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Biomedical subjects

B Hanchard

Publications and source records attributed to B Hanchard.

At least 19 recordsLinked to original sources
PubMed1999

Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy.

Human T cell lymphotropic virus-I (HTLV-I)-associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetramers loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR Vbeta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.

Adult↗
PubMed1999

Adeno-associated virus and development of cervical neoplasia.

Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) -control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.

Adolescent↗
PubMed1999

Quantitative proviral DNA and antibody levels in the natural history of HTLV-I infection.

The pathogenesis of human T-cell lymphotropic virus type I (HTLV-I) in adult T-cell leukemia/lymphoma (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is poorly understood. We prospectively followed up and evaluated the virologic correlates of infection in transfusion recipients after seroconversion, in asymptomatic carriers, and in ATL and HAM/TSP patients. Proviral DNA levels (copies/105 lymphocytes) were determined by real-time automated polymerase chain reaction and antibody titers by end-point dilution by use of an HTLV-I enzyme-linked immunoassay. In early infection, proviral load was initially elevated (median, 212 copies/105 lymphocytes at time 1) and later decreased (median, 99 copies at time 2, and 27 copies at time 3). Corresponding antibody titers were low at time 1 (1:2154), had significantly increased by time 2 (1:12312), and were stable by time 3 (1:4694). These viral markers were significantly lower in asymptomatic carriers than in HAM/TSP or ATL patients. Therefore, proviral load and antibody titers may be useful as predictive markers of disease among carriers.

Adolescent↗
PubMed1999

Malignant lymphoma of gastric mucosa-associated lymphoid tissue in Jamaica.

The recently appreciated concept of Mucosa-Associated Lymphoid Tissue (MALT) and the characteristics of the lymphomas arising therein are discussed with reference to the clinical, histological and immunohistochemical features of the first four cases of gastric MALT lymphomas diagnosed at the University Hospital of the West Indies. These tumours are low-grade B-cell lymphomas, which may undergo high-grade transformation. They are aetiologically associated with Helicobacter pylori (H pylori) infection in the stomach and may be cured in the early stages with antibiotics. Our cases were diagnosed from gastrectomy specimens removed for suspected carcinoma. All were high-grade, and associated with H pylori; 3 cases presented as advanced disease. Documentation of the features of these lymphomas will increase awareness and earlier recognition.

Aged↗
PubMed1998

Human leukocyte antigen class II alleles associated with human T-cell lymphotropic virus type I infection and adult T-cell leukemia/lymphoma in a Black population.

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I-related diseases. METHODS: We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51). All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reaction-based methods to examine HLA class II DRB1 and DQB1 alleles. RESULTS: Two antigens determined by serotyping, DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42% versus 22% for DR15 [odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.0-7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP. CONCLUSIONS: These data suggest that host genetic background is an important factor in determining whether HTLV-I carriers develop either ATL or HAM/TSP.

Alleles↗
PubMed1998

Clinical, pathologic, and immunologic features of human T-lymphotrophic virus type I-associated infective dermatitis in children.

OBJECTIVES: To define the clinical and laboratory features associated with infective dermatitis (ID) and confirm its association with human T-lymphotrophic virus type I (HTLV-I). DESIGN: A case series of patients with ID were compared with patients with atopic dermatitis (AD), which is an important disease in the differential diagnosis of ID. SETTING: Patients were recruited from dermatology and pediatric clinics at the University Hospital of the West Indies and the Bustamante Children's Hospital, Kingston, Jamaica. MAIN OUTCOME MEASURES: Clinical and laboratory features of patients with AD were compared with those of patients with ID. PATIENTS: Consecutive patients older than 1 1/2 years diagnosed as having ID (n=50) and AD (n=35) were enrolled based on clinical findings. RESULTS: The mean ages of patients with ID and AD were 6.9 and 7.8 years, respectively. Histologically, both diseases were predominantly chronic dermatitis with propensity for skin colonization with Staphylococcus aureus and beta-hemolytic streptococci; however, the distribution of sites of skin involvement differed. Infection with HTLV-I was the most distinguishing feature among patients with ID, with seropositive results in 100%; only 5 (14%) of the 35 patients with AD had results seropositive for HTLV-I. Infective dermatitis was further characterized by dermatopathic lymphadenitis in 16 (67%) of 24 patients with palpable nodes. Anemia, lymphocytosis, and low albumin and elevated serum globulin levels were more prevalent among patients with ID. Significant elevations of IgA, IgD, and IgG levels were observed among patients with ID compared with those with AD. However, both patients with AD and those with ID had levels of IgD and IgE elevated above the normal range. T-cell subsets among patients with ID revealed T-cell activation with a high percentage of HLA-DR antigen positivity, elevated CD4 (2.4 x 10(9)/L) and CD8 (1.4 x 10(9)/L) cell counts, with an increased CD4/CD8 ratio of 1:73. CONCLUSION: Infective dermatitis is a distinct clinical entity associated with HTLV-I, which plays a role in the pathogenesis and immune perturbations observed.

Adolescent↗
PubMed1997

Hepatic cirrhosis in Jamaica.

The aetiology, biochemistry, clinical features and complications of histologically confirmed hepatic cirrhosis in 45 patients (26 females, 19 males) seen at the University Hospital of the West Indies, Jamaica, between 1984 and 1994 are presented. The age range was 1 to 72 years (mean 48 years). Abdominal swelling and weight loss were the commonest symptoms, occurring in 51% and 47% of patients, respectively. Jaundice was a presenting feature in 44%. Hepatomegaly was present in 71% of patients and splenomegaly in 33%. The aetiological factors were: alcohol (36%), bush tea (18%), chronic active hepatitis (11%), drugs (7%), and haemochromatosis (2%). Hepatitis B surface antigen was detected in 2 of 20 patients tested. 24% of the patients also had diabetes mellitus., 29% were anaemic, 29% were thrombocytopenic, 4% were leukopenic, and the prothrombin time was prolonged in 22%. The albumin/globulin ratio was reversed in 71% of the patients. The alkaline phosphatase was elevated in 56%, the aspartate aminotransferase was increased in 58% and the gamma glutamyl transpeptidase in 56%. 56% of the patients had macronodular cirrhosis; the liver showed a micronodular pattern in 18%; 7% had biliary cirrhosis; 7% chronic active hepatitis with cirrhosis; and 13% showed a mixed macro-micronodular pattern. Ascites and fluid overload developed in 44% of the patients. Hepatic encephalopathy occurred in 18% and upper gastrointestinal bleeding in 18%.

Adolescent↗
PubMed1996

HLA DRB1*DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis.

A possible causal association between infective dermatitis and HTLV-I infection was reported in 1990 and confirmed in 1992. We now report familial infective dermatitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West Indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major histocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB1*DQB1* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune response to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I-seropositive younger son requires close clinical follow-up.

Adult↗
PubMed1996

A case-control study of risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I) in Jamaica.

BACKGROUND: We investigated behavioural and environmental risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I). METHODS: A nested case-control study of 201 HTLV-I seropositive subjects and 225 age- and sex-matched seronegative controls was performed using questionnaire data from the enrollment visit of a cohort study in 1987-1988. HTLV-I serostatus was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot. RESULTS: Among women, the number of lifetime sexual partners (P < 0.05, chi 2 trend) and the number of different men fathering a child by the woman (P < 0.06, chi 2 trend) were associated with HTLV-I seropositivity. Use by the female subject of an intrauterine device (IUD) was associated with an increased risk of seropositivity (odds ratio (OR) = 2.67, 95% confidence interval (CI): 1.13-6.23); condom use was rare in this population. Among male subjects, a larger number of lifetime sexual partners was also associated with HTLV-I seropositivity (P < 0.05, chi 2 trend). No association was found between HTLV-I seropositivity and educational attainment, income, or occupation. Having been breastfed as a child or receipt of a blood transfusion had elevated but imprecise OR due to very high and low prevalence of the risk factors, respectively. Several variables relating to insect or animal exposure showed no association with HTLV-I seropositivity. CONCLUSIONS: These data confirm that heterosexual intercourse is a major route of HTLV-I transmission, but do not support suggestions of insect or environmental vectors.

Adult↗
PubMed1996

Health effects of human T-lymphotropic virus type I (HTLV-I) in a Jamaican cohort.

BACKGROUND: Other than adult T-cell leukaemia (ATL) and HTLV-I associated myelopathy (HAM), the health effects of infection with human T-lymphotropic virus type I (HTLV-I) are not well defined. METHOD: A cohort of 201 confirmed HTLV-I seropositive Jamaican food service workers and 225 seronegative controls of similar age and sex from the same population was examined. A health questionnaire, physical examination, and laboratory tests were performed at enrollment into the cohort in 1987-1988. RESULTS: One of 201 HTLV-I seropositives, but no controls were diagnosed with HAM, for a prevalence of 0.5% (95% confidence interval) (CI) 0.01-2.7%); no cases of ATL were diagnosed. While there was no difference in current symptoms, the HTLV-I seropositive group was more likely to report a past medical history of hepatitis or jaundice (OR = 3.49, 95% CI: 0.93-13.08), malaria (OR = 2.13, 95% CI: 0.96-4.73), and dengue fever (OR = 1.37, 95% CI: 0.82-2.29); however, these differences were of borderline statistical significance. Low income HTLV-I seropositive women had lower body weight (P < 0.01) and body mass index (P < 0.009) than their seronegative counterparts; similar differences were seen in the smaller male group. A trend toward higher prevalence of severe anaemia (haemoglobin < 10 g/dl) (12.6% versus 7.7%, P < 0.105) and a significantly lower prevalence of eosinophilia (1.0% versus 6.3%, P < 0.004) was seen among HTLV-I seropositives compared to controls. CONCLUSIONS: Although most HTLV-I seropositives are asymptomatic, HAM may be diagnosed in approximately 0.5% of carriers. Chronic HTLV-I infection may also exert subtle effects on body mass and haematological parameters.

Adult↗
PubMed1996

Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients.

Human papillomavirus (HPV) types differ in their association with cervical cancer. Therefore, the types of HPV in precancerous lesions are important. In many regions with high cancer incidence, the HPV types in precancerous lesions have not been well studied. In Jamaica, a country that has high cervical cancer incidence, 174 colposcopy patients were tested for HPV DNA using polymerase chain reaction. HPV DNA detection was strongly related to presence and grade of cervical neoplasia (P<.001). Furthermore, severe neoplastic change was most highly associated with HPV DNA types also considered high-risk for severe neoplasia in other populations. HPV-45 DNA, a high-risk type uncommon in most previously tested countries, was detected in 12% of patients who had neoplasia. Thus, cervical neoplasia in Jamaica, as elsewhere, is linked to HPV. The high prevalence of HPV-45 was notable, and its relation to high cervical cancer incidence in Jamaica must be assessed.

Adult↗
PubMed1996

Adult T-cell leukemia/lymphoma in Jamaica: 1986-1995.

Adult T-cell leukemia/lymphoma (ATL) is the commonest lymphoid malignancy in adult Jamaicans, reflecting the role of the causative agent, human T-cell lymphotrophic virus type I (HTLV-I), in altering the pattern of non-Hodgkin lymphoma in an endemic area. A total of 126 cases of ATL were registered in Jamaica between January 1985 and July 1995. There were 65 male and 61 female patients (male-female ratio, 1:1), with a mean age of 43 years (17-85 years). The majority of cases were acute subtype (46.8%), followed by lymphoma (27%), chronic (20.6%), and smoldering (5.6%) types. The disease is associated with a high mortality, with only five of the 126 patients currently alive. The median survival rate is 20 weeks. The epidemiologic, clinical, and laboratory features are similar to those reported in Japan and Brazil, except that the mean age of patients, identical in Jamaica and Brazil (43 years), is 11 years younger than that in Japan (54 years). Given the theory that ATL develops after a long incubation period after early life exposure to HTLV-I facilitated by mother-to-child transmission via breast milk, and the fact that mothers of ATL patients have a high incidence of HTLV-I seropositivity, it would appear that reduction in the incidence of this disease could be achieved by methods aimed at preventing this mode of transmission.

Adolescent↗