Clinical evaluation of HB vaccine as a component of combination vaccines.
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Adult↗
Biomedical subjects
M A Kane
Publications and source records attributed to M A Kane.
Novel soluble, high-affinity gastrin-releasing peptide binding proteins in Swiss 3T3 fibroblasts.
Swiss 3T3 cells contained substantial amounts of soluble and specific [125I]GRP binders. Like the membrane-associated GRP receptor, they were of high affinity, saturable, bound to GRP(14-27) affinity gels, and exhibited specificity for GRP(14-27) binding. They differed in that acid or freezing destroyed specific binding, specific binding exhibited different time and temperature effects, no detergent was required for their solubilization, ammonium sulfate fractionation yielded different profiles, the M(rs) were lower, GRP(1-16) also blocked binding, and a polyclonal anti-GRP receptor antiserum did not bind on Western blots. The isolated, soluble GRP binding protein(s) rapidly degraded [125I]GRP. These soluble GRP binding proteins may play a role in the regulation of the mitogenic effects of GRP on these cells.
3T3 Cells↗
Serum melatonin levels in melanoma patients after repeated oral administration.
The goal of this study was to determine the effect of oral melatonin in divided doses on plasma melatonin levels in patients with metastatic melanoma. Hourly blood samples were obtained from five patients for 24 h prior to melatonin administration and for 24 h during oral administration of melatonin, 50 mg every 4 h. In two of the five patients, the expected nocturnal plasma melatonin peak was observed. Oral melatonin was well absorbed. Plasma melatonin levels exhibited six peaks and troughs, were two to four-fold higher during peaks than troughs, and remained more than 25 times higher than peak pretreatment melatonin levels, even during troughs. Divided oral doses of melatonin were well tolerated and maintained plasma melatonin levels 25-80 times higher than endogenous peak values.
Administration, Oral↗
Novel bombesin-like peptide binding proteins from lung.
Gastrin-releasing peptide (GRP) and other bombesin-like peptides (BLP) play an important role in lung development, response to injury, and carcinogenesis. However, the mRNAs from previously cloned BLP receptors are not detectable on Northern blots of normal lung. The purpose of this study was to isolate and characterize BLP binding proteins from normal mouse lung. Soluble cytoplasmic and detergent-solubilized membrane fractions were prepared from mouse lung and evaluated for specific 125I-GRP binding. Unexpectedly, not only the solubilized membrane but also the soluble cytoplasmic fractions demonstrated saturable, high-affinity, specific GRP binding activity with Kd = 1.6 nM, Bmax = 135 fmol/mg protein and Kd = 7.5 nM, Bmax = 323 fmol/mg protein, respectively. BLP binding proteins were isolated using GRP14-27 affinity chromatography and analyzed by SDS-PAGE. In each fraction, a major unique band of approximate M(r) = 70 kD was obtained and flanked by two weaker bands of approximate M(r) = 65 and 75 kD. Preincubating samples of the cytoplasmic fraction with various neuropeptides demonstrated specificity in that only incubation with GRP14-27, the bioactive portion of the molecule, blocked affinity purification of these BLP binding proteins. The BLP binding proteins isolated from the cytoplasmic fraction were purified by HPLC, digested with trypsin, and sequenced via Edman degradation. These BLP binding proteins yielded peptides with the sequences IXGIYTDGQNTPXG and RAIMVEXXSEAXXSLLTP, both of which are unique compared with the GenBank/EMBL data base.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Effect of a hepatitis B vaccination program on the prevalence of hepatitis B virus infection.
In April 1991, surveys for serologic evidence of hepatitis B virus (HBV) infection were conducted among 3- to 4-year-old children born after a hepatitis B immunization program of newborns began and among 6- to 11-year-old children targeted for early childhood vaccination in American Samoa. Compared with 3- to 4-year-olds tested in 1991, children tested at baseline in 1985 were more likely to have been infected with HBV (5/40 vs. 2/93; prevalence ratio [PR] = 5.8, 95% confidence limits [CL] = 1.2, 28.7) and to have chronic infection with HBV (3/40 vs. 0/95; PR = undefined, lower CL = 1.2). Compared with 6- to 11-year-olds tested in 1991, children in 1985 were more likely to have been infected with HBV (32/121 vs. 53/386; PR = 1.9, CL = 1.3, 2.8) and to have chronic infection with HBV (8/121 vs. 7/386; PR = 3.6, CL = 1.3, 9.8). The incorporation of hepatitis B vaccine into routine childhood vaccination schedules can prevent acute and chronic HBV infection in areas of high endemicity.
Child↗
Melatonin interactions with cultured murine B16 melanoma cells.
Both in vitro and in vivo observations have suggested that melatonin modulates malignant cell growth. The present studies aimed to characterize the interactions of melatonin with cultured murine B16 melanoma cells. Time- and temperature-dependent specific melatonin accumulation by B16 murine melanoma cells was observed. B16 cells possessed a high affinity binding site (KD = 1.4 nM) which exhibited structural specificity in its affinity for analogues of melatonin (melatonin > 6-hydroxymelatonin = N-acetyl-5-hydroxytryptamine > 5-methoxytryptamine >> 5-hydroxytryptamine). Evidence for a lower affinity uptake system without structural specificity was also observed. Ninety-five per cent of the specific cell-associated melatonin in B16 cells was present in the soluble subcellular fraction of lysed cells; more than 97% of the cell-associated radioactivity was authentic melatonin. When the solubilized cell extracts from the binding assay were analysed by gel filtration immediately, all of the bound counts eluted at the void volume. Continuous exposure to melatonin for 48-120 h did not affect B16 cell proliferation as determined by cell counts, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay or [3H]thymidine incorporation. After 8-h pulse exposures to melatonin daily for 3 days, a 15% stimulation of B16 cell proliferation (p < 0.02) was observed at melatonin concentrations of 0.1 and 1 nM. The anti-oestrogen, tamoxifen, inhibited B16 cell growth and increased specific melatonin accumulation by B16 cells at 1 x 10(-6) M (p < 0.02). Cultured B16 murine melanoma cells possessed a specific, high affinity uptake system for melatonin which appeared to be altered by anti-oestrogen exposure.
Animals↗
Progress on the control of hepatitis B infection through immunisation.
Hepatitis B virus (HBV) infection and its sequelae, one of the major diseases of mankind, is now a disease preventable by vaccine. During the last few years, the price of these vaccines has fallen to the point where widespread use in infant immunisation programmes is feasible. This paper reports the great progress that has been made in the control of HBV infection and describes the targets that must be met if HBV control on a global basis is to be achieved.
Cost-Benefit Analysis↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Prospects for the introduction of hepatitis A vaccine into public health use.
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Hepatitis A↗