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J A Noble

Publications and source records attributed to J A Noble.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sequence analysis of the diabetes-protective human leukocyte antigen-DQB1*0602 allele in unaffected, islet cell antibody-positive first degree relatives and in rare patients with type 1 diabetes.

The human leukocyte antigen (HLA)-DQA1*0102/DQB1*0602/DRB1*1501 (DR2) haplotype confers strong protection from type 1 diabetes. Growing evidence suggests that such protection may be mostly encoded by the DQB1*0602 allele, and we reported that even first degree relatives with islet cell antibodies (ICA) have an extremely low diabetes risk if they carry DQB1*0602. Recently, novel variants of the DQB1*0602 and *0603 alleles were reported in four patients with type 1 diabetes originally typed as DQB1*0602 with conventional techniques. One inference from this observation is that DQB1*0602 may confer absolute protection and may never occur in type 1 diabetes. By this hypothesis, all patients typed as DQB1*0602 positive with conventional techniques should carry one of the above diabetes-permissive variants instead of the protective DQB1*0602. Such variants could also occur in ICA/DQB1*0602-positive relatives, with the implication that their diabetes risk could be significantly higher than previously estimated. We therefore sequenced the DQB1*0602 and DQA1*0102 alleles in all ICA/DQB1*0602-positive relatives (n = 8) previously described and in six rare patients with type 1 diabetes and DQB1*0602. We found that all relatives and patients carry the known DQB1*0602 and DQA1*0102 sequences, and none of them has the mtDNA A3243G mutation associated with late-onset diabetes in ICA-positive individuals. These findings suggest that diabetes-permissive DQB1*0602/3 variants may be very rare. Thus, although the protective effect associated with DQB1*0602 is extremely powerful, it is not absolute. Nonetheless, the development of diabetes in individuals with DQB1*0602 remains extremely unlikely, even in the presence of ICA, as confirmed by our further evaluation of ICA/DQB1*0602-positive relatives, none of whom has yet developed diabetes.

Adult↗
PubMed1999

Association between type 1 diabetes age of onset and HLA among sibling pairs.

In this study, we report type 1 diabetes age-of-onset association with HLA class II (DRB1, DQB1, and DPB1) and class I (A) genes in 222 multiplex families from the Human Biological Data Interchange. Linear regression showed a small (R2 = 0.26) but significant correlation in the ages of onset among sib pairs. A strong association in age of onset between members of sib pairs was observed when the analysis was performed using contingency tables that split sibs into three age-at-onset ranges (0-10, 11-20, and 21-36 years). The association is strongest for sib pairs that share both haplotypes and is nonsignificant for sib pairs that do not share any DR-DQ haplotypes. A goodness-of-fit test revealed that DR-DQ haplotype sharing cannot account for all the association in age of onset among sib pairs. The age-of-onset distribution of DR-DQ haplotypes is affected by the DPB1 and A alleles present. The strongest associations were found with the A locus: DR3/DR4 genotype frequency decreases with age of onset in this data set only among A*0101- individuals, and A*2402 is strongly associated with younger age of onset in many DR-DQ haplotypes.

Adolescent↗
PubMed1997

Fungal colonization of air filters from hospitals.

Air filters of various types, selected on the basis of discoloration, were collected from the primary and secondary filter banks of the heating, ventilating, and air-conditioning systems in seven hospitals in the eastern United States and examined with direct microscopy for fungal colonization. Microscopic observations and culture results showed that filters from five of the hospitals were colonized with fungi including species of Acremonium, Alternaria, Aspergillus, Cladosporium, Epicoccum, Penicillium, and Rhinocladiella, and a Beauveria-like fungus. Several of these commonly airborne species, e.g., Epicoccum purpurescens (syn. E. nigrum) and Rhinocladiella sp., had not been previously reported to colonize (with conidiogenesis) air filters.

Air Conditioning↗
PubMed1996

Fungal colonization of fiberglass insulation in the air distribution system of a multi-story office building: VOC production and possible relationship to a sick building syndrome.

Complaints characteristic of those for sick building syndrome prompted mycological investigations of a modern multi-story office building on the Gulf coast in the Southeastern United States (Houston-Galveston area). The air handling units and fiberglass duct liner of the heating, ventilating and air conditioning system of the building, without a history of catastrophic or chronic water damage, demonstrated extensive colonization with Penicillium spp and Cladosporium herbarum. Although dense fungal growth was observed on surfaces within the heating-cooling system, most air samples yielded fewer than 200 CFU m-3. Several volatile compounds found in the building air were released also from colonized fiberglass. Removal of colonized insulation from the floor receiving the majority of complaints of mouldy air and continuous operation of the units supplying this floor resulted in a reduction in the number of complaints.

Air Conditioning↗
PubMed1996

Results of Expedicion Humana. II. Analysis of HLA class II alleles in three African American populations from Colombia using the PCR/SSOP: identification of a novel DQB1*02 (*0203) allele.

PCR/SSOP typing methods were used to analyze the HLA Class II DRB1, DQA1, DQB1 and DPB1 loci of samples from three African American populations of Colombia. Forty samples from the Cauca (Pacific), and twenty samples each from the Choco (North Pacific Coast) and the Providencia (Caribbean island) populations, were collected and the Class II loci analyzed under the auspices of the Expedicion Humana. Despite the limited number of samples analyzed, the African Colombian populations exhibit a very high degree of class II polymorphism. A great diversity of DRB1 alleles was found, with representatives from all serological classes, including 19 DRB1 alleles in the Providencia, 16 in the Cauca and 14 in the Choco groups. In addition, a novel DQB1*02 allele (*0203) was found in two individuals from the Cauca population of the Pacific Coast. The sequence of the DQB1*0203 allele, associated with DR3, differs from DQB1*0201 by only one nucleotide substitution (C-->A) in the second position of codon 57, resulting in an Ala to Asp change. The addition of DQB1*0203 brings the total number of DQB1 alleles identified to date to 26. HLA class II diversity is much greater in these African Colombian populations than that seen in nearby Amerindian populations. Analysis of regional Colombian African American HLA population genetics is discussed with respect to the Colombian Amerindian HLA genetics described in an accompanying paper.

Alleles↗
PubMed1996

The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families.

We report here our analysis of HLA class II alleles in 180 Caucasian nuclear families with at least two children with insulin-dependent diabetes mellitus (IDDM). DRB1, DQA1, DQB1, and DPB1 genotypes were determined with PCR/sequence-specific oligonucleotide probe typing methods. The data allowed unambiguous determination of four-locus haplotypes in all but three of the families. Consistent with other studies, our data indicate an increase in DR3/DR4, DR3/DR3, and DR4/DR4 genotypes in patients compared to controls. In addition, we found an increase in DR1/DR4, DR1/DR3, and DR4/DR8 genotypes. While the frequency of DQB1*0302 on DR4 haplotypes is dramatically increased in DR3/DR4 patients, DR4 haplotypes in DR1/DR4 patients exhibit frequencies of DQB1*0302 and DQB1*0301 more closely resembling those in control populations. The protective effect of DR2 is evident in this data set and is limited to the common DRB1*1501-DQB1*0602 haplotype. Most DR2+ patients carry the less common DR2 haplotype DRB1*1601-DQB1*0502, which is not decreased in patients relative to controls. DPB1 also appears to play a role in disease susceptibility. DPB1*0301 is increased in patients (P < .001) and may contribute to the disease risk of a number of different DR-DQ haplotypes. DPB1*0101, found almost exclusively on DR3 haplotypes in patients, is slightly increased, and maternal transmissions of DRB1*0301-DPB1*0101 haplotypes to affected children occur twice as frequently as do paternal transmissions. Transmissions of DR3 haplotypes carrying other DPB1 alleles occur at approximately equal maternal and paternal frequencies. The complex, multigenic nature of HLA class II-associated IDDM susceptibility is evident from these data.

Adolescent↗
PubMed1995

Production of live offspring with predicted genotypes using PCR-RFLP analysis of polar bodies from mouse oocytes.

Accurate identification of genotypes in gametes and early embryos could facilitate the efficient production of offspring with desirable traits. This study demonstrates the feasibility of producing offspring with predictable genotypes from micromanipulated mouse oocytes. The Polymerase Chain Reaction (PCR) was used to amplify genes in the IA subregion of the major histocompatibility complex of the mouse. The validity of the approach was demonstrated in experiment 1 with IA haplotypes of unfertilized mouse ova amplified via PCR and distinguished by restriction fragment length polymorphism (RFLP) analysis. In experiment 2, fertilized oocytes were micromanipulated to remove the first and second polar bodies, which were then genotyped by validated PCR-RFLP procedures. Primary oocytes of heterozygous females contain two copies of each of the different alleles. Following meiosis I and II, the genotype of the ovum was predicted by subtracting the alleles observed in micromanipulated polar body samples. Sixty-two fertilized ova were micromanipulated and transferred to recipient females resulting in 27 live offspring (44%). The correct maternal contribution to the embryonic genotype was predicted in 19 of 27 (71%) offspring as confirmed by PCR-RFLP analysis of DNA from pup tails. Predicted genotypes of two pups were not confirmed (7%), whereas no prediction could be made in six cases (22%).

Animals↗
PubMed1995

Alcohol use in combination with cocaine, heroin and methadone by medical examiner cases.

OBJECTIVE: The purpose of this review of all appropriate, available medical examiner (ME) studies is to provide information on cases with positive toxicologies for cocaine, morphine (the heroin metabolite) and methadone that have positive blood or brain alcohol concentrations (BACs). METHODS: Criteria for inclusion of U.S. ME studies in this review are (1) at least 20 cases with a positive toxicology for cocaine, morphine or methadone and (2) BAC test findings according to specific drug positivity. Only 19 studies conducted from 1969 to 1992 met these criteria; most studies reviewed were not included primarily because of their failure to present or link available BAC test findings with positive toxicologies for these other drugs. RESULTS: The BAC-positive ranges were similar for cocaine and heroin. In reports on both heroin and methadone or on all three drugs, heroin-positive cases had the highest proportions and methadone-positive cases had the lowest proportions with positive BACs. CONCLUSIONS: Published data confirm the substantial presence of alcohol in combination with cocaine, heroin and methadone among ME cases. Future ME studies should endeavor to link BAC and toxicology findings for other drugs according to drug-induced or drug-related manner of death. These data would advance our knowledge about the role of alcohol in drug deaths and provide additional information on substance abuse trends.

Adolescent↗
PubMed1994

Effect of relative humidity on fungal colonization of fiberglass insulation.

Fiberglass duct liners and fiberglass duct boards from eight buildings whose occupants complained of unacceptable or moldy odors in the air were found to be heavily colonized by fungi, particularly by Aspergillus versicolor. Unused fiberglass was found to be susceptible to fungal colonization in environmental chambers dependent upon relative humidity. No colonization was observed at relative humidities below 50%.

Construction Materials↗
PubMed1993

The Escherichia coli hflA locus encodes a putative GTP-binding protein and two membrane proteins, one of which contains a protease-like domain.

The hflA (high frequency of lysogenization) locus of Escherichia coli governs the lysis-lysogeny decision of bacteriophage lambda by controlling stability of the phage cII protein. hflA contains three genes, hflX, hflK, and hflC, encoding polypeptides of 50, 46, and 37 kDa, respectively. We have determined the nucleotide sequence of 3843 base pairs containing hflA and have found three large open reading frames corresponding to hflX, hflK, and hflC. HflX contains the three sequence motifs typical of GTP-binding proteins and appears to be a member of a distinct family of putative GTPases. HflC and HflK appear to be integral membrane proteins which show some similarity to each other and to a human membrane protein. The C-terminal region of HflC contains a domain resembling the catalytic domain of ClpP, a bacterial ATP-dependent protease. We hypothesize that HflK and HflC constitute a distinct membrane-bound protease whose activity may be modulated by HflX GTPase.

Adenosine Triphosphate↗
PubMed1993

Phenotypic analysis of proteinase A mutants. Implications for autoactivation and the maturation pathway of the vacuolar hydrolases of Saccharomyces cerevisiae.

We have isolated a number of mutants deficient in activity of the vacuolar hydrolase proteinase A (PrA). The mutations were sequenced and although they all map in the PEP4 gene, which encodes the precursor to PrA, three distinguishable phenotypes have surfaced. The properties of the pep4-7 missense mutant suggested that the activation of the precursor to proteinase A is due to an autocatalytic cleavage. PrA active site mutations were constructed and resulted in accumulation of PrA antigen in the inactive precursor form. Although protease B (PrB), another vacuolar hydrolase, is not required for the production of active PrA, the active form of PrA that accumulates in a strain lacking PrB is larger than that found in a strain containing active PrB. We have purified this larger form of PrA and determined that it bears 7 additional amino acids at its NH2 terminus. It has become apparent from all the studies performed on the maturation pathway of the vacuolar hydrolases that there is a great deal of redundancy built into the system.

Amino Acid Sequence↗
PubMed1991

The effect of Ca2+ channel antagonists (cadmium, omega-conotoxin GIVA, and nitrendipine) on the release of angiotensin II from fetal rat brain in vitro.

We have shown previously that K+ stimulation of dissociated cell cultures of fetal rat brain results in a graded release of angiotensin II (ANG II) that is dependent on the availability of extracellular Ca2+. In this study, using dissociated cell cultures of fetal rat hypothalamus, thalamus, septum, and midbrain (HTSM), we further examined the role of calcium channels on ANG II release using specific channel blockers (cadmium, omega-conotoxin, and nitrendipine) and a calcium ionophore (A23187). Levels of ANG II release were quantitated by radioimmunoassay and HPLC. For control levels of ANG II release, cells were incubated in a stock buffer containing 89 mM choline chloride/58 mM KCl/2 mM CaCl2. Pretreatment of the cells with either 100 microM Cd2+ (to block N-, L-, and T-type calcium channels), 100 nM omega-conotoxin (to block N- and L-type calcium channels), or 500 nM nitrendipine (to block L-type calcium channels) decreased ANG II release by approximately 71%, 71% and 22%, respectively, when compared to control levels. In contrast, pretreatment of the cells with 1.6 microM A23187 (a calcium ionophore) increased ANG II release by approximately 90% over control levels. These findings suggest that angiotensin release is dependent on the intracellular entry of Ca2+ ions through primarily N-type channels, and to a lesser extent, L-type channels.

Angiotensin II↗
PubMed1990

Intracellular localization of pp60c-src in human platelets.

We have studied the intracellular distribution of the proto-oncogene product pp60c-src in human platelets by immunofluorescence microscopy and by immunogold electron microscopy on frozen thin sections. Virtually all of the immunoreactive pp60c-src was found to be associated with the plasma membrane and with membranes of the surface-connected canalicular system. This localization suggests that pp60c-src may relay signals from an as yet unidentified cell surface protein to intracellular targets.

Antibodies, Monoclonal↗
PubMed1989

Alcoholism treatment in general hospitals.

This article examines recent developments in the role of general hospitals in providing treatment for alcoholism. It employs data on 5,000 U.S. short-term general hospitals and on all patients discharged from a subsample of 400 of these hospitals in the years 1980 through 1985. The article describes the growth in alcoholism treatment resources in short-term hospitals (1980-85) and examines linked hospital and patient data for the 400 hospitals in the subsample to describe patient diagnoses and resource use (1980 and 1985). Patients are classified by the stage of their alcohol problem, and hospital use is examined for patients in different stages.

Alcohol Withdrawal Delirium↗
PubMed1988

cDNA cloning and expression of murine macrophage colony-stimulating factor from L929 cells.

A 4-kilobase and a 2-kilobase cDNA clone encoding a murine macrophage colony-stimulating factor have been isolated. Except for 2 amino acid residue differences, these two clones encode the same 520 amino acid residue protein, which is preceded by a 32-amino acid residue signal peptide. The two clones, whose molecular masses correspond to the two transcripts observed in murine L929 fibroblasts, contain 3' untranslated regions that are markedly different in sequence and length. Both clones can be expressed in COS cells and the recombinant protein is active in a mouse bone marrow colony assay.

Amino Acid Sequence↗
PubMed1987

Human CSF-1: gene structure and alternative splicing of mRNA precursors.

Bone marrow progenitor cells differentiate into mononuclear phagocytes in the presence of colony stimulating factor-1 (CSF-1). Characterization of the human CSF-1 gene shows that it contains 10 exons and 9 introns, which span 20 kb. Analysis of multiple CSF-1 transcripts demonstrates that alternate use of exon 6 splice acceptor sites and 3' noncoding sequence exons occurs. These alternatively spliced transcripts can encode either a 224 or a 522 amino acid CSF-1. Implications of differential splicing for the production and function of CSF-1 are discussed.

Amino Acid Sequence↗