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Biomedical subjects

C M Nolan

Publications and source records attributed to C M Nolan.

At least 19 recordsLinked to original sources
PubMed1992

Long-range physical map of the Ly-6 complex: mapping the Ly-6 multigene family by field-inversion and two-dimensional gel electrophoresis.

The Ly-6 proteins are encoded by a recently identified multigene family. Much attention has been focused on these proteins because they may be involved in lymphocyte activation, and expression of some of them occurs at critical times in the differentiation of lymphocytes. These features make it important to investigate and to characterize further this family of molecules and the genes that encode them. To aid our investigation of these issues, we have constructed a physical map of the entire Ly-6 complex in the C57BL/6 murine genome using the combined techniques of field-inversion gel electrophoresis (FIGE), phage and cosmid genomic library screening, and two-dimensional DNA electrophoresis. This map spans approximately 1600 kb, and comparison of the FIGE map and cosmids indicates that most of the Ly-6 complex has been isolated in the cosmid clones.

Animals↗
PubMed1992

Failure of therapy for tuberculosis in human immunodeficiency virus infection.

Optimum treatment of tuberculosis in persons with human immunodeficiency virus (HIV) infection is still being defined. Tuberculosis treatment failure in an HIV-infected patient is described and 10 similar cases from the medical literature are reviewed to search for common patterns associated with an adverse outcome of therapy in this setting. Six patients were poorly compliant. In nine patients, the subsequent episode of tuberculosis was disseminated or extrapulmonary; in four the central nervous system was involved. In five patients, a problem with rifampin usage was encountered: Three had rifampin-resistant Mycobacterium tuberculosis, one experienced an adverse reaction to rifampin, leading to withdrawal from the regimen after 1 week, and one was receiving a drug that may interfere with rifampin's antimycobacterial effect. This case report and literature review suggest that particular attention should be directed toward ensuring that patients with HIV infection comply with treatment of tuberculosis. For the majority of patients, the already stretched resources available for the treatment of tuberculosis and HIV infection should be devoted to compliance enhancement rather than to more prolonged or intensive drug regimens. However, it should be emphasized that patients with disseminated tuberculosis or central nervous system disease and those who are not able to receive rifampin because of drug resistance or an adverse reaction should be managed individually.

AIDS-Related Opportunistic Infections↗
PubMed1992

Results of a directly observed intermittent isoniazid preventive therapy program in a shelter for homeless men.

We offered directly supervised isoniazid preventive therapy to middle-aged and elderly men who were exposed to tuberculosis during an outbreak of cases at a homeless shelter. Isoniazid, 900 mg, was administered twice weekly to men at the shelter and at the downtown Public Health Clinic. We report on compliance and adverse reactions associated with this preventive regimen. Isoniazid preventive therapy was offered to 64 men. Forty-seven men (73%) began therapy, and 23 of them (49%) completed the 6- to 12-month regimen. Men who failed to complete isoniazid therapy received a median of 11 biweekly doses (range, 1 to 41 doses) over a median of 9 wk (range, 3 to 37 wk). The most common reason for incomplete treatment was that the men no longer frequented the shelter. One hepatotoxic reaction occurred, for a 2.1% cumulative incidence among all men who started therapy and a 3.7% cumulative incidence among the 27 known alcoholic men who began therapy. In addition, we sought to identify personal characteristics of the men that might be associated with noncompliance. Out-of-state location of personal contacts in case of emergency was strongly associated with poor compliance. These data provide some assurance that directly supervised isoniazid preventive therapy may be offered safely to sheltered elderly men with a high prevalence of alcoholism. Further improvements in compliance with isoniazid preventive therapy in homeless populations may depend on the development of a therapeutic regimen of only 2 to 3 months duration.

Aged↗
PubMed1992

The impact of human immunodeficiency virus infection on tuberculosis in young men in Seattle-King County, Washington.

We conducted a population-based case-control study to determine the magnitude of the excess risk of tuberculosis in those infected with the human immunodeficiency virus (HIV) in Seattle-King County, Washington. Patients were 39 of the 54 cases of tuberculosis in white and in black (including Hispanic) men aged 20 through 49 reported to the Seattle-King County Department of Public Health between January 1986 and June 1988. Controls were 34 white and black men of similar age who had tuberculin testing as a condition of employment. Eleven (28 percent) of the 39 patients with tuberculosis and 2 (6 percent) of the 34 controls tested positive for antibody to HIV (odds ratio adjusted for age and race = 6.2; 95 percent confidence interval 1.2 to 31.9). Calculation of the etiologic fashion indicated that 24 percent of the tuberculosis cases in this population of young black and white men were attributable to concurrent HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

An outbreak of soft-tissue infections due to Mycobacterium fortuitum associated with electromyography.

An outbreak of infections due to Mycobacterium fortuitum associated with electromyography (EMG) is described. During a 6-week period, six patients who received EMG at one facility developed soft-tissue infections manifested by slowly expanding suppurative nodules at sites of needle electrode insertion. M. fortuitum was isolated from five patients; four isolates that were evaluated further were M. fortuitum biovariant fortuitum. EMG procedures were done in one laboratory by one physician and assistant. Standard procedures included use of reusable needle electrodes disinfected with 2% glutaraldehyde and then rinsed with tap water. On recognition of the outbreak, the procedure was changed to include autoclaving of needle electrodes. Active surveillance for 1 year revealed no further cases. M. fortuitum could not be isolated from the laboratory, EMG equipment and reagents, or skin of the medical personnel. The outbreak demonstrates that nontuberculous mycobacterial infection may be associated with EMG.

Adult↗
PubMed1991

An outbreak of tuberculosis in a shelter for homeless men. A description of its evolution and control.

An outbreak of tuberculosis at a shelter for homeless men was studied in detail to further the understanding of the epidemiology of tuberculosis in this setting. The shelter provides evening accommodations for men aged 50 yr and older. The capacity is approximately 200 clients, and the client pool is approximately 1,000 men/yr. During a 6-wk period in December 1986 and January 1987, seven cases of tuberculosis were diagnosed in shelter clients. Nine cases were reported in clients during the preceding 12 months, and four cases in the year previous to that. The majority of outbreak cases were pulmonary tuberculosis, sputum smear positive. Drug resistance was rare. Phage typing of 15 Mycobacterium tuberculosis isolates revealed one predominant type and four other types. The goals of the control plan (and the steps taken to achieve them) were to render known infectious cases noninfectious (directly observed therapy); to find undiagnosed infectious cases (repetitive mass screenings); to protect exposed clients (repetitive tuberculin skin testing and isoniazid preventive therapy); and to make the shelter environment safe (exclude infectious, noncompliant clients and improve the shelter's ventilation system). Implementation of this plan rapidly terminated the outbreak; following the first mass screening in January 1987, at which six asymptomatic cases were detected, only five additional cases occurred in shelter clients during a 2-yr period of follow-up. The investigation suggested that the outbreak evolved during 1986 as a result of the presence at the shelter of an increasing number of men with undiagnosed infectious pulmonary tuberculosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗
PubMed1990

Binding of insulin-like growth factor II (IGF-II) by human cation-independent mannose 6-phosphate receptor/IGF-II receptor expressed in receptor-deficient mouse L cells.

Mouse L cells deficient in expression of the murine cation-independent mannose 6-phosphate receptor/insulin-like growth factor II receptor (CI-MPR/IGF-IIR) were stably transfected with a plasmid containing the cDNA for the human receptor. Transfected cells expressed high levels of the human receptor which functioned in the transport of lysosomal enzymes and was capable of binding 125I-IGF-II, both at the cell surface and intracellularly. Cell surface binding of 125I-IGF-II by the receptor could be inhibited by pretreatment of cells with antibodies to the receptor or by coincubation with the lysosomal enzyme, beta-glucuronidase. Expression of the receptor conferred on transfected cells the ability to internalize and degrade 125I-IGF-II. Cells transfected with the parental vector and those expressing the human CI-MRP/IGF-IIR were found to express an atypical binding site for IGF-II that was distinct from the CI-MPR/IGF-IIR and the type I IGF-receptor. The availability of two cell lines, one of which overexpresses the human CI-MPR/IGF-IIR and one deficient in expression of the murine receptor, may help in the analysis of the role of the receptor in mediating the biological effects of IGF-II. They should also be useful in examining the significance of binding of ligands, such as transforming growth factor-beta 1 precursor and proliferin to this receptor.

Animals↗
PubMed1989

Diphtheria among alcoholic urban adults. A decade of experience in Seattle.

Three outbreaks of Corynebacterium diphtheriae infection occurred in Seattle's Skid Road from 1972 through 1982. The first involved a single toxigenic, intermedius biotype clone, whereas the second and third outbreaks involved nontoxigenic mitis and gravis strains. Of 1100 total infections, 947 (86%) were cutaneous. The incidence was highest in winter and spring. In Skid Road, the estimated attack rate during 17 months in 1974 to 1975 was 5% for whites and 27% for native Americans. Streptococcus pyogenes was isolated from 73% of diphtheritic and 41% of nondiphtheritic skin lesions (P less than 0.001). Skin infection and environmental contamination by C. diphtheriae were correlated. Complications occurred in 21% of symptomatic nasopharyngeal and 3% of cutaneous toxigenic intermedius infections (P less than 0.001), and were significantly correlated with ages 60 years or more. Preferential use of erythromycin for diphtheria and pyodermas preceded plasmid-mediated resistance to erythromycin in C. diphtheriae. Diphtheria outbreaks in urban alcoholic persons are associated with poor hygiene, crowding, season, contaminated fomites, underlying skin disease, hyperendemic streptococcal pyoderma, and introduction of new strains from exogenous reservoirs.

Adult↗
PubMed1989

The use of sputum cultures in the evaluation of immigrants classified as tuberculosis suspects.

Because of possible deficiencies in the evaluation, based on symptoms and chest roentgenogram review, of new immigrants classified during the visa application process as tuberculosis suspects, a prospective (cohort) and a retrospective (case control) study were done to test the usefulness of routinely obtaining sputum specimens for culture in that setting. In the prospective study, 249 consecutive classified immigrants who were considered on the basis of clinical and roentgenographic findings to have nonprogressive tuberculosis submitted at least two sputums for culture: 13 (5.2%) had at least one culture positive for M. tuberculosis. Immigrants younger than 50 yr of age and refugees from Kampuchea and Laos had a fivefold to tenfold elevated risk of having a positive sputum culture. The cost per case detected of obtaining and processing sputum cultures was estimated to be +1,996 to +2,994. In the case-control study, 37 classified immigrants evaluated from 1981 through 1986 who had sputum cultures positive for M. tuberculosis even though they fulfilled clinical and roentgenographic criteria for nonprogressive tuberculosis served as control subjects. Several demographic, clinical, and roentgenographic factors were associated with an increased risk of being culture-positive: age younger than 50 yr, a positive tuberculin test, report of a cough, and a cavitary lesion on chest roentgenogram. The history of prior receipt of antituberculosis drugs was associated with having a negative culture, including a marked dose-response effect.

Asia, Southeastern↗
PubMed1988

Expression of human cation-independent mannose 6-phosphate receptor cDNA in receptor-negative mouse P388D1 cells following gene transfer.

We recently reported the cDNA cloning, sequence, and expression of the human cation-independent mannose 6-phosphate receptor (hCI-MPR) (Oshima, A., Nolan, C. M., Kyle, J. W., Grubb, J. H., and Sly, W. S. (1988) J. Biol. Chem. 263, 2553-2562). The sequence of the hCI-MPR was virtually identical to that of the human insulin-like growth factor II receptor cDNA (Morgan, D. O., Edman, J. C., Standring, D. N., Fried, V. A., Smith, M. C., Roth, R. A., and Rutter, W. J. (1987) Nature 329, 301-307). To test the role of the putative bifunctional receptor in intracellular sorting of acid hydrolases, we studied its effect on lysosomal enzyme transport following gene transfer to receptor-negative cells. Receptor-negative mouse P388D1 cells were transfected with a cDNA construct containing the entire coding sequence of hCI-MPR under the control of the mouse metallothionine I promoter. Stable transformants were isolated and characterized. The expressed hCI-MPR was localized in membranes including the plasma membrane, bound mannose 6-phosphate containing ligands, and mediated endocytosis which could be specifically blocked by mannose 6-phosphate. We next measured the effect of the expressed hCI-MPR on intracellular and secreted acid hydrolases. The intracellular activity of the lysosomal marker enzymes beta-glucuronidase and beta-hexosaminidase increased up to 2-fold following transformation. In addition, expression of the receptor greatly reduced the fraction of acid hydrolases secreted. These phenotypic changes in the transformed cell lines support the proposed role of the cation-independent mannose 6-phosphate receptor in intracellular sorting and targeting of lysosomal enzymes.

Animals↗
PubMed1988

The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells.

We have cloned and sequenced the full-length cDNA for the human cation-independent mannose 6-phosphate receptor from four overlapping clones. The 9104-nucleotide sequence contains 7473 nucleotides which encode a protein of 2491 amino acids. The amino acid sequence includes a putative signal sequence of 40 amino acids, an extracytoplasmic domain consisting of 15 homologous repeat sequences of 134-167 amino acids, a transmembrane region of 23 amino acids, and a cytoplasmic domain of 164 amino acids. The predicted molecular size is greater than 270 kDa. Repeats 7-15 of the extracytoplasmic domain of the human receptor are highly homologous with the sequence recently reported for the partial cDNA for the bovine receptor (Lobel, P., Dahms, N. M., Breitmeyer, J., Chirgwin, J. M., and Kornfeld, S. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 2233-2237). The nucleotide sequence for the full-length cDNA and the deduced amino acid sequence for the cation-independent mannose 6-phosphate receptor, which are reported here, are strikingly similar (99.8% identical at the nucleotide level and 99.4% identical at the amino acid level) to those recently reported for the human insulin-like growth factor II receptor from HepG2 hepatoma cells (Morgan, D. O., Edman, J.D., Standring, D. N., Fried, V. A., Smith, M. C., Roth, R. A., and Rutter, W. J. (1987) Nature 329, 301-307). These findings support the suggestion that the cation-independent mannose 6-phosphate receptor for lysosomal enzymes is a multifunctional binding protein which is identical with the insulin-like growth factor II receptor. A cDNA construct containing the full coding sequence for the cation-independent mannose 6-phosphate receptor in the expression vector pSVL was used to transfect COS cells. Expression of the cDNA in transfected COS cells produced a cell-surface protein which co-migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with authentic human receptor, bound to an affinity column and was specifically eluted with mannose 6-phosphate, mediated cell-surface binding and endocytosis of beta-glucuronidase, and targeted the endocytosed enzyme to lysosomes.

Amino Acid Sequence↗
PubMed1988

Tuberculosis in a cohort of Southeast Asian Refugees. A five-year surveillance study.

Morbidity caused by tuberculosis was determined in a cohort of 9,328 refugees from Southeast Asia during the first 5 yr after their immigration to the United States. The entire cohort was screened at the time of entry, and isoniazid preventive therapy was offered according to ATS-CDC guidelines. During the period of study, 25 cases of tuberculosis were reported from the cohort. The 5-yr cumulative incidence of tuberculosis (26.8 cases per 10,000 in the entire cohort) was greatest in tuberculin-positive refugees who had abnormal screening chest roentgenograms (324.3 cases per 10,000) and least in those with nonsignificant tuberculin reactions (5.0 cases per 10,000). The annual incidence of tuberculosis in the cohort decreased from an estimated 30.6 cases per 10,000 at the time of immigration to less than 5 cases per 10,000 during the fourth and fifth years. The prevalence of resistance to isoniazid was greater in culture-positive cases arising after immigration (7 of 22, 32%) than in those diagnosed at the time of immigration (5 of 36, 14%), probably because of a reduction in isoniazid-susceptible cases by isoniazid preventive therapy. Currently recommended screening and preventive services may be favorably impacting tuberculosis morbidity in newly arriving refugees from Southeast Asia.

Age Factors↗
PubMed1988

Intentional isoniazid overdosage in young Southeast Asian refugee women.

During a two-year period, from January 1984 through December 1985, six cases of intentional overdosage with isoniazid were reported in young Southeast Asian refugee women. The patients were aged 14 to 23 years, had all immigrated within one year and were receiving isoniazid preventive therapy for tuberculosis infection without disease. Clinically, all patients experienced generalized seizures, and three sustained moderate metabolic acidosis. All recovered uneventfully. Psychiatric evaluations revealed that two patients had major depression; two, adjustment disorders with depressed mood; and two, no psychiatric illness. The latter two patients and two others ingested an excessive amount of isoniazid immediately following an argument with a family member. Because tuberculosis infection is prevalent in refugees immigrating from Southeast Asia, isoniazid, given for six months to one year as preventive therapy, is one of the most frequently prescribed drugs during the early resettlement period. There may be an increased risk of intentional isoniazid overdosage during preventive therapy of young refugee women.

Adolescent↗
PubMed1988

Marketing strategies of nurse practitioners in New York State.

As competition within the health care field increases, marketing strategies are becoming more important for all members of the health care team, including nurse practitioners. The purpose of this research was to identify marketing strategies being used by nurse practitioners in New York state. A total of 285 practitioners responded to a survey containing questions related to marketing techniques traditionally used in the business world: service differentiation, market segmentation and practice promotion. A majority of respondents did not report using many of the marketing strategies contained in the survey, although most nurse practitioners did report identifying themselves as primary care providers in one-on-one interactions with clients. Significantly higher marketing scores were found for nurse practitioners who attended a workshop or seminar on marketing strategies, had three or more years of experience, or who practiced in private outpatient settings.

Adult↗
PubMed1987

Antibody to the phosphomannosyl receptor inhibits recycling of receptor in fibroblasts.

The 215-kd phosphomannosyl receptor is involved in the transport of newly synthesized acid hydrolases to lysosomes and also mediates the pinocytosis of lysosomal enzymes by fibroblasts in culture. Recycling of receptors to the sorting sites is an integral part of both these processes. In this report, we describe the inhibition in human fibroblasts of both functions of the phosphomannosyl receptor by a rabbit antiserum to the bovine liver receptor. This inhibition cannot be completely accounted for by inhibition of ligand-receptor interaction. Rather the antibody appears to cross-link receptors and cause a removal of receptors from the sorting sites (plasma membrane and Golgi apparatus) and their accumulation in a compartment from which they do not recycle. Removal of receptors from the recycling pool by antibody is irreversible, and return of receptors requires synthesis of new protein. Degradation of "trapped receptors" is enhanced (t1/2 = 7.5 hr), but much more gradual than their removal from the functional receptor pool (t1/2 = 30 min).

Animals↗
PubMed1987

Intracellular traffic of the mannose 6-phosphate receptor and its ligands.

The role of the mannose 6-phosphate recognition marker and the phosphomannosyl receptor in the intracellular transport of acid hydrolases is well established. Several details of the process, however, are presently unclear and warrant further investigation (Table 1). The development of in vitro systems for the reconstitution of receptor-mediated endocytosis and intracellular transport, together with the application of the techniques of molecular biology to this field, should lead to major advances in our understanding of the targeting of enzymes to lysosomes.

Animals↗