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Biomedical subjects

H Sakaguchi

Publications and source records attributed to H Sakaguchi.

At least 181 records · Page 10Linked to original sources

Expression of E-cadherin and alpha- and beta-catenin mRNAs in uterine cervical cancers.

To show the mRNA expressions of E-cadherin and alpha- and beta-catenin-which mainly compose the adherens junction-associated with invasion and metastasis of uterine cervical cancers, we studied the expression of E-cadherin and alpha- and beta-catenin mRNAs in cancers in comparison with normal counterparts. The integral expression of E-cadherin and alpha- and beta-catenin mRNAs was suppressed in the metastatic lesions of advanced uterine cervical cancers, while it was not in the primary tumors. Therefore, the suppressed expression of main adhesion molecules in the adherens junction might contribute to adherens-junctional dysfunction, which might lead to invasiveness and metastatic potential of advanced uterine cervical cancers as one rate-limiting step.

Adult↗

A case of nonfunctioning pituitary adenoma resembling so-called silent corticotroph adenoma.

It has been indicated that some subsets of clinically nonfunctioning pituitary adenoma exhibit immunohistochemical and ultrastructural features of somatotroph or corticotroph cells, which are described as silent somatotroph and corticotroph adenomas, respectively. We here describe a 70-year-old woman with nonfunctioning pituitary adenoma presenting with visual disturbance. None of the pituitary hormones show abnormal finding. Magnetic resonance imaging study revealed a pituitary tumor which developed inferiorly into the sphenoidal sinus. Tumor resection was performed by a transsphenoidal approach, and resulted in a partial resection of the tumor. The specimen indicated chromophobic adenoma. Immunohistochemical examination revealed a characteristic distribution pattern of cytokeratin staining for ACTH cell adenoma, although immunostaining for ACTH was only weakly positive. After the operation, only ACTH secretion was impaired, requiring replacement therapy with glucocorticoid. Bromocriptine was administered in order to prevent the recurrence of the tumor. It remains to be elucidated whether the present case could be classified as silent corticotroph adenoma, which was originally indicated to have aggressive characteristics, i.e., progressive visual defect, high incidence of infarction and frequent recurrence.

Adenoma, Chromophobe↗

Expression of estrogen receptor wild type and exon 5 splicing variant mRNAs in normal and endometriotic endometria during the menstrual cycle.

Expression of estrogen receptor exon 5 splicing variant (ER-E5SV) mRNA contributes to dominant positive properties and metastatic potential of gynecological cancers. Therefore, in endometriotic endometria, which conserve implantation and tumor-like spreading potentials, the expression of ER-E5SV and estrogen receptor wild type (ER-WT) mRNA was analyzed, to investigate the biological implications. Estrogen receptor wild type mRNA in normal endometria was downregulated after ovulation, but not in endometriotic endometria. Therefore the wild type cascade in endometriotic endometria might be partly disorganized. The level of ER-E5SV mRNA in endometriotic endometria was lower than that in normal endometria, regardless of the stage in the menstrual cycle. However, there was no significant difference in the ratio of ER-E5SV to ER-WT mRNA in both normal and endometriotic endometria. On the other hand, the level of ER-E5SV mRNA in both normal and endometriotic endometria did not vary during the menstrual cycle. The dominant positive behavior of ER-E5SV might be masked by the functional cascade of ER-WT in normal endometria, but not in endometriotic endometria. This status might result in an incomplete response to endogenous steroids, and contribute to implantation and spreading potentials of endometriosis.

Adult↗

The multiple roles of macrophage scavenger receptors (MSR) in vivo: resistance to atherosclerosis and susceptibility to infection in MSR knockout mice.

Both type I and type II MSRs are integral membrane proteins containing a collagenous domain and elicit an extraordinarily wide range of ligand binding capability. They were found during the search for the molecule(s) responsible for the accumulation of modified LDL during atherogenesis. However, all prior the evidence relating to their physiological and pathophysiological roles in vivo had been indirect. Targeted disruption of the MSR gene results in a reduction in the size of atherosclerotic lesions in an apo E deficient animal. Macrophages from MSR deficient mice exhibit a marked decrease in modified LDL uptake in vitro, whereas modified LDL clearance from plasma remains normal, suggesting that there are alternative mechanisms for the uptake of modified LDL from the circulation. In addition, MSR knockout mice are more susceptible to L. monocytogenes and HSV-1 infection, indicating a role for MSR in host defense against various pathogens.

Animals↗

[A case of asymptomatic posterior mediastinal pheochromocytoma diagnosed during the procedure of video-assisted thoracic surgery (VATS)].

The patient was a 20-year-old male. On routine check-ups, a posterior mediastinal tumor was found radiologically and referred to our hospital for the operation. During the Video-Assisted Thoracic Surgery (VATS), sudden elevation of the blood pressure up to 270 mmHg was observed by the tumor palpation. At once we diagnosed as pheochromocytoma. Changing the VATS to usual thoracotomy the tumor was completely removed and histologically confirmed. After the operation the patient was uneventful and the value of norèpinephrine reduced to normal range from 2912 pg/ml. The posterior mediastinal pheochromocytoma is rare and this report is the 6 th case in Japan. Clinical characteristics were discussed in addition to the review of the literature.

Adult↗

Optimal lipiodol volume in transcatheter arterial chemoembolotherapy for hepatocellular carcinoma: study based on lipiodol accumulation patterns and histopathologic findings.

To clarify the optimal dose of Lipiodol (Andre Guerbet, Aulnay-sous-Bois, France) during Lipiodol-transcatheter arterial embolization (L-TAE) and segmental L-TAE used to treat hepatocellular carcinoma, we studied the relationship between the volume of Lipiodol used during these procedures and the necrosis rates in resected specimens, as well as the correlation with the Lipiodol accumulation pattern based on the computed tomography findings (L-CT) and the volume of Lipiodol in resected and nonresected cases after L-TAE or segmental L-TAE. The L-CT and the dose of Lipiodol injected (mL) were studied correlatively in 198 cases (28 resected cases and 170 nonresected cases; tumor size < or = 5 cm in 52 cases and > 5 cm in 118 cases) that underwent L-TAE and in 80 cases (14 resected cases and 66 nonresected cases, tumor size < or = 5 cm in 52 cases and > 5 cm in 14 cases) that underwent segmental L-TAE. The L-CT was classified into four types: type I, homogeneous accumulation (type Ia, accumulation around the tumor; type Ib, no accumulation around the tumor); type II, partial defect; type III, sporadic accumulation; and type IV, punctate or no accumulation. In the 42 resected cases (L-TAE, 28 cases; segmental L-TAE, 14 cases), type I was seen in 68% (Ib, 100%) of the L-TAE cases and 93% (Ia, 79%; Ib, 14%) of the segmental L-TAE cases. The necrosis rate of the cases with type Ib L-CT was 90% to 100%, and all type Ia cases showed complete necrosis. In the 236 nonresected cases (L-TAE, 170 cases; segmental L-TAE, 66 cases), the volume of Lipiodol injected correlated with the L-CT type. In the L-TAE cases with a tumor size < or =5 cm, the frequency of the injected Lipiodol volume (D) being greater than the tumor diameter (d) (D > or = d) was 90%, and 87% of the cases with D > or = d showed type Ib L-CT. In the group whose tumor diameter (d) was more than 5 cm, the frequency of D > or = d was 25%, and 70% of the cases of D > or = d were type Ib. The frequency of D < d was 75%, and in 13% of these cases the L-CT was type Ib and the maximum dose was approximately 10 mL. In segmental L-TAE using the same dose of Lipiodol as in L-TAE, the frequency of D > or = d was 83%, and 93% of those cases showed type I, including 85% of type Ia. There was a correlation between the L-CT type and the necrosis rate, and type I, especially Ia in segmental L-TAE, showed complete necrosis in almost all cases. In L-TAE, standards for the optimal dose of Lipiodol are thought to be as follows: D > or = d in cases with d < or = 5, and slightly D < d and 10 mL maximally in cases with d > 5. In segmental L-TAE using the same dose of Lipiodol as in L-TAE, enhancement of the therapeutic effect was seen compared with L-TAE. This is surmised to have been because of the higher Lipiodol volume with anticancer agents per unit volume of the tumor in segmental L-TAE.

Carcinoma, Hepatocellular↗

[Propofol anesthesia for a schizophrenic patient].

A 41-year-old man weighing 68 kg was scheduled for bilateral tonsillectomy because of palmoplantar pustulosis. The patient had been diagnosed as schizophrenic 10 years earlier. Psychotropic agents, mosapramine (75 mg.day-1), bromperidol (6 mg.day-1), cloxazolam (3 mg.day-1), biperiden (1 mg.day-1) and nitrazepam (5 mg as needed), were administered until the day before surgery. On the day of surgery, atropine (0.g mg) and midazolam (4 mg) were administered intramuscularly as premedication. Anesthesia was induced by intravenous propofol (120 mg) and fentanyl (100 microgram) followed by nasotracheal intubation using vecuronium (7 mg). Anesthesia was maintained with inhalation of oxygen and nitrous oxide (2 l.min-1 each) and the intravenous infusion of propofol (5-10 mg.kg-1 x h-1) supplemented by fentanyl (100 microgram). The patient recovered from anesthesia uneventfully. Immediately after surgery, intravenous haloperidol (5 mg) and intramuscular biperiden (1 mg) were given. The daily oral administration of psychotropics was resumed on the first postoperative day. There were no complications such as hypotension, arrhythmia, or worsening of the mental condition, throughout the course.

Adult↗

Ex vivo study of the effects of dietary magnesium deficiency on the formation and release of NO from endothelial cells and the sensitivity to NO of smooth muscle cells of thoracic aortas isolated from rats.

We found that the contractile responses to phenylephrine (PE) of isolated endothelium-intact thoracic aortas were enhanced by a nitric oxide (NO) synthase inhibitor, nitro-L-arginine (LNAG). and the magnitude of this enhancement was significantly greater in Mg-deficient than control rats. In this study, we used a sandwich method to evaluate the effects of dietary Mg deficiency on the ability of vascular endothelial cells to form and/or release NO and on the sensitivity to NO of vascular smooth muscle cells. Male Wistar rats were fed a Mg-deficient (10 mg Mg/kg diet) or control (700 mg Mg/kg diet) diet for 30 days. With the sandwich method, when endothelium-denuded thoracic aortas from chow fed rats were used as the assay vessels, and endothelium-intact aortas from control or Mg-deficient rats were used as the NO-donor vessels, neither the aortic contractile responses to PE nor the enhancement by LNAG of these responses in control and Mg-deficient rats differed significantly. When endothelium-denuded thoracic aortas from control or Mg deficient rats were used as the assay vessels and endothelium-intact aortas from chow fed rats were used as NO-donor vessels, LNAG enhanced PE-induced contractions to a significantly greater extent in Mg-deficient than control rats. Furthermore, sodium nitroprusside (a NO donor) had a greater relaxant effect on endothelium-denuded thoracic aortas isolated from Mg-deficient than control rats. These ex vivo results suggest that dietary Mg deficiency in rats has little effect on the formation and/or release of NO by aortic endothelial cells. but it does appear to increase the sensitivity to NO of aortic smooth muscle cells.

Animals↗

Ex vivo study of the increased sensitivity to NO of endothelium-denuded thoracic aortas isolated from dietary magnesium-deficient rats.

The mechanisms underlying the enhanced relaxant responses to sodium nitroprusside (SNP) associated with magnesium (Mg) deficiency were examined using endothelium-denuded thoracic aortas isolated from rats with dietary Mg deficiency. This enhancement of SNP-induced relaxation was abolished or depressed in the presence of methylene blue (a guanylate cyclase inhibitor). The relaxant responses to 8-bromo cyclic GMP (8-Br cGMP; a membrane-permeable cGMP) of thoracic aortas isolated from Mg-deficient rats were enhanced like those to SNP. These enhanced relaxant responses were depressed by tetraethylammonium (a non-specific K+ channel blocker). Charybdotoxin, a large conductance Ca2+-activated K+ (K[Ca]) channel blocker, inhibited 8-Br cGMP-induced relaxations of aortas from Mg-deficient and control rats. Apamin, a small conductance K(Ca) channel blocker, inhibited 8-Br cGMP-induced relaxations of aortas from Mg-deficient, but not control rats. The relaxant responses to cromakalim (an ATP-sensitive K+ channel opener) of the two groups were not significantly different. These ex vivo results show that dietary Mg deficiency in rats leads to increased sensitivity to NO of endothelium-denuded thoracic aortas in vitro and K(Ca) channel activation via cGMP may be involved in this enhancement.

Animals↗

Expression of basic fibroblast growth factor and its mRNA in advanced ovarian cancers.

To investigate whether growth, invasion and metastasis of ovarian cancer cells is associated with neovascularization, the expression of basic fibroblast growth factor (FGF) and its mRNA in ovarian cancers and normal ovaries as controls were determined by ELISA and reverse transcription-polymerase chain reaction-Southern blot, respectively. The relationships between the expression and the histological grading, clinical backgrounds or clinical staging in ovarian cancers were analyzed. The levels of basic FGF and its mRNA were significantly higher in advanced primary ovarian cancers, regardless of histological types and some clinical backgrounds. Therefore, this status might contribute to the acceleration of growth, invasion, and metastasis with neovascularization in advanced ovarian cancers.

Adult↗

[Successful operation on giant solitary fibrous tumor of the pleura].

A 68-year-old man began complaining of dizziness and dyspnea on exertion 2 months ago. Chest X-ray and CT scan taken on admission revealed a giant tumor occupying almost all of the right thoracic cavity. The mediastinum, especially RA and IVC, was markedly oppressed and shifted by the tumor. MRI showed no invasive lesions of the tumor into adjacent organs. An operation was performed under the tentative diagnosis of solitary fibrous tumor (SFT) of the pleura by transcutaneous needle biopsy. The tumor was encapsulated and resected from the lower lobe of the right lung using a surgical stapler. Then the tumor was carefully dissected from the chest wall, pericardium and diaphragma, and removed completely. It weighed 3920 g and measured 22 x 20 x 20 cm. Various immunohistochemical properties of the specimen were morphologically compatible with SFT. The postoperative course was uneventful and the patient is now free of complaints. Because malignant cases of SFT have been reported a careful follow-up will be performed.

Aged↗

Suppression of E-cadherin and alpha- and beta-catenin mRNA expression in the metastatic lesions of gynecological cancers.

To know the biological role of adherens junction, mainly consisting of E-cadherin and alpha- and beta-catenins, associated with invasion and metastasis of ovarian, uterine endometrial and cervical cancers, we studied the expression of E-cadherin and alpha- and beta-catenin mRNAs in the metastatic lesions in comparison with those in the primary tumors. The integral expression of E-cadherin and alpha- and beta-catenin mRNAs in the metastatic lesions in comparison with that of the primary tumors was suppressed in 4 of 5 cases of ovarian cancers, all cases of uterine endometrial cancers, and 4 of 5 cases of uterine cervical cancers. Therefore, the suppressed expression of the main adhesion molecules in the adherence junction might contribute to the cell-to-cell junctional dysfunction, which might lead to the acquisition of invasiveness and metastatic potential of gynecological cancers as one of the rate-limiting steps.

Aged↗

Developmental changes in axon terminals visualized by immunofluorescence for the growth-associated protein, GAP-43, in the robust nucleus of the archistriatum of the zebra finch.

Two afferents to the robust nucleus of the archistriatum (RA) are important for song learning by the zebra finch. The growth-associated protein-43 (GAP-43) has been used as a molecular marker for axonal growth. In these experiments, the axon terminals were visualized by immunofluorescence with antibodies against GAP-43 and we studied the developmental processes in the zebra finch after the invasion of the RA by afferent fibers. After waiting at the dorsal border of the RA before invading the RA, the axon terminals from the higher vocal center (HVc) first contacted the soma, and then redistributed and established synapses on the dendrites. This initial contact with the soma may be closely related to the neurotrophic properties of the axon terminals from the HVc neurons.

Animals↗

Characteristics of current induced potential oscillations of a triolein impregnated membrane placed between identical salt solutions.

Periodic oscillations of electric potential were induced by DC electric current between identical salt solutions separated by a membrane filter impregnated with triolein. The oscillation period was controlled by the base electric potential, and temperature dependence of base conductance and conductance amplitude were both close to that of the electric conductivity of the aqueous salt solution. Effects of salt concentration on membrane conductance and on oscillation characteristics were experimentally investigated, and the lifetime of the membrane and of each oscillation were much improved by regulating the concentration of the salt solution. Moreover, characteristics of oscillation curves could be controlled. All the experimental results could be explained by a model where the oscillation was generated by a periodic change of the diameter of a hole through the membrane, which opened in one of the pores filled with triolein.

Electric Conductivity↗

Expression of antigens related to apoptosis and cell proliferation in chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis.

The initial injury in primary biliary cirrhosis (PBC) is the destruction of portal bile ducts. Little information is available on apoptosis and cell proliferation in such bile ducts, so we used immunohistochemical techniques to locate molecules related to apoptosis [Fas antigen, Lewis Y antigen (BM1/JIMRO), and bcl-2 protein] and to cell proliferation (proliferating cell nuclear antigen, PCNA) in 21 patients with PBC. In addition, nick-end labelling was done to locate DNA fragmentation. The expression of these molecules in chronic nonsuppurative destructive cholangitis (CNSDC) was examined. Cell death and PCNA expression were both found in portal bile ducts affected by CNSDC in 7 of the 13 CNSDC patients examined. Fas antigen was found on the plasma membrane and rough endoplasmic reticulum of bile-duct cells with CNSDC in the frozen sections of all 6 patients with CNSDC out of the 9 patients inspected, and this antigen was found also in bile-duct cells without CNSDC in 2 of these 9 patients. It was not found in anatomically normal liver (from 2 patients with Gilbert's disease). The Lewis Y antigen was found in bile ducts with CNSDC and in proliferated ductules in all 16 patients examined. No bcl-2 protein was found in any bile-duct or ductule cells, but it was found in the cytoplasm of lymphocytes surrounding or invading CNSDC. DNA fragmentation was found in the nuclei of bile-duct cells with CNSDC by nick-end labelling. Our study indicated that Fas-mediated apoptosis might be involved in CNSDC, but that bcl-2 protein seems to participate less than Fas. Although the Lewis Y antigen was found in many bile ducts, the relationship between the antigen and apoptosis remains unknown because there was no evidence that this antigen mediates apoptosis.

Adult↗

Sex differences in the developmental changes of GABAergic neurons in zebra finch song control nuclei.

Small neurons in a sexually dimorphic nucleus of the zebra finch, the robust nucleus of the archistriatum (RA), were immunoreactive for gamma-aminobutyric acid (GABA). This dimorphism arose from the sex differences in the development of the RA neurons. We examined whether neurons with GABA-like immunoreactivity (GABA-LI) undergo the same developmental changes as the cresyl-violet-stained neurons in the RA. Somata with GABA-LI from male finches became larger during development, while somata with GABA-LI from female finches became smaller, at a rate similar to that in the total population of RA neurons. However, there were marked sex differences in the development of the number of RA neurons with GABA-LI. In the female, neurons with GABA-LI were lost at a rate which was similar to the rate of loss of the total population of RA neurons. On the other hand, in the male, the number of neurons with GABA-LI increased transiently during the sensitive period of song learning, while the total number of RA neurons did not change. This transient increase may be related to the fact that only male birds learn their song during a sensitive period.

Animals↗