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Biomedical subjects

I Nakamura

Publications and source records attributed to I Nakamura.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Neoadjuvant chemotherapy for advanced gastric cancer with para-aortic lymph node metastasis].

Neoadjuvant chemotherapy was applied to patients with advanced gastric cancer and confirmed para-aortic lymph node metastasis. Subjects were 7 patients. The response to the neoadjuvant chemotherapy was a PR in 5 cases, MR in 2 cases for the primary lesion and CR in 2 cases PR in 5 cases for the para-aortic lymph node metastasis. The grades of histological response assessed on the resected specimen were Grade 0 in three cases, Grade 1a in one, Grade 1b in one and Grade 2 in two. While there was no significant difference in survival rate between patient groups with and without neoadjuvant chemotherapy, the 2-year survival rate in patients with neoadjuvant chemotherapy was a good 42.9%, compared with 10% in patients groups without neoadjuvant chemotherapy. It is concluded that a better prognosis can be expected for advanced gastric cancer patients with neoadjuvant chemotherapy.

Aged↗
PubMed2001

Microsatellite instability in thyroid cancer: hot spots, clinicopathological implications, and prognostic significance.

PURPOSE: To determine whether microsatellite instability (MSI) in particular loci has clinicopathological significance in thyroid cancer. EXPERIMENTAL DESIGN: Seventy-six cases of surgically resected thyroid cancer were screened for MSI at nine microsatellites: THRA1, TSHR, D2S123, D11S912, D2S115, D2S399, p53, RET, or BAT-26. Multivariate analysis was performed to test for links between MSI and the clinical parameters of gender, age, histology, stage, nodal involvement, and prognosis. RESULTS: THRA1, residing in the thyroid hormone receptor alpha gene, displayed the highest levels of MSI at 36.5%. MSI in TSHR, located within the thyroid-stimulating hormone receptor gene, was found to be linked to cancer in the elderly (>70 years of age) and with high-grade (N 3, 4) nodal involvement. In follicular cancer, MSI in D2S123 occurred at a frequency of 100% (7/7) with no (0%) occurrence of MSI at the nearby D2S115, D2S399, or BAT-26 loci. Regarding prognosis, patients with MSI-positive cancer showed better long-term survival. BAT-26, which is an important marker in colorectal cancer, displayed the lowest frequency of MSI in our panel of thyroid tumors. CONCLUSION: Whereas patients with MSI-positive cancer showed better long-term survival, as is the case for colorectal cancer, our finding of the low frequency of MSI in BAT-26 suggests that the biochemical defects governing the spectrum of MSI in thyroid and colorectal cancer are different. MSI in THRA1, TSHR, and D2S123 appears to be an integral part of thyroid carcinogenesis, as evidenced by the high frequency of MSI and significant correlation to clinical data.

Adult↗
PubMed2000

Inhibition of osteoclast function by adenovirus expressing antisense protein-tyrosine kinase 2.

Osteoclast activation is initiated by adhesion to bone, cytoskeletal rearrangement, formation of the sealing zone, and formation of the polarized ruffled membrane. Previous findings suggest that protein-tyrosine kinase 2 (PYK2), a cytoplasmic kinase related to focal adhesion kinase, participates in these events. This study examines the role of PYK2 in adhesion-mediated signaling and osteoclast function, using PYK2 antisense. We produced a recombinant adenovirus containing a 300-base pair reversed 5'-coding region of PYK2 and used full-length PYK2 as a control. Murine osteoclast-like cells or their mononuclear precursors were generated in a co-culture of bone marrow and osteoblasts. Infection with antisense adenovirus significantly reduced the expression of endogenous PYK2 protein relative to uninfected cells or to cells infected with sense PYK2 and caused: 1) a reduction in osteoclast formation in vitro; 2) inhibition of cell spreading and of actin ring formation in osteoclasts plated on glass or bone and of attachment and spreading of osteoclast precursors plated on vitronectin; 3) inhibition of bone resorption in vitro; 4) marked reduction in p130(Cas) tyrosine phosphorylation; and 5) no change in alpha(v)beta(3) integrin expression or c-Src tyrosine phosphorylation. Taken together, these findings support the hypothesis that PYK2 plays a central role in the adhesion-dependent cytoskeletal organization and sealing zone formation required for osteoclastic bone resorption.

Actins↗
PubMed2000

Long-term assessment of serum vitamin B(12) concentrations in patients with various types of orthotopic intestinal neobladder.

OBJECTIVES: Vitamin B(12) deficiency is an important long-term problem after urinary diversion using an intestinal segment. In this study, we examined serum vitamin B(12) concentrations in patients with neobladders constructed from various intestinal segments to determine the anatomic factors important for avoiding vitamin B(12) deficiency. METHODS: Twenty-two patients (19 men and 3 women) had an ileal neobladder (modified Studer type); 9 men had an ascending colonic neobladder (Goldwasser type); 30 patients (24 men and 6 women) had a sigmoid neobladder (modified Reddy type); and 18 (15 men and 3 women) had an ileocolic neobladder (Mainz type). The postoperative follow-up ranged from 3 months to 11 years (mean +/- SD, 3.4 +/- 2.8 years). The serum vitamin B(12) concentration was determined at several points after surgery. RESULTS: No patient with a neobladder fashioned from ascending or sigmoid colon developed a low vitamin B(12) concentration. Of the 18 patients with an ileocolic neobladder, 3 (16.6%) developed decreased serum vitamin B(12) concentrations after 5 to 6 years. Of the 22 patients with an ileal neobladder, 3 (13.6%) developed a low serum concentration of vitamin B(12) between 9 months and 3 years after surgery. No patient developed megaloblastic anemia or neurologic symptoms. CONCLUSIONS: Preservation of the terminal 15 cm of ileum is not sufficient to ensure adequate vitamin B(12) absorption, and thus, preserving the ileal length is important. Use of colonic segments to construct neobladders appears to be preferable to ileal segments to preserve vitamin B(12) absorption.

Aged↗
PubMed2000

Rhabdomyosarcoma presenting as an anterior cervical mass in an adult: report of a case.

We report herein the case of a 61-year-old man who was referred to our hospital for treatment of a rapidly growing tumor in the right anterior cervical region. A 13 x 14 x 15 cm mass was palpated on physical examination. Computed tomography (CT) findings indicated a thyroid tumor, but cytology results suggested rhabdomyosarcoma. A tumor, measuring 9.3 x 7.2 x 5.2 cm and weighing 220 g, was resected and histopathological examination confirmed a diagnosis of rhabdomyosarcoma. Cervical rhabdomyosarcoma is rarely found in adults.

Diagnosis, Differential↗
PubMed2000

Pre- and postoperative bone metabolism of primary hyperparathyroidism.

UNLABELLED: Primary hyperparathyroidism (PHPT) is a well-known indicator of severe bone loss. However, the recovery process of bone mineral density after surgery in PHPT patients is not sufficiently clear. We examined postoperative bone metabolism in 24 PHPT patients. PATIENTS AND METHODS: Subjects were 24 patients with PHPT upon whom we performed parathyroidectomy in the Department of Surgery II, Fukushima Medical University. Mean age was 54.2 years and the male-to-female ratio was 10:14; mean time of follow-up was 27.3 months. Patients were divided histopathologically into 16 adenomas and eight hyperplasias, and classified by heredity into seven familial (six, MEN 1; one, MEN 2) and 17 sporadic types. Bone mineral density was measured by dual energy X-ray absorptometry (DXA) and digital image processing (DIP). Age-matched values of these parameters were obtained. Serum bone metabolic parameters; ionized calcium (CaF), phosphorus, intact PTH (iPTH), c-PTH, ALP, osteocalcin (OC) and PTHrP were measured. RESULTS: PHPT patient preoperative bone mineral densities were significantly lower than those of healthy controls. Those by DIP method were lower than those by DXA. High CaF, iPTH, OC and ALP levels were indicated before surgery, but all parameters immediately became normal. Longitudinal bone mineral density changes of asymptomatic cases increased more than those of patients with renal stone and/or ostitis fibrosa. In adenoma cases, tumor weights were significantly inversely, which correlated with preoperative DIP bone density measurements. CONCLUSION: Preoperative PHPT patients showed decreased bone density; bone loss in symptomatic cases was especially prominent compared to asymptomatic cases. Most PHPT patients had not completed the BMD recovery after surgery, so even asymptomatic and mild PHPT patients should undergo parathyroidectomy to minimize irreversible bone loss.

Absorptiometry, Photon↗
PubMed2000

Integrins and signaling in osteoclast function.

Integrins are heterodimeric adhesion receptors that mediate cell-matrix and cell-cell interactions. Osteoclasts highly express the alphavbeta3 integrin, which binds to a variety of extracellular matrix proteins including vitronectin, osteopontin and bone sialoprotein. RGD-containing peptides, RGD-mimetics and alphavbeta3 blocking antibodies inhibit bone resorption in vitro and in vivo, suggesting that this integrin plays an important role in osteoclast function. RGD-containing peptides were shown to raise cytosolic calcium in osteoclasts. Furthermore, several signaling and adaptor molecules were found to be involved in alphavbeta3 integrin-dependent signaling pathways, including phosphatidylinositol 3-kinase, c-Src, PYK2 and p130(cas). In addition, cytoskeletal molecules such as paxillin, vinculin, gelsolin and F-actin are recruited to adhesion contacts upon integrin activation. Many of these molecules signaling and cytoskeletal localize to the sealing zone of actively resorbing osteoclasts, suggesting that they play a role in linking the adhesion of osteoclasts to the bone matrix with the cytoskeletal organization and the polarization and activation of these cells for bone resorption.

Animals↗
PubMed2000

SHP-1/immunoreceptor tyrosine-based inhibition motif-independent inhibitory signalling through murine natural killer cell receptor Ly-49A in a transfected B-cell line.

Ly-49A is a member of the Ly-49 family of mouse natural killer cell receptors that inhibit cytotoxicity upon recognition of their ligands, the major histocompatibility complex (MHC) class I molecules, on the target cell surface. Although Ly-49A has an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail, relatively little is known about the mechanisms underlying its inhibitory function. We report here that antibody-mediated co-ligation of the B-cell receptor (BCR) with the transfected Ly-49A molecule results in abrogation of BCR-induced interleukin-2 (IL-2) secretion and mild reduction in activation of Erk1/2 and p38 mitogen-activated protein (MAP) kinases in the B-cell line A20. Surprisingly, BCR-induced calcium mobilization was unaffected by cross-linking of BCR with Ly-49A. Furthermore, substitution of the single tyrosine residue in ITIM with phenylalanine, did not result in a complete loss of inhibitory function, as measured by BCR-induced IL-2 secretion. Deletion of the N-terminal 37 amino acid peptide, which includes the ITIM, did abrogate the inhibitory activity. Co-immunoprecipitation experiments revealed that, upon induction of tyrosine phosphorylation, Ly-49A recruits tyrosine phosphatase src-homology 2 (SH2) containing tyrosine phosphatases-1 (SHP-1), but not inositol phosphatase src-homology 2 (SH2) containing inositol phosphatase (SHIP), and that the tyrosine residue in the ITIM is critical for this interaction. These results suggest that transfected Ly-49A utilizes two different inhibitory mechanisms in B-cell signalling: ITIM-dependent and ITIM-independent.

Animals↗
PubMed2000

Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo.

BACKGROUND: The fibrinolytic system plays an important role in degrading fibrin-rich thrombi and in vascular and tissue remodeling. Elevated levels of plasminogen activator inhibitor-1 (PAI-1) can reduce the efficiency of the endogenous fibrinolytic system. Angiotensin (Ang) has been shown to regulate PAI-1 expression via the Ang type 1 (AT1) receptor in some tissues and via the AT4 receptor in cultured endothelium. The purpose of this study was to examine the tissue-specific pattern of PAI-1 expression in response to infusion of Ang II in vivo. METHODS: Adult male Sprague-Dawley rats (N = 5 in each group) were treated with four hours of intravenous infusions of Ang II or vehicle control while mean arterial pressure (MAP) was monitored: group 1, 600 ng/kg/min Ang II; group 2, Ang II + 10 mg/kg of the AT1 receptor antagonist (AT1RA) L158-809 q2 hour; group 3, Ang II + 0.01 to 0.1 mg/kg hydralazine as required to maintain normal blood pressure; and group 4, saline-infused controls. After infusion, tissue was harvested for Northern blotting, immunohistochemical analysis, and in situ hybridization. RESULTS: In group 1, Ang II infusion increased MAP from 105 +/- 8 to 160 +/- 9 mm Hg (mean +/- SE, P < 0. 01). Ang II induced increased expression of PAI-1 mRNA in all tissues examined from 5.1-fold in the heart, 9.7-fold in the kidney, 10.0-fold in the aorta, and up to 30.0-fold in the liver (all P < 0. 01 vs. control). While both AT1RA (group 3) and hydralazine (group 4) prevented Ang II-induced elevation in blood pressure, the Ang II-dependent expression of PAI-1 mRNA was reduced by only AT1 receptor blockade. CONCLUSIONS: We conclude that in the rat, PAI-1 is induced in a variety of tissues by Ang II directly through the AT1 receptor, independent of its effects on blood pressure.

Angiotensin II↗
PubMed2000

Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo.

BACKGROUND: Aldosterone promotes nephrosclerosis in several rat models, whereas aldosterone receptor antagonism blunts the effect of activation of the renin-angiotensin-aldosterone system (RAAS) on nephrosclerosis, independent of effects on blood pressure. Based on recent findings linking activation of the RAAS with impaired fibrinolytic balance, we hypothesized that aldosterone induces sclerosis through effects on plasminogen activator inhibitor-1 (PAI-1), the major physiological inhibitor of plasminogen activation. METHODS: We examined the effect of aldosterone antagonism on the development of sclerosis and on renal PAI-1 expression following radiation injury in the rat. Following a single dose of 12 Gy to the kidneys, male Sprague-Dawley rats were treated with placebo, the aldosterone antagonist spironolactone (4.5 mg/day by time-release subcutaneous pellet), the angiotensin type 1 receptor antagonist L158-809 (AT1RA; 80 mg/L drinking water), or combined spironolactone and AT1RA. RESULTS: Rats treated with placebo developed significant proteinuria and nephrosclerosis 12 weeks following radiation associated with hypertension. Kidney PAI-1 mRNA expression was increased eightfold (P < 0.001 vs. nonradiated controls). Spironolactone alone had no effect on blood pressure (systolic blood pressure 149.0 +/- 5.4 mm Hg) compared with placebo (151.6 +/- 11.2 mm Hg, P = NS), whereas AT1RA alone (107.7 +/- 8.9 mm Hg, P = 0.013 vs. placebo) or in combination therapy (102.1 +/- 6.2 mm Hg, P = 0.001 vs. placebo) lowered blood pressure. Both the AT1RA and spironolactone decreased proteinuria following radiation (P < 0.001 vs. placebo for either drug), and the combination of AT1RA + spironolactone had a greater effect on proteinuria than spironolactone alone (P = 0.003). Aldosterone antagonism significantly decreased (P = 0.016 vs. placebo) and AT1RA virtually abolished (P = 0.001 vs. placebo) the development of sclerosis. Spironolactone significantly decreased PAI-1 mRNA expression in the kidneys of radiated animals (PAI-1 mRNA/GAPDH ratio 0.39 +/- 0.13 vs. placebo 0.84 +/- 0.05, P = 0.006), and there was a significant correlation between the degree of sclerosis and the level of PAI-1 immunostaining within individual rats (R2 = 0.97, P < 0.0001). CONCLUSION: This study is, to our knowledge, the first to demonstrate that aldosterone regulates PAI-1 expression in vivo, and supports the hypothesis that aldosterone induces renal injury through its effects on PAI-1 expression.

Aldosterone↗
PubMed2000

Temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection.

Acute hepatitis B virus (HBV) infections either resolve or progress to chronicity. Identification of early deviations in host-virus responses associated with these outcomes can further differentiate cause-effect mechanisms that initiate and maintain chronicity. Neonatal woodchucks were infected experimentally with the woodchuck hepatitis virus (WHV) at 3 days of age. At 8 or 14 weeks of age (i.e. , the early- or mid-acute stage of infection), whole blood and large surgical biopsies of the liver were obtained from infected animals and uninfected controls. These were stored for later correlating histopathologic responses and viral load with the subsequently determined outcome of infection. As of 1 year postinfection, half of the surgically treated infected woodchucks had developed self-limited infections, while the other half developed chronic infections. The self-limited outcome was characterized by decreased viral load in acute-phase liver and plasma and a generally robust acute hepatic inflammatory response. Comparisons at the same early time points revealed that the chronic outcome was characterized by increasing initial viral load in liver and plasma, and a detectable, but diminished, acute hepatic inflammation. These cotemporal comparisons indicate that there is an early host-response deviation during the acute phase of a developing chronic infection. Continued analysis of the tissues banked from this study will facilitate further temporal characterization of acute-phase mechanisms that determine resolution versus chronicity in WHV infection. Understanding such mechanisms may be useful in the rational design of therapy for established chronic HBV infection.

Acute Disease↗
PubMed2000

Presynaptic modulation of the norepinephrine-induced beta-adrenergic receptor desensitization phenomenon in vivo.

BACKGROUND: In vivo administration of norepinephrine fails to cause beta-adrenergic receptor desensitization. However, short-term exposure of cultured cells to norepinephrine induces the phenomenon in vitro. We sought to identify the local regulatory mechanisms responsible for in vivo beta-adrenergic receptor desensitization in congestive heart failure. METHODS AND RESULTS: Control rabbits received norepinephrine (n = 7) or saline (n = 7) for 1 week, and rabbits with chemical denervation induced by 6-hydroxydopamine also received norepinephrine (n = 7) or saline (n = 7). Myocardial norepinephrine content decreased 80% in both groups of denervated rabbits. beta1-Adrenergic receptor density in denervated rabbits receiving norepinephrine was lower than in those receiving saline but not in control rabbits receiving norepinephrine. Isoproterenol-competition assay revealed that there was a lower number of high-affinity binding sites with loss of guanosine triphosphate shift in denervated rabbits receiving norepinephrine. Isoproterenol-stimulated adenylyl cyclase activity in control rabbits receiving norepinephrine was lower than in those receiving saline. In denervated rabbits receiving norepinephrine, forskolin-stimulated adenylyl cyclase activity was also reduced. Immunoreactive G-protein coupled receptor kinase-2 level was increased in denervated rabbits receiving norepinephrine. CONCLUSION: There are profound alterations in beta-adrenergic receptor signaling after exposure to norepinephrine in the denervated heart. Defects in neuronal uptake may play a pivotal role in beta-adrenergic receptor desensitization in vivo.

Animals↗
PubMed2000

Discrimination among three species of medicinal Scutellaria plants using RAPD markers.

An analysis of random amplified polymorphic DNA (RAPD) was performed using nine accessions of three species of medicinal plants in the genus Scutellaria (S. galericulata, S. lateriflora and S. baicalensis; known collectively as skullcap) in an effort to distinguish between members of these three species. Dried aerial parts of the two species S. galericulata and S. lateriflora are difficult to distinguish morphologically. Ten arbitrary primers produced 92 fragments, and eight of the primers yielded 23 species-specific fragments among the three species. Six fragments were specific for S. galericulata, seven for S. lateriflora and ten for S. baicalensis. When primers A02 and A06 were used in the polymerase chain reaction, RAPD fragments that were specific for each of the three species were generated simultaneously. Primer A02 produced five species-specific fragments: one was specific for S. galericulata; two for S. lateriflora; and two for S. baicalensis. Primer A06 produced three species-specific fragments: one for S. galericulata; one for S. lateriflora; and one for S. baicalensis. The RAPD markers that were generated with these two primers should rapidly identify members of the three species of Scutellaria. The consistency of the identifications made with these species-specific RAPD markers was demonstrated by the observation that each respective marker was generated from three accessions of each species, all with different origins. Furthermore, cluster analysis using the 92 RAPD fragments produced a dendrogram of genetic relatedness that was in good agreement with the taxonomic designations of the three species. Thus, the RAPD markers should be useful for the future identification of members of the three species of medicinal Scutellaria plants.

Plants, Medicinal↗
PubMed2000

Fetal death from abruptio placentae associated with incorrect use of a seatbelt.

A female driver, 24 weeks pregnant, was wearing a three-point seatbelt in the manner usual for nonpregnant women, when her automobile collided head-on with another vehicle. A cardiotocographic examination after the accident revealed the fetus to be alive. Five days after the accident, however, a cardiotocographic examination showed fetal death. At that time, a transverse ecchymotic band on the lower abdominal wall that had not been observed at the first examination was noticed. Eight days after the accident, the mother delivered a macerated female fetus. At autopsy, the baby showed no abnormality, but there was a hematoma on the placental surface toward the uterus. These results suggest that the fetus died of abruptio placentae associated with incorrect placement of the lap belt.

Abruptio Placentae↗
PubMed2000

Traumatic rupture of the basilar artery: report of two cases and review of the literature.

Two cases of traumatic rupture of the basilar artery are reported. In the first case, severe basal subarachnoid hemorrhage (SAH) due to a complete transverse tear of the basilar artery was observed in a 53-year-old restrained male driver who was involved in a head-on collision while intoxicated and drowsy. He lost consciousness shortly after the accident and was admitted to hospital in cardiopulmonary arrest. Intensive resuscitative therapies produced cardiac response, but he died 50 minutes after the accident. The ethanol concentration in his blood and urine was 0.35 and 0.55 mg/ml, respectively. In the second case, SAH due to a similar tear of the basilar artery was observed in a 47-year-old man who received several fist blows to the face while intoxicated. He suddenly lost consciousness after the final blow and was admitted to hospital in cardiopulmonary arrest. Intensive resuscitative therapies produced cardiac response, but he died 6 hours after the event. In these cases, the mechanism of the traumatic rupture of the basilar artery is thought to be overstretching due to hyperextension of the head, and intoxication, drowsiness, or both may have interfered with the decedents' ability to protect themselves; thus, the hyperextension of the head may have been rather forceful.

Accidents, Traffic↗
PubMed2000

Nifedipine-induced inhibition of parasympathetic-mediated vasodilation in the orofacial areas of the cat.

In anesthetized cats, we 1) compared the effects of antihypertensive agents (nifedipine, clonidine, phentolamine, propranolol, and nitroprusside) on the parasympathetic vasodilations elicited by lingual nerve (LN) stimulation in the lower lip and tongue and 2) investigated the mechanisms underlying the inhibitory effect of nifedipine on parasympathetic lower lip vasodilation. At the doses used, each antihypertensive agent reduced systemic arterial blood pressure by approximately 20 mmHg; however, the parasympathetic vasodilation elicited by LN stimulation was significantly reduced only by nifedipine. This inhibitory effect of nifedipine was not seen when LN was stimulated during ongoing repetitive stimulation of the superior cervical sympathetic trunk at 1-Hz frequency. This suggests that the ability of lip and tongue blood vessels to relax to parasympathetic stimulation is not directly impaired by this calcium channel blocker and that the inhibitory effects of nifedipine seen here probably resulted from an action on postsynaptic sites in vascular smooth muscle that caused a reduction in preexisting sympathetic vasoconstrictor tone (by inhibiting calcium influx into the vascular smooth muscle cell).

Administration, Sublingual↗