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Biomedical subjects

K Mizuno

Publications and source records attributed to K Mizuno.

At least 19 recordsLinked to original sources

Calcium/calmodulin kinase kinase beta has a male-specific role in memory formation.

The calcium/calmodulin (CaM) kinase cascade regulates gene transcription, which is required for long-term memory formation. Previous studies with Camkk2 null mutant mice have shown that in males calcium/calmodulin kinase kinase beta (CaMKKbeta) is required for spatial memory formation and for activation of the transcription factor cyclic AMP-responsive element binding protein (CREB) in the hippocampus by spatial training. Here we show that CaMKKbeta is not required for spatial memory formation in female mice as female Camkk2 null mutants were not impaired in spatial memory formation and they had the same level of hippocampal CREB phosphorylation after spatial training as female wild-type mice. Furthermore, we show that male but not female Camkk2 null mutants were impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Finally, a transcriptional analysis of male Camkk2 null mutants led to the identification of a gene, glycosyl phosphatidyl-inositol anchor attachment protein 1 (GAA1), whose hippocampal mRNA expression was up-regulated by spatial and contextual training in male but not in female wild-type mice. Taken together, we conclude that CaMKKbeta has a male-specific function in hippocampal memory formation and we have identified male-restricted transcription occurring during hippocampal memory formation.

Animals↗

Mental fatigue-induced decrease in levels of several plasma amino acids.

To investigate the relation between plasma amino acid levels and mental fatigue, we measured the plasma concentrations of 20 amino acids in 9 healthy volunteers before and after a fatigue-inducing mental task session for 8 hr. As fatigue-inducing mental tasks, the subjects performed an advanced trail making test, a Japanese KANA pick up test, and a mirror drawing test. As a control, 8-hr relaxation session was performed in the same subjects at an interval of 4 weeks. Immediately after the fatigue session, the plasma levels of branched-chain amino acids, tyrosine, cysteine, methionine, lysine, and arginine were below those after a relaxation session. The values for other blood parameters including total protein, albumin, glucose, and total cholesterol did not show any differences between the 2 sessions. These results indicate that mental fatigue may be characterized by a decrease in the plasma level of these amino acids.

Adult↗

Transient decreases in Bispectral Index without associated changes in the level of consciousness during photic stimulation in an epileptic patient.

This case report describes a patient with a history of epileptic seizures who showed unusual decreases in the Bispectral Index (BIS) attributable to the induction of abnormal slow electroencephalographic (EEG) waves by photic stimulation, without any associated decrease in his level of consciousness. After starting anticonvulsive therapy, photic stimulation no longer induced abnormal EEG activity nor decreased BIS values. These findings suggest that BIS values may not accurately reflect a patient's actual level of consciousness in the presence of epilepsy-related abnormal EEG activity and that the BIS monitor may be able to track such EEG changes.

Adult↗

Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells.

OBJECTIVES: Human bone-marrow stromal cells are believed to be multipotent even in adults. This study assessed the effectiveness of autologous bone-marrow stromal cells, which were embedded within a collagen scaffold, to repair a full-thickness articular cartilage defect in the medial femoral condyle of an athlete. PATIENT AND METHODS: A 31-year-old male judo player suffering from pain in the right knee was reviewed. A 20 x 30-mm full-thickness cartilage defect (International Cartilage Repair Society classification (ICRS) grade IV) was revealed in the weight-bearing area of the medial femoral condyle. With the informed consent of the patient, the defect was treated with autologous bone-marrow stromal cells. Bone marrow was aspirated from the iliac crest of the patient 4 weeks before surgery. After removing the erythrocytes, the remaining cells were expanded in culture. Adherent cells were collected and embedded within a collagen gel, which was transferred to the articular cartilage defect in the medial femoral condyle. The implant was covered with an autologous periosteal flap. RESULTS: Seven months after surgery, arthroscopy revealed the defect to be covered with smooth tissues. Histologically, the defect was filled with a hyaline-like type of cartilage tissue which stained positively with Safranin-O. One year after surgery, the clinical symptoms had improved significantly. The patient had reattained his previous activity level and experienced neither pain nor other complications. CONCLUSIONS: Our findings indicate that the transplantation of autologous bone-marrow stromal cells can promote the repair of large focal articular cartilage defects in young, active patients.

Adult↗

Intracytoplasmic lumina in invasive micropapillary carcinoma of the lung.

Micropapillary carcinoma of the lung is a rare neoplasm, and several reports on micropapillary carcinoma of the lung have been presented to date. We present a case of micropapillary carcinoma of the lung here. A 75-yr-old Japanese man received the medical checkup and his chest X-ray disclosed the abnormal shadow of the lower lobe of the left lung. The histological examination of resected lung and extirpated lymph node showed the finding of micropapillary carcinoma. Some neoplastic cells of primary site contained intracytoplasmic lumina positive for Alcian blue and PAS stains. Pleural effusion appeared 9-mo after the operation. The cytology of pleural effusion showed cohesive clusters of neoplastic cells consisting of 3-20 cells without fibrovascular core. Additionally, intracytoplasmic lumina were observed in some neoplastic cells. Finally, carcinoma cells with micropapillary morphology may possess the intracytoplasmic lumina in the cytoplasm of metastatic site as well as primary site.

Aged↗

Lung adenocarcinoma with a micropapillary pattern: a clinicopathological study of 25 cases.

Lung adenocarcinoma with a micropapillary pattern has recently been described, but its biological behavior is as yet uncertain. In this article we present a clinicopathological study of lung adenocarcinoma with micropapillary morphology. We selected 25 patients with lung adenocarcinoma with micropapillary morphology from the 2001-2004 pathology files (age range 54 to 81 years; mean 64.5 years). Micropapillary carcinoma is predominantly located at the periphery of the tumor nodule or mass and occurs irrespective of the subtype of the adenocarcinoma. A micropapillary component was seen against a mucinous background in three cases and microcalcifications resembling psammoma bodies were seen in one case. Four cases showed intensive invasive growth such as micropapillary adenocarcinoma of the breast and 21 showed alveolar type morphology with piling-up of the neoplastic cells with or without stromal invasion. Seven of twenty-three (30.4%) showed lymph node metastases at time of operation. Twelve of twenty-five (48%) showed pleural invasion. Regarding clinical outcome, 14 patients were alive without disease, 5 were alive with disease, and 5 died of the lung adenocarcinoma. No significant relationship was found between the extent of the micropapillary component and prognosis. However, the carcinoma seen in the five patients who died showed breast type histology with intensive invasive growth in three cases and alveolar type histology with intensive stromal invasion in two. Lung micropapillary carcinoma of breast type may behave more aggressively than the alveolar type.

Adenocarcinoma↗

Female urethral adenocarcinoma with a heterogeneous phenotype.

We here report a very rare case of female urethral adenocarcinoma. A 77-year-old woman presented with urinary retention. Cystoscopy showed a urethral tumor and the biopsy material showed adenocarcinoma. Macroscopically, the tumor measuring 3.0 x 3.0 x 2.4 cm was predominantly observed around the periurethral area on the proximal side. Histologically, patterns of columnar/mucinous adenocarcinoma, clear cell adenocarcinoma and papillary/micropapillary carcinoma were observed, but there was no evidence of a cribriform pattern. Immunohistochemically, neoplastic cells of at least one of three components were positive for CK7 and CK20 or CA125. We suggest that female urethral adenocarcinoma with a histologically and immunohistochemically heterogeneous phenotype may originate from cells within urethral or paraurethral tissue, such as urethritis glandularis or intestinal metaplastic epithelium and Mullerian tissue.

Adenocarcinoma↗

Bridging necrosis and reticulin bridging fibrosis induced by intrahepatic involvement of acute biphenotypic leukemia.

A 47-year-old Japanese woman was diagnosed as having acute biphenotypic leukemia with association of t(9;22)(q34;q11). Cholestatic liver dysfunction arose, and she died of cachexia and intracranial hemorrhage. Autopsy showed unusual hepatic fibrosis. In the liver, bridging infiltration, bridging necrosis and bridging fibrosis by leukemic cells were seen. It seemed that the degree of fibrosis was associated with the number of aggregates of infiltrating leukemic cells. The fibrotic foci were predominantly composed of reticulin and collagen fibers, and distortion of the lobules was observed. Immunohistochemically, dense bundles of alpha-smooth muscle actin (ASMA)-positive stromal cells, namely activated hepatic stellate cells (HSCs), were observed in the immature fibrotic foci as well as along the sinusoids densely infiltrated by leukemic cells. No cells positive for TGF-beta1 or PDGF-BB were identified. In conclusion, extensive intrahepatic involvement by neoplastic cells in adult acute biphenotypic leukemia may cause the unusual "disorganized" hepatic fibrosis.

Becaplermin↗

Analysis of feeding behavior with direct linear transformation.

AIM: The sucking pattern of term infants is composed of a rhythmic alteration of expression and suction movements. The aim is to evaluate if direct linear transformation (DLT) method could be used for the assessment of infant feeding. SUBJECT AND METHODS: A total of 10 gnormalh infants and two infants with neurological disorders were studied using DLT procedures and expression/suction pressure recordings. Feeding pattern of seven gnormalh infants were evaluated simultaneously recording DLT and pressures. The other infants were tested non-simultaneously. We placed markers on the lateral angle of the eye, tip of the jaw, and throat. The faces of infants while sucking were recorded in profile. The jaw and throat movements were calculated using the DLT procedure. Regression analysis was implemented to investigate the relationship between suction and expression pressures and eye-jaw and eye-throat movement. All regression analyses investigated univariate relationships and adjusted for other covariates. RESULTS: Ten gnormalh infants demonstrated higher suction pressure than expression pressure, and their throat movements were larger than jaw movements. Two infants with neurological problems did not generate suction pressure and demonstrated larger movements in their jaw than throat. The simultaneous measurement (n=7) showed a significant correlation, not only between eye-jaw distance and the expression pressure, but also between eye-throat distance and suction pressure. The change in the eye-jaw distance was smaller than the changes in the eye-throat distance in gnormalh infants (p<0.001). CONCLUSIONS: The DLT method can be used to evaluate feeding performance without any special device.

Humans↗

High-transmission waveguide with a small radius of curvature at a bend fabricated by use of a circular photonic crystal.

A bent photonic crystal waveguide was fabricated by use of a lattice pattern of a circular photonic crystal that allowed high transmission for a broad band of wavelengths with a small radius of curvature at a bend. The waveguide was fabricated by use of alumina rods with a diameter of 3 mm. Windows of high transmission as a result of waveguiding were observed near 9 and 15 GHz. By measurement of the relative wave intensity [E]2 along the line defects, the propagation losses in the straight and the bent sections were estimated at 9.3 GHz to be 0.04 and 0.03 dB/mm, respectively.

Journal Article↗

Clinical investigation: increased serum stromal derived factor 1 alpha levels in pulmonary tuberculosis.

Pulmonary tuberculosis, a granulomatous disease, has few serological markers for its activity. Recently, an increased plasma level of stromal derived factor 1 alpha (SDF-1alpha), which can induce strong chemotaxis of cells through its receptor CXCR4, was detected in patients with tuberculosis. In this study we investigated serum SDF-1alpha levels and CXCR4 expression on peripheral blood mononuclear cells (PBMCs). Fifty-five active tuberculosis patients, 30 resolved tuberculosis patients, 27 acute bronchitis patients and 8 healthy volunteers were examined. Histological expression of SDF-1alpha in the tuberculosis lesion and CXCR4 expression of PBMCs were also analysed. Serum SDF-1alpha levels in active tuberculosis patients were significantly higher than other groups. The sensitivity and specificity for the diagnosis of active tuberculosis was 88.5% and 85.3% (cutoff value = 650 pg/ml), respectively. CXCR4 expression levels on PBMCs showed a significant negative correlation with serum SDF-1alpha levels. Inflammatory cells including multinuclear giant cells in the lesion expressed SDF-1alpha. Measurement of serum SDF-1alpha could be a useful screening marker for the identification of active pulmonary tuberuculosis. We propose that interaction of SDF-1alpha and CXCR4 might be involved in the pathogenesis of pulmonary tuberculosis.

Acute Disease↗

Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation.

Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16(high)CCR2(-) subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16(high)CCR2(-) monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16(low)CCR2(+) subpopulation produced little. These results were contrary to the generally accepted notion that the CD16(high)CCR2(-) monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16(high)CCR2(-) subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16(high)CCR2(-) subpopulations are of a distinct lineage from CD16(low)CCR2(+) monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo.

Acute Disease↗

Effects of mild heat exposure on sleep stages and body temperature in older men.

The purpose of this study was to examine the effects of mild heat exposure on sleep stages and body temperature in older men. Ten healthy male volunteers with a mean age of 69.2 +/- 1.35 years served as subjects. The experiments were carried out under two different sets of conditions: 26 degrees C 50% relative humidity (RH) and 32 degrees C 50% RH. The subjects slept from 2200 hours to 0600 hours with a cotton blanket and wearing short-sleeve pajamas and shorts on a bed covered by a sheet. Electroencephalogram, electro-occulogram and mental electromyogram recordings were made through the night. Rectal and skin temperatures were measured continuously. No significant differences were observed in sleep onset latency. In time spent in each sleep stage, wakefulness was significantly increased at 32 degrees C than at 26 degrees C. The total amount of wakefulness increased and rapid eye movement sleep (REM) decreased at 32 degrees C compared to 26 degrees C. The fall in rectal temperature was significantly suppressed and the mean skin temperature was significantly higher at 32 degrees C than at 26 degrees C. These results suggest that, for older men, even mild heat exposure during the nighttime sleep period may increase thermal load, suppress the decrease of rectal temperature, decrease REM, and increase wakefulness and whole-body sweat loss.

Aged↗

Isotropic photonic gaps in a circular photonic crystal.

We investigated the optical properties of a circular photonic crystal (CPC) for which the distance between lattices was systematically distributed. The transmission spectra of CPC composed of alumina cylinders were examined in the frequency region from 0 to 20 GHz. We show that photonic gaps are obtained not only in CPCs but also in phase-shifted CPCs. The isotropic photonic gaps are evidenced by changes in the incident angle of a millimeter wave.

Journal Article↗

Mother-infant skin-to-skin contact after delivery results in early recognition of own mother's milk odour.

AIM: To determine the effects of mother-infant skin-to-skin contact immediately after birth on infant recognition of their own mother's milk odour and breastfeeding duration until 1 y of age. METHODS: Sixty healthy, full-term neonates were randomly assigned to group A with skin-to-skin contact and group B without. One and 4 d after birth, infant responses to the following odour stimuli were observed: own mother's milk, another mother's milk, formula, orange juice and distilled water. Infant facial action was videotaped and the frequency of mouthing movements was evaluated for each stimulus. Nutritional assessment, focused particularly on breastfeeding, was performed every 3 mo on participating infants. Statistical analysis comparing the frequency of mouthing movements with the aforementioned five different odour exposures was performed by ANOVA with Fisher's PLSD. Kaplan-Meier analysis with a log-rank test was used to compare breastfeeding rates between groups. RESULTS: Infants in both groups responded differently to mother's milk odour (either their own or another mother's milk) compared to the other stimuli on days 1 and 4. However, infants in group A demonstrated a larger difference in mouthing movements between their own and another mother's milk odour at 4 d of age (2.6 +/- 1.6) compared to infants in group B (0.9 +/- 2.0, p = 0.01). Infants in group A were breastfed an average of 1.9 mo longer than the others. CONCLUSION: Our study provides evidence that mother-infant skin-to-skin contact for more than 50 min immediately after birth results in enhanced infant recognition of their own mother's milk odour and longer breastfeeding duration.

Adult↗

Inhibitory influences of xanthine oxidase inhibitor and angiotensin I-converting enzyme inhibitor on multinucleated giant cell formation from monocytes by downregulation of adhesion molecules and purinergic receptors.

BACKGROUND: Allopurinol, a xanthine oxidase inhibitor, and captopril, an inhibitor of angiotensin I-converting enzyme, are widely used for hyperuricaemia and hypertension, respectively. There have been reported cases showing that these two agents are effective for the treatment of granulomatous diseases such as sarcoidosis, although the mode of action is not elucidated. OBJECTIVES: We examined the in vitro effects of these agents on the formation of multinucleated giant cells (MGC) from human monocytes by concanavalin A-stimulated mononuclear cell supernatants (conditioned medium). METHODS: We cultured monocytes with conditioned medium and each agent and compared the rate of MGC formation as well as the expression of adhesion molecules and P2X7 receptor, which are involved in MGC formation. RESULTS: The addition of 25 or 100 microg mL(-1) allopurinol or 0.125-1.0 microg mL(-1) captopril inhibited MGC formation. Monocytes treated with these agents exhibited less expression of intercellular adhesion molecular-1 (ICAM-1) than untreated monocytes. The susceptibility of monocytes cultured in conditioned medium for 24 h to 2'-and 3'-o-(4-benzoyl-benzoyl)adenosine triphosphate-mediated cytolysis was significantly lower in monocytes treated with these agents than in untreated monocytes. CONCLUSIONS: Allopurinol and captopril have a therapeutic effect on granulomatous disorders by a direct action on monocyte/macrophage lineage cells partly through downregulation of ICAM-1 and P2X7 receptor.

Allopurinol↗

Oligoclonal expansion of circulating and tissue-infiltrating CD8+ T cells with killer/effector phenotypes in juvenile dermatomyositis syndrome.

Although triggering by infectious agents and abnormal immune responses may play some role in the pathogenesis of juvenile dermatomyositis syndrome (JDMS), the precise mechanism of muscle destruction and vascular damage is largely unknown. In this study, we tried to elucidate the role of cytotoxic T cells in two patients with JDMS, who were diagnosed based on the characteristic symptoms, laboratory data, MRI findings and electromyographic patterns. Peripheral blood T cell phenotypes were determined by flow cytometry, using mAbs against specific T cell receptor (TCR) Vbetas. Complementarity-determining region3 (CDR3) size analysis was performed by gene scanning of CDR3 polymerase chain reaction (PCR) amplification products specific for each Vbeta. Subsequently, CDR3 nucleotide sequences were obtained after cloning of the predominant products. The distribution of lymphocytes infiltrating the muscle tissue was analysed by immunohistochemistry. In both patients examined, a unique combination of TCR Vbeta repertoires was increased within the CD8+ T cells. These subpopulations expressed a characteristic phenotype, indicating that they are memory/effector T cells with killer functions. At the same time, immunohistological and molecular biological examinations of the biopsied muscle samples revealed that identical CD8+ T cell clones with identical phenotypes/TCR Vbeta infiltrated within the inflammatory tissue, in particular around vessels. These findings indicate that oligoclonal expansion of CD8+ T cells plays a central role in the pathogenesis of muscle injury in the juvenile form of dermatomyositis syndrome and may provide a useful clinical parameter of disease activity and responsiveness to anti-inflammatory therapy.

Antigens, CD↗