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Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 721 records · Page 40Linked to original sources
PubMed1997

Hematogenous metastases of the human brain--characteristics of peritumoral brain changes: a review.

The brain is an important site of hematogenous metastases from malignant tumors in other organs. The effects on the brain is a combination of tissue destruction induced by invading tumor cells and reactive alterations occurring around the metastases. This review focuses on neuropathological changes around hematogenous metastases of the human brain. The peritumoral brain parenchyma shows structural and functional changes of the intracerebral microvessels and edema. The endothelial cells of peritumoral microvessels express glucose transporter protein (GLUT 1) in the same way as the normal brain. Reduction in immunostaining to GLUT 1 may occur in the microvessels located within the metastases. This would indicate abnormalities of the blood-brain barrier in tumor vessels but normal barrier function in the peritumoral region. Reactive astrocytes and activated microglial cells are both involved in the process of peritumoral gliosis. Activated glial cells produce numerous biological active compounds including endothelin-1 which after release from such cells can influence the structure and function of the peritumoral brain tissue. Lesions of oligodendrocytes and edema may be implicated in myelin degeneration. Finally, metastases will induce axonal and neuronal injuries as indicated by a recent study on expression of beta-amyloid precursor protein (beta APP) in reactive axonal swellings.

Axons↗
PubMed1997

Feasibility and cost-effectiveness of outpatient autotransplants in multiple myeloma.

This report summarizes 2 years experience in performing 336 autotransplant procedures in 251 consecutive patients with multiple myeloma, using high-dose melphalan at 200 mg/m2 in the context of a tandem transplant program. A total of 91 patients received 118 transplants as outpatients while the remaining 160 patients received 218 transplants as inpatients. Outpatients were more often younger, with better stem cell products, normal serum albumin and beta-2-microglobulin levels as well as chemotherapy-sensitive disease compared to inpatients. There were no differences in hematopoietic recovery and non-hematologic toxicities between outpatient and inpatient transplant recipients. Post-transplant febrile neutropenia and most other post-transplant toxicities were managed successfully in an ambulatory setting. Although liberal criteria were developed for hospitalization of outpatients, including clinical parameters as well as patient desire and physician/nurse judgement, only 21% of outpatients required admission after transplantation. Median hospital stay for these outpatients was 9 days, while inpatients were hospitalized for a median of 15 days (P = 0.0001). After adjusting for differences in disease and host features, our study showed outpatient management resulted in significant financial savings due to lower pharmacy (42%), hospitalization (50%) and pathology/laboratory charges (36%). We conclude that outpatient transplants should facilitate access to myeloablative therapy, thereby improving complete remission rates and survival of myeloma patients.

Adult↗
PubMed1997

Fictive oesophageal peristalsis evoked by activation of muscarinic acetylcholine receptors in rat nucleus tractus solitarii.

The aim of the present study was to determine if muscarinic acetylcholine receptor-mediated peristaltic rhythmogenesis in the rat oesophagus is a central motor program that can be generated without peripheral sensory support. In anaesthetized male Sprague-Dawley rats, pressure-ejection of glutamate (10-20 pmol) and muscarine (5-10 pmol) in the sub-nucleus centralis of the nucleus tractus solitarii (NTSC) evoked monophasic pressure waves and rhythmic oesophageal peristalsis, respectively, but did not change mean arterial blood pressure or respiration. Application of muscarine (50-100 pmol) to the NTS extraventricular surface evoked rhythmic multi-unit burst discharges in the compact formation of the nucleus ambiguus (AMBC) that led to oesophageal peristalsis in a phase-locked manner. Evoked rhythmic AMBC activity persisted during neuromuscular blockade with curare, although the peak frequency of individual bursts was decreased. In a brainstem slice preparation, intracellular and whole cell patch recordings from AMBC neurones during focal stimulation of the NTSC region with muscarine revealed rhythmic depolarizing waves that showed a pattern similar to that of rhythmic oesophageal peristalsis. The present findings support the concept that medullary circuits comprising premotor neurones of the NTSC are intrinsically capable of generating rhythmic oesophagomotor output, but are subject to a powerful modulation by peripheral sensory feedback.

Animals↗
PubMed1997

High level expression of recombinant plasminogen activator inhibitor-1 in Escherichia coli and generation of its mutants involving Asp125, Glu128 and Glu130.

Plasminogen activator inhibitor-1 (PAI-1) cDNA was expressed in Escherichia coli (E. coli) with high efficiency using a heat-inducible vector. About 100 mg of recombinant PAI-1 (rPAI-1) could be obtained from 1 liter of bacteria culture. rPAI-1 in inclusion bodies was purified by pI precipitation and Sephadex G-75 chromatography. After treatment with 4 mol/L guanidinium chloride and dialysis, the largely inactive PAI-1 gained considerably in activity as judged by its reaction with low molecular weight u-PA (LMW-u-PA). Degenerated oligonucleotides containing ApaI site and mutations at Asp125, Glu128, Glu130 in PAI-1 cDNA were synthesized. To facilitate the introduction of mutations, an ApaI site was first generated in PAI-1 cDNA using one of the oligonucleotides. Taking advantage of the APaI site, thirteen PAI-1 mutants involving Asp125, Glu128 and Glu130 were produced with these oligonucleotides using PCR. Most of the PAI-1 mutants had a similar activity as compared to wild type PAI-1, while some of the triple-site mutants had completely lost their activity.

DNA, Complementary↗
PubMed1997

A cross-cultural validation of coping strategies and their associations with caregiving distress.

Coping strategies were compared among family caregivers of Alzheimer's disease patients in Shanghai, China (n = 110) and San Diego, California (n = 139). Four coping factors were reliably consistent in both samples, supporting their widespread relevance to life adversity; behavioral confronting, behavioral distancing/social support, cognitive confronting, and cognitive distancing. Shanghai and San Diego caregivers endorsed similar rates of coping, but Shanghai caregivers reported fewer symptoms of depression and anxiety. Although coping strategies were similar, cultural ideals promoting family interdependence, veneration of elderly family members, and acceptance of traditional family roles may have reduced the psychological impacts of caregiving in the Shanghai sample.

Adaptation, Psychological↗
PubMed1997

Detection of altered adhesion molecule expression in experimental tumors by a radiolabeled monoclonal antibody.

Adhesion molecules play a major role in the processes of invasion and metastasis of malignant tumors. Their expression within tumors has been reported to be quantitatively and qualitatively altered according to the invasiveness and metastatic potential of the tumor. The present study tested whether the intratumoral expression of integrin alpha 3 can be detected by a radiolabeled monoclonal antibody. The in vitro binding study with four different human cancer cells showed that radioiodinated GA17 antibody recognizing integrin alpha 3 bound specifically to these cells to varying degrees, according to the antigen density on each cell. The biodistribution study with 125I- and 111In-labeled antibodies showed specific localization of radiolabeled GA17 to the xenografts. However, the in vivo tumor localization was not proportional to the antigen density calculated in vitro, and antibody metabolism varied among the tumors, as was also confirmed by in vitro radionuclide retention assay. The intratumoral distribution of radioactivities varied reflecting the antigen expression within the tumor. These results indicate that 1) integrin alpha 3 was expressed in various kinds of tumors and could be localized by the radiolabeled antibody, and 2) the expression of integrin alpha 3 and the metabolism of the radiolabeled antibody after binding to the antigen within the tumor were variable among the tumors, which affected the radionuclide distribution characteristics. The expression of adhesion molecules within these tumors was noninvasively detected by a radiolabeled antibody. It may be possible to use integrin alpha 3, when it is overexpressed, as a target of therapy with antibodies radiolabeled with alpha or beta emitters.

Animals↗
PubMed1997

Anti-murine antibody response to mouse monoclonal antibodies in cancer patients.

Although development of human anti-murine immunoglobulin antibody (HAMA) is often seen in patients receiving murine antibodies, the variety of methods used for detecting HAMA makes it difficult to compare directly the HAMA responses measured by different assays. In the present study, several parameters of the HAMA response to two murine monoclonal antibodies were evaluated. The anti-sialosyl Tn antibody MLS102 and anti-CA125 antibody 145-9, which were labeled with 111In, were injected intravenously into 17 colorectal cancer patients and 11 ovarian cancer patients for immunoscintigraphy, respectively. HAMA was measured by enzyme-linked immunosorbent assay. There was no difference in baseline HAMA levels before antibody injection between the two groups. HAMA developed more frequently in ovarian cancer patients receiving the 145-9 antibody than in colorectal cancer patients receiving the MLS102 antibody (9/11 vs. 6/17, P < 0.05). No significant difference was observed in maximal HAMA levels between the two groups of patients. However, time to reach the maximal levels was delayed and the duration of the response seemed longer in ovarian cancer patients. Among 11 patients receiving the 145-9 antibody three patients became positive for HAMA more than 2 months after antibody injection and the other two had HAMA activity in their sera for more than 17 months. HAMA response was different between the two antibodies, and late onset or long duration of HAMA response against the 145-9 antibody suggests the importance of HAMA measurement in patients who receive a second injection of murine antibodies even after a long interval.

Adult↗
PubMed1997

Granulocyte-colony stimulating factor maintains a thermally stable, compact, partially folded structure at pH2.

At acidic pH many proteins exist in a partially unfolded form, called the "A" state. This is defined as a flexible, expanded structure with well-defined, usually native-like secondary structure, but no unique tertiary structure, and showing no cooperativity during thermal-induced denaturation. Granulocyte-colony stimulating factor (G-CSF), a four-helix bundle cytokine, maintains both thermal stability and tertiary structure at pH 2.0. We therefore examined the conformation and thermal unfolding of G-CSF at pH 2.0, 4.0 and 7.0 using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR). The secondary structure of the molecule remains highly helical as the pH is lowered from 7.0 to 2.0. The tertiary structure of the protein is slightly different at each pH value, but even at pH 2.0 G-CSF maintains a regular three-dimensional structure. The structure is hydrodynamically compact at these different pH values, with no increase in Stoke's radius even at pH 2.0. The thermal-induced denaturation of G-CSF was determined by monitoring changes in the CD or FTIR spectra. At pH 2.0 the temperature at which thermal-induced denaturation begins is higher than it is at pH 4.0 or 7.0, the thermal unfolding transition remains cooperative and some alpha-helical structure persists even at 86 degrees C. At pH 4.0 and 7.0, secondary and tertiary structures disappear simultaneously during thermal denaturation, whereas at pH 2.0 small changes in the far-UV CD region begin to occur first, followed by the simultaneous cooperative loss of tertiary structure and much of the remaining secondary structure. The structure of G-CSF at pH 2.0 is thus revealed as compact, with a unique, three-dimensional structure, highly helical secondary structure, and most importantly, a cooperative thermal unfolding transition. G-CSF at acid pH thus does not adopt the "A" state.

Circular Dichroism↗
PubMed1997

Effects of middle ear pressure on otoacoustic emission measures.

An animal surgical model was established to manipulate pressure in the middle ear. The 2 f1-f2 cochlear microphonic distortion product (CMDP) and distortion product otoacoustic emission (DPOAE) were simultaneously measured in order to analyze the effects of middle ear pressure on sound transmission. The frequency ratio of the two stimulus tones f2/f1 was held at 1.2 and the level ratio L1/L2 was 10 dB. The effect of middle ear pressure on forward transmission was determined form the CMDP data. The effect on backward transmission was determined from the DPOAE data after the effect on forward transmission was subtracted out. The results showed a similar effect on forward and backward transmission. In general, negative pressure had a greater effect than positive pressure. Positive pressures of 10 and 20-cm H2O affected transmission for low-frequency stimuli (f2 = 1620 and 2680 Hz) but had little effect for high-frequency stimuli (f2 = 6980 and 10,250 Hz). Negative pressures of -2.5 to -10-cm H2O affected transmission across all frequencies tested. The effect at low frequencies is hypothesized to be related to tympanic membrane stiffness. The effect of negative pressure at high frequencies may be related to changes in the incudostapedial joint.

Acoustic Stimulation↗
PubMed1997

Structure/activity relationships in lysophosphatidic acid: the 2-hydroxyl moiety.

Although lipid phosphoric acid mediators such as lysophosphatidic acid (LPA) are now recognized widely as intercellular signaling molecules, the medicinal chemistry of these mediators is poorly developed. With the goal of achieving a better understanding of the structure activity relationships in LPA, we have synthesized and tested a series of LPA analogs that lack the 2-hydroxyl moiety. Our series consisted of compounds with 2, 3, or 4 carbon diol or amino alcohol backbones and oleoyl or palmitoleoyl acyl groups. These molecules cannot be acylated further to form phosphatidic acids, nor do they have chiral centers. The rank order potency of these compounds in mobilization of calcium in MDA MB-231 cells suggested a maximum optimal chain length of 24-25 atoms. However, high potency for the inhibition of adenylyl cyclase in these cells was achieved only by one compound that also contained a dissociable proton five bond lengths from the phosphorus atom. That compound, N-oleoyl-2-hydroxyethyl-1-phosphate, was nearly equipotent to 1-oleoyl LPA in both assays. The striking mimicry of LPA by the ethanolamine-based compound and the presence of fatty acid amides in tissue prompts us to propose that phosphorylated N-acyl ethanolamides occur naturally.

Humans↗
PubMed1997

Synthetic-peptide-based enzyme-linked immunosorbent assay for screening human serum or plasma for antibodies to human immunodeficiency virus type 1 and type 2.

A synthetic-peptide-based enzyme-linked immunosorbent assay (EIA) capable of screening for antibodies to both human immunodeficiency virus type 1 (HIV-1) and HIV-2 has been developed for use in blood banks and diagnostic laboratories. Microtiter wells are coated with two synthetic peptides, one corresponding to the highly conserved envelope region of HIV-1 and another corresponding to the conserved envelope region of HIV-2. Overall, sensitivity was 100% in 303 individuals diagnosed with AIDS and 96 individuals diagnosed with AIDS-related complex, 14.8% in a study of 500 high-risk group members, 99.9% in 600 EIA repeatedly reactive (RR)-HIV-1 Western blot (WB)-positive repository specimens, and 100% for 222 geographically diverse HIV-1 specimens and 216 confirmed HIV-2-positive specimens evaluated. The specificity was determined to be 99.72% for a total of 13,004 serum and plasma samples from random volunteer donors evaluated across five blood banks. Forty donors who were found to be EIA RR-WB indeterminate but nonreactive on the United Biomedical, Inc., test (UBI HIV 1/2 EIA) were prospectively followed as an additional measure of specificity. None of the 40 low-risk cases evolved into a positive WB pattern at follow-up. The sensitivity and specificity of this new assay are comparable to those of other Food and Drug Administration-licensed HIV-1 and HIV-1-HIV-2 assays that are currently available in the United States. The UBI HIV 1/2 EIA affords laboratories another choice in the detection of antibodies for HIV-1 and HIV-2 with a test based on an alternative antigen format.

AIDS Serodiagnosis↗
PubMed1997

Effects of Mycobacterium tuberculosis on the bioelectric properties of the alveolar epithelium.

To investigate the hypothesis that Mycobacterium tuberculosis penetrates the alveolar epithelium by downregulating its barrier properties, we evaluated the interactions between M. tuberculosis and rat alveolar epithelial cell monolayers that are believed to share electrophysiologic properties of the human alveolar epithelium. Nonproteinaceous components of M. tuberculosis caused marked declines in electrical resistance and equivalent short-circuit current of the alveolar epithelial cell monolayers, indicating a reduction in the capacity to maintain tight intercellular junctions and to actively reabsorb sodium. M. tuberculosis elicited production of TNF-alpha mRNA and protein by alveolar epithelial cells, and the effects of recombinant TNF-alpha on the bioelectric properties of the alveolar epithelial paralleled those of M. tuberculosis. Furthermore, the effects of M. tuberculosis on alveolar epithelial resistance were abrogated by neutralizing anti-TNF-alpha antibodies. These results indicate that M. tuberculosis elicits production of TNF-alpha, which in turn reduces the bioelectric barrier properties of the alveolar epithelium. These findings provide insight into potential mechanisms by which M. tuberculosis establishes infection and disease in the lung.

Animals↗
PubMed1997

Solitary pulmonary nodules: evaluation of blood flow patterns with dynamic CT.

PURPOSE: To evaluate the efficacy of dynamic computed tomography (CT) for differentiating benign from malignant solitary pulmonary nodules (SPNs). MATERIALS AND METHODS: Sixty-five patients with noncalcified SPNs (diameter, < or = 30 mm; 42 malignant, 16 benign, seven inflammatory) underwent single-location dynamic contrast material-enhanced (100 mL, 4 mL/sec) serial CT. Peak height of time-attenuation curves and ratio of peak height of the SPN to that of the aorta were measured. Precontrast attenuation and enhancement pattern were recorded. Perfusion was calculated from the maximum gradient of the time-attenuation curve and the peak height of the aorta. RESULTS: Peak heights of malignant (41.9 HU +/- 2.8) and inflammatory (43.6 HU +/- 7.7) SPNs were significantly higher than that (13.4 HU +/- 2.2) of benign SPNs (P < .001; P < .01). SPN-to-aorta ratios in malignant and inflammatory SPNs were significantly higher than that in benign SPNs (P < .001, P < .05). No statistically significant differences in the peak height and SPN-to-aorta ratio were found between malignant and inflammatory SPNs. Precontrast attenuation of inflammatory SPNs was lower than that of malignant SPNs (P < .05). Perfusion values in malignant and inflammatory SPNs were significantly higher than that of the benign SPNs (P < .01). CONCLUSION: Dynamic CT provides quantitative information about blood flow patterns of SPNs and is an applicable diagnostic method for differentiating SPNs.

Adult↗
PubMed1997

New perspectives in mental health services in Shanghai.

This article reports developments in mental health services in Shanghai during the past several years, including family education and involvement, new forms of community services, psychological consultation programs, hot line services and crisis intervention, dealing with psychological problems in general hospitals, and nursing care for elderly patients with dementia. The authors reevaluate and outline the new perspectives in mental health services in Shanghai.

Adolescent↗
PubMed1997

Kinin generation in acute pneumonia and chronic bronchitis.

Kinins are potent inflammatory mediators, liberated from kininogens by different kininogenases. The aim of this study was to investigate the kinin generation pathways in acute and chronic inflammation of the lower airways. We studied bronchoalveolar lavage fluid (BALF) of patients with acute pneumonia, patients with chronic bronchitis and healthy controls. Kinins were determined by radioimmunoassay (RIA). Plasma kallikrein (pl-Kal), alpha2-macroglobulin (alpha2-M) and toluenesulphonylarginine methyl ester (TAME) esterase activity (TAME-ea) were studied in BALF before and after gel filtration chromatography. Plasma kallikrein and alpha2-M were measured using two newly developed sandwich enzyme-linked immunosorbent assays (ELISAs). TAME-ea was measured by a radiochemical assay. After gel filtration, inhibition of TAME-ea with benzamidine, soy-bean-trypsin inhibitor (SBTI) and aprotinin was performed. Kinins and TAME-ea did not differ significantly between acute pneumonia and chronic bronchitis, whereas pl-Kal and alpha2-M values were significantly higher in acute pneumonia. Gel filtration revealed the highest TAME-ea peak in acute pneumonia corresponding with the first alpha2-M peak at approximately 800 kDa, whereas in chronic bronchitis the highest peak was found at approximately 40 kDa. The inhibition test showed that the TAME-ea peak at approximately 800 kDa was due to pl-Kal and the TAME-ea peak at approximately 40 kDa was mainly due to tissue kallikrein. High peaks of alpha2-M and pl-Kal were found in pneumonia and only small peaks were seen in chronic bronchitis. We conclude that in acute airway inflammation kinins seem to be mainly generated by plasma kallikrein whereas in chronic inflammation, kininogenases other than plasma kallikrein, such as tissue kallikrein, seem to be more important.

Acute Disease↗
PubMed1997

The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats.

A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-alpha2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-beta, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous bone loss in the unloaded limb in excess of that induced by gonadal hormone deficiency. This additional bone loss was arrested by estrogen replacement. We conclude from these studies that estrogen alters the expression of signaling peptides believed to mediate skeletal adaptation to changes in mechanical usage and likewise modifies the skeletal response to mechanical unloading.

Animals↗
PubMed1997

T-type calcium channels facilitate insulin secretion by enhancing general excitability in the insulin-secreting beta-cell line, INS-1.

The present study addresses the function of T-type voltage-gated calcium channels in insulin-secreting cells. We used whole-cell voltage and current recordings, capacitance measurements, and RIA techniques to determine the contribution of T-type calcium channels in modulation of electrical activity and in stimulus-secretion coupling in a rat insulin secreting cell line, INS-1. By employing a double pulse protocol in the current-clamp mode, we found that activation of T-type calcium channels provided a low threshold depolarizing potential that decreased the latency of onset of action potentials and furthermore increased the frequency of action potentials, both of which are abolished by administration of nickel chloride (NiCl2), a selective T-type calcium channel blocker. Moreover application of high frequency stimulation, as compared with low frequency stimulation, caused a greater change in membrane capacitance (deltaCm), suggesting higher insulin secretion. We demonstrated that glucose stimulated insulin secretion in INS-1 is reduced dose dependently by NiCl2. We conclude that T-type calcium channels facilitate insulin secretion by enhancing the general excitability of these cells. In light of the pathological effects of both hypo and hyperinsulinemia, the T-type calcium channel may be a therapeutic target.

Action Potentials↗