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Biomedical subjects

H Ozawa

Publications and source records attributed to H Ozawa.

At least 19 recordsLinked to original sources

New technique of laparoscopic colectomy with the LAP DISC and a 5-mm flexible scope.

PURPOSE: We devised a new method for the safe introduction of the first trocar and induction of pneumoperitoneum for laparoscopic excision of the large intestine. METHODS: With this method, a small laparotomy is first conducted according to the size of the exposed affected intestinal tract or tumor size, prior to the application of a LAP DISC (LD) to the wound and introduction of a 12-mm trocar for the establishment of pneumoperitoneum. The method is advantageous in that organ injury and vessel injury are avoided when the small laparotomy is conducted first, and prompt transition to a conventional laparotomy is possible. The diaphragm of the iris bulb can be controlled in a non-stepwise manner. In addition, trocars, the stapler, and other instruments, can be inserted under the pneumoperitoneum. Furthermore, the use of a 5-mm flexible scope allows surgical maneuvers, except for application of LD, to be conducted via 5-mm trocars. In addition, the 5-mm scope can be inserted through any trocar, allowing multidirectional avoidance of dead space and intraperitoneal observation. When only 5-mm trocars are used, it is not necessary for the sites of trocar puncture to be closed by sutures, and this minimizes the risk of adhesions and port-site herniation. The method is also considered to be excellent from the point of view of esthetics. RESULTS: We employed this surgical approach in 50 patients with colorectal cancer at our hospital. None of the patients developed any traumatic complications associated with the insertion of trocars, and none of the patients, even those with a past history of abdominal operation, required conversion to conventional laparotomy. CONCLUSIONS: Based on these results, this method involving a small laparotomy prior to the application of an LD and introduction of a 12-mm trocar for establishing pneumoperitoneum, with the efficient use of a 5-mm flexible camera, is considered to be safe and useful for laparoscopic excision of the large intestine.

Adult↗

Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin disrupts sealing zones without affecting microtubule networks.

Bone-resorbing osteoclasts form sealing zones and ruffled borders toward the bone surface. The sealing zone consists of a ring-like alignment of F-actin dots and surrounds the ruffled border, from which protons are secreted into the bone surface. Vacuolar-type proton ATPase (V-ATPase) in osteoclasts is a ruffled border-associated enzyme responsible for the proton secretion. We studied the interaction between microtubules and the actin cytoskeleton in osteoclasts. Confocal microscopic observation revealed that osteoclasts on glass coverslips, dentine slices and Osteologictrade mark discs formed the ring-like structure of F-actin dots, and microtubules overlapped the top of the F-actin dots. Osteoclasts cultured on dentine formed resorption pits within 48 h. The treatment of osteoclasts with cytochalasin D, an F-actin-depolymerizing reagent, induced perturbation of the microtubules in osteoclasts on glass and inhibited their pit-forming activity on dentine in a dose-dependent and reversible manner. Conversely, nocodazole, a microtubule-depolymerizing reagent, disrupted sealing zones and inhibited pit-forming activity of osteoclasts in a dose-dependent and reversible manner. V-ATPase showed a tendency to be localized inside sealing zones in osteoclasts. Treatment of osteoclasts with calcitonin induced both disruption of sealing zones and dispersion of V-ATPase to the whole area of the cytoplasm within 60 min. The microtubule networks in osteoclasts remained unchanged for 60 min even in the presence of calcitonin. These results suggest that coordination of the actin cytoskeleton and microtubules is important in the function of osteoclasts, but calcitonin selectively affects the actin cytoskeleton and induces the dispersion of V-ATPase without causing significant changes in the microtubules.

Actins↗

Diffusion MRI abnormalities after prolonged febrile seizures with encephalopathy.

BACKGROUND: Patients with encephalopathy heralded by a prolonged seizure as the initial symptom often have abnormal subcortical white matter on diffusion-weighted MRI (DWI). OBJECTIVE: To determine if these patients share other common features. METHODS: Patients with encephalopathy heralded by a prolonged seizure and followed by the identification of abnormal subcortical white matter on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Seventeen patients were identified, ages 10 months to 4 years. All had a prolonged febrile seizure (longer than 1 hour in 12 patients) as their initial symptom. Subsequent seizures, most often in clusters of complex partial seizures, were seen 4 to 6 days after the initial seizure in 16 patients. Outcome ranged from almost normal to severe mental retardation. MRI performed within 2 days of presentation showed no abnormality. Subcortical white matter lesions were observed on DWI between 3 and 9 days in all 17 patients. T2-weighted images showed linear high intensity of subcortical U fibers in 13 patients. The lesions were predominantly frontal or frontoparietal in location with sparing of the perirolandic region. The diffusion abnormality disappeared between days 9 and 25, and cerebral atrophy was detected later than 2 weeks. Three patients having only frontal lesions had relatively good clinical outcome. CONCLUSIONS: Although the pathophysiologic mechanism remains unknown, these patients seem to have a distinctive encephalopathy syndrome. MRI is helpful in establishing the diagnosis of this encephalopathy.

Atrophy↗

One-stage lateral rhachotomy and posterior spinal fusion with compression hooks for Pott's paralysis in the elderly.

PURPOSE: To evaluate the safety and effectiveness of one-stage lateral rhachotomy and posterior fusion with compression hooks, for the treatment of Pott's paralysis in the elderly. METHODS: 11 elderly patients underwent lateral rhachotomy (costotransversectomy and pediculectomy) to debride the tuberculosis focus extending into the epidural space and to decompress the spinal cord. After debridement, the interbody cavity was packed with autologous iliac bone chips. For stabilisation, posterior fusion was performed using a compression lamina hook system. Patients were followed up for at least 2 years for complications. Neurological status was assessed using the Frankel score. The kyphotic deformity was measured on lateral radiographs taken before surgery and at follow-up. RESULTS: During separation of the adhesion around the abscess, a dural tear occurred in one patient and a pleural tear in another. Both tears were successfully repaired. One patient had mild pneumonia after surgery. The Frankel scores of the 11 patients improved from C or D before surgery to D or E after surgery. No relapse of spinal tuberculosis was encountered. The mean deformity angle was 25.5 degrees before surgery and 23.2 degrees at the final follow-up. Spinal fusion was achieved in all patients. CONCLUSION: Without the need of thoracotomy, one-stage lateral rhachotomy with posterior spinal fusion using compression hooks was an effective option for treating Pott's paralysis in the elderly.

Aged↗

Geranylgeranylacetone inhibits formation and function of human osteoclasts and prevents bone loss in tail-suspended rats and ovariectomized rats.

Vitamin K is used for protecting against osteoporosis. Recently, it has been reported that the inhibitory effect of vitamin K(2) (menatetrenone) on bone resorption may be related to its side chain. Geranylgeranylacetone (GGA), known as teprenone, an antiulcer drug, has almost the same chemical structure as that of the side chain of menatetrenone. We hypothesized that GGA also has an inhibitory effect on osteoclastogenesis both in vitro and in vivo. GGA in pharmacological concentrations directly inhibited osteoclastogenesis from human monocytes induced by soluble receptor activator of nuclear factor-kappaB ligand. In addition, GGA induced degradation of actin rings in mature osteoclasts, which was reversed by adding geranylgeranylpyrophosphatase. Moreover, GGA increased the bone mineral density of total femur, proximal metaphysis, and diaphysis of femur in ovariectomized rats. GGA also prevented bone loss induced by hindlimb unloading in tail-suspended rats. These results indicate that GGA prevents bone loss by maintaining a positive balance of bone turnover through suppression of both the formation and the activity of osteoclasts. Thus, GGA could be used to prevent and improve osteoporosis.

Animals↗

A survey of Japanese patients with Menkes disease from 1990 to 2003: incidence and early signs before typical symptomatic onset, pointing the way to earlier diagnosis.

Menkes disease (MNK) is a lethal, X-linked recessive disorder of copper metabolism dominated by neurodegenerative symptoms and connective tissue disturbances. The incidence of MNK in Asia is not known. Most patients die by the age of 3 years if adequate treatment is not carried out. Early parenteral administration of copper can prevent the neurological disturbances and lead to a better outcome. In the present study, a survey on MNK in Japan was performed. There were in total 53 live-born Japanese patients with MNK collected from 1990 to 2003, including two females. The incidence of live-born MNK patients between 1992 and 2002 was 2.8 per million live births (95% confidence interval (CI): 1.8 to 3.7), 4.9 per million male live births (95% CI: 3.2 to 6.6). One-third of the patients were born before 37 weeks or weighing less than 2500 g. Seventeen per cent were born both before 37 gestational weeks and weighing less than 2500 g. These proportions were higher than those in Japanese live-birth babies according to a nationwide estimate. The hair on these Japanese patients appeared not only as white or grey but also brown and blond. We also found that many signs had been noted before the patient was brought to a hospital with typical symptoms. These signs may be a clue to early diagnosis of MNK.

Age Factors↗

An X-ray outburst from the rapidly accreting young star that illuminates McNeil's nebula.

Young, low-mass stars are luminous X-ray sources whose powerful X-ray flares may exert a profound influence over the process of planet formation. The origin of the X-ray emission is uncertain. Although many (or perhaps most) recently formed, low-mass stars emit X-rays as a consequence of solar-like coronal activity, it has also been suggested that X-ray emission may be a direct result of mass accretion onto the forming star. Here we report X-ray imaging spectroscopy observations which reveal a factor approximately 50 increase in the X-ray flux from a young star that is at present undergoing a spectacular optical/infrared outburst (this star illuminates McNeil's nebula). The outburst seems to be due to the sudden onset of a phase of rapid accretion. The coincidence of a surge in X-ray brightness with the optical/infrared eruption demonstrates that strongly enhanced high-energy emission from young stars can occur as a consequence of high accretion rates. We suggest that such accretion-enhanced X-ray emission from erupting young stars may be short-lived, because intense star-disk magnetospheric interactions are quenched rapidly by the subsequent flood of new material onto the star.

Journal Article↗

Neurotoxic potential of haloperidol in comparison with risperidone: implication of Akt-mediated signal changes by haloperidol.

The neurotoxicity of conventional antipsychotic drugs has emerged as a potential pathogenic event in extrapyramidal side effects (EPS) and in their limited efficacy for negative-cognitive symptoms in schizophrenic patients. The atypical antipsychotics, recently developed, have superior therapeutic efficacy to treat not only positive symptoms but negative symptoms and cognitive dysfunctions with much lower potentials of side effects, although the influence of atypical antipsychotics on the regulation of neuronal survival has been less investigated. It is important to clarify the effects of typical and atypical antipsychotics on neuronal survival and their contributions to the therapeutic development and understanding of the pathophysiology of schizophrenia. We measured the neurotoxicity of two antipsychotic drug treatments, haloperidol and risperidone, in primary cultured rat cortical neurons. Immunoblotting and pharmacological agent analyses were used to determine the signal transduction changes implicated in the mechanisms of the neurotoxicity. Haloperidol induced apoptotic injury in cultured cortical neurons, but risperidone showed weak potential to injure the neurons. Treatment with haloperidol also led the reduction of phosphorylation levels of Akt, and activated caspase-3. The D2 agonist bromocriptine and 5-HT2A antagonist, ketanserin attenuated the haloperidol-induced neuronal toxicity. Moreover, brain-derived neurotrophic factor (BDNF) reduced the caspase-3 activity and protected neurons from haloperidol-induced apoptosis. BDNF also reversed the reduced levels of phosphorylation of Akt caused by treatment with haloperidol. Haloperidol but not risperidone induces caspase-dependent apoptosis by reducing cellular survival signaling, which possibly contributes to the differential clinical therapeutic efficacy and expression of side effects in schizophrenia.

Animals↗

Histochemical evaluation for the biological effect of menatetrenone on metaphyseal trabeculae of ovariectomized rats.

To evaluate the biological effects of vitamin K2 (menatetrenone, MK-4) on ovariectomy (OVX)-induced bone loss, we have examined histological alterations of femoral metaphyses of sham-operated (sham group), ovariectomized (OVX group), and MK-4 dietary-supplemented OVX (MK-4 group; 50 mg/kg per day) female Fischer rats 1, 2, 5, and 8 weeks after OVX. In the first week, rats of the OVX and MK-4 groups showed discontinuous trabeculae compared with sham-operated rats. At 2 weeks after OVX, the OVX rats revealed many large tartrate resistant acid phosphatase (TRAP)-positive osteoclasts, while osteoclasts in the MK-4-treated rats were similar in size to those of the sham group. At 5 weeks, the OVX and MK-4 groups revealed fragmented trabeculae in femoral metaphyses. The cartilage matrix was partially exposed due to stimulated bone resorption in the OVX group, but not in the MK-4 group. After 8 weeks, the OVX rats had little metaphyseal trabeculae, whereas the MK-4-treated rats had maintained short trabeculae. Despite the presence of intense alkaline phosphatase-positive osteoblasts on trabeculae in the MK-4 group, TRAP-positive osteoclasts were flattened without developing ruffled borders. Therefore, MK-4 appeared to lessen the increase in osteoclastic bone resorption induced by OVX, as well as to maintain the accelerated osteoblastic activity. It is of importance to identify the target cells for MK-4 in bone. Autoradiography localized [3H]-labeled MK-4 mainly in osteoblasts and adjacent bone matrices, but not in osteoclasts, indicating that MK-4 targets osteoblasts. Thus, MK-4 appears to target osteoblasts, consequently inhibiting bone loss induced by ovariectomy.

Animals↗

Impairment of G(salpha) function in human brain cortex of Alzheimer's disease: comparison with normal aging.

We examined the quantity and quality of G proteins in membrane preparations of post-mortem human brain, i.e. in parietal, temporal and occipital cortical regions, from normal subjects over age (17-89 years old) and with Alzheimer's disease (AD) in comparison with aged-matched controls. In normal aging, the immunoreactivities determined of G(ialpha), G(qalpha) and G(beta) were inversely correlated with age. The function of G proteins was examined by photoaffinity GTP analogue [azidoanilido GTP (AAGTP)] labelling. AAGTP labelling to G(salpha) and G(i/oalpha), and the ratio of G(salpha) to G(i/oalpha) AAGTP labelling showed no age-dependent changes. In AD compared to age-matched controls, there were no significant differences in the levels of G(sHalpha), G(sLalpha), G(ialpha), G(oalpha), G(qalpha) and G(beta) subunits. Functional effects of G proteins, however, as measured by AAGTP labelling to G(salpha), but not to G(i/oalpha), was significantly decreased in AD compared to controls in the parietal and temporal cortex, but not in the occipital cortex. These results suggest that the disturbances of post-receptor trans-membrane signalling in AD can be attributed to functional changes of G(salpha), and these are independent of alterations in the level for those proteins in normal aging.

Adolescent↗

Reduced phosphorylation of cyclic AMP-responsive element binding protein in the postmortem orbitofrontal cortex of patients with major depressive disorder.

In this study, we examined the amounts of cAMP-responsive element binding protein (CREB) and its phosphorylated form in homogenate preparations from postmortem orbitofrontal cortices of antidepressant drug-free patients with major depressive disorder and age-matched controls by immunoblotting. Immunoreactivies of both CREB and phosphorylated CREB were significantly decreased in depressive subjects compared to controls. The immunoreactivity of phosphorylated CREB was diminished to a greater extent than that of CREB in depressive patients. It has been indicated from animal studies that a transcription factor likely mediates neural plasticity in the mammalian brain and neural tissues. Our results suggest that alterations in the cAMP signaling system, especially in CREB, may be involved in the pathophysiology of depression and be potential targets for antidepressant treatment.

Aged↗

[Total arch replacement for right aortic arch with Kommerell diverticulum and aberrant left subclavian artery].

A 57-year-old man suspected of having angina pectoris underwent coronary angiography and comprehensive examination, which revealed a right-side aortic arch accompanying Kommerell diverticulum and a aberrant left subclavian artery. Esophagography indicated that the esophagus was compressed on its right posterior side and the computed tomography (CT) revealed that the posterior side of the tracheal was compressed, however, the patient experienced no difficulty in breathing, hoarseness of voice or dysphasia. The size of the aortic diverticulum was less than 5 cm and the patient showed no symptom, however, if it was left untreated, there was a risk of rupture in the future. Also the esophagus and tracheal may develop complications due to prolonged compression. Therefore, we decided that the case required surgical operation. Total arch replacement was performed through mediastinotomy and right posterolateral in the 4th intercostal. The postoperative condition was good, and the patient was discharged without any complications.

Aorta, Thoracic↗

Different modes of action of catecholamine-O-methyltransferase inhibitors entacapone and tolcapone on adenylyl cyclase activity in vitro.

Catechol-O-methyltransferase (COMT) inhibitors such as entacapone and tolcapone are used as adjuncts to L-DOPA ( l-3,4-dihydroxyphenylalanine, levodopa) in the treatment of Parkinson's disease. Tolcapone has been reported to associate with diarrhoea, a common reason for study withdrawal. The mechanism of this adverse effect is not yet understood. Cholera toxin causes diarrhoea by permanent activation of G(s) proteins, resulting in increased adenylyl cyclase (AC) activity. The aim of this study was to examine the effects of the COMT inhibitors entacapone and tolcapone on AC activity in membranes isolated from rat striatum, a brain structure enriched with dopaminergic G-protein-coupled receptors and AC activity. This study demonstrates differential effects of tolcapone and entacapone on Gpp(NH)p/dopamine-stimulated AC activity. Entacapone enhanced the stimulatory effect of Gpp(NH)p/dopamine, whereas tolcapone attentuated this effect, suggesting that diarrhoea associated with tolcapone treatment is not caused by permanent activation of G(s) proteins.

Adenylyl Cyclase Inhibitors↗

Effects of oestrogen deficiency on osteoclastogenesis in the rat periodontium.

This study was designed to investigate quantitative changes in osteoclast generation in rat periodontium following ovariectomy. Wistar rats, aged 9 weeks, were subjected to either ovariectomy (OVX) or sham surgery. Osmotic pumps were implanted in 24 rats and either 17beta-oestradiol or vehicle solution were infused continuously. The rats were assigned to one of the following groups: (1) OVX+vehicle; (2) sham+vehicle; or (3) OVX+ 17beta-oestradiol. On the days 7 and 14 after surgery, four rats in each group were killed. Mandibles were demineralized and embedded in paraffin. Frontal sections of alveolar bone in the region of the first molar were cut for enzyme histochemistry and immunohistochemistry. On day 7, there was no significant difference in the number of tartrate-resistant acid phosphatase (TRAP)-positive cells located on bone surfaces in either group. However, the number of TRAP-positive mononuclear cells that were separated from the bone surface was significantly higher in group 1 than in groups 2 and 3. On the day 14, the number of TRAP-positive cells in group 1, which were attached to the bone surface, was significantly higher than had been apparent on day 7. There were also significant increases in the number of nuclei of TRAP-positive cells attached to the bone in group 1 compared with groups 2 and 3 on day 14. These findings demonstrate that oestrogen deficiency induces of osteoclastogenesis in the rat periodontium and that quantitative changes in osteoclastogenesis could be prevented by E2 infusion.

Acid Phosphatase↗

Immunolocalization of osteoclast differentiation factor in rat periodontium.

The aim here was to observe the immunohistochemical localization of osteoclast differentiation factor (ODF)/receptor activator of NF kappa B ligand (RANKL) in the rat periodontium. Rat mandibles were demineralized and embedded in paraffin, and horizontal and frontal sections were prepared for immunohistochemical analysis. In horizontal sections, immunolocalization of RANKL was marked in the distal area of the periodontium of molars in which osteoclasts appeared, due to physiological tooth drift. In frontal sections, RANKL immunoreactivity was localized on spindle-shaped mesenchymal cells around blood vessels near the bone surface in the periodontium. In addition, immunoreaction for RANKL was detected on structures that appeared to be elongated cell processes near blood vessels in frontal sections. Immunohistochemical examination for the general antigen of nerve-specific protein suggested a similarity between these structures and nerve fibres.

Acid Phosphatase↗

Langerhans cell expression of neuropeptide Y and peptide YY.

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides with a variety of known functions. The role of these peptides in the skin is largely unknown, although NPY-like immunoreactivity has been reported in the epidermis. The recent report that these peptides have antimicrobial properties suggests that NPY and PYY may contribute to the skin's defense mechanisms against invading microorganisms. We have demonstrated that Langerhans cells (LC) and a certain BALB/c epidermis-derived dendritic cell line contain mRNA for NPY and PYY using RT-PCR. Furthermore, this dendritic cell line as well as an epidermis-derived dendritic cell line from A/J mice were found to produce NPY and PYY and LC produced PYY, as assessed by radioimmunoassay. These data suggest that the protective function of LC include not only antigen presentation, but also production of antimicrobial peptides.

Animals↗

Effects of ovariectomy on trabecular structures of rat alveolar bone.

An association between postmenopausal osteoporosis and tooth loss has been proposed. However, histomorphometrical changes in alveolar bone following estrogen deficiency are rarely reported with data on microtrabecular structural changes. To clarify the relationship between estrogen deficiency and tooth loss, we histomorphometrically analyzed the trabecular structural changes of mandibular alveolar bone in ovariectomized rats. Twenty-four adult female Fischer rats were used. Eight rats were sacrificed on day 0 (baseline). The remaining 16 rats were divided into two groups. One group was ovariectomized bilaterally (OVX) and the other group was subjected to sham surgery (Sham). After administration of tetracycline and calcein, the animals were sacrificed 60 days after surgery. Bone histomorphometry, node-strut analysis and measurement of thickness of alveolar bone proper were performed on the interradicular septum of the first molar on the sagittal surface. The trabecular bone volume and trabecular number of the OVX group were significantly lower than those of the baseline and Sham groups. All of the bone resorptive and formative parameters of the OVX group were significantly higher (about one-and-a-half times) than those of the Sham group. Several osteoclasts were seen lining the irregular, eroded surface facing the bone marrow in the OVX group. Furthermore, the OVX group tended to have low microtrabecular stiffness and showed significantly thinner distal alveolar bone proper than in the baseline and Sham groups. In summary, estrogen deficiency caused osteoporotic changes and thin alveolar bone proper in the interradicular septum of rat first molar. This phenomenon might accelerate destruction of alveolar bone and tooth loss, especially in elderly women affected by periodontal disease.

Alveolar Process↗

Annexin-1 (lipocortin-1)-immunoreactivity in the folliculo-stellate cells of rat anterior pituitary: the effect of adrenalectomy and corticosterone treatment on its subcellular distribution.

In the pituitary gland, annexin-1 (lipocortin-1) located in folliculo-stellate (FS) cells has been advocated as one of the candidates for paracrine agents produced by FS cells that modulate the release of pituitary hormones. However, the expression and distribution pattern of annexin-1 in FS cells under different circulating corticosteroid conditions has not been examined. Thus, by means of pre-embedding immunoelectron microscopy, we investigated the expression of annexin-1 in FS cells under different corticosteroid conditions. Annexin-1-immunoreactivity was observed in the cytoplasm; especially intense immunoreactivity was detected in the follicle surface of FS cells under control conditions. After adrenalectomy, annexin-1-immunoreactivity almost disappeared, but the immunoreactivity recovered with corticosterone replacement. The expression of glucocorticoid receptor immunoreactivity in the nucleus of FS cells also showed a similar pattern to annexin-1 associated with the changes in the corticosteroid conditions. However, S-100 immunoreactivity, a marker for FS cells, was not changed whatever the corticosteroid conditions. These results confirm that glucocorticoids regulate the annexin-1 expression and demonstrate the translocation of annexin-1 from intracellular to pericellular sites in the FS cells of the rat anterior pituitary gland.

Adrenalectomy↗