Search PubMed⌕ Search

Biomedical subjects

Y Tominaga

Publications and source records attributed to Y Tominaga.

At least 19 recordsLinked to original sources
PubMed2001

Statistical analysis of diagnostic failure of fine needle aspiration cytology (FNAC) in breast cancer.

Fine-needle aspiration cytology (FNAC) was performed on 300 patients. Among those, 57 cases failed in accurate diagnosis of malignancy and 243 were successful. Fourteen clinicopathological factors altogether were analyzed to elucidate any correlation with FNAC failure using uni- and multivariate analysis. The univariate analysis in each clinicopathlogical factor showed that these error cases were vaguely palpable cancers, estrogen receptor (ER) positive cancers, small-sized of tumors, scattered type of cancer cell distribution in tumor tissues, with low tumor grade, with low Nottingham prognostic index (NPI), with benign-like ultrasound findings and with low TNM stage. The multivariate analysis revealed tumor grade was the strongest factor for all, followed by cellular distribution type of cancer cells and benign-like ultrasound findings. From these results, we speculated that diagnostic failure of FNAC at first clinic visit seemed to be caused by mainly two histocytological factors: extrinsic factor (structural factors of tissue-like tumor cells' distribution pattern, etc.); and intrinsic one (cellular factors of low atypism such as benign-like ultrasound finding, low tumor grade, and so on).

Analysis of Variance↗
PubMed2000

Quantification of optical signals with electrophysiological signals in neural activities of Di-4-ANEPPS stained rat hippocampal slices.

We have quantified the optical signals of synaptically induced neural activities in an in vitro brain slice preparation in terms of electrophysiological signals. The qualification was done using electrophysiologically well known neural activities in the CA1 area of rat hippocampal slices stained with externally applied fluorescent voltage-sensitive dye (VSD; Di-4-ANEPPS). Together with a newly designed CCD-based digital high-speed camera system and epi-fluorescent optics, our improvements were made on a protocol for staining using a newly designed chamber system. These improvements enabled us to make stable and reliable recordings of optical signals and electrophysiological measurements without affecting the physiological status and to make a quantitative comparison between them. The time course and amplitude of the optical signal showed fair agreement with intracellular and extracellular recordings, and was stable over 2 h. The optical signal followed synaptically induced long-term potentiation (LTP) as monitored by the electrophysiological signals. A regional difference in the amount of LTP was found in optical signals and was confirmed in the electrophysiological signals. These results demonstrate the capabilities of our improved method as an alternative but more potent tool to measure the neuronal activities of brain slice in addition to electrophysiological method.

Action Potentials↗
PubMed2000

High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia.

High serum concentrations of soluble adhesion molecules are present in diabetics, but whether similar levels are present in patients with impaired glucose tolerance (IGT) is unclear. We measured serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin in 128 nondiabetic Japanese subjects. The concentrations of sICAM-1, sVCAM-1, and sE-selectin in IGT patients (n=47) were not different from those in subjects with normal glucose tolerance (NGT; n=81). IGT patients were subdivided into two groups by the results of 75 g OGTT, those with low- (hypoinsulinemia; n=23) or high-insulin (hyperinsulinemia; n=24). The levels of sICAM-1 and sVCAM-1 were not different among NGT and IGT with high-insulin or with low-insulin. However, sE-selectin concentrations were significantly higher in IGT patients with high-insulin than in NGT and IGT with low-insulin (61.1+/-3.4, 47.1+/-1.8 and 43.7+/-3.9 ng/ml, respectively, P<0.001). Adjustment for age and gender did not influence the results. Serum sE-selectin concentrations correlated significantly with the area under the curve of insulin (AUC(insulin)), AUC(glucose), diastolic blood pressure, and triglyceride levels (r=0.35, 0.26, 0.18 and 0.21, respectively), and negatively with HDL-cholesterol levels (r=-0.20). Multiple regression analysis showed that AUC(insulin) was the only independent factor that correlated with sE-selectin levels (P<0.001). Our results indicate that hyperinsulinemia/insulin resistance may be responsible for the elevation of sE-selectin levels.

E-Selectin↗
PubMed2000

Management of renal hyperparathyroidism.

Histopathological and pathophysiological investigations including the genetic approach have been contributing to management of renal hyperparathyroidism (HPT). In renal failure, parathyroid glands initially proliferate diffusely and polyclonally, and then are transformed to monoclonal nodular hyperplasia with aggressive growth potential and diminished expression of both the vitamin D receptor and calcium-sensing receptor. When more than one parathyroid gland progresses to nodular hyperplasia, HPT is refractory to medical treatment. To prevent advanced renal HPT, progression to nodular hyperplasia should be avoided. Control of hyperphosphatemia is very important to prevent advanced renal HPT, but it is usually difficult. Administration of vitamin D metabolites constitutes the most promising form of prophylaxis and should be performed with monitoring of the PTH level to avoid adynamic bone disease. Calcitriol pulse therapy is effective for advanced renal HPT; however, when parathyroid glands progress to nodular hyperplasia, surgical treatment should be considered. Measuring parathyroid volume by ultrasonography is useful for detecting nodular glands and deciding treatment options. Parathyroidectomy (PTx) is an effective treatment for advanced renal HPT. However, the timing of the operation is important, because the improvement of skeletal deformity and vessel calcification inducing high mortality risk cannot be expected even after successful surgery. Total PTx with forearm autograft is a suitable procedure for renal HPT. Recently. selective percutaneous ethanol injection therapy has been adopted as an alternative treatment to PTx, and new vitamin D analogues, phosphate binders without calcium, and calcimimetics have been developed as new options for management of renal HPT.

Humans↗
PubMed2000

Bone metabolic analysis in patients with primary hyperparathyroidism.

Surgical treatment for primary hyperparathyroidism (PHPT) improves not only the calcium and phosphate metabolism but also the bone metabolism. This study was conducted to analyze the bone metabolism after PHPT operations. Bone mineral density (BMD) was measured by dual-photon absorptiometry in 50 patients before and after operation. Osteocalcin (OC) and alkaline-phosphatase activity (Alp) in serum were measured before and after surgery as markers of bone formation, and urinary deoxypiridinorine (DPD) as an index of osteoclast activity. The 50 patients under study were 40 women (80%) and ten men (20%). Increases in BMD at the lumbar spine were remarkable at three months following operation. Slow but steady progress was made until six months, reaching a plateau thereafter. The increase in BMD of lumbar spine was approximately 10%. Urinary DPD was the most sensitive among the three bone metabolic markers. Although serum Alp and OC remained high after operation, urinary DPD was normalized earlier. The discrepancy of bone formation and resorption was shown after operation and this contributed to the increases in BMD in the first six months.

Absorptiometry, Photon↗
PubMed2000

Recognition and catabolism of synthetic heterotrimeric collagen peptides by matrix metalloproteinases.

BACKGROUND: The general consensus is that interstitial collagens are digested by collagenases and denatured collagen by gelatinases, although processing of fibrillar and acetic-acid-soluble collagen by gelatinase A has also been reported. One of the main difficulties in studying the mechanism of action of these matrix metalloproteinases (MMPs) derives from the physicochemical properties of the natural triple-helical collagen, which makes it difficult to handle. RESULTS: Synthetic heterotrimeric collagenous peptides that contain the collagenase cleavage site of human collagen type I and differ in the thermal stability of the triple-helical fold were used to mimic natural collagen and gelatin, respectively. Results from digestion of these substrates by fibroblast and neutrophil collagenases (MMP-1 and MMP-8), as well as by gelatinase A (MMP-2), confirmed that the two classes of enzymes operate within the context of strong conformational dependency of the substrates. It was also found that gelatinases and collagenases exhibit two distinct proteolytic mechanisms: gelatinase digests the gelatin-like heterotrimer rapidly in individual steps with intermediate releases of partially processed substrate into the medium, whereas collagenases degrade the triple-helical heterotrimer by trapping it until scission through all three alpha chains is achieved. CONCLUSIONS: The results confirm the usefulness of synthetic heterotrimeric collagenous peptides in the folded and unfolded state as mimics of the natural substrates collagen and gelatin, respectively, to gain a better a insight into the proteolytic mechanisms of matrix metalloproteinases.

Binding Sites↗
PubMed2000

Acute humoral rejection of kidney allografts in patients with a positive flow cytometry crossmatch (FCXM).

The patients with a positive flow cytometry crossmatch (FCXM) are categorized as a high-risk group causing hyperacute or accelerated acute rejection after kidney transplantation. According to the successful results of ABO-incompatible renal transplantation, we have performed the living related transplant operations in the recipients with positive FCXM for donor T cells, but having a negative complement-dependent lymphocytotoxic reaction test. We have followed the clinical course of 4 FCXM-positive patients, and 2 of them have developed acute humoral rejection. We report the strategies for FCXM-positive living kidney transplantations and the characteristics of pathological findings of acute humoral rejection in FCXM-positive renal transplants. We have had few episodes of acute humoral rejection in ABO-incompatible kidney transplantations under immunosuppressive regimens, including cyclophosphamide, but 2 patients of 4 with FCXM-positive kidney transplantations developed acute humoral rejections. The differences in immunosuppressive regimen between ABO-incompatible and FCXM-positive kidney transplantations concern anti-lymphocyte globulin (ALG) and splenectomy. We have not performed splenectomy and ALG administration in FCXM-positive kidney transplantations. Severe acute rejection episodes have been experienced on post-operative days 7 and 9 in 2 of 4 FCXM-positive recipients. The early acute rejection episodes were clinically and pathologically diagnosed as typical humoral rejections. We have examined an immunofluorescent study to prove the diagnosis of humoral rejection in FCXM-positive kidney transplantations; both immunoglobulin M and C3 were positive for the whole course of humoral rejection. The 2 patients with acute humoral rejection recovered after treatment with double filtration plasmapheresis or plasma exchange to remove their anti-donor antibodies. The gold standard of success in FCXM-positive kidney transplantations is to suppress the production and reduce the level of anti-donor antibodies after transplant operations.

ABO Blood-Group System↗
PubMed2000

Increased insulin sensitivity and decreased insulin secretion in offspring of insulin-sensitive type 2 diabetic patients.

To investigate the early defects of glucose metabolism in insulin-sensitive type 2 diabetes, we performed oral and frequently sampled intravenous glucose tolerance tests (OGTT and FSIGT) with minimal model analysis in 15 offspring of Japanese type 2 diabetics with normal insulin sensitivity (insulin resistance index of homeostasis model assessment [HOMA-R] < 2.0) and in 20 healthy control subjects without a family history of type 2 diabetes. The frequency of impaired glucose tolerance (IGT) was 40% (6 of 15) in the offspring and 0% (0 of 20) in the controls. Fasting plasma glucose (4.8 +/- 0.1 v4.6 +/- 0.1 mmol/L, P = .18) and immunoreactive insulin ([IRI] 29.9 +/- 2.5 v 28.3 +/- 2.5 pmol/L, P = .64) were comparable between the offspring and the controls. The rate of glucose disappearance (KG) was significantly lower in the offspring versus the control group (2.00 +/- 0.22 v 2.60 +/- 0.17 min(-1), P= .03). The insulin sensitivity index (Si) was significantly greater in the offspring versus the controls (2.68 +/- 0.41 v 1.71 +/- 0.17 x 10(-4) min(-1) x pmol/L , P = .02). First-phase insulin secretion (FPI) to intravenous glucose was significantly lower in the offspring versus the control group (886 +/- 110 v 2,296 +/- 267 min x pmol/L, P< .01). Glucose effectiveness (SG) was comparable between the offspring and control groups. The disposition index (Si x FPI) was significantly lower in the offspring versus the controls (2,106 +/- 256 v 3,652 +/- 490 x 10(-4), P = .02). When the offspring were subdivided into 2 groups by glucose tolerance status, both normal glucose tolerance (NGT) offspring and IGT offspring showed a significant decrease in FPI and increase in Si. Thus, although the offspring of insulin-sensitive type 2 diabetics had increased insulin sensitivity, the impairment in insulin secretion was more dominant. Our results suggest that the early metabolic abnormality in insulin-sensitive type 2 diabetes is an insulin secretory dysfunction despite increased insulin sensitivity.

Adult↗
PubMed2000

Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia.

BACKGROUND: Heart-rate (HR) variability is an important predictor of mortality in patients with heart disease. We examined the effects of cilostazol, a quinolinone derivative, on HR and HR variability in patients with chronic atrial fibrillation associated with bradycardia episodes. PATIENTS AND METHODS: Thirteen patients with chronic atrial fibrillation associated with bradycardia episodes (minimal HR <40/min and/or pauses, ie, episodes with an RR interval > 2.5 sec) received cilostazol (100 or 200 mg/day) orally for at least 2 months and 24-hour Holter electrocardiography was performed before and after the start of cilostazol administration. RESULTS: Minimal HR was significantly increased, by an average of 14 beats/min (bpm), at 3.3 +/- 0.8 weeks (mean +/- SD) after the start of cilostazol treatment. The number of pauses was significantly decreased. As a consequence, mean HR was increased by an average of 18 bpm. Maximal HR was also increased by an average of 19 bpm. The circadian variation of the HR, determined by cosine fitting, was not changed by cilostazol treatment. The time-domain HR variabilities, ie, the SD of the mean RR interval and the SD of the 5-minute mean RR intervals, were also unchanged. New York Heart Association functional class was significantly improved and the plasma atrial natriuretic polypeptide level was significantly decreased after the initiation of cilostazol treatment. CONCLUSION: Cilostazol improves the slow HR episodes associated with chronic atrial fibrillation and maintains the HR circadian variation and time-domain variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with chronic atrial fibrillation.

Aged↗
PubMed2000

Evaluation of filtration leucocytapheresis for use in the treatment of patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the efficacy of filtration leucocytapheresis (LCP) for rheumatoid arthritis (RA). METHODS: LCP was carried out three times, with 1 week separating each session, in 25 drug-resistant RA patients. RESULTS: During each session, 96, 98, 61, 84 and 8% of the granulocytes, monocytes, lymphocytes, platelets and erythrocytes, respectively, that entered the LCP filter were removed. The number of granulocytes, monocytes and lymphocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. On average, 110 x 10(8) granulocytes, 5.23 x 10(8) monocytes, and 20.5 x 10(8) lymphocytes were removed during LCP therapy. Assessment of RA before and after LCP showed a substantial and rapid improvement in the tender joints counts, swollen joint counts, and patient's and physician's assessments. No adverse reactions or complications were noted. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels decreased following LCP, although the change in the latter parameter was statistically insignificant. The concentrations of serum albumin, gamma-globulin, IgG, IgM, CH50 and rheumatoid factor titres did not change during or after LCP. Careful analysis indicated that 16 of 25 patients with RA showed > or =20% improvement following LCP therapy. CONCLUSIONS: Our results suggest that filtration LCP to remove leucocytes from the peripheral blood exerts an immunomodulatory effect in patients with RA.

Arthritis, Rheumatoid↗
PubMed2000

Secretory leukoprotease inhibitor augments hepatocyte growth factor production in human lung fibroblasts.

Secretory leukoprotease inhibitor (SLPI), an 11.7-kD nonglycosylated serine protease inhibitor, is produced and released into the fluids of mucosal surfaces including human lung. It comprises two domains with homologous amino acid sequences: the N-terminal domain possessing antibacterial activity, and the C-terminal domain with antiprotease activity. Here we report the positive regulation of hepatocyte growth factor (HGF) production in human lung fibroblasts exerted by SLPI or its C-terminal domain under physiologic concentrations (1 to 10 microM). This HGF production by SLPI was unaffected by the addition of interleukin (IL)-1 receptor antagonist. In contrast, human skin fibroblasts exerted no SLPI-stimulated increase in HGF production, despite the fact that IL-1beta increased HGF production with an intensity similar to that of human lung fibroblasts. Both the time-course and dose-response studies in human lung fibroblasts revealed that the induction of HGF messenger RNA (mRNA) and protein occurred in parallel, indicating that the mechanism existed at the steady-state mRNA level. A synthetic elastase inhibitor failed to induce HGF, but alpha(1)-antitrypsin also stimulated HGF production in lung fibroblasts. Inactivation of the antiprotease activity of SLPI or its C-terminal domain by an oxidizing agent (N-chlorosuccinimide) abolished their stimulatory effect on HGF production. These findings demonstrate that SLPI exerts a novel HGF induction and functions as an anti-inflammatory and regenerative factor in addition to its role in protease inhibition.

Binding Sites↗
PubMed2000

Inhibitory effects of amlexanox on carbachol-induced contractions of rabbit ciliary muscle and guinea-pig taenia caecum.

Instillation of amlexanox, an anti-allergic drug, over a long period improves myopia in some allergy patients and in monkeys. The relaxing effect of amlexanox on persistent contraction of ciliary muscle may be involved in the improvement of myopia. In this study, the mechanism of the noncompetitive inhibition of carbachol-induced contractions by amlexanox (1-100 microM) was investigated in isolated smooth muscle preparations of the rabbit ciliary body and guinea-pig taenia caecum. In ciliary muscles, amlexanox (100 microM) inhibited both the phasic and tonic components of carbachol-induced contractions even in the presence of cyclopiazonic acid (10 microM) where the function of the sarcoplasmic reticulum was impaired, while diltiazem (3.2, 32 microM) did not. In taenia caecum, diltiazem (3.2 microM) slightly inhibited the phasic component and abolished the tonic component of carbachol-induced contractions. Amlexanox also abolished the tonic component, but it did not decrease the 45Ca2+ uptake into taenia caecum smooth muscle cells induced by carbachol. Amlexanox did not increase the cyclic adenosine monophosphate (cyclicAMP) content of ciliary muscles in the presence of 3-isobutyl-1-methylxanthine (10 microM), while forskolin (1 microM) did. Gel-shift assay showed that the inhibition of carbachol-induced contractions by amlexanox was accompanied by a decrease in phosphorylation of the 20-kDa myosin light chain in taenia caecum tissue preparations. Amlexanox had no effect on calmodulin activity, whereas it inhibited phosphorylation of the myosin light chain by purified myosin light-chain kinase from chicken gizzard. These results suggested that amlexanox may not affect either Ca2+ mobilization or calmodulin activity, although it inhibits myosin light-chain kinase, which may inhibit carbachol-induced contraction.

Aminopyridines↗
PubMed2000

Exponential hyperbolic sine function fitting of heart rate response to constant load exercise.

We attempted to fit heart rate (HR) changes induced by constant exercise loads of different intensities to an exponential hyperbolic sine curve by the least-squares method, and we compared the results with the fitting of the changes to exponential curves. Seven healthy male volunteers performed three different intensities of constant-load exercise on a bicycle ergometer. The exponential hyperbolic sine function adequately fitted the HR responses induced by all three different intensities of loads: low (30 W: correlation coefficient, r = 0.68 +/- 0.13, mean +/- SD), moderate (75 W: r = 0.93 +/- 0.07) and high (125 W: r = 0.97 +/- 0.02). The first-order exponential curve fitted only the moderate load response. Although the second-order exponential equation fitted the HR response for both the moderate and high loads, the equation did not fit the low-load response (r = 0.43 +/- 0.26). In low-load exercise, the sum of the power of the residuals for the exponential hyperbolic sine curve fitting was significantly smaller than that for the first- or second-order exponential curve fitting. In conclusion, the exponential hyperbolic sine function is useful for quantitative analyses of the HR response to exercise loads of various intensities.

Adult↗
PubMed1999

Development of a cell-free binding assay for rat ICAM-1/LFA-1 interactions using a novel anti-rat LFA-1 monoclonal antibody and comparison with a cell-based assay.

The importance of the interaction between lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) in the progression of inflammatory responses in vivo has been demonstrated mainly in rats. The present study was undertaken to develop binding assays suitable for measuring the rat ICAM-1/LFA-1 interaction in vitro. We first examined binding of rat T lymphoma FTL43 cells, which express LFA-1, to immobilized rat ICAM-1. Although FTL43 cells bound avidly to immobilized ICAM-1 and the binding was abolished with anti-LFA-1 monoclonal antibodies (mAbs), the binding was not completely inhibited by most anti-ICAM-1 mAbs. We next purified rat LFA-1 from FTL43 cells and constructed a cell-free binding assay. By using a newly developed anti-rat LFA-1 mAb RL14/9, which does not inhibit ICAM-1/LFA-1 interactions, binding of purified rat LFA-1 to immobilized ICAM-1 was successfully detected, whereas only a low signal to noise ratio was observed when binding of ICAM-1 to immobilized LFA-1 was examined. Moreover, we found that simultaneous addition of purified LFA-1 and biotinylated RL14/9 to ICAM-1-coated wells resulted in more sensitive detection of rat ICAM-1/LFA-1 binding. The binding was completely blocked with both anti-LFA-1 and anti-ICAM-1 mAbs and was much more sensitive to inhibition by the ICAM-1-IgG chimera, as compared with the cell-based assay. These results indicate that the cell-free binding assay provides a rapid and sensitive method for screening rat ICAM-1/LFA-1 antagonists, whose therapeutic effect on inflammatory diseases can further be evaluated in vivo.

Animals↗
PubMed1999

Synaptic organization in the lamina of the superposition eye of a skipper butterfly, Parnara guttata.

The first optic neuropil of the compound eye, the lamina, of the skipper butterfly Parnara guttata, was examined by light microscopy after Golgi-impregnation and by electron microscopy (EM) to clarify the cellular and synaptic organization. In the lamina, five different types of lamina neurons (L neurons) were characterized by using Golgi-impregnation. By EM, each cartridge was found to contain all nine receptor axons from an ommatidium, five L neurons, and a few putative centrifugal elements. Axons from photoreceptors (retinula cells) R2, R3, R4, R6, R7, and R8 terminate as short visual fibers (svfs) in the lamina cartridge. Those from R1, R5, and R9 penetrate the lamina and terminate in the medulla as long visual fibers (lvfs). In the cartridges, the synaptic contacts were formed from svfs onto L neurons, from the lvfs of R1 and/or R5 to the lvf of R9 and L neurons, and from the lvf of R9 to L neurons. The putative centrifugal fibers also make synapses to svfs and L neurons. At the most distal level of the cartridge, one of the centrifugal fibers containing dense-core vesicles makes presynaptic contacts to the putative long collaterals of the L neuron. A novel characteristic feature of this lamina is that svfs of R3 and R7 and the lvfs of R1 or R5 have long collaterals extending into neighboring cartridges. Presynaptic contacts were confirmed in such long collaterals from the svf. These results imply that receptor axons provide direct intercartridge connections as well as providing indirect connections to neighboring cartridges by way of their input upon L neurons.

Adaptation, Ocular↗