Biomedical subjects

Y Shirai

Publications and source records attributed to Y Shirai.

At least 37 records · Page 2Linked to original sources

PubMed2001

Early gallbladder carcinoma does not warrant radical resection.

BACKGROUND: This study was designed to address whether gallbladder cancer invading the muscle layer (stage pT(1b)) is a local disease and whether radical resection is necessary. METHODS: A retrospective analysis of 25 patients with pT(1b) gallbladder tumours, 13 of whom underwent simple cholecystectomy and 12 radical resection with regional lymph node dissection, was performed. A total of 147 regional lymph nodes was examined for metastasis. The median follow-up time was 95 months. RESULTS: No patient had blood vessel or perineural invasion on histology. Lymphatic vessel invasion was seen in one patient. Both overt metastasis and micrometastases were absent in all lymph nodes examined. Overall 10-year survival was 87 per cent. The outcome after simple cholecystectomy was comparable to that after radical resection (P = 0.16). Two patients who underwent radical resection died from tumour relapse in distant sites. CONCLUSION: Most pT(1b) gallbladder carcinomas spread only locally. Additional radical resection is not necessary when the depth of invasion of gallbladder carcinoma is limited to the muscle layer after simple cholecystectomy.

Adult↗

PubMed2001

Distinct regulatory mechanism for p70 S6 kinase beta from that for p70 S6 kinase alpha.

BACKGROUND: A novel ribosomal S6 kinase, termed p70 S6 kinase beta (p70beta), has a highly homologous amino acid sequence to that of p70/p85 S6 kinase (p70alpha). This includes the critical phosphorylation sites, Thr252, Ser394 and Thr412 in p70alpha1, which correspond to Thr241, Ser383 and Thr401 in p70beta1, respectively. However, the regulatory mechanism for p70beta remains to be elucidated. RESULTS: We report here the expression and the mechanism of in vivo regulation of p70beta. Two isoforms, p70beta1 and p70beta2, were expressed in a variety of tissues at a different level. p70beta1 was mainly targeted to the nucleus, whereas p70beta2 dispersed throughout the cytoplasm including nucleoplasm. The kinase activity of p70beta1 was less sensitive to the inhibition induced by rapamycin, wortmannin and amino acid withdrawal than that of p70alpha. The portion of p70beta activity inhibited by rapamycin was rescued by the rapamycin-resistant mutant of the mammalian target of rapamycin (mTOR). Mutational analysis revealed that the phosphorylation of Thr241 and Thr401 in p70beta1 was indispensable for the kinase activity. In contrast, a p70beta1 mutant in which Ser383 was substituted with Gly (S383G) still retained nearly the half maximal activity. Sequential phosphorylation of wild-type and S383G mutant of p70beta1 with mTOR and 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vitro synergistically activated their kinase activities. CONCLUSION: These results indicate that p70beta is regulated by the mTOR- and PDK1-signalling pathways through a synergistic interaction between phosphorylated Thr241 and Thr401, while Ser383 plays minor role in their activation mechanism. Activated p70beta may be less sensitive to dephosphorylation mediated by putative phosphatases activated by rapamycin, amino acid withdrawal, and probably wortmannin.

Androstadienes↗

PubMed2001

Clinical significance of lymph node micrometastasis in gallbladder carcinoma.

BACKGROUND: This retrospective study was intended to define the clinical significance of lymph node micrometastasis in gallbladder carcinoma. METHODS: A total of 1136 regional lymph nodes taken from 63 consecutive patients undergoing radical resection were examined histologically. Micrometastasis was defined as a metastasis missed on routine histologic examination with hematoxylin-and-eosin but detected by immunohistochemical examination with an antibody against cytokeratins 8 and 18. RESULTS: None of 9 patients (0%) with pT1 disease and 19 of 54 patients (35%) with pT2-4 disease had nodal micrometastases. Univariate analysis identified nodal micrometastasis, type of radical resection, M classification, pT classification, perineural invasion, pTNM stage, timing of radical resection, lymphatic vessel invasion, and pN classification as significant variables. Multivariate analysis revealed that nodal micrometastasis (P =.0003) and type of radical resection (P=.0044) were independent prognostic factors. Nodal micrometastasis affected survival adversely, despite the absence (P=.0002) or presence (P <.0001) of overt nodal metastasis. Nodal micrometastasis correlated significantly with invasive characteristics: lymphatic vessel invasion, perineural invasion, and distant metastasis. CONCLUSIONS: Lymph node micrometastasis is the strongest independent predictor of worse survival regardless of the overt nodal status and may indicate aggressive tumor biology among patients undergoing curative resection for gallbladder carcinoma.

Adult↗

PubMed2001

CD4 T cells monospecific to ovalbumin produced by Escherichia coli can induce colitis upon transfer to BALB/c and SCID mice.

Although some animal models suggest an involvement of CD4 T cells reactive to luminal microbial antigen(s) for the pathogenesis of inflammatory bowel diseases (IBD), direct linkage between microflora-driven clonal expansion of CD4 T cells and the development of colitis has not been well studied. Here, BALB/c and SCID mice were given CD4 T cells purified from Rag-2(-/-) mice crossed to transgenic mice expressing TCR specific to ovalbumin (OVA) then administered with antibiotic-resistant Escherichia coli producing OVA (ECOVA) or LacZ (ECLacZ) via the rectum. The ECOVA-inoculated BALB/c and SCID mice developed a subacute colitis with microscopic features of distortion of crypt architecture, loss of goblet cells, and focal infiltration by mononuclear cells in the lamina propria (LP) and submucosa. Expanding OVA-specific CD4 T cells were detected in colonic follicles of mice with ECOVA. Early in colitis, OVA-specific CD4 T cells producing IFN-gamma predominate in the LP of the colon, which was followed by an emergence of OVA-specific CD4 T cells producing IL-4 and IL-10 at a later time point. Co-transfer of an IL-10-secreting OVA-specific CD4 T cell line prevented colitis. Thus, an expansion of CD4 T cells monospecific to OVA, an antigen non-cross-reactive to colonic tissue, can mediate both induction and inhibition of the colitis which was associated with hyperplasia of lymph follicles.

Administration, Rectal↗

PubMed2001

Subtype-specific translocation of the delta subtype of protein kinase C and its activation by tyrosine phosphorylation induced by ceramide in HeLa cells.

We investigated the functional roles of ceramide, an intracellular lipid mediator, in cell signaling pathways by monitoring the intracellular movement of protein kinase C (PKC) subtypes fused to green fluorescent protein (GFP) in HeLa living cells. C(2)-ceramide but not C(2)-dihydroceramide induced translocation of delta PKC-GFP to the Golgi complex, while alpha PKC- and zeta PKC-GFP did not respond to ceramide. The Golgi-associated delta PKC-GFP induced by ceramide was further translocated to the plasma membrane by phorbol ester treatment. Ceramide itself accumulated to the Golgi complex where delta PKC was translocated by ceramide. Gamma interferon also induced the delta PKC-specific translocation from the cytoplasm to the Golgi complex via the activation of Janus kinase and Mg(2+)-dependent neutral sphingomyelinase. Photobleaching studies showed that ceramide does not evoke tight binding of delta PKC-GFP to the Golgi complex but induces the continuous association and dissociation of delta PKC with the Golgi complex. Ceramide inhibited the kinase activity of delta PKC-GFP in the presence of phosphatidylserine and diolein in vitro, while the kinase activity of delta PKC-GFP immunoprecipitated from ceramide-treated cells was increased. The immunoprecipitated delta PKC-GFP was tyrosine phosphorylated after ceramide treatment. Tyrosine kinase inhibitor abolished the ceramide-induced activation and tyrosine phosphorylation of delta PKC-GFP. These results suggested that gamma interferon stimulation followed by ceramide generation through Mg(2+)-dependent sphingomyelinase induced delta PKC-specific translocation to the Golgi complex and that translocation results in delta PKC activation through tyrosine phosphorylation of the enzyme.

Adenoviridae↗

PubMed2001

Acetylcholine increases intracellular Ca2+ in the rat pituitary folliculostellate cells in primary culture.

Pituitary folliculostellate cells (FSCs) are thought to partially inhibit pituitary hormone secretion through a paracrine mechanism. In this process, one of the important questions is what factors regulate the function of FSCs. Because ACh is synthesized in and possibly released from the corticotrophs and lactotrophs, we examined whether FSCs respond to ACh by the method of Ca2+ imaging in primary cultured FSCs from male Wistar rats. ACh (30 nM-3 microM) increased intracellular calcium concentration ([Ca2+](i)) of FSCs in a concentration-dependent manner, with an initial rapid rise followed by a relatively sustained increase. The complete block of the response by atropine and pirenzepine suggests involvement of muscarinic receptors. Depletion of the stored Ca2+ by thapsigargin blocked the response completely. Blockers of phospholipase C, U-73122 and neomycin, suppressed significantly the rise of [Ca2+](i). These results suggest that ACh increases [Ca2+](i) in FSCs by activating phospholipase C, presumably through activation of M(1) receptors. The rise in [Ca2+](i) could trigger a variety of Ca2+-dependent cellular processes, including the synthesis and release of bioactive substances, which in turn act on endocrine cells.

Acetylcholine↗

PubMed2001

Induction of long-term depression in cerebellar Purkinje cells requires a rapidly turned over protein.

Evidence is presented indicating that the induction of long-term depression (LTD) in Purkinje cells (PCs) requires a rapidly turned over protein(s) during a critical time period within 15 min after the onset of LTD-inducing stimulation and that synthesis of this protein is maintained by mRNAs supplied via transcription. LTD was induced in granule cell axon (GA)-to-PC synapses by stimulation of these synapses at 1 Hz for 5 min in conjunction with the climbing fibers (CFs) forming synapses on the same PCs and represented by a persistent reduction in the GA-induced excitatory postsynaptic potentials (EPSPs). Not only a prolonged but also a brief (5 min) pulse application of translational inhibitors (anisomycin, puromycin, or cycloheximide) effectively blocked the LTD induction. Pulses applied during the period from 30 min before to 10 min after the onset of conjunctive stimulation blocked the LTD induction, but those applied 15 min after were ineffective. The three translational inhibitors blocked the LTD induction similarly, suggesting that the effect is due to their common action of inhibiting protein synthesis. Infusion of a mRNA cap analogue (7-methyl GTP) into PCs also blocked LTD induction, ensuring that the postsynaptic protein synthesis within PCs is required for LTD induction. Transcriptional inhibitors, actinomycin D and 5,6-dichloro-l-beta-D-ribofuranosyl-benzimidazole, also blocked the LTD induction, but this effect was apparent when 5-min pulses of the transcriptional inhibitors preceded the conjunctive stimulation by 30 min or more. This time lag of 30 min is presumed to be required for depletion of the protein(s) required for LTD induction. The presently observed effects of translational and transcriptional inhibitors on the LTD induction are of temporal characteristics corresponding to their depressant effects on the type-1 metabotropic glutamate-receptor (mGluR1)-mediated slow EPSPs in PCs as we have reported recently. An antagonist of mGluR1s [(RS)-1-aminoindan-1,5-dicarboxylic acid], however, did not block LTD induction when it was applied during the 10-min period following conjunctive stimulation, where translational inhibitors effectively blocked LTD induction. This discrepancy in time course suggests that the rapidly turned over protein(s) required for LTD induction is involved in a process occurring downstream of the activation of mGluR1s.

Animals↗

PubMed2001

Resection of spleno-renal shunt resulting in enhanced liver volume in a patient with congenital portosystemic shunt concomitant with early gastric cancer. Review of Japanese cases.

A 73-year-old man recurring hepatic encephalopathy due to a congenital splenorenal shunt concomitant with early gastric cancer was successfully treated by surgical intervention. The portal pressures before and after the shunt resection were 13.5 and 18 cm H2O, respectively. The liver was slightly atrophic and the histological specimen showed slight fibrosis and mild infiltration of lymphocytes in the portal area. After the operation, the encephalopathy was improved and the several factors of liver function also recovered. Interestingly, the liver volume estimated by abdominal CT clearly increased 1 month after the shunt resection. The encephalopathy in congenital portosystemic shunt might result from chronic liver ischemia and atrophy. Moreover, the shunt resection may enlarge the functional liver volume by increasing the portal blood flow.

Aged↗

PubMed2001

Roles of mast cells and histamine in mosquito bite-induced allergic itch-associated responses in mice.

We investigated itch-associated responses (scratching) to mosquito bites and the role of histamine and mast cells in mosquito-induced itching in mice. Although the first bites of mosquito Aedes albopictus did not increase scratching, repeated bites increased scratching. The response was not diminished even after an interval of 2 months. Similarly, repeated intradermal (i.d.) injections of salivary gland extract (SGE) from Aedes albopictus increased scratching after SGE injection itself and mosquito bites. The scratching peaked within 10 min and almost subsided by 60 min. The opioid antagonist naloxone (1 mg/kg, s.c.) inhibited scratching following SGE injection. Although the non-sedative H1-histamine-receptor antagonist terfenadine (30 mg/kg, p.o.) significantly suppressed scratching induced by histamine (100 nmol/site, i.d.) in either naive or mosquito-sensitized mice, it did not affect mosquito-induced scratching in mosquito-sensitized mice. Repeated injections of SGE increased scratching in mast cell-deficient (WBB6F1-W/Wv) mice as well as in normal (WBB6F1-+/+) littermates. Repeated exposure to mosquito bites roughly doubled serum concentrations of total IgE and IgG1, but not IgG2a. Repeated injections of SGE markedly increased plasma extravasation induced by mosquito bites and such an increase was almost completely suppressed by terfenadine (30 mg/kg, p.o.). The results show the presence of histamine-mediated and histamine-independent mechanisms in cutaneous itching and suggest that histamine probably released from mast cells does not play an important role in itching in immediate allergic reaction. Our murine model of mosquito itching may be useful for studying the mechanisms of immediate allergic itching.

Aedes↗

PubMed2001

The efficacy of ununited tibial fracture treatment using pulsing electromagnetic fields: relation to biological activity on nonunion bone ends.

Thirty ununited tibial fractures with a median time since injury of 18+/-9 months were treated by electrical stimulation using pulsing electromagnetic field therapy. Union was achieved in 25 cases (83.3%) in a median interval of 8.6+/-3.2 months. Patient age and gender, the presence of surgical hardware, length of disability, and the number of surgical procedures did not affect the outcome. Ununited fractures that appeared to be hypertrophic or sclerotic type radiographically, indicating a good blood supply to the bone ends, all healed. Treatment failures occurred only among lesions with a poor blood supply, and in necrotic or defective radiopraphic types. Pulsing electromagnetic field therapy is an effective treatment for ununited tibial fractures with good blood supply to the bone ends.

Adult↗

PubMed2001

Serum and synovial fluid levels of chondroitin sulfate in patients with osteoarthritis of the knee joint.

We measured serum and synovial fluid levels of chondroitin sulfate (CS) in patients with osteoarthritis (OA) of the knee joint to clarify whether CS levels differ in various stages of OA, and whether measurement of CS levels is useful in evaluating the pathology of OA. The study population was 117 OA patients and 23 healthy young volunteers. Synovial fluid was obtained from 69 of 117 OA patients. The mean serum level of C4S in all of the OA patients was significantly higher than that in the controls (p< 0.05). However, there was little difference between respective OA stages. A small amount of serum C6S (0.2 to 0.6 nmol/ml) was detected in 31.6% of the OA patients and in 26.1%of the control subjects. The mean serum C0S level in all OA patients was significantly higher than that in the controls (p< 0.01). However no significant difference was found between respective OA stages. As for synovial fluid CS, the C4S level in the early stage of OA tended to be higher than that in the advanced stage. C6S levels showed a markedly decreasing trend with advancing OA stage. C0S was not detected in synovial fluid. The present study demonstrated that serum levels of C4S and C0S in OA patients are elevated compared with normal subjects, and that synovial fluid levels of C4S and C6S may provide useful in assessing the pathology of OA.

Adult↗

PubMed2001

A case report of spondyloepiphyseal dysplasia congenita.

Spondyloepiphyseal dysplasia congenita (SED) is a rare form of skeletal systemic disease, characterized by congenital dwarfism with a short trunk and epiphysial dysplasia in the long bones and vertebral bodies. Patients also frequently suffer from atlanto-axial instability due to os odontoideum. Compression of the spinal cord caused by atlanto-axial instability is a common, serious complication in SED patients, and causes severe spinal cord symptoms or occasionally sudden death. We present an SED patient who underwent a posterior fusion of the occiput to the cervical spine for severe spinal cord symptoms due to atlanto-axial instability.

Atlanto-Axial Joint↗

PubMed2001

A suspension procedure using the extensor carpi ulnaris tendon for distal radioulnar joint disorders.

Recently the Sauve-Kapandji (S-K) procedure has become popular for the treatment of various distal radioulnar joint (DRUJ) disorders. However, some complications, especially pain over the proximal stump of the ulna due to instability of the ulna have been reported in more recent follow-up studies. To prevent the occurrence of this pain, we devised a modified S-K procedure, which we called the suspension procedure, in which the extensor carpi ulnaris (ECU) tendon was used to suspend the proximal ulnar stump. We report here the surgical technique and compare clinical and radiographic results between the suspension procedure and the S-K procedure alone. We performed the S-K procedure alone on 8 patients (original group) and the suspension procedure on 5 (suspension group). Clinical results were assessed according to the clinical evaluation scoring system described by Inoue. Radiographic evaluations included the radio-ulnar distance, the gap of the ulna, and the distance between the articular surface of the wrist and the proximal ulnar stump. In the original group, 4 patients were rated as excellent, 2 as good and 2 as fair, whereas in the suspension group, 3 were rated as excellent, 2 as good and none as fair. In regard to radiographic evaluations, there were no significant differences in any of the 3 parameters between the 2 group. This suspension procedure had an advantage over the S-K procedure alone, especially in preventing the occurrence of stump pain. As there was no significant difference in radiographic findings between the two procedures regarding the site of osteotomy, the amount of bone resection, and radio-ulnar distance, stump pain may be attributed to dynamic instability rather than to static instability.

Adult↗

PubMed2001

Meniscal tears after anterior cruciate ligament reconstruction.

The aim of this study was to follow patients in whom preoperative MRI demonstrated grade-3 lesions in the medial meniscus but no visible tears at arthroscopic ACL reconstruction, and to ascertain whether these meniscal lesions would progress to definite tears after reconstruction. The Study population consisted of 19 patients with a mean age of 23.2 years. Intraoperative arthroscopy showed normal appearance in 16 of 19 menisci and mild degree superficial legions in 3 menisci. None of the patients had any special treatment for the menisci at surgery. As controls, 39 patients who showed no tears on MRI and arthroscopy were studied. All MR studies were performed on a 0.5 T MR unit with field echo pulse sequences. A slice thickness of 1.5 mm was used with no interslice gap. Grade-3 legions progressed to definite tears in 8 of the 19 studied patients (42.1%) 12 to 33 months after ACL reconstruction. The Remaining 11 patients showed only symptoms or signs suggesting meniscal tears during a mean follow-up of 26.1 months. In the controls, medial meniscal tears occurred in 2 of the 39 patients (5.1%) 15 to 18 months after reconstruction. The studied patients were divided into a tear group (n=8) and a no-tear group (n=11). When the number of slices with grade-3 lesions was compared between the 2 groups, the mean slice number in the tear group (5.8 slices) was significantly greater than that in the no-tear group (3.1 slices) (P<0.05). These results suggest that even if no visible tear is found at surgery, patients in whom grade-3 lesions are identified in many slices have a high risk of developing definite tears after ACL reconstruction.

Adolescent↗

PubMed2001

An epidemiological study on occupational low back pain among people who work in construction.

People who work at construction sites have one of the highest incidences of low back pain (LBP). The purpose of this study is to evaluate the status of LBP, and to investigate the risk factors of LBP in construction workers. The subjects were 33, 530 workers who were sent our questionnaires in September and October 1996. Of the final respondents, 29.3% had LBP. The results of multi-regression analysis revealed that risk factors having significant relationships with the onset of LBP were 1) stress due to personal relations at work, 2) postures during work, and 3) unstable body balance on scaffoldings. In addition, two factors were found to be important in decreasing the incidence of LBP: 1) having sufficient space for taking a rest and 2) using pre-work exercises. These findings have led us to the conclusion that not only providing good physical working environments, but also giving instructive and psychological care are important in preventing the onset of LBP in construction workers.

Adult↗

PubMed2001

The accuracy of MRI in assessing graft integrity after anterior cruciate ligament reconstruction.

To evaluate the efficacy of MRI in assessing anterior cruciate ligament (ACL) reconstruction graft integrity, we compared MRI findings with arthroscopic findings in 52 patients who had undergone arthroscopically assisted ACL reconstruction using semitendinosus and gracilis tendons augmented by woven polyester. MRI and arthroscopy were carried out 12 months after the operation. The MR appearance of ACL grafts was categorized into 3 types by signal intensity and continuity of the ligament according to Rak's method: 1. well-defined type: the graft was visualized as a smoothly continuous band with low signal over the entire course; 2. intermediate type: signal intensity increased and a low-signal band was visualized only in part of the graft; 3. indiscernible type: the graft was not identified through the joint cavity due to markedly increased signal intensity. When the MR appearance of intermediate or indiscernible types was defined as torn, the grafts were presumed to be torn in 9 patients whose arthroscopic findings were 7 intact and 2 torn grafts. All cases with intact MRI findings were intact on arthroscopic examination. Thus, the sensitivity, specificity and accuracy of MRI as an evaluative tool for ACL graft tears were 100%, 86% and 86.5%, respectively.

Adolescent↗

PubMed2001

Surgical results of lumbar disc herniation in the elderly.

We investigated the surgical results of lumbar disc herniation in the elderly. Ten elderly patients underwent surgical treatment between 1990 and 1999. There were 7 males and 3 females with a mean age of 68.2 years (range: 60~85 years). Thirteen patients in their 20s and 30s were used as a control. Preoperatively, severe leg pain and gait disturbance, and higher rates of negative straight leg-raising were shown in the elderly group. Higher levels of herniation and higher graded disc degeneration were shown compared with the young. The mean total of the Japanese Orthopedic Association score in the elderly group improved from 5.1 points to 13.1 points postoperatively, and that in the young group improved from 6.9 points to 14.5 points. The recovery rate was 82.6% in the elderly group and 94.3% in the young group. Postoperatively, the recovery of gait disturbance in the elderly group tended to be poor compared with the young group. The elderly patients would not tolerate bed rest and would often do poorly if kept recumbent and in pain for long periods of time. Satisfactory results are being sought with regard to the operative management of lumbar disc herniation in the elderly.

Aged↗

PubMed2001

L-lactic acid as a mosquito (Diptera: Culicidae) repellent on human and mouse skin.

The attraction of Aedes albopictus (Skuse) to hands and forearms of human subjects treated with several concentrations of L-LA solution were studied in a test chamber containing proboscis-amputated mosquitoes. Fewer mosquitoes alighted on L-LA treated human skin than on water-treated control skin. Similar results were found using normal mosquitoes following L-LA and water treatment of mouse skin. The relative repellent effects of L-LA varied with concentration. The minimum repellent concentration was lower than previously reported for human skin. The number of alightments decreased at increasing concentrations of L-LA, demonstrating the absolute repellency of L-LA. Unlike previous reports suggesting that L-LA attracted mosquitoes, our studies using human and mouse skin showed that L-LA exhibited both relative and absolute repellency.

Aedes↗