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Biomedical subjects

A Manns

Publications and source records attributed to A Manns.

At least 55 records · Page 3Linked to original sources
PubMed1995

Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac.

Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months; no chemotherapy regimen appears successful in inducing long-term disease-free survival. The scientific basis of the present study is that ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference, we administered anti-Tac armed with Yttrium-90 (90Y) to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of 90Y-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5- to 15-mCi doses used, 9 of 16 evaluable patients responded to 90Y anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (> or = grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with 90Y anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy.

Adult↗
PubMed1995

Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma incidence.

BACKGROUND: We previously reported from a case-control analysis that T-cell non-Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphotropic virus type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for HTLV-I infection was very high in younger patients. PURPOSE: The objective of this study was to estimate the age-specific incidence rates of NHL among HTLV-I-infected and HTLV-I-uninfected adults in Jamaica and Trinidad. METHODS: Population rates of HTLV-I infection were calculated from available census reports and serosurvey data. Incidence rates for NHL were calculated from all incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined whether the immunophenotype of the tumor cells was T cell, B cell, or other. NHL incidence rates were computed according to HTLV-I status, age, sex, and tumor phenotype for each country separately and for both countries combined by weighting to the relative population size of each country. RESULTS: The age-standardized NHL incidence rate (mean +/- SE) in Jamaica was 1.9 +/- 0.2 per 100,000 person-years (PY). In Trinidad, the rate was 2.9 +/- 0.4 per 100,000 PY. Overall, the incidence of NHL increased with age and was higher in males than in females. In the HTLV-I-infected population, the incidence of NHL was inversely related to age, and age-specific rates were higher in males than in females. The NHL incidence in those estimated to have acquired HTLV-I infection in childhood, however, showed no sex difference, and one in 1300 such carriers (95% confidence interval: one in 1100 to one in 1600) per annum were estimated to be at such risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was highest in those patients infected with HTLV-I early in life (perinatally or via breast milk), with high, sustained risk from early adulthood in both sexes. CONCLUSIONS: While overall NHL incidence rates reveal that HTLV-I endemicity does not impose an exaggerated lymphoma burden on these populations, the risk for lymphoma among carriers who acquire infection early in life is dramatic and is consistent with the hypothesis that virus exposure early in life is most important for lymphoma-genesis. IMPLICATIONS: Studies of HTLV-I carriers known to be infected in childhood may provide insight into markers intermediate in the lympho-magnetic process. Strategies to disrupt early-life transmission of HTLV-I, notably mother-infant transmission, may be critical in reducing the burden of lymphoreticular disease in these populations.

Adolescent↗
PubMed1995

Human T-cell lymphotropic virus type I and severe neoplasia of the cervix in Jamaica.

Human T-cell lymphotropic virus type I (HTLV-I) was associated with carcinoma of the cervix in Japan in a recent study that compared hospital cases with healthy population-based controls. To test this relationship in women more alike for cervical neoplasia risk factors (including sexual behavior and human papilloma virus; HPV), we enrolled consecutive patients from a colposcopy clinic in Kingston, Jamaica (an HTLV-I endemic area). Patients underwent Pap smear, colposcopy, biopsy and cervical swab for detection of HPV by polymerase chain reaction. Cases were defined as women with CIN-3 or invasive cancer (CIN-3/CA). Controls included all patients with either CIN-I or koilocytotic atypia, atypical squamous cells of undetermined significance or benign cervical pathology (all but one had at least inflammatory changes). Patients with CIN-2 were excluded to minimize risk of case-control misclassification. Cases were much more likely to be HTLV-I seropositive than controls. Although mean age differed significantly between cases (mean age = 39 years) and controls (mean age = 33 years), control for age did not explain the relation of CIN-3/CA with HTLV-I. Among HPV DNA positive subjects the age-adjusted association was not diminished but lost statistical significance. HTLV-I seroprevalence may be independently associated with progression to severe neoplasia of the cervix.

Adult↗
PubMed1995

Comparison of HHV-6 antibody titers in West Africa and the Caribbean.

Human herpesvirus-6 (HHV-6) infection seems to be ubiquitous early in life, but antibody responses vary by geographic area. We compared HHV-6 antibody titer in 123 West African and 122 Caribbean serum samples. A quantitative immunofluorescence assay (IFA) using antigens derived from an HSB-2 cell line was used to test for IgG HHV-6 (GS strain) antibodies. The prevalence of HHV-6 antibodies was high (98%) in both sites. African samples had a significantly higher geometric mean titer (GMT: 697) than did Caribbean samples (GMT: 99). There was no difference between males (GMT: 260) and females (GMT: 270) overall. Children up to and including 9 years old had significantly higher titers (GMT: 483) than did all others (GMT: 237), and female children tended to have higher titers than did male children. In both areas there was a trend towards highest titer at younger age, followed by a decrease in titer during adulthood and middle age, and a secondary rise in titer in the oldest age group. Environmental and host factors may explain these geographic differences in antibody responses between two groups of African origin.

Adolescent↗
PubMed1995

The relative distribution of T cell subsets is altered in Jamaican children infected with human T cell lymphotropic virus type I.

Early childhood infection with human T cell lymphotropic virus type I (HTLV-I) has been suggested to be involved in the pathogenesis of infective dermatitis and adult T cell leukemia/lymphoma. Since only a very small percentage of HTLV-I-infected children develop disease later in life, identification of early interim markers for persons at risk for developing disease would enable monitoring and might provide insight into the pathophysiology of the various diseases associated with HTLV-I infection. A cross-sectional study analyzed T cell subsets in 35 HTLV-I-seronegative and 16 HTLV-I-seropositive Jamaican children 11-31 months old. HTLV-I seropositivity was associated with an increase in the mean percentage of CD4 cells expressing HLA-DR, a marker for T cell activation (P = .02). This increase was positively correlated with duration of infection (r = .74, P = .009). These data demonstrate perturbation of regulatory cells of the immune system in HTLV-I-infected children.

Breast Feeding↗
PubMed1995

Follow-up of electromyographic and cephalometric findings in patients with unilateral cleft lip and palate after fifteen months of continuous wearing of a special removable appliance.

A 15-month follow-up study was conducted on 13 children with unilateral cleft lip and palate. The patients presented with short upper lip, abnormal lip seal, and maxillary retrusion. All had undergone surgery in childhood. Cephalometric and electromyographic measurements were made prior to the start of treatment, 4 months into treatment, and after 15 months of continuous wear of a special removable appliance. The cephalometric measurements on paired comparison showed major improvement in both the sagittal maxillary and dentoalveolar positions. The electromyographic activity of the superior orbicularis oris muscle demonstrated no significant changes over the treatment period. Improvement in the sagittal maxillary and dentoalveolar positions seems to suggest that the elimination of the restrictive effect of the superior orbicularis oris muscle is a good therapeutic approach to promote normal growth potential in children with cleft lip and palate.

Activator Appliances↗
PubMed1995

Tropical spastic paraparesis occurring in HTLV-1 associated infective dermatitis. Report of two cases.

An association between HTLV-1 infection and infective dermatitis (ID) a relapsing eczematous condition of Jamaican children, was reported in 1990. These patients are at risk of developing other known HTLV-1 related diseases. We have observed the development of HTLV-1 associated myelopathy/tropical spastic paraparesis in two patients, ages 14 and 35 years, who were diagnosed with ID at ages 2 and 10 years, respectively. Infective dermatitis of children serves as an early marker of HTLV-I infection and may predict later development of either the malignant outcome, adult T-cell leukaemia/lymphoma or the neurologic manifestation HAM/TSP among adult carriers of HTLV-1 infection.

Adolescent↗
PubMed1994

Adult T-cell leukemia/lymphoma: a working point-score classification for epidemiological studies.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy that occurs most frequently in south-western Japan and the Caribbean basin. The primary etiologic agent for this disease, human T-lymphotropic virus type I (HTLV-I), is endemic in these areas. Only a small percentage of individuals infected with HTLV-I develop ATL. The factors that determine the development of malignant disease as an outcome of HTLV-I infection in an individual are unknown. ATL is histopathologically heterogeneous and firm diagnosis is made on the contribution of clinical, laboratory and histopathologic features. The wide variety of laboratory assays available to geographically diverse populations has led to a need to standardize the criteria for determining the diagnosis of this disease for epidemiologic studies. This report summarizes current information regarding ATL and proposes a classification facilitating comparison of case series in geographically and ethnically different populations.

Adult↗
PubMed1994

The effect of ethnic differences on the pattern of HTLV-I-associated T-cell leukemia/lymphoma (HATL) in the United States.

Human T-cell lymphotropic virus Type I (HTLV-I) is the primary etiologic factor for adult T-cell leukemia/lymphoma (ATL). Although HTLV-I is endemic in Japan and the Caribbean islands, the reported clinical and epidemiologic features of ATL in these 2 parts of the world are quite different. ATL has been diagnosed at a younger age and is reported more frequently as the lymphomatous type rather than the acute type with leukemia in the Caribbean basin as compared with the presentation in Japan. In order to characterize ATL in the United States, a registry has been established at the National Cancer Institute for the purpose of recording all cases originally diagnosed in the United States. This registry was utilized to examine the effect of ethnic differences on age of onset and clinical features of ATL, using the same data base. Clinical and laboratory information was obtained from 177 patients suspected of having ATL, who were treated at the National Institutes of Health, or had biological samples sent for evaluation, or were reported in the literature. Histopathologic review and virologic studies were performed by standardized methods. Of 177 patients registered, 127 were considered as having ATL, according to an algorithm combining clinical, pathologic and laboratory features. Presenting features in the confirmed cases consisted primarily of lymphadenopathy (76.6%), hypercalcemia (72.5%), leukemia (82%), skin involvement (48.2%) and hepatomegaly (53.6%). Patients of Japanese ancestry were generally older (median age 63, range 51 to 73 years) than patients of African-American descent (median age 39, range 7 to 75 years) and presented more often with leukemia (90 vs. 69%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Presence of human T lymphotropic virus types I and II in Ghana, west Africa.

Until recently, HTLV-I was considered to be an Old World virus and HTLV-II was thought to be endemic in the Americas. However, the presence of HTLV-II among Pygmies and other populations of Africa has raised doubts as to whether HTLV-II is primarily a New World virus. The large serosurveys conducted in the urban and rural areas of southern Ghana have identified a 1-2% prevalence for HTLV-I/II. To define the HTLV type, we have used a Western blot assay (HTLV-2.3 blot) that allows simultaneous confirmation and differentiation between HTLVs. Samples (n = 139) were chosen on the basis of previous reactivity with either an enzyme immune assay or r21e-spiked WB results. The WB 2.3 analysis of these specimens identified 55 (40%) to be HTLV positive, 70 (50%) to be HTLV indeterminant, and 14 (10%) to be HTLV negative for HTLV. HTLV seroindeterminant patterns ranged from both gag and env (14 were r21+, p24+, and/or p19+ [all were RIPA negative]) to gag only (21 were p24+/p19+, 16 were p19+, and 7 were p24+), and env only (8 were r21+ and 4 were rgp46+) reactivities. Of the 55 HTLV-positive specimens, 41 were typed as HTLV-I, 9 were HTLV-II, and 5 could not be typed (HTLV-I/II). Of the nine HTLV-II-positive specimens, three were from patients with Burkitt's lymphoma and six were from healthy individuals (two pregnant women) with no obvious risk factors for HTLV-II.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1994

Viral-specific humoral immune responses following transfusion-related transmission of human T cell lymphotropic virus type-I infection.

The immunoglobulin (Ig) isotypes of antibodies to specific proteins of the human T cell lymphotropic virus type I (HTLV-I) were determined by Western blot analysis of serial specimens from six individuals who experienced HTLV-I seroconversion following blood transfusion; five remained asymptomatic carriers, while one developed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) 32 weeks posttransfusion. Analysis of Ig isotypes demonstrated that while IgM was the most frequent early response to gag (p19, p24) and env (r21e) proteins within the first 3 months following transfusion, IgG and IgA responses could also be detected within this period. HTLV-I-specific antibody responses plateaued in all Ig isotypes, including IgM, within the next 4- to 6-month period following transfusion and persisted through the entire study period (> 4 years). Comparison of antibody profiles in Ig isotypes and IgG1 and IgG3 subclass among asymptomatic carriers and one individual who developed HAM/TSP demonstrated no evidence of isotypic prominence or IgG subclass restriction in either group. These results indicate the appearance of HTLV-I-specific IgM that persists even after the primary infection and suggest that such response does not appear to provide an early marker of seroconversion. Further, we found no evidence of isotypic prominence or restriction of the antibody response in recipients who remained asymptomatic compared to one who developed HAM/TSP.

Blotting, Western↗
PubMed1994

Demonstration of human T lymphotropic virus type I (HTLV-I)-specific T cell responses from seronegative and polymerase chain reaction-negative persons exposed to HTLV-I.

Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to adult T cell leukemia and the progressive chronic neurologic disease HTLV-I-associated myelopathy/tropical spastic paraparesis. Described is a method that measures the production of interleukin-2 from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I-infected persons. The peptides correspond to immunogenic regions of the HTLV-I Env and Tax proteins. Significantly, this assay demonstrated T cell responses to these HTLV-I peptides from coded PBL samples in 7 of 19 HTLV-I-seronegative polymerase chain reaction-negative persons known to have been exposed to HTLV-I but in none of 16 matched controls without risk factors for exposure (P = .007). The implications of this finding are discussed.

Adult↗
PubMed1994

Electromyographic and cephalometric findings in patients with unilateral cleft lip and palate after the use of a special removable appliance.

Cephalometric measurements and electromyographic analysis of the superior orbicularis oris muscle were undertaken in 13 children with unilateral cleft lip and palate with a short upper lip length who have undergone surgery in childhood. Initially, cephalometric and electromyographic records were evaluated and again after the subjects had continuously worn, for 4 months, a removable appliance specially designed to avoid the restraining effect of superior orbicularis oris muscle activity over the maxilla. Comparison between pretreatment and posttreatment cephalometric measurements showed a significant improvement in both the sagittal position of the maxilla and the dentoalveolar position. No significant changes were observed in electromyographic activity during rest or when saliva swallowing. Cephalometric changes suggest that the removable appliance used improves the growth of the maxilla.

Activator Appliances↗
PubMed1993

Role of HTLV-I in development of non-Hodgkin lymphoma in Jamaica and Trinidad and Tobago. The HTLV Lymphoma Study Group.

Human T-cell lymphotropic virus type I (HTLV-I) has been implicated in the aetiology of adult T-cell leukaemia/lymphoma in Japan and elsewhere, particularly the Caribbean. We have carried out parallel case-control studies in Jamaica and in Trinidad and Tobago to quantify the role of HTLV-I in the development of non-Hodgkin lymphoma (NHL). 135 cases of NHL were enrolled in Jamaica and 104 in Trinidad and Tobago. Controls were selected from patients treated in the same wards or clinics at the same time as the cases. Overall, patients with NHL were 10 times more likely than were controls to be seropositive for HTLV-I (Jamaica odds ratio 10.3 [95% CI 6.0-18.0], Trinidad and Tobago 14.4 [7.6-27.2]). In both countries the association between NHL and HTLV-I was greatest for T-cell lymphomas (18.3 [9.5-35.6] and 63.3 [25-167]). Among T-cell lymphomas especially, there was no significant difference between men and women in the association between NHL and HTLV-I, but there was a significant inverse relation between age and likelihood of HTLV-I seropositivity. B-cell lymphomas were predominant in the older age groups and were not associated with HTLV-I seropositivity. These findings are consistent with the hypothesis that early life exposure to HTLV-I is important for risk of subsequent ATL. Prevention of vertical transmission of HTLV-I could reduce by 70-80% cases of NHL in people under 60 years in this region.

Adult↗
PubMed1993

Sibling adult T-cell leukemia/lymphoma and clustering of human T-cell lymphotropic virus type I infection in a Jamaican family.

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) infection is endemic in Jamaica, with an estimated crude seroprevalence of 5%. Adult T-cell lymphoma/leukemia (ATL), a disease caused by HTLV-I, has an incidence of 1-2/100,000 in the Jamaican population. Familial ATL has not previously been reported from Jamaica. METHODS: Hospital records and histologic specimens of the two cases were reviewed. HTLV-I infection was confirmed by antibody testing and by polymerase chain reaction on paraffin-embedded tissue, where serum was unavailable. Family members were identified by the patients' parents. After giving informed consent, family members were asked to complete an interviewer-administered questionnaire and to agree to phlebotomy. RESULTS: ATL developed 10 years apart in two siblings from a Jamaican family at age 16 and 24 years. A study of 19 members of their extended family, including both parents, 2 grandparents, and 3 siblings, revealed an overall HTLV-I seroprevalence of 17%. This compared with 75% among parents and siblings living in the same household as the patients. HTLV-I antibody-positive (HTLV-I-positive) and negative family members had similar mean age. Three of 3 HTLV-I-positive subjects were breast-fed, compared with 10 of 15 HTLV-I-negative subjects. Intravenous drug abuse, sex with prostitutes, homosexuality, and blood transfusion were not reported. The mean number of sexual partners were similar. Both parents, who were antibody-positive, had polylobated atypical lymphocytes in their peripheral blood. CONCLUSION: The HTLV-I antibody seroprevalence is greater in the family than in the general population, consistent with the modes of transmission. The antibody seronegativity of both grandmothers suggests sexual transmission between parents. The development of ATL at age 16 and 24 years is consistent with maternal-infant transmission and a long latent period, as reported by other authors.

Adolescent↗
PubMed1993

HTLV-I and HTLV-II world-wide distribution: reanalysis of 4,832 immunoblot results.

Mapping the geographic distribution of human T-lymphotrophic virus types 1 and 2 (HTLV-I and -II) has been complicated because conventional serologic approaches cannot distinguish between these 2 viruses. To more precisely define the epidemiology of HTLV-I and HTLV-II, we evaluated a convenience sample of 4,832 HTLV-I immunoblot results from over 140,000 samples screened for HTLV-I, collected in 16 countries for 35 separate studies. An algorithm that compares reactivity against p19 and p24, 2 gag (HTLV-I core) proteins, was employed to characterize the immunoblots: type I, p19 stronger than p24 (presumptive HTLV-I), type 2, p24 stronger than p19 (presumptive HTLV-II), or indeterminate (p19 and p24 weakly positive or p19 weakly positive in the presence of p21e). Geographic areas could be grouped into 4 patterns. Patterns A (> 75% type I) and B (> 75% type 2) were usually observed where the specific type of HTLV or its characteristic diseases had been found. Pattern C (mixed type 1 and 2 pattern) was observed predominantly in intravenous-drug-using and other populations in which both virus types have been reported. Pattern D (> 10% indeterminate), suggests the presence of non-specific reactivity, perhaps resulting from exposure to non-virus-related antigens or an HTLV-related virus. HTLV-I predominates in southern Japan, the South Pacific, parts of West Africa, and in Afro-populations of the Western hemisphere. HTLV-II clusters in Native American populations and among intravenous drug users. Pattern-D areas in Africa and Venezuela might prove to be fertile in the search for new and variant HTLV virus types.

Blotting, Western↗