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PubMed2006

Increased heat shock protein 70 expression in the pancreas of rats with endotoxic shock.

AIM: To investigate the ultra-structural changes and heat shock protein 70 (HSP70) expression in the pancreas of rats with endotoxic shock and to detect their possible relationship. METHODS: A total of 33 Wistar rats were randomly divided into three groups: control group (given normal saline), small dose lipopolysaccharide (LPS) group (given LPS 5 mg/kg) and large dose LPS group (given LPS 10 mg/kg). Pancreas was explanted to detect the ultra-structural changes by TEM and the HSP70 expression by immunohistochemistry and Western blot. RESULTS: Rats given small doses of LPS showed swelling and loss of mitochondrial cristae of acinar cells and increased number of autophagic vacuoles in the cytoplasm of acinar cells. Rats given large doses of LPS showed swelling, vacuolization, and obvious myeloid changes of mitochondrial cristae of acinar cells, increased number of autophagic vacuoles in the cytoplasm of acinar cells. HSP70 expression was increased compared to the control group (P<0.05). CONCLUSION: Small doses of LPS may induce stronger expression of HSP70, promote autophagocytosis and ameliorate ultra-structural injuries.

Animals↗
PubMed1996

Distinctive immunohistochemical profiles of small heat shock proteins (heat shock protein 27 and alpha B-crystallin) in human brain tumors.

BACKGROUND: Recent studies have described alpha B-crystallin as a member of the small heat shock protein (HSP) family, and the expressions of alpha-crystallin-related small heat shock proteins, namely HSP27 and alpha B-crystallin, in the brain appear to be regulated in a similar way by various stress conditions. METHODS: A comparative immunohistochemical analysis was performed on 198 human brain tumors to examine the expressions of HSP27 and alpha B-crystallin. RESULTS: Positive staining with HSP27 was frequently observed in schwannomas, craniopharyngiomas, epidermoid cysts, and metastatic tumors to the brain. The immunopositivity of HSP27 was relatively low in tumors originating from neuroepithelium as well as in meningiomas; however, a statistically significantly higher percentage of HSP27-positive cells was noted in their anaplastic counterparts, such as glioblastomas, anaplastic oligodendrogliomas, anaplastic ependymomas, and anaplastic meningiomas (P < 0.005). Conversely, a positive immunoexpression of alpha B-crystallin was frequently observed among astrocytic tumors, schwannomas, hemangioblastomas, and chordomas. CONCLUSIONS: The immunohistochemical expression of HSP27 and alpha B-crystallin differed among histologic types of tumors. Furthermore, the immunopositivity of HSP27, which was considered to play a role not only in drug resistance but also in the regulation of cell proliferation, increased in proportion to the anaplasia of the tumors.

Astrocytoma↗
PubMed2000

Medical anti-shock trousers (pneumatic anti-shock garments) for circulatory support in patients with trauma.

BACKGROUND: Medical antishock trousers (MAST) have been used to increase venous return to the heart until definitive care could be given. This, combined with compression of blood vessels, is believed to cause the movement of blood from the lower body to the brain, heart and lungs. However, the equipment is expensive, and may have adverse effects. OBJECTIVES: To quantify the effect on mortality and morbidity of the use of medical anti-shock trousers (MAST)/ pneumatic anti-shock garments (PASG) in patients following trauma. SEARCH STRATEGY: Trials were identified by searches of the Cochrane Injuries Group Trials Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, BIDS ISI Service and Science Citation Index. References in relevant papers identified were followed up. A citation analysis of references to randomised controlled trials was conducted using the Science Citation Index. Authors of identified trials were contacted and asked about any other trials that may have been conducted, whether published or unpublished. SELECTION CRITERIA: Randomised and quasi-randomised trials of MAST/PASG in patients following trauma (excluding fractures of the extremities in which MAST/PASG may be used as a splint). DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Data were collected on mortality, duration of hospitalisation and ICU stay, and quality of allocation concealment. MAIN RESULTS: Two trials were identified that met the inclusion criteria. These trials included 1202 randomised patients in total; however, data for only 1075 of these were available. The relative risk of death with MAST was 1.13 (95% CI 0.97 to 1.32). Duration of hospitalisation and of intensive care unit stay was longer in the MAST treated group. The weighted mean difference in the length of intensive care unit stay was 1.7 days (95% CI 0.33 to 2.98). REVIEWER'S CONCLUSIONS: There is no evidence to suggest that MAST/PASG application reduces mortality, length of hospitalisation or length of ICU stay in trauma patients and it is possible that it may increase these. These data do not support the continued use of MAST/PASG in the situation described. However, it should be recognised that, due to the poor quality of the trials, conclusions should be drawn with caution.

Bandages↗
PubMed1988

A heat shock protein localized to chloroplasts is a member of a eukaryotic superfamily of heat shock proteins.

We have isolated cDNA clones from soybean and pea that specify nuclear-encoded heat shock proteins (HSPs) which localize to chloroplasts. The mRNAs for these HSPs are undetectable at control temperatures, but increase approximately 150-fold during a 2-h heat shock. Hybridization-selection followed by in vitro translation demonstrates that these HSPs are synthesized as precursor proteins which are processed by the removal of 5-6.5 kd during import into isolated chloroplasts. The nucleotide sequence of the cDNAs shows the derived amino acid sequences of the mature pea and soybean proteins are 79% identical. While the predicted transit peptide encoded by the pea cDNA has some characteristics typical of transit sequences, including high Ser content, multiple basic residues and no acidic residues, it lacks two domains proposed to be important for import and maturation of other chloroplast proteins. The carboxy-terminal region of the chloroplast HSP has significant homology to cytoplasmic HSPs from soybean and other eukaryotes. We hypothesize that the chloroplast HSP shares a common structural and functional domain with low mol. wt HSPs which localize to other parts of the cell, and may have evolved from a nuclear gene.

Amino Acid Sequence↗
PubMed1994

Characterization of high-molecular-mass heat shock proteins and 42 degrees C-specific heat shock proteins of murine cells.

There are two isoforms of high-molecular-mass heat shock protein (HMM-HSP), hsp105A and hsp105B, in murine FM3A cells. To characterize the HMM-HSPs, we here purified hsp105A and hsp105B, as well as 42 degrees C-specific HSPs that are specifically induced by continuous heating at 42 degrees C, from the cytoplasmic extracts of the FM3A cells heat-shocked at 42 degrees C for 8 h. Digestion of the hsp105A, hsp105B, and 42 degrees C-specific HSPs with lysyl endopeptidase generated 17,000-Da polypeptide fragments in common, and the N-terminal amino acid sequences of the fragments revealed a homology with those of the adenosine binding domain of hsp70 family proteins and actin. Thus, the two isoforms of hsp105 and the 42 degrees C-specific HSPs seemed to be very similar proteins having a ATP binding domain in common, and these HSPs may constitute a HMM-HSP family in murine cells.

Amino Acid Sequence↗
PubMed1987

Heat shock phenomena in Aspergillus nidulans. II. Combined effect of heat and bleomycin to heat shock protein synthesis, survival rate and induction of mutations.

The combined action of hyperthermia and Bleomycin on Aspergillus nidulans was studied at three different levels: mycelial protein synthesis, spore viability and induction of mutations. It was found that Bleomycin treatment of preincubated mycelia during the heat shock enhances the incorporation of 35S-methionine into heat shock bands. Furthermore, simultaneous treatment with hyperthermia (43 degrees C) and Bleomycin results in greater cytotoxic activity in spores and in a higher induction rate of point mutations.

Aspergillus nidulans↗
PubMed1982

Changes in spontaneous ureteral peristalsis in experimental shock with and without administration of adrenaline during shock.

In a control group of anaesthetized dogs, a reduction in the number and speed of peristaltic movements of the ureter was observed during anaphylactic and dye shock. In the second, experimental, group of dogs the effect during fully-developed shock of an intravenous injection of adrenaline at the maximum active dose on the ureter dynamics was investigated. It was found that adrenaline increased the number and, to an even greater extent, the speed of peristaltic movements over a period of a few minutes' duration during which the arterial pressure remained high. It seems that adrenaline first and foremost facilitates the conduction of peristaltic stimuli in the ureter.

Anaphylaxis↗
PubMed1992

Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient focal ischemia in rat brain.

The distribution of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNA after 30 min of middle cerebral artery (MCA) occlusion was investigated in rat brain by in situ hybridization using cloned cDNA probes selective for the mRNAs. While HSP70 mRNA was hardly present at caudate and dorsal hippocampal levels of the sham brain this mRNA was greatly induced in cells of the MCA territory 1 h after reperfusion. Although the maximum amount of induced HSP70 mRNA in the caudate was much smaller than that in the cortex the maximum induction in the caudate (3 h) preceded that in the cortex (8 h). In contrast to the case of HSP70 mRNA, HSC70 mRNA was present in most cells of the sham brain, and was especially dense in hippocampal CA3 cells. Further induction of HSC70 mRNA was observed after reperfusion in the same cell populations, as in the case of HSP70 mRNA. HSC70 mRNA levels were significantly reduced in the caudate at 8 h when small amounts of HSP70 mRNA were still elevated. In the ipsilateral granule cells of the dentate gyrus and hippocampal CA3 cells a slight but significant induction of HSC70 mRNA was observed from 1 h to 1 day, while obvious induction of HSP70 mRNA never occurred. All the induced signals of HSP70 and HSC70 mRNA were diminished or returned to the sham level by 7 days, except for HSC70 mRNA in the caudate. These results are the first observations of the distribution of HSP70 and HSC70 mRNA after transient focal ischemia of rat brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Temporal profile of the induction of heat shock protein 70 and heat shock cognate protein 70 mRNAs after transient ischemia in gerbil brain.

Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after 2, 5 and 15 min of transient global ischemia in gerbil forebrain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Morphological studies were also performed at the dorsal hippocampal level of coronal sections from the identical brains until 7 days after the reperfusion. Following 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal dentate granule cells at 1 and 3 h of the reperfusion. No histological change was observed in brain cells. Following 5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The induction of HSP70 mRNA in hippocampal CA1 cells sustained until 2 days, while that of HSC70 mRNA declined gradually. Only CA1 cells were lost at 7 days of the reperfusion. Following 15 min of ischemia, the mRNAs were induced in more extensive brain regions including neocortex and thalamic nuclei. In hippocampal CA1 cells, inductions of HSP70 and HSC70 mRNAs diminished by 2 days corresponding with the neuronal damage. HSC70 mRNA induction was not so much as HSP70 mRNA induction especially in hippocampal CA1 and thalamic cells. Our results showed that HSP70 and HSC70 mRNAs were generally induced together after transient ischemia, but that the inductions were spatially and chronologically different after different periods of ischemia. The dissociation of the induction was also found in cells severely injured after 5 and 15 min of ischemia.

Animals↗
PubMed1988

Phosphorylation of the 90 kDa heat shock protein in heat shocked HeLa cell lysates.

The 90 kDa heat shock protein (hsp 90) is a major phosphorylated protein under normal growth conditions. However, it does not incorporate detectable levels of phosphate by incubation of control HeLa cell lysates with [gamma-32P]ATP in vitro. In this paper we show that strong phosphorylation of hsp 90 occurs in lysates prepared from heat shocked HeLa cells. Possible involvement of the eukaryotic initiation factor 2 kinase of the heme-controlled repressor of translation is discussed.

HeLa Cells↗
PubMed1986

Anti-shock properties of the prostacyclin analog, iloprost, in traumatic shock.

The effects of iloprost, a synthetic carbacyclin derivative of prostacyclin (PGI2) was studied in a standardized model of traumatic shock. Pentobarbital anesthetized rats (35 mg/kg) subjected to Noble-Collip drum trauma were characterized by a 84 +/- 10 minute survival time, a 16-fold increase in plasma cathepsin D activity, and a 5-fold increase in plasma myocardial depressant factor (MDF) activity. Iloprost significantly attenuated the accumulation of MDF activity in the plasma (69 +/- 14 vs. 20 +/- 6 U/ml) vehicle vs. drug (p less than 0.01), respectively, and significantly prolonged survival time to 243 +/- 36 minutes (p less than 0.01). Plasma cathepsin D activity was also significantly attenuated (12 +/- 1.8 vs. 6.2 +/- 2.1 U/ml), vehicle vs. drug, respectively (p less than 0.02). Iloprost exhibited significant anti-proteolytic activity in pancreatic homogenates. Iloprost appears to exert a membrane stabilizing effect decreasing plasma cathepsin D activity and attenuating MDF production, probably secondarily to its anti-proteolytic effect and its maintenance of the splanchnic circulation. Iloprost may therefore prove to be a useful therapeutic agent in acute ischemic disorders including traumatic shock.

Animals↗
PubMed2005

Silencing heat shock factor 1 by small interfering RNA abrogates heat shock-induced cardioprotection against ischemia-reperfusion injury in mice.

Induction of heat shock factor 1 (HSF1) is known to associate with cellular response to divergent pathophysiological stresses including whole body hyperthermia (WBH) and ischemia-reperfusion. However, a direct cause-effect relationship between HSF1 activation and cytoprotection induced by myocardial preconditioning has not been conclusively established, mainly due to the limitations of available experiment tools. In the present studies, we used a novel approach to block HSF1 with small interfering RNA (siRNA) technique in vivo. Male adult ICR mice were treated intraperitoneally with amine (vehicle) or siRNA specific to HSF1 (siRNA-HSF1). Three days later, WBH preconditioning protocol (rectal temperature 42 degrees C for 15 min) was applied to these mice under light anesthesia. WBH preconditioning resulted in 2.7-fold and 3.4-fold increase in cardiac HSF1 mRNA and protein expression respectively 2 hours after WBH, which was inhibited in the siRNA-treated mice. The silencing effect of siRNA on HSF1 was associated with complete loss of the infarct- limiting protection by WBH preconditioning after 48 hours. Pretreatment with siRNA-HSF1 had no effect on infarct size in the sham control animals as compared with the amine-treated group. DNA micro-array analysis revealed that siRNA-HSF1 caused a general inhibition on multiple members of HSP family, except Hsp32, Hsp47 and Hsp60. In addition, the silencing effect of siRNA on HSF1 and HSPs gene expression was transient and its inhibitory effect disappeared by 10 days after treatment. siRNA-HSF1 also impaired the thermotolerance of the heat shocked mice as indicated by higher mortality following WBH. For the first time, we have applied siRNA technique in the field of myocardial preconditioning to demonstrate HSF1 activation as an essential step in WBH preconditioning against cardiac ischemia-reperfusion injury.

Animals↗
PubMed1999

Pharmacokinetics of the nitric oxide synthase inhibitor L-NG-methylarginine hydrochloride in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group.

OBJECTIVES: To characterize the pharmacokinetics of L-NG-methylarginine in patients with septic shock. METHODS: This was an international, uncontrolled, open-label study of L-NG-methylarginine (546C88) therapy given to 32 patients with septic shock. It was conducted in hospital-based intensive care units that admit general surgical and medical patients. Patient cohorts received an infusion of L-NG-methylarginine at fixed dose rates of 1, 2.5, 5, 10, and 20 mg/kg/h for up to 8 hours. The 5 dosing regimens were administered sequentially to separate groups of patients. RESULTS: Of the 32 patients studied, 23 received complete 8-hour infusions. In the other 9 patients, the infusion was terminated prematurely within the first 1/2 to 4 hours. Median clearance of L-NG-methylarginine averaged 485 mL/h/kg for the 1 and 2.5 mg/kg/h dosing cohorts combined but decreased to 283, 181, and 98 mL/h/kg for the 5, 10, and 20 mg/kg/h dosing cohorts, respectively. Median renal clearance was similar at 9 to 26 mL/h for the 1, 2.5, and 5 mg/kg/h dosing cohorts but increased to 156 and 284 mL/h for the 10 and 20 mg/kg/h dosing cohorts, respectively. Median steady-state volume of distribution was similar in all 5 dosing cohorts, averaging 0.66 to 0.82 L/kg. CONCLUSIONS: The 80% decrease in clearance from 485 to 98 mL/h/kg with the increase in dose suggests that a predominant metabolic pathway(s) of L-NG-methylarginine, accounting for at least 80% of clearance, is becoming progressively saturable in association with L-NG-methylarginine infusion rates > or = 5 mg/kg/h. Therefore the use of L-NG-methylarginine infusion rates > or = 5 mg/kg/h are typically expected to result in progressive inhibition of nitric oxide synthase activity. Consequently, patient hemodynamics should be monitored closely to avoid an excessive increase in vasomotor tone, which would be manifest by either an increase in mean arterial pressure or a decrease in cardiac output. The infusion rates of conventional vasopressor(s) (eg, norepinephrine [BAN, noradrenaline]) or L-NG-methylarginine or both may need to be reduced accordingly.

Adult↗
PubMed1995

Protective effect of heat shock pretreatment with heat shock protein induction before hepatic warm ischemic injury caused by Pringle's maneuver.

BACKGROUND: Induction of heat shock proteins is thought to have a > cytoprotective effect against environmental stress and to result in a better ischemic tolerance. The protective ability of heat exposure and heat shock protein 72 (HSP 72) induction before warm ischemia caused by Pringle's maneuver was evaluated in rats. METHODS: Heat exposed rats (HS) were compared with control animals (C). The gene expression (messenger RNA) of HSP 72 and HSP 72 were detected by Northern and Western blot analyses. During 40 minutes of in situ reperfusion, liver energy metabolism and levels of standard liver enzymes were evaluated. The survival rate was determined after postoperative day 7. RESULTS: After heat exposure and recovery, messenger RNA of HSP 72 and HSP 72 can be detected strongly in HS group but not in C group. During reperfusion HS group exhibited a significantly (p < 0.01) improved energy metabolism, and the release of liver enzymes was significantly (p < 0.001) reduced compared with C group. Seven-day survival rate was 100% in HS group but at 50% was significantly impaired (p < 0.05) in C group. CONCLUSIONS: Heat exposure associated with HSP induction has a significant protective effect against warm ischemic liver injury, which results in a relevant improvement of survival rate.

Adenosine Triphosphate↗
PubMed1992

Distributions of heat shock protein-70 mRNAs and heat shock cognate protein-70 mRNAs after transient global ischemia in gerbil brain.

Distributions of heat shock protein (HSP)-70 mRNAs and heat shock cognate protein (HSC)-70 mRNAs after 10 min of transient global ischemia were investigated in gerbil forebrain by in situ hybridization using cloned cDNA probes selective for the mRNAs. Expression of HSP70 immunoreactivity was also examined in the same brains. In hippocampal CA1 neuronal cells, in which only a minimal induction of immunoreactive HSP70 protein was found, the strong hybridization for HSP70 mRNA disappeared at around 2 days before the death of CA1 cells became evident. Furthermore, in hippocampal CA3 cells, a striking induction of HSP70 mRNA was sustained even at 2 days along with a prominent accumulation of HSP70 immunoreactivity. In contrast to the case of HSP70 mRNA, HSC70 mRNA was present in most neuronal cells, especially dense in CA3 cells, of the sham brain. A co-induction of HSP70 and HSC70 mRNAs was observed in several cell populations after the reperfusion with a peak at 8 h, although the magnitude of HSC70 mRNA induction was lower than that of HSP70 mRNA, particularly in CA1 cells. The expression of HSC70 mRNA in CA1 cells also disappeared at around 2 days. All the induced signals of HSP70 and HSC70 mRNAs in other cell populations were diminished and returned to the sham level, respectively, by 7 days. These results are the first to show the time courses of distribution of HSP70 and HSC70 mRNAs and the immunoreactive HSP70 protein in the same gerbil brain after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Toxic shock-like syndrome with flu-like prodrome: a possible role of 'enhancing tissue focus' for streptococcal toxic shock.

We describe three patients with invasive group A streptococcal infection, admitted during the 3 months between November 1996 and February 1997. All patients were previously healthy Japanese women who developed a profound shock, with a rapidly fatal outcome, after experiencing flu-like symptoms. All cases conformed to the case definition of toxic shock-like syndrome (TSLS).Currently, the pathogenic mechanism of TSLS remains unclear. Known microbial virulence factors can not sufficiently explain the occurrence of TSLS, and it has been generally considered that host factors may be contributory. On pathological examination, each patient had one organ or tissue that was most severely involved: Case 1 a non-penetrating trauma; Case 2 a pregnant uterus; and Case 3 a pulmonary lesion reminiscent of lymphocytic interstitial pneumonia. On the basis of clinicopathological features of these cases, we propose that the coexistence of 'enhancing tissue focus' may be one of host factors for the progression of TSLS in patients infected with non-invasive GAS.

Adult↗
PubMed1982

Drosophila gene related to the major heat shock-induced gene is transcribed at normal temperatures and not induced by heat shock.

A gene related to the major heat shock-induced (hsp70) gene of Drosophila has been isolated from the sibling species D. melanogaster and D. simulans. This heat shock-cognate (hsc70) gene is present at cytological locus 70C. The primary sequence of approximately one-third of the protein-coding region has been compared with that of the hsp70 gene; 72% homology of the base sequence and 74% homology of the deduced amino acid sequence was found. In the codon specifying amino acid 66, the hsc70 gene contains an insertion of 1.7 kilobases; the hsp70 genes contain no intervening sequences. The sequence at the 5' and 3' junctions of the insertion is similar to that found in many intervening sequences. cDNA extension experiments indicate that the hsc70 gene is transcribed at normal temperatures in adult flies and that transcription is not enhanced by heat treatment.

Amino Acid Sequence↗
PubMed1983

"Prompt" heat shock proteins: translationally regulated synthesis of new proteins associated with the nuclear matrix-intermediate filaments as an early response to heat shock.

The response of mammalian cells, such as HeLa cells, to prolong exposure to increased temperature (termed heat shock) has been well characterized. In these studies new mRNA is synthesized for several proteins whose translation is best seen after a return to 37 degrees C. We show here another response to increased temperature of a distinctively different character. A set of at least 50 newly detectable proteins, exclusively associated with the nuclear matrix-intermediate filaments (NM-IF) fraction, is synthesized immediately upon exposure to high temperature. These are of very low abundance or nonexistent in the unstressed cell and none appear to correspond to the "classic" heat shock proteins produced after new transcription. Prior treatment with actinomycin D has little effect on these "prompt" proteins, and they appear to be made from preexisting mRNAs that are activated at the increased temperature. The protein synthesis in the soluble, cytoskeletal, and chromatin fractions is strongly reduced by the increased temperature, while the labeling of the prompt proteins associated with NM-IF complex rapidly rises severalfold above that in control cells. Additionally these results suggest that the four cell fractions are not arbitrary cell divisions; rather they represent physiologically significant compartments in the cell.

Autoradiography↗