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Biomedical subjects

M Zhou

Publications and source records attributed to M Zhou.

At least 19 recordsLinked to original sources

Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II.

The intracellular concentration of the 27-kDa mammalian heat shock protein, HSP27, increases several-fold after heat and other metabolic stresses and is closely associated with the acquisition of thermotolerance. Posttranslational modifications may also affect the function of HSP27. Heat shock of HeLa cell cultures, or treatment with arsenite, phorbol ester, or tumor necrosis factor, caused a rapid phosphorylation of preexisting HSP27 and the appearance of three phosphorylated isoforms, HSP27 B, C, and D. Digestion with trypsin and fractionation of the peptides by reverse phase high performance liquid chromatography revealed three 32P-labeled phosphopeptides. Microsequence analysis identified peak I as Ala76-Leu77-Ser78-Arg79 and peak II as Gln80-Leu81-Ser82-Ser83-Gly84-Val85- Ser86-Glu87-Ile88-Arg89; peak III contained the undigested peptide pair Ala76-Arg89. Ser82 was the major site and Ser78 the minor site of phosphorylation. Mutant proteins with Ser78 or Ser82 altered to glycine or Ser78-Ser82 double mutants were phosphorylated to reduced extents in vivo after heat or arsenite treatment. Ser78 and Ser82 (and Ser15) occur in the sequence motif RXXS, which is recognized by ribosomal protein S6 kinase II. Mitogenic stimulation of serum-deprived, Go-arrested Chinese hamster cells with serum, thrombin, or fibroblast growth factor also stimulated phosphorylation of HSP27 Ser78 and Ser82, and mitogenic stimulation and heat shock activated protein kinase activities that phosphorylated HSP27 and protein S6 in vitro. These results suggest that HSP27 may exert phosphorylation-activated functions linked with growth signaling pathways in unstressed cells. A homeostatic function at this level could protect cells from adverse effects of signal transduction systems which may be activated inappropriately during stress.

Amino Acid Sequence

Protective effects of preheparinization on the microvasculature during and after hemorrhagic shock.

Despite the fact that trauma patients are not heparinized at the time of injury, most models of hemorrhagic shock involve heparinization before the initiation of hemorrhage. To determine whether preheparinization has any effects on the microvasculature of organs during or after hemorrhage, rats (with and without preheparinization) were bled to a mean arterial blood pressure (BP) of 40 mm Hg. In two groups, this pressure was maintained by withdrawing additional blood until BP could no longer be maintained at 40 mm Hg (maximal bleedout, MB). In another two groups, the BP was maintained at 40 mm Hg until 40% of the MB volume was returned in the form of lactated Ringer's solution. The rats were then resuscitated with four times the volume of MB with lactated Ringer's. At MB or immediately after resuscitation, colloidal carbon black was rapidly infused and the liver, kidney, and spleen were excised, fixed, and sectioned. In additional animals, blood samples for platelet counts and total body fibrinogen estimates were taken before hemorrhage and at MB or at the end of resuscitation. The results indicate that at MB, microvascular patency in the kidney and liver was significantly depressed in the nonheparinized rats but not depressed in the preheparinized rats. This protective effect of heparin is not directly attributable to its anticoagulant properties, since there were no differences in the consumption of platelets or fibrinogen between the nonheparinized and preheparinized groups. Although the microvascular patency improved with resuscitation in the nonheparinized group, the glomeruli counts and perfusion of the spleen remained significantly lower than in the preheparinized group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

ATP-MgCl2 restores renal microcirculation following trauma and severe hemorrhage.

Although ATP-MgCl2 enhances the recovery of renal function after ischemia and reperfusion, it is not known whether this agent has any beneficial effects on renal microcirculation and function in a nonheparinized model of trauma and severe hemorrhage. To study this, a midline laparotomy was performed (i.e., trauma induced) and the rats were bled to and maintained at a mean arterial pressure of 40 mmHg (1 mmHg = 133.32 Pa) until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL) solution. Animals were then resuscitated with 4 times the volume of the shed blood in the form of RL. ATP-MgCl2, 50 mumol/kg body weight, or an equivalent volume of saline, was infused intravenously during and following resuscitation. Renal microcirculation was examined by using colloidal carbon infusion and laser Doppler flow-metry. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance and cardiac output (CO) was determined by dye dilution technique. The results indicate that the depressed renal microcirculation following hemorrhage and resuscitation was restored by ATP-MgCl2 treatment. GFR was significantly higher in ATP-MgCl2-treated than saline-treated rats. ATP-MgCl2 also increased urine output, restored the decreased CO, and prevented the occurrence of renal edema after hemorrhage and resuscitation. Thus, ATP-MgCl2 appears to be a useful adjunct to crystalloid resuscitation following trauma and severe hemorrhagic shock even in the absence of blood resuscitation.

Adenosine Triphosphate

Differential alterations in microvascular perfusion in various organs during early and late sepsis.

Although cellular dysfunction occurs very early in sepsis, it remains controversial whether this is solely due to a decrease in tissue perfusion. Recent studies have indicated that while active hepatocellular function was depressed, hepatic surface microvascular blood flow (MBF) increased in early sepsis but decreased in late sepsis as produced by cecal ligation and puncture (CLP). However, it is not known whether microvascular hyperperfusion in early sepsis and microvascular hypoperfusion in late sepsis are common events in other organs under such conditions. To study this, rats were subjected to sepsis by CLP, after which these and the corresponding shams received 3 ml/100 g body wt normal saline. Microvascular perfusion and MBF in various tissues were assessed by colloidal carbon infusion and laser-Doppler flowmetry, respectively, at 5 h (i.e., early sepsis) or 20 h (late sepsis) after CLP or sham operation. Carbon-perfused areas were quantitated by an Optomax image analyzer. The results indicate that the carbon-perfused areas and MBF in the liver, renal cortex, spleen, and small intestinal serosa (only MBF) increased significantly 5 h after CLP. In late sepsis, however, the carbon-perfused areas and MBF were found to be significantly decreased. A highly linear relationship was observed between the changes of carbon-perfused areas and MBF during sepsis in the tested organs. Thus the microvascular responses in the fluid-resuscitated sepsis model are characterized by hyperperfusion in the early stage and hypoperfusion in the late stage of sepsis in the tested tissues. The cellular dysfunctions observed during the early stage of sepsis are, therefore, not due to any reduction in tissue perfusion.

Animals

Antitumor activity of siwenmycin: a novel anthracycline antibiotic.

A novel anthracycline antibiotic, siwenmycin, isolated from the culture of Streptomyces galilaeus var. siwenesis, was examined for its antitumor activities against P388, K562, B16-F10, HeLa, HEp-2 and Lewis lung carcinoma cell lines. The results showed that siwenmycin was effective against P388, K562, HeLa and HEp-2 tumor cell lines in vitro, and significantly inhibited the growth of the Lewis lung carcinoma cell line in vivo. Siwenmycin could also suppress spontaneous and artificial pulmonary metastases of B16-F10 and Lewis lung carcinoma cell lines in C57BL/6 mice. The inhibitory effect of siwenmycin on spontaneous pulmonary metastasis of Lewis lung carcinoma in C57BL/6 mice was even stronger than that of adriamycin (ADM), which is, at present, commonly used in clinical practice. Furthermore, the double-labeling test used in this study has verified that siwenmycin can inhibit cellular RNA synthesis at about one tenth the concentration required to inhibit DNA synthesis to the same degree, indicating that the antitumor mechanism of siwenmycin also differs from that of ADM. The acute toxicity of siwenmycin was very low, and it was as effective in vivo as in vitro, suggesting that this newly found antibiotic should be studied for possible clinical antitumor applications.

Aclarubicin

The effect of recombinant GM-CSF and G-CSF on the bone marrow cells of children with acute lymphoblastic leukemia.

Colony stimulating factors (CSFs) are glycoprotein hormones that regulate growth and differentiation of hematopoietic progenitor cells. Their use to stimulate granulocyte precursors during periods of neutropenia in patients with acute myeloid leukemia (AML) is limited by their concomitant stimulation of the proliferation of myeloblasts. The effects of these agents on leukemic lymphoblasts is not entirely known. We have investigated the in vitro effects of granulocyte-CSF (G-CSF) and granulocyte/macrophage-CSF (GM-CSF) on leukemic cells from children with acute lymphoblastic leukemia (ALL). DNA synthesis of bone marrow cells from 22 children with ALL, either at diagnosis or in relapse, was examined with and without CSFs. Proliferative potential was also tested in a clonogenic assay with 13 bone marrow specimens. These factors did not stimulate the growth of ALL cells in either assay. Our results indicate that G-CSF and GM-CSF should be able to stimulate granulocyte proliferation without enhancing leukemic proliferation during periods of neutropenia in children with ALL.

Bone Marrow

[The effect of 211At labelled monoclonal antibody against gastric cancer on DNA, RNA and protein synthesis in gastric cancer cell].

By means of nuclide precursor incorporation, the effects of 211At labelled monoclonal antibody against gastric cancer (211At-3H11McAb) on DNA, RNA and protein synthesis in gastric cancer cell were studied. The results show that 211At-3H11McAb and Na211At-3 inhibit 3H-TdR, 3H-UR and 3H-Leu incorporation, especially 3H-UR incorporation, into gastric cancer cell at 3.7 x 10(4)Bq and 1.85 x 10(5)Bq; the inhibiting rates depend on concentration. The DNA biosynthesis in gastric cancer cell gradually recover after the drug is removed, suggesting that the drug should exert an inhibiting action on DNA biosynthesis in tumor cell through interference of DNA metabolism.

Antibodies, Monoclonal

[Influence of moxibustion on TXA2 and PGI2 in plasma of rat infected epidemic hemorrhagic fever virus (EHFV)].

In this paper, the model of rat infected EHFV was made and the influence of moxibustion on TXA2 and PGI2 in its plasma was observed. The results show that the content of TXA2 increased and PGI2 decreased in rat significantly after the abdominal inoculation of EHFV, and the content of TXA2 decreased and PGI2 increased markedly in rat infected EHFV to normal level after treatment with moxibustion, suggesting that the regulative function of moxibustion on TXA2 and PGI2 is one of its nerve-endocrine-immune regulations to the body, and there is an important significance. This study provides an important reference for mechanism exploration of moxibustion preventing and treating EHF.

6-Ketoprostaglandin F1 alpha

Preliminary result of mixed bacterial vaccine as adjuvant treatment of hepatocellular carcinoma.

Mixed bacterial vaccine (MBV) was employed in the multi-modality treatment of hepatocellular carcinoma (HCC) during 1985-1988. Thirty eight patients undergoing palliative resection and cisplatin therapy (Series 1) and 48 patients with unresectable HCC who received hepatic artery ligation + intraarterial cisplatin infusion + radiotherapy (Series 2) were randomized to receive MBV or not. In series 1, the 1- and 2-year survival rates of MBV group and control were 75% vs 58% (P = 0.19) and 45% vs 39% (P = 0.23). In series 2, the 1-, 2- and 3-year survival rates were 59%, 41% and 41% for MBV group and 39%, 25% and 20% for the control, respectively (P1 = 0.07, P2 = 0.09, P3 = 0.07). In addition, MBV improved the "second look" resection rate to 40% as compared to 17% in the control (P greater than 0.05). MBV could also prevent such immunosuppression as decrease of macrophage activity caused by radiotherapy. We consider MBV a potential nonspecific immunostimulant in the multimodality treatment of HCC.

Adult

Effects of taurine and ketamine on bovine retinal membrane lipid peroxidation.

Lipid peroxidation disrupts membrane integrity and causes structural and functional alterations in ischemic tissues. Taurine and ketamine are putative ischemic protectants that affect Ca2+ influx. Here we report the influence of these compounds on lipid peroxidation in subcellular fractions, isolated cells and intact tissue from bovine retinas. P2 membrane fractions and isolated cells were exposed to the lipid peroxidation inducers cadmium chloride (200 microM) or L-ascorbic acid (1 mM) in the presence of 0-50 mM taurine, 0-10 mM ketamine, 1 mM kynurenic acid or 1 mM dextromethorphan. The latter compounds are N-methyl-D-aspartate receptor antagonists. Lipid peroxidation in isolated eyes reperfused after 1 h of ischemia either with or without protectants was determined by thiobarbituric acid assay. Glutathione was measured in isolated retinas subjected in vitro to simulated ischemia (no glucose or oxygenation) for 60 min either alone or in the presence of taurine or ketamine. Ketamine inhibited chemical- or ischemia-induced lipid peroxidation as well as ischemic glutathione depletion. Under the same conditions, taurine failed to affect lipid peroxidation or glutathione. The data show a direct effect of ketamine on lipid peroxidation and point to separate mechanisms of action for ketamine and taurine.

Animals

Hepatic artery ligation and infusion chemotherapy for unresectable primary liver cancer.

During the period of 1958-1989, 356 patients with pathologically proven primary liver cancer (PLC) were determined by laparotomy to be unresectable. Of the 356 patients, 51 (14.3%) were of subclinical stage, 287 (80.6%) of moderate stage and 18 (5.1%) of late stage. The association of liver cirrhosis was present in 310 patients (87.1%). Treatment modalities in 356 patients were divided into 4 groups: hepatic artery ligation (HAL) (51), hepatic artery infusion (HAI) of chemotherapeutic agents (114), HAL + HAI (117), and HAL + HAI + radiotherapy (74). The 5-year survival rate was zero in the 4 groups in the period of 1958-1977. During 1978-1989, however, the 5-year survival rate was zero in HAL, 7.9% in HAI, 24.4% in HAL + HAI (with second look resection in 10 patients), and 36.5% in HAL + HAI + radiotherapy (with second look resection in 19). The marked improvement in survival in later period was attributable to the accurate site of hepatic artery catheter, longer infusion chemotherapy, and combination treatment, particularly second look resection in some of the patients. These results indicate that HAL + HAI + combination treatment might provide a possible prolongation of survival or even resection in some patients with original unresectable PLC.

Adolescent

[Change of T lymphocyte subsets in peripherial blood of children with malnutrition and zinc deficiency].

Sixty children with malnutrition were investigated in this study. The results showed a reduction of serum zinc in moderate and severe cases compared with the mild and normal groups. OKT3+, OKT4+ and OKT8+ cells in peripheral blood of mild malnutrition were significantly decreased in contrast to normal control. The reductive degree of OKT8+ and OKT4+ cells correlated with the severity of malnutrition. OKT8+, OKT4+ and OKT4+/OKT8+ ratio of moderate and severe malnutrition with infection were much lower than those without infection. Our findings suggested that main effective and regulative cells of cell-mediated immunity were impaired. OKT3+ and OKT4+ cells might be used as a sensitive index for early assessment of the immune function in malnutrition children.

CD4-CD8 Ratio

[Improvement of memory in mice by extracts from leaves of Ginkgo biloba L].

The study has shown that the extracts from leaves of Ginkgo biloba can significantly improve the NaNO2 and scopolamine induced impaired memory in mice. The potency of the ethanolic extract is greater than that of the aqueous extract. The ethanolic extract acts favorably on the memory function of normal animals. Both extracts help to prolong the survival time of mice receiving 200 mg/kg(ip)NaNO2.

Animals

Importance of viability and attachment to an ascites tumor in the release of plasminogen activator.

Tumor plasminogen activator (PA) has been alleged to play a role in the growth and metastasis of tumors. Before such a role can be realized, PA first must be released from tumor cells. Having determined intra- and extracellular PA and PA-inhibitor activities in an experimental pancreatic ascites tumor grown in hamsters, the release of PA from these cells was investigated. No PA activity was detected in the suspension medium of freshly isolated tumor cells; inclusion of plasminogen, fibrinogen, or collagen in the medium yielded similar negative results. On the other hand, PA activity was demonstrated to be released in a time-dependent manner from these tumor cells embedded in fibrin clots. Plasminogen activator activity also was not found in the suspension medium of frozen-thawed tumor cells, despite the fact that most of them had breaks on their cell membrane. Unlike freshly isolated tumor cells, PA was not released from frozen-thawed cells embedded in fibrin clots. Full PA activity was demonstrated in frozen-thawed cells treated with Triton X-100, however. Frozen-thawed cells exhibited signs of severe damage, and more than 80% of them failed to exclude trypan blue. Obviously PA is released from viable tumor cells embedded in fibrin clots but not suspended in artificial medium. The PA-release mechanism, not PA itself, is destroyed in cells rendered nonviable by freeze thawing.

Animals

Ageing alters the myosin heavy chain composition of single fibres from human skeletal muscle.

The myosin heavy chain composition of single fibres (n = 1088) was analysed with an electrophoretic technique in biopsy material from m. vastus lateralis (n = 5) and m. biceps brachii (n = 4) of young (23-31 years old) and elderly men (68-70 years old). In m. vastus lateralis, elderly subjects had a higher proportion of fibres showing a coexistence of myosin heavy chain types I and IIa (20 +/- 3% vs 8 +/- 1%, P less than 0.05) and of myosin heavy chain types IIa and IIb (33 +/- 2% vs 12 +/- 4%, P less than 0.05). In contrast, the young subjects had a higher proportion of fibres containing only myosin heavy chain type I (50 +/- 5% vs 33 +/- %, P less than 0.05) and type IIa (26 +/- 3% vs 12 +/- 2%, P less than 0.05). A similar pattern of myosin heavy chain expression was found in single fibres from m. biceps brachii, with the exception that the elderly subjects had a lower proportion of fibres with coexistence of types IIa and IIb (23 +/- 1% vs 34 +/- 2%, P less than 0.05) and a higher proportion of fibres containing only myosin heavy chain type IIa (25 +/- 5% vs 12 +/- 2%, P less than 0.05). Three fibres from m. biceps brachii contained all three isoforms. These results indicate that coexistence of myosin heavy chain isoforms in single fibres is present in skeletal muscles of young adults, and that there is an increased occurrence of this phenomenon with ageing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Myosin heavy chain composition of single fibres from m. biceps brachii of male body builders.

The myosin heavy chain (MHC) composition of single fibres from m. biceps brachii of young sedentary men (28 +/- 0.4 years, mean +/- SE, n = 4) and male body builders (25 +/- 2.0 years, n = 4) was analysed with a sensitive one-dimensional electrophoretic technique. Compared with sedentary men, the body builders had a higher proportion of fibres containing only MHC type IIa (36 +/- 4 vs 12 +/- 2%; P less than 0.05), but a lower proportion of fibres with a coexistence of MHC types IIa and IIb (16 +/- 3 vs 34 +/- 2%; P less than 0.05) and nearly no fibres containing only MHC type IIb (1 +/- 1 vs 12 +/- 1%; P less than 0.05). Myofibrillar ATPase histochemistry only demonstrated a trend towards a higher proportion of type IIa fibres (31 +/- 6 vs 25 +/- 6%) and a lower proportion of type IIb fibres (18 +/- 5 vs 26 +/- 6%) within the body builders. These results, therefore, suggest an altered expression of MHC isoforms within histochemical type II fibres of human skeletal muscle with body building. Furthermore, in human skeletal muscle differences in expression of MHC isoforms may not always be reflected in the traditional histochemical classification of types I, IIa, IIb and IIc fibres.

Adenosine Triphosphatases