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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 163 records · Page 9Linked to original sources
PubMed1998

Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1 or ELAM-1 expression by human vascular endothelial cells.

A previous study reported that intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells (HUVEC) is augmented by intracellular signal transmission mainly through the protein kinase C (PKC) system stimulated by TXA2 receptors. In the present study, we show that a TXA2 receptor agonist, U46619, augments the expression of not only ICAM-1, but also vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the extent of U46619-induced mRNA accumulation and surface expression of the adhesion molecules. An inhibitor of nuclear factor kappaB (NF-kappaB) activation, PDTC, diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-kappaB and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM-1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by induction of NF-kappaB and AP-1 binding activity through the PKC system, and that VCAM-1 expression is augmented by induction of NF-kappaB binding activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Cloning and sequencing of a cDNA encoding chicken mannan-binding lectin (MBL) and comparison with mammalian analogues.

The serum lectin, mannan-binding lectin (MBL) (also denoted mannan-binding protein or mannose-binding protein, MBP) has been identified in mammals (humans, monkey, cow, rabbit, mouse and rat). Upon binding to carbohydrates on the surface of microorganisms, MBL mediates activation of the complement system, leading to killing of the microorganism. MBL thus exerts a role in the innate immune defence. We have described the isolation and partial characterization of an analogous protein in chicken serum. Oligonucleotides based on the N-terminal sequence of this protein were used in a reverse transcription-polymerase chain reaction (RT-PCR) with chicken liver RNA as template. The PCR product was sequenced and found to encode part of the NH2 terminus of chicken MBL. A perfect match probe was synthesized and used to screen a chicken liver cDNA library. The isolated clones carried a cDNA insert of 1692 bp with an open reading frame of 714 bp encoding a mature protein of 238 amino acids including a signal peptide of five amino acids. The deduced amino acid sequence agrees with those determined by conventional amino acid sequence analysis of the peptides except for four residues. We have compared the deduced primary structure of chicken MBL with the mammalian analogues. The phylogenetic analysis indicates that the gene duplication leading to two different MBL forms in mammals occurred after the split from birds and reptiles. This concurs with the finding of only one form of MBL in chickens.

Amino Acid Sequence↗
PubMed1998

Changes of the interleukin-6 levels in skin at different sites after thermal injury.

OBJECTIVE: To delineate the regulation of IL-6 production in unburned skin adjacent to a burn in an animal model. METHODS: In C57BL/6 mice, at 15, 30, and 60 minutes after a 20% full-thickness burn, skin was removed from various sites. Control samples were obtained from unburned mice. Normal skins were incubated with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), IL-1 beta, and IL-6. Unburned skin specimens were incubated with anti-TNF-alpha and IL-1alpha antibodies. Cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: The burn increased the IL-6 levels at 30 minutes (p < 0.05) and the IL-1alpha levels at 15 and 60 minutes in the unburned skin. TNF-alpha, IL-1alpha, and IL-1beta increased IL-6 production in normal skin (p < 0.05). Anti-IL-1alpha antibody decreased IL-6 production in the unburned skin (p < 0.05). CONCLUSIONS: IL-1alpha modulates IL-6 production in unburned skin after injury. IL-6 and IL-1alpha might contribute to the alterations after a burn.

Animals↗
PubMed1998

Superoxide anion radical-triggered Ca2+ release from cardiac sarcoplasmic reticulum through ryanodine receptor Ca2+ channel.

The ryanodine receptor Ca2+ channel (RyRC) constitutes the Ca2+-release pathway in sarcoplasmic reticulum (SR) of cardiac muscle. A direct mechanical and a Ca2+-triggered mechanism (Ca2+-induced Ca2+ release) have been proposed to explain the in situ activation of Ca2+ release in cardiac muscle. A variety of chemical oxidants have been shown to activate RyRC; however, the role of modification induced by oxygen-derived free radicals in pathological states of the muscle remains to be elucidated. It has been hypothesized that oxygen-derived free radicals initiate Ca2+-mediated functional changes in or damage to cardiac muscle by acting on the SR and promoting an increase in Ca2+ release. We confirmed that superoxide anion radical (O2-) generated from hypoxanthine-xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles; hypoxanthine-xanthine oxidase also decreases Ca2+ free within the intravesicular space of the SR with no effect on Ca2+-ATPase activity. Current fluctuations through single Ca2+-release channels have been monitored after incorporation into planar phospholipid bilayers. We demonstrate that activation of the channel by O2- is dependent of the presence of calmodulin and identified calmodulin as a functional mediator of O2--triggered Ca2+ release through the RyRC. For the first time, we show that O2- stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O2-. The decreased calmodulin content induced by oxygen-derived free radicals, especially O2-, is a likely mechanism of accumulation of cytosolic Ca2+ (due to increased Ca2+ release from SR) after reperfusion of the ischemic heart.

Animals↗
PubMed1998

Hyaluronan production in human rheumatoid fibroblastic synovial lining cells is increased by interleukin 1 beta but inhibited by transforming growth factor beta 1.

OBJECTIVES: To investigate the regulatory roles of interleukin 1 beta (IL1 beta), tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or transforming growth factor beta 1 (TGF beta 1) on hyaluronan (HA) synthesis by human fibroblastic synovial lining cells. METHODS: Concentrations of HA in culture supernatants of fibroblastic synovial lining cell line (RAMAK-1 cell line) with or without stimulation by IL1 beta, TNF alpha, IFN gamma or TGF beta 1 were measured by sandwich binding protein assay. Levels of HA synthase mRNA of the cells with or without stimulation were detected by reverse transcribed polymerase chain reaction. Molecular weights of HA in the culture supernatants of the cells with or without stimulation were measured using high performance gel permeation liquid chromatography. RESULTS: HA synthesis by the cells was not significantly augmented by TNF alpha or by IFN gamma. It was significantly stimulated by IL1 beta but inhibited by TGF beta 1. Molecular weights of HA in the culture supernatants of the cells were unchanged by stimulation with TNF alpha. They were remarkably increased by stimulation with IL1 beta and IFN gamma, but reduced with TGF beta 1. CONCLUSION: IL 1 beta is an up regulator of HA synthesis, while TGF beta 1 is a down regulator. HA production in the synovial lining cells of inflamed joints (for example, rheumatoid arthritis) might be regulated by the balance of these cytokines.

Arthritis, Rheumatoid↗
PubMed1998

Effects of in vitro and in vivo exposure to doxorubicin (adriamycin) on caffeine-induced Ca2+ release from sarcoplasmic reticulum and contractile protein function in 'chemically-skinned' rabbit ventricular trabeculae.

Doxorubicin is an anthracycline antibiotic that is used widely as a chemotherapeutic agent. However, the usefulness of this agent is limited due to its cardiotoxic effects. The mechanisms associated with this cardiotoxicity remain essentially unknown, despite numerous studies describing a range of structural and functional abnormalities. The purpose of the present study was to determine the in vivo and in vitro effects of doxorubicin exposure on sarcoplasmic reticulum (SR) Ca2+-content and contractile protein function. The Ca2+-content of SR is shown to have a biphasic response to in vivo and in vitro doxorubicin exposure that is time- and dose-dependent. In vitro doxorubicin exposure initially reduces the SR Ca2+-content, but the predominant action to block the SR Ca2+-release channel increases SR Ca2+-content within 60 min. Similar results are observed with in vivo doxorubicin exposure: it leads to Ca2+-overload. These data are consistent with the view that doxorubicin acts in a similar manner to ryanodine and results in cardiomyopathy due to Ca2+-overload.

Animals↗
PubMed1998

Apoptosis in adenoma and early adenocarcinoma of the colon.

Twenty-six specimens of tubular adenoma and 7 specimens of adenocarcinoma in adenoma of the colon were examined to evaluate apoptosis between adenoma and early adenocarcinoma. Cell proliferation and cell death seemed to be balanced in adenoma with mild and moderate atypia, but unbalanced in adenoma with severe atypia and cancer. Apoptosis was considered to be suppressed at cancer in some cases. However, a number of apoptosis increased at cancer in other cases. Necrosis was seen only in cancer areas. The ratio of cells simultaneously stained by anti-Ki-67 antibody (MIB-1) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) tended to be high from adenoma with moderate atypia to cancer, suggesting the unstableness of DNA. It is possible that cancer cells having highly unstable DNA easily underwent apoptosis as well as necrosis, accidentally. The p53 protein was positive only in cancer areas of three cases. One of these three showed decreased apoptosis in a cancer area, but the other two cases showed increased apoptosis. Furthermore, certain numbers of cancer cells were double-stained by p53 immunohistochemistry and TUNEL. These results suggest that the p53 protein may contribute to suppress apoptosis in the last stage of carcinogenesis of the colonic adenocarcinoma, but other factors including extrinsic stimulation may cause apoptosis despite the mutation of p53 protein.

Adenocarcinoma↗
PubMed1998

Permethrin emulsion ingestion: clinical manifestations and clearance of isomers.

BACKGROUND: Oral intoxication with permethrin, an insecticide which prolongs axonal sodium channel depolarization, has not been documented in humans. We treated a 59-year-old man who drank approximately 600 mL of 20% permethrin emulsion in a suicide attempt. METHODS: Sequential blood samples were obtained to determine permethrin isomer levels using high-performance liquid chromatography. RESULTS: Vomiting and diarrhea occurred after ingestion. On admission, loss of consciousness and metabolic acidosis were observed. On regaining consciousness, the patient complained of a burning sensation in the oral cavity. He received fluid therapy after gastric lavage and recovered without severe complications. Apart from initially impaired consciousness, no clinical neurotoxicity such as tremor, hyperexcitation, ataxia, convulsions, or paralysis occurred, though these have been reported in permethrin-intoxicated animals. Serum permethrin concentrations peaked 3-4 hours after ingestion at 868 ng/mL. Clearance of trans permethrin was more rapid than that of cis permethrin. CONCLUSION: The unequal clearance of permethrin isomers paralleled findings in animal experiments. Vomiting and diarrhea probably limited absorption in the present case, resulting in a peak serum concentration and a degree of neurotoxicity far less than those seen in animals.

Administration, Oral↗
PubMed1998

[A case of aneurysmal bone cyst arising from the left 4th rib].

We reported a case of aneurysmal bone cyst originating in the left 4th rib. This disease originating in a rib was recorded in only 18 cases in Japan in the literature. The patient was a 16-year-old man and he was first found to have an abnormal shadow in the left upper lung field on the chest roentgenogram. In this case, MRI was very useful to show internal septation of the tumor. We performed a thoracotomy through the left 4th intercostal space with an anteroaxillary skin incision and removed the tumor and the 4th rib completely. Pathological findings showed multiple cysts filled with blood and fibrous trabecullae containing osteoid tissue and multinucleated giant cells, confirming the diagnosis of aneurysmal bone cyst. There has been no evidence of recurrence during the 9 months postoperatively.

Adolescent↗
PubMed1998

[Immunological alterations after extensive burn injury].

It is recognized that extensively burned patients have an increased susceptibility to infection and often succumb to multiple organ failure related to sepsis. Numerous investigations performed over more than 30 years have demonstrated immunologic abnormalities in burn patients, including changes in serum immunoglobulin and opsonin levels, alterations in the complement system, impairment of phagocyte and neutrophil function, suppression of delayed hypersensitive reactions, and prolongation of allograft survival. Recent progress in immunology has shown that inadequate production of both cytokines and arachidonic acid derivatives is profoundly involved in immunosuppression after severe burn injury. A better understanding of immunologic status is necessary to reduce the mortality rate from infection in extensively burned patients. This may also lead to discovering the therapeutic control mechanisms for their immunity.

Burns↗
PubMed1998

Possible mechanism of painful radiculopathy in lumbar disc herniation.

The pathophysiologic mechanisms of painful radiculopathy caused by a herniated intervertebral disc remain unknown. This study sought to determine whether the autologous intervertebral disc produces pain related behavior and whether phospholipase A2 and nitric oxide are involved in the pathophysiologic mechanism producing the behavior. A rat model, in which autologous intervertebral discs were implanted on the nerve root in the lumbar spine, was used to measure hyperalgesia, which is a pain related behavior in the rat. In this experimental model, autologous nucleus pulposus and anulus fibrosus transplanted to lumbar nerve roots produced mechanical and thermal hyperalgesia, respectively. Epidural injection of a selective inhibitor for phospholipase A2 resulted in the disappearance of hypersensitivity to noxious mechanical stimuli. Thermal hyperalgesia produced by application of the anulus fibrosus was abated and abolished by epidural injections of saline and one of the inhibitors for nitric oxide synthase, respectively. The authors suggest that chemical mediators such as phospholipase A2 and nitric oxide, induced by extruded or sequestrated intervertebral discs, are involved in the pathophysiologic mechanisms of painful radiculopathy in lumbar disc herniations. This study may be useful in attempting to develop new medical approaches for treatments of lumbar disc herniation.

Analysis of Variance↗
PubMed1998

Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects.

OBJECTIVE: To examine the effect of grapefruit juice on the disposition of oral administered itraconazole in healthy subjects. METHODS: Twenty-two healthy male subjects received a single 100 mg dose of itraconazole with either 350 ml grapefruit juice, orange juice or mineral water. Plasma concentrations of itraconazole were measured by HPLC, and pharmacokinetic parameters; Cmax, Tmax, T1/2, AUC, and AUC corrected by human body surface area: AUC/S, were calculated. RESULTS: Grapefruit juice had no effect on any pharmacokinetic parameter of itraconazole. However, T1/2, AUC, or AUC/S were significantly decreased in orange juice treatment group compared to those in mineral water group (average decrease 56%, p < 0.01, 41%, p < 0.05, and 43%, p < 0.05, respectively). CONCLUSION: Coadministration of grapefruit juice did not affect any pharmacokinetic parameter of itraconazole while that of orange juice decreased the parameters of T1/2, AUC, and AUC/S of the drug.

Adult↗
PubMed1998

[Informed consent and surgical treatment in a 38-year-old female, Jehovah's witness with lung cancer].

A 38-year-old female was found to have abnormal lesion in the left lower lung by chest X-ray examination which was done for her periodical health examination in March, 1997. She was referred to our Institution for operation of the pulmonary lesion by her family physician. The pathology was reported to be adenocarcinoma by the preoperative bronchofiberscopy. As she was Jehovah's witness, she refused to receive either homologous or autologous blood transfusion on the ground of her faith. Prior to the operation, the consultation was held together with the patient, family and doctors in reference to the informed consent. In June, 1997, she had left lower lobectomy without blood transfusion. Postoperative course was uneventful. The problems of surgical treatment in Jehovah's witness rejected blood transfusion are discussed.

Adenocarcinoma↗
PubMed1998

[A case report of asymptomatical large carinal bronchial cyst].

A 36-year-old man with a mediastinal bronchial cyst was reported. CT showed a mass with water density in the posterior mediastinum. MRI revealed that this mediastinal mass had high signal intensity on both T1-weighted and T2-weighted images. MRI was considered to be useful for the qualitative diagnosis of mediastinal tumors as cystic or solid. An operation was performed and histological diagnosis was bronchial cyst. Intracystic fluid study revealed high titer of total protein, amylase and tumor markers, low titer of glucose and LDH.

Adult↗
PubMed1998

[Pulmonary pseudallescheriasis in a patient with diabetes mellitus and alcoholic liver cirrhosis].

A 62-year-old man with diabetes mellitus and alcoholic liver cirrhosis was admitted to the hospital because of hemoptysis. Chest X-ray films and computed tomograms showed a dense infiltrative lesion and a healed tuberculous cavity with a possible fungus ball in the upper lobe of the right lung. Bronchoscopy revealed that the hemoptysis originated from the right upper-lobe bronchus. The bleeding stopped after thrombin was applied into the bronchus. Filamentous fungi were seen in lavage fluid from the right upper-lobe bronchus. The fungi were identified as Pseudallescheria boydii, and pulmonary pseudallescheriasis was diagnosed. the patient was treated successfully with miconazole (400 mg/day) for 2 months. Pseudallescheriasis should be taken into account in the differential diagnosis of aspergilloma-like lesions.

Antifungal Agents↗