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Biomedical subjects

Y Wada

Publications and source records attributed to Y Wada.

At least 1,189 records · Page 66Linked to original sources

Ectopic transcription and the possibility of RNA editing of the human arrestin gene.

PURPOSE: To investigate the ectopic transcription of arrestin in various human organs and tissues. METHODS: Reverse transcriptase-polymerase chain reaction was used to investigate the ectopic transcription of the arrestin gene in the retina, anterior capsule of the lens, iris, bulbar conjunctiva, muscle, skin, placenta, intestine, and human blood. In addition, we examined the expression of arrestin mRNA isolated from whole blood cells of patients with Oguchi disease who had the 1147delA mutation in the arrestin gene. RESULTS: Arrestin was expressed at the mRNA level in all our samples. The mRNA isolated from the blood cells of Oguchi patients was not associated with the same 1147delA mutation as was reported earlier in the arrestin gene but had the normal sequence. CONCLUSIONS: These results demonstrate the ectopic transcription of the arrestin gene in various tissues and also suggest the possibility of RNA editing in the blood cells of Oguchi patients.

Arrestin↗

Mycoplasma bovis-associated suppurative otitis media and pneumonia in bull calves.

Outbreaks of Mycoplasma bovis-associated otitis media and pneumonia occurred on four beef cattle farms in Hokkaido, Japan between 2000 and 2001. The morbidity and mortality were estimated at 8-40 and 30-100%, respectively. Eight calves with bilateral ear droop and exudative otitis media were examined bacteriologically and histopathologically. M. bovis was isolated post mortem from nasal swabs and from the ears, lungs, lymph nodes (cranial and pulmonary), brain and heart of all calves. At necropsy, suppurative exudates were observed in the tympanic bullae of all cases. Numerous abscesses were also found in the petrous portion of the temporal bone and lungs in seven cases. Histopathologically, the exudates within the tympanic bullae consisted of a mixture of neutrophils, necrotic cell debris and fibrin, and the tympanic mucosa was thickened with neutrophil and macrophage infiltration and proliferation of fibrous connective tissue. Pulmonary lesions included extensive foci of coagulative necrosis surrounded by numerous neutrophils. Hepatocytes or renal tubular epithelial cells were enlarged with hyaline cytoplasmic inclusions in four calves. Immunohistochemical labelling confirmed the presence of M. bovis antigen in the cytoplasm of the inflammatory cells in the middle ear, temporal bone and lungs, and was also demonstrated within the cytoplasmic inclusions of the hepatocytes and renal tubular epithelial cells. Ultrastructurally, mycoplasma-like organisms, 200-500 microm in diameter, were found within not only hepatocytes and renal tubular epithelia but also within axons of the facial nerves. The present results show that M. bovis spreads to multiple organs and is capable of invading various kinds of host cell. The intracellular localization may be favourable for evading host immune responses.

Animals↗

Combined hepatocellular and cholangiocarcinoma: correlation between CT findings and clinicopathological features.

PURPOSE: The purpose of this study was to clarify characteristics of combined hepatocellular and cholangiocarcinoma (HCC-CC) on CT and clinicopathological examinations. METHODS: Dynamic incremental CT was performed on 15 combined HCC-CC patients. CT of the early phase was started at 30 s and of the late phase at 120-140 s, after the start of contrast medium injection at a rate of 3 ml/s. The images and clinicopathological findings were retrospectively compared. RESULTS: Lesions grossly resembling HCC (HCC type, n = 6) were well enhanced in the early phase and changed to low attenuation areas in the late phase. In lesions grossly resembling CC (CC type, n = 9), 8 of 9 lesions were enhanced only at the peripheral portions in the early phase and changed to low attenuation areas or had only central portions enhanced in the late phase. The other CC-type lesion was not enhanced in either the early or the late phase. In all 15 cases, there was no dilatation of the intrahepatic bile ducts. Hepatitis B virus surface antigen was positive in five cases. Hepatitis C virus antibody was positive in 10 cases. Serum alpha-fetoprotein (AFP) levels were > or = 200 ng/ml in seven cases. CONCLUSION: In the CC type, enhanced CT images were compatible with CC, but positivities for virus markers and serum AFP levels were almost equivalent to those in HCC. Therefore, the CC type can be diagnosed as combined HCC-CC by evaluating virus markers and serum AFP levels with CT. In addition, no association of intrahepatic bile duct dilatation was considered to be a characteristic feature of combined HCC-CC.

Aged↗

Coronary vasodilator compared to cardiac effects of PY 108-068, a new dihydropyridine vasodilator, on isolated, blood-perfused dog-heart preparations.

We evaluated coronary vasodilator and cardiac effects of PY 108-068 on isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. PY 108-068 was administered intra-arterially (i.a.). PY 108-068 increased (coronary) blood flow in all preparations. In SA node preparations, the drug produced a decrease in sinus rate and, in large doses, atrial standstill. In AV node preparations, the drug produced an increase in AV conduction time. Large doses caused second- or third-degree AV block, but only when injected into the artery supplying the AV node. The doses producing a 15% (nearly half maximum) decrease in sinus rate or a 15% (nearly half maximum) increase in AV conduction time were two to three times the doses that doubled coronary blood flow. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. However, the dose required to reduce the force of contraction of the papillary muscle by 50% was about 30 times the dose that doubled coronary blood flow. The drug was entirely ineffective on rate of ventricular automaticity. We conclude that PY 108-068 is not likely to produce reflex tachycardia when administered systemically in coronary vasodilator doses.

Animals↗

Separation of the coronary vasodilator from the cardiac effects of PN 200-110, a new dihydropyridine calcium antagonist, in the dog heart.

Coronary vasodilator and cardiac effects of PN 200-110 were compared by use of isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. PN 200-110 was administered intraarterially. In all preparations PN 200-110 produced an increase in coronary blood flow. In SA node preparations, the drug produced a decrease in sinus rate and atrial standstill as well, but only in large doses. The dose that produced a 15% (nearly half-maximum) decrease in sinus rate was about three times the dose that doubled coronary blood flow. In AV node preparations, the drug produced an increase in AV conduction time and, in large doses, second- or third-degree AV block only when it was injected into the artery supplying the AV node. The dose that produced a 15% (nearly half-maximum) increase in AV conduction time was approximately 12 times the dose that doubled coronary blood flow. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. However, the dose that produced a 50% decrease in the force of contraction of the papillary muscle was approximately 14 times the dose that doubled coronary blood flow. These effects of PN 200-110 were of long duration. The drug was entirely ineffective in changing the rate of ventricular automaticity. The order of selectivity of PN 200-110 was as follows: coronary blood flow greater than SA nodal automaticity greater than AV nodal conduction greater than ventricular muscle contraction. This cardiovascular profile of PN 200-110 is slightly different from that of PY 108-068, a compound closely related to PN 200-110 in chemical structure.

Animals↗

A new experimental model for drug studies: effects of phenobarbital and phenytoin on photosensitivity in the lateral geniculate-kindled cat.

Photosensitivity was acquired as a result of kindling in the lateral geniculate body (GL), and the GL-kindled cat pretreated with DL-allylglycine showed a stable level of photosensitivity. To test the usefulness as a model for the evaluation of anticonvulsant drugs, the effects of phenobarbital (PB) and phenytoin (PHT) on photosensitivity were studied in the GL-kindled cat under DL-allylglycine. PB (5 and 10 mg/kg intravenously, i.v.) completely suppressed photically induced seizures in most subjects at plasma concentrations of 7-16 micrograms/ml, and this anticonvulsant action persisted for at least 4 h after the injection. PHT (15 mg/kg, i.v.) at plasma concentrations of 9-15 micrograms/ml produced toxic signs, e.g., pupil dilatation, hypersalivation, and tachypnea. At this dose, PHT was inactive against photically induced myoclonus but prevented the elicitation of a generalized tonic-clonic convulsion. From these results showing that the effects of anticonvulsant drugs on photically induced seizures can be assessed in relation to plasma concentration and acute neurologic toxicity, we suggest that the GL-kindled cat is a potentially useful animal model of epilepsy for testing the efficacy of anticonvulsant drugs.

Allylglycine↗

O,O,S-trimethyl phosphorothioate increases Ca2+ independent nitric oxide synthase activity in the lung but decreases Ca2+/calmodulin dependent type in the cerebellum in Fischer 344 rats.

In the present study, we investigated the possible role of nitric oxide synthase in lung injury using female Fischer 344 rats as a model animal and O,O,S-trimethyl phosphorothioate as an example of lung toxicants. One form of nitric oxide synthase, Ca2+/calmodulin dependent type, decreased monotonously in a dose-dependent manner in the cerebellum. In contrast, O,O,S-trimethyl phosphorothioate increased activities of Ca2+ independent nitric oxide synthase in the lung in a dose-associated manner from 5 mg/kg to 15 mg/kg, but decreased at 30 mg/kg. Lung toxicity of O,O,S-trimethyl phosphorothioate, however, as judged both by functional impairments (PaCO2 and [HCO3-]) and histopathological changes, increased sharply at 30 mg/kg. We thus tested the hypothesis that a potent nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester, may modify lung injury induced by O,O,S-trimethyl phosphorothioate. Treatment with NG-nitro-L-arginine-methyl ester at 20 mg/kg/day aggravated lung injury induced by O,O,S-trimethyl phosphorothioate: Pulmonary oedema and bleeding occurred, leading to an increase in mortalities at 15 mg/kg of O,O,S-trimethyl phosphorothioate, at which level it did not induce such changes as when dosed alone. These findings indicate that nitric oxide synthase in the lung might play a protective role in lung injury.

Amino Acid Oxidoreductases↗

Inhibition by eicosapentaenoic acid of oxidized-LDL- and lysophosphatidylcholine-induced human coronary artery smooth muscle cell production of endothelin.

The objectives of the present study were (1) to determine whether oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (lyso-PC), a major phospholipid component of oxidized LDL, stimulate the production of endothelin-1 (ET)-1 in cultured human coronary artery smooth muscle cells (SMCs), and (2) to examine the possible effect of an antiatherogenic agent, eicosapentaenoic acid (EPA), on oxidized-LDL- and lyso-PC-stimulated ET-1 production in these cells. Oxidized LDL (10-50 microg/ml) and lyso-PC (10(-7) to 10(-5) mol/l) stimulated ET-1 production in a concentration-dependent manner. By contrast, the effects of native LDL and phosphatidylcholine were modest or absent. Lyso-PC (10(-7) to 10(-5) mol/l) and oxidized LDL (10-50 microg/ml) significantly induced particulate protein kinase C (PKC) activation. Lyso-PC- and oxidized-LDL-stimulated ET-1 production was significantly inhibited by PKC inhibitor, PKC (19-36). EPA (80-160 micromol/l) clearly suppressed ET-1 production stimulated by oxidized LDL and lyso-PC in a concentration-dependent manner. Furthermore, EPA (160 micromol/l) significantly inhibited lyso-PC (10(-5) mol/l)- and oxidized LDL (50 microg/ml)-induced particulate PKC activation. Results suggest that oxidized LDL and lyso-PC stimulate ET-1 production by a mechanism involving activation of PKC, and that EPA suppresses ET-1 production stimulated by lyso-PC as well as oxidized LDL probably through the modulation of PKC in human coronary artery SMCs. EPA may exert an antiatherosclerotic effect, in part, through these mechanisms.

Angiotensin II↗

Age-related changes in energy production in fresh senescence-accelerated mouse brain slices as revealed by positron autoradiography.

To investigate age-related changes in cerebral energy production, we compared senescence-accelerated prone mice (SAMP8) as an animal model of accelerated aging and senescence-accelerated resistant mice (SAMR1) as a control. Considering that the cerebral glucose metabolic rate (CMRglc) at the time of O(2) deprivation and 2,4-dinitrophenol (DNP) loading would reflect anaerobic glycolytic capacity and mitochondrial function, respectively, we investigated dynamic changes in CMRglc before and after loading with these perturbations. Fresh brain slices were incubated with [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [(18)F]FDG uptake in these slices were obtained on the imaging plates. The fractional rate constant (=k(3)*) of [(18)F]FDG proportional to the CMRglc was evaluated by applying the Gjedde-Patlak graphical method to the image data. The k(3)* value before the hypoxic perturbation in all of the brain sites analyzed was higher in SAMP8 than SAMR1 in both the 2- and 10-month-old groups. With O(2) deprivation, k(3)* values were higher without site specificity in the 2-month-old SAMP8 than in 2-month-old SAMR1, whereas in 10-month-old mice, there was no significant difference between the two groups. In contrast, with DNP loading, while no significant difference was noted between 2-month-old SAMP8 and 2-month-old SAMR1, in 10-month-old mice, the SAMP8 group showed lower values in certain regions than SAMR1 mice. These results suggest that in the brain tissue of SAMP8, a marked transient enhancement of anaerobic glycolytic capacity in the 2-month-olds and a decrease in mitochondrial function in the subsequent period occur, as a result of which glucose metabolism appears to be enhanced in both the 2- and 10-month-old groups compared to SAMR1 mice.

Age Factors↗

Effect of central and continuous intravenous injection of interleukin-1 beta on brain c-fos expression in the rat: involvement of prostaglandins.

Utilizing immunohistochemistry for the c-fos protein to detect neuronal activity, we examined the effects of continuous intravenous and intracerebroventricular infusion of interleukin (IL)-1 beta in the rat brain, and the involvement of prostaglandins (PGs) in IL-1 beta-induced c-fos expression. Continuous intravenous infusion of IL-1 beta (10 ng/min) markedly augmented c-fos expression in the paraventricular (PVN) and the supraoptic (SON) nuclei of the hypothalamus as well as in the central amygdaloid nucleus (CeA). The number of IL-1 beta-induced c-fos-positive cells in the PVN and SON was significantly lower in rats pretreated with indomethacin than in vehicle-treated rats. However, the number of IL-1 beta-induced c-fos-positive cells in the CeA remained unchanged. c-fos protein was induced after intracerebroventricular infusion of IL-1 beta (200 ng) in the PVN, SON, and arcuate nuclei of the hypothalamus, and in the CeA. The induction of c-fos immunoreactivity by central administration of IL-1 beta was blocked by indomethacin (500 micrograms/rat), except in the CeA. These findings suggest that PGs are involved in the complex transmission of signals from circulating or central IL-1 beta to hypothalamic neurons.

Amygdala↗

Delirium in the elderly: relationship of clinical symptoms to outcome.

Twenty-eight elderly patients meeting the DSM-III-R criteria for delirium were evaluated using the Delirium Rating Scale (DRS) in order to examine the relation between the clinical symptoms of delirium and its outcome. Patients whose delirious episode improved within 1 week had a significantly lower DRS score at the time of psychiatric consultation than patients whose delirium lasted more than 1 week. Neither the difference between the mean ages nor the sex distribution in the two groups was statistically significant. The present study suggests that the DRS is a valuable instrument for predicting the clinical outcome of delirium.

Aged↗

Relationship of serum testosterone level with proliferating cell nuclear antigen and nm23 protein in human prostatic carcinoma tissue.

OBJECTIVE: To elucidate the biological significance of proliferating cell nuclear antigen (PCNA) and nm23 immunoreactivity in prostatic carcinoma (PC) tissue, both expressions were immunohistochemically analyzed, and the results were compared with the change of the serum testosterone (T) level. METHODS: The paraffin-embedded materials obtained from 49 untreated PC and 16 hormonally refractory PC (hr-PC) were used. Of the 49 untreated PC, 35 received luteinizing hormone-releasing hormone (LH-RH) analogue treatment, while 14 received a cisplatin-based chemotherapy. The immunohistochemistry of PCNA and nm23 protein was performed using an anti-PCNA monoclonal antibody (PC-10) and an antihuman nm23 polyclonal antibody (OA-11-890), respectively. The serum T level was measured by means of radioimmunoassay. RESULTS: In both untreated PC and hr-PC, the immunoreactivity of nm23 protein significantly correlated with the PCNA expression. Both PCNA expression and nm23 protein immunoreactivity were higher in poorly differentiated PC than those observed in well-differentiated PC, while no significant difference in the serum T level was observed between poorly and well-differentiated PCs. On the other hand, both PCNA expression and nm23 protein immunoreactivity were significantly higher in hr-PC than those observed in untreated PC, whereas the serum T level was significantly lower in hr-PC. In 35 PCs treated with LH-RH analogue, no significant difference in both PCNA expression and nm23 protein immunoreactivity was found between those specimens obtained before and at 3 months after the treatment, while a significant reduction of the serum T level was noted at 3 months after the treatment. Similarly, in 14 PCs treated with a cisplatin-based chemotherapy, the same change of PCNA expression and nm23 protein immunoreactivity as observed in LH-RH analogue treatment was found, while no significant difference of the serum T level was found. CONCLUSIONS: These findings appear to indicate that (1) nm23 protein immunoreactivity is interrelated with cellular proliferation in PC tissue and (2) alteration of the serum T level during a short period was not enough to explain the essential change of cellular proliferation of PC tissue, but might reflect other aspects of tumor growth such as apoptosis.

Antigens, Neoplasm↗

The effects of hyaluronan on the meniscus and on the articular cartilage after partial meniscectomy.

The effect of hyaluronan (molecular weight = 8 x 10(5)) on the meniscus and on the articular cartilage was assessed after partial meniscectomy in a rabbit model. On gross examination, remodeled meniscus appeared as newly synthesized translucent tissue, and was seen in both vehicle- and hyaluronan-treated menisci. Histologically, safranin O staining revealed the strong presence of glycosaminoglycans in the newly remodeled tissue, and polarized light demonstrated the absence of mature collagen architecture. Hydration of the hyaluronan-treated menisci was significantly less than that of the vehicle-treated menisci, and the reducible collagen cross-link dihydroxylysinonorleucine was significantly increased in the hyaluronan-treated menisci compared with the vehicle-treated menisci, indicative of a greater degree of collagen remodeling. In situ hybridization of vehicle- and hyaluronan-treated menisci revealed a high level of type I procollagen mRNA expression and minor expressions of types II and III mRNA. Expression of the type I collagen gene appeared to be more pronounced in the hyaluronan-treated menisci than in the vehicle-treated menisci. The tibial plateaus revealed mild cartilage fibrillation after partial meniscectomy. A statistically significant difference between vehicle- and hyaluronan-treated cartilage was not demonstrated in the present study because of the slow development (i.e., 12 weeks) of osteoarthritis after partial meniscectomy in the rabbit model. These results suggest that in the rabbit model, hyaluronan enhances collagen remodeling and inhibits meniscal swelling after partial meniscectomy in the avascular region.

Analysis of Variance↗

Neoadjuvant intraarterial high-dose chemotherapy and autologous peripheral blood stem cell transplantation for advanced breast cancer.

Eight locally advanced breast cancer patients were treated with neoadjuvant intraarterial high-dose chemotherapy (epirubicin) plus MPA combined with autologous PBSCT. All patients completed the scheduled treatment, and there were no toxic deaths. Patients were treated with an escalating dose of epirubicin (370-480 mg) and cyclophosphamide (0-6000 mg). The rate of clinical response was 100%. The rate of good histologic response was 87.5% in the main tumor and 75% in diseased lymph nodes. The 2-year survival rate was 100%. Six patients were disease-free at the time of writing. This treatment resulted in higher rates of clinical and histologic response when compared with standard-dose intraarterial chemotherapy.

Adult↗

A case report of cribriform carcinoma of the pancreas with long time survival.

A 62-year-old man had complained of left abdominal pain and tenderness and a body weight loss. Abdominal ultrasonography and computed tomography revealed homogeneous tumor with clear margin, and an irregular shape (3.5 x 2.0 cm) in the body of the pancreas. Endoscopic retrograde cholangiopancreatography showed a shadow defect in the main pancreatic duct adjacent to the tumor, which suggested intraductal tumor spread. Distal pancreatectomy with splenectomy and left paraaortic lymph node dissection was performed. Microscopically, the tumor showed microtubular carcinoma, which was characterized by a cribriform pattern, medullary growth, and little interstitium. The tumor was encapsulated by a relatively thick fibrous capsule. The patient was discharged uneventfully, and he is alive 33 months after operation without a distinct sign of recurrence. In conclusion, cribriform carcinoma of the pancreas has specific characteristics, such as good prognosis, expansive growth with little invasion, intraductal growth and spread without mucin production and histological marked cribriform pattern. This type of carcinoma should be classified as a new disease entity of carcinoma of the pancreas.

Carcinoma↗