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Biomedical subjects

Y Huang

Publications and source records attributed to Y Huang.

At least 1,081 records · Page 60Linked to original sources
PubMed1993

Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions.

PURPOSE: To determine the cataractogenic potential dose of high velocity iron ions as a fixation of dose administered singly or fractionated. The dose is critical to risk assessment and to theories of radiation action and cataractogenesis. METHODS: Twenty-eight-day-old rats were examined by slit-lamp biomicroscopy on a weekly-bi-weekly basis for more than 2 yr after radiation exposure. For the acute exposure study doses of 1, 2, 5, 25, and 50 cGy were evaluated. The fractionated regimens involved total doses of 2, 25, and 50 cGy. The reference radiation consisted of 50, 100, 200, or 700 cGy of 250 kilovolt (peak) x-rays. RESULTS: In accordance with previous findings in the rat using 570 MeV/amu 40Ar ions, the relative biologic effectiveness increased rapidly with decreasing dose, reaching values as high as 100. Unlike 40Ar ions, fractionation of the 56Fe doses did not produce a consistent enhancement at any of the doses examined. CONCLUSIONS: The data support the previous findings of a high cataractogenic potential for high linear energy transfer (LET) radiation. The effectiveness for the production of cataracts increases with decreasing dose relative to x-rays and is independent of dose protraction. Although the present study did not reveal a consistent enhancement of effect when the ions were applied in fractions, the results are consistent with at least one theory of the inverse dose-rate effect observed for high-LET radiation.

Animals↗
PubMed1993

Accelerated heavy particles and the lens. VIII. Comparisons between the effects of acute low doses of iron ions (190 keV/microns) and argon ions (88 keV/microns).

The nature of the RBE-LET relationship for radiation-induced effects in vivo is not well known in the high-LET range above about 100 keV/microns. Here, we compare the cataractogenic effects of acute doses of 190 keV/microns iron ions on the eyes of rats with those of 88 keV/microns argon ions. The RBEs of the two radiations cannot be distinguished statistically, both being between 50 and 200 at our lowest dose of 0.01 Gy and decreasing to between 2 and 14 at our highest dose of 0.5 Gy; these values are consistent with results obtained in vivo, both for cataractogenesis and for oncogenesis. For this end point, therefore, the RBE-LET relationship probably varies very slowly between 88 and 190 keV/microns. On the basis of these studies with acute doses of 88 and 190 keV/microns particles, the detailed distribution in LET of the very high-LET galactic cosmic-ray dose to which astronauts in deep space are exposed may not be critical for the prediction of biological hazard. Such a conclusion might simplify the task of high-LET radiation risk estimation in space.

Animals↗
PubMed1992

Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers.

Loss of heterozygosity occurring on various chromosomes has been described in the majority of human tumors. The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppressor genes. We examined 72 esophageal tumors (46 squamous cell carcinomas and 26 adenocarcinomas) for loss of heterozygosity at the p53, Rb, APC, MCC, and DCC loci. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing polymerase chain reaction at polymorphic sites within the genes. Loss of heterozygosity occurred in 55% of informative cases at p53, in 48% of informative cases at Rb, in 66% at APC, in 63% at MCC, and in 24% at DCC. Ninety-three % of tumors informative at all loci (fully informative) lost heterozygosity of at least one locus. A high percentage of fully informative tumors (71%) also lost heterozygosity at more than one locus. There were no significant differences among histological types in the prevalence of loss of heterozygosity at any locus. There were correlations of losses involving MCC versus DCC, Rb, and p53. These data suggest that (a) allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletions involving MCC may not occur independently of deletions involving other tumor suppressor genes; and (c) the accumulation of multiple allelic deletions involving specific tumor suppressor genes may be important in most esophageal tumorigenesis or tumor evolution.

Adenocarcinoma↗
PubMed1992

Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein (pIXY 321) enhances high-dose Ara-C-induced programmed cell death or apoptosis in human myeloid leukemia cells.

High dose Ara-C (HIDAC) induces programmed cell death (PCD) or apoptosis in vitro in human myeloid leukemia cells, which correlates with the inhibition of their clonogenic survival. Hematopoietic growth factors (HGFs) granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) have been demonstrated to enhance the metabolism and cytotoxic effects of HIDAC against leukemic progenitor cells. We examined the effect of pIXY 321 (a GM-CSF/IL-3 fusion protein) on HIDAC-induced PCD and related gene expressions as well as HIDAC-mediated colony growth inhibition of human myeloid leukemia cells. Unlike the previously described effects of HGFs on normal bone marrow progenitor cells, exposure to pIXY 321 alone for up to 24 hours did not suppress PCD in HL-60 or KG-1 cells. However, exposure to pIXY 321 for 20 hours followed by a combined treatment with Ara-C plus pIXY 321 for 4 or 24 hours versus treatment with Ara-C alone significantly enhanced the oligonucleosomal DNA fragmentation characteristic of PCD. This was temporally associated with a marked induction of c-jun expression and a significant decrease in BCL-2. In addition, the treatment with pIXY 321 plus HIDAC versus HIDAC alone produced a significantly greater inhibition of HL-60 colony growth. These findings highlight an additional mechanism of HIDAC-induced leukemic cell death that is augmented by cotreatment with pIXY 321 and may contribute toward an improved antileukemic activity of HIDAC.

Actins↗
PubMed1992

Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers.

The tumor suppressor gene APC was recently identified, and the cDNA was cloned from chromosome 5q21. Point mutations affecting APC are seen in the hereditary syndrome familial adenomatous polyposis, and point mutations in APC and a closely linked gene, MCC, as well as loss of heterozygosity involving chromosome 5q have been reported in sporadic colon cancer. To our knowledge, loss of heterozygosity involving APC or MCC or both has not yet been described in any other human cancer besides lung cancer. We used the polymerase chain reaction and DNA content flow cytometric nuclear sorting to examine 30 primary human esophageal cancers for loss of heterozygosity of APC or MCC or both. Loss of one allele was detected in 77% of 26 informative cases. These data suggest that loss of heterozygosity of regions on 5q including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers. They imply that inactivation of APC, MCC, and/or a linked gene on chromosome 5q plays a role in the pathogenesis of some cancers of the upper gastrointestinal tract, as well as in colon cancer and familial adenomatous polyposis.

Adenocarcinoma↗
PubMed1992

On the identity of the major postsynaptic density protein.

Increasing evidence suggests that the postsynaptic density (PSD) plays a critical role in synaptic communication and plasticity. The major PSD protein (mPSDp), a calcium/calmodulin-dependent protein kinase, appears to be central to PSD function. The mPSDp has long been considered identical to the alpha subunit of the soluble calmodulin kinase II (alpha-CKII). However, mPSDp and alpha-CKII do differ in solubility and antigenicity, raising the possibility that the two proteins are distinct. To further define the relationship between the two proteins, we purified the mPSDp to homogeneity from adult rat cerebral cortex and compared the proteins. In contrast to alpha-CKII, the purified mPSDp was insoluble in high concentrations of salt, various detergents, chelators of divalent cations, and the strong denaturant guanidine hydrochloride. The pI value of the mPSDp was 6.2, whereas that of alpha-CKII was 6.7-7.2. The purified mPSDp bound calmodulin in the presence of Ca2+ and was autophosphorylated in a Ca2+/calmodulin-dependent manner. Polyclonal antiserum raised against mPSDp (anti-mPSDp) recognized purified mPSDp or mPSDp in synaptic membrane, indicating immunologic specificity among the synaptic proteins. Anti-mPSDp did not recognize alpha-CKII, whereas anti-alpha-CKII antibodies reacted only weakly with mPSDp, suggesting that the proteins are distinct but structurally similar. Moreover, sequence analysis of protease V8-digested polypeptides revealed that there was at least an 8-amino acid sequence, MLKVPNIS, that is not present in alpha-CKII. Finally, HPLC analysis of V8-digested fragments of mPSDp and alpha-CKII in parallel revealed dissimilar peptide patterns. Thus our observations suggest that mPSDp and alpha-CKII are similar but not identical. The unique physicochemical and structural properties of the mPSDp may provide insights into molecular mechanisms mediating synaptic plasticity.

Amino Acid Sequence↗
PubMed1992

Loss of heterozygosity affecting the p53, Rb, and mcc/apc tumor suppressor gene loci in dysplastic and cancerous ulcerative colitis.

Allelic deletions of tumor suppressor genes have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancer. Three of the most frequently deleted chromosomal loci contain the tumor suppressor genes p53, retinoblastoma (Rb), and mcc/apc. In order to detect loss of heterozygosity (LOH) within these genes in dysplastic and cancerous ulcerative colitis, we used an application of the polymerase chain reaction. LOH affecting p53 was observed in 8 of 17 (47%) of heterozygous patients, while LOH of Rb and the mcc/apc locus was observed in 9 of 27 (33%) and 13 of 39 (33%) of heterozygotes, respectively. Among 35 patients heterozygous at 2 or more loci, LOH of p53, Rb, and/or mcc/apc was observed in 18 (51%). LOH was more common in left-sided neoplasms. These data suggest that allelic deletion of p53, Rb, mcc, and/or apc is involved in the pathogenesis and/or progression of at least a subset of colonic dysplasias and carcinomas occurring in the setting of ulcerative colitis.

Adenocarcinoma↗
PubMed1992

Individual somatotopy of primary sensorimotor cortex revealed by intermodal matching of MEG, PET, and MRI.

A method for comparing estimated magnetoencephalographic (MEG) dipole localizations with regional cerebral blood flow (rCBF) activation areas is presented. This approach utilizes individual intermodal matching of MEG data, of rCBF measurements with [15O]-butanol and positron emission tomography (PET), and of anatomical information obtained from magnetic resonance (MR) images. The MEG data and the rCBF measurements were recorded in a healthy subject during right-sided simple voluntary movements of the foot, thumb, index finger, and mouth. High resolution 3D-FLASH MR images of the brain consisting of 128 contiguous sagittal slices of 1.17-mm thickness were used. MEG/MR integration was performed by superimposing the 3D head coordinate system constructed during the MEG measurement onto the MR image data using identical anatomical landmarks as references. PET/MR integration was achieved by a phantom-validated iterative front-to-back-projection algorithm resulting in one integrated MEG/PET/MR image. The estimated dipole locations followed the somatotopic organisation of the task-specific rCBF increases as evident from PET, although they did not match point-to-point. Our results demonstrate that intermodal matching of MEG, PET and MR data provides a tool for relating estimated neuromagnetic field locations to task-specific rCBF changes in individual subjects. Our method offers the perspective of refined dipole modelling.

Adult↗
PubMed1992

Schistosomiasis and the social patterning of infection.

Social, cultural, behavioural and economic factors interact with local environmental and ecological factors to produce extraordinary variation in the epidemiology of schistosomiasis, including with respect to prevalence and intensity of infection and the potential for control. This article reviews the literature on schistosomiasis infection, primarily derived from African studies, to identify its major social themes. Research has demonstrated a strong link between economic development strategies, where irrigation has been introduced to boost agricultural production, and the increased transmission of infection. Water-contact studies have provided the fullest and most detailed descriptions of social risk factors, and have isolated age, sex, religion and occupation as primary risk factors. However, fuller explorations of the social and cultural context of infection have yet to be undertaken. The social context of water-related behaviour and patterns of water use within communities and households, the intersection of social and economic activities, and the significance that people give to these activities, remains poorly explored, and although research papers concerned with community-based interventions refer to poor community understanding of the cause, prevention and treatment of the disease, this domain has also received little scholarly attention. Finally, economic studies have focused primarily on working capacity, and extrapolated these findings to generalize about the impact that this might have on productivity, but have yet to address either household or community costs of schistosomiasis infection.

Africa↗
PubMed1992

Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone.

Electron microscopic morphometry was used to study the development of lung injury during and after chronic (78 weeks) exposure to a pattern of ozone (O3) designed to simulate high urban ambient concentrations that occur in some environments. The daily exposure regimen consisted of a 13-hr background of 0.06 ppm, an exposure peak that rose from 0.06 to 0.25 ppm, and returned to the background level over a 9-hr period, and 2-hr downtime for maintenance. Rats were exposed for 1, 3, 13, and 78 weeks. Additional groups of rats exposed for 13 or 78 weeks were allowed to recover in filtered clean air for 6 or 17 weeks, respectively. Rats exposed to filtered air for the same lengths of time were used as controls. Samples from proximal alveolar regions and terminal bronchioles were obtained by microdissection. Analysis of the proximal alveolar region revealed a biphasic response. Acute tissue reactions after 1 week of exposure included epithelial inflammation, interstitial edema, interstitial cell hypertrophy, and influx of macrophages. These responses subsided after 3 weeks of exposure. Progressive epithelial and interstitial tissue responses developed with prolonged exposure and included epithelial hyperplasia, fibroblast proliferation, and interstitial matrix accumulation. The epithelial responses involved both type I and type II epithelial cells. Alveolar type I cells increased in number, became thicker, and covered a smaller average surface area. These changes persisted throughout the entire exposure and did not change during the recovery period, indicating the sensitivity of these cells to injury. The main response of type II epithelial cells was cell proliferation. The accumulation of interstitial matrix after chronic exposure consisted of deposition of both increased amounts of basement membrane and collagen fibers. Interstitial matrix accumulation underwent partial recovery during follow-up periods in air; however, the thickening of the basement membrane did not resolve. Analysis of terminal bronchioles showed that short-term exposure to O3 caused a loss of ciliated cells and differentiation of preciliated and Clara cells. The bronchiolar cell population stabilized on continued exposure; however, chronic exposure resulted in structural changes, suggesting injury to both ciliated and Clara cells. We conclude that chronic exposure to low levels of O3 causes epithelial inflammation and interstitial fibrosis in the proximal alveolar region and bronchiolar epithelial cell injury.

Administration, Inhalation↗
PubMed1992

On the feasibility of pulse-echo speed of sound estimation in small regions: simulation studies.

Computer simulations are used to study the feasibility of the estimation of sound speed in small regions with precision better than 1% using the Beam Tracking method. The speed of sound is estimated in a 10-mm by 10-mm region by considering a number of parallel tracks confined to the small region. The transducer focusing and the step sizes for the tracking and tracked transducers required to extract the maximum amount of uncorrelated data from the 10-mm by 10-mm region is evaluated. The results show that the speed of sound can be estimated with error less than 1% in a small region using a typical medical transducer. The statistical comparison of estimates in small areas with different speed of sound is also considered.

Acoustics↗
PubMed1992

Enhancement of differentiation and cytotoxicity of leukemia cells by combinations of fluorinated pyrimidines and differentiation inducers: development of DNA double-strand breaks.

We have previously shown that pretreatment of mouse erythroleukemia (MEL) cells with the fluorinated pyrimidines 5-fluorouracil (FUra) or 5-fluorodeoxyuridine (FUdR) followed by the differentiation inducer hexamethylene bisacetamide (HMBA) greatly enhanced the magnitude of their differentiation and caused extensive cell death. We have now extended these studies to address the mechanism that may be responsible for this enhancement and have also examined a human leukemic cell line (HL-60) for its sensitivity to this combination cytotoxic-differentiation therapy. We found that in HL-60 cells, pretreatment with FUdR, but not FUra, followed by 1.2% dimethylsulfoxide (DMSO) led to an 8 to 10-fold enhancement of cell death as compared to FUdR alone. When all-trans-retinoic acid (ATRA) was used instead of DMSO, the enhancement of differentiation and cytotoxicity was 5-fold. The percent of cells induced to differentiate was dependent on the concentration of both FUdR and ATRA. In HL-60 cells resistant to ATRA-induced differentiation, the combination of FUdR and ATRA did not result in enhanced cytotoxicity. Leucovorin (LV), a compound known to enhance the inhibitory effect of FUra or FUdR on DNA synthesis, increased the effectiveness of the cytotoxic-differentiation therapy, whereas thymidine inhibited its effectiveness. This suggests that inhibition of DNA metabolism may be an integral part of the differentiation-enhancing cytotoxic mechanism. To further explore inhibition of DNA synthesis, DNA was extracted under alkaline or neutral conditions from 3H-thymidine-labelled cells that were treated with FUra/LV and HMBA individually or in combination. The emergence of single and double-strand DNA breaks was monitored by agarose gel electrophoresis. In parallel to the enhancement of cytotoxicity, the combination treatment (FUra/LV followed by HMBA) also produced a 2.5-3-fold increase in the DNA breaks when compared to the same effect obtained by the agents applied individually. Thus, we propose that DNA degradation may be the mechanism responsible for the enhanced loss of cell viability. In summary, we report here an approach which is targeted to increasing the death rate of leukemic cells through the combined use of low doses of cytotoxic drugs and differentiation inducers.

Cell Differentiation↗