and idiotype expression has already been suspected for RF, we now report the molecular characterization of the junction regions of these rearranged V kappa gens. Surprisingly, our data show that in 55% of the cases there is addition of a proline and/or glycine amino acid residue at the recombination site between V kappa and J kappa. The sequence analysis of our patients' germ-line Vg and J kappa 4 genes segments and their flanking regions demonstrates that the additional codons are not readily explicable by recombination between germ-line sequences and probably result from an N addition process. Since we could not find such an additional codon in 15 previously published mRF kappa chains we suggest that "pathogenic" RF during RA and mRF derive from different, although overlapping, B cell subsets. Moreover, since additional codons at the recombination site of V kappa and J kappa seem exceptional in expressed human kappa chains and because the resulting amino acid residue is a proline in most cases, we think that RF kappa chain CDR3 is under a very strong selective pressure during RA.

Amino Acid Sequence↗
PubMed1992

Does elective sclerotherapy improve the efficacy of long-term propranolol for prevention of recurrent bleeding in patients with severe cirrhosis? A prospective multicenter, randomized trial.

We conducted a prospective, multicenter, randomized trial to compare the efficacy of sclerotherapy plus propranolol with that of propranolol alone in the prevention of recurrent gastroesophageal bleeding in severely cirrhotic patients. For 2 yr (1987 to 1988) 131 patients (96% of whom were alcoholic) with Child-Pugh class B or C cirrhosis (56% were class B and 44% were class C) were randomly assigned to one of our two treatment groups after cessation of variceal bleeding, without hemostatic sclerosis, and were observed for at least 2 yr. Treatment observance was good in 89% of cases; alcohol withdrawal was observed in 62% of cases. Sclerotherapy was performed weekly with 1% polidocanol, and variceal obliteration was obtained in 83% of cases, in a mean number of four sessions. The cumulative percentages (expressed as mean +/- S.D.) of recurrent bleeding at 2 yr were 42% +/- 6% for propranolol plus sclerotherapy and 59% +/- 6% for propranolol alone (a nonsignificant difference). Twenty-eight patients from the propranolol group but only 12 patients from the propranolol-plus-sclerotherapy group had recurrent bleeding from esophageal variceal rupture (p less than 0.01). The total number of blood units per patient with recurrent bleeding was slightly but not significantly more important in the propranolol group (8 +/- 7) than in the propranolol-plus-sclerotherapy group (5 +/- 5; p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal Diseases↗
PubMed1992

Structure and expression of a sugarcane gene encoding a housekeeping phosphoenolpyruvate carboxylase.

A gene (SCPEPCD1) encoding phosphoenolpyruvate carboxylase (PEPC) was isolated from the C-4 monocot sugarcane (Saccharum hybrid var. H32-8560). SCPEPCD1 is ca. 6800 bp long, with 10 exons. The entire gene sequence from -1561 to 262 bp downstream of the putative poly(A) addition signal is reported. A low-level, essentially constitutive pattern of expression, amino acid sequence similarities to other 'housekeeping' PEPC enzymes, and the absence of DNA sequence elements conserved in the upstream region of maize and sorghum C-4-specific PEPC genes indicate that SCPEPCD1 encodes a housekeeping PEPC. Despite this, a motif proposed to act as a phosphorylation site in light-mediated activation of photosynthetic PEPC enzymes [10] is present in the SCPEPCD1 protein; evidence is presented for the presence of this site in other housekeeping PEPC proteins.

Amino Acid Sequence↗
PubMed1992

Racemized D-aspartate in Alzheimer neurofibrillary tangles.

Normal protein-bound L-aspartyl/L-asparaginyl residues may undergo posttranslational modification by racemization to D-aspartate. Based on preliminary results reported here, proteins associated with Alzheimer neurofibrillary tangle preparations contain a greater number of these racemized D-aspartyl residues than the unaffected proteins from the surrounding gray matter or in comparable preparations from normal brains.

Alzheimer Disease↗
PubMed1992

Double reactivity of monoclonal and polyclonal rheumatoid factors for IgG and histones: mapping of binding sites by means of histone synthetic peptides and anti-Id antibodies.

Polyreactive antibodies able to bind various apparently unrelated structures represent a frequent antibody population in autoimmune diseases. In this work, the structural basis of the double reactivity of such autoantibodies was investigated using as models polyclonal and monoclonal human rheumatoid factors (RF) reacting with histones. Both direct ELISA binding and competitive inhibition experiments were performed. A more precise delineation of the histone regions recognized by the RFs was made by means of 27 synthetic peptides of these proteins. Anti-idiotope (Id) murine antibodies were used to map the binding sites involved on RF in the interaction with IgG and histones. Among the 13 polyclonal and six monoclonal RFs tested, four and two respectively were found to cross-react with IgG and histones. The fragments shown to be the most frequently recognized by RFs were located in residues 1-16 and 204-218 of H1, 1-20 and 65-85 of H2A, and 1-21 of H3. The results obtained by competitive ELISA assays using IgG, histone peptides and anti-Id monoclonal antibodies led us to confirm and characterize more precisely our previous finding suggesting the existence of topographically distinct binding sites for the different targets recognized by RFs.

Animals↗
PubMed1992

Should children drink before discharge from day surgery?

The ability to drink clear liquids without vomiting after anesthesia and surgery is a commonly used criteria for discharge of pediatric day surgery patients. We hypothesized that the ability to drink as a prerequisite for discharge would not affect the frequency of vomiting, delay discharge, or increase the frequency of readmission of children for dehydration after day surgical procedures. We randomized 989 patients between the ages of 1 month and 18.0 yr to one of two groups. The 464 "mandatory drinkers" were required to demonstrate the ability to drink clear liquids without vomiting prior to discharge from the hospital, whereas 525 "elective drinkers" were allowed but not required to drink. Other than the discharge criteria, the patients were managed in an identical fashion; the minimum volume of intravenous fluids received by all patients was adequate to supply a calculated 8-h fluid deficit prior to discharge from the hospital. There were no differences between the two groups in the incidence of vomiting in the operating room, the postanesthesia care unit, or after discharge from the hospital. However, in the day surgery unit, only 14% of the elective drinkers vomited compared to 23% of the mandatory drinker group (P less than 0.001). The mandatory drinkers had a more prolonged stay in the day surgical unit, averaging 101 +/- 58 min (mean +/- SD) compared to 84 +/- 40 min for elective drinkers (P less than 0.001). No patient in either group required admission to the hospital for persistent vomiting on the day of surgery, and no patient required readmission for vomiting or dehydration after discharge from the day surgery unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

CD5 negative IGM rheumatoid factor B cells in B-chronic lymphocytic leukemia and benign mixed cryoglobulinemia.

IgM-RF B cell precursors are abnormally overrepresented in "well differentiated" lymphoid monoclonal proliferations while data on less mature lymphoid malignancies are still awaited. This nevertheless suggests that RF activity plays a role in the transforming process perhaps by inducing constant stimulation of the precursor B cells. Despite the preferential use of similar VH and VL genes with little or no somatic hypermutations in both malignant B-cell CLL and nonmalignant mixed cryoglobulinemia, these proliferations do differ in CD5 membrane expression and in their clinical evolution. One possibility could be that CD5 glycoprotein is lost during maturation of the lymphocyte into a secreting cell as suggested by data on Waldenström's disease and the LES-CLL and by in vitro studies. Alternatively, CD5 expression could play an additional direct role in malignant transformation as suggested by recent data on the CD5 receptor ligand. Further data on the proliferating cells in both situations as well as on the genetic control of CD5 expression in B cells and its physiology should shed additional light on the mechanisms of B-cell malignancy.

Antigens, CD↗
PubMed1992

[Rheumatoid factors].

Rheumatoid factors (RF), which are auto-antibodies recognising the Fc fragment of IgGs, are the commonest auto-antibodies in man. They are present in polyclonal form in a large number of auto-immune disorders as well as in certain inflammatory states. In monoclonal form, they are frequently the product of "mature" malignant (chiefly Waldenström's macroglobulinemia and chronic lymphoid leukemia) and allegedly benign (such as cryoglobulinemias) lymphoid proliferations. In addition, RF account for a significant part of the normal antibody repertory, notably during the fetal and neonatal periods, suggesting that they may play an important role in the development and regulation of the immune system. As a result, RF are an excellent model for the analysis of auto-immunity in man. Thus many indirect (analysis of antigens recognised and of idiotopes carried) and, more recently, direct (protein or nucleotide sequencing of their various regions) studies have now provided the following conclusions. RF are coded by a very limited repertory of V genes. These genes are present in the normal genome and appear to be highly preserved in the human species. They are used with very few somatic mutations by monoclonal B proliferations (which opens up valuable therapeutic possibilities) as well as probably by RF producing B lymphocytes in normal individuals. In contrast, in the context of auto-immune disorders, these same genes have many somatic mutations suggesting maturation governed by the antigen and/or escape from idiotype control.

Autoimmune Diseases↗
PubMed1991

Localization of heterogeneous nuclear ribonucleoprotein in the interphase nuclear matrix core filaments and on perichromosomal filaments at mitosis.

Although heterogeneous nuclear RNA (hnRNA) has been localized to the core filament substructure of the nuclear matrix, its precise location in the filament network has been unknown. The fA12 monoclonal antibody can localize, at high resolution, hn ribonucleoproteins (hnRNPs) and, presumably, hnRNA. Gold bead immunolabeling of resinless electron microscopy sections showed the fA12 antigens were in the fibrogranular material enmeshed in the filament network and not in the filaments themselves. At mitosis, hnRNP antigens became dispersed into a halo surrounding the chromosomes and spindle poles. Immunogold staining showed fA12 stained fibrogranular material associated with perichromosomal and pericentriolar filaments distinct from the mitotic spindle fibers. fA12 also labeled the midbody remaining after cytokinesis.

Cell Line↗
PubMed1991

Rhodococcus infection of the skin with lymphadenitis in a nonimmunocompromised girl.

A 7-year-old girl had a 4 X 3 X 3 cm nodule on the left wrist with axillary lymphadenopathy. Acid-fast bacilli were seen on a smear from a biopsy specimen of this granulomatous skin lesion. A Rhodococcus species grew on culture. Skin infections caused by Rhodococcus may be more common than the few prior case reports suggest.

Actinomycetales Infections↗
PubMed1991

Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon.

Current models of the virus-like agents of scrapie and bovine spongiform encephalopathy (BSE) have to take into account that structural changes in a host-encoded protein (PrP protein) exhibit an effect on the time course of these diseases and the survival time of any man or animal exposed to these pathogens. We report here the sequence of different forms of the bovine PrP gene which contain either five or six copies of a short, G-C-rich element which encodes the octapeptide Pro-His-Gly-Gly-Gly-Trp-Gly-Gln or its longer variants Pro-Gln/His-Gly-Gly-Gly-Gly-Trp-Gly-Gln. Out of 12 cattle, we found eight animals homozygous for genes with six copies of the Gly-rich peptide (6:6), while four were heterozygous (6:5). Two confirmed cases of BSE occurred in (6:6) homozygous animals.

Alleles↗
PubMed1991

Obstetric accidents: the patient's perspective.

Cases from the files of Action for Victims of Medical Accidents which had resulted in stillbirth, perinatal or neonatal death and long term mental or physical handicap were reviewed. In 41 cases there was both a detailed letter from the parents and an independent review by a senior obstetrician. The reviewer's main criticisms were of inadequate fetal heart monitoring, lack of involvement of senior staff and inadequate records. The fetal heart trace was missing in 7 cases and over half of the remaining 34 traces available were misinterpreted or not acted on. In 17 cases junior doctors failed to recognize fetal distress and managed a delivery that they did not have the experience to deal with. In a further 6 cases, senior staff were called but did not come. Records were criticized for being incomplete, illegible or missing. In a few cases unjustified alterations appeared to have been made. Women reported that on some occasions staff ignored their worries, were unsympathetic and gave too little information. Some parents also experienced considerable difficulty in obtaining a clear explanation of the nature and cause of their child's condition.

Birth Injuries↗
PubMed1991

Psychiatric aspects of male genital self-mutilation.

From the beginning of the century to this day 57 cases of male genital self-mutilation have been reported in the English literature. In German publications we found 5 case descriptions. Although no precise data are available on the prevalence of male genital self-mutilation, such acts are presumably much more frequent than the small number of published cases would suggest. In the literature several features are regarded as risk factors for self-mutilation, such as e.g. homosexual or transsexual tendencies, repudiation of the male genitals, absence of a competent male for identification during childhood, feeling of guilt for sexual offences, and self-injury in the anamnesis. The most frequent diagnoses are schizophrenia and affective psychosis; alcohol intoxication was diagnosed in about one-fourth of the cases published. In the present paper we summarize data from the literature on epidemiology, psychopathology, psychodynamic and sociocultural factors in male genital automutilation and we describe 2 new cases of self-castration in which several of the risk factors described above were observed. We conclude that although it is difficult to estimate the risk of self-castration in view of the heterogeneity of the respective patient groups, the danger of such deeds should be kept in mind if the above factors are present.

Adult↗
PubMed1991

Phase II trial of carboplatin plus cisplatin in recurrent and advanced squamous cell carcinoma of the head and neck.

Cisplatin is one of the most active chemotherapeutic agents for the treatment of squamous carcinoma of the head and neck; however, neurotoxicity and nephrotoxicity are dose-limiting. The analog, carboplatin, is a promising new agent with similar activity but a different spectrum of toxicity. To evaluate if a therapeutic advantage could be achieved with acceptable toxicity, a combination of carboplatin 350 mg/m2 and cisplatin 50 mg/m2 were administered every 28 days to patients with recurrent or metastatic disease who had received no prior chemotherapy. Of 24 patients enrolled in this study, 21 were assessable for response and toxicity. Five partial responses were observed (24%; 95% confidence interval [Cl], 4.9% to 38.6%). No complete response occurred. Two of these patients received definitive radiotherapy and achieved complete responses. The median survival of all patients was 24 weeks. Hematologic toxicity was dose-limiting necessitating a decrease in the starting dose of carboplatin to 300 mg/m2. Nonhematologic toxicity was infrequent and mild. Significant renal impairment occurred in only two patients. Although treatment with the combination of carboplatin and cisplatin is feasible, we found no therapeutic advantage in terms of an increased response or survival.

Adult↗