Search PubMed⌕ Search

Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 253 records · Page 14Linked to original sources

Large-vessel arteritis associated with chronic active Epstein-Barr virus infection.

This report describes an autopsy case of large-vessel arteritis associated with chronic active Epstein-Barr virus (EBV) infection in a 10-year-old Japanese girl. All of the 3 main coronary arteries, bilateral common carotid and subclavian arteries, abdominal aorta and its major branches, and bilateral common iliac arteries were involved, and all showed aneurysmal dilation of the lumens. Histopathologic examination revealed mesoarteritis characterized by moth-eaten-appearing destruction of the medial elastic laminae, with T lymphocyte infiltration around the vasa vasorum and severe intimal thickening. The EBV DNA genome was detected in the diseased aortic tissue by polymerase chain reaction, and in the infiltrating lymphocytes by in situ hybridization. The clinical symptoms and histopathologic manifestations of the arterial lesions in this patient were obviously different from those of Kawasaki disease and Takayasu arteritis, and the arteritis was considered to be associated with the EBV infection.

Arteries↗

Identification of minor proteins of human colostrum and mature milk by two-dimensional electrophoresis.

Two-dimensional electrophoresis (2-DE) followed by electroblotting and microsequencing is considered to be the most powerful method for the isolation and characterization of proteins. In this paper, we report the separation and determination of the N-terminal and/or internal amino acid sequences of the minor proteins of human colostral and mature milk by 2-DE and microsequencing. In order to analyze the minor proteins of human milk, we use immunoabsorbents to remove three major proteins, alpha-lactalbumin, lactoferrin and secretory immunoglobulin A. The major proteins removed by this process accounted for about 79 and 93% of the total whey proteins of mature and colostral milk, respectively. The remaining milk proteins were then separated by isoelectric focusing gel electrophoresis between pH 3 and 10, and subjected to 12.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Approximately 400 spots were detected in both colostral and mature milk by silver staining after 2-DE. Twenty-two major, well-resolved proteins (out of 400) were microsequenced (N-termini as well as internal). These include fatty acid binding protein, beta 2-microglobulin, complement C4, clusterin, alpha 1-antritrypsin, lysozyme C, alpha- and beta-casein, prealbumin, serotransferrin, fructose-bisphosphate aldolase A, and beta-casein fragments. No major differences in the protein patterns were observed between the minor proteins of colostrum and mature milk, indicating that the minor proteins remained relatively constant during lactation. These results suggest that the minor milk proteins are important for the health and development of breast-fed infants throughout lactation.

Amino Acid Sequence↗

The Tsukuba hypertensive mouse (transgenic mouse carrying human genes for both renin and angiotensinogen) as a model of human malignant hypertension: development of lesions and morphometric analysis.

The renin-angiotensin system has a pivotal role in hypertension. The Tsukuba hypertensive mouse (THM; a transgenic mouse carrying human genes for both renin and angiotensinogen) was generated to allow further examination of the renin-angiotensin system in a variety of pathologic conditions. We evaluated the development of renal lesions in these mice and in controls by morphometric, immunohistochemical and ultrastructural methods. Blood pressure was significantly higher in THM than in control mice; 1 year after birth, it was approximately 40 mmHg higher. The kidney-to-body weight ratio was also higher in THM than in control. Morphometrical analysis revealed that the glomerular sclerosis index was significantly elevated in THM with 10% of the glomeruli sclerotic at 18 months. The grade of vascular lesion and the frequency of fibronoid arteritis of the kidney exhibited the same tendency as the glomerular sclerosis index. Murine renin was located exclusively in the juxtaglomerular apparatus, whereas human renin was expressed not only in the juxtaglomerular apparatus, but also in periarteriolar smooth muscle cells and in mesangial and epithelial cells of the glomeruli. Light and electron microscopy revealed significant fibrinoid arteritis of the kidney in THM and also "onion skinning", both pathognomonic for malignant nephrosclerosis. THM may be an excellent model of human malignant hypertension.

Animals↗

Angiotensin II maintains the structure and function of glomerular mesangium via type 1a receptor. What we have learned from null mutant mice minus the angiotensin II type 1a receptor gene.

The angiotensin II type 1a (AT1a) receptor is the major receptor effecting the multiple actions of angiotensin II on the cardiovascular system. It is expressed abundantly in the glomerular mesangial cells of the kidney. We investigated glomerular changes in null mutant mice minus the AT1a receptor gene to gain an understanding of the in vivo action of angiotensin II via AT1a on the mesangium. Morphological observations and morphometric analysis revealed that the glomerular volume was greatly increased owing to the expansion of the mesangial area, which contained fluid-filled spaces with a small amount of fibrillar components. The mesangial cells lost contact with each other and with the perimesangial area of the glomerular basement membrane (GBM), so that the glomerular capillary neck was greatly widened. These findings suggest a defect of the anchoring function of mesangial cells resulting from some abnormality in mesangial matrix formation. We conclude that angiotensin II has an important role in the structural and functional maintenance of the mesangium via the AT1a receptor, especially by reinforcing the connection between mesangial cells and GBM via the mesangial matrix.

Angiotensin II↗

Type IIa early gastric cancer with proliferation of xanthoma cells.

We report a type IIa early gastric cancer associated with xanthoma cell proliferation in a 61-year-old man. The patient was admitted to our hospital because of a gastric polyp detected at a medical checkup. An irregular protruding lesion with xanthoma cell proliferation was detected endoscopically. Histological examination showed a well differentiated tubular adenocarcinoma in the mucosa associated with xanthoma cell proliferation. The distribution of the xanthoma cells in the stroma corresponded closely with that of the cancer cells. Neither atypism nor mitotic figures were recognized in the xanthoma cells. In an immunohistochemical study, almost all the xanthoma cells were stained positive for alpha 1-antitrypsin, while relatively few exhibited positive S-100 protein staining. Specific monocyte chemotactic and activating factor immunoreactivity was present only in the xanthoma cells, and not in the cancer cells. On the basis of these findings, it was speculated that the gastric cancer cells may have caused the xanthoma cell proliferation via an autocrine mechanism i.e., by a chemical mediator acting in a paracrine or juxtacrine manner.

Adenocarcinoma↗

Clinical effect of immunochemotherapy for a patient with advanced gallbladder cancer: report of a case.

A 56-year-old woman was admitted presenting with a sensation of abdominal fullness. She was diagnosed to have advanced gallbladder cancer with carcinomatous peritonitis, as well as lymph node and liver metastases. We obtained highly purified tumor cells and tumor-infiltrating lymphocytes (TIL) from extirpated cervical lymph nodes and peritoneal effusion, and the chemosensitivity of these cells was tested with an MTT assay. Intensive chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU) was then performed according to the results of the MTT assay. Thereafter, cytotoxic T-lymphocytes (CTL) were induced in mixed cultures of autologous tumor cells and peripheral blood lymphocytes, and adoptive immunotherapy was performed with TIL and CTL. The malignant ascites and metastatic lesions disappeared after the intraperitoneal administration of CDDP and the transfer of TIL and CTL, and subsequently the patient's quality of life improved. This patient could return to work; however, liver metastasis was later observed, and she died 14 months after the initial diagnosis. Combination therapy with anticancer drugs and activated killer cells was thus found to be effective in a patient with advanced gallbladder cancer.

Adenocarcinoma↗

Role of neutrophil elastase in stress-induced gastric mucosal injury in rats.

Activated neutrophils play an important role in tissue injury by releasing various inflammatory mediators capable of damaging endothelial cells. To investigate whether neutrophil elastase (NE) is involved in stress-induced gastric mucosal injury, we examined the effects of 2 NE inhibitors (ONO-5046 and L-658 758) as well as nitrogen mustard-induced leukocytopenia on the formation of gastric mucosal lesions, gastric mucosal blood flow, gastric mucosal microvascular permeability, and gastric neutrophil accumulation in rats subjected to water immersion-restraint stress (WIR). Gastric mucosal injury peaked 8 hours after WIR. Gastric mucosal blood flow, as measured by laser-Doppler flow cytometry, decreased to 45% of its initial level 8 hours after WIR. Gastric mucosal microvascular permeability, evaluated by Evans blue dye leakage to the gastric mucosa, showed an increase, peaking 8 hours after WIR. Gastric accumulation of neutrophils, determined by measuring gastric myeloperoxidase activity and by histologic examination, was also significantly increased 8 hours after WIR. Both of the NE inhibitors markedly prevented the formation of gastric mucosal lesions. They also decreased the reduction in gastric mucosal blood flow seen in animals subjected to WIR while preventing increases in gastric mucosal microvascular permeability. Gastric neutrophil accumulation was significantly reduced in animals given either inhibitor 8 hours after WIR. Leukocytopenia produced effects similar to those produced by the inhibitors. Taken together, these observations strongly suggest that NE promotes stress-induced gastric mucosal injury in rats by reducing gastric mucosal blood flow and increasing neutrophil accumulation.

Animals↗

Deferential roles of angiotensin receptor subtypes in adrenocortical function in mice.

The functional significance of angiotensin II (Ang II) receptor subtypes in adrenals remains unknown. Ang II receptor type 1a (AT1a) expression was localized by in situ hybridization to the zona glomerulosa and zona fasciculata, while AT1b was localized to the zona glomerulosa. Plasma aldosterone and corticosterone levels were measured after injection with Ang II or the type 2 receptor (AT2) agonist CGP-42112 in wild-type and AT1a deficient mice. Aldosterone and corticosterone levels were lower in AT1a deficient mice. Ang II increased plasma aldosterone levels in AT1a deficient mice, but to a lesser extent in mice pretreated with nonselective AT1a/AT1b antagonist, CV-11974. CGP-42112 did not affect aldosterone levels. Ang II increased corticosterone levels in wild-type mice but not in AT1a deficient mice. Results suggest Ang II stimulates aldosterone secretion via AT1a and AT1b in the zona glomerulosa and corticosterone secretion via AT1a in the zona fasciculata, and provide first evidence for differential roles of AT1a and AT1b in the adrenals.

Adrenal Cortex↗

The use of a new bilayer artificial dermis for vestibular extension.

In this study we evaluated the usefulness of a new bilayer artificial dermis (TERUDERMIS; Terumo Corporation, Japan) for vestibular extension. It is composed of a collagen sponge with the silicone layer which is sloughed off as the mucous membrane heals. We have used it for vestibular extension in 50 patients. The material was effective in nearly all patients in promoting haemostasis, relieving pain, inducing granulation, promoting rapid epithelialization, and preventing contracture. There were no side-effects. The greatest problem with such materials in the past has been contracture at the vestibular extension area. However, we found that the degree of contracture was similar to that seen with autogenous mucosa or free skin graft. Our results indicate that the material might be useful for vestibular extension.

Adolescent↗

An ultrastructural study of the neural circuit between the prefrontal cortex and the mediodorsal nucleus of the thalamus.

Synaptic connectivity between the prefrontal cortex (PFC) and the mediodorsal thalamic nucleus (MD) of the rat has been investigated with the electron microscope after labeling both the pre- and postsynaptic elements. Prefrontal corticothalamic fibers end exclusively as small axon terminals with round synaptic vesicles (SR boutons), which make asymmetrical synaptic contacts with distal dendritic segments of MD neurons. Thalamocortical terminals from MD in PFC are also of the SR type and form asymmetrical synaptic contacts predominantly with dendritic spines arising from the apical or basal dendrites of pyramidal cells whose somata reside in layers III, V and VI. At least some pyramidal cells in layer III that receive MD afferents are callosal cells, whereas deep layer pyramidal cells projecting to MD receive directly some of the thalamocortical terminations from MD, suggesting that the recurrent loop to MD is monosynaptically mediated. Thus, taken together with recent evidence that both the PFC-MD and MD-PFC pathways are glutamatergic and excitatory, the cortical excitation exerted by afferent fibers from MD is transferred, not only back to MD itself through deep pyramidal cells, but also the contralateral prefrontal cortex via pyramidal cells in layer III of the ipsilateral prefrontal cortex. Concerning modulatory and inhibitory inputs, fibers to MD from the ventral pallidum and substantia nigra pars reticulata have been shown to be inhibitory and GABAergic. In addition, fibers from the ventral tegmental area preferentially make symmetrical membrane thickenings (i.e. inhibitory synapses) on deep pyramidal cells in PFC that receive synaptic endings from MD. From these morphological grounds, therefore, cells in the ventral pallidum, the substantia nigra pars reticulata and the ventral tegmental area may mediate, to some extent, an inhibitory effect on the reverberatory excitation between PFC and MD.

Animals↗

The effects of preanesthetic oral clonidine on total requirement of propofol for general anesthesia.

STUDY OBJECTIVE: To investigate the effects of preanesthetic oral clonidine on total propofol requirement for uniform minor surgery (breast conservative surgery: breast cancer removal with axillary lymph node dissection), and to compare the action of clonidine with that of preanesthetic oral diazepam, a commonly used benzodiazepine. DESIGN: Randomized double-blinded study. SETTING: Operating room ASA physical status I and II room and recovery room of the cancer center. PATIENTS: 80 breast cancer patients scheduled for surgery. INTERVENTIONS: Patients were randomized to one of four treatment groups (placebo, clonidine 75 micrograms, or 150 micrograms of clonidine, or 10 mg of diazepam were orally administered 60 min before induction of anesthesia); n = 20 per group. After evaluating the sedation and anxiety levels of patients using a visual analog scale, anesthesia was induced with propofol (1.5 mg/kg), and maintained with oxygen (O2): nitrous oxide (N2O) (30:70) with a continuous infusion of propofol. The propofol infusion was started at 10 mg/kg/h for 10 minutes, then decreased to 8 mg/kg/h, and 6 mg/kg/h thereafter, and the rate of infusion was adjusted to obtain adequate anesthesia (maintaining hemodynamic parameters within 20% of that prior to premedication). Fentanyl 0.2 mg (each 0.1 mg was given for intubation and axillary lymph node dissection, respectively) was administered. MEASUREMENTS AND MAIN RESULTS: Preanesthetic oral clonidine (150 micrograms) and diazepam (10 mg) induced anxiolysis without sedation. The total requirement (the mean infusion rates) of propofol in placebo, clonidine 75 micrograms, clonidine 150 micrograms, and 10 mg of diazepam groups were 841 +/- 70 (9.0 +/- 0.3), 720 +/- 63 (7.1 +/- 0.4), 491 +/- 39 (5.6 +/- 0.2), and 829 +/- 77 mg (7.9 +/- 0.4 mg/kg/h), respectively. The cost of propofol in these groups was $51.0 +/- 3.8, $45.5 +/- 3.2, $33.5 +/- 2.3, and $50.5 +/- 4.4, respectively. CONCLUSIONS: Preanesthetic oral clonidine (150 micrograms) but not diazepam (10 mg) reduced the total requirement of propofol while stabilizing hemodynamic parameters. In addition, 150 micrograms of oral clonidine attenuates the hemodynamic responses associated with tracheal intubation.

Administration, Oral↗

Effectiveness of kampo medicine (sai-boku-to) in treatment of patients with glossodynia.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of a Kampo medicine (Sai-boku-to) for treatment of patients with glossodynia. STUDY DESIGN: Sai-boku-to or an antianxiety drug (diazepam) with vitamin B complex was administered orally for 3 months to each of 200 patients with glossodynia. Clinical examination evaluated the following subjective symptoms: pain, burning sensation, and discomfort. Effectiveness was evaluated as follows: "markedly effective," all 3 symptoms disappeared; "effective," pain improved; "ineffective," no improvement in pain. RESULTS: The effective rates were 70% after 1 month, 85% after 2 months, and 92% after 3 months of administration of Sai-boku-to (the Kampo group) and 74% after 1 month, 71% after 2 months, and 69% after 3 months of administration of the antianxiety drug with vitamin B complex (the control group). No significant side effect was noted in the Kampo group, but sleepiness was recorded in 33 cases in the control group. CONCLUSIONS: The results indicate that Sai-boku-to may be a clinically useful medicine for the long-term treatment of patients with glossodynia.

Adult↗

TAC-101, a benzoic acid derivative, inhibits liver metastasis of human gastrointestinal cancer and prolongs the life-span.

We examined the anti-tumor effect of a novel benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid) on models with liver metastasis. Oral administration of TAC-101 significantly inhibited spontaneous liver metastasis of AZ-521 (human gastric cancer ) by orthotopic implantation to athymic nude mice. It also inhibited both the liver metastasis of AZ-521 induced by intrasplenic injection and the secondary lung metastasis from the liver. In addition, TAC-101 inhibited the proliferation of Co-3 (human colon adenocarcinoma) that formed a single nodule in the liver of athymic nude mice by intrahepatic implantation. The growth inhibitory effect of TAC-101 on AZ-521 experimental liver metastasis was observed when treatment was started on day 7, 14, or 21 which may correspond to the progressive stage of liver metastasis in clinical settings. Multiple administration of TAC-101 (8 mg/kg/day) significantly prolonged survival time of the animals with liver metastasis by intrasplenic injection of AZ-521 (T/C = 230%) and A549 (human lung adenocarcinoma; T/C = 186%). These effects of TAC-101 were stronger than those of 5-FU, CDDP or ATRA. Furthermore, TAC-101 inhibited the binding of AP-1 to DNA on electrophoretic mobility shift assay using nuclear extract of AZ-521 cells, although ATRA did not inhibit. These findings suggested that TAC-101 may be a candidate for a new class of anti-cancer agents for liver metastasis.

Adenocarcinoma↗

4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) inhibits the intrahepatic spread of hepatocellular carcinoma and prolongs the life-span of tumor-bearing animals.

We examined the in vivo anti-tumor activity of the benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid), for intrahepatic spread of JHH-7 human hepatocellular carcinoma (HCC) cells and its mechanism of action. Oral administration of TAC-101 markedly inhibited liver tumor of JHH-7 cells and prolonged the life-span of tumor-bearing mice without affecting the body weight. The life-prolonging effect of TAC-101 was more effective than that of other anti-cancer agents including CDDP, 5-FU, and CPT-11 (T/C (%) of life-span; 181 to 219, 128, 133, and 142%, respectively). In vitro, TAC-101 at the concentration of more than 10 microM showed direct cytotoxicity against JHH-7 cells caused by induction of apoptosis. Hepatocyte growth factor (HGF) enhanced the invasive ability of JHH-7 cells without affecting the cell viability. Non-cytotoxic concentrations of TAC-101 inhibited the JHH-7 invasion induced by HGF and down-regulated the expression of c-MET protein in a concentration-dependent manner. In summary, these results suggest that TAC-101 would be useful for a new class of therapeutic agents and that it may improve the prognosis of patients with liver-tumors including metastasizing tumor and HCC.

Animals↗

Amount of hydroxyl radical on calcium-ion-implanted titanium and point of zero charge of constituent oxide of the surface-modified layer.

To compare the surface properties of calcium-ion (Ca2+)-implanted titanium with those of titanium and to investigate the mechanism of bone conductivity of Ca2+-implanted titanium, amounts of hydroxyl radical of Ca2+-implanted titanium and titanium were estimated. Also, the point of zero charge (p.z.c.) of oxide constituting surface oxides of Ca2+-implanted titanium and titanium was determined. Results showed that the amount of active hydroxyl radical on Ca2+-implanted titanium was found to be significantly larger than that on titanium, indicating that the number of electric-charging sites of Ca2+-implanted titanium in electrolyte is more than that of titanium. The p.z.c. values of rutile (TiO2), anatase (TiO2), and perovskite (CaTiO3), were estimated to be 4.6, 5.9, and 8.1, respectively. Thus, Ca2+-implanted titanium surface is charged more positively in bioliquid than titanium, accelerating the adsorption of phosphate ions.

Journal Article↗