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Biomedical subjects

M A Kane

Publications and source records attributed to M A Kane.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Failure of gloves and other protective devices to prevent transmission of hepatitis B virus to oral surgeons.

A survey of 434 oral surgeons was conducted to examine risk factors for hepatitis B virus (HBV) infection. Overall, 112 (26%) of the participants demonstrated serologic evidence of past or current infection with HBV. Seropositivity was significantly associated with age, number of years in practice, and year of graduation from dental school but not with other variables examined, such as the number of patients seen annually or the number of patients seen who were at high risk of HBV infection. The strong correlation between years in practice and seropositivity was unaffected by reported use of gloves, face masks, or eye shields. The use of gloves and other protective devices does not appear to offer substantial protection against HBV exposure in oral surgeons, and all oral surgeons should receive HBV vaccine.

Adult↗

Influence on immunoreactive folate-binding proteins of extracellular folate concentration in cultured human cells.

The influence of extracellular folate concentration on cellular levels of the folate transport protein and its soluble product was studied directly in cultured human nasopharyngeal carcinoma (KB) cells. As determined by radioimmunoassay, levels of the folate transport protein and the soluble folate-binding protein were 58 +/- 17 (mean +/- SD) and 5 +/- 2 pmol/mg cell protein, respectively, in KB cells maintained in standard medium (containing 2,300 nM folic acid). These levels significantly increased to 182 +/- 34 and 26 +/- 6 pmol/mg cell protein, respectively, in KB cells serially passaged in low folate medium (containing 2-10 nM 5-methyltetrahydrofolate). Increases in folate-binding protein levels occurred more rapidly in KB cells serially passaged in very low folate medium containing less than 2 nM folate and were prevented by the addition of 100 nM 5-methyltetrahydrofolate or 0.1-1 microM 5-formyltetrahydrofolate to this medium. When KB cells which had been passaged in low folate medium were passaged back into either standard medium or low folate medium supplemented with reduced folates, the levels of both folate-binding proteins fell linearly towards the levels in KB cells continuously maintained in standard medium. The folate transport protein was identified in and underwent similar changes in human and mouse mammary tumor cells. These studies indicate that the folate transport system is probably regulated by the extracellular folate concentration through changes in intracellular metabolite levels.

Animals↗

Transmission of hepatitis B virus from adopted Asian children to their American families.

In 1985, 6,991 Asian children were adopted by Americans. To estimate the risk that such children may transmit hepatitis B virus to their adoptive families, we conducted a cumulative-incidence follow-up study in the State of Washington. We examined the association between having adopted a hepatitis B surface antigen (HBsAg)-seropositive Asian child and serologic evidence of past or present hepatitis B virus infection in adoptive family members. Seven (9 per cent) of 77 family members exposed to an HBsAg-seropositive child had evidence of past or present infection compared with four (2 per cent) of 232 nonexposed (relative risk = 5.3; 90% confidence limits [CL] = 2.0-13.9). The risk was higher for those with prolonged exposure and was entirely restricted to parents.

Adolescent↗

Immunization policies and vaccine coverage among adults. The risk for missed opportunities.

A substantial proportion of vaccine-preventable diseases occur among adults. Each year, there are more than 20,000 influenza-associated deaths during epidemics, approximately 40,000 deaths related to pneumococcal disease, and one to five cases of diphtheria. More than 300,000 hepatitis B infections occur annually, mostly in patients 15 to 29 years old. From 1982 to 1986, 96% of patients with tetanus were age 20 and older. Among young adults, 5% to 20% are susceptible to rubella and measles, and outbreaks occur where these persons congregate. Most adults are not immunized, despite recommendations for vaccines against these diseases. Vigorous efforts are needed to implement strategies to reduce disease incidence, morbidity, and death among adults.

Adult↗

Effect of intracellular folate concentration on the modulation of 5-fluorouracil cytotoxicity by the elevation of phosphoribosylpyrophosphate in cultured human KB cells.

The effects of extracellular folate concentration on intracellular folate and phosphoribosylpyrophosphate (PRPP) levels and the cytotoxicity of methotrexate and 5-fluorouracil were studied in human KB cells grown in fetal bovine serum-supplemented Eagle's minimum essential medium, which contained standard high folic acid levels (2.3 microM) (standard or S medium), or folic acid-free serum-supplemented medium containing approximately 4 nM 5-methyltetrahydrofolate (physiological or P medium), a folate level and form more comparable to that in normal human serum. Macrocytosis and prolongation of the doubling time by 150% were observed after 5-10 serial passes in P medium, but after 10-15 serial passes, KB cells became "adapted" to P medium with return of size and doubling time to values indistinguishable from cells maintained in S medium. Cellular folate levels fell, and marked elevations in PRPP levels from 68 +/- 43 to 642 +/- 287 pmol/mg cell protein (mean +/- SD) were observed as KB cells were serially passed through P medium. Human leukemia HL-60 and K562 cells and MJY-alpha mouse mammary tumor cells serially passed in P medium also exhibited 10- to 20-fold elevations in PRPP levels. Glucose consumption, glucose decarboxylation, thymidine and adenosine specific uptake, thymidine incorporation into DNA, and 5-fluorouracil uptake were studied in KB cells with elevated and control PRPP levels. As determined by clonal assay, despite elevated PRPP levels, KB cells cultured in P medium were less sensitive to 5-fluorouracil than cells cultured in S medium unless exogenous folate was added. These data support the concept that endogenous folate levels may be inadequate for optimal 5-FU pharmacological action in KB cells with a modulated increase in PRPP levels.

Adenosine↗

A hepatitis B vaccination program in a community teaching hospital.

Prior to offering the hepatitis B (HB) vaccine, a prescreen for hepatitis B virus (HBV) antibodies was conducted in a 565 bed hospital in Pasadena, California. Antibodies to the hepatitis B virus were detected in 14.5% of 1,745 employees tested. There was a significantly higher prevalence in those with a previous history of hepatitis, blood transfusions, exposure to needlesticks, number of years in the same occupation, and in the same hospital work area. Employees of Asian extraction (33.3%) and blacks (23.1%) had a higher prevalence of antibodies to the hepatitis B virus than Hispanics (13.7%) and whites (10.2%). Anti-HBs was detected in 92.6% of 865 employees who received three doses of the hepatitis B vaccine. Only 28.6% of nonresponders receiving a fourth dose of hepatitis B vaccine produced anti-HBs. The nonresponders to the HB vaccine were older (average age 64.9 years) when compared to the responders (average age 37.5 years), and more males failed to produce anti-HBs after vaccination than females. Hepatitis B vaccination of the majority of individuals with either "low level" anti-HBs alone or anti-HBc alone did not elicit an anamnestic response after one dose of vaccine, implying that these "low level" antibodies are nonspecific and do not represent antiviral antibodies. Adverse reactions to the hepatitis B vaccine were minor and included a flu-like syndrome, sore arm, and rash and swelling at the injection site. The reasons for nonparticipation were obtained from 179 individuals, and the main issue was concern about safety of the hepatitis B vaccine.

Adult↗

Hepatitis B vaccine usage among dental practitioners in the United States: an epidemiological survey.

A telephone survey of 283 nonfederally affiliated dental practitioners in the United States was completed in April 1986. The study's objectives were to determine hepatitis B vaccine usage among dentists nationwide, and to examine the epidemiologic characteristics of vaccinated and unvaccinated subjects. Forty-four percent of the participants had received at least the first of the three doses of HB vaccine. Acceptance of the vaccine was associated with the use of gloves during dental procedures and the subject's perception of high-risk patients in his or her dental practice. The most common reasons for not being vaccinated were concerns about vaccine safety and a lack of perceived need for the vaccine. The vaccination rate in this survey is higher than in earlier studies, indicating that acceptance of the vaccine by dental practitioners is increasing.

Adult↗

Hepatitis B virus transmission in a public school: effects of mentally retarded HBsAG carrier students.

In 1980, 18 institutionalized children, carriers of hepatitis B virus (HBV), were enrolled into two special education schools, and staff and students were monitored for HBV markers. Eleven HBV exposures were observed and those exposed were given hepatitis B immune globulin. After 3.5 years, no remaining staff showed serological evidence of HBV infection but three of 61 susceptible students did so. The three students probably acquired the infection outside the school. At the conclusion of the project, one school located in the community decided not to institute a vaccine program for students or staff. The other school, located inside the mental retardation institution, established an organized vaccine initiative. Indications for use of hepatitis vaccine in schools should be individualized to accommodate for differences in student and staff interaction, physical design of the school, and number and behaviors of HBsAg carrier students.

Adolescent↗