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Biomedical subjects

M A Kane

Publications and source records attributed to M A Kane.

At least 73 records · Page 4Linked to original sources

Hepatitis B infection in a day school for mentally retarded students: transmission from students to staff.

We carried out a seroepidemiologic study to evaluate the transmission of hepatitis B virus (HBV) from students to staff in a day school for mentally retarded students. Of 505 students tested, 37 (7.3 per cent) had HBsAg; 74 per cent of HBsAg-positive sera tested were HBeAg-positive. Of 162 staff members tested, 21 (13.0 per cent) were HBV marker positive and two (1.2 per cent) had HBsAg; specialized educators and teachers showed the highest HBV marker prevalence (22.2 per cent and 21.3 per cent, respectively). The prevalence of HBV markers among staff was independently associated with classroom contact with a HBsAg-positive student, duration of employment at the school, and previous work with mentally retarded individuals. The incidence of HBV infection among teaching staff with regular classroom contact, estimated by logistic regression analysis, was 2.6 per cent per year. This observation indicates that teaching staff in schools for mentally retarded students with direct classroom contact may carry an occupational risk of HBV infection.

Adolescent↗

The isolation, characterization, and comparison of the membrane-associated and soluble folate-binding proteins from human KB cells.

Human nasopharyngeal epidermoid carcinoma (KB) cells contain a membrane-associated particulate folate-binding protein which is important in the cellular accumulation of physiologic folates (Antony, A. C., Kane, M. A., Portillo, R. M., Elwood, P. C., and Kolhouse, J. F. (1985) J. Biol. Chem. 260, 14911-14917) and in the binding of methotrexate (Kane, M. A., Portillo, R. M., Elwood, P. C., Antony, A. C., and Kolhouse, J. F. (1986) J. Biol. Chem. 261, 44-49). A soluble folate-binding protein appears in media exposed to proliferating KB cells. We have purified to homogeneity both the membrane-associated and the soluble folate-binding proteins from the KB cell tissue culture system. The purified membrane-associated and soluble folate-binding proteins give single bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with apparent Mr values of 50,000 and 40,000, respectively. The membrane-associated folate-binding protein contains 45,000 g of amino acids and the soluble folate-binding protein contains 24,000 g of amino acids per mole of folate bound. Each of the purified proteins has a single folate-binding site, and the carbohydrate content is approximately 25% for each species of protein. The affinity constants for 5-methyltetrahydrofolate of the membrane-associated and soluble folate-binding proteins are 0.3 and 2.5 X 10(9) liters/mol, respectively. The affinities of various polyglutamated forms of methotrexate are similar for each protein, increase as the chain length of the polyglutamate increases (from approximately 0.004 X 10(9) liters/mol for methotrexate to 0.3 X 10(9) liters/mol for methotrexate heptaglutamate), are equal to the affinity for 5-methyltetrahydrofolate, and exceed the reported increase in affinity of methotrexate polyglutamates for dihydrofolate reductase.

Amino Acids↗

The interrelationship of the soluble and membrane-associated folate-binding proteins in human KB cells.

Human KB cells produce two immunologically cross-reactive folate-binding proteins: a particulate cell-associated protein which is solubilized by Triton X-100, and a soluble protein which is released into their growth medium. This compartmentation of these two folate-binding proteins provides a convenient system for studies of their biochemical relationship. The two folate-binding proteins behave similarly to the purified particulate and soluble folate-binding proteins of human milk in analysis by radioactive folate binding, Sephacryl S-200 gel filtration profiles, polyacrylamide gel electrophoresis in either Triton X-100 or sodium dodecyl sulfate, and in Triton X-100 binding based on sucrose density gradient ultracentrifugation in H2O and D2O. The two folate-binding proteins were endogenously labeled by pulsing methionine-starved KB cells with [35S]methionine, and each protein was purified to apparent homogeneity by affinity chromatography at different times during the chase with nonradioactive methionine. The time course of the changes in specific activity (moles of [35S]methionine per mole of folate-binding protein) revealed a more rapid initial rate of synthesis and an earlier maximum in specific activity for the cell-associated folate-binding protein than for the soluble folate-binding protein released into the growth medium. Differences in the levels and specific activities of the two folate-binding proteins of cells exposed to cycloheximide compared with simultaneous controls after pulsing with [35S]methionine suggest that, whereas the cell-associated folate-binding protein is probably produced by de novo protein synthesis, the soluble folate-binding protein seems to be produced from a cellular pool of an already synthesized protein. These results combined with the immunologic cross-reactivity of the two folate-binding proteins strongly suggest a precursor-product relationship between them.

Carrier Proteins↗

The influence of extracellular folate concentration on methotrexate uptake by human KB cells. Partial characterization of a membrane-associated methotrexate binding protein.

Methotrexate accumulation, subcellular distribution, metabolism, and cytotoxicity were studied in human epidermoid carcinoma (KB) cells that were exposed to a low extracellular concentration of methotrexate (25 nM) following culture in widely differing concentrations of folic acid. KB cells cultured in standard medium with a high folic acid concentration (2.3 microM) had high levels of cellular folate (21.4 pmol/10(6) cells). Five passages through low folate (2.7 nM) medium reduced the level of cellular folate to near physiologic levels (0.4-1.0 pmol/10(6) cells). In contrast to KB cells cultured in standard medium, in KB cells cultured in low folate medium, 1) methotrexate inhibited growth; 2) methotrexate uptake was markedly increased; 3) methotrexate polyglutamation was almost complete; 4) methotrexate binding to dihydrofolate reductase was markedly enhanced; and 5) significant methotrexate binding to a previously undescribed membrane-associated protein occurred. The amount of methotrexate bound to the membrane-associated protein from KB cells cultured in low folate medium equaled the quantities bound by dihydrofolate reductase. Further characterization of this membrane-associated protein indicated that it was soluble in solutions containing Triton X-100, was capable of binding folic acid as well as methotrexate, had an apparent Mr of 160,000 by gel filtration in the presence of Triton X-100, and was precipitated by antiserum to human placental folate receptor. This membrane-associated protein may play an important role in the uptake and metabolism of methotrexate under physiologic conditions.

Animals↗

Hepatitis B infection in ophthalmologists.

A seroepidemiologic survey of ophthalmologists in Western Pennsylvania was performed to define the hepatitis B virus (HBV) exposure risk for this subspecialty population. Of 70 participating ophthalmologists, only 5 (7.1%) had serologic evidence of prior hepatitis (positive hepatitis B surface antibody and antibody to the core antigen of hepatitis B). No participants were found to be HBsAg (hepatitis B surface antigen) positive. The infection rate for ophthalmologists appears lower than that previously described for physicians involved in surgical and nonsurgical medical specialties. However, caution is still recommended since hands and surgical instruments may become contaminated with HBV from the blood and secretions of hepatitis B patients or carriers.

Adult↗

Transmission of hepatitis B virus to classroom contacts of mentally retarded carriers.

The risk of the spread of hepatitis B virus infection from deinstitutionalized, mentally retarded carriers to pupil and staff school contacts in the New York City public school system was measured serologically in a three-phase study from 1978 to 1982. In the third phase, undertaken in 1982, blood samples were drawn and questionnaires were completed on students and staff tested in either of the first two phases and on comparison groups with intermediate and no known school exposure to deinstitutionalized carriers. Univariate and logistic regression analyses revealed that staff and pupils with a history of classroom exposure to a hepatitis B virus carrier had significantly increased prevalences of hepatitis B virus infection (13.4%, odds ratio = 1.9; 9.3%, odds ratio = 2.5, respectively). Similarly, yearly seroconversion rates of 1.3% and 0.67% indicate that staff and, to a lesser extent, pupils are at increased risk of infection.

Adolescent↗

Studies of the role of a particulate folate-binding protein in the uptake of 5-methyltetrahydrofolate by cultured human KB cells.

The characteristics of the uptake by human epidermoid carcinoma (KB) cells of 5-methyltetrahydrofolate at extracellular concentrations in the physiologic range and the possible role of a membrane-associated folate binder in folate uptake by KB cells have been investigated. Uptake of 5-methyltetrahydrofolate was specific, saturable, and time-, temperature-, and concentration-dependent. Trypsin treatment released 50% of the 5-methyltetrahydrofolate accumulated by KB cells at 4 degrees C, but only 12% at 37 degrees C, indicating that most of the accumulated ligand was intracellular at 37 degrees C, thus demonstrating transport. Accumulated 5-methyltetrahydrofolate was bound to a membrane-associated protein which required detergent for its solubilization, and a significant amount of which was oriented to the cell exterior as demonstrated by its release by trypsin treatment of intact KB cells. The membrane-associated folate binder was immunoprecipitated by antiserum to purified human placental folate receptor, and this antiserum inhibited 5-methyltetrahydrofolate uptake by intact KB cells in a concentration-dependent manner. These data support the hypothesis that the membrane-associated folate-binding protein of human cells participates in the transport of folates under physiologic conditions.

Carcinoma, Squamous Cell↗

A seroprevalence survey of hepatitis B markers among Haitians in a southwest Florida farming community.

We determined the seroprevalence of hepatitis B virus markers among 123 Haitian mothers and children in a southwest Florida farming community. Fifty-five per cent of mothers had one or more markers including two who were HBsAg positive. Only seven (10 per cent) children had markers; none were HBsAg positive. Pregnant Haitian women should be screened for HBsAg and infants born to those who are positive should receive immunoprophylaxis. Medical, dental, and laboratory workers caring for Haitian patients should also receive hepatitis B vaccine.

Adult↗

A multicenter study of the epidemiology of hepatitis B in anesthesia residents.

Practicing anesthesiologists are at high risk of hepatitis B infection, but the risk for anesthesia residents has not been assessed. Anesthesia residents at seven universities were surveyed to study the epidemiology of hepatitis B in these trainees. Hepatitis B virus markers in serum were measured and data from questionnaires were used to determine characteristics of anesthetic practice, effectiveness of strategies for hepatitis B virus infection control, and nonvocational hepatitis B risk factors. Of 267 participants, 12.7% (range of the seven centers, 8.7%-22.7%) had serum markers for hepatitis B virus. The seropositivity (17.8%) in anesthesia residents who had completed more than 12 months of nonanesthesia postgraduate clinical training, or who had practiced medicine in another specialty prior to anesthesia, was greater than in the other trainees (9.4%). Based on their risk and the ineffectiveness of current control measures, anesthesia residents who lack hepatitis B virus immunity should be vaccinated prior to or as early as possible in their training.

Anesthesiology↗

Epidemic non-A, non-B hepatitis in Nepal. Recovery of a possible etiologic agent and transmission studies in marmosets.

An epidemic of non-A, non-B hepatitis occurred in Kathmandu Valley, Nepal, during 1981-1982, with approximately 7.6% of households and 1.4% of individuals affected. Cases occurred preponderantly in the 15- to 34-year-old age group (70%), with most cases (75%) occurring in males. A high mortality rate (21%) occurred in pregnant women admitted to the hospital. No single water source was implicated, but epidemic peaks occurred during monsoon rains, and multiple opportunities for enteric transmission existed. One of eight patient stools examined by immune electron microscopy revealed aggregated, antibody-coated, 27-nm viruslike particles when convalescent serum samples were used as sources of antibody. Inoculation of two chimpanzees and four marmosets with a suspension of this stool resulted in elevated liver enzyme activity in three marmosets. Fecal excretion of 27-nm particles during the acute phase of disease (with temporally coincident antigen activity by radioimmunoassay) was observed in one marmoset, which also developed convalescent antibody against the particles in the original inoculum.

Adolescent↗

Posttransfusion hepatitis A in a neonatal intensive care unit.

A single unit of infected blood transfused into 11 neonates resulted in a large multistate outbreak of 55 cases of hepatitis A, 35 of which were symptomatic. The person who donated the blood to the 11 neonates became ill with hepatitis A one week after the donation. Hepatitis A infection was then acquired by nurses and physicians having direct contact with the neonates and by parents and relatives. Three additional newborns who had not received transfusions with the infected unit also acquired hepatitis A. The neonates with hepatitis A were all asymptomatic. The attack rate in susceptible nurses was 16%; in susceptible physicians, 4%. A survey of the relatives of the 11 newborns who received transfusions revealed eight symptomatic cases of hepatitis A in 32 immediate family contacts, ie, mother, father, and siblings, with a resulting attack rate of 25% uncorrected for prior immunity. The setting of the neonatal intensive care unit appears to be ideal for the transmission of hepatitis A.

Adult↗

Disinfection procedures and infection control in the outpatient oral surgery practice.

The infection control and disinfection procedures employed by 434 oral surgeons were surveyed. Gloving practices varied substantially, with 55% of respondents wearing gloves during less than or equal to 10% of patient contacts and only 24% wearing gloves routinely. Gloving practices correlated strongly with having been taught in dental school or during residency training to wear gloves. While 100% of participants had received instruction in the use of intravenous fluids in dental school or residency training, usage patterns differed substantially from those currently recommended in hospitals and in outpatient, nondental surgical settings. Of the respondents who used intravenous fluids in an office setting, 68% used a single bag or bottle for more than one patient. The median number of patients receiving intravenous fluid from a single bag or bottle was 12, and the median duration of use of a single unit was three days. It was noted that infection control and disinfection procedures varied significantly by type of practice (private vs. other nonmilitary vs. military practices).

Adult↗

The prevalence of hepatitis B viral markers in anesthesia personnel.

The prevalence of hepatitis B viral markers is increased in some groups of medical workers who are exposed to blood from patients carrying the virus, but this has not been studied critically in physicians and others who administer anesthesia. Physician anesthesiologists (M.D.) and nurse anesthetists and anesthesia assistants (non-M.D.) at four university-affiliated hospitals were evaluated for hepatitis B markers as determined by seropositivity for hepatitis B surface antigen, antibody to the hepatitis B surface antigen, or antibody to the hepatitis B core antigen. In the 86 subjects (38 M.D., 48 non-M.D.) who represented 80.4% of possible participants, the overall prevalence of serologic markers of hepatitis B was 23.3%. The frequency did not differ between M.D. (23.7%) and non-M.D. (22.9%) groups or between men (20.3%) and women (26.9%). Of 81 subjects who had no clinical history of hepatitis, 16 (19.8%) had positive serologic markers. The frequency of seropositivity increased with time since graduation from medical school (M.D.) or nursing school or college (non-M.D.). The prevalence of serologic markers of hepatitis B virus in this study of anesthesia personnel is five to eight times that of the general population but is similar to that of other medical workers who frequently are exposed to blood.

Adult↗

Epidemiological analysis of the significance of low-positive test results for antibody to hepatitis B surface and core antigens.

To determine the significance of certain serological test results commonly encountered in hepatitis B virus testing, we reviewed serological test data from nine studies of hepatitis B conducted between 1980 and 1982. Three tests, for hepatitis B surface antigen and for antibodies to hepatitis B surface antigen and hepatitis B core antigen (anti-HBs and anti-HBc), were used to measure hepatitis B virus infection risk in various populations. Two results, low levels of anti-HBs alone and low levels of anti-HBc alone, occurred at constant frequencies (2.72 and 0.4%, respectively), regardless of the prevalence of HBV infection in the population. Positivity for low levels of anti-HBs alone persisted for 1 year in less than one-half of those studied; in addition, response to hepatitis B virus vaccine was augmented in only one-third of this group. Positivity for low levels of anti-HBc alone did not persist in any of 11 persons studied. These findings indicate that presently available tests for anti-HBs and anti-HBc at low levels are often nonspecific and should be interpreted with caution.

Alaska↗

A multicenter study of the prevalence of hepatitis B viral serologic markers in anesthesia personnel.

Health care workers with frequent blood contact are at high risk of infection with hepatitis B virus. We surveyed 154 physician anesthesiologists (MD) and certified registered nurse anesthetists (CRNA) at four university-affiliated medical centers to determine the prevalence of serologic markers of hepatitis B virus (HBV). Questionnaires were used to ascertain historical and demographic information, nonoccupational risk factors, and characteristics of the participants' anesthesia practice. The overall prevalence of seropositivity was 18.8% (range 10.2-30.3%), and there were no statistically significant differences among the four centers, MD and CRNA groups, or males and females. In contrast to other studies, the prevalence of seropositive markers did not increase with an increase in the participants' age or length of time in the specialty. For the groups sampled in this study, geographic location or type of practice did not influence the increased prevalence of HBV seropositivity in anesthesia personnel. The current methods of HBV infection control were not associated with a decreased prevalence of serum markers. The majority of the susceptible anesthesia personnel at these four institutions did not plan to receive the hepatitis B vaccine when surveyed at the time of this study.

Anesthesiology↗

Transmission of hepatitis B by an oral surgeon.

An outbreak of hepatitis B in southeastern Connecticut was traced to an oral surgeon. In a serosurvey of his 754 noninstitutionalized patients, 511 (68%) participated. The rates of seropositivity for hepatitis B surface antigen (HBsAg) or antibody to HBsAg by year of oral surgery were 4.8% in 1977, 7.4% in 1978, and 14.8% in 1979. The transmission of hepatitis B, as measured by seropositivity, occurred between November 1978 and August 1979; the peak transmission was in February (31.2% seropositivity). Seropositivity was strongly correlated with the extent of surgical trauma (P less than 0.0001). HBsAg subtyping revealed that the oral surgeon and all four subtypable patients demonstrated both d and y reactivity, as did the patient from whom it was most likely the oral surgeon acquired his infection: a mentally retarded patient who had 24 extraction in March 1978. This study demonstrates that the transmission of hepatitis B between dental practitioners and their patients frequently results in subclinical infections.

Adolescent↗