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Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 847 records · Page 47Linked to original sources

Reactions of astrocytes and microglial cells around hematogenous metastases of the human brain. Expression of endothelin-like immunoreactivity in reactive astrocytes and activation of microglial cells.

An immunohistochemical study was made on the peritumoral gliosis which is produced around hematogenous metastases of the human brain. The material was derived from 73 autopsy cases with different primary malignancies and six control cases without evidence of brain disease. Reactive astrocytes of hypertrophic and gemistocytic types were present around and within all the metastases. Eighty-five percent of the cases with metastases showed expression of endothelin-like immunoreactivity in the peritumoral astrocytes. Such immunoreactive astrocytes were not present in the normal controls but have previously been found in reactive astrocytes around infarcts, lacunas, inflammatory and degenerative brain diseases. The endothelin-like immunoreactivity probably reflects an increased intracellular content of endothelin. If this peptide is released from the reactive astrocytes it may act as a mitogen and influence microcirculation by inducing vasoconstriction. Activation of microglial cells, detected by ferritin immunohistochemistry, was another frequent and widespread glial cell alteration around the metastases. In conclusion, the reactive gliosis, which is formed around metastases involves activated astrocytes as well as activated microglial cells. Both cell types can release numerous biologically active compounds which may influence the structure and function of the brain tissue around the metastases.

Adolescent↗

Activation of adenylate cyclase and phosphodiesterase inhibition enhance neutral endopeptidase activity in human endothelial cells.

Endothelial neutral endopeptidase (EC 3.4.24.11, NEP) contributes to the inactivation of vasoactive and inflammatory peptides such as f-Met-Leu-Phe, substance P, atrial natriuretic peptide, and bradykinin. The aim of the present study was to investigate the cellular regulation of NEP expression in human endothelial cells, focusing on the role of cyclic nucleotides and cellular phosphodiesterases (PDE). Activation of adenylate cyclase by forskolin or prostaglandin E1 (PGE1) induced an increase of NEP activity and NEP protein after 24 h of incubation. This effect was mimicked by two activators of protein kinase A, dibutyryl-cAMP and 8-bromo-cAMP. The nonspecific PDE inhibitor, 3-isobutyl-1-methylxanthine (200 microM), increased NEP activity up to 192%. The activator of guanylate cyclase, sodium nitroprusside (SNP), did not affect NEP activity but completely inhibited the 3-isobutyl-1-methylxanthine-mediated increase of NEP activity. The PDE-III inhibitors motapizone (100 microM) and enoximone (100 microM) enhanced NEP activity up to 188% and 213%, the PDE-IV inhibitor rolipram (3 microM) up to 162%, and the combined PDE-III/IV inhibitor zardaverine (1 microM) up to 176% of control values. The present data provide evidence for a cAMP-mediated increase of NEP activity in human endothelial cells.

Adenylyl Cyclases↗

OHC response recruitment and its correlation with loudness recruitment.

After proper noise exposure, Hensen's cells, which have been shown to follow closely the response characteristics of the outer hair cells, suffered a loss of sensitivity at low and moderate SPLs. The lower the stimulus level, the greater was the loss. When the low-SPL loss did not exceed about 40 dB, input-output functions showed an increased rate of amplitude growth, so that the post-exposure response caught up with its pre-exposure counterpart between 60 and 90 dB SPL, depending on the severity of the loss. These results, together with preceding clinical observations, led us to the conclusion that loudness recruitment occurs at least in part at the hair cell level and is basically a local event as opposed to a pathological spread of excitation. The response recruitment we have discovered appears to result from a decreased effect of the active feedback when the passive cochlear mechanisms are intact. Evidence for these relationships is presented and an explanation is offered for previous experimental successes and failures in observing a steepening of rate-intensity functions in auditory nerve fibers after noise exposures or administration of ototoxic drugs.

Acoustic Stimulation↗

A reversible ischemia model in gerbil cochlea.

A completely reversible cochlear-ischemia animal model was developed, and an initial study of ischemia/reperfusion-induced cochlear function change is presented. The bulla of the anesthetized gerbil was opened through a ventral approach and the anterior inferior cerebellar artery and its branches were exposed. Cochlear blood flow (CBF) from the basal turn of the cochlea was monitored with a laser Doppler flowmeter. An electrically isolated microclamp was used to occlude the labyrinthine artery (LA). During LA clamping, the cubic distortion product (DP) was continuously recorded. The LA was repeatedly clamped for different durations in all animals, and CBF consistently showed full recovery after clamp release. No obvious change in vessel diameter or flow pattern was observed under a stereomicroscope. Mean blood pressure did not show significant change during clamping. Immediately upon LA clamping, CBF decreased rapidly nearly to zero. After clamp release, CBF demonstrated an immediate rapid increase, followed by a secondary gradual recovery to baseline. CBF recovery patterns were clamp duration-related. Within a few seconds of occlusion, DP decreased and reached a minimum of approximately 24% of the initial level in less that 30 s. Following reperfusion of the cochlea, DP gradually increased, decreased again, then slowly recovered. Time delay between CBF reperfusion and the first increase of DP was proportional to clamping duration, and the increased amplitudes demonstrated a negative relationship to clamp duration. We assume that the first decrease in DP during clamping was caused by ischemia in the cochlea; the second decrease, during the cochlear reperfusion, could be a form of reperfusion-induced change in cochlear function. This ischemia/reperfusion model in gerbil cochlea demonstrates excellent repeatability and reversibility. Since DP and other measurements can be used to dynamically monitor cochlear or hair cell functions, this model is useful in studies of auditory physiology and pathophysiology.

Animals↗

Radioimmunoimaging of colon cancer xenografts with anti-Tn monoclonal antibody.

Tn antigen is a glycosylated tumor associated antigen and a murine monoclonal antibody, MLS128, has been identified to react with it. The potential of MLS128 for the radioimmunoimaging of colorectal cancer was studied. MLS128 was labeled with radioiodine by the chloramine-T method or indium-111 (111In) by using isothiocyanatobenzyl EDTA, and was injected into nude mice bearing human colon cancer xenografts. Radiolabeled MLS128 showed a high and specific localization in xenografted tumor. At 48 h after injection, the %ID/g of 125I-labeled MLS128 in the tumor was 34.69, whereas that of isotype matched control antibody, FLOPC21, was 5.58 and the tumor-to-nontumor radioactivity ratios of 125I-labeled MLS128 reached to 4.56, 17.84 and 23.62 for the blood, liver and bone, respectively. 111In-labeled MLS128 showed similar results. High accumulation of MLS128 in xenografted tumors suggested that the monoclonal antibody MLS128 is promising for radioimmunoimaging of colorectal cancer.

Animals↗

Development of a non-linear finite element modelling of the below-knee prosthetic socket interface.

A non-linear finite element model has been established to predict the pressure and shear stress distribution at the limb-socket interface in below-knee amputees with consideration of the skin-liner interface friction and slip. In this model, the limb tissue and socket liner were respectively meshed into 954 and 450 three-dimensional eight-node isoparametric brick elements, based on measurements of an individual's amputated limb surface; the bone was meshed into three-dimensional six-node triangular prism elements, based on radiographic measurements of the individual's residual limb. The socket shell was assumed to be a rigid boundary. An important feature of this model is the use of 450 interface elements (ABAQUS INTER4) which mimic the interface friction condition. The results indicate that a maximum pressure of 226 kPa, shear stress of 53 kPa and less than 4 mm slip exist at the skin-liner interface when the full body weight of 800 N is applied to the limb. The results also show that the coefficient of friction is a very sensitive parameter in determining the interface pressures, shear stresses and slip. With the growth of coefficient of friction, the shear stresses will increase, while the pressure and slip will decrease.

Artificial Limbs↗

Calcium-induced conformational transition revealed by the solution structure of apo calmodulin.

The solution structure of Ca(2+)-free calmodulin has been determined by NMR spectroscopy, and is compared to the previously reported structure of the Ca(2+)-saturated form. The removal of Ca2+ causes the interhelical angles of four EF-hand motifs to increase by 36 degrees-44 degrees. This leads to major changes in surface properties, including the closure of the deep hydrophobic cavity essential for target protein recognition. Concerted movements of helices A and D with respect to B and C, and of helices E and H with respect to F and G are likely responsible for the cooperative Ca(2+)-binding property observed between two adjacent EF-hand sites in the amino- and carboxy-terminal domains.

Animals↗

ADL dependence and medical conditions in Chinese older persons: a population-based survey in Shanghai, China.

OBJECTIVE: To describe the prevalence of activities of daily living (ADL) dependence and medical conditions and the relationship between illnesses and ADL performance in the older population of Shanghai, China. DESIGN: Probability sample survey of community residents. SETTING: The Jing An district of Shanghai, China. The interviews were carried out at the homes of the older persons. PARTICIPANTS: There were 3763 noninstitutionalized elders screened, 3745 of whom completed the interview. MEASUREMENTS: The dependent variables were the five basic ADL items: eating, dressing, transferring, toileting, and bathing. The independent variables were dementia and 19 self-reported medical conditions, along with age, gender and education level. MAIN RESULTS: Of those in Shanghai aged 65 and older, 8.28% (6.52% of males, 9.17% of females) were functionally dependent in one or more ADLs. The most prevalent self-reported illness was cardiovascular disease, including hypertension (29.12%) and heart disease (26.65%). ADL performance was associated with dementia and a number of medical conditions in univariate analysis. The best predictors of functional dependence in both age groups (65-74 years; 75 years and older), based on the multiple logistic regression analysis and after controlling for age, gender, and education, were stroke, dementia, Parkinson's disease, diabetes, and emphysema. CONCLUSIONS: The authors have successfully applied five ADL items selected and culturally adapted from Older Americans Resources and Services to the study of older Chinese. A consistent and reliable estimate of functional dependence among older persons is obtained. The prevalence of dementia and many self-reported illness, as well as the ADL status by medical condition, are reported. The findings reveal certain patterns of relationship between illness conditions and ADL performance.

Activities of Daily Living↗

T-cell cytokine responses in human infection with Mycobacterium tuberculosis.

Compared with healthy tuberculin reactors, Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells from tuberculosis patients had diminished production and mRNA expression of the Th1 cytokines gamma interferon and interleukin 2 (IL-2), with no change in production and mRNA expression for the Th2 cytokines IL-4, IL-10, and IL-13. These results were confirmed by evaluation of T cells and CD4+ cells. At the level of systemic T cells, development of tuberculosis is associated with diminished Th1 but not enhanced Th2 responses.

Adult↗

Regulation and differential expression of neutral endopeptidase 24.11 in human endothelial cells.

Neutral endopeptidase 24.11, a membrane-bound metallopeptidase, cleaves, and degrades vasoactive peptides such as atrial natriuretic peptide, endothelin, angiotensin I, substance P, and bradykinin. Therefore, the presence of this metallopeptidase may contribute to the regulation of vascular tone and local inflammatory responses in the vascular endothelium and elsewhere. We determined neutral endopeptidase in cultured human endothelial cells from different vascular beds and studied its regulation by protein kinase C. Neutral endopeptidase was detected in all cultured endothelial cell types. Lowest concentrations were measured in human endothelial cells from umbilical veins (360 +/- 14 pg/mg protein), followed by pulmonary and coronary arteries; higher concentrations were found in endothelial cells from the cardiac microcirculation (1099 +/- 73 pg/mg protein). Neutral endopeptidase content increased during cell growth but was not affected by endothelial cell growth factor or modifications of the growth medium. Stimulation of protein kinase C with 1-oleoyl-2-acetyl-rac-glycerol (0.1 to 1 mumol/L) and phorbol 12-myristate 13-acetate (0.01 to 0.1 mumol/L) induced a time- and concentration-dependent increase of endothelial cells that was inhibited by cycloheximide (5 mumol/L), an inhibitor of protein synthesis. Incubation with phospholipase C (1 mumol/L) and thrombin (10 IU/mL) induced upregulation of neutral endopeptidase, resulting in 158 +/- 26% and 150 +/- 22% increases, respectively, compared with controls. The thrombin effect was inhibited by calphostin C (1 mumol/L), an inhibitor of protein kinase C. Endothelial neutral endopeptidase is constitutively expressed in endothelial cells from different origins and is inducible by thrombin via activation of the protein kinase C pathway.

Cell Division↗

Breastfeeding practices in Chengdu, Sichuan, China.

Barriers to increased breastfeeding rates in Chengdu, Sichuan were investigated in 1992 and 1993. Responses of focus groups showed that ignorance about breastfeeding and belief that the mother's milk was inadequate, and lack of support from their families, places of employment, and the health system acted as barriers to the women's breastfeeding their infants up to the age of four to six months. Subsequently, 363 mothers of 4- to 12-month-old Chengdu infants were surveyed. Although most mothers in both studies said breastmilk was the best food for their infant up to age of four to six months, only about half of the mothers breastfed for longer than one month. Both studies showed that infants who roomed with their mothers after birth were more likely to have been put to their mother's breast earlier, fed colostrum, breastfed somewhat longer, and exclusively breastfed for a somewhat longer period, although their mothers' infant feeding knowledge did not differ. The researchers conclude that Chengdu health workers should teach parents and parents-to-be more about breastfeeding, and that rooming-in be expanded in Chengdu hospitals.

Breast Feeding↗

Physicians contracting with managed care.

It has been observed that enrollees in managed care systems such as HMOs and PPOs have lower expenditures and utilization rates than those in conventional insurance plans. Few studies have investigated this issue by examining providers. This paper studies whether physicians with low costs are more likely to sign contracts with HMOs and PPOs in order to help explain the observation of lower expenditures and utilization rates by HMO and PPO enrollees. A logistic regression is applied to the data from the 1984-1985 Physician Practice Costs and Income Survey. The results do not show strong evidence that a physician's likelihood of contracting with HMOs and PPOs is related to the physician's practice costs and utilization pattern. Instead, major factors that significantly affect a physician's decision of contracting with managed care systems are the physician's socio-demographics, the physician's practice region, and the market conditions.

Contract Services↗

Hospitals contracting with managed care.

It has been observed that enrollees in managed care systems such as health maintenance organizations (HMOs) and preferred provider organizations (PPOs) have lower utilization rates and lower expenditures than those in conventional fee-for-service health insurance programs. To date, no study has investigated this issue by examining providers. This paper studies whether lower cost hospitals are more likely to sign contracts with HMOs and PPOs and thus explain the observed lower utilization rates and lower expenditures by HMO and PPO enrollees. A logistic regression is applied to the data from the 1988 AHA Annual Survey of Hospitals. The results show that private hospitals, teaching hospitals, hospitals accredited by JCAHO, hospitals with high case mix index, and hospitals located in MSAs are more likely to contract with HMOs and PPOs than their counterparts. If hospitals with these characteristics have higher costs, then the results do not suggest that hospital costs can explain the lower utilizations and lower expenditures by HMO and PPO enrollees.

Contract Services↗

Heart beat modulation of spontaneous otoacoustic emissions in guinea pig.

It has been reported that background variation in the frequency of spontaneous otoacoustic emission (SOAEs) may arise from the cardiovascular system and that the side-bands in the spectra of SOAEs may be modulated by heartbeat. For better understanding of the mechanical influence of the cardiac cycle on cochlear functions under physiological and pathophysiological conditions, this study investigated heartbeat-induced modulation of SOAEs in guinea pig. Possible mechanisms of these phenomena are also discussed. The external ear canal acoustic signal, round window electric signal, and the ECG were recorded for off-line analysis from five pigmented guinea pigs with SOAEs. Time and frequency domain averages with synchronization of the heartbeat indicate that both the external ear canal acoustic and round window electric signal contain some component contributed by ECG and phonocardiography. High resolution FFT spectra suggest that SOAEs were modulated by heartbeat and respiration. Theoretically the change in the SOAEs could be from frequency modulation or a combination of frequency and amplitude modulations. Results of a heartbeat-synchronized average of a wave analyzer output at SOAE frequency indicates that amplitude modulation of SOAE does occur. Data obtained in the current experiment support the hypothesis that the heartbeat-related modulation of SOAE in guinea pig is a combination of frequency and amplitude modulation. The proposed mechanism is that pulsatile cochlear blood flow may cause oscillations in cochlear pressure and affect cochlear performance, resulting in heartbeat modulation of SOAEs.

Animals↗

[The effect of diethyl-dithiocarbamate on the distribution of pingyangmycin in vivo].

Diethyl-dithiocarbamate (DDC) is a compound with wide spectrum of pharmacologic activities. It has been shown to enhance the tumor cytotoxic effect of Pingyangmycin (PYM). In this paper, the effect of DDC on the distribution of 99mTc-labeled PYM in mice bearing subcutaneous transplant of Ehrlich carcinoma is reported. The results indicate that DDC did not affect the absolute concentration of PYM in the tumor but it accelerated its excretion in the urine and decreased the concentration of PYM in the non-tumorous tissues. Therefore, DDC could help alleviate the damaging effect of PYM on normal tissues without affecting its tumor cytotoxic activity.

Animals↗

Molecular cloning and expression of human granulocyte-macrophage colony stimulating factor in Escherichia coli system.

Human granulocyte-macrophage stimulating factor (hGM-CSF) is an important hematopoietic growth factor. hGM-CSF is able to stimulate hematopoietic progenitors to produce granulocytes, macrophages and eosinophils. hGM-CSF also shows the potential to treat myeloid leukemias. In order to prepare enough hGM-CSF, a genetically engineered strain E. coli HB101/pZW.GM47 was constructed by DNA recombination technologies in the present study, and characterized by restriction analysis, DNA sequencing, SDS-PAGE, Western blotting and bioassays. The strain has been shown to produce a 14kDa mature hGM-CSF protein with expression level higher than 40% and a specific activity of 5.0 x 10(7) u/mg which shows a good potential for clinical applications.

Bacterial Proteins↗