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Biomedical subjects

K Yamaguchi

Publications and source records attributed to K Yamaguchi.

At least 433 records · Page 24Linked to original sources

A novel molecular mechanism modulating osteoclast differentiation and function.

Osteoclasts, the multinucleated giant cells that resorb bone, develop from hematopoietic cells of the monocyte/ macrophage lineage. Osteoblasts, as well as bone marrow stromal cells, support osteoclast development through a mechanism of cell-to-cell interaction with osteoclast progenitors. We recently purified and molecularly cloned osteoclastogenesis inhibitory factor (OCIF), which was identical to osteoprotegerin (OPG). OPG/OCIF, a secreted member of the tumor necrosis factor (TNF) receptor family, inhibited differentiation and activation of osteoclasts. A single class of high-affinity binding sites for OPG/OCIF appeared on a mouse bone marrow stromal cell line, ST2, in response to 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] and dexamethasone (Dex). When the binding sites were occupied by OPG/OCIF, ST2 cells failed to support the osteoclast formation from spleen cells. To identify an OPG/OCIF ligand, we screened a cDNA expression library of ST2 cells treated with 1,25(OH)2D3 and Dex using OPG/OCIF as a probe. The cloned molecule was found to be a member of the membrane-associated TNF ligand family, and it induced osteoclast formation from mouse and human osteoclast progenitors in the presence of macrophage colony-stimulating factor (M-CSF) in vitro. Expression of its gene in osteoblasts/stromal cells was up-regulated by osteotropic factors, such as 1,25(OH)2D3, prostaglandin E2 (P(GE2), parathyroid hormone (PTH), and interleukin (IL)-11. A polyclonal antibody against this protein, as well as OPG/OCIF, negated not only the osteoclastogenesis induced by the protein, but also bone resorption elicited by various osteotropic factors in a fetal mouse long bone culture system. These findings led us to conclude that the protein is osteoclast differentiation factor (ODF), a long sought-after ligand that mediates an essential signal to osteoclast progenitors for their differentiation into active osteoclasts. Recent analyses of ODF receptor demonstrated that RANK, a member of the TNF receptor family, is the signaling receptor for ODF in osteoclastogenesis, and that OPG/OCIF acts as a decoy receptor for ODF to compete against RANK. The discovery of ODF, OPG/OCIF, and RANK opens a new era in the investigation of the regulation of osteoclast differentiation and function.

Animals↗

Relationship between clear cell/compact cell ratio and computed tomographic attenuation number in adrenocortical adenoma.

Clear cell/compact cell ratio in histologic sections from 21 resected adrenocortical adenomas was assessed. Seven patients had Cushing's syndrome another 7 had primary aldosteronism caused by adrenal adenomas and 7 had non-hyperfunctioning adenomas. The results were correlated with the corresponding unenhanced CT attenuation numbers. There was a negative correlation between clear cell/compact cell ratios and unenhanced CT attenuation numbers. However, CT attenuation numbers did not show significant differences between cortisol-producing, aldosterone-producing and nonfunctioning adenomas. These facts suggest that clear cell/compact cell ratio in adrenocortical adenomas accounts for their attenuation number on unenhanced CT scans. However, it is difficult with the use of unenhanced CT attenuation numbers to differentiate cortisol-producing adenomas from aldosterone-producing and nonhyperfunctioning adenomas.

Adrenal Cortex Neoplasms↗

Inhibition of inflammatory actions of aminobisphosphonates by dichloromethylene bisphosphonate, a non-aminobisphosphonate.

1. When injected intraperitoneally into mice in doses larger than those used clinically, all the amino derivatives of bisphosphonates (aminoBPs) tested induce a variety of inflammatory reactions such as induction of histidine decarboxylase (HDC, the histamine-forming enzyme), hypertrophy of the spleen, atrophy of the thymus, hypoglycaemia, ascites and accumulation of exudate in the thorax, and an increase in the number of macrophages and/or granulocytes in the peritoneal cavity of blood. On the other hand, dichloromethylene bisphosphonate (Cl2MBP) a typical non-aminoBP, has no such inflammatory actions. In the present study, we found that this agent can suppress the inflammatory actions of aminoBPs. 2. Cl2MBP, when injected into mice before or after injection of 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP; a typical aminoBP), inhibited the induction of HDC activity by AHBuBP in a dose- and time-dependent manner. The increase in HDC activity induced by AHBuBP was largely suppressed by the injection of an equimolar dose of Cl2MBP. Cl2MBP also inhibited other AHBuBP-induced inflammatory reactions, as well as the inflammatory actions of two other aminoBPs. However, Cl2MBP did not inhibit the increase in HDC activity induced by lipopolysaccharide (LPS). 3. We have previously reported that AHBuBP augments the elevation of HDC activity and the production of interleukin-1beta (IL-1beta) that are induced by LPS. These actions of AHBuBP were also inhibited by Cl2MBP. 4. Based on these results and reported actions of bisphosphonates, the mechanisms underlying the contrasting effects of aminoBPs and Cl2MBP, a non-aminoBP are discussed. The results suggest that combined administration of Cl2MBP and an aminoBP in patients might be a useful way of suppressing the inflammatory side effects of aminoBPs.

Animals↗

Enhancement by galactosamine of lipopolysaccharide(LPS)-induced tumour necrosis factor production and lethality: its suppression by LPS pretreatment.

1. D-Galactosamine (GalN) depletes UTP primarily in the liver, resulting in decreased RNA synthesis in hepatocytes. Co-injection of GalN and lipopolysaccharide (LPS) into mice produces fulminant hepatitis with severe hepatic congestion, resulting in rapid death. Although the underlying mechanism is uncertain, GalN enhances the sensitivity to tumour necrosis factor (TNF). Administration of uridine (a precursor of UTP) prior injection of either LPS itself or interleukin-1 (IL-1) reduces the lethality of GalN+LPS. The present study focused on the effects of these agents on TNF production. 2. Intraperitoneal injection of GalN+LPS into mice greatly elevated serum TNF. Although large doses of LPS alone also greatly elevated serum TNF, LPS itself induced neither hepatic congestion nor rapid death. Administration of a macrophage depletor, liposomes encapsulated with dichloromethylene bisphosphonate, reduced both the TNF production and mortality induced by GalN+LPS. 3. Uridine, when injected 0.5 h after the injection of GalN+LPS, reduced the production of TNF. Prior injection of LPS, but not of IL-1, also reduced this TNF production. 4. Serum from LPS-injected mice reduced the TNF production induced by GalN+LPS, but it was less effective at reducing the lethality. Its ability to reduce TNF production was abolished by heat-treatment. 5. We hypothesize that a factor inhibiting TNF production by macrophages is produced by hepatocytes in response to LPS. Possibly, production of this hepatocyte-derived TNF-down-regulator (TNF-DRh) may be: (i) inhibited by GalN, causing over-production of TNF by macrophages and (ii) stimulated by LPS-pretreatment (and restored by uridine), causing reduced TNF production.

Animals↗

Influences of vertical occlusal discrepancies on condylar responses and craniofacial growth in growing rats.

The present study was conducted to investigate the influence of vertical occlusal discrepancies on condylar remodeling and the subsequent craniofacial growth in growing rats. Thirty 4-week-old male Wistar strain rats were used. A 1-mm-thick metal plate was bonded onto the occlusal surface of the maxillary molars to increase posterior dentoalveolar height. During the early phase of the experiment, the thickness of the proliferative and maturative/hypertrophic zones in the anterior and superior portions of the condyle was significantly smaller in the experimental group than in the controls. The number of TRAP-positive cells was significantly greater in the experimental group than in the controls. At the end of the experiment, decreased ramus height and a large gonial angle were found in the experimental group. Changes in the intra-articular environment associated with vertical occlusal discrepancies may influence condylar and craniofacial growth in growing individuals, although some adaptive response of the condyle may be induced if growth potential remains.

Acid Phosphatase↗

Influence of dietary n-3 polyunsaturated fatty acid on experimental tooth movement in rats.

This study was conducted to investigate the influence of dietary n-3 polyunsaturated fatty acid on experimental tooth movement. This acid substantially reduces the production of arachidonic acid. Sixty 4-week-old male Wistar strain rats were divided into experimental and control groups. Animals in the experimental group were fed a purified diet containing 10% refined fish oil (rich in n-3 fatty acid); control animals were fed a diet containing 10% corn oil (rich in n-6 fatty acid). After 6 weeks, the maxillary first molars were moved buccally with an initial force of 20 g for periods of 0, 3, 7, or 14 days. Tooth movement in the experimental group was 80% of that seen in the controls. The number of osteoclasts on the pressure side during tooth movement was nearly 60% of that seen in controls, and the degree of bone resorption was 80%. The data suggest that a diet enriched with fish oil reduces osteoclastic activity and subsequent alveolar bone resorption that is the key to experimental tooth movement.

Alveolar Bone Loss↗

Effects of controlled hypotension with sevoflurane anaesthesia on hepatic function of surgical patients.

The effects of controlled hypotension induced with trimethaphan (TMP), nitroglycerin (TNG) or prostaglandin E1 (PGE1) during sevoflurane anaesthesia on hepatic function were studied in 28 patients undergoing spinal fusion surgery. Patients were randomly divided into three groups to receive TMP (group A, n = 10), TNG (group B, n = 10) or PGE1 (group C, n = 8). Anaesthesia was maintained with N2O and sevoflurane. The mean arterial blood pressure was maintained at 60 mmHg for 90 min. Measurements included arterial ketone body ratio (AKBR-acetoacetate/3-hydroxybutyrate), SGOT, SGPT, LDH, blood glucose and blood gases were made. Measurements were taken before hypotension, 60 min and 90 min after starting hypotension, 60 min after recovery from hypotension and on the post-operative day. AKBR showed no significant change. SGOT, SGPT and LDH were within normal limits. Controlled hypotension induced with TMP, TNG or PGE1 under sevoflurane anaesthesia in surgical patients did not cause hepatocellular damage.

Adult↗

FliK, the protein responsible for flagellar hook length control in Salmonella, is exported during hook assembly.

In wild-type Salmonella, the length of the flagellar hook, a structure consisting of subunits of the hook protein FlgE, is fairly tightly controlled at approximately 55 nm. Because fliK mutants produce abnormally elongated hook structures that lack the filament structure, FliK appears to be involved in both the termination of hook elongation and the initiation of filament formation. FliK, a soluble protein, is believed to function together with a membrane protein, FlhB, of the export apparatus to mediate the switching of export substrate specificity (from hook protein to flagellin) upon completion of hook assembly. We have examined the location of FliK during flagellar morphogenesis. FliK was found in the culture supernatants from the wild-type strain and from flgD (hook capping protein), flgE (hook protein) and flgK (hook-filament junction protein) mutants, but not in that from a flgB (rod protein) mutant. The amount of FliK in the culture supernatant from the flgE mutant was much higher than in that from the flgK mutant, indicating that FliK is most efficiently exported prior to the completion of hook assembly. Export was impaired by deletions within the N-terminal region of FliK, but not by C-terminal truncations. A decrease in the level of exported FliK resulted in elongated hook structures, sometimes with filaments attached. Our results suggest that the export of FliK during hook assembly is important for hook-length control and the switching of export substrate specificity.

Bacterial Proteins↗

Characterization of ureteral lesions associated with impacted stones.

BACKGROUND: Few studies have addressed the various types of ureteral lesions apparent in patients treated for ureteral stones, especially in those with impacted stones. Macroscopic and microscopic analyses of ureteral lesions associated with impacted stones were therefore undertaken. METHODS: From May 1994 to October 1996, 36 patients with ureteral stones, 21 of whom showed stone impaction, were treated with transurethral ureterolithotripsy. After ureteroscopic examination, biopsied specimens were obtained from six patients with impacted stones and were examined microscopically by conventional hematoxylin and eosin staining. RESULTS: Ureteroscopy revealed two types of mucosal lesions in the patients with impacted stones: Type 1 lesions were defined as edematous or cystic hemispheric lesions and occurred in 18 patients, whereas type 2 lesions had a villous appearance and were present in three patients. Microscopically, type 1 lesions appeared as submucosal edema without specific findings, whereas type 2 lesions appeared as columnar mesenchymal tissue coated with several layers of transitional epithelium. With regard to factors that might contribute to lesion formation, duration of stone presence was significantly greater for patients with impacted stones than for those with-non-impacted stones. However, no differences in such parameters were apparent between patients with type 1 lesions and those with type 2 lesions. CONCLUSIONS: Two types of ureteral lesions associated with impacted stones were confirmed microscopically. The duration of stone presence is a potential contributing factor in the development of ureteral lesions, but factors that determine the type of ureteral lesion remain unclear.

Adult↗

A case of pelvic arteriovenous malformation in a male.

BACKGROUND: Congenital pelvic arteriovenous malformation (AVM) is rare especially in males. We present a case of pelvic AVM in a 38-year-old male. He was admitted to our hospital with left flank abdominal pain and painless gross hematuria. METHODS/DISCUSSION: Pelvic computed tomography demonstrated a homogeneous contrast-enhanced mass, 6 cm in diameter. For diagnosis, non-invasive magnetic resonance imaging (MRI) and color Doppler ultrasonography were very useful in our case. Though the treatment is controversial, we decided to monitor his clinical course.

Abdominal Pain↗

Effects of ebselen on cerebral ischemia and reperfusion evaluated by microdialysis.

Since ebselen is known to have glutathione peroxidase-like activity and inhibitory effects on lipoxygenase and cyclo-oxygenase, we investigated its protective effects against cerebral ischemia in the rat using microdialysis. Ebselen was given through a gastric tube 30 min before occlusion in the experimental groups. Ischemia was induced using 4-vessel occlusion either transiently (20-min occlusion of the arteries followed by reperfusion), or over a prolonged period (120-min occlusion). Extracellular lactate, pyruvate and purine catabolites were sampled using microdialysis and measured by high performance liquid chromatography. During ischemia, the level of lactate, adenosine, inosine and hypoxanthine in the control group increased markedly. The lactate: pyruvate ratio increased during ischemia and decreased after reperfusion. Although the level of lactate and adenosine decreased immediately after reperfusion, those of inosine and hypoxanthine showed delayed decrease. Ebselen reduced the maximum values of lactate and purine catabolites significantly and markedly in transient ischemia. Although it reduced the values significantly in prolonged ischemia, the decrements were less marked than those in transient ischemia. Based on these results we consider ebselen to protect against ischemic metabolic changes and to accelerate the recovery during reperfusion.

Animals↗

Paraclinoid aneurysms of the internal carotid artery: hydraulic simulation study on their locations and shape of the carotid siphon.

Hemodynamics of paraclinoid aneurysms were investigated focusing on the effects of their locations and shape of the carotid siphon. A transparent silicon model of the carotid siphon was constructed and a model aneurysm was attached to the outside of the curvature at three different sites. Glycerol solution was perfused into the model, and the half-life of the dye injected into the aneurysm was calculated as an index of the stagnant flow. Values of half-life changed significantly depending on the aneurysmal location and the siphon angle. When the siphon angle was 0 degree where C2 and C4 segments were parallel to each other, the half-life value was the lowest in the C2-C3 junction aneurysm, highest in the C3 segment aneurysm and intermediate in the C2 segment aneurysm. While the C2-C3 junction aneurysm maintained low values regardless of the angle, the C3 segment aneurysm values decreased and C2 segment aneurysm values increased with increases in the angle. These changes of half-life occur because the point at which the faster moving fluid component strikes the curved wall changes according to the siphon angle. These results are considered useful to determine the surgical indications, treatment modalities and post-surgical management of the aneurysms.

Adult↗

Intraductal papillary neoplasm of the pancreas: a clinical review of 13 benign and four malignant tumours.

OBJECTIVE: To assess of the grade of malignancy of intraductal papillary neoplasm of the pancreas (IPNP). DESIGN: Retrospective analysis. SETTING: University hospital, Japan. PATIENTS: 8 men and 9 women, mean age 67 years, with IPNP. RESULTS: 12 lesions were in the head of the pancreas, two in the body and three in the tail. There were no differences in the age and sex of the patients, the presence of diabetes mellitus or history of pancreatitis, serum concentrations of carcinoembryonic antigen, and CA 19-9, pancreatic function test, and the site of origin of benign and malignant IPNP. The mean diameter of the main pancreatic duct was 16 mm in the four malignant tumours, but 6 mm in the 13 benign IPNP (p < 0.05). 10 of the 13 benign IPNP were located in the branch duct, two in the main pancreatic duct, and another in both the main and branch ducts, while all four malignant IPNP were situated in the main duct (p < 0.01). Mural nodules were detectable preoperatively in all four malignant IPNP but in only 5 of the 13 benign tumours (39%). The mean diameter of the mural nodules in the five benign IPNPs was 3 mm, whereas that in the four malignant ones was 24 mm (p < 0.01). All but one patient (who had a malignant IPNP) were alive for one to 36 months (mean 16 months) after resection. CONCLUSIONS: IPNP is a unique variant of pancreatic exocrine neoplasm with a good prognosis after resection. The diameter of the main pancreatic duct, size of the mural nodule, and site of the tumour (main pancreatic duct or branch duct) differ significantly between benign and malignant tumours.

Adenocarcinoma, Papillary↗

Polymorphism of the 5'-flanking region of the tumor necrosis factor (TNF)-alpha gene and susceptibility to human T-cell lymphotropic virus type I (HTLV-I) uveitis.

The genetic background of human T-cell lymphotropic virus type I (HTLV-I) uveitis (HU) was investigated by studying the distribution of 5 polymorphisms of the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-alpha gene in patients with HU, together with patients with adult T-cell leukemia (ATL), asymptomatic HTLV-I carriers, and healthy controls. The frequencies of the -1,031C allele (T-->C transition at position -1,031) and -863A allele (C-->A transition at position -863) in the HU patients, but neither in the ATL patients nor in the carriers, were significantly higher than those in the controls. The -1,031C and -863A alleles, in the absence of the HLA B61 or the DRB1*0901 allele which is in linkage disequilibrium with these alleles, were associated with increased susceptibility to HU. These results suggest that the -1,031C and -863A alleles might be genetic risk factors for HU.

Adult↗

Efficacy of beta-lactam antibiotics combined with gentamicin against penicillin-resistant pneumococcal pneumonia in CBA/J mice.

We examined the efficacy of gentamicin combined with beta-lactam antibiotics against penicillin-resistant Streptococcus pneumoniae (PRSP) in a noncompromised mouse model of pneumonia. In the presence of 8 mg/L (0.25 x MIC) and 16 mg/L (0.5 x MIC) of gentamicin, MICs of penicillin G against 23 strains of PRSP decreased from 1-4 mg/L to 0.03 mg/L in 14 (61%) and 23 strains (100%), respectively. A short-time killing study using strain 741 showed that 8 mg/L of gentamicin (0.25 x MIC) increased the killing activity of penicillin G, cefotaxime and imipenem (at 0.25, 1 and 4 x MIC) during a 6 h incubation period. Survival studies showed that the combined treatment of penicillin-G (160 mg/kg) and gentamicin (10 mg/kg), which commenced 2 days after infection (twice a day for 5 days), provided complete protection, while no animal survived when either antibiotic was used alone. A significant improvement in mortality was observed when a small dose of imipenem (2.5 and 10 mg/kg) was used with gentamicin. Our results suggest that gentamicin, when combined with beta-lactam antibiotics, especially imipenem, may be potentially useful against PRSP pneumonia in noncompromised individuals.

Animals↗

HPC-1/syntaxin 1A suppresses exocytosis of PC12 cells.

The membrane protein syntaxin (originally named HPC-1) is involved in vesicle trafficking and required for neurotransmitter release at nerve terminals. The presence of syntaxin on target membranes is hypothesized to confer specificity to targeting and fusion via interactions with complementary vesicle-associated proteins. To elucidate the function of syntaxin 1A in exocytosis, HPC-1/syntaxin 1A-reduced PC12h cells (PC12h/Deltasyx) that were stably transfected with a plasmid for antisense syntaxin 1A expression were constructed. Depolarizing stimulation of PC12h/Deltasyx enhanced dopamine release, compared with PC12h. There was a strong inverse correlation between syntaxin 1A protein expression and enhancement of dopamine release. Reduction of syntaxin 1A had no effect on increase of the cytoplasmic free Ca2+ concentration by depolarized stimulation. Moreover, PC12h/Deltasyx clones similarly enhanced of exocytosis by native secretagogues. These results indicate that syntaxin 1A has more than one function in exocytosis.

Animals↗

Delayed gastric emptying after Billroth I pylorus-preserving pancreatoduodenectomy: effect of postoperative time and cisapride.

OBJECTIVE: To study the recovery course of gastric emptying after Billroth I pylorus-preserving pancreatoduodenectomy (PPPD) and therapeutic effects of cisapride. METHODS: To examine gastric emptying, acetaminophen was given, admixed in a pasty liquid meal, to 16 patients undergoing PPPD before surgery and at 1, 3, 6, 9, and 12 months after surgery. Cisapride was given orally to 10 patients before they received the acetaminophen regimen. Electrogastrography was performed at 2 weeks to 1 month after surgery in eight patients and at 6 to 12 months after surgery in seven patients. RESULTS: Gastric emptying was delayed but returned to the preoperative level by 6 months after surgery. Pretreatment with cisapride accelerated gastric emptying during months 1 to 6 but not during months 6 to 12 after surgery. Electrogastrography frequently showed tachygastria 2 weeks to 1 month after surgery, but seldom 6 to 12 months after surgery. CONCLUSIONS: After Billroth I PPPD, gastric emptying is delayed but recovers by 6 months after surgery. Tachygastria may play a part in the pathogenesis of delayed gastric emptying, but it can be treated with cisapride.

Adult↗