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Biomedical subjects

H Hu

Publications and source records attributed to H Hu.

At least 343 records · Page 19Linked to original sources

Localization of neuropeptide Y-like immunoreactivity in the cat hypothalamus.

The distribution pattern of neuropeptide Y-like immunoreactivity (NPY-Li) in cat hypothalamus was studied using avidin-biotin modification of immunocytochemical method. This study showed cell bodies containing NPY-Li in the periventricular and the infundibular nuclei and also a moderate number of neurons with NPY-Li in the ventromedial nucleus, an observation not reported in earlier studies. Fibers with NPY-Li were noted throughout the hypothalamus, but most prominently within the periventricular regions. The location of NPY cells within the hypothalamus suggests the possibility of an interaction with dopaminergic and other proopiomelanocortinergic neurons.

Animals↗

The distribution pattern of alpha-MSH-like immunoreactivity in the cat central nervous system.

The distribution pattern of alpha-melanocyte stimulating hormone-like immunoreactivity (alpha-MSH-Li) was studied in cats using avidin-biotin modification of immunocytochemical method. Cell bodies containing alpha-MSH-Li were observed in the medial basal hypothalamus, especially in the infundibular nucleus, the lateral hypothalamus and near zona incerta. Fibers with alpha-MSH-Li extended beyond the hypothalamus, into the paraventricular nucleus of the thalamus, rostral amygdala, periaqueductal gray, locus ceruleus, parabrachial nucleus and medial nucleus of the nucleus tractus solitarius. Axons with alpha-MSH-Li were also seen diffusely in various cortical areas, but more extensively in the limbic cortical regions. The distribution pattern of the cell bodies and fibers containing alpha-MSH-Li bears several similarities to that seen in rats, but differs in that the alpha-MSH-Li was not observed in cell bodies in locations other than the medial basal and lateral hypothalamus.

Animals↗

Relations of bone and blood lead to cognitive function: the VA Normative Aging Study.

The relationship between performance on cognitive tasks and circulating levels of lead in blood and accumulated levels of lead in bone was examined in 141 middle-aged and elderly men from a longitudinal study of aging. The mean (SD) blood lead level was low [5.5 (3.5) micrograms/dl], and mean patella and tibia lead levels were 31.7 (19.2) and 22.5 (12.2) micrograms/g bone mineral, respectively. Cognitive tests measured attention, perceptual speed, memory, language, and spatial copying. Regression models, adjusted for age and education, demonstrated that men with higher levels of blood lead recalled and defined fewer words, identified fewer line-drawn objects, and required more time to attain the same level of accuracy on a perceptual comparison test as men with the lowest level of blood lead. Men with higher levels of blood and bone (tibia) lead copied spatial figures less accurately; men with higher levels of bone (tibia) lead had slower responses for pattern memory. These findings suggest that low levels of lead contribute to impairments in cognitive function among elderly men.

Aged↗

Genetic construction and characterization of an anti-monkey CD3 single-chain immunotoxin with a truncated diphtheria toxin.

We have previously developed a chemically conjugated anti-rhesus monkey CD3 immunotoxin FN18-CRM9 that can deplete in vivo T cells and induce long term tolerance of mismatched renal allograft in rhesus monkeys. This immunotoxin is a monkey analogue of anti-human CD3 immunotoxin UCHT1-CRM9. In this study, we cloned the light and heavy chain variable regions of anti-monkey CD3 monoclonal antibody FN18 and constructed a single-chain Fv (sFv) by linking variable light and variable heavy regions with a (Gly4Ser)3 linker. The single-chain immunotoxin DT390-FN18sFv was constructed by ligating the sFv to the carboxyl terminus of DT390, a truncated form of diphtheria toxin. The DT390-FN18sFv fusion protein was expressed in Escherichia coli and purified with Ni-RTA affinity and anion exchange columns. Similar to the chemically conjugated immunotoxin FN18-CRM9, DT390-FN18sFv can also specifically inhibit protein synthesis in primary monkey T cells in a dose-dependent manner. DT390-FN18sFv at 10(-7) mol/L or FN18-CRM9 at 10(-8) mol/L is sufficient to reduce protein synthesis of monkey primary T cells to less than 5% of the control. The 50% inhibition dosage (IC50) of FN18-CRM9 is 1 x 10(-10) mol/L, while the IC50 of DT390-FN18sFv is 1 x 10(-8) mol/ L, reflecting the lowered affinity of monovalent Fab' FN18 to its parental divalent antibody. The availability of functional FN18sFv will provide the basis for the construction of divalent anti-CD3 immunotoxins for preclinical studies on the induction of tolerance in organ transplantation and experimental autoimmune diseases.

Adenosine Diphosphate Ribose↗

Parallel synthesis and biocatalytic amplification of a cross-conjugated cyclopentenone library.

A combination of parallel chemical synthesis and biocatalysis has been used to prepare and amplify a library of cross-conjugated cyclopentenones. A number of marine and terrestrial natural products with antibiotic activity are known to incorporate this pharmacophore. The library was screened for anticancer, antimycobacterial, antifungal, and antibacterial activity. The positive results from the screens provide an indication of the structural features that are associated with activity in the various assays and suggest promising avenues for further inquiry.

Biotransformation↗

Determinants of blood lead levels across the menopausal transition.

In this study, the authors sought to evaluate the impact of menopause on lead remobilization from bone-lead stores. The study was conducted between 1993 and 1995 in Mexico City and included 903 women (mean age = 46.8 y [standard deviation = 8.2 y]). Participants provided information about reproductive variables and known risk factors for high PbB levels. PbB levels were determined with graphite furnace atomic absorption spectrophotometry. The authors used linear-regression models to describe the relationship between PbB levels and variables of interest. PbB levels ranged from 1.0 microg/dl to 43.8 microg/dl (mean = 11.0 microg/dl). Menopausal women at baseline had the highest PbB levels; the mean difference between pre- and postmenopausal women was 0.76 microg/dl (95% confidence interval = 0.024, 1.48). We observed an inverted U-shaped relationship between PbB level and age. The highest PbB levels were observed in women aged 47-50 y. Other important predictors of PbB levels were use of lead-glazed ceramics, number of pregnancies, history of cigarette smoking, and height. Our results support the hypothesis that bone lead may be mobilized during menopause and may constitute an important source of exposure.

Adult↗

X-ray fluorescence measurements of lead burden in subjects with low-level community lead exposure.

A k-x-ray fluorescence (K-XRF) instrument that can measure in vivo bone lead at low levels was used on a population of 34 adults with no known history of excessive lead exposure. A questionnaire that gathered information relevant to occupational and environmental lead exposure was administered prior to the measurement. A 30-min measurement that produced an average estimated uncertainty of 6 mcg lead/g bone mineral was taken at the mid-tibial diaphysis for each subject. Eighteen subjects had bone lead levels below the measurement uncertainty. The remainder had bone lead levels ranging up to 21 mcg lead/g bone mineral. Bone lead levels were greater among older subjects. Among young adult subjects, bone lead levels greater than the measurement uncertainty were confined entirely to subjects who had grown up in housing that was estimated to have been build prior to 1955. Such a childhood environment is at high risk of fostering exposure to biologically absorbable lead through ingestion of lead paint-contaminated dust and lead pipe-contaminated water. We conclude that the K-XRF technique has the potential to distinguish between low levels of lead burden in epidemiologic studies.

Adult↗

Attentional correlates of dentin and bone lead levels in adolescents.

In an effort to determine whether specific aspects of attention are impaired by lead, the performance of 79 subjects (aged 19 and 20 y) on a neuropsychologically based battery of tests of attention was examined in relation to lead levels in deciduous teeth (dentin), current blood, and tibia and patella bones measured by K-X-ray fluorescence. Dentin lead levels averaged 14 micrograms/g. Most bone lead levels were less than 10 micrograms/g. Dentin lead levels were related inversely to scores on two of four attention factors: focus-execute (ability to select and respond to critical information) and shift (ability to shift focus adaptively). Few significant associations were observed between bone lead levels and performance. Five individuals with the ALA-D 1-2 isozyme phenotype tended to achieve more optimal scores. Executive and self-regulation functions may be among the cognitive skills targeted by lead.

Adolescent↗

Longitudinal relationship between dentin lead levels in childhood and bone lead levels in young adulthood.

A retrospective cohort study was conducted to examine the relationship between tooth lead in children and bone lead levels in young adults. Members of a cohort of young adults were reassessed 13 y after initial examination at an ambulatory clinical research center. Dentin lead levels were measured by anodic stripping voltammetry during the years 1975-1978, and bone lead levels of the tibia and patella were measured by K-x-ray fluorescence technique during 1989 and 1990. A total of 63 subjects who had no history of chelation or had no missing information on potential confounders were studied. The median follow-up interval was 13.2 y. Dentin lead levels averaged 13.4 micrograms/g (standard deviation [SD] = 10.7 micrograms/g, range = 2.9-51.8 micrograms/g), and bone lead levels averaged 1.3 micrograms/g (SD = 4.4 micrograms/g, range = -9-13 micrograms/g) for tibia and 5.4 micrograms/g (SD = 8.4 micrograms/g, range = -10-25 micrograms/g) for patella. The authors controlled for age, sex, race, and mother's socioeconomic status, and dentin lead levels were predictive of higher tibia, patella, and mean bone lead levels in 32 subjects (follow-up interval of 11.8-13.2 y). A correction for measurement errors in dentin lead measurements was made, and it was determined that a 10-micrograms/g increase in dentin lead levels in childhood was predictive of a 1-microgram/g increase in tibia lead levels, a 5-micrograms/g increase in patella lead levels, and a 3-micrograms/g increase in mean bone lead levels among the young adults. It was concluded, therefore, that lead exposure in early life may be used to predict elevated body burden up to 13 y later.

Adolescent↗

Levels of lead in blood and bone of women giving birth in a Boston hospital.

Blood lead levels declined among Americans aged 1-74 y between the years 1976 and 1991 (National Health and Examination Survey [NHANES III]). In 1990, umbilical cord blood lead levels were surveyed among 223 women who gave birth in a Boston hospital obstetrical service. In a survey conducted 10 y earlier, women had a mean umbilical cord blood lead level of 6.56 micrograms/dl (standard deviation = 3.19). In another subgroup of 41 women who were 1-4 wk postpartum, bone lead levels were surveyed with a K-x-ray fluorescence instrument and by analysis of venous blood lead levels. In 1990, umbilical cord blood lead levels were very low (i.e., mean and median of 1.19 [standard deviation = 1.32] and 1.0 micrograms/dl, respectively. In the subgroup of postpartum women, lead levels in cortical bone (i.e., tibia) and trabecular bone (i.e., patella) were also low (i.e., tibia mean and median of 4.5 [standard deviation = 4.0] and 4 micrograms/g bone mineral, respectively); patella mean and median of 5.8 [standard deviation = 4.5] and 5 micrograms/g, respectively). Maternal age was the only factor associated (i.e., borderline [p=.076]) with bone lead. Umbilical cord blood lead levels among women served by this Boston hospital from 1980 to 1990 declined dramatically, thus paralleling the National Health and Examination Survey. Bone lead levels were also low, but lead remains a reproductive hazard to women in select high-risk groups.

Adolescent↗

Phase II multicenter open-label study of carboplatin and pegylated liposomal doxorubicin in uterine and cervical malignancies.

The results of a multicenter phase II study investigating carboplatin and pegylated liposomal doxorubicin (PLD) in patients with recurrent/metastatic uterine and cervical malignancies (UCM) are presented here. Fifty-three subjects with measurable, untreated, advanced UCM were enrolled. Fifty-one were evaluable for response. Prior combined-modality treatment was permitted if a component of primary therapy. Patients received carboplatin AUC = 5 with PLD 35 mg/m(2) intravenously once every 4 weeks. Overall response rate was 33% (35% stable disease). Overall survival (OS) at six months was 86% (95% CI 76%-96%). Six-month progression-free survival (PFS) was 43% (95% CI 30%-57%). Median PFS was 22.9 weeks (range 16.0-35.3) and median OS was 49.1 weeks (range 41.4-75.1). The most frequent grade 3-4 nonhematological adverse events were: abdominal pain (n = 7), fatigue (4), vomiting (4), nausea (3), and shortness of breath (3). There was 1 report of grade 3 hand-foot syndrome and none of grade 4. Twelve patients had first infusion reactions with only 1 discontinuing treatment. Grade 3-4 neutropenia occurred in 26/230 cycles (11.3%). There were no treatment-related deaths. The combination of carboplatin and PLD is well tolerated with sufficient activity to justify additional evaluation in clinical trials and might be suited to the addition of a taxane.

Adolescent↗

Relationship of hemoglobin to occupational exposure to motor vehicle exhaust.

OBJECTIVE: To study the relationship of hemoglobin to exposure to motor vehicle exhaust. DESIGN: Survey. PARTICIPANTS: Traffic police, bus drivers, and auto-shop workers (all exposed to auto exhaust in Madras, India) and unexposed office workers. MAIN OUTCOME MEASURES: We measured levels of blood lead (by graphite furnace atomic absorption spectrophotometry), and hemoglobin. Information also was collected on age, employment duration, smoking status, alcohol ingestion, and diet type (vegetarian or nonvegetarian). RESULTS: Increasing exposure to motor vehicle exhaust, as reflected by job category, was significantly associated with lower levels of hemoglobin (p < 0.01). A final multivariate regression model was constructed that began with indicator variables for each job (with office workers as the reference category) and included age, duration of employment, blood lead level, alcohol ingestion, dietary type, and smoking status. After a backward-elimination procedure, employment duration as an auto-shop worker or bus driver remained as significant correlates of lower hemoglobin level and current smoking and long employment duration as significant correlates of higher hemoglobin level. CONCLUSIONS: Occupational exposure to automobile exhaust may be a risk factor for decreased hemoglobin level in Madras. This effect appears to be independent of blood lead level and may represent hematopoietic suppression incurred by benzene or accumulated lead burden (which is not well reflected by blood lead levels). Smoking probably increased hemoglobin level through the chronic effects of exposure to carbon monoxide. In this study, a long employment duration may have served as a proxy for better socioeconomic, and therefore, better nutritional status.

Adult↗

Effect of iron deficiency anemia on lead distribution after intravenous dosing in rats.

OBJECTIVE: To determine the effect of iron deficiency anemia on blood and tissue lead distribution. METHODS: 24 weanling rats were divided into 2 groups. One group received an iron replete diet (200 ppm); the other received a low iron diet (20 ppm). After 24 days, each group was further subdivided into two doses of lead (5 mg/kg and 10 mg/kg) which was administered intravenously. Rats were continued on their respective diets for 7 days post-lead injection to allow tissue distribution, then sacrificed and blood and tissue lead concentration measured. RESULTS: Prior to lead administration, baseline blood lead concentrations were not significantly different between groups. At sacrifice, whole blood lead levels were significantly higher in iron deficient animals than in iron replete at both 5 and 10 mg/kg administered lead. Iron deficient animals had comparable lead concentrations to iron replete animals in brain, kidney and liver. Femur lead concentrations were higher at 10 mg/kg administered lead. CONCLUSION: Iron deficiency alters lead distribution such as that increased lead is found in blood for a given exposure.

Anemia, Iron-Deficiency↗

Environmental lead contamination and pediatric lead intoxication in an Andean Ecuadorian village.

Environmental lead (Pb) contamination was measured in samples of soil and locally grown food produce in a remote Ecuadorian village where Pb glazing of ceramics is the local cottage industry. The Pb concentration levels of local soil samples collected at varying distances from a cluster of backyard Pb baking kilns were 29,213 ppm (microg/g) at 0.001 km, 172 ppm at 0.005 km, 81 ppm at 0.01 km, 55 ppm at 1 km, 19 ppm at 2 km, and 1.4 ppm at 6 km, significantly higher than levels in control soil samples from non-Pb-glazing reference areas. Samples of locally grown food produce were also found to be Pb contaminated. Venous blood samples from 166 schoolchildren (ages 4 months to 15 years) in the study area and 56 children in the reference area showed mean blood lead levels of 40.0 microg/dl (SD: 24.5; range: 6.2. - 119.1 microg/dL) and 6.6 microg/dL (SD: 3.4; range: 1.9 - 18.1 microg/dL), respectively, which were significantly different (p = 0.0001). The Pb levels in milk from breastfeeding mothers ranged from 1.44 to 39 ng/g. Lead isotope ratios of the children's blood and of samples of village soil revealed a common Pb source or "fingerprint."

Adolescent↗

Functional relationship and gene ontology classification of breast cancer biomarkers.

Breast cancer is a complex disease that still imposes a significant healthcare burden on women worldwide. The etiology of breast cancer is not known but significant advances have been made in the area of early detection and treatment. The advent of advanced molecular biology techniques, mapping of the human genome and availability of high throughput genomic and proteomic strategies opens up new opportunities and will potentially lead to the discovery of novel biomarkers for early detection and prognostication of breast cancer. Currently, many biomarkers, particularly the hormonal and epidermal growth factor receptors, are being utilized for breast cancer prognosis. Unfortunately, none of the biomarkers in use have sufficient diagnostic, prognostic and/or predictive power across all categories and stages of breast cancer. It is recognized that more useful information can be generated if tumors are interrogated with multiple markers. But choosing the right combination of biomarkers is challenging, because 1) multiple pathways are involved, 2) up to 62 genes and their protein products are potentially involved in breast cancer-related mechanisms and 3) the more markers evaluated, the more the time and cost involved. This review summarizes the current literature on selected biomarkers for breast cancer, discusses the functional relationships, and groups the selected genes based on a Gene Ontology classification.

Biomarkers, Tumor↗

[Occupational exposure to inorganic lead in a printing plant in Mexico City].

OBJECTIVE: To describe occupational lead exposure and its biological indicators in workers in a printing company. MATERIAL AND METHODS: An epidemiological and industrial hygiene research was undertaken. Lead was measured in the air of work environment and on the hands of the participants; additionally, subjects underwent a venous blood samples for the determination of whole blood lead by atomic absorption spectrophotometry; and a bone lead measurement using a spot-source 109Cd K-X-ray fluorescence instrument. Also, a standardized questionnaire was applied. We obtained information on demographic and life styles factors, work history, type of work, position and activity within the company. RESULTS: Of the 209 workers, 117 agreed to participate and 90 (83.3% males and 16.7% females) completed all phases of the study. The average lead concentrations were: in air samples, of 0.94 microgram/m3; in hands before washing, of 6,802 micrograms/m2; in hands after washing, of 194 micrograms/m2; in whole blood, of 12.3 micrograms/dl; and in tibia and fibula, of 25.9 and 43.3 micrograms Pb/g of bone mineral, respectively. Important variations in these measurements were observed according to the workers post. CONCLUSIONS: Worldwide, lead exposure levels have been used to evaluate acute exposures being in the workplace. The higher lead levels find in the bone of the workers in this study are similar to other occupational studies in the United States of America and suggest that the accumulated metal in bone may be an important endogenous exposure source, and here its measurement importance. However in developing countries because its high costs per application, the measurements in bone lead become limited to epidemiological research, although not as an instrument for occupational epidemiological surveillance. In Mexico, there are no reliable studies of occupational lead exposure, which would allow the establishment of both, maximum permissible ambient and biological levels. This study is intended to contribute to blood lead standard setting, which is being discussed in Mexico.

Adult↗

Cytotoxic T lymphocytes infiltrating the human cardiac allograft show a restriction in T-cell receptor V beta gene usage: a study on serial biopsy and blood specimens.

T lymphocytes were propagated in vitro from endomyocardial biopsy specimens that were obtained weekly from four patients during the first 2 to 3 months after heart transplantation. The culture was performed in the presence of recombinant interleukin-2 and interleukin-4, with or without mitogen, in which especially CD8+ donor-specific cytotoxic T cells expanded. These cells, presumably reflecting an in vivo activated population, could even be cultured from biopsy specimens without histopathologic signs of rejection. A preferential expression of T cell receptor V beta gene families was found in these T-cell lines. This finding is in contrast with the heterogenous expression in peripheral blood T cells of the same patient. The restriction in V beta gene family expression was substantiated in the evaluation of clones obtained from two cell lines. Among 17 donor-specific cytotoxic T-cell clones derived from one cell line, only four V beta gene families were expressed. All five clones from the other cell line used the V beta 8 family. Some clones expressing a distinct V beta gene family used the same V-D-J junction sequence, indicative of their origin from the same precursor. With the use of oligonucleotide probes complementary to clone-specific V-D-J junction sequences, four of five clones were detected not only in the parent T-cell line but also in T-cell lines derived from biopsy specimens with rejection reactions taken 1 week earlier and 2 weeks later and in blood cells taken before and 0.5, 3, and 6 months after transplantation; these clones were not detected in blood cells harvested 12 months after transplantation. This study showed a restricted usage of the V beta gene families by activated donor-specific cytotoxic T lymphocytes in the heart transplant.

Antigens, CD↗