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Biomedical subjects

M Shimizu

Publications and source records attributed to M Shimizu.

At least 523 records · Page 29Linked to original sources

Isolation and amino acid sequence of flavostatin, a novel disintegrin from the venom of Trimeresurus flavoviridis.

Flavostatin, a novel disintegrin purified from the venom of Trimeresurus flavoviridis, consists of 68 amino acids, including an Arg-Gly-Asp sequence and 12 Cys residues at positions highly conserved among disintegrins. The N-terminal sequence of flavostatin was identical to those of triflavin and flavoridin, previously reported disintegrins from the Trimeresurus flavoviridis venom. Differences among the C-terminal sequences of these disintegrins are considered to affect their biological potencies. Isolated flavostatin inhibited ADP collage, and thrombin receptor agonist peptide-induced platelet aggregation in human platelet-rich plasma with an IC50 range of 59 to 98 nM. Contrary to expectations, these values were similar to those for triflavin.

Adenosine Diphosphate↗

Transepithelial transport of oligopeptides in the human intestinal cell, Caco-2.

The transepithelial transport of oligopeptides (of more than 4 residues) was studied by using human intestinal Caco-2 cell monolyers. The susceptibility to the brush-border peptidases was observed to be one of the primary factors which decide the transport rate. The apical-to-basolateral transport mechanism was investigated by using bradykinin and GGYR which were resistant to cellular peptidases. The intracellular pathway, probably the adsorptive transcytosis, was suggested to be involved in the transport of bradykinin and its analogues, the transport rate being particularly dependent on the hydrophobic properties of the peptides. On the other hand, the tetrapeptide such as GGYR was suggested to be transported mainly via the paracellular pathway.

Biological Transport↗

Effects of triphenyltin chloride and five other organotin compounds on the development of imposex in the rock shell, Thais clavigera.

The imposex promotion activities of six organotin compounds--tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPT), diphenyltin (DPT) and monophenyltin (MPT)--were examined by injection experiments with the rock shell, Thais clavigera (Prosobranchia; Muricidae). TPT and TBT had strong effects on the development of imposex in the rock shell (p<0.001). The other organotin compounds (DBT, MBT, DPT and MPT) had no or less effects on the development of imposex in T. clavigera. The difference between the effects of TPT and TBT was statistically insignificant (p>0.01). The effects of these compounds are estimated, from the relationships between TBT or TPT concentration in tissue and mean penis length of females after injections, to be approximately the same.

Journal Article↗

Transition of serum vitellogenin cycle in Sakhalin taimen (Hucho perryi).

A specific and sensitive enzyme-linked immunosorbent assay (ELISA) and a single radial immunodiffusion (SRID) were developed for measurement of serum vitellogenin (Vg) levels in Sakhalin taimen (Hucho perryi). Regarding specificity for serum Vg, an antiserum raised against lipovitellin of taimen (a-Lv) was adequate for both assays. ELISA and SRID could detect Vg in serum at concentrations as low as 10 ng/ml and 25 micrograms/ml, respectively. In estrogen administration experiments, the level of serum Vg began clearly increasing within 12 to 24 hr after injection of immature females with estradiol-17 beta (E2). The appearance and levels of Vg in males treated with E2 were delayed and smaller, respectively, than for females. Vg levels varied throughout natural vitellogenesis from 0-4 micrograms/ml (3 years old) to approximately 30 mg/ml (5-6 years old). We observed an early transitory peak of serum Vg levels (primary reaction) at the time of early vitellogenesis and chronic high Vg levels (for 6-7 months) in winter period before ovulation. Changes of serum E2 levels were correlated with Vg levels. However, E2 levels decreased a month earlier than Vg levels near ovulation. It appears that the duration of vitellogenesis in taimen is considerably longer than that in other salmonids, lasting more than 2 years.

Animals↗

Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice.

Neuropilin is a neuronal cell surface protein and has been shown to function as a receptor for a secreted protein, semaphorin III/D, that can induce neuronal growth cone collapse and repulsion of neurites in vitro. The roles of neuropilin in vivo, however, are unknown. Here, we report that neuropilin-deficient mutant mice produced by targeted disruption of the neuropilin gene show severe abnormalities in the trajectory of efferent fibers of the PNS. We also describe that neuropilin-deprived dorsal root ganglion neurons are perfectly protected from growth cone collapse elicited by semaphorin III/D. Our results indicate that neuropilin-semaphorin III/D-mediated chemorepulsive signals play a major role in guidance of PNS efferents.

Animals↗

Role of increased production of monocytes TNF-alpha, IL-1beta and IL-6 in psoriasis: relation to focal infection, disease activity and responses to treatments.

To evaluate the immunological function of peripheral blood monocytes (PBMC) in psoriasis, we measured spontaneous production of the inflammatory cytokines, TNF-alpha, IL-1beta and IL-6 from the PBMC of psoriasis patients, by enzyme linked immunosorbent assay (ELISA). The production of all three inflammatory cytokines by psoriatic PBMC was significantly higher than that by normal control PBMC. PBMC sampled from active psoriasis produced three cytokines significantly higher than samples from inactive psoriasis. In addition, IL-1beta and TNF-alpha production showed a positive relation to clinical severity, but IL-6 did not. TNF-alpha production increased much more than did the others. Therefore, the TNF-alpha to IL-1beta ratio was significantly higher, even in inactive psoriasis, than that of the normal control. In relation to focal infection, psoriatic PBMC sampled 3 h after a tonsillar provocation test increased cytokine production, compared with the level before provocation. The cases which responded to tonsillectomy or systemic methotrexate therapy, but not the non-responding cases, showed a significant decrease in PBMC cytokine productivity. These results strongly suggest that inflammatory cytokines, especially TNF-alpha, from monocytes are involved in the pathogenesis of psoriasis, and activated monocytes may work as an effective mediator of focal infection in skin lesions.

Adolescent↗

Submandibular gland duct endoscopy. Diagnostic value for salivary duct disorders in comparison to conventional radiography, sialography, and ultrasonography.

The purpose of this study is to evaluate the usefulness of endoscopy as a procedure for the diagnosis of submandibular gland duct disorders. Endoscopy of the submandibular glands was performed on 12 patients with symptoms of obstructive sialoadenitis to identify the cause of obstruction. The endoscopic findings were then compared to those of diagnostic procedures such as conventional radiography, sialography, and ultrasonography. Six normal subjects also underwent endoscopy to better understand the normal findings of the duct system. Endoscopy demonstrated salivary gland calculus in 5 of 12 patients, which was revealed as filling defects on sialograms and as strongly echogenic structures on ultrasonograms in 4 of the patients. Endoscopy revealed secretion plugs, secretion plaques, and/or stenosis, which could not be seen by any other diagnostic procedures in 5 patients, as the cause of recurrent swelling in all 7 patients not demonstrating sialolith. Abnormal findings of the duct wall such as vasodilatation, fibrosis, edema, or erythema were seen in four patients, three of whom exhibited dilatation of the duct system on sialograms. In four patients, a decreasing internal echo level of the gland was seen on ultrasonograms. Our initial results for submandibular gland duct endoscopy thus appear to be promising.

Adult↗

Experimental detection of canine haemoglobin (occult blood) in canine faeces by reversed passive latex agglutination.

A reversed passive latex agglutination test (RPLA) using anti-canine haemoglobin (Hb) antibody was developed for detecting bleeding in the lower digestive organs in dogs, and its applicability as a simple test for faecal occult blood was assessed. In Ouchterlony's gel immunodiffusion test, the anti-canine Hb antibody used to sensitize the latex reacted with canine Hb but not with Hbs, plasmas or meat extracts from pigs, goats, sheep, cattle, horses or chickens, or with fish extracts. Using latex sensitized with 50 micrograms/mg of anti-canine Hb IgG antibody, the lowest limit of detection for canine Hb was 21 micrograms/ml, and the latex reacted negatively with all test specimens other than canine Hb. In an in vitro experiment with a mixture of canine faeces and erythrocytes, the antigenicity of the Hb was found to undergo only very slight changes even when the specimens were allowed to stand for 12 h at room temperature. Hb could not be detected by RPLA in any of four successive faecal samples from three experimental dogs after infusion of autologous blood (5, 3 or 1 ml) into the stomach. In 3 other experimental dogs given an infusion of autologous blood (5, 3 or 1 ml) into the ascending colon, the presence of Hb was confirmed by RPLA in all four successive faecal samples obtained from those which received 5 or 3 ml of blood and in all except that obtained following the first defecation from the animal which had received 1 ml of blood.

Animals↗

Computed tomography of carcinoma of the upper gingiva and hard palate: correlation with the surgical and histopathological findings.

OBJECTIVES: To clarify the diagnostic utility of CT in the evaluation of carcinoma of the maxillary gingiva and hard palate. METHODS: The CT scans of 27 patients with squamous cell carcinoma of the upper gingiva and hard palate were reviewed. Tumor extent and bone destruction were compared with the surgical and histopathological findings to estimate the sensitivity, specificity and accuracy of CT. RESULTS: The primary tumor was detected by CT in 89% of patients. The grade of bone destruction determined by CT correlated well with that verified at surgery or by histopathological examination. The sensitivity, specificity, and accuracy of CT for invasion to the buccal mucosa were 64%, 89% and 75% respectively. For maxillary sinus invasion, CT showed low specificity but high sensitivity. The accuracy was 86% when the criterion for sinus invasion was the presence of an enhanced mass continuous with the primary tumor. CONCLUSION: CT is helpful for the evaluation of tumor extent in the upper gingiva and hard palate carcinoma. However, invasion of the maxillary sinus should be considered carefully, because CT findings suggestive of destruction of the floor of the maxillary sinus are not always consistent with sinus invasion.

Adult↗

Transmission of GB virus C by blood transfusions during heart surgery.

BACKGROUND AND OBJECTIVES: Hepatitis-causing viral agents other than those designated A to E are being reported. Their epidemiology, modes of transmission, and infectivity are not yet clear, although they may be transmitted by transfusion. MATERIALS AND METHODS: Thirty five patients underwent open-heart surgery, receiving an average of 10.2 +/- 10.8 (range 1 to 35) units of blood. The patients were investigated postoperatively for the RNA of the putative non-A-to-E hepatitis virus designated as GB virus C (GBV-C). RESULTS: Four patients (12%) acquired GBV-C RNA in the serum within 2 to 4 weeks after the operation. GBV-C RNA was detected in at least one of the blood units received by three patients, all of whose units were available for testing, with a sequence in the nonstructural 3 region identical to that from the corresponding patient. Three patients developed elevated alanine aminotransferase levels which persisted for two weeks or longer in two of them. CONCLUSIONS: GBV-C is transmissible by transfusion and can induce elevated transaminase levels.

Adolescent↗

Serum pyridinoline crosslinks as markers of tumour-induced bone resorption.

OBJECTIVE: To assess serum pyridinoline (Py) and deoxypyridinoline (dPy), using a new high-performance liquid chromatography (HPLC) method, as a serum marker to determine the incidence of metastatic bone disease in an animal model and in the monitoring of patients with or without metastatic bone disease from prostate cancer and renal cell carcinoma (RCC). PATIENTS, MATERIALS AND METHODS: Female C3H/He mice (8-12 weeks old) received a subcutaneous injection of tumour-cell suspensions of serially transplanted MBT tumours. The tumour cells induced osteolysis associated with osteoclast proliferation and serum samples were evaluated for Py and dPy using HPLC. The growth of the tumour macroscopically and histologically, and the extent of bone loss assessed by radiography, were compared with the serum Py and dPy level. In the clinical study, patients with or without bone metastases from RCC (24 patients) or prostate cancer (37 patients) were monitored using the same techniques and the number and extent of bone metastases compared with serum Py and dPy levels both in these patients and in 84 healthy control subjects. RESULTS: There was a significant correlation between the bone loss evaluated by radiography and the level of serum Py in the animal model. Patients with bone metastases from RCC had higher values of Py and dPy than patients without known metastatic bone disease. The serum Py level increased in two patients as metastatic bone disease progressed. Similarly, in patients with prostate cancer, the mean level of serum Py and dPy was higher in patients with bone metastasis than in the control group, and also higher than that in patients without metastases. The serum Py and dPy levels could also distinguish patients with metastatic bone disease with and without a lytic component. CONCLUSION: Measurements of serum Py appear to provide a good index of increased bone resorption induced by experimental tumours and in patients with bone metastases from RCC and prostate cancer.

Aged↗

Down-regulation of 5-hydroxytryptamine7 receptors by dexamethasone in rat frontocortical astrocytes.

Astrocytes derived from rat frontal cortex contain 5-hydroxytryptamine7 (5-HT)7 receptors positively coupled to adenylyl cyclase. In the present study, we investigated the effects of glucocorticoids on adenylyl cyclase activity and 5-HT7 receptor gene expression in astrocytes. Addition of dexamethasone (0.01-100 nM, 12-72 h) to the culture medium decreased cyclic AMP formation induced by 5-HT in a time- and concentration-dependent manner. Dexamethasone treatment (10 nM, 48 h) reduced maximum responses of cyclic AMP formation induced by 5-HT and 5-carboxamidotryptamine without alterations in the EC50 value. In contrast, treatment with the mineralocorticoid aldosterone (48 h) had no significant effects on 5-HT-induced cyclic AMP formation with concentrations up to 10 nM. It was observed that dexamethasone treatment (1-100 nM, 3-72 h) also decreased the expression of 5-HT7 receptor mRNA, using reverse transcription and polymerase chain reaction analysis. A significant reduction in expression of 5-HT7 mRNA appeared at 3 h of dexamethasone treatment and reached a maximum at 6 h of treatment. On the other hand, dexamethasone treatment (10 nM, 48 h) did not affect basal levels of cyclic AMP and cyclic AMP synthesis stimulated by isoproterenol, N-ethylcarboxamidoadenosine, cholera toxin, and forskolin. These results suggest that dexamethasone decreases the expression of the 5-HT7 receptor gene and, consequently, 5-HT7 receptor-mediated signal transduction in frontocortical astrocytes.

Adenosine↗

[Differential diagnosis of tumorous space-occupying lesions of the parotid gland: angiolymphoid hyperplasia with eosinophilia and Kimura disease].

BACKGROUND: Subcutaneous mass lesions of the head and neck are common in angiolymphoid hyperplasia with eosinophilia (ALHE) as well as in Kimura's disease, most often in a periauricular location in young and middle aged adults. Often these benign angioproliferative lesions of unknown etiology will be misdiagnosed as parotid tumors although the majority are paraglandular. Whereas ill-defined lesions involving the parotid gland are frequently observed in Kimura's disease, only one case of intraparotid ALHE is reported in the literature. CASE REPORT: To this we add one further case: a 24-year-old man with a solid and well displaceable tumor of the left preauricular region. At ultrasound and intraoperatively we found a well demarcated tumor with high central vascularization surrounded by multiple networks of veins. One larger artery entered the lesion directly, visible as vascular structure on the cut surface. This blood vessel may have represented a vascular pattern (3 mm in diameter) that was identified as an artery by flow velocity measurement at duplex sonography. Histopathologically we saw the characteristic features of ALHE: numerous capillary proliferations showing prominent epithelioid endothelia cells with typical "hop nail" appearance, focal lympho-plasmacellular infiltrations and many eosinophils. The most conspicuous microscopic feature was a large thick-walled artery with total occlusions of the lumen that partially corresponded to duplex sonographic and macroscopic findings. CONCLUSION: In our opinion, this may be indicative of a primary arterial disorder with secondary vascular proliferation and chronic inflammation. The treatment of choice is local excision with a safe margin of healthy tissue, since insufficient removal can result in recurrence.

Adult↗

Characterization and regulation of taurine transport in Caco-2, human intestinal cells.

We characterized the taurine transport system in human intestinal Caco-2 cells and showed that it is subject to adaptive regulation. The activity of taurine transport in Caco-2 cells was evaluated by means of an Na+- and Cl(-)-dependent high-affinity transport system, the characteristics of which were similar to those of the beta-amino acid-specific taurine transport system previously described for various tissues. The activity of taurine transport was down-regulated on culturing in taurine-containing medium. This taurine-induced down-regulation was dependent on both the incubation time with taurine and the concentration of taurine. Hypotaurine and beta-alanine were also capable of inducing this adaptive regulation, whereas alpha-amino acids and gamma-aminoisobutyric acid were not. Kinetic analysis of control and taurine-treated cells suggested that the down-regulation was associated with a decrease in the maximal velocity of taurine transport and also with a decrease in the affinity of the taurine transporter. Cycloheximide treatment weakened the taurine-induced down-regulation. The mRNA level of the taurine transporter (HTAU type) in taurine-treated cells was markedly decreased compared with in control cells. These results indicate that a complex regulatory mechanism is involved in this down-regulation.

Adaptation, Physiological↗

A case of systemic malignant lymphoma with intestinal involvement of lymphomatous polyposis type.

Multiple lymphomatous polyposis is a rare type of intestinal lymphoma characterized by non-Hodgkin's lymphoma of follicular mantle cell origin and extremely poor prognosis. We report a case of systemic lymphoma with the intestinal involvement of multiple lymphomatous polyposis. Although radiographic and endoscopic features of the case were compatible with multiple lymphomatous polyposis, histologic evidence suggested the diagnosis of diffuse large cell lymphoma rather than mantle cell lymphoma. Our case seems to be unique in its histologic findings and also in its prognosis, because the patient has been alive for more than 50 months after diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗

Sequential subtraction scintigraphy with 99Tcm-RBC for the early detection of gastrointestinal bleeding and the calculation of bleeding rates: phantom and animal studies.

To improve the detectability of gastrointestinal (GI) bleeding, we have developed a new method, 'sequential subtraction scintigraphy' (SSS) with 99Tcm-labelled red blood cells (RBC). Sequential subtraction scintigrams were obtained by subtracting 5 min interval images from each other using a digital gamma camera. With this method, we are able to detect the bleeding site and calculate the bleeding rate earlier because of the lower background activity. The results of the present study demonstrate that the minimum detectable bleeding rate was 0.05 ml min-1 in both a phantom and an animal model. The minimum detectable activity volumes within 10 min were 0.5 ml by SSS and more that 3 ml by conventional non-subtraction scintigraphy (CNS). The bleeding rates calculated with the subtraction method correlated well with the actual syringe pump rates. The detectability of GI bleeding by SSS and CNS in animal models was compared using the area under receiver operator characteristic (ROC) curves. The results showed that SSS significantly increased the area under the ROC curves from 0.55 +/- 0.05 to 0.79 +/- 0.04 for the 10 min image set and from 0.65 +/- 0.05 to 0.83 +/- 0.04 for the 30 min image set (Z = 5.45, P < 0.0001 and Z = 4.36, P < 0.0001, respectively). These results suggest that sequential subtraction scintigraphy with 99Tcm-RBC is an effective method for the early detection of GI bleeding when compared with the conventional non-subtraction method.

Adult↗

Scleroderma renal crisis complicated by hemolytic uremic syndrome in a case of elderly onset systemic sclerosis.

We report a case of renal crisis in a patient with elderly onset systemic scleroderma (SSc). A sixty-one-year-old woman was diagnosed as having SSc with rapidly advancing generalized skin sclerosis. After experiencing an upper respiratory infection, she suddenly developed renal failure, hemolytic anemia and malignant hypertension. Laboratory examination revealed uremia with a significantly high plasma renin level. Ophthalmologic study revealed Keith-Wagner's retinopathy Grade IV. Combination therapy including captopril, systemic corticosteroid and prostaglandin E1 venous infusion for the hemolytic uremic syndrome was effective and saved her from the renal crisis. However, her renal function deteriorated and she needs permanent hemodialysis. Rapidly progressive skin sclerosis in SSc, especially in elderly onset cases, suggests a high risk for renal crisis and indicates the need for careful consideration of hypertension and renal function.

Acute Disease↗