[Prevention and treatment of toxic and adverse effects of cisplatin].
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Biomedical subjects
Publications and source records attributed to R Huang.
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The morphology and morphogenesis of isolated hepatitis E virus (HEV, strain 87A) were observed by electron microscopy (EM) and immune electron microscopy (IEM). Progressively developing local vesicles, virions accumulation in crystalline arrays and viroplasmic focus were seen in cytoplasm of infected cells. Replication and assembly of the new generation viruses were closely associated with rough endoplasmic reticulum (RER), inclusion body (IB) and microfibrils. Condensation and margination of chromatin, dispersion of nucleolar material, nuclear membrane alteration and masses of threads, granular material, and fibrillar component of the nucleus were frequently found. These changes revealed that this strain virus was confirmed as a RNA virus. The shape of the virus particles appeared approximately spherical whether the specimens were from the tissue culture crude suspension or purified highly concentrated preparations. The size of the virion was about 30 nm in diameter. The viral particles appeared unsmooth and irregular in outline. The spike-like structures may be occasionally observed on the surface of some viral capsides. The diameter of the strain 87 A virus is larger than the picornavirus and smaller than the calicivirus. This strain virus is different from classical calicivirus in without the cup-shaped surface depressions. The new genus, heparnavirus genus of caliciviridae family should be proposed for HEV.
Twenty-eight cases of abdominal scar endometriosis from January, 1980 to December, 1993 are reported. Of these patients, twenty-four underwent term cesarean section, and four underwent a midtrimester abortion by abdominal hysterotomy. The majority of patients manifested symptoms 1 year after the operation. The most common was a painful mass of scar tissue that became swollen and tender during menstruation. The pathogenesis, diagnosis and treatment are discussed. In correlation with the pathological findings, the effects of drug therapy are evaluated. It was found that surgical excision is the best method of treatment.
Immunoreactivity to nitric oxide synthase (NOS-IR) was detected in a small population of rat neocortical neurons scattered throughout the frontal, parietal, temporal and occipital cortices. Two-color double-labeling studies revealed that the number of NOS-IR neocortical neurons expressing immunoreactivity to the calcium binding proteins parvalbumin (PV-IR), calbindin-D28K (CB-IR) or calretinin (CR-IR), was low. The absence or low level of calcium binding proteins may imply a reduced Ca2+ buffering capacity in NOS-containing neurons, thereby contributing to their vulnerability to Ca2+ influx through the activated AMPA/kainate receptors reported by others.
Synthesis and release of glutamate formed from labeled glutamine were studied in primary cultures of the glutamatergic cerebellar granule cells and of the mainly GABAergic cerebral cortical neurons under anoxic conditions and under normoxic control conditions. Under both control and anoxic conditions cerebellar granule cells synthesized and released glutamate more intensely than cerebral cortical neurons, but this difference was enhanced under anoxic conditions. Thus, under normoxic conditions synthesis of intracellular labeled glutamate from glutamine was twice as high in cerebellar granule cell neurons as in cerebral cortical neurons during 30 min of incubation, but the release of newly synthesized labeled glutamate to the extracellular medium from cerebellar granule cell neurons was more than 4 times higher than the release from cerebral cortical neurons during 30 min of incubation. Based on these observations it is suggested that a major reason for the increase in extracellular glutamate concentration during brain ischemia may be enhanced production and release of glutamate, especially in glutamatergic neurons.
Platelets accumulate PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in response to thrombin and thrombin-receptor-directed peptide in a GTP-dependent manner. These phosphoinositides are considered to be mediators of signaling events in a variety of cells. We have examined the metabolic route by which PtdIns(3,4,5)P3 and PtdIns(3,4)P2 are synthesized by briefly (10 min) incubating platelets with high activities of [32P]Pi, followed by 20 or 60 s exposure to thrombin, and analysing the relative radioactivities of the individual phosphate groups in the resulting labelled PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The phosphate group possessing the highest specific activity under such non-equilibrium labelling conditions indicates the last one added in a metabolic sequence. The thrombin-stimulated rate of labelling of PtdIns(3,4)P2 was significantly slower than that of PtdIns(3,4,5)P3. Increased labelled PtdIns3P was not detected within 60 s. The measured relative radioactivities decreased in the order 3 > 5 > 4 >> 1 for PtdIns(3,4,5)P3 and 3 > 4 >> 1 for PtdIns(3,4)P2. On the basis of the results of both rate-of-labelling and specific radioactivity analyses we conclude that PtdIns(3,4,5)Pa is formed by 3-OH phosphorylation of PtdIns(4,5)P2, whereas PtdIns(3,4)P2, may be formed by 3-OH phosphorylation of PtdIns4P and/or dephosphorylation of PtdIns(3,4,5)P3. These findings point to the activation of phosphoinositide 3-kinase as a critical receptor-regulated step in thrombin-stimulated platelets.
The alpha 2-adrenergic agonist clonidine stimulates glutamine uptake and metabolism in primary cultures of mouse astrocytes. This is important because glutamine is a metabolic substrate for these cells. The alpha 2-antagonist yohimbine inhibits the clonidine stimulation, although not completely. The residual effect in the presence of yohimbine can be explained by the fact that this drug is also a serotonin agonist. Idazoxan, which specifically inhibits imidazoline preferring receptors, exerts no inhibition of glutamine uptake. These results suggest that the stimulatory effect of clonidine on glutamine accumulation in mouse astrocytes is due to its effect at an authentic alpha 2-adrenergic receptor site, not at the imidazoline preferring receptor site.
Trypsin-related serine proteases are encoded by a very large gene family in mammals. We describe here a comparative analysis of the genomic DNA sequences of mouse, rat, and human mast-cell-specific serine protease genes. Strong evidence was found for multiple exchanges of genetic information between closely related members of this gene family. The 5' regulatory regions of MMCP-1 and MMCP-L share a remarkably high degree of sequence identity (98%), starting 10 base pairs downstream of exon 1 and extending to the end of the presently sequenced region at position -1347 of the MMCP-1 gene. The remaining parts of the two genes share approximately 80% sequence identity. Evidence for at least two additional, but not so recent, exchanges was found in the 3' regions of the MMCP-4 and MMCP-L genes and in the 5' regions of the genes for MMCP-1 and MMCP-2. The 5' regulatory regions of all presently characterized mouse mast-cell-specific chymotrypsin-like serine protease genes exhibit over 88% sequence identity in the region from the transcription initiation site to approximately position -600. An exception is MMCP-5 which is the most distantly related member of this subfamily. The high degree of sequence similarities indicates a strong evolutionary homogenization of the 5' regulatory region, possibly by several gene conversion events. In addition, several insertions of genetic information have been identified in genes for mast-cell chymases and genes for T-cell granzymes. A number of these have been found to represent repetitive sequences, such as L1. The previously characterized tissue-specific enhancer element of the RMCP II gene was identified as a member of a middle repetitive sequence. A cDNA for a newly discovered pseudogene, closely related to the mouse mast cell chymases was isolated by polymerase chain reaction amplification from a mouse connective tissue-like mast cell line. The structure of this cDNA is presented. We also present the characterization of a novel spliced variant of MMCP-6 that contains an alternative 3' terminal exon (exon 6). The function of this variant, if any, is still unknown. A comparative analysis of amino acid sequence identities between different hematopoietic serine proteases shows that a high degree of sequence similarity does not always correlate with relateness in cleavage specificity. This indicates that the substrate specificity evolved with a higher evolutionary rate than the degree of overall amino acid sequence identity of these proteases.
The early somite of avian embryos is made up of an epithelial wall and mesenchymal cells located within the somitocoele. We have studied the fate of somitocoele cells for a period of up to 6 days, using the quail-chick marker technique. We also applied the QH-1 antibody, which specifically stains hemangiopoietic cells of quail origin, and studied the proliferative activity of epithelial somites with the BrdU anti-BrdU method. Our results show that somitocoele cells mainly give rise to the ribs and peripheral parts of the intervertebral discs. After 1 and 2 days of reincubation, the grafted somitocoele cells were located in the lateral part of the sclerotome, and only a few cells migrated axially towards the notochord. In frontal sections, the cells were located in a triangular area within the cranial part of the caudal sclerotome half. After 3 days of reincubation, some of the cells had migrated cranially along the myotome. After longer reincubation periods, cells grafted into one somite could be found in two adjacent ribs. The studies with the QH-1 antibody show that a subpopulation of somitocoele cells has angiogenic potency. Endothelial cells originating from the mesenchyme of the somitocoele migrated actively and even invaded the ipsilateral half of the neural tube. In the epithelial wall of the somite, BrdU-labelled nuclei were found basally, whereas more apically the nuclei were not stained, but mitotic figures were frequently present. The somitocoele cells also showed a high proliferative activity with about 26% of nuclei labelled with BrdU.
Accumulation of radioactivity was studied in primary cultures of mouse astrocytes as a function of time of exposure (4-60 min) to 50 microM glutamate and 200 microM glutamine (initial concentrations), of which either glutamate or glutamine was 14C-labeled. Both the glutamate pool and the glutamine pool were compartmentalized. Initially, by far the major intracellular glutamate pool (> or = 90%) was derived from extracellular glutamate and could be converted to glutamine. This allowed a rather accurate determination of metabolic flux from glutamate to glutamine, which under control conditions amounted to 2.0-2.2 nmol/min per mg protein. After chronic exposure to 3 mM ammonia for 3 days this flux was significantly increased to 3.1-3.6 nmol/min per mg protein. Acute exposure to ammonia caused a smaller, apparent increase, which was not statistically significant. The glutamine content was compartmentalized at all stages of the incubation. It consisted of at least two different pools. One of these was accessible to extracellular glutamine and could be converted to intracellular glutamate (constituting a sizeable fraction of the total glutamate pool after longer incubation), whereas the other constituted endogenously derived glutamine, formed from accumulated glutamate. The specific activity of the precursor pool for glutamate synthesis could not be accurately determined and relatively exact fluxes therefore not be calculated. There was, however, no evidence that chronic exposure to ammonia decreases the rate of glutamine hydrolysis.
The effects of elevated K+ concentrations and monoamine transmitters on different cell types in the CNS and on different subcellular structures in these cells are reviewed. Pronounced differences exist in the metabolic processes that are stimulated by excess K+ and by adrenergic agonists, e.g., noradrenaline. An elevation in the extracellular K+ concentration appears to enhance neuronal-astrocytic interaction by stimulating metabolic processes involved in (1) the promotion of supply of precursors for transmitter glutamate, and (2) reestablishment of resting ion distribution following neuronal excitation. The monoamine transmitters stimulate energy production and Na+,K(+)-ATPase activity in astrocytes in a complex manner and, in so doing, facilitate their role in ion regulation. However, in contrast to excess K+, they do not enhance the production of astrocytic precursors for neuronal glutamate production. Emphasis is placed on possible profound differences in metabolic effects on excitatory and inhibitory neurotransmission and on the importance of stimulation of glycolytic metabolism in astrocytes versus oxidative metabolism in neurons.
A bone and cartilage enzyme with both 5'-nucleotide phosphodiesterase I and nucleotide pyrophosphohydrolase (NTPPPH) activity modulates physiologic mineralization and pathologic chondrocalcinosis by generating inorganic pyrophosphate. We hypothesized that, as for alkaline phosphatase, expression of an NTPPPH gene can be shared by cells from bone, cartilage, and liver and by certain leukocytes. Recently, we demonstrated the hepatocyte and murine plasma cell membrane glycoprotein PC-1 to have both 5'-nucleotide phosphodiesterase I and NTPPPH activity. We detected polypeptides cross-reactive with PC-1 in human U20S osteosarcoma cells, articular chondrocytes, homogenized human knee cartilages, human knee synovial fluids, hepatoma cells, and murine plasmacytoma cells. Constitutive low abundance PC-1 mRNA expression was detected in U20S cells and chondrocytes by a nested RNA-PCR assay and by Northern blotting. TGF beta is known to substantially increase NTPPPH activity in primary osteoblast cultures. We demonstrated that TGF beta 1 increased NTPPPH activity and the level of PC-1 mRNA and immunoprecipitable [35S]-methionine-labeled PC-1 polypeptides in U20S cells. The identification of PC-1 as an NTPPPH expressed in cells derived from bone and cartilage may prove useful in furthering the understanding of the role of NTPPPH i n physiologic and pathologic mineralization.
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"Quality inspection of census results may be conducted in three areas: failure to report...,repetitive reportage...,and erroneous reportage.... This study focuses on error report on age by people of different nationalities in China.... Discussions in this paper are mainly devoted to the accuracy of age reporting...in the fourth census [of 1990]."
"This article offers a detailed discussion of Chinese mortality as confirmed by data from the 1982 and 1990 censuses. It points out that, in measuring the actual mortality in China in the 1980s, attention should be paid not only to infant mortality but also to failures in reporting deaths of old people. Based on age-differentiated population as reported by the two censuses, the author computes the population's average life span and re-evaluates the error in age-differentiated mortality as calculated by using mortality data from the censuses."
This article reported the image analysis of normal epithelia of bronchi (group 1), hyperplasia epithelia (group 2), atypical hyperplasia epithelia (group 3) and adenocarcinoma (group 4) of the lung in the hamsters induced by tin mine dust and chimney dust in Yunnan Tin Min CO. 16 parameters were observed and compared. Each value was tested by stepwise discriminational classification and an accuracy rate of 95% was reached. DNA ploidy was investigated, and no case of > 5C cell was found in normal and hyperplasia group. Severe atypia had a lower percentage, (4.00%) and lung adenocarcinoma was characterized by a high percentage of > 5C cell (10.75%), A significant difference was shown between the percentage of > 5C cell of severe atypia and that of adenocarcinoma. Significantly different (P < 0.01).
Three human monocytic cell lines, U-937, THP-1 and Mono Mac 6 have, because of their morphology and staining properties, been classed as cell lines frozen in a window of the monocyte differentiation lineage corresponding to monoblasts and/or immature monocytes. These cell lines were analyzed for expression of a panel of hematopoietic differentiation markers by Northern blot analysis. They were all found to express one or several biochemical markers characteristic of immature cells in monocytic development, including myeloperoxidase, N-elastase, cathepsin G, myeloblastin, and azurocidin. Normal peripheral blood monocytes did not express these markers. Moreover, several markers expressed at high levels in mature monocytes, such as lysozyme, CD14, MHC class II and alpha-1 antitrypsin were either not expressed or were expressed only at low levels in the three cell lines analyzed. These results show that arrested differentiation at a relatively early stage of monoblast development is a common denominator for these human monocytic cell lines. Thus, transforming mutations acting at such an immature differentiation stage may frequently lead to neoplastic transformation, whereas similar mutations occurring at a more mature differentiation stage never give rise to any leukemias due to the loss of proliferative potential in committed cells.
During brain ischemia in vivo the extracellular concentration of the excitotoxic amino acid, glutamate, increases. This increase could be caused either by an enhanced formation rate of glutamate (from glutamine) or by an impaired re-uptake (or both). This re-uptake occurs to a large extent in astrocytes. In the present study we have determined glutamate uptake and the ability of the cells to maintain their glutamate content during exposure to anoxia, substrate deprivation and combined substrate deprivation and anoxia ('simulated ischemia') for a duration of up to 4 h. Isolated anoxia had no significant effect, whereas both substrate deprivation alone and 'simulated ischemia' reduced glutamate uptake and glutamate content by one-half after 2 h. Under hypothermic conditions (incubation at 32 degrees C), which in in vivo experiments exerts some protection against ischemic cell death in neurons, ischemia of intermediate duration (2 h) decreased glutamate uptake and glutamate content to a less extent than at 37 degrees C. Hypothermia did not have a similar effect during exposure to isolated substrate deprivation.