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Biomedical subjects

P H Levine

Publications and source records attributed to P H Levine.

At least 19 recordsLinked to original sources
PubMed2001

Haemophilus influenzae type b serology in childhood leukaemia: a case-control study.

Antibody to Haemophilus influenzae type b (Hib) polysaccharide (PRP) was measured in 42 children with acute lymphoblastic leukaemia (ALL) and 42 non-leukaemic hospital controls. Modelling anti-PRP concentrations as a function of age revealed that the slopes of the trend lines differed significantly between cases and controls (P = 0.05); anti-PRP concentrations were lower among younger cases, and higher among older cases, than among controls of the same ages.

Adolescent↗
PubMed2001

Extrauterine low-grade endometrial stromal sarcoma with florid endometrioid glandular differentiation.

Endometrial stromal sarcoma of the uterus (ESS) is a rare lesion that can cause diagnostic difficulty especially when it presents with unusual histologic features such as diffuse endometrioid glandular differentiation. Only three such cases have been reported, all primary in the uterus. We report the first case of an extrauterine low-grade ESS with extensive glandular differentiation that appeared to arise in endometriosis.

Adult↗
PubMed2001

Occupational exposure to wood, formaldehyde, and solvents and risk of nasopharyngeal carcinoma.

Our objective was to evaluate the link between occupational exposures to wood dust, formaldehyde, and solvents and the development of nasopharyngeal carcinoma (NPC). A case-control study was conducted among 375 newly diagnosed cases of NPC in Taipei, Taiwan, and 325 community controls matched to cases on sex, age, and geographical residence (99 and 87% response rates, respectively). Most cases (>90%) were diagnosed with WHO Types 2 or 3 (nonkeratinizing and undifferentiated carcinomas), whereas the remaining cases were diagnosed with WHO Type 1 (squamous cell carcinomas). A complete occupational history was obtained via a personal interview and blindly assessed by an industrial hygienist for intensity and probability of exposure to wood dust, formaldehyde, and solvents. Information on socio-demographic characteristics, cigarette smoking, dietary consumption of nitrosamines, and other potential confounding factors was obtained via a personal interview. Blood specimens were tested for human leukocyte antigen class I/II genotypes, polymorphisms in cytochrome P450 2E1 genotype, and various anti-EBV antibodies known to be associated with NPC. Analysis was performed using logistic regression; relative risk (RR) estimates and 95% confidence intervals (CI) were calculated. Individuals exposed to wood dust had an adjusted RR of 1.7 (95% CI = 1.0-3.0). Those exposed to wood dust for >10 years had an adjusted RR of 2.4 (95% CI = 1.1-5.0; p(trend) = 0.02). Risk was strongest for those first exposed before the age of 25 years and those seropositive to EBV. Individuals exposed to formaldehyde were at a more modest and nonsignificant increased risk of NPC (RR = 1.4; 95% CI = 0.93-2.2). Those exposed to formaldehyde for >10 years had an adjusted RR of 1.6 (95% CI = 0.91-2.9). The association between formaldehyde and NPC was stronger in analyses restricted to EBV seropositive individuals (RR = 2.7; 95% CI = 1.2-5.9). However, no dose response was observed with increasing duration or cumulative use. No association was observed between solvent exposure and NPC (RR = 1.2; 95% CI = 0.86-1.7). Occupational exposure to wood dust is likely to be involved in the development of NPC, a finding that is consistent with the known link between wood exposure and nasal adenocarcinomas. Formaldehyde exposure is less clearly linked to NPC, whereas exposure to solvents is unlikely to be involved in NPC pathogenesis.

Adolescent↗
PubMed2000

Dietary exposure to nitrite and nitrosamines and risk of nasopharyngeal carcinoma in Taiwan.

Previous studies of nasopharyngeal carcinoma (NPC) have found elevated risks with higher consumption of salted fish and preserved foods, particularly during childhood. These foods can contain high levels of nitrosamines; however, most studies have not estimated exposure to nitrosamines directly. We conducted a case-control study in Taiwan to evaluate dietary intakes and NPC risk. A total of 375 cases (99% response rate) and 327 controls (88% response rate) were interviewed about their diet as an adult and at age 10 using a food-frequency questionnaire. We interviewed mothers of participants about their child's diet at age 10, age 3 and during weaning and the mother's diet while she was breast-feeding. Mothers of 96 cases and 120 controls were interviewed. Nitrosamine and nitrite levels were assigned to 66 foods based on published values. Intake of nitrosamines and nitrite as an adult was not associated with risk of NPC. High intakes of nitrosamines and nitrite during childhood and weaning were associated with increased risks of NPC for foods other than soy products. Adjusted odds ratios for the highest quartile were 2.2 [95% confidence interval (CI) 0.8-5.6] for age 10, 2.6 (95% CI 1.0-7.0) for age 3 and 3.9 (95% CI 1.4-10.4) for weaning diet. Intakes of nitrite and nitrosamines from soybean products during childhood and weaning were inversely associated with risk. Soybeans contain known inhibitors of nitrosation, and thus may explain the inverse association we observed. Our results suggest that nitrosamine and nitrite intake during childhood may play a role in the development of NPC.

Adult↗
PubMed1999

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn.

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.

Adult↗
PubMed1999

Bone marrow stromal cell-mediated gene therapy for hemophilia A: in vitro expression of human factor VIII with high biological activity requires the inclusion of the proteolytic site at amino acid 1648.

To evaluate the potential of the ex vivo bone marrow stromal cell (BMSC) system as a gene therapy for hemophilia A, we studied the in vitro expression of human factor VIII (hFVIII) in canine BMSCs following transfection with plasmid vectors and transduction with retroviral vectors. Vectors were composed of B domain-deleted forms of hFVIII that either retain or delete the proteolytic site at amino acid 1648. On transfection of BMSCs, vectors supported expression and secretion of similar levels of up to 386 mU/10(6) cells/24 hr, even though only 3-9% of the cells expressed hFVIII while 42-48% of transfected cells harbored plasmid vector. Much higher percentages (approximately 70%) of cells expressing hFVIII were achieved when BMSCs were transduced by retroviral vectors, resulting in expression and secretion as high as 1000-4000 mU/10(6) cells/24 hr. Western analysis demonstrated that the B domain-deleted forms possessing the proteolytic site were secreted predominantly as heavy and light chain heterodimers that resemble native forms found in plasma. In contrast, the hFVIII lacking the proteolytic site was expressed mostly as unprocessed, single heavy-light chains. Both hFVIII forms were correctly cleaved and activated by thrombin. The proteolyzed hFVIII form possessed > or = 93% normal biological activity while the unproteolyzed form possessed consistently less than 55% normal biological activity and was therefore considered less suitable for therapeutic application. These results demonstrate that the BMSC system has potential utility in gene therapy for hemophilia A and stress the importance of selecting the appropriate hFVIII structure for prospective clinical use.

Animals↗
PubMed1999

Cigarette smoking, alcohol consumption and risk of nasopharyngeal carcinoma in Taiwan.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is rare in most countries but occurs with relatively high frequency among southern Chinese populations throughout the world. A case-control study of NPC was conducted in Taiwan to investigate the importance of active and passive cigarette exposure and alcohol consumption as risk factors for this disease. METHODS: 375 histologically confirmed incident NPC cases (99% response rate) were prospectively identified from two hospitals in Taipei between July 1991 and December 1994 and administered a detailed questionnaire. 327 healthy community controls individually matched to cases on sex, age and residence were selected (88% response rate). RESULTS: After multivariate adjustment, the odds ratio (OR) and 95% confidence interval (CI) was 1.7 (1.1-2.9 with p = 0.03 for increasing dose-response) for those who smoked for > or = 25 years compared with non-smokers. Passive smoking during childhood or adult life was not associated with an increased risk of disease. Alcohol consumption was not associated with NPC risk. The OR for subjects with > or = 15 grams of ethanol per day compared to non-drinkers was 1.1 (95% CI = 0.7-1.7). CONCLUSIONS: Our results suggest that long term cigarette smoking is associated with NPC but that low level exposure to cigarette smoke via passive exposure and alcohol consumption are not associated with disease risk.

Adult↗
PubMed1999

Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa.

Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries in both the healthy and the HIV-infected populations. This correlates with the fact that hardly any AIDS-related Kaposi's sarcoma has been reported in these countries. In contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in both healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres show that only 3/82 (3.7%) have antibody to HHV-8, demonstrating that there is little, if any, cross-reactivity between antibodies to these two gamma viruses.

Adolescent↗
PubMed1999

Risk factors for human T cell lymphotropic virus type II infection among the Guaymi Indians of Panama.

To examine risk factors for human T cell lymphotropic virus type II (HTLV-II) infection, a case-control study was conducted among the Guaymi Indians of Panama. In females, HTLV-II seropositivity was associated with early sexual intercourse (</=13 vs. >15 years; odds ratio [OR], 2.50; 95% confidence interval [CI], 1.11-6.14) and number of lifetime sex partners. One partner increased risk of seropositivity by 30% (OR, 1.30; CI, 1.05-1.64), and risk increased with number of partners. Similar risk was associated with number of long-term sexual relationships. Among males, intercourse with prostitutes was associated with HTLV-II seropositivity (OR, 1.68; CI, 1.04-2.72). These data support a role for sexual transmission in HTLV-II infection. Association of seropositivity with primary residence in a traditional village (OR, 3.75; CI, 1.02-15.38) and lack of formal education (0 vs. >6 years [OR, 3.89; CI, 1.67-9.82]) observed in males may reflect differences in sexual practices associated with acculturation.

Adolescent↗
PubMed1998

What we know about chronic fatigue syndrome and its relevance to the practicing physician.

A number of recent reports have emphasized laboratory abnormalities, clinical tests, and therapeutic approaches that appear to have great promise in the evaluation and management of chronic fatigue syndrome (CFS). Because of the heterogeneity of CFS, the cost of many of these assays and procedures, and the frequent lack of skilled consultants able to apply relevant sophisticated procedures, the solo healthcare provider is often left with uncertain options in patient management. This article summarizes current approaches to patient management, utilizing available information relevant to CFS.

Diagnosis, Differential↗
PubMed1998

Retroviral vector-modified bone marrow stromal cells secrete biologically active factor IX in vitro and transiently deliver therapeutic levels of human factor IX to the plasma of dogs after reinfusion.

Canine bone marrow stromal cells (BMSCs), transduced ex vivo with retroviral vectors, expressed and secreted biologically active human and canine coagulation factor IX (hFIX and cFIX) in vitro, and on autologous reinfusion expressed hFIX into the circulation of normal (nonhemophiliac) dogs. Human FIX, when expressed in vitro by BMSCs of two dogs at 1.22 and 1.39 microg/10(6) cells/24 hr in medium supplemented with vitamin K, respectively, exhibited 28.1 and 27.3% normal biological activity as determined on the basis of a one-stage clotting assay. BMSCs of two additional dogs expressed 1.54 and 4.81 microg of cFIX/10(6) cells/24 hr in vitamin K-supplemented medium and the expressed cFIX possessed 58.4 and 32.9% normal activity, respectively. Between 2.33 and 3.35 x 10(8) transduced BMSCs, expressing 1.22 and 2.61 microg of hFIX/10(6) cells/24 hr or 3.24 and 7.82 microg of cFIX/10(6) cells/24 hr were reintroduced into the four donor dogs by intravenous infusion. Human FIX was detected in plasma for 7 or 12 days after BMSC reinfusion, with peak levels of 85.8 and 233.0 ng/ml observed at 2 days. Canine anti-hFIX antibodies, which were detected as early as 2-4 days after reinfusion of BMSCs expressing hFIX, may have masked potentially longer duration expression in vivo. Peak plasma levels of hFIX represented 2.1 and 5.8% normal human hFIX levels. When adjusted for percent normal one-stage clotting activity determined in vitro, these levels represented 0.6 and 1.6% normal human hFIX activity levels. Thus, we have demonstrated that retroviral vector-modified BMSCs can deliver human therapeutic levels of hFIX to the circulation of dogs.

Animals↗
PubMed1998

Dysfunction of natural killer activity in a family with chronic fatigue syndrome.

A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed chronic fatigue syndrome (CFS) as adults. All 8 met criteria for the CFS case definition as recommended by the Centers for Disease Control and Prevention. Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity in 4-h 51Cr-release assays and for the number of circulating CD3-CD56(+) and CD3-CD16(+) by flow cytometry. NK activity of the affected immediate family members (cases, n = 8) was significantly lower (P = 0.006, two-sided) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and the pairwise comparison of unaffected family members to either cases or controls showed no statistically significant difference (P = 0.29, two-sided). No differences were seen between the groups in the absolute number of CD3-CD56(+) or CD3-CD16(+) lymphocytes in the peripheral blood. Familial CFS was associated with persistently low NK activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had pediatric malignancies. Low NK activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer.

Adolescent↗
PubMed1998

Cancer and a fatiguing illness in Northern Nevada--a causal hypothesis.

PURPOSE: We investigated the possibility that chronic fatigue syndrome (CFS) predisposes to cancer by comparing the cancer pattern in an area in northern Nevada, where an outbreak of a fatiguing illness, which included cases of CFS, was reported, to an area in southern Nevada, where no such illness was reported. METHODS: Data from the computerized Nevada Cancer Registry were utilized to compare incidence rates of four malignancies--brain cancer, non-Hodgkin lymphoma (NHL), lung cancer, and breast cancer--in Washoe and Lyon Counties, where an unexplained fatiguing illness was reported during 1984-86, with comparably sized Clark County, where no such illness was reported. RESULTS: Higher incidences of NHL and primary brain tumors were noted in the two northern Nevada counties (Washoe and Lyon) in 1986 and 1987 respectively, compared to the southern Nevada (Clark) county. Similar patterns were not seen for breast or lung cancer. CONCLUSIONS: This study provides a model for investigating the possible predisposition of CFS patients to develop cancer using other cohorts, but it is currently premature to accept such a link at this time.

Adult↗
PubMed1997

Epidemic neuromyasthenia and chronic fatigue syndrome in west Otago, New Zealand. A 10-year follow-up.

BACKGROUND: In 1984, an outbreak of an illness characterized by prolonged unexplained fatigue was reported in West Otago, New Zealand. This outbreak resembled other reported outbreaks of epidemic neuromyasthenia in that affected individuals presented with a spectrum of complaints ranging from transient diarrhea and upper respiratory disorders to chronic fatigue syndrome (CFS). OBJECTIVE: To obtain a perspective on the natural history of CFS not possible in clinic-based studies. METHODS: Twenty-three of the 28 patients in the original report were contacted and asked to complete written questionnaires. Interviews were obtained in person or via telephone. RESULTS: Ten (48%) of the 21 patients with satisfactory interviews appeared to meet the current Centers for Disease Control and Prevention (CDC) case definition of CFS, and 11 were classified as having prolonged or idiopathic fatigue. A return to premorbid activity was seen in most (n = 16) patients, although some reported the need to modify their lifestyle to prevent relapses. A female predominance was noted in those meeting the CDC case definition for CFS, whereas males predominated in patients diagnosed as having prolonged or idiopathic fatigue. CONCLUSIONS: The high proportion of patients recovering from CFS in the West Otago cluster suggests that epidemic-associated CFS has a better prognosis than sporadic cases. Female sex was confirmed as an important risk factor for CFS.

Adolescent↗
PubMed1997

Systemic delivery of human growth hormone or human factor IX in dogs by reintroduced genetically modified autologous bone marrow stromal cells.

Canine bone marrow stromal cells were expanded to numbers in excess of 10(9) cells from the initial 10-20 ml of marrow aspirates and transfected to express high levels of human growth hormone (hGH) in vitro. Ex vivo-modified marrow stromal cells were used in a gene therapy model system for the systemic delivery of transgene products in dogs. Adherent bone marrow stromal cell cultures, established and expanded from iliac crest marrow aspirates from each of 8 dogs, were transfected with a hGH gene plasmid expression vector and shown to express from 0.54-3.84 micrograms/10(6) cells per 24 hr hGH in vitro. The transfected plasmid vector does not possess a eukaryotic origin of replication nor does it possess sequences required for efficient integration into the host cell genome. As such, expression was expected to be transient. Transfected cells were autologously reintroduced into each dog by either infusion into a foreleg vein or directly into iliac crest marrow. In two cases, the stromal cells were cryopreserved following transfection, and subsequently thawed and infused. In one case, the expanded stromal cells were first cryopreserved, and then thawed, recultured, transfected, and infused. Reintroduced cell numbers ranged from 2.2 x 10(7) to 2.6 x 10(9), with total hGH expression capacities ranging from 62 to 1,400 micrograms/24 hr. Plasma of each of the dogs contained detectable hGH for a mean of 3.1 days (SD +/- 0.8 day) ranging from 2 to 5 days following reinfusion of cells. Peak plasma levels ranged from 0.10 to 1.76 ng/ml. Similar hGH expression values, based upon total expression capacity of the cells infused and dog body weight, were obtained for all dogs. Vector-modified stromal cells were detectable, by polymerase chain reaction (PCR) analysis, in the peripheral circulation following reinfusion in all 4 dogs analyzed. In 3 of the dogs, modified stromal cells were detected for 8.5-15 weeks. In addition, modified stromal cells were detected in iliac crest marrow of 2 dogs for 9 and 13 weeks, respectively, following reinfusion. In another experiment, cultured bone marrow stromal cells were transfected with a human factor IX (hFIX) plasmid vector. Modified cells (5.57 x 10(8)), with a total hFIX expression capacity of 281 micrograms/24 hr, were reinfused, resulting in detectable hFIX in plasma continuously for 9 days with a peak level of 8 ng/ml on day 1. These results demonstrate that the ex vivo bone marrow stromal cell system is a potentially powerful method by which to deliver secreted transgene product to the systemic circulation of large animals.

Animals↗
PubMed1996

Epstein-Barr virus and familial Hodgkin's disease.

Several studies suggest that the Epstein-Barr virus (EBV) is etiologically linked to Hodgkin's disease (HD). This study was undertaken to examine the role of EBV in familial HD (FHD). Among 60 FHD patients from 27 families with two or more cases per family, we tested available paraffinized tumor tissues from 46 cases by in situ hybridization for EBV-encoded RNA (EBER1) expression. Thirteen of 46 FHD patients (28%) had EBER1 expressed in the Reed-Sternberg cells. Concordance rate of EBV positivity was evaluated among 34 first-degree related pairs from 17 families for which both cases had available paraffinized tumor tissues. Only two of 17 pairs were concordant for EBER1 positivity. There was no excess of positive concordance (P = .18). Serologically, FHD patients had higher geometric mean antibody titers (GMTs) to the viral capsid antigen (VCA) and early antigen D (EA-D). There was no difference in seroprevalence between patients and control groups, nor was there concordance in elevated serology among 15 pairs of first-degree related FHD cases. Young adult unaffected family members (UFM) may not react to EBV in the same way as the general population as evidenced by the lower titer of VCA, although not statistically significant, and significantly lower titers of EA-D, compared with age-matched controls. While EBV might have some role in a subset of HD, lack of concordance of EBER1 expression and EBV serology among the FHD cases in the same family suggest that EBV does not play an important role in FHD.

Adolescent↗
PubMed1996

Genetic variants of human T-lymphotrophic virus type II in American Indian groups.

The human T-lymphotropic virus type II (HTLV-II) is found in many New World Indian groups in North and South America and may have entered the New World from Asia with the earliest migration of ancestral Amerindians over 15,000 years ago. To characterize the phylogenetic relationships of HTLV-II strains infecting geographically diverse Indian populations, we used polymerase chain reaction to amplify HTLV-II sequences from lymphocytes of seropositive Amerindians from Brazil (Kraho, Kayapo, and Kaxuyana), Panama (Guaymi), and the United States (the Navajo and Pueblo tribes of the southwestern states and the Seminoles of Florida). Sequence analysis of a 780-base pair fragment (located between the env gene and the second exons of tax/rex) revealed that Amerindian viruses clustered in the same two genetic subtypes (IIa and IIb) previously identified for viruses from intravenous drug users. Most infected North and Central American Indians had subtype IIb, while HTLV-II infected members of three remote Amazonian tribes clustered as a distinct group within subtype IIa. These findings suggest that the ancestral Amerindians migrating to the New World brought at least two genetic subtypes, IIa and IIb. Because HTLV-II strains from Amazonian Indians form a distinct group within subtype HTLV-IIa, these Brazilian tribes are unlikely to be the source of IIa viruses in North American drug users. Finally, the near identity of viral sequences from geographically diverse populations indicate that HTLV-II is a very ancient virus of man.

Amino Acid Sequence↗