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Biomedical subjects

A Tokunaga

Publications and source records attributed to A Tokunaga.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential effect of brain-derived neurotrophic factor on high-threshold mechanosensitivity in a rat neuropathic pain model.

We investigated the effect of the systemic infusion of brain derived neurotrophic factor (BDNF) on the behavioral response in a rat neuropathic pain model. One microgram per hour infusion of BDNF significantly attenuated mechanical hyperalgesia tested by the pin-prick test, however, 20 microg/h-BDNF infusion, on the contrary, enhanced the response. Neither 0.5 nor 10 microg/h-BDNF infusion influenced the mechanical hyperalgesia. Mechanical allodynia and thermal hyperalgesia, tested using a von Frey filament (23.0 mN) and the plantar test, were not influenced by BDNF treatment. These data suggest that systemic BDNF treatment can specifically alter high-threshold mechanosensitivity.

Animals↗
PubMed2000

Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury.

Activating transcription factor 3 (ATF3), a member of ATF/CREB family of transcription factors, is induced in a variety of stressed tissue. ATF3 regulates transcription by binding to DNA sites as a homodimer or heterodimer with Jun proteins. The purpose of this study was to examine the expression and regulation of ATF3 after axonal injury in neurons in dorsal root ganglia (DRG) and spinal cord. In naive rats, ATF3 was not expressed in the DRG and spinal cord. Following the cut of peripheral nerve, ATF3 was immediately induced in virtually all DRG neurons and motoneurons that were axotomized, and the time course of induction was dependent on the distance between the injury site and the cell body. Double labeling using immunohistochemistry revealed that the population of DRG neurons expressing ATF3 included those expressing c-jun, and in motoneurons ATF3 and c-jun were concurrently expressed after axotomy. In contrast to c-jun, ATF3 was not induced transsynaptically in spinal dorsal horn neurons. We conclude that ATF3 is specifically induced in sensory and motoneurons in the spinal cord following nerve injury and should be regarded as an unique neuronal marker of nerve injury in the nervous system.

Activating Transcription Factor 3↗
PubMed2000

Effect of early postoperative feeding on the healing of colonic anastomoses in the presence of intra-abdominal sepsis in rats.

PURPOSE: Intra-abdominal infection is generally considered a major risk factor for dehiscence of primary colon anastomosis. To elucidate the indications for nutritional support during intra-abdominal sepsis, we investigated the healing of anastomoses in an animal model. METHODS: Twenty male Sprague-Dawley rats (280-320 g) underwent cecal ligation and single puncture. After 24 hours the perforated cecum was removed, and the left colon was transected and anastomosed in a single-layer inverted fashion. Animals were randomly assigned to receive both chow and water (early-fed group; n = 10) or water alone for the first 72 hours and chow thereafter (late-fed group; n = 10). Colon-bursting pressure was measured five days after the anastomosis, at which time the anastomosis was excised. RESULTS: The survival rate after cecal ligation and single puncture was 100 percent, and blood cultures were positive in 20 percent of animals five days after surgery. All data are expressed as means +/- standard error of the mean. Body weight increased more in the early-fed group than in the late-fed group (15.6+/-3 vs. -6.3+/-2.8 g; P < 0.001). Early feeding resulted in increased anastomotic bursting pressure (200+/-11 vs. 161+/-12 mmHg; P < 0.05) and total collagen concentration at the site of anastomosis (2.36+/-0.09 vs. 2.01+/-0.07 microg/mg wet tissue; P < 0.01) compared with the late-fed group. CONCLUSION: Early feeding has a positive effect on anastomotic healing in the presence of intraabdominal sepsis. The mechanism by which early feeding enhances the colonic anastomotic healing is unclear, although preservation of colonic collagen seems to play a significant role.

Anastomosis, Surgical↗
PubMed2000

Suppression of neuropeptides' mRNA expression by herbal medicines in a rat model of peripheral inflammation.

The traditional Chinese medicines have been used clinically for a long time in some Asian countries, however, very few studies have been done to demonstrate the working mechanisms of these medicines using recently developed biochemical methodologies. In this study, we examined the anti-inflammatory effect of Huang-Lian-Jie-Du-Tang (HLJDT), a combination of herbs used in traditional Chinese medicine, on paw edema, thermal hyperalgesia and the mRNA increase of neuropeptides in spinal dorsal horn and hypothalamic neurons using a rat model of peripheral inflammation and hyperalgesia. The rats that received HLJDT from 3 days before the injection of complete Freund's adjuvant (CFA) into the plantar had significantly less edema and reduced thermal hyperalgesia compared to control rats that received CFA injection. The up-regulation of preprodynorphin mRNA in L4-5 dorsal horn neurons 8 hours after CFA injection that was observed in control rats, was also decreased in the HLJDT-treated rats. Moreover, there was a significant decrease in mRNA level of corticotropin-releasing factor in the paraventricular hypothalamic nucleus in the HLJDT-treated rats. These data demonstrate that HLJDT is anti-inflammatory, and produces changes in mRNA expression in dorsal horn and hypothalamic neurons. This is the first demonstrated that a traditional Chinese medicine can affect the excitability of neurons through an anti-inflammatory action.

Animals↗
PubMed2000

Regional differences in the expression of DNA topoisomerase IIbeta in the pyramidal neurons of the rat hippocampus.

A detailed analysis of the differential expression of a nuclear enzyme, DNA topoisomerase (topo) IIbeta, was performed in the rat hippocampal pyramidal layer. Three-dimensional (3-D) reconstruction from serial sections immunostained with anti-topo IIbeta antibody showed that the immunoreactivity was apparently weak in the entire CA3 region. Almost all CA1 pyramidal cells showed similar immunoreactivity to that seen in the dentate granular cells, the subicular neurons, and the cerebral neocortical neurons. In addition, immunoblotting analysis in the adult dorsal hippocampus showed that the expression level of topo IIbeta in the CA3 was significantly lower than that in the CA1 region. The dissociation in the expression level between CA1 and CA3 occurred in postnatal days 4 (P4) through P6. The present finding suggests that the enzyme is possibly involved in activities of the hippocampal pyramidal neurons.

Animals↗
PubMed2000

The effects of binocular suture and dark rearing on the induction of c-fos protein in the rat visual cortex during and after the critical period.

It has been demonstrated in kittens that binocular lid suture has more deleterious and irreversible effects on plasticity of the developing visual system than rearing in complete darkness. The present study using immunocytochemistry focuses on the effects of the two types of visual deprivation on the inducibility of c-fos protein in visual cortical neurons of rats. Rats were subjected to binocular suture or dark rearing for 1 week during (postnatal days 14-21; P14-P21) and after (P50-P57) the critical period for activity-dependent modifiability of cortical ocular dominance. In rats of both age groups reared in the normal light-dark condition, only a small number of Fos-immunoreactive neurons was obtained in the visual cortex. By contrast, in dark-reared pups and adult rats, numerous c-fos neurons were detected in the layers II-IV and VI of the visual cortex following a brief light exposure (1 h). In rats of both ages subjected to binocular suture, Fos neurons were detected in the same layers as in the dark-reared rats, but significantly less in number. We speculate that the reduced plasticity of the visual cortex in the rats subjected to binocular suture may be due partly to the repressed AP-1 activity in visual cortical neurons. No significant difference was detected in c-fos expression in the visual cortex between visually manipulated pups and adult rats.

Aging↗
PubMed2000

[Comparison of the families of terminal stage cancer patients who underwent HPN and the nurses who cared those patients in their thoughts on home care].

In the home care for terminal stage cancer patients, the quality of life of patients has been regarded as more important than the QOL of their family. Now, however, we think the QOL of the family of the patients is as important as that of the patients themselves. We investigated the opinion of the families and nurses by questionnaire in the HPN care for terminal stage cancer patients and compared them. The family answered positively about HPN, but they had a negative opinion in that they do not want to undergo HPN because they felt a heavy burden and responsibility in caring for patients, and they do not want to cause these feelings in others in their family. The nurses also answered positively about HPN, and they answered that they want to undergo HPN if they have terminal stage cancer. These results suggest that the family feels a greater burden and responsibility in caring for patients at home than the medical staff realize. The medical staff should support the family as well as terminal stage cancer patients and should not force our own opinions as medical staff.

Family↗
PubMed2000

[How the lifestyle of families who care for home parenteral nutrition patients changes].

The role of families who care for home parenteral nutrition (HPN) patients is extremely important. They face many problems not only in caring for patients but also in their own lifestyle. We investigated by questionnaire the changes in the family of terminal stage cancer patients receiving HPN. Replies submitted to the questionnaire were obtained from 20 out of 32 families who underwent HPN in the Osaka Prefectural General Hospital. Ten out of 20 people answered that they changed their lifestyle during HPN. The changes were decreased opportunity to communicate with other people and decreased time for to spend on a hobby or other activity. The care of the HPN patients affects the wife, daughter-in-law and children more than the husband of the patient, because the former have to manage housekeeping as well as patient care. This result suggests that the quality of life of the family of terminal stage cancer patients at home with HPN declined because they had to change their own lifestyle in order to spare time to care for the patients.

Family↗
PubMed1999

Excitability of spinal cord and gracile nucleus neurons in rats with chronically injured sciatic nerve examined by c-fos expression.

Low-threshold sensory pathways have been suggested to have an important role in the formation and maintenance of sensory abnormalities which are observed after peripheral nerve injury. Fos-like immunoreactive (Fos-LI) neurons are expressed in spinal cord laminae III-IV and the gracile nucleus by electrically stimulating the injured nerves at Abeta strength after sciatic nerve transection in rats. This suggests that the excitability of these neurons is increased by nerve injury. In this study, we investigated which receptors are involved in the regulation of the increased excitability in spinal and gracile nucleus neurons. The sciatic nerve of Sprague-Dawley rats (150 g) was transected 7 days before the experiment day. The rats were administered morphine, muscimol, baclofen, MK-801, CNQX, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or clonidine i.p., and then electrically stimulated at 0.1 mA to the proximal region to the nerve injury site under urethane anesthesia. Two hours after the stimulation, Fos-LI expression was increased in the spinal cord dorsal horn and the gracile nucleus in control rats. Baclofen inhibited the Fos-LI expression both in the spinal cord and the gracile nucleus. Morphine inhibited only the Fos-LI expression in the posterior cutaneous (PC) nerve territory of laminae I-II, but not in the sciatic nerve (SC) territory, laminae III-IV nor the gracile nucleus. MK-801 had an inhibitory but complicated effect in laminae I-II and the gracile nucleus. The other drugs were not effective on Fos-LI expression. It is suggested that the GABA(B) receptor has a pivotal role in the regulation of Fos-LI expression after electrical stimulation to the injured low-threshold sensory fibers, and other receptors have little effect on the Fos-LI expression.

Analgesics↗
PubMed1999

Bcl-xL is a negative regulator of caspase-3 activation in immature neurons during development.

Caspases and Bcl-xL, the mammalian homologues of the Caenorhabditis elegans (C. elegans) ced-3 and ced-9 genes, respectively, regulate apoptosis of various cells. Caspase-3 is processed into an active form (p20 or p17 and p12) during apoptosis. We investigated the relation between caspase-3 and Bcl-xL during development by examining activation of caspase-3 and apoptotic cells in Bcl-x-deficient (bcl-x(-/-)) mice at embryonic (E) day 11.5. We used a double-staining technique with a cleavage site-directed antibody against caspase-3 (anti-p20/17) and terminal-deoxytransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). Bcl-xL-deficiency increased both numbers of p20/17-positive and -negative apoptotic cells in dorsal root ganglia (DRG); the numbers of p20/17-positive apoptotic cells in the caudal parts of the ventral hindbrain and ventral spinal cord; and the numbers of p20/17-negative apoptotic cells in the dorsal midbrain, dorsal hindbrain, and dorsal spinal cord. Thus, Bcl-xL blocks the caspase-3-dependent apoptotic pathway in the restricted regions of the nervous system during development. Furthermore, these observations suggest that Bcl-xL protects against activation of the caspase-3-independent apoptotic pathway. Other caspases or apoptotic mechanisms may also be activated in the nervous systems of bcl-x(-/-) mice.

Animals↗
PubMed1999

Differential regulation of alpha- and beta-CGRP mRNAs within oculomotor, trochlear, abducens, and trigeminal motoneurons in response to axotomy.

Spinal and cranial motoneurons express alpha- and beta-calcitonin gene-related peptide (CGRP) mRNAs constitutively at variable ratios, and these two mRNAs are differentially regulated following axotomy in spinal, facial, and hypoglossal motoneurons. The purpose of this study was to investigate the change in CGRP mRNA expression following nerve injury in oculomotor, trochlear, abducens, and trigeminal motor nuclei in which beta-CGRP mRNA is predominantly expressed under normal conditions. Using male Sprague-Dawley rats, either the left eyeball and the orbital contents including the bulbar muscles were removed, or the left masseter nerve was ligated and transected. The rats were allowed to survive for 1, 3, 7, 14, 28, 56 days following these procedures. The levels of mRNAs for alpha- and beta-CGRP and growth-associated protein (GAP)-43 were analyzed by in situ hybridization histochemistry using 35S-labeled oligonucleotide probes. Following nerve injury, the expression of alpha-CGRP mRNA rapidly increased on the directly-injured side in all of these nuclei. Thereafter, it gradually decreased and returned to about the control level at postoperative day 56 within oculomotor, trochlear, and abducens motoneurons, but it sustained at a high level within trigeminal motoneurons. The expression of beta-CGRP was quite variable among these nuclei, and significant changes were also seen on the side contralateral to the directly-injured side. These data indicate that the up-regulation of alpha-CGRP mRNA may be a common response of cranial motor neurons following axotomy even if the constitutive expression of beta-CGRP mRNA exceeds that of alpha-CGRP mRNA in these neurons.

Abducens Nerve↗
PubMed1999

The usefulness of conducting investigations on intra-abdominal bacterial contamination in digestive tract operations.

A bacteriological study of 108 cases of gastrointestinal surgery was conducted by analyzing intra-abdominal bacterial contamination (IABC) and postoperative surgical site infections (SSI). We utilized an anaerobic porter to detect intra-abdominal bacterial infection and transport bacteria to the laboratory. The positive IABC rate was 42.9% for gastric cancer surgery, 22.6% for biliary tract surgery, and 85.7% for colorectal cancer surgery. Most cases of SSI were IABC-positive, and isolated bacterial species from the SSI were similar to those from the IABC. In colorectal cancer surgery, a preoperative chemical intestinal preparation and the prophylactic use of antibiotics had a major influence on the sensitivity of bacteria isolated from the SSI. These data suggest that prophylactic antibiotics should be chosen from among those to which bacteria from the IABC are highly sensitive, and that therapeutic antibiotics should be chosen from among those to which bacteria isolated from the SSI are highly sensitive. Finally, the exploration of IABC enables us to predict the incidence of SSI.

Adult↗
PubMed1999

A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region.

The adenovirus E1B19K protein inhibits apoptosis induced by E1A and other divergent signals. The cellular proteins that interact with E1B19K have been analyzed by isolating cDNA clones by the yeast two hybrid system. One of these clones encodes B5 which consists of 219 amino acid residues and contains the putative BH3 and transmembrane regions. B5 binds strongly to Nip3 and itself, weakly to E1B19K, but not to Bcl-2 and localizes in nuclear envelope, endoplasmic reticulum and mitochondria. B5 has sequence homology with Nip3 in the middle and C-terminal regions, but not in the N-terminal region. Unlike other E1B19K binding BH3 proteins so far characterized, B5 does not induce apoptosis, but inhibits apoptosis induced by Nip3. However the deletion mutant B5Delta1-31 lacking the N-terminus does induce apoptosis, although weaker than does Nip3, suggesting that the N-terminal region is masking the apoptosis-inducing capacity of B5.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Death signals from the B cell antigen receptor target mitochondria, activating necrotic and apoptotic death cascades in a murine B cell line, WEHI-231.

B cell antigen receptor (BCR)-mediated cell death has been proposed as a mechanism for purging the immune repertoire of anti-self specificities during B cell differentiation in bone marrow. Mitochondrial alterations and activation of caspases are required for certain aspects of apoptotic cell death, but how the mitochondria and caspases contribute to BCR-mediated cell death is not well understood. In the present study, we used the mouse WEHI-231 B cell line to demonstrate that mitochondrial alterations and activation of caspases are indeed participants in BCR-mediated cell death. The peptide inhibitor of caspases, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), blocked cleavage of poly(ADP-ribose) polymerase and various manifestation of nuclear apoptosis such as nuclear fragmentation, hypodiploidy and DNA fragmentation, indicating that signals from the BCR induced the activation of caspases. In addition, z-VAD-fmk delayed apoptosis-associated changes in cellular reduction-oxidation potentials as determined by hypergeneration of superoxide anion, as well as exposure of phosphatidylserine residues in the outer plasma membrane. By contrast, although z-VAD-fmk retarded cytolysis, it was incapable of preventing disruption of the plasma membrane even under the same condition in which it completely blocked nuclear apoptosis. Mitochondrial membrane potential loss was also not blocked by z-VAD-fmk. Bongkrekic acid, a specific inhibitor of mitochondrial permeability transition pores, suppressed not only the mitochondrial membrane potential but also the change of plasma membrane permeability. Overexpression of Bcl-xL prevented mitochondrial dysfunction, nuclear apoptosis and membrane permeability cell death triggered by BCR signal transduction. These observations indicate that death signals from BCR may first cause mitochondrial alterations followed by activation of both necrotic and apoptotic cascades.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Spontaneous gastrointestinal perforation in patients with lymphoma receiving chemotherapy and steroids. Report of three cases.

Spontaneous gastrointestinal perforations in three patients with lymphoma were considered to be treatment-related conditions. All three were diagnosed as having malignant lymphoma by histological examination, and treated with chemotherapy and steroids. Four to 14 days after the start of chemotherapy, they complained of abdominal pain and plain roentgenograms revealed pneumoperitoneum. The interval between the onset of peritonitis and operation was almost 24 h. Emergency operations were carried out; one patient with a jejunal perforation underwent resection of the jejunum, another with a gastric perforation received a simple closure with omental patch, and the third with a gastric perforation underwent gastrectomy. Two patients recovered from the surgery, while the gastrectomy patient died due to sepsis. The favorable outcome of the surgical intervention is attributed to early diagnosis, prompt exploration, and selective operative procedures. We recommended a simple closure with omental patch for gastroduodenal perforation. Resection and primary anastomosis are possible only in the small bowel.

Adult↗
PubMed1998

Effects of halothane, ketamine and nitrous oxide on dynorphin mRNA expression in dorsal horn neurons after peripheral tissue injury.

Peripheral tissue injury is known to induce changes in gene expression in spinal neurons and result in a prolonged alteration of neuronal excitability. The purpose of this study was to examine the effect of halothane on the dynorphin mRNA expression in spinal dorsal horn neurons after peripheral tissue injury by formalin injection and compare the effect to that of ketamine and nitrous oxide. Male Sprague-Dawley rats were anesthetized with 1.3% halothane, ketamine, or 67% nitrous oxide. Fifteen minutes after induction of anesthesia, rats received an intraplantar injection of 150 microliter 5% formalin into the unilateral hindpaw. General anesthesia was maintained for 8 h, and the expression of preprodynorphin (PPD) and preproenkephalin (PPE) mRNAs in the spinal cord (L4-5) was examined by in situ hybridization. The degree of edema of the inflamed foot was not different among the three anesthesia groups and the control (no anesthesia) group. The number of neurons expressing PPD mRNA dramatically increased in the superficial dorsal horn ipsilateral to the formalin injection in the control group compared to the contralateral side. The number of neurons labeled for PPD mRNA in the halothane group was significantly less than the control group. However, the number of PPD mRNA-expressing neurons in both the ketamine and nitrous oxide groups was significantly less than the halothane group. The expression of PPE mRNA was not influenced by these anesthetics. These data indicate that the suppressive effect of halothane anesthesia on the induction of PPD mRNA in dorsal horn neurons was smaller than those of ketamine and nitrous oxide, suggesting an important supplemental way to control the alteration of gene expression in spinal neurons for clinical settings.

Anesthetics, General↗