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N Mueller

Publications and source records attributed to N Mueller.

At least 19 recordsLinked to original sources
PubMed1992

Case-control study of factors associated with human T-cell leukemia virus type I infection in southern Miyazaki, Japan.

BACKGROUND: An unusual age- and sex-specific distribution and a remarkably restricted geographic seroprevalence characterize human T-cell leukemia virus type I (HTLV-I) infection. Although the transmission routes of HTLV-I are known, these seroepidemiologic features cannot be fully explained. PURPOSE: This study was designed to identify potential characteristics associated with HTLV-I infection in a highly endemic Japanese community. METHODS: We evaluated occupational, residential, dietary, and medical histories in a case-control study conducted in two neighboring villages in southeastern Miyazaki Prefecture. One hundred forty-four case subjects and 276 control subjects, frequency matched by age, sex, and village, were interviewed. Village-specific profiles of demographic determinants of HTLV-I seroprevalence were generated using multiple logistic regression. RESULTS: Although a different pattern of factors was found for each village, occupations of the subjects and their fathers were associated with HTLV-I infection in both communities--farming in village A and fishing and farming in village B. For village A, there was more than a twofold association both with residence in the township for 55 years or more and with living in a particular area within the village. In addition, case subjects were more likely to have a mother who was deceased (odds ratio = 1.7; 95% confidence interval = 0.96-2.9). CONCLUSIONS: HTLV-I infection is characterized by a high degree of microepidemicity in this population, with seroprevalence related to both sociologic and geographic determinants. Moreover, as carriers' mothers themselves have a higher probability of being HTLV-I positive, an increased mortality among those infected with the virus is suggested.

Adult↗
PubMed1992

Sexual behavior and status for human immunodeficiency virus type 1 among homosexual and bisexual males in Mexico City.

The authors examined sexual behaviors, the seroprevalence of human immunodeficiency virus type 1 (HIV-1), and condom use among 2,314 homosexual and bisexual men tested during 1988-1989 at the AIDS (acquired immunodeficiency syndrome) National Center in Mexico City. Bisexuals constituted 24% of the sample; the seroprevalence rate was lower for bisexuals than homosexuals (21 vs. 34%). In logistic regressions, HIV-1 seropositivity was independently related to age, education, pattern of insertive/receptive behavior in anal sex, lifetime number of male sex partners, having sex with someone with AIDS, homosexual versus bisexual behavior, and a history of condyloma. The same logistic regressions were found to fit bisexuals and homosexuals. The rate of HIV-1 was reduced in individuals who indicated always requiring their partners to use a condom when practicing receptive anal sex (1% of the total). The most common practice for both homosexuals and bisexuals was "mixed" behavior (i.e., both insertive and receptive anal sex); this was also the practice with the highest risk. Bisexuals practiced both vaginal and anal sex with women and reported little condom use. The substantial seroprevalence among bisexuals, their frequent sexual contact with women, and their low rate of condom use imply a continuing role as a bridge of infection to females. Whether this risk will lead to a sustained heterosexual epidemic remains to be determined.

Adolescent↗
PubMed1992

Successful graft of HTLV-I-transformed human T-cells (MT-2) in severe combined immunodeficiency mice treated with anti-asialo GM-1 antibody.

To develop an experimental model of adult T-cell leukemia/lymphoma in small animals, severe combined immunodeficiency (SCID) mice treated with anti-asialo GM-1 antibody were inoculated with MT-2 cells, a cell line transformed by the human T-cell leukemia virus (HTLV-I). Three mice injected with 4 x 10(7) cells subcutaneously or intramuscularly developed tumors at or near inoculation sites. Immunofluorescent antibody (IFA) staining for HTLV-I structural protein, p19, revealed the specific antigen in the cytoplasm of most cells from tumors and the DNA signals of HTLV-I proviral DNA were also positive in cellular DNA by polymerase chain reaction assay with HTLV-I tax gene primers, SK43/SK44. The MT-2 cells did not invade in mouse organs.

Animals↗
PubMed1992

Determinants of HTLV-1 seroprevalence in Miyazaki Prefecture, Japan: a cross-sectional study.

To evaluate determinants of the prevalence of human T-cell leukemia virus type I (HTLV-I) antibody positivity in an endemic region, Miyazaki Prefecture, Japan, demographic and serologic data were collected on 7,055 individuals consecutively seen at Miyazaki City Health Promotion Center between September 1983 and December 1984. The overall HTLV-I seroprevalence was 8.5%; age and gender distributions of HTLV-1 antibody positivity were consistent with previous findings for endemic populations. The prefecture could be divided into two geographic areas based on seroprevalence: high prevalence (12.1%) in the southwest and medium prevalence (6.6%) for the rest of the prefecture. Current occupation in fishing, forestry, or livestock raising significantly correlated with HTLV-1 seropositivity [relative risk (RR) = 3.0, 2.5, 2.0, respectively]; farming also was associated but only in the medium prevalence region (RR = 1.3; p = 0.06). For a subset of 157 HTLV-I-positives and 175 negative controls screened for antibodies to the toxoplasmosis organisms, toxoplasma exposure was not significantly associated with HTLV-I infection. In this endemic Japanese population, both geographic and sociologic factors characterized the distribution of HTLV-I seroprevalence, reflecting transmission patterns and historical duration of the infection.

Adolescent↗
PubMed1992

A model for the AIDS epidemic in Mexico: short-term projections.

As in many developing countries, the AIDS epidemic in Mexico has become a major public health problem. Given the competition for scarce health resources in Mexico, where hospitals are overcrowded and care for AIDS patients is often unavailable, planning depends on accurate estimates of the incidence of AIDS and the prevalence of HIV-1 infection. This article presents estimates of AIDS incidence in Mexico corrected for delays in reporting and short-term projections based on the corrected AIDS incidence. Trends in incidence cannot be assessed without such correction because only about 50% of AIDS cases are reported within 4 months of diagnosis. In addition to information on AIDS incidence, short-term projections also require estimates of the latency distribution between infection with HIV-1 and onset of AIDS. Latency periods with medians of 8 and 10 years lead to estimates that 22,000 and 24,000 new AIDS cases infected before June 1989 will be diagnosed between 1989 and 1994.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Unusual pattern of antibodies to human T-cell leukemia virus type-I in family members of adult T-cell leukemia patients.

Detection methods for the human T-cell leukemia virus type-I (HTLV-I) for blood screening and diagnosis generally rely on antibody tests that use the structural proteins of HTLV-I as antigen. We have found an unusual pattern of antibody reactivity among people who are at high risk of HTLV infection due to being a family member of an adult T-cell leukemia (ATL) patient: a specific antibody reaction exclusively directed to the HTLV regulatory protein tax, and not to the HTLV-I structural proteins. Sera from 7 of 82 (8.5%) structural antibody-undetectable family members of ATL patients had the anti-tax reactivity. Two seroconverters were observed. One seroconverter a healthy resident of Miyazaki, tested negative for structural antibody, but positive for tax antibody. Two years later she tested positive for both. The other seroconverter, an Israeli hemophiliac, tested negative for both antibodies, but converted to tax antibody-positive/structural antibody-negative. The HTLV-I tax-only antibody profile was also observed in sera sets from two other populations at risk for HTLV infection, human immunodeficiency virus-1-infected patients at the Bronx-Lebanon Hospital in New York and Israeli hemophiliacs. DNA samples from lymphocytes of four individuals with antibody reactivity only to HTLV-I tax were tested in polymerase chain reaction experiments; no HTLV-I or -II DNA was detected.

Animals↗
PubMed1991

Inhibitory effect of maternal antibody on mother-to-child transmission of human T-lymphotropic virus type I. The Mother-to-Child Transmission Study Group.

In order to evaluate the protective role of the maternal antibody against mother-to-child transmission of HTLV-I, we followed a total of 780 children born to HTLV-I carrier mothers by investigating the level of anti-HTLV-I antibody transferred in utero, decline of the maternal antibody and seroconversion in post-natal life. The anti-HTLV-I antibody was positively detected within the first 3-6 months of life and declined at 6-12 months after birth in all children. After the maternal antibody declined, seroconversion occurred in some of the children following either breast feeding or bottle feeding. The seroconversion rates of short-term (less than or equal to 6 months) and long-term (greater than or equal to 7 months) breast feeders were 4.4% (4/90 cases) and 14.4% (20/139 cases), and the rate of bottle feeders was 5.7% (9/158 cases). Long-term breast feeding yielded more seroconverters than short-term breast feeding; 14.4% (20/139 cases) vs. 4.4% (4/90 cases), RR = 3.68, p = 0.018. The seroconversion rate of short-term breast feeders was nearly equal to that of bottle feeders; 4.4% (4/90 cases) vs. 5.7% (9/158 cases), RR = 0.770, p = 0.471. When neonatal lymphocytes were cultured with breast milk cells of HTLV-I carrier mothers, the in vitro infection of HTLV-I was inhibited by the addition of HTLV-I-seropositive cord-blood plasma. Our results suggest that the maternal antibody may inhibit HTLV-I infection by short-term breast feeding but not by long-term breast feeding after decline of the maternal antibody.

Adolescent↗
PubMed1991

Epstein-Barr virus antibody patterns preceding the diagnosis of non-Hodgkin's lymphoma.

Immunosuppressed patients who develop non-Hodgkin's lymphoma (NHL) have abnormal antibody responses against the Epstein-Barr virus (EBV) prior to the diagnosis of malignancy. To see if this is also true of "spontaneous" cases in the general population, we undertook a collaborative serologic case-control study. From 4 serum banks containing specimens from over 240,000 persons, 104 subjects were identified for whom a blood specimen had been stored an average of 63 months before diagnosis of NHL, and 259 controls matched for age, sex, ethnic group and date of serum collection. The relative risks (RR) for subsequent development of NHL associated with elevated levels of IgG and IgM antibodies against viral capsid antigen were 2.5 (95% confidence interval = 1.1-5.7) and 3.2 (1.3-7.5), respectively; these associations increased with age at diagnosis. For the nuclear antigen, the distribution of titers for cases was more restricted than that of controls, with fewer cases having either elevated or low titers, RR = 0.5 (0.2-1.4) and 0.5 (0.2-1.2), respectively. Cases had significantly lower antibody titers against the cytomegalovirus, RR = 0.4 (0.2-0.9). These findings suggest that, at least for some patients, NHL is preceded by an enhanced level of endogenous immunosuppression with resultant EBV activation. This observation supports the role of EBV either directly in the development of NHL or as a primary marker of immune dysfunction.

Adult↗
PubMed1991

Sexual transmission of human T-cell leukemia virus type I associated with the presence of anti-Tax antibody.

The tax gene product (Tax protein) of human T-cell leukemia virus type I (HTLV-I) is a specific transcriptional activator of the viral long terminal repeat sequence and is essential for the replication cycle of the virus. To elucidate the relationship between the presence of anti-Tax antibody and the transmission of the viral infection, annual consecutive serum samples from married couples serologically discordant or concordant for HTLV-I were examined. These included 5 individuals whose spouses seroconverted during this 5-year follow-up study period. The samples were tested by a Western blot assay using a recombinant Tax protein as the antigen. The results showed that 24 of 32 (75%) men in the concordant couples (both husband and wife were HTLV-I carriers) had anti-Tax antibody, while only 5 of 18 (27.8%) men in the discordant couples (husband was carrier and wife was seronegative to HTLV-I) were positive for anti-Tax antibody (P = 0.0012). Furthermore, all spouses of the 5 seroconverters (4 women and 1 man) had anti-Tax antibody, while only 23 of 46 (50%) age-matched randomly selected HTLV-I carriers from the discordant-couple group had anti-Tax antibody. When the data were analyzed by gender, all husbands of the female seroconverters had anti-Tax antibodies, which was significantly higher than the prevalence of anti-Tax antibodies in men who did not transmit the virus to their spouses during the follow-up period (P = 0.017). In addition, antibody reactivity to other HTLV-I antigens (including Env gp46, transmembrane protein gp21, and Gag p19 and p24) were examined. The results indicated no significant differences between the prevalence of antibody reactivity to any of the antigens in the spouses of the seroconverters and the reference group. We conclude that the presence of anti-Tax antibody in men may indicate a high risk of viral transmission to their wives via heterosexual routes.

Agglutination Tests↗
PubMed1991

An epidemiologist's view of the new molecular biology findings in Hodgkin's disease.

Recent advances in molecular biology provide new strategies to address the pathogenesis of Hodgkin's disease (HD). Immunophenotyping studies of Reed-Sternberg cells suggest lymphoid cells, 'frozen in a state of activation.' Clonal rearrangement studies find heavy and light chain immunoglobulin and beta and gamma T-cell receptor gene changes. Chromosomal studies find a complex but nonrandom mixture of structural rearrangements including many seen in other hematologic disorders. These findings are consistent with a pathogenesis involving chronic antigenic stimulation. This interpretation is supported by the epidemiologic features of HD which suggest that HD may develop as a rare consequence of infection with a common latent virus where risk is increased if infection is delayed until adolescence or young adulthood. Such 'late' infections are generally more clinically severe and may result in more chronicity of virus replication. Serologic and genome probe studies of the Epstein-Barr virus--a candidate agent--in HD specimens support this hypothesis. In summary, the new molecular biology findings in HD converge with the previous epidemiologic, immunologic, and clinical data to support a unifying hypothesis of pathogenesis in which genetic abnormalities occur secondarily to a sustained host response to chronic tissue-based antigenic stimulation.

Adolescent↗
PubMed1991

The epidemiology of HTLV-I infection.

It has been 10 years since the discovery of the human T-cell lymphotropic virus type I (HTLV-I), the first human retrovirus. During the past decade, significant progress has been made in understanding the transmission of the virus and defining its geographic distribution. It has been shown conclusively that HTLV-I is a causal factor in the induction of both adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy. However, the pathogenesis of each of these conditions is not clear, and in the light of the evidence of immune dysfunction seen among carriers of the infection, it is likely that other associated diseases will be identified. The challenge in the next decade will be to develop and implement therapeutic interventions among carriers to prevent such diseases as well as to curtail transmission within endemic populations.

HTLV-I Infections↗
PubMed1991

Epstein-Barr virus antibody patterns preceding the diagnosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) patients have elevated IgG and IgA antibody titers against the Epstein-Barr viral capsid antigen (VCA) and the diffuse component of the early antigen complex (EA-D) at diagnosis. Several studies have implied that the presence of anti-VCA-IgA can be used as a screening marker for early NPC. To evaluate this further, we undertook a serologic case-control study based on four serum banks which together had specimens from over 240,000 persons. Seven cases of undifferentiated or poorly differentiated NPC were diagnosed in the period after serum collection ranging from 26 months to 154 months. Two controls per case matched on serum bank, age, sex, race, and date of serum collection were selected by a predetermined random process. For anti-VCA-IgG, the geometric mean titer for cases (88.3) was significantly higher than that for controls (75.5, P less than 0.05). The difference was greatest among the Asian patients. No significant differences were found for anti-VCA-IgA, anti-EA-D, and anti-EA-R or anti-EBNA. No time effects were evident when titers were plotted against time of blood collection preceding diagnosis. Our results do not suggest EBV activation in the period preceding NPC diagnosis, nor that detectable IgA antibody against VCA is a marker for early disease.

Adult↗
PubMed1990

Antibody profile of early HTLV-I infection.

To define the antibody profile of early seroconversion in infection with human T-cell lymphotropic virus type I (HTLV-I), consecutive serum samples from 10 subjects presumed to have seroconverted on the basis of the particle agglutination test were studied by three enzyme immunoassays and two confirmatory tests (radioimmunoprecipitation and western blot). 3 samples positive and 1 sample indeterminate in the confirmatory tests were reactive in one enzyme immunoassay, which used recombinant envelope antigen, but not in the other two enzyme immunoassays. 2 of 38 particle-agglutination-negative samples had a prozone effect. The confirmatory tests identified 8 seroconverters (7 women, 1 man); their serum samples were used to study the antibody reactivity by western blot assays to HTLV-I specific antigens (three recombinant proteins spanning the N-terminal, middle, and C-terminal env glycoprotein gp46; a recombinant transmembrane protein gp21; a recombinant tax protein; and three gag proteins [p28, p24, and p19]). All 8 seroconverters had antibody reactivities to the C-terminal region (aminoacid residues 229-308) of gp46 and to gag p19 and p24 when their seroconversion was detected.

Adult↗
PubMed1990

Suppression of delayed-type hypersensitivity to PPD and PHA in elderly HTLV-I carriers.

In a previous study on immune responsiveness among asymptomatic human T-cell leukemia virus type I (HTLV-I) carriers, we found that carriers had significantly reduced delayed-type hypersensitivity (DTH) response to purified protein derivative (PPD) skin testing. The association was strongest among persons at least 60 years of age. In order to evaluate this finding further, we evaluated the response to both PPD and phytohemagglutinin (PHA) in an elderly population. Fifty-six consecutive hospitalized patients with nonimmunosuppressive diseases were examined. None had a history of tuberculosis nor evidence of the known HTLV-I-associated diseases. The subjects' ages ranged from 62-93 years (median = 75 years); 43 were women and 13 were men. Twenty-two of the subjects were HTLV-I antibody positive. Among the carriers, there was an increased level of nonreactivity to PPD, the relative risk adjusted for age (RR) being 1.9 (95% confidence interval, 0.62-5.8), as well as to PHA of RR = 2.3 (0.60-9.0). When subjects were cross-classified for response to both skin tests, 15 of 17 carriers were nonreactive to either or both antigens compared to 15 of 25 noncarriers [RR = 5.1 (0.99-25.9) (p value, one-sided = 0.026)]. The decline in reactivity to both antigens increased with age, but was consistently lower among the carriers. Among subjects with positive reactions to PPD, the degree of reaction as measured by the size of erythema was reduced among the carriers; however, for PHA responders, the response in carriers appeared to be normal. Among the HTLV-I antibody negative subjects, the size of erythema for both antigens was strongly correlated (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

The prevalence of antibody to p42 of HTLV-I among ATLL patients in comparison with healthy carriers in Japan.

A gene product (p42) of the long open reading frame, now termed tax, of the viral genome of human T-cell leukemia virus type I (HTLV-I) may be related to the transformation of T cells in adult T-cell leukemia-lymphoma (ATLL). To evaluate its association with the disease, we compared the prevalence of antibody to p42 in sera obtained from 105 HTLV-I carriers and 64 ATLL patients from southwest Japan. The prevalence of the anti-p42 antibody reactivity was 63% among carriers and 31% among cases. The cases were more than 3 times as likely to lack antibody to p42 than carriers, the relative odds (OR) = 3.4, p = 0.001. When the samples were tested for antibody against p24, the most immunogenic core protein, the prevalence was somewhat higher among carriers (65%) than in cases (52%), but not significantly so (p = 0.15). Among the healthy carriers, the correlation between the prevalence of both antibodies was high (p = 0.001), and only 25% of those who had antibody to p24 lacked antibody to p42. However, among the cases, reactivity to both antigens was independent (p = 0.52), and 65% of those with antibody to p24 lacked antibody to p42, OR = 6.3, p = 0.0004. Thus the strongest serologic marker of ATLL following diagnosis was lack of reactivity to p42, particularly among those subjects with anti-p24. Whether this altered response is present prior to disease remains to be determined.

Autoradiography↗
PubMed1989

Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis.

In patients with Hodgkin's disease, titers of IgG antibody against viral capsid antigen of Epstein-Barr virus and the prevalence of antibodies against early antigen are higher than expected. To evaluate whether this condition antedates diagnosis, we identified 43 persons with Hodgkin's disease, from whom blood had been drawn and stored for an average of 50.5 months before diagnosis, and 96 controls from the same populations, from whom blood had been drawn at the same time. The relative risks of Hodgkin's disease associated with elevated levels of IgG and IgA antibodies against capsid antigen were 2.6 (90 percent confidence interval, 1.1 to 6.1) and 3.7 (1.4 to 9.3), respectively. For Epstein-Barr nuclear antigen, the relative risk was 4.0 (1.4 to 11.4), and for early antigen D it was 2.6 (1.1 to 6.1). However, the prevalence of IgM antibody against capsid antigen was substantially lower in patients with Hodgkin's disease (0.22 [0.04 to 1.3]). These associations were stronger in serum samples obtained at least three years before diagnosis than in serum samples obtained closer to diagnosis. We conclude that the development of Hodgkin's disease may in some patients be preceded by enhanced activation of Epstein-Barr virus. Whether Epstein-Barr virus has a direct role in the pathogenesis of the disease or is simply a marker for a more fundamental factor affecting the immune control of latent infections is unknown.

Antibodies, Viral↗