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Biomedical subjects

N E Hall

Publications and source records attributed to N E Hall.

16 recordsLinked to original sources
PubMed1999

Disulfide bond structure and N-glycosylation sites of the extracellular domain of the human interleukin-6 receptor.

The high affinity interleukin-6 (IL-6) receptor is a hexameric complex consisting of two molecules each of IL-6, IL-6 receptor (IL-6R), and the high affinity converter and signaling molecule, gp130. The extracellular "soluble" part of the IL-6R (sIL-6R) consists of three domains: an amino-terminal Ig-like domain and two fibronectin-type III (FN III) domains. The two FN III domains comprise the cytokine-binding domain defined by a set of 4 conserved cysteine residues and a WSXWS sequence motif. Here, we have determined the disulfide structure of the human sIL-6R by peptide mapping in the absence and presence of reducing agent. Mass spectrometric analysis of these peptides revealed four disulfide bonds and two free cysteines. The disulfides Cys102-Cys113 and Cys146-Cys157 are consistent with known cytokine-binding domain motifs, and Cys28-Cys77 with known Ig superfamily domains. An unusual cysteine connectivity between Cys6-Cys174, which links the Ig-like and NH2-terminal FN III domains causing them to fold back onto each other, has not previously been observed among cytokine receptors. The two free cysteines (Cys192 and Cys258) were detected as cysteinyl-cysteines, although a small proportion of Cys258 was reactive with the alkylating agent 4-vinylpyridine. Of the four potential N-glycosylation sites, carbohydrate moieties were identified on Asn36, Asn74, and Asn202, but not on Asn226.

Amino Acid Sequence↗
PubMed1998

An automated method for discriminating aneugen- vs. clastogen-induced micronuclei.

A flow cytometric (FCM) procedure for quantitating micronucleated reticulocytes in mouse peripheral blood samples was evaluated for its ability to discriminate between aneugen- and clastogen-induced micronuclei (MN). In this experiment, BALB/c mice were injected with 0.9% saline, the model clastogen methyl methanesulfonate (100 mg/kg bw) or the aneugen vincristine (0.2 mg/kg bw). Peripheral blood samples were collected 48 hr after injection and were subsequently fixed and stained for flow cytometric analysis. The staining method utilized FITC-conjugated anti-CD71 to differentially label reticulocytes, and the nucleic acid dye propidium iodide to resolve erythrocyte populations with and without micronuclei. The frequency of micronucleated reticulocytes was determined by analyzing 10,000 total reticulocytes per blood sample. A second analysis was performed on each sample whereby the propidium iodide associated fluorescent signals of 250 MN were collected and graphed as a single-parameter histogram. The histogram statistic "median channel" was recorded for each sample and provided a quantitative description of MN distribution according to DNA content. Cumulatively, the results of this study suggest that 1) flow cytometry can be employed to measure the incidence of MN resulting from clastogenic or aneugenic activity, and 2) MN resulting from aneugens can be discriminated from those arising spontaneously or from clastogen treatment based on flow cytometric analysis of DNA content.

Animals↗
PubMed1997

Structure and mechanism of a sub-family of enzymes related to N-acetylneuraminate lyase.

We describe here a sub-family of enzymes related both structurally and functionally to N-acetylneuraminate lyase. Two members of this family (N-acetylneuraminate lyase and dihydrodipicolinate synthase) have known three-dimensional structures and we now proceed to show their structural and functional relationship to two further proteins, trans-o-hydroxybenzylidenepyruvate hydratase-aldolase and D-4-deoxy-5-oxoglucarate dehydratase. These enzymes are all thought to involve intermediate Schiff-base formation with their respective substrates. In order to understand the nature of this intermediate, we have determined the three-dimensional structure of N-acetylneuraminate lyase in complex with hydroxypyruvate (a product analogue) and in complex with one of its products (pyruvate). From these structures we deduce the presence of a closely similar Schiff-base forming motif in all members of the N-acetylneuraminate lyase sub-family. A fifth protein, MosA, is also confirmed to be a member of the sub-family although the involvement of an intermediate Schiff-base in its proposed reaction is unclear.

Amino Acid Sequence↗
PubMed1997

Developmental language disorders.

Developmental language disorders are among the most common disorders of childhood referred to the pediatric neurologist. This article presents an overview of developmental language disorders, a discussion of the definition of developmental language disorders, potential causal factors, and a description of possible subtypes of language disorders in children. The article concludes with a review of the pediatric neurologist's role in developmental language disorders and recommendations for assessment and management.

Child↗
PubMed1993

Relationship between language and fluency in children with developmental language disorders.

The present investigation addresses two primary hypotheses: (a) that a subset of children with developmental language disorders exhibits significantly more disfluencies than other children with language disorders and (b) that differences between the disfluent and nondisfluent groups observed in fluency may be related to differences in language deficits. Spontaneous language samples from 60 preschool children with developmental language disorders were analyzed for frequency and type of disfluencies. Comparisons of the frequency of disfluencies across subjects revealed that a subset of 10 subjects exhibited significantly more disfluencies than the other subjects with language disorders. Demographic, intelligence, and language variables were compared across the two groups to determine whether such factors could account for the differences in fluency. The subjects with greater percentages of disfluencies were found to be significantly older and demonstrated significantly higher scores on two standard measures of vocabulary. These findings were interpreted in light of two models of disfluencies: the neuropsycholinguistic (Perkins, Kent, & Curlee, 1991) and Demands and Capacities (Adams, 1990; Starkweather, 1987). This suggests that some children with language disorders are at risk for fluency breakdown because of dysynchronies in the development of lexical and syntactic aspects of language or as a result of mismathces between speaking demands and capacities.

Age Factors↗
PubMed1993

Clinical and research congruence in identifying children with specific language impairment.

This paper reports on the results of a large multicenter project designed to develop an empirically based classification of preschool children with language impairments. A clinically selected population of 252 children with specific language impairments (SLI) was used to evaluate the reliability, coverage, and usefulness of both standard clinical and research definitions of such children. Varying degrees of congruence were found between the clinically identified children with SLI and those identified as SLI using discrepancy, deficit, and standardized operational criteria. Such mismatch between the original clinical identification and more standardized operational criteria may be related to different clinical perspectives, professional training, and limited assessment measures. These results suggest that there is a significant gulf between the clinical diagnosis of children with specific language impairment and more standardized operational criteria. It is suggested that the global concept of a "specific language impairment" may not be a useful concept for either clinical or research activities.

Age Factors↗
PubMed1992

The validity of discrepancy criteria for identifying children with developmental language disorders.

Empirical data from two studies address the clinical validity of discrepancy criteria for identification of children with developmental language disorders (DLD). Study 1 involved 256 preschoolers clinically defined as DLD and meeting inclusionary criteria for normal hearing, intellectual, neurological, and psychiatric status. Application of alternative psychometrically derived discrepancy criteria identified only 40% to 60% of the clinically defined group as language disordered. Study 2 applied nonverbal IQ-language performance discrepancy criteria to 368 eight-year-old, randomly selected control subjects, resulting in over 45% of the controls being identified as DLD. Factors contributing to underidentification in Study 1 and over-identification in Study 2 are discussed, raising questions regarding the validity of discrepancy criteria for identification of DLD children.

Achievement↗
PubMed1992

Completeness of case ascertainment of the State Cancer Registry.

The authors evaluated the ability of the New Jersey State Cancer Registry to detect known cancer cases during an investigation of a cancer cluster occurring in professional football players. The Registry was found to be a valuable tool for the detection of cancer cases for New Jersey residents.

Adult↗
PubMed1991

Cancer by industry: analysis of a population-based cancer registry with an emphasis on blue-collar workers.

This paper uses information on occupation and industry routinely collected in a state-based cancer registry to assess potential associations between work place exposures and cancer incidence. Industry-specific proportional cancer incidence ratios (PCIR) were calculated by race and sex for all individuals and for white males with blue-collar occupations. Expected numbers of cancers were derived both from cancers occurring among all occupations and just among blue-collar occupations. This latter analysis was done as a control for differences in the prevalence of life-style habits between blue- and white-collar workers. Increased lung cancer PCIR were seen in most industries previously reported to be associated with lung cancer risk. The effects of socioeconomic status on these results are discussed. Other results include an increased ratio of melanoma in blue-collar white male rubber and plastic product workers, an increased ratio of non-Hodgkin's lymphomas in motor vehicle manufacture workers, and an increased PCIR of chronic lymphocytic leukemia in general construction workers. Uterine cancer was increased in proportion in white females for a number of industries including rubber and plastic product manufacture, apparel manufacture, and electrical equipment manufacture.

Humans↗
PubMed1986

Case-control study of decaffeinated coffee consumption and pancreatic cancer.

The relationship between decaffeinated coffee consumption and pancreatic cancer was examined using data from a hospital-based case-control study of individuals aged 20-80 years in 18 hospitals in 6 United States cities, from January 1981 to December 1984. Among the males, 127 cases and 371 controls were examined, while for females, the figures were 111 and 325 for cases and controls, respectively. Decaffeinated coffee use was not associated with an increased risk of pancreatic cancer in males (odds ratio = 0.7 for 3 or more cups/day; 95% confidence interval = 0.4-1.4). For females, an elevated risk was seen for drinkers of 1-2 cups/day (odds ratio = 1.6; 95% confidence interval = 1.0-2.7), but this finding was of borderline significance and elevation in risk was not found for drinkers of 3 or more cups/day (odds ratio = 0.9; 95% confidence interval = 0.4-1.9). Cigarette smoking was significantly associated with pancreatic cancer in both males and females. Factors examined and not found to be related to pancreatic cancer included education, occupation, religion, marital status, alcohol drinking, saccharin use, height, weight 5 years before hospitalization, history of previous diseases, and residence.

Adult↗
PubMed1985

A case-control study of diesel exhaust exposure and bladder cancer.

The relationship between bladder cancer and employment in occupations involving exposure to diesel exhaust was examined using data from a hospital-based case-control study of men aged 20 to 80 years in 18 hospitals in six U.S. cities, from January 1981 to May 1983. In this analysis, 194 cases and 582 controls were compared according to occupation, smoking history, alcohol and coffee consumption, and various demographic variables. No difference was found in the proportion of bladder cancer cases employed in occupations with exposure to diesel exhaust compared to controls. This relationship did not change after taking smoking habits into account. Bladder cancer cases were significantly more likely to be current smokers of cigarettes than were controls.

Adult↗
PubMed1984

Diesel exhaust exposure and lung cancer: a case--control study.

The presence of polyaromatic hydrocarbons in the particulate phase of diesel engine exhaust has raised questions concerning potential carcinogenicity of diesel exhaust exposure. A case-control study was conducted of 502 male lung cancer cases and 502 controls without tobacco-related diseases to investigate the association of occupational diesel exhaust exposure and lung cancer. Diesel exhaust exposure was appraised by job title. The results show no association between diesel exhaust exposure and risk of lung cancer. They do, however, show the strong association between smoking and lung cancer and as such highlight the importance of smoking information in studies of occupational effect on lung cancer risk.

Adult↗
PubMed1983

Epidemiology of coffee and pancreatic cancer.

The association between pancreatic cancer and putative risk factors was examined using 275 incident cases and 7994 controls interviewed in six United States cities for a major study of tobacco-related diseases. From the comparison population were excluded patients with other diseases postulated to be associated with pancreatic cancer (e.g., other pancreatic diseases and diseases of the gallbladder) and those admitted for disorders known to be associated with smoking. After carefully controlling for age, the data failed to indicate an association between coffee consumption and pancreatic cancer (odds ratio congruent to 1.0). This was true both before and after adjustment for cigarette smoking and in both males and females. There was a statistically significant association between pancreatic cancer and smoking in both males and females (odds ratio 3.0 for males who smoked more than 1.5 packs/day and 2.0 for females who smoked more than 1 pack/day).

Adult↗
PubMed1978

Sporulation competence in Aspergillus nidulans: a role for iron in development.

There is a difference in the response of DNA from mycelial extracts of Aspergillus nidulans to hot acid hydrolysis depending upon the state of sporulation competence. The DNA in incompetent culture mycelia is not hydrolyzable while the DNA in competent culture is hydrolyzable. The inhibition of DNA hydrolysis is due to the presence of iron. Although the concentration of iron decreases in mycelia during growth, there is sufficient iron present in competent mycelia to inhibit DNA hydrolysis. The change in DNA hydrolyzability may be the result of a change in intracellular iron distribution, or a change in an iron binding component. We suggest that these changes are related to the altered capacity for gene expression which occurs at the time of acquisition of sporulation competence.

Aspergillus nidulans↗