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Biomedical subjects

M A Kane

Publications and source records attributed to M A Kane.

At least 19 recordsLinked to original sources
PubMed1992

Urinary levels of bombesin-like peptides in asymptomatic cigarette smokers: a potential risk marker for smoking-related diseases.

Bombesin-like peptides (BLP) produced by pulmonary neuroendocrine cells have many physiological actions which are relevant to the pathobiology of cigarette smoking. The objectives of this study were to determine whether cigarette smokers excrete increased levels of BLP in their urine compared with nonsmokers, to determine the relationship between BLP levels in urine and bronchoalveolar lavage (BAL) fluid, and whether urinary BLP levels are merely a reflection of exposure to cigarette smoke. Simultaneous BAL fluid and urine samples were obtained from ten clinically normal smokers and 22 normal nonsmoker volunteers. Urine samples were also obtained from 39 normal smokers and 30 normal nonsmokers who did not have BAL performed. BLP levels were measured in urine and BAL fluid using an enzyme-linked immunoassay. Expired air content of carbon monoxide, which reflects recent exposure to cigarette smoke, was determined in 34 of the clinically normal smokers and correlated with urinary BLP levels. We found that, in addition to having increased BLP levels in BAL fluid (P = 0.04), asymptomatic cigarette smokers also have increased BLP levels in their urine compared with normal nonsmokers (P = 0.007). Of note, a subgroup of smokers have markedly increased BLP levels which do not overlap with the nonsmokers. Urinary BLP levels correlated with expired air content of carbon monoxide (r = 0.49, P less than 0.01). However, not all smokers with increased expired air content of carbon monoxide exhibited increased BLP levels. Finally, all smokers with detectable BLP levels in BAL fluid had detectable urinary BLP levels, and there was a positive correlation between BLP levels in urine and BAL fluid (r = 0.625, P less than 0.001). We conclude that a subgroup of asymptomatic cigarette smokers exhibited increased BLP levels, measurable in both urine and BAL fluid, which precede the onset of clinically detectable disease and which are not strictly dependent on smoking intensity. We speculate that smokers with increased BLP levels may have a greater risk for smoking-related diseases.

Biomarkers↗
PubMed1992

Perspectives on the control of hepatitis A by vaccination.

The availability of an inactivated hepatitis A virus (HAV) vaccine, and the development of live attenuated virus vaccines against hepatitis represent great advances in the effort to control an important cause of viral hepatitis. There are a number of ways hepatitis A vaccines could be used, depending on the epidemiology of HAV infection in the country concerned, the cost of the product, the duration of protection that the vaccine affords and its effectiveness for postexposure prophylaxis. Expert groups could recommend vaccine to individuals who are at higher risk of exposure to hepatitis A as a result of behaviour, lifestyle or occupation, or to all infants and/or adolescents. The major public health problem with hepatitis A occurs in developing countries and regions with 'transitional economies' such as Eastern Europe and certain Middle Eastern countries. These countries have high levels of viral circulation, large cohorts of susceptible older children and adults, and high rates of HAV morbidity. Given the experience with hepatitis B vaccine and the economic and political realities of global immunization policy, it is unlikely that the Expanded Programme on Immunization and traditional vaccine donors will take a great interest in HAV vaccine in the near future. Individual countries may, however, decide to use hepatitis A vaccine on a widespread basis. Model cost effectiveness studies are needed for both developing and developed countries to help decide the feasibility of such widespread use. WHO has been involved in activities relevant to hepatitis A vaccine for many years.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗
PubMed1991

Isolation of the bombesin/gastrin-releasing peptide receptor from human small cell lung carcinoma NCI-H345 cells.

Purification of the gastrin-releasing peptide (GRP) or bombesin receptor has proved elusive in part due to technical difficulties. In the present studies, the problem of oxidized radioligand was avoided by the use of 125I-GRP, which was verified to be not oxidized by high performance liquid chromatography. Specific 125I-GRP binding (at 0 degrees C) to intact human small cell lung carcinoma NCI-H345 cells which had been subjected to a dilute acid wash was 6 fmol/10(6) cells. Inhibition of GRP degradation by human H345 cell membranes through the use of phenanthroline or phosphoramidon permitted the development of binding assays for the GRP receptor in detergent-solubilized crude membrane preparations. The solubilized GRP receptor exhibited saturable, high affinity (KD = 1.3 nM), temperature-dependent specific binding averaging 402 +/- 65 fmol/mg protein (mean +/- S.E. for eight separate membrane preparations with 125I-GRP concentration = 3 nM), with a Bmax = 434 fmol/mg protein using a gel filtration binding assay. That the GRP receptor had been solubilized was demonstrated by its failure to pellet when centrifuged at 100,000 x g for 60 min, its passage through a 0.22-micron filter without loss of binding activity, and its elution in the void volume of a Sephadex G-50 gel filtration column, but within the inclusion volume of a Sephacryl S-200 column (Ve/V0 = 1.1). Isolation of the GRP receptor from human H345 cell-solubilized membranes was achieved by ligand affinity chromatography. A unique 70-kDa band on silver-stained reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis was reproducibly eluted from GRP14-27 affinity columns by an acidic high salt buffer, but binding activity was denatured by these conditions. The protein nature of the GRP receptor was demonstrated by its sensitivity to proteases after isolation. In addition, two unique bands of 65 and 70 kDa were eluted from the GRP14-27 affinity column with GRP14-27 in neutral buffer, and this eluate possessed specific 125I-GRP binding with a stoichiometry of approximately 1:1. Thus, reported here is the isolation of a functional membrane-associated, saturable, high affinity GRP receptor with temperature-dependent binding from the solubilized membranes of human H345 cells.

Bombesin↗
PubMed1991

Growth factors in lung cancer: possible etiologic role and clinical target.

Growth factors play an important role in the pathogenesis and progression of all histologic types of lung cancer. Ideas for the exploitation of growth factors in lung cancer management are growing. The inhibition of the interaction between growth factors and their receptors, utilization of negative growth factors, interruption of the signal transduction pathways, or effecting decreased growth factor and/or receptor expression, could result in cell death, and all seem logical possibilities for new and specific treatment approaches. There can be no question that observations of the abnormal expression of growth factors have made a startling impact in every aspect of cancer research. The elucidation of their role in cell proliferation, coupled with our growing knowledge of the functions of oncogenes, has given birth to a unifying concept for the etiology of malignant transformation, which hopefully will translate into new, less toxic, more effective, and desperately needed lung cancer treatment.

Amino Acid Sequence↗
PubMed1991

Transesophageal color Doppler echocardiography of the normal St. Jude Medical mitral valve prosthesis.

Transesophageal color flow Doppler findings are reported in 36 patients with a St. Jude Medical mechanical mitral valve prosthesis who had no auscultatory evidence for prosthetic valve dysfunction. Multiple jets consistent with mitral regurgitation originating from the central and lateral portion of the prosthesis were found in all patients. Maximum jet length ranged from 11 to 51 mm (mean 21 +/- 9 mm). Maximum jet area ranged from 0.2 to 4.1 cm3 (mean 1.2 +/- 0.9 cm2). The color M-mode Doppler interrogation showed two distinct components of the regurgitant jet: brief early systolic flow consistent with valve closure followed by holosystolic regurgitant flow consistent with transvalvular leakage. Four patients (11%) had a maximum regurgitant jet length exceeding 30 mm and absence of early systolic closure regurgitant flow by M-mode color imaging, suggesting clinically silent paravalvular leakage. Two pin-sized paravalvular suture line defects were confirmed in one patient at cardiac transplantation. We conclude that transesophageal echocardiography is a highly sensitive method for detection of mitral regurgitation in the St. Jude Medical mitral prosthesis. Clinically silent paravalvular leakage should be suspected if the maximum jet length exceeds 30 mm and color M-mode interrogation fails to demonstrate an early systolic closure regurgitant flow component.

Echocardiography, Doppler↗
PubMed1991

Cost-effectiveness of hepatitis-B vaccine in Greece. A country of intermediate HBV endemicity.

We evaluated the cost-effectiveness of (a) a vaccination program for the prevention of hepatitis B; and (b) the two commercially available vaccines (Merck Sharp and Dohme; Pasteur Institute) in Greece, a country of intermediate endemicity. We examined cases of hepatitis-B infection prevented and the expected medical costs among the high-risk groups of medical and nursing students, hospital personnel, and the general population. Employing a vaccination program reduces considerably the risk of infection, especially in the high-risk groups, while it increases the total cost. The vaccines are very comparable in terms of both health and economic outcomes. Sensitivity analysis indicated that vaccine cost, incidence of hepatitis B, and compliance were the key factors for the choice of (a) whether to undertake an extensive program to prevent hepatitis-B infection and its chronic sequelae; and (b) which vaccine to administer.

Adult↗
PubMed1991

Transmission of HIV, hepatitis B virus, and other bloodborne pathogens in health care settings: a review of risk factors and guidelines for prevention. World Health Organization.

Recent reports of the transmission of human immunodeficiency virus (HIV) in health care settings have caused considerable public health concern. HIV as well as hepatitis B virus (HBV) and other bloodborne pathogens do constitute infectious hazards in certain settings. Transmission has been reported from patient to patient, patient to health care workers, and rarely, from health care worker to patient. Although the risk of bloodborne pathogen transmission is largely preventable, it may occur due to the use of infected blood for transfusion, the use of improperly sterilized medical or dental equipment, and accidental punctures with contaminated instruments. The risk of transmission of bloodborne pathogens is dependent on a number of factors and appears to be greater for HBV than for HIV. General guidelines for the prevention of transmission in health care settings are given, including the concept of "universal precautions", the need for adequate supplies of sterile equipment, the reduction of unnecessary injections and transfusions, and the appropriate use of hepatitis B vaccine. In addition, areas for research are highlighted that could improve understanding of transmission risks in different health situations and provide the information necessary to develop more effective measures to protect both care providers and patients.

Cross Infection↗
PubMed1990

Development of recommendations for control of hepatitis B virus infections: the role of cost analysis.

Hepatitis B (HBV) infection produces a number of acute and chronic consequences including fulminant hepatitis, chronic liver disease and cirrhosis. The development of safe and effective hepatitis B vaccines has led to the development of several prevention strategies based on the endemicity and primary age of infection in the population. In areas of high endemicity of infection, universal immunization of infants has been advocated and appears feasible. However, in areas of low endemicity of infection, selected high risk group immunization of adults has been recommended but has not been successful in changing infection rates. In 1981, an analysis of the economic consequences of acute and chronic HBV-related liver disease showed an expenditure of at least US$197 million for direct medical costs and US$126 million for the associated cost of work-loss. These results suggest the more widespread use of hepatitis B vaccine to prevent these high health-related costs.

Chronic Disease↗
PubMed1990

Medical oncology in a sophomore medical student pathophysiology course.

At the University of Colorado School of Medicine, a Medical Oncology unit was first included in the Sophomore Medical Student Pathophysiology Course (MED 6000) in the academic year 1985-1986. Cancer education is important in the preclinical curriculum, because medical students and physicians in most specialties will encounter a significant number of patients with cancer, the second leading cause of death in the United States. Described here is the development of the Medical Oncology unit in MED 6000, how both the mechanics and objectives of the course have changed, and how these changes have affected the student evaluation of the course.

Colorado↗
PubMed1990

Increased pulmonary neuroendocrine cells with bombesin-like immunoreactivity in adult patients with eosinophilic granuloma.

Cigarette smoking is associated with hyperplasia of pulmonary neuroendocrine cells and variably increased levels of bombesin-like peptides in the lower respiratory tract. Because the neuropeptide bombesin is a chemoattractant for monocytes and a mitogen for 3T3 fibroblasts, we hypothesized that an excess of neuroendocrine cells and bombesin-like peptides could contribute to lung inflammation and fibrosis in certain cigarette smokers. Eosinophilic granuloma is a fibrotic lung disease of unknown etiology that in adults occurs almost invariably in cigarette smokers. We quantitated neuroendocrine cells with bombesin-like immunoreactivity in open lung biopsies from patients with eosinophilic granuloma (n = 6) and compared these with cigarette smokers (n = 6) who underwent lung resection for reasons other than primary lung disease. In addition, we compared them with patients with idiopathic pulmonary fibrosis (n = 8), a disease not associated with cigarette smoking. Finally, we also examined the mitogenic effect of bombesin on cultured human adult lung fibroblasts. The patients with eosinophilic granuloma exhibited a 10-fold increase in neuroendocrine cells with bombesin-like immunoreactivity compared to both smokers (P = 0.005) and patients with idiopathic pulmonary fibrosis (P = 0.005). In addition, bombesin produced a significant mitogenic effect on cultured human adult lung fibroblasts at concentrations of 1 nM and above. We conclude that increased numbers of pulmonary neuroendocrine cells with bombesin-like immunoreactivity are commonly found in patients with eosinophilic granuloma and, since bombesin-like peptides are chemotactic for monocytes and mitogenic for human lung fibroblasts, we speculate that neuroendocrine cell hyperplasia may be important in the pathogenesis of eosinophilic granuloma in adult cigarette smokers.

Adult↗
PubMed1989

Hepatitis B virus infection among children born in the United States to Southeast Asian refugees.

Since 1975 nearly 1 million persons have entered the United States from Southeast Asia, where infection with hepatitis B virus (HBV) is hyperendemic. To evaluate the prevalence and patterns of transmission of HBV infection among the children of refugees from Southeast Asia, we studied 196 refugee families with 257 children born in the United States. Of 31 children born in the United States to mothers with infectious disease, 17 (55 percent) had been infected with HBV. Of 226 children whose mothers did not have infectious disease, 15 had HBV infection--a prevalence of 6.6 percent (95 percent confidence interval, 4.1 to 10.7). The risk of infection was greatest (26 percent) among children living in households with children with infectious disease (relative risk, 5.5; confidence interval, 2.3 to 13.4). Exposure to fathers or other adults with infectious disease was not significantly associated with infection. Of children from households with no persons with infectious disease, 3.9 percent (confidence interval, 1.7 to 8.8) were infected. Nearly half (46 percent) the cases of HBV infection among the U.S.-born children of refugees were not attributable to perinatal transmission from a mother with infectious disease. We conclude that child-to-child transmission may be occurring within and between households. Current recommendations to immunize the newborns of mothers with infectious disease are not sufficient to protect all U.S.-born children of Southeast Asian refugees from HBV infection early in life, when the risk of chronic sequelae and premature death is highest. We recommend that the HBV vaccination policy be expanded to include all newborns of Southeast Asian immigrants.

Asia, Southeastern↗
PubMed1989

Hepatitis B infection in the United States. Recent trends and future strategies for control.

Viral hepatitis is the second most common reportable infectious disease in the United States, with hepatitis B accounting for about 45 percent of cases. Although approximately 25,000 cases of hepatitis B are reported to the Centers for Disease Control each year, it is estimated that there are actually about 300,000 annual infections (up from 200,000 in the early 1980s). This increase has occurred despite the availability of a safe and effective hepatitis B vaccine since 1982. Hepatitis B occurs primarily in young adults because of lifestyle or occupationally related exposure. Reported cases in homosexual men have decreased, probably because of changes in behavior related to the acquired immunodeficiency syndrome epidemic. Cases due to heterosexual transmission and intravenous drug use are increasing. The proportion of cases in health care workers has decreased, possibly because 30 to 40 percent of high-risk health care workers have been vaccinated. Because of the increase in hepatitis B infection, the strategy of controlling this disease by vaccinating high-risk groups must be reconsidered. Alternative strategies include selective or universal immunization of infants or adolescents. Although integrating hepatitis B vaccine into infant immunization programs takes advantage of the existing system, it would not lead to measurable disease reduction for two decades. Immunizing adolescents would more rapidly reduce the incidence of hepatitis B, but currently no structured health care setting reaches them.

Diagnosis, Differential↗
PubMed1989

Folate (pteroylglutamate) uptake in human red blood cells, erythroid precursors and KB cells at high extracellular folate concentrations. Evidence against a role for specific folate-binding and transport proteins.

Membrane-associated folate (pteroylglutamate, PteGlu)-binding proteins (FBPs) play an important role as PteGlu-transport proteins in malignant and normal human cells. Since high extracellular folate (PteGlu) concentrations (EFC) profoundly influenced uptake and toxicity of the anti-PteGlu methotrexate in malignant KB cells, we studied human cells to determine additional mechanisms for PteGlu uptake when the EFC was varied. At low EFC (less than 10 nM), the predominant mechanism for folate uptake in mature erythrocytes was through binding to externally oriented FBPs which were quantitatively insignificant (4-6 orders of magnitude lower) and of no apparent physiological relevance when compared with KB cells. However, the predominant mechanism of PteGlu accumulation at high EFC [10-250 nM] in intact erythrocytes and sealed right-side-out (RSO) ghosts was not FBP-mediated and non-specific. This conclusion was based on the findings that radiolabelled PteGlu uptake: (i) continued even in the presence of a 1000-fold excess of unlabelled PteGlu and was linear and not saturable up to 250 nM; (ii) was two-fold higher at pH 4.5 than 7.5; (iii) was less than 2-fold increased at 37 degrees C compared with 4 degrees C; and (iv) was unaffected after trypsin-mediated proteolysis of greater than 75% FBPs. The [3H]PteGlu and 125I-PteGlu (histamine derivative) accumulated intracellularly through the non-specific PteGlu-uptake mechanism was unaltered biochemically and in a soluble compartment. Raising the EFC 500-fold higher than controls during erythropoiesis in vitro resulted in reversal of the expected anti-(placental folate-receptor)-antiserum-induced megaloblastic changes in orthochromatic normoblasts derived from burst-forming unit-erythroid colonies. Furthermore, at EFC greater than 0.1 microM, KB-cell accumulation of [3H]PteGlu was also predominantly through a mechanism that did not involve specific FBPs. Thus, at high EFC, a major component of PteGlu transport in human cells is not mediated through FBPs and is likely to be a passive diffusion process.

Carrier Proteins↗
PubMed1989

Hepatitis D virus infection in Illinois state facilities for the developmentally disabled. Epidemiology and clinical manifestations.

OBJECTIVE: To define the epidemiology and clinical manifestations of hepatitis D virus infection in an institutionalized population. DESIGN: A case-control study of hepatitis B carriers with and without serologic evidence of hepatitis D virus infection. Demographic, institutional, and medical data were obtained through questionnaires and chart review. Clinical status was assessed by liver function assays. SETTING: Thirteen Illinois state facilities for the developmentally disabled. PARTICIPANTS: Clients (238) who were hepatitis B carriers. RESULTS: Antibody to hepatitis D virus (anti-HDV) was detected in 71 of 238 (30%) hepatitis B carriers. Nine of thirteen facilities housed positive clients. Previous residence at one facility, designated B, was the strongest correlate of anti-HDV positivity; 85% of positive persons had lived there compared with 16% of negative controls (odds ratio 28.3 [95% CI, 13.2 to 60.7], P less than 0.001). Past hepatitis episodes were more common among anti-HDV-positive clients (37% compared with 7%) (odds ratio, 7.5 [95% CI, 3.0 to 19.1], P less than 0.001) and occurred mainly at facility B from 1950 to 1975. Liver function tests were infrequently abnormal among anti-HDV-positive clients. CONCLUSIONS: Results show widespread hepatitis D virus infection in our institutionalized population and suggest that transmission occurred mainly in the past at the overcrowded facility B. The low prevalence of laboratory evidence of chronic liver disease in the anti-HDV-positive clients may be explained by increased mortality among those originally infected from 1950 to 1975.

Acute Disease↗
PubMed1989

Hepatitis B virus transmission between children in day care.

We investigated two situations involving hepatitis B virus exposure among children in day care. In the first a 4-year-old boy who attended a day care center developed acute hepatitis B; another child at the center, who had a history of aggressive behavior (biting/scratching), was subsequently found to be a hepatitis B carrier. No other source of infection among family and other contacts was identified and no other persons at the center became infected. In the second situation a 4-year-old boy with frequently bleeding eczematous lesions was discovered to be a hepatitis B carrier after having attended a day care center for 17 months. Testing of contacts at the center revealed no transmission to other children or staff (representing 887 person months of exposure). Nationwide surveillance data showed that for the period 1983 to 1987, 161 children 1 to 4 years of age were reported with acute hepatitis B. After children with known hepatitis B risk factors were excluded, 25% (7 of 28) of children with known day care status were reported as day care attendees, a percentage comparable to national estimates of day care attendance by this age group. This is the first reported case of hepatitis B virus transmission between children in day care in the United States. Although it appears that day care transmission of hepatitis B is infrequent, further studies are needed to define the risk more accurately.

Adult↗
PubMed1989

Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers.

Bombesin-related peptides are growth factors for a variety of cells, including normal human bronchial epithelial cells. An ELISA for bombesin-like peptides (BLP) has been devised using the MAb BBC353, which is specific for the biologically active carboxy-terminal fragment shared by all known BLP. Using this ELISA, we measured bronchoalveolar lavage (BAL) fluid levels of BLP in normal cigarette smokers (n = 15) and normal nonsmokers (n = 18). Smokers' BAL fluid contained increased levels of BLP, whether expressed in terms of BAL fluid volume (P = 0.0001) or protein content (P less than 0.05). BLP levels did not correlate with any cellular constituent in the BAL fluid but immunostaining of lung tissue with BBC353 revealed an intense specific staining of neuroendocrine cells, implying these as a potential source. Two peaks of bombesin-like immunoreactivity were purified using sequential reverse phase and gel filtration HPLC. Both BLP have apparent molecular weights similar to gastrin-releasing peptide on gel filtration HPLC analysis. However, the amino acid composition of these BLP is different from that of gastrin-releasing peptide or neuromedin B, the only known mammalian forms of BLP, suggesting either incomplete purification or novel peptides. Sequence analysis could not be performed due to blocking groups at the amino terminus of these peptides. Our data demonstrate that cigarette smoking is associated with increased levels of pulmonary BLP and imply a potential role for these neuropeptides in the lung's response to tobacco smoke.

Adult↗
PubMed1989

Role of folate binding proteins in folate metabolism.

The essential role of folates in cellular biochemistry is well established, but the nature of the participation by folate-binding proteins has been disputed. This review will define folate-binding proteins and distinguish them from low-affinity, nonspecific folate binders and folate-dependent intracellular enzymes. We outline changes in plasma folate-binding proteins in various clinical states, review their postulated functions, detail the biochemistry of mammalian soluble folate-binding proteins and their membrane-bound immunologically cross-reactive possible precursors, and present evidence that the latter proteins may function as the physiologic folate receptors and intracellular regulators of folate coenzyme availability.

Animals↗