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Biomedical subjects

K Zhang

Publications and source records attributed to K Zhang.

At least 307 records · Page 17Linked to original sources

Human acute myeloid leukemias may be etiologically associated with new human retroviral infection.

The etiology of human acute myeloid leukemias (AML) remains uncertain. In order to examine the possibility of retroviral etiology in AML, we determined retroviral antigens related to HTLV-I in leukemic cell samples from 32 AML cases and peripheral blood mononuclear cells (PBMNCs) from 20 healthy donors by D-IGSS with high sensitivity and specificity, reverse transcriptase (RT) activity by a simple and sensitive non-radioisotopic RT assay, and retroviral particles by electron microscopy. The HTLV-I-related antigens were detected in 50.0% (16/32) of fresh leukemic cell samples and 87.5% (28/32) of cultured leukemic cell samples. The HTLV-I-related antigen-positive cells in fresh and cultured leukemic samples were 10.2% and 52.8%, respectively. Both frequency and level of HTLV-I-related antigens in cultured samples were much higher than in fresh samples. In contrast, no HTLV-I-related antigens were found in normal hematopoietic cells from 20 healthy donors. Further study results show that RT activity was detected not only in HTLV-I-related antigen-positive samples, but was also well correlated with the level of HTLV-I-related antigens in these samples, and preferred Mn+2 to Mg+2 as a cation. Moreover, typical retroviral particles were localized in most cultured HTLV-I-related antigen-positive samples by immunoelectron microscope. These data suggest that human acute myeloid leukemias may be etiologically associated with new human retroviral infection.

Acute Disease↗

Direct evidence that gamma 1 and gamma 3 switching in human B cells is interleukin-10 dependent.

Interleukin-10 (IL-10) has various effects on B cell immunoglobulin (Ig) production. Indirect evidence suggests that IL-10 functions as a switch factor for IgG production. In this study, the switch deleted Ig gene DNA was isolated and characterized, as direct evidence that IL-10 induced isotype switching in human B cells. In addition, 16 chimeric Ig fragments were isolated, representing deleted DNA generated by in vitro isotype switching from mu to gamma in human B cells, following stimulation with IL-10 and anti-CD40 monoclonal antibodies (CD40 mAb). These clones consisted solely of S gamma 1/S mu and S gamma 3/S mu chimeric switch circular DNAs, no S gamma 2/S mu or S gamma 4/S mu switch DNA was observed. In addition, IL-10 alone induced only gamma 1 and gamma 3 germ-line mRNA transcripts, as determined by restriction digestion of the reverse transcription-polymerase chain reaction products. Three modes of mu-gamma 3 isotype switching were detected: (1) direct switching; (2) internal deletion of S mu proceeding mu to gamma 3 switching; and (3) internal deletion of S gamma 3 proceeding mu to gamma 3 switching. These results directly demonstrate that gamma 1 and gamma 3 switching in human B cells is specifically induced by IL-10 in the presence of CD40 mAb.

Antibodies, Monoclonal↗

Superconducting receiver coils for sodium magnetic resonance imaging.

We present the results from sodium magnetic resonance imaging (MRI) experiments using high-temperature superconducting (HTS) receiver coils. Sodium imaging has been shown to have great potential for the assessment of cell integrity but suffers from a substantially lower signal-to-noise ratio (SNR) than that of a hydrogen imaging. The use of an HTS receiver coil was found to significantly increase the SNR relative to an equivalent copper receiver coil at room temperature. The SNR gains afforded by HTS coils can also be used to decrease the imaging time.

Copper↗

Keratinocytes in human wounds express alpha v beta 6 integrin.

Cell adhesion receptors of the integrin family play a major role during re-epithelialization of human wounds. We have previously documented that the expression of alpha v family integrins is induced in keratinocytes of mucosal wounds [1]. In the present investigation, we extended these studies to determine whether alpha v beta 6 integrin is expressed during wound healing in humans. Mucosal and epidermal wound sections from 1- to 7-day-old wounds were used for immunolocalization of integrins and their putative ligands. In addition, freshly isolated epidermal keratinocytes were used to study integrin expression in vitro. Expression of alpha v beta 6 integrin appeared relatively late during mucosal and dermal wound healing. Maximal expression was seen in 7-day-old wounds in which epithelial sheets had fused and granulation tissue was present. Fibronectin and tenascin, both possible ligands for alpha v beta 6 integrin, were found concentrated underneath the basal epithelial cells expressing this receptor, and the maximal expression of tenascin coincided with that of alpha v beta 6 integrin. Freshly isolated epidermal keratinocytes did not stain for alpha v beta 6 integrin but began to express this integrin after subculturing. Our results suggest that the expression of alpha v beta 6 integrin, a putative binding integrin for fibronectin and tenascin, is induced in keratinocytes when epithelial sheets fuse during wound healing.

Antigens, Neoplasm↗

Neurohumoral activation in heart failure: role of paraventricular nucleus.

1. A number of neurohumoral processes are activated in heart failure (HF), including an increase in the plasma concentration of noradrenaline. 2. Few studies have been performed to examine the role of the central nervous system (CNS) in the activation of sympathetic outflow during HF. In the present paper we review the limited studies performed to examine the role of the CNS in the activation of sympathetic outflow, with particular emphasis on our recent study that examined the activity of discrete regions of the brain as assessed by histological localization and photodensitometric quantification of the metabolic enzyme hexokinase during HF. 3. There were significant increases in hexokinase activity in the parvocellular (pPVN) and magnocellular (mPVN) divisions of the paraventricular nucleus of the hypothalamus and in the locus coeruleus (LC) in rats with HF. No changes in hexokinase activity were observed in the median preoptic area, supraoptic nucleus (SON) or posterior hypothalamus. 4. We conclude that HF is associated with changes in specific areas in the brain and that alterations in the activation of neurons in the pPVN, mPVN and LC are likely to be related to alterations in vasopressin production, blood volume regulation and sympathoexcitation observed in the HF state.

Animals↗

Invasive phenotype of Trypanosoma cruzi restricted to a population expressing trans-sialidase.

Trypanosoma cruzi expresses a developmentally regulated trans-sialidase implicated in the pathogenesis of Chagas' disease. On inhabitation of the extracellular milieu of cultured cells by infective trypomastigotes, the enzyme is restricted to a small (20 to 30%) population of parasites. The biological significance of trans-sialidase expression on this subset, termed TS+, and not on the majority (70 to 80%) of morphologically similar trypanosomes, named TS-, is unknown. To determine the roles of the TS+ and TS- subsets in T. cruzi invasion, we prepared pure populations of TS- and TS+ trypanosomes using magnetic beads coated with a monoclonal antibody specific for the tandem repeat unit of the trans-sialidase C terminus. After removal of nonadherent TS- trypomastigotes, the TS+ trypomastigotes were isolated from the beads by specific elusion with a synthetic peptide epitope of the trans-sialidase monoclonal antibody. Confirmation of TS+ and TS- phenotypes was obtained by immunofluorescence, immunoblotting, and sialidase or sialyl transferase activity measurements. The TS+ trypanosomes were highly invasive, as they attached to, penetrated, and thrived in cultured mammalian cells much more efficiently than did unfractionated parasites. The critical role of the trans-sialidase in invasion was underscored by the observation that infection was neutralized by human antibodies to transsialidase. What's more, the TS- parasites, in sharp contrast to their TS+ counterparts, were extremely inefficient in invading epithelial cells and fibroblasts. Further, introduction of small amounts of exogenous trans-sialidase into suspensions of nonpenetrating TS- parasites converted them to a highly invasive phenotype indistinguishable from that of the TS+ population. Rescue of the invasive phenotype was specific for the T. cruzi enzyme, for it didn't happen with bacterial and viral sialidases. The in vitro results were confirmed in the murine model of Chagas' disease, as TS- trypomastigotes were relatively avirulent while TS+ trypomastigotes were more virulent than unfractionated parasites.

Animals↗

HIV infection and AIDS in China, 1985 through 1994.

OBJECTIVES: This paper analyzes data on the distribution of and risk factors for the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection in China. METHODS: Ten years of data on persons tested for HIV infection and AIDS and the proportion who tested positive were analyzed against the background of China's population count. The Chinese- and English-language literature on HIV and AIDS from 1985 through 1995 was also reviewed. RESULTS: Overall, more males than females had HIV infection. Intravenous drug use was the primary source of transmission, followed by heterosexual contacts. Only a small number of the persons tested were homosexual, but their proportion of HIV seropositivity ranked third to that of drug users; that of general hospital patients ranked fourth. CONCLUSIONS: HIV infection and AIDS in China began as a highly regionalized and largely rural problem in Yunnan Province. However, HIV infection and AIDS have become an emerging urban problem. HIV seropositivity is low among several groups thought to have an elevated risk.

Acquired Immunodeficiency Syndrome↗

Restricted expression and function of laminin 1-binding integrins in normal and malignant oral mucosal keratinocytes.

Squamous cell carcinoma of the oral cavity spreads by initial invasion of the laminin-rich basement membrane. We examined the adhesion and motility of human oral SCC cells and normal mucosal keratinocytes and found that the SCC cells readily attached and migrated on laminin 1 substrates but migrated poorly on collagen type I and fibronectin. The normal keratinocytes, however, adhered poorly to and were non-motile on laminin 1 yet readily and preferentially attached and migrated on fibronectin and collagen type I. Analysis with blocking anti-integrin antibodies showed that the SCC cells used the alpha 6 beta 1 complex to attach and migrate on laminin 1 and that this activity was confined to the E8 long arm fragment of laminin. Affinity chromatography on laminin-Sepharose columns revealed that the SCC cells, but not normal keratinocytes, expressed high levels of the alpha 6 beta 1 laminin 1 receptor. Metabolic pulse-chase analysis indicated that in contrast to the SCC cells, keratinocytes did not have a stable pool of beta 1 subunit precursor. Preferential pairing of alpha 6 with beta 4 and the deficiency in pre-beta 1 levels appear to account for the failure of keratinocytes to form significant alpha 6 beta 1 complex. Additionally, the presence of laminin 1 in co-coating experiments blocked keratinocyte adhesion to other immobilized ligands, such as collagen type I or fibronectin. This anti-adhesive effect seemed to reflect a general paralysis of cell adhesive function, since laminin 1 also diminished the adhesion of keratinocytes to substrates coated with immobilized anti-integrin subunit antibody. The inhibitory activity of laminin 1 resided in the E1' and E8 fragments, and not in the E3, E4 or G domains. Collectively, our results indicate that laminin 1 is a restrictive ligand for normal keratinocytes, apparently because of their failure to assemble and express the alpha 6 beta 1 complex or other functional laminin receptors and their sensitivity to the anti-adhesive activity of laminin itself. The elevated expression of alpha 6 beta 1 following malignant conversion of muscosal keratinocytes promotes their migration on laminin, a process important during invasion and metastasis.

Binding, Competitive↗

Lung fibroblast alpha-smooth muscle actin expression and contractile phenotype in bleomycin-induced pulmonary fibrosis.

The emergence of the myofibroblast phenotype (characterized by alpha-smooth muscle actin expression) in wound healing and in tissues undergoing fibrosis is thought to be responsible for the increased contractility of the affected tissues. In bleomycin-induced pulmonary fibrosis, the myofibroblast is also responsible for the observed increase in collagen gene expression. To evaluate further these phenotypic changes in lung fibroblasts, contractile and other phenotypic properties of fibroblasts isolated from lungs of rats with bleomycin-induced fibrosis were compared with those of normal rats using in vitro models. Pulmonary fibrosis was induced in rats by endotracheal injection on day 0, and 7 and 14 days later the animals were sacrificed and lung fibroblasts isolated. Using immunofluorescence, < 10% of fibroblasts from control animals express alpha-smooth muscle actin when cultured as a monolayer. In contrast, 19% and 21% of cells from day 7 and day 14 bleomycin-treated animals, respectively, expressed this actin and with greater intensity than in control lung cells. This increase in actin expression was associated with enhanced contractility when evaluated using a three-dimensional cell culture model consisting of fibroblast-populated collagen gels. This enhanced contractility was abolished by treatment with antibody to transforming growth factor-beta (TGF-beta), whereas exogenous TGF-beta 1 and serum-stimulated contraction of control lung fibroblasts. TGF-beta 1 gene expression was greater in cells from bleomycin-treated animals than those from control lungs. These results show that cells with the myofibroblast phenotype are more abundant in fibrotic lung, and that these cells possess greater contractile capacity in vitro at least partly by virtue of their enhanced endogenous TGF-beta 1 gene expression.

Actins↗

Renal sympathetic nerve discharge mediated by the paraventricular nucleus is altered in STZ induced diabetic rats.

The purpose of this study was to determine if the renal sympathetic nerve discharge (RSND), mediated by the paraventricular nucleus of the hypothalamus (PVN), is altered in streptozotocin (STZ) induced diabetic rats. Two to three weeks prior to the start of the experiment the diabetic group was treated with a single injection of STZ (65 mg/kg ip) in a 2% solution of cold 0.1 M citrate buffer (pH = 4.5). The control group was injected with the vehicle alone. Bicuculline (BIC) was injected into the PVN in three different doses (0.5, 1.0 & 2.0 nmol) while the RSND was being monitored. BIC is an antagonist of gamma-aminobutyric acid (GABA) which is an inhibitory neurotransmitter that is thought to exert a tonic inhibitory effect on the PVN. Microinjection of BIC produced a significantly lower response of RSND in the diabetic group compared to the control group. Microinjection of BIC produced a 13, 35 and 33% change in RSND in diabetic rats compared to control group in response to 0.5, 1.0, and 2.0 nmol doses, respectively. Mean blood pressure and heart rate were statistically not different between the control and the diabetic groups. However there were tendencies of the blood pressure and heart rate to be blunted upon injection of BIC into PVN in diabetic rats. This study demonstrates that RSND in response to microinjection of BIC in PVN is decreased significantly in anesthetized diabetic rats, indicating that STZ induced diabetic rats have a blunted RSND response to microinjection of BIC. There is also some evidence, although not statistically significant, for a blunted blood pressure and heart rate were diabetics. These findings suggest that there is a reduced endogenous inhibitory influence of GABAergic mechanisms within the PVN involved in regulating renal sympathetic outflow in the diabetic state.

Adrenergic Fibers↗

Exercise hemodynamic benefits of rate adaptive ventricular pacing.

OBJECTIVE: To investigate the exercise hemodynamic benefits of activity-sensing rate adaptive ventricular pacing (VVIR) over fixed rate pacing (VVI) mode. METHODS: Activity sensing rate adaptive pacemaker was implanted in 19 patients (13 males and 6 females, mean age 54.8 years) with bradycardia. All patients underwent symptom-limited upright bicycle exercise in VVIR and VVI pacing modes in random order after implantation. With electrocardiogram monitor and M-mode echocardiography, heart rate, stroke volume and cardiac output were measured at rest and at each stage of exercise. RESULTS: All patients were pacemaker dependent, without any spontaneous heart rhythm throughout this study. In the activity sensing ventricular pacing mode, all patients achieved a significant increase in exercise duration compared to fixed rate ventricular pacing mode (mean +/- s, 437 +/- 45 vs 323 +/- 23sec; P < 0.01), with a mean maximum pacing rate of 113 +/- 23ppm. Although the cardiac output was significantly improved in both pacing modes (10.2 +/- 1.4L/min with VVIR and 7.5 +/- 1.1L/min with VVI), the maximum exercise cardiac output in VVIR was increased over VVI by 46% (P < 0.05). Additionally, the stroke volume was significantly increased by 50% or more at rest in VVI mode, but was relatively maintained in VVIR mode (P > 0.05). CONCLUSION: Rate adaptive ventricular pacing can significantly improve the exercise capacity and cardiac output in patients with bradycardia. The increment of exercise cardiac output in VVIR mode is mainly dependent upon the pacing rate during exercise.

Cardiac Output↗

[Experimental and ultrastructural study of synapses in the substantia gelatinosa after electrical acupuncture].

Ultrastructural changes of synapses in the rat substantia gelationsa of the spinal caudal trigeminal nucleus were quantitatively examined following electrical acupuncture at "Sibai" for 30 minutes. Various structural changes were observed: Spherical synaptic vesicles were clustered toward the presynaptic membrane, the number of the vesicles tended to decrease, the width of the postsyiincreased and mitochondria were also increased in the bouton. These various types of synaptic alterations related to boutons are interpreted as the morphological changes induced by the acupuncture in the region corresponding to "Sibai".

Acupuncture Points↗

[A study on non-ulcer dyspepsia patients with electrogastrography and gastric emptying by using SPECT technique].

Non-ulcer dyspepsia (NUD) is very common in community population. However, its pathogenesis was controversial, particularly with respect to motility disorder. In this study electrogastrogram (EGG) and gastric emptying rate (GER) by using SPECT technique (test meal labelled with 99mTc-PHY and 113In-DTPA) were carried out in healthy subjects and 27 NUD patients. In EGG examination, the authors first proposed four parameters, i.e. peak time (PT), return time (RT), degeneration rate (DR) and arrhythemia rate (AR). Comparison of EGG between NUD patients and controls showed that AR, RT, DR in NUD patients were significantly higher or longer than these in the controls (P > 0.05). Solid phase GET in NUD patients were significantly delayed than that in the controls. No significant correlation was found between EGG and GET. A delay gastric emptying cannot be predicted with EGG examination only.

Adult↗

[Cervical intervertebral disc calcification in children: report of 10 patients].

Eleven cervical intervertebral space calcifications were studied in ten children (5 boys, 5 girls), with mean age of 9.4 years. The aetiology, symptoms, roentgenographic clinic features were analyzied. All ten patients showed evidence of calcification of the cervical intervertebral disc. One had calcification in two disc spaces of the cervical spine and associated with subluxation of C1,2. Two patients had calcification protruded into the spinal canal without symptoms of spinal cord compression. One had symptom of nerve root irritation. Eight of ten patients had symptoms which disappeared in two weeks after treatment. Eight patients had been followed over one year. The calcification disappeared from 2 to 8 months. The diagnostic criteria for the syndrome of this study are: (1) pediatric age group only; (2) local or referred pain; (3) limited cervical spine motiion; (4) evidence of inflammation; (5) visible calcification of the cervercal intervertebral disc on roentgenogram; (6) self-limited course; (7) good result after conservative treatment and good prognosis.

Adolescent↗