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Biomedical subjects

K Sakuma

Publications and source records attributed to K Sakuma.

At least 19 recordsLinked to original sources

Several herpesviruses can reactivate in a severe drug-induced multiorgan reaction in the same sequential order as in graft-versus-host disease.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is a severe multiorgan systemic reaction. Numerous studies have linked reactivation of human herpesvirus (HHV)-6 with the development of DIHS. Recent articles have suggested that reactivation of other herpesviruses besides HHV-6 might also be involved in the development of DIHS. On the other hand, recent studies have provided evidence for a role of reactivation of various herpesviruses in the development of graft-versus-host disease (GVHD). OBJECTIVES: We attempted to determine whether sequential herpesvirus reactivation could be detected in four patients with severe DIHS, as observed in patients with GVHD, and be coincident with various clinical manifestations that developed after discontinuation of the causative drugs. METHODS: Detection and quantification of viral DNA [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HHV-6 and HHV-7] in sequential blood samples were performed using real-time polymerase chain reaction assays, based on TaqMan technology. RESULTS: In these patients, the cascade of virus reactivation initiated by HHV-6 or EBV extended to EBV or HHV-7, and eventually to CMV. Clinical manifestations of this syndrome followed by failure of various organs occurring despite discontinuation of the drug were coincident with these herpesvirus reactivations. CONCLUSIONS: These results suggest that various herpesviruses can reactivate in the setting of severe drug reactions in a similar sequential order to that described in GVHD. The sequential reactivation of these herpesviruses is responsible for the development of multiorgan failure occurring after discontinuation of the causative drug.

Aged↗

The expression of IGF-I and myostatin mRNAs in skeletal muscle of hypophysectomized and underfed rats during postnatal growth.

AIM: To determine the roles of myostatin and insulin-like growth factor-I (IGF-I) during postnatal growth, we examined IGF-I and myostatin mRNA expression in the skeletal muscles of hypophysectomized and underfed rats during postnatal growth. METHODS: Five-week-old rats were divided into four groups: freely fed control, moderately underfed, severely underfed and hypophysectomized. Four weeks later, blood and muscle samples were gathered to determine serum IGF-I, myosin heavy chain (MHC) isoforms, IGF-I Ea, IGF-I Eb and myostatin mRNA. RESULTS: The weights of soleus, plantaris and masseter muscles were decreased in underfed and hypophysectomized rats. Hypophysectomy resulted in significant increases of type I MHC at the expense of type IIx in plantaris muscle and of neonatal MHC at the expense of types IIx and IIb in masseter muscle. Serum IGF-I was decreased by underfeeding and hypophysectomy. Plantaris muscle IGF-I Ea mRNA in underfed and hypophysectomized rats was significantly lower than in normal controls. Plantaris muscle IGF-I Eb mRNA in underfed rats was significantly lower than in normal controls. Masseter muscle IGF-I Eb mRNA in severely underfed rats was significantly lower than in normal control and hypophysectomized rats. Soleus muscle myostatin mRNA in hypophysectomized rats was significantly higher than in normal and significantly underfed rats. No significant differences in plantaris and masseter muscle myostatin mRNA were observed between groups. CONCLUSION: Suppressed muscle growth caused by hypophysectomy and underfeeding may be attributed mainly to reduced circulating IGF-I and partially to reduced IGF-I mRNA, rather than to a change in myostatin.

Animals↗

[Aortic root enlargement in elderly patients].

From January 2003 to June 2005, 12 elderly patients with severe aortic stenosis underwent aortic root enlargement (ARE) by Nicks procedure. Their ages ranged from 74 to 87 with a mean of 79.3. Stented bioprosthesis were used in 11 cases. There was no death. Cardiothoracic ratio on chest X-ray decreased from 59.4 to 53.6% and New York Heart Association (NYHA) functional class improved from 3.4 to 1.3. Echocardiography also showed remarkable improvement, in peak pressure gradient (PG) from 98.3 to 20.7 mmHg, in left ventricular mass index (LVMI) 181 to 137 g/m2. LVM and LVMI regression rates were 25.3 and 22.3%, respectively. Comparative study of those with ARE alone and those with combined operation showed much hazardous effect in the latter, but no significant difference in echocardiographic findings postoperatively. ARE by Nicks procedure, if it could be performed without concomitant procedure, is a safe and effective option also in elderly patients with small aortic annulus.

Aged↗

The HDL2/HDL3 ratio in menopause.

OBJECTIVES: The influence of the menopause on the HDL2/HDL3 ratio was assessed in association with hypertriglyceridemia. METHODS: Fasting blood samples were collected from 607 patients. Commercially available enzymatic methods were used for determination of TG, and total HDL-C. HDL2 and HDL3 were measured by ultracentrifugation. RESULTS: The HDL2/HDL3 ratio had a strong negative correlation with TG (r=-0.272, P<0.0001 and r=-0.314, P<0.0001) in both pre- and postmenopausal women. No significant differences were observed in HDL2, HDL3, and HDL2/HDL3 ratio between pre- and postmenopausal women without hypertriglyceridemia. Postmenopausal women had a significantly higher HDL2/HDL3 ratio than premenopausal women with hypertriglyceridemia. CONCLUSIONS: These results indicate that menopausal status not only increases plasma LDL-cholesterol and triglyceride levels, but also increases the HDL2/HDL3 ratio when associated with elevation of plasma triglyceride levels. These changes may increase the risk for CHD due to enlargement of the lipid pool.

Adult↗

Interleukin-8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease.

BACKGROUND: It has been reported that inflammatory cell infiltration can be detected in patients with endoscopically negative gastroesophageal reflux disease (GERD) as well as those with erosive reflux esophagitis. In this study, we examined the expression of mRNA for interleukin (IL)-8, a potent chemokine for neutrophils, in the esophageal mucosa of patients with GERD and compared the results with their endoscopic findings and symptoms. METHODS: Biopsy samples were obtained from 80 patients. Endoscopic diagnosis was performed according to the Los Angeles classification. Patients with typical symptoms such as heartburn despite normal endoscopic findings were classified as the non-erosive GERD group. Total cellular RNA was extracted from the biopsy samples and IL-8 mRNA was quantified by real-time polymerase chain reaction (PCR). Localization of IL-8 protein in the esophageal mucosa was done by immunostaining. RESULTS: Expression of IL-8 mRNA was correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration, but not with the symptoms of the patients. Expression of IL-8 mRNA was also detected in all patients with non-erosive GERD. The level of IL-8 expression in non-erosive GERD was low compared with that in erosive GERD, but was higher than that in normal controls. IL-8 immunostaining was found in the basal layers of the esophageal mucosa. Administration of lansoprazole, a proton-pump inhibitor, decreased both IL-8 mRNA and protein levels in the esophageal mucosa. CONCLUSION: These results suggest that IL-8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non-erosive GERD.

Base Sequence↗

[A successful management of acute myocardial infarction with severe left main trunk lesion using beating heart coronary artery bypass grafting: report of a case].

A 56-year-old male was admitted for sudden onset of severe chest pain and diagnosed as acute myocardial infarction (AMI). Emergency coronary angiography revealed complete obstruction of the left anterior descending artery (LAD) and 99% stenosis of left circumflex coronary artery (LCX), which was almost same with obstruction of the left main trunk coronary artery. Emergency coronary artery bypass grafting (CABG) to LAD and LCX was performed under a beating-heart. Left ventricular wall motion was improved after bypass grafting. CABG under a beating-heart is a new strategy for critical cases such as acute coronary syndrome. The better patency rate and the more complete revascularization that may be achieved with the new generation of stabilizers and retractors may improve long-term results.

Coronary Angiography↗

Does decreased T1 signal intensity in the retrodiscal tissue of the temporomandibular joint reflect increased density of collagen fibres?

OBJECTIVE: To evaluate whether decreased signal intensity on T(1) weighted MR images of the retrodiscal tissue of the temporomandibular joint (TMJ) reflects increased density of collagen fibres. METHODS: Corrected sagittal T(1) weighted MR images of six TMJs from six fresh cadavers (three males and three females; age range 76-87 years, mean 80.8 years) were obtained. Following MRI, slices of tissue samples were taken from the cadavers that exactly matched the planes of the MR image. These samples were fixed, decalcified and stained (haematoxylin-eosin stain, Elastica van Gieson's stain) for light microscopy. The samples were evaluated for density of collagen fibres according to Hall et al (1984) and for vascularity, arterial wall thickness, fat content and elastin. In these sagittal samples, the retrodiscal tissue was divided anteroposteriorly and vertically into six areas and each area was classified by histological parameters. The MR images were similarly divided into six areas. Areas with reduced signal intensity were classified as the low signal group and those with no reduced signals were classified as the control group. RESULTS: Collagen density assessed histologically differed between the low signal intensity group and the control group, and loose collage density on the histological samples was observed significantly more often in the low signal group (Fisher's exact test, P=0.03). There were no statistically significant differences in the other categories between the two groups. CONCLUSION: The results suggest that reduced T1 signals of retrodiscal tissue do not necessarily reflect a dense distribution of collagen fibres.

Aged↗

[Coronary vasospasm during off-pump coronary artery bypass grafting; report of two cases].

Coronary vasospasm is one of the most dangerous and fatal complications of coronary artery bypass grafting (CABG) operation. Our experiences in recent 2 cases happened during off-pump CABG (OPCAB) are presented. Case 1: A 63-year-old male who had 3 vessels disease underwent OPCAB using left internal thoracic artery (LITA) and the radial artery. When the sternotomy was going to be closed, ST elevation of electrocardiogram (ECG) occurred and was followed by ventricular fibrillation. Intra-aortic balloon pumping (IABP) and percutaneous cardiopulmonary support (PCPS) were applied immediately and an additional grafting to first diagonal artery (D 1) was carried out using a saphenous vein. Case 2: A 67-year-old male underwent OPCAB using LITA and the radial artery. ST elevation of ECG suddenly occurred and was followed by complete atrio-ventricular (AV) block when the sternum was closed. IABP and the ventricular pacing were applied immediately. While OPCAB may be less invasive operating method than conventional CABG, we should pay more attention to the coronary vasospasm.

Aged↗

Method of producing tissue sections from endometrial scrapings.

Endometrial cytology is important not only for observing cytological findings, but also for assessing histological architecture. Therefore, we attempted to produce a histological preparation from the sample using an automatic fixation apparatus (ACF 1000) which employs a membrane filter method. After observation of the cytological features, the cover slip was removed and a paraffin-embedded section was prepared. Producing a histological section from a cytological specimen prepared with the ACF 1000 apparatus was more useful and easier than with the techniques described to date. Peelability of the cell was avoided by using a silane-coated membrane filter. Observation of the same cell cluster as that observed in the cytological sample was also facilitated in the histological section by this technique.

Biopsy↗

A possible role for BDNF, NT-4 and TrkB in the spinal cord and muscle of rat subjected to mechanical overload, bupivacaine injection and axotomy.

Neurotrophins play a crucial role in the regulation of survival and the maintenance of specific functions for various populations of neurons. Neurotrophin-4 (NT-4) is most abundant in skeletal muscle, and is thought to promote sciatic nerve sprouting, inhibit agrin-induced acetylcholine receptor (AChR) clustering, evoke postsynaptic potentiation and induce mitochondrial proliferation. Using Western blot analysis, immunoprecipitation and immunohistochemistry, we investigated the distribution of NT-4 in slow- and fast-type muscles. We also tested the adaptive response of this protein in the mechanically overloaded muscle, in the regenerating muscle following bupivacaine injection and in the denervated muscle. Additionally, we investigated whether TrkB phosphorylation in the spinal cord and in the sciatic nerve occurs through the interaction with BDNF or NT-4 when the innervating muscle is damaged. Markedly more NT-4 was expressed in fast-type muscles compared with the slow types. TrkB protein was more frequently observed around the edge of myofibers (neuromuscular junction) of the soleus muscle compared with the gastrocnemius muscle. TrkB tyrosine phosphorylation occurred in the spinal cord but not in the sciatic nerve 24 h after bupivacaine injection of the innervating muscle. At the same time, the amount of TrkB co-precipitating with BDNF was markedly increased in the spinal cord. A rapid activation of TrkB (1-8 h) was also observed in the spinal cord after axotomy,while the amount of TrkB co-precipitating with NT-4 was markedly lower after axotomy. These results indicate that NT-4 is preferentially distributed in fast-type muscles. Furthermore, by interacting with BDNF and NT-4, the TrkB in the spinal cord may be important for the survival of motoneurons and outgrowth of injured peripheral axons following muscle damage.

Animals↗

Serial activation of distinct cytoarchitectonic areas of the human S1 cortex after posterior tibial nerve stimulation.

MEG recordings visualized non-invasively a dynamic anterior-posterior activation in the pyramidal cell population of the human primary somatosensory cortex (S1) after posterior tibial nerve stimulation. Somatosensory evoked fields (SEFs) were recorded over the foot area in response to right posterior tibial nerve stimulation at the ankle in six normal subjects. A newly developed MEG vector beamformer technique applied to the SEFs revealed two distinct sources in the mesial wall of the left hemisphere around the primary P37m response typically separated by 1.3 cm. The first source was located in area 3b and oriented toward the contralateral hemisphere. The second source was assumed to be in an area near the marginal sulcus and the source orientation was directed posteriorly. The first source began to be active during the initial slope of the P37m. The second source was active after the P37m peak and the signal intensities of the first and second sources were equal at a mean latency of 2.6 ms after the peak of P37m. Then the first source became inactive and the second source was dominant after about 5 ms post-P37m peak. These findings suggest that a single peaked posterior tibial nerve P37m consists of partially overlapping two subcomponents generated in area 3b and an area near the marginal sulcus.

Adult↗

Cryopreserved aortic homograft replacement in 3 patients with noninfectious inflammatory vascular disease.

OBJECTIVE: Although mechanical prosthetic heart valves are most commonly used for aortic valve replacement in patients with aortic regurgitation due to noninfectious inflammatory vascular disease, postoperative perivalvular leakage and/or detachment of the prosthetic valve occurs due to the fragility of the aortic annulus. Aortic root replacement with cryopreserved homografts is reported to be useful in such patients. METHODS: Three patients having aortic regurgitation associated with severe long standing noninfectious inflammatory vascular disease-2 patients with Takayasu's arteritis and 1 patient with Behçet disease--had the aortic root replacement by a cryopreserved aortic homograft valve and conduit. RESULTS: All surgery was successful and the postoperative course uneventful. Echocardiography showed neither aortic regurgitation nor graft detachment at 6-39 months after operation. CONCLUSIONS: Homograft valve and conduit replacement is appropriate in patients with aortic regurgitation associated with noninfectious inflammatory vascular disease, with mid-term results favorable.

Adult↗

Bronchial artery aneurysm treated with percutaneous transluminal coil embolization.

We present a case with asymptomatic mediastinal bronchial artery aneurysm at the origin of the left bronchial artery. This bronchial artery aneurysm was successfully treated with percutaneous transluminal coil embolization. Complete embolization of the feeding artery and tributaries from the aneurysm is the key to successful isolation of a large bronchial artery aneurysm from the circulation. Percutaneous transluminal embolization is one of the treatment options for a patient with asymptomatic, incidentally-identified bronchial artery aneurysm.

Aneurysm↗

Chronic docosahexaenoic acid intake enhances expression of the gene for uncoupling protein 3 and affects pleiotropic mRNA levels in skeletal muscle of aged C57BL/6NJcl mice.

Docosahexaenoic acid [DHA, 22:6(n-3)] prevents cardiovascular disease by decreasing obesity. It also prevents cancer and other geriatric diseases. We studied the chronic pleiotropic effects of DHA on transcription including that of mRNAs for uncoupling proteins (UCP). Male and female mice (9 mo old) were fed high (n-6) or high (n-3) fatty acid diets for 4 mo. Compared with controls fed high (n-6) fatty acid diets [high (n-6) group], the livers of male and female mice fed DHA [high (n-3) group] contained six- (P < 0.001) and fivefold (P < 0.001) more DHA, respectively. The high (n-3) group had less white adipose tissue [35.3% in males (P < 0.001) and 27.3% in females (P < 0.001)]. The high (n-3) group expressed more uncoupling protein 3 (UCP3) in the gastrocnemius, 108% higher (P < 0.001) and 104% higher (P < 0.001) in males and females, respectively, than those in the high (n-6) group. However, the prevention of many diseases by DHA is not explained by UCP3. Thus, the gene expression profiles of both high (n-3) and high (n-6) groups were analyzed in skeletal muscle using cDNA expression array. Of 588 genes surveyed in the array, the high (n-3) group showed 12 genes (2%) including those for glucose regulators (e.g., CD38) and tumor suppressors (e.g., CTCF) that were expressed 100-340% more than those of the high (n-6) group. Furthermore, 28 genes (4.8%), including growth factors (e.g., ErbB-2 receptor) and immune regulators (e.g., interleukin-1 beta precursor) were expressed 50-90% less in the high (n-3) group than in the high (n-6) group. These results explain in part the important pleiotropic effects of DHA, which are independent of obesity control by UCP3 suppression.

Aging↗

The dynamic processes for word and picture encoding in the human brain as revealed by magnetoencephalography.

Subjects were asked to memorize either the size or the meaning of the first stimulus (encoding) of a stimulus pair, and to match it to the second stimulus. Words and pictures were used as the stimuli in separate tests. Two components named 1M and 2M in both hemispheres for word or picture stimuli could be detected by magnetoencephalography (MEG). The dipole location of 1M in bilateral hemispheres for words is different from that for pictures, but that of 2M is not. It is considered that picture and word are processed in different systems at the initial stage, mainly in the lateral temporal cortex for words and in the parietal cortex for pictures, whereas they are processed in a common semantic system at the late stage.

Adult↗

Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles.

Mice genetically deficient in growth and differentiation factor 8 (GDF8/myostatin) had markedly increased muscle fiber numbers and fiber hypertrophy. In the regenerating muscle of mice possessing FGF6 mutation, fiber remodeling was delayed. Although myostatin and FGF6 may be important for the maintenance, regeneration and/or hypertrophy of muscle, little work has been done on the possible role of these proteins in adult muscle in vivo. Using Western blot and immunohistochemical analysis, we investigated, in rats, the distribution of myostatin, FGF6 and LIF proteins between slow- and fast-type muscles, and the adaptive response of these proteins in mechanically overloaded muscles, in regenerating muscles following bupivacaine injection and in denervated muscles after section of the sciatic nerve. The amounts of myostatin and LIF protein were markedly greater in normal slow-type muscles. In the soleus muscle, myostatin and LIF proteins were detected at the site of the myonucleus in both slow-twitch and fast-twitch fibers. In contrast, FGF6 protein was selectively expressed in normal fast-type muscles. Mechanical overloading rapidly enhanced the myostatin and LIF but not FGF6 protein level. In the regenerating muscles, marked diminution of myostatin and FGF6 was observed besides enhancement of LIF. Denervation of fast-type muscles rapidly increased the LIF, but decreased the FGF6 expression. Therefore, the increased expressions of myostatin and LIF play an important role in muscle hypertrophy following mechanical overloading. The marked reduction of FGF6 in the hypertrophied and regenerating muscle would imply that FGF6 regulates muscle differentiation but not proliferation of satellite cells and/or myoblasts.

Animals↗

Dynamic mediolateral activation of the pyramidal cell population in human somatosensory 3b area can be visualized by magnetic recordings.

Dynamic mediolateral activation in the pyramidal cell population of the human somatosensory 3b area was studied non-invasively. Somatosensory evoked fields (SEFs) were recorded over the hand area contralateral to the right median nerve stimulation at the wrist. Localization of an equivalent current dipole (ECD) for N20m primary cortical response was successively calculated for periods of 2.4 ms around N20m peak where the signal-to-noise ratio exceeded 100 and the spatial resolution was approximately 0.3 mm. The ECD moved toward the anterior, lateral and inferior direction for a distance of 8.7 mm at a propagation velocity of 3.6 m/s. This direction was orthogonal to the orientation of apical dendrites of the pyramidal neurons in area 3b and parallel to the surface of the posterior bank of the central sulcus. These findings suggest that the sequential mediolateral activation of the pyramidal cells in the somatosensory cortex is mediated by horizontal connections running parallel to the cortical surface.

Adult↗

Postnatal profiles of myogenic regulatory factors and the receptors of TGF-beta 2, LIF and IGF-I in the gastrocnemius and rectus femoris muscles of dy mouse.

The dystrophin-deficient mdx mouse presents muscle fiber necrosis but active muscle regeneration, probably due to an extensive recruitment of myogenic regulatory factors (MRF), several growth factors and cytokines, and favorable interaction of satellite cells. In contrast, the laminin alpha 2 (merosin)-deficient dy mouse shows progressive muscle fiber necrosis and ineffective muscle regeneration. Using Western blot and immunohistochemical analyses, we investigated the adaptive changes in MRF, growth factors and cytokines and their receptors in the muscles of dy mice during postnatal growth. The relative volume of MyoD, myogenin and Myf-5 proteins was markedly lower in the gastrocnemius and rectus femoris muscles of dy mice. Transforming growth factor-beta 2, leukemia inhibitory factor (LIF) and basic fibroblast growth factor were not up-regulated in the muscles of dy mice. The levels of the LIF receptor and insulin-like growth factor-I receptor levels were markedly decreased in the muscles of dy mice during the entire postnatal period observed in this study. Therefore, unlike the situation in mdx mice, the milieu of regeneration following repetitive damage seems to be degraded in the muscles of dy mice.

Aging↗