Biomedical subjects

H Miyazaki

Publications and source records attributed to H Miyazaki.

At least 73 records · Page 4Linked to original sources

PubMed2001

The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing biliary drainage and their association with the impairment of biliary secretory function.

OBJECTIVES: Percutaneous transhepatic biliary drainage (PTBD) has been believed to reduce hyperbilirubinemia in patients with obstructive cholestasis and to lessen liver injury through bile acid retention. The efficacy may be closely related to the capability of cholestatic liver to produce and secrete bile, which in turn depends on the expressions and functional activities of plasma membrane transporters in the liver. The aim of the present study was to determine the expression levels of these transporters in the cholestatic liver of patients undergoing PTBD. METHODS: A total of 24 patients who had experienced obstructive cholestasis and had undergone preoperative PTBD were included in the study. Liver biopsy specimens were analyzed to determine the expression levels of the multidrug resistance-associated proteins (MRP) MRP2 and MRP3 and the canalicular bile salt export pump BSEP in the liver. RESULTS: The messenger RNA (mRNA) levels of MRP2, the canalicular bilirubin conjugate export pump, and bile salt export pump (BSEP) were unchanged in liver specimens from the 14 patients well drained by PTBD but were reduced in specimens from the 10 patients poorly drained, compared to the levels of control subjects. Immunostainings of MRP2 and BSEP outlined the canalicular membrane domain but seemed fuzzy to varying degrees in specimens obtained from cholestatic liver, especially in specimens from liver that had been poorly drained, in contrast to the linear and intense localization in the liver of control subjects, correlating with the impaired bilirubin conjugate and bile acid secretion. The mRNA of MRP3, functioning as an inducible export pump for bilirubin conjugate and bile acid, was expressed not only in the cholestatic liver but also in the liver of control subjects, and the mRNA level was increased in specimens from both the cholestatic liver that had been well drained and from the liver that had been poorly drained. Immunostaining of MRP3 was observed in the epithelia of intrahepatic bile ducts in the liver of both control subjects and cholestatic patients, and in the epithelia of proliferated bile ductules and the hepatocytes surrounding the portal tracts in the cholestatic liver. CONCLUSIONS: From the results of the present study, it is concluded that 1) the mRNA and immunohistochemical expression levels of MRP2 and BSEP may be altered in the cholestatic liver of patients undergoing PTBD; 2) both the decreased mRNA levels and the diminished canalicular membrane localization may be associated with the impairment of bile formation and secretion, i.e., the efficacy of PTBD; and 3) upregulated MRP3 in the cholangiocytes and hepatocytes may play a significant role in bile acid transport in the cholestatic hepatobiliary system.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

Short-Term biomechanical adaptation of the rat carotid to acute hypertension: contribution of smooth muscle.

The biomechanical adaptation of the arterial wall to hypertension has been studied extensively in recent years; however, the exact biomechanical contribution of vascular smooth muscle cells (VSMCs) during the adaptation process in conduit vessels is not known. We induced hypertension in 8 wk old Wistar rats by total ligation of the aorta between the two kidneys. Mean blood pressure increased from 92 +/- 2 (mean +/- SE) mm Hg to approximately 150 mmHg. Rats were sacrificed 2, 4, and 8 d after surgery and the left common carotid artery was excised for analysis. Wall thickness increased by 18% in 8 d and the opening angle by 32% in 4 d. The elastic properties were measured under normal VSMC tone (i.e., the amount of VSMC tone under normal conditions also called basal VSMC tone or normal resting VSMC tone), under maximally contracted VSMC (NE, 5 x 10(-7) mol/L) and under totally relaxed VSMC conditions (papaverine, 10(-4) mol/L). The most pronounced modifications were the changes in elastic properties related to normal VSMC tone. The functional contraction ratio at 100 mm Hg, defined as the relative contraction under normal conditions (normal VSMC tone), increased by 439% 4 d after the induction of hypertension. The total contraction capacity of the VSMC increased by 38% within 8 d. The changes in normal VSMC tone led to important changes in the mechanical properties of the arterial wall. Under normal VSMC conditions, compliance at mean pressure (148 mm Hg) increased by 159% within 8 d, whereas in the absence of VSMC tone, compliance did not increase significantly. We conclude that in conduit vessels, the VSMC, which is the sensing and effecting element of the adaptation process, is subjected to large-scale changes during the early phase of arterial adaptation to acute hypertension.

Adaptation, Physiological↗

PubMed2001

Physiological and pathological cardiac hypertrophy induce different molecular phenotypes in the rat.

Pressure overload, such as hypertension, to the heart causes pathological cardiac hypertrophy, whereas chronic exercise causes physiological cardiac hypertrophy, which is defined as athletic heart. There are differences in cardiac properties between these two types of hypertrophy. We investigated whether mRNA expression of various cardiovascular regulating factors differs in rat hearts that are physiologically and pathologically hypertrophied, because we hypothesized that these two types of cardiac hypertrophy induce different molecular phenotypes. We used the spontaneously hypertensive rat (SHR group; 19 wk old) as a model of pathological hypertrophy and swim-trained rats (trained group; 19 wk old, swim training for 15 wk) as a model of physiological hypertrophy. We also used sedentary Wistar-Kyoto rats as the control group (19 wk old). Left ventricular mass index for body weight was significantly higher in SHR and trained groups than in the control group. Expression of brain natriuretic peptide, angiotensin-converting enzyme, and endothelin-1 mRNA in the heart was significantly higher in the SHR group than in control and trained groups. Expression of adrenomedullin mRNA in the heart was significantly lower in the trained group than in control and SHR groups. Expression of beta(1)-adrenergic receptor mRNA in the heart was significantly higher in SHR and trained groups than in the control group. Expression of beta(1)-adrenergic receptor kinase mRNA, which inhibits beta(1)-adrenergic receptor activity, in the heart was markedly higher in the SHR group than in control and trained groups. We demonstrated for the first time that the manner of mRNA expression of various cardiovascular regulating factors in the heart differs between physiological and pathological cardiac hypertrophy.

Actins↗

PubMed2001

Influence of dentition status on physical disability, mental impairment, and mortality in institutionalized elderly people.

The loss of teeth is known to influence the mastication of foods and nutritional status. Therefore, we hypothesize that poor dentition status can impair the systemic health of the aged. To clarify the influence of dentition status on deterioration in physical ability, mental impairment, and mortality, we conducted a six-year prospective cohort study of the institutionalized elderly living in 29 of the 30 institutions for the elderly in Kitakyushu, Japan. Bivariate analysis revealed that worse dentition status at baseline led to significantly worse physical and mental impairment, and higher mortality. In a multiple logistic regression analysis, the physical ability of edentulous subjects without dentures significantly deteriorated compared with that of dentate subjects with 20 or more teeth. The six-year mortality rate of the edentulous subjects without dentures was significantly higher than that of the subjects with 20 or more teeth. Poorer dentition status, especially edentulousness without dentures, may therefore be related to deterioration in the systemic health of the aged.

Aged↗

PubMed2001

Increased frequency of FcgammaRIIIb-NA1 allele in periodontitis-resistant subjects in an elderly Japanese population.

Many elderly people show minimum periodontal tissue destruction, which might be partly due to genetic advantages in host immune response against periodontopathic bacteria. The human IgG Fc receptor IIIb on neutrophils bears a NA1-NA2 polymorphism. The FcgammaRIIIb-NA1 displays a more efficient interaction with IgG1- and IgG3-opsonized bacteria, compared with the FcgammaRIIIb-NA2. We investigated a 70-year-old Japanese population (n = 599) to determine whether the FcgammaRIIIb polymorphism was associated with resistance to periodontitis. Among subjects with > or = 20 teeth present, periodontitis-resistant (n = 46) and periodontitis-susceptible groups (n = 73) were selected based on the percentage of sites with > or = 4 mm probing attachment loss in the entire dentition. The FcgammaRIIIb-NA1 allotype was overrepresented in the periodontitis-resistant group, compared with the periodontitis-susceptible group (chi2 = 4.89, p = 0.03, odds ratio = 1.87, 95% CI, 1.07 to 3.28). This suggests that FcgammaRIIIb-NA1 may be associated with resistance to periodontitis.

Aged↗

PubMed2001

Analysis of vitamin D and Fcgamma receptor polymorphisms in Japanese patients with generalized early-onset periodontitis.

Early-onset periodontitis (EOP) is considered to have a genetic basis which has not been clearly defined. Genetic polymorphisms of the vitamin D receptor (VDR-B-b) and the immunoglobulin-Fc-gamma receptor IIIb (FcgammaRIIIb-NA1-NA2) are associated with bone metabolism and infectious diseases, respectively. The purpose of this study was to investigate the associations of EOP with VDR and FcgammaRIIIb polymorphisms. Subjects were comprised of those with generalized EOP (G-EOP, n = 42), adult periodontitis (AP, n = 52), and healthy control (HC, n = 55). VDR and FcgammaRIIIb genotypes were determined by allele-specific polymerase chain-reactions. Our results indicated that frequencies of the VDR-B non-carrier and the FcgammaRIIIb-NA2 carrier were lower in the G-EOP compared with the AP and HC groups. Furthermore, we found a strong association between G-EOP and the VDR-Fc-gammaRIIIb composite genotype (G-EOP vs. AP - OR = 5.09, p = 0.009; G-EOP vs. HC - OR = 5.93, p = 0.004). In conclusion, no correlation was found between the VDR genotype and G-EOP. However, the VDR and Fc-gammaRIIIb genotype combination may be associated with susceptibility to G-EOP.

Adult↗

PubMed2001

Oral health condition and endemic goitre, in an iodine-deficient area in Bali, Indonesia.

Iodine deficiency is a major determinant of endemic goiter which affects bone growth. The purpose of this study was to clarify the relationship between iodine deficiency and oral health. A cross-sectional survey was carried out on 181 inhabitants aged 17 to 40 years in two villages in an iodine-deficient area in Bali, Indonesia. Thyroid swelling, serum level of thyroid-stimulating hormone, DMFT index, plaque index, gingival index, dietary habits and socioeconomic status were examined. Thirty two subjects (21%) had thyroid swelling considered to be endemic goiter, with the highest prevalence in females aged 21 to 30 years (40-41%). The DMFT, food habits, and socioeconomic status were different between both villages. Multiple regression analysis adjusted for age, sex, and location (village) did not detect any association between DMFT and serum thyroid-stimulating hormone level or thyroid swelling. Further studies will be required to confirm these findings.

Adolescent↗

PubMed2001

Hepatic necrosis with cholestasis induced by long-term voglibose administration.

A 76-year-old woman admitted to our hospital for jaundice had been treated for diabetes mellitus with insulin for 9 years and voglibose had been added for the 39 months preceding admission. Elevated serum bilirubin and transaminase concentration began to normalize with initiation of corticosteroid treatment 1 week after discontinuation of voglibose. In the in vitro testing of the patient's peripheral blood, lymphocytes showed stimulation by voglibose. In dramatic contrast to an initial liver biopsy specimen that demonstrated cholestasis with submassive and zonal necrosis, the follow-up specimen was normal 1 year later. We believe that patients treated with voglibose should be monitored long-term with monthly determinations of transaminases and bilirubin in serum.

Aged↗

PubMed2001

Asymptomatic brain tumor detected at brain check-up.

Brain check-up was performed in 4000 healthy subjects who underwent medical and radiological examinations for possible brain diseases in our hospital from April 1996 to March 2000. Magnetic resonance imaging revealed 11 brain tumors which consisted of six meningiomas, three pituitary adenomas, one astrocytoma, and one epidermoid cyst. The detection rate of incidental brain tumor in our hospital was 0.3%. Nine patients underwent surgery, with one case of morbidity due to postoperative transient oculomotor nerve paresis. The widespread use of brain check-up may increasingly detect asymptomatic brain tumors. Surgical indications for such lesions remain unclear, and the strategy for treatment should be determined with consideration of the patient's wishes.

Adenoma↗

PubMed2001

Computer-assisted neurosurgical navigational system for transsphenoidal surgery--technical note.

Transsphenoidal surgery carries the risk of carotid artery injury even for very experienced neurosurgeons. The computer-assisted neurosurgical (CANS) navigational system was used to obtain more precise guidance, based on the axial and coronal images during the transsphenoidal approach for nine pituitary adenomas. The CANS navigator consists of a three-dimensional digitizer, a computer, and a graphic unit, which utilizes electromagnetic coupling technology to detect the spatial position of a suction tube attached to a magnetic sensor. Preoperatively, the magnetic resonance images are transferred and stored in the computer and the tip of the suction tube is shown on a real-time basis superimposed on the preoperative images. The CANS navigation system correctly displayed the surgical orientation and provided localization in all nine patients. No intraoperative complications were associated with the use of this system. However, outflow of cerebrospinal fluid during tumor removal may affect the accuracy, so the position of the probe when the tumor is removed must be accurately determined. The CANS navigator enables precise localization of the suction tube during the transsphenoidal approach and allows safer and less-invasive surgery.

Acromegaly↗

PubMed2001

Platelets exposed to elevated levels of endogenous thrombopoietin in vivo have a reduced response to megakaryocyte growth and development factor in vitro.

Thrombopoietin (TPO), or megakaryocyte growth and development factor (MGDF), has been shown to potentiate the sensitivity of normal human platelets to various agonists in vitro. The present study investigated the functional and biochemical properties of platelets from mice rendered thrombocytopenic by sublethal irradiation with regard to the reactivity to recombinant murine MGDF (rmMGDF) in vitro. During the course of reversible thrombocytopenia following irradiation, platelets from irradiated mice which had lower platelet counts and reciprocally higher plasma TPO levels showed lower reactivity to rmMGDF in agonist-induced platelet aggregation. Intravenous injections of recombinant soluble murine c-Mpl (sMpl), which has the ability to capture TPO, after irradiation restored the reactivity of platelets at the platelet nadir to rmMGDF. On the other hand, platelets prepared from normal mice 3 h after a single intravenous injection of pegylated rmMGDF did not respond to rmMGDF. There was a marked decrease in c-Mpl and Janus kinase 2 (JAK2) in platelets from irradiated mice at the platelet nadir. Similar results were observed with platelets from mice administered pegylated rmMGDF. JAK2 was only moderately decreased, however, in platelets from mice given sMpl after irradiation. These results indicate that exposure of platelets to increased endogenous TPO levels in vivo in thrombocytopenic mice leads to a reduction in the platelet reactivity to rmMGDF in vitro. Further, these results suggest that the c-Mpl-mediated signaling pathway, which is essential for the priming effect of rmMGDF, is defective in thrombocytopenic murine platelets.

Animals↗

PubMed2001

[A case of breast cancer 5 cm in diameter treated with a breast preserving approach after preoperative intra-arterial chemotherapy].

The patient was a 59-year-old female with a mass in the right breast (area C). At the initial examination, the mass was 5.0 x 4.5 cm on palpation, aspiration cytology was Class V, and a diagnosis of T2aN1aM0, Stage II breast cancer was made. Since the patient strongly desired a breast preserving treatment, a reduction in the size of the mass was attempted by local intra-arterial chemotherapy. Docetaxel (TXT) was administered at 60 mg into the internal thoracic artery and lateral thoracic artery at a rate of once a month for a total of 5 times. After the fifth treatment, the mass was reduced in size to 2.8 x 2.5 cm on palpation, and breast-preserving resection was then carried out. On histopathological examination, cancer was observed in an area of 3.0 x 2.2 cm. Careful follow-up is still needed, but preoperative intra-arterial chemotherapy is considered to be significant as a step before breast preserving surgery for breast cancer with a diameter of 3-5 cm.

Antineoplastic Agents, Phytogenic↗

PubMed2001

A novel cytochrome P450 enzyme responsible for the metabolism of ebastine in monkey small intestine.

Small intestinal microsomes of cynomolgus monkeys were found to catalyze hydroxylation and dealkylation of an H(1)-antihistamine prodrug, ebastine. To identify the main enzyme responsible for ebastine hydroxylation, which has been hitherto unknown, we purified two cytochrome P450 isoforms, named P450 MI-2 and P450 MI-3, from the intestinal microsomes on the basis of the hydroxylation activity. P450 MI-2 and P450 MI-3 showed the respective apparent molecular weights of 56,000 and 53,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The internal amino acid sequence of P450 MI-2 had high similarity with those of human CYP4F2, CYP4F3, and CYP4F8. The first 27 amino acid residues of P450 MI-3 were highly homologous with those of monkey CYP3A8 and human CYP3A4/5/7. Furthermore, P450 MI-2 and P450 MI-3 were recognized by anti-CYP4F and anti-CYP3A antibodies, respectively, in immunoblot analysis and catalyzed leukotriene B(4) omega-hydroxylation and testosterone 6beta-hydroxylation, which are known to be mediated by CYP4F and CYP3A, respectively. Although both enzymes had ebastine hydroxylation activity, the V(max) value of P450 MI-2 was much higher than that of P450 MI-3 (37.0 versus 0.406 nmol/min/nmol of P450), and the former K(M) (5.1 microM) was smaller than the latter K(M) (10 microM). Anti-CYP4F antibody inhibited the hydroxylation in small intestinal microsomes strongly (70%), but anti-CYP3A antibody did not. These results indicate that P450 MI-2 belongs to the CYP4F subfamily and is mainly responsible for hydroxylation of ebastine in monkey small intestinal microsomes. This suggests that the small intestinal CYP4F enzyme, P450 MI-2, can play an important role in the metabolism of drugs given orally.

Amino Acid Sequence↗

PubMed2001

Involvement of protein kinase C-epsilon in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitive hematopoietic progenitors.

We studied the effect of thrombopoietin (TPO) on interleukin-3 (IL-3)-dependent bone marrow cell colony formation of mice to clarify the role of protein kinase C (PKC) in the signal transduction of TPO for the proliferation of primitive hematopoietic progenitors. TPO alone hardly yielded colonies. However, TPO in combination with IL-3 increased colony numbers synergistically from 2- to 4-fold, compared with those supported by IL-3 alone. Serial observation of colony development showed that TPO may hasten the appearance of colonies by shortening the dormant period (G(0)) of primitive progenitors. Immunocytochemical studies on PKC isoforms in progenitor cells stimulated with TPO have revealed that the expression pattern of PKC-epsilon is changed, but not that of PKC-alpha, -beta, -gamma, -delta, or -zeta. Selective PKC inhibitors, such as calphostin C and GF 109203X, and PKC-epsilon-specific translocation inhibitor peptide abrogated the enhancing effect of TPO on IL-3-dependent colony formation and the changes in the intracellular expression pattern of PKC-epsilon. These data taken together suggest that TPO has a direct effect on primitive progenitors and enhances IL-3-dependent colony formation, at least partly through the activation of PKC-epsilon.

Animals↗

PubMed2001

Periodontitis and serum interleukin-6 levels in the elderly.

The elderly lose teeth as a result of dental caries and periodontitis caused by pathogenic oral bacteria. Periodontitis produces inflammatory cytokines due to the presence of lipopolysaccharides from oral gram-negative bacteria. Although the number of circulating inflammatory cytokines is related to the severity of the periodontitis, it is unclear whether the concentrations also correlate with periodontitis in the elderly. We investigated the relationship between periodontitis status and the concentrations of serum interleukin-6 (IL-6) in the serum from 276 subjects of 70- and 80-year-olds. Of the 276 subjects, 227 (82%) were dentate, 149 (54%) were found to be positive for serum IL-6, and 29 (13%) of the dentate subjects had severe periodontitis. However, there were no significant differences between the severity of periodontitis or the number of teeth and the mean serum IL-6 concentrations. These results provided no evidence to support an association between circulating IL-6 and periodontitis in the elderly.

Aged↗

PubMed2001

[The early hemorrhage and development of a bacterial aneurysm after a cerebral ischemic attack caused by a septic embolism--a case report].

A 71-year-old female was admitted with the complaints of dysarthria and right hemiparesis. CT scan revealed subarachnoid hemorrhage in the left cerebral sulcus. The first angiography was performed 3 days after the onset and left carotid angiography revealed a small aneurysm arising from the left middle cerebral artery. After 3 weeks of antibiotic therapy, the second angiography showed the aneurysm to be clearly enlarged, so it was resected. The patient complained of marked dysarthria a day after the operation and CT scan revealed a new infarction in the right frontal lobe. The third angiography showed an aneurysm arising from the right middle cerebral artery and the fact that two peripheral arteries of the aneurysm had disappeared 3 weeks after the first operation. The second operation was performed and a bacterial aneurysm was resected. The patient left the hospital without any neurological deficits. Septic embolism is the most important complication of infective endocarditis and it is usually presented with subarachnoid hemorrhage and intracerebral hemorrhage caused by ruptured bacterial aneurysms. In this case the septic embolism occurred two times. At each time cerebral ischemic attacks were presented. The reason why this case presented with ischemic symptoms was suspected to be that embolisms occurred at the trifurcation of the distal middle cerebral arteries. We were able to detect a bacterial aneurysm angiographically 3 days after the ischemic attack and we suspected that a bacterial aneurysm had been able to develop within 3 days after the septic embolism.

Aged↗

PubMed2001

[Aspiration and drainage for a gas-producing brain abscess causing delayed bleeding from the abscess capsule--a case report].

A 65-year-old man was admitted with the complaint of gait disturbance. CT scan revealed a low density lesion in the right parietal lobe. MRI was carried out 3 days after admission, the lesion showing low intensity on T1 WI and T2 WI. Gd-DTPA enhanced T1 WI showing abnormal enhancement surround it. CT scan then revealed a gas bubble in the lesion 12 days after admission, so we diagnosed it as gas-producing brain abscess and aspiration, drainage and irrigation with antibiotics were performed. Although, the brain abscess was reduced in size after the operation, the lesion expanded again 2 weeks after the operation. MRI was performed and the lesion showed iso-intensity on T1 WI and high intensity on T2 WI. Emergent aspiration and drainage were performed and uncoagulated old-hematoma-like matter such as chronic subdural hematoma was removed. As significant neovascularization with inflammatory cells had been detected in the capsule of the brain abscess, we suspected that aspiration and drainage surgery for brain abscess may cause delayed bleeding from the capsule of the abscess. We conclude that attention should be drawn to such a complication.

Aged↗

PubMed2001

[Spontaneous partial thrombosis of an unruptured peripheral, superior cerebellar artery aneurysm: a case report].

A 52-year-old female suddenly developed headache and dizziness. On admission she complained of gait disturbance with dizziness but cranial nerve palsy could not be detected. CT scan revealed a mild high density lesion in the right ambient cistern and the density of the lesion had become much higher 5 days after admission. MRI revealed a homogeneous iso-intense lesion on T1WI, T2WI 2 days after admission and the lesion had changed to homogeneous high. The lesion was suspected to be a fresh thrombus. Right vertebral angiography showed a part of aneurysm arising from the ambient segment of the right superior cerebellar artery and we diagnosed the lesion as a partially thrombosed superior cerebellar artery aneurysm. About forty cases of peripheral superior cerebellar artery aneurysm have been described in the literature, but cases of spontaneous thrombosis of the aneurysms have been very rare. Spontaneous thrombosis of aneurysms was usually thought to occur in large aneurysms, but the aneurysm in our case was not large. We suspected that in our case spontaneous thrombosis may have been caused by occlusion of the parent artery of the aneurysm.

Cerebellum↗