Search PubMed⌕ Search

Biomedical subjects

H Sugihara

Publications and source records attributed to H Sugihara.

At least 145 records · Page 8Linked to original sources

Papillary carcinoma of the thyroid with exuberant nodular fasciitis-like stroma.

We describe a rare case of papillary carcinoma with extensive proliferation of stromal cells. The stromal cells were immunocytochemically positive for vimentin, alpha-smooth muscle actin and desmin, but negative for cytokeratin, epithelial membrane antigen, S-100, thyroglobulin and CD34. These results and the ultrastructure of the stromal cells, which exhibited the characteristics of both fibroblasts and smooth muscle cells, indicated an origin from myofibroblasts. We conclude that myofibroblastic proliferation may contribute to the stromal response in the slow growth of the papillary carcinoma.

Carcinoma, Papillary↗

Amplification of growth factor receptor genes and DNA ploidy pattern in the progression of gastric cancer.

To study the background of oncogene amplification in gastric cancers, we examined the correlation between occurrence of oncogene amplification and DNA ploidy pattern. In 57 primary gastric cancers, amplifications of c-erbB, c-erbB-2, c-met and K-sam genes were investigated by Southern blot analysis, and the DNA ploidy pattern was determined by static cytofluorometry and by flow cytometry. Oncogene amplification was detected in 11 cancers, 10 of which were advanced gastric cancers and 1 was an early differentiated type. The amplification of c-erbB-2 and K-sam genes was found exclusively in differentiated- and undifferentiated-type cancers, respectively. Of the 11 cancers, 5 were DNA-diploid and 6 were DNA-aneuploid. All the 11 tumours with oncogene amplification contained polyploid cell populations (polyploidy), whereas none of the tumours without polyploidy showed oncogene amplification. In differentiated-type cancers the incidence of polyploidy was high in both early and advanced stages, while in undifferentiated-type cancers it was low in early stages but significantly higher in advanced stages. It was shown that amplification of growth factor receptor genes is closely related to the presence of polyploidy, irrespective of any different stemline DNA-ploidy mode. The time-course of oncogene amplification and kinds of genes amplified may differ between differentiated- and undifferentiated-type gastric cancers.

Adenocarcinoma↗

Reconstruction of prostatic acinus-like structure from ventral and dorsolateral prostatic epithelial cells of the rat in three-dimensional collagen gel matrix culture.

PURPOSE: The study was carried out to reconstruct a prostatic acinus-like structure from prostatic epithelial cells in a new culture system which can provide a more physiological condition than conventional cell culture methods. MATERIALS AND METHODS: Prostatic epithelial cells were isolated from ventral and dorsolateral prostates of the rat and were separately cultured in three-dimensional collagen gel matrix. The cultured cells were observed by photo-microscopy and transmission electron microscopy. Differentiation and proliferation of the cultured cells were examined by immunohistochemistry using PAP and PSA kits and a bromodeoxy-uridine (BrdU) kit. The cell area of acinus-like structures in the transverse sections was measured by computer with the Interaktive Bild-Analyse System. RESULTS: Dissociated prostatic epithelial cells were organized into three-dimensional spherical or branching cellular aggregates in collagen gel matrix. Through cell proliferation and differentiation, the cellular aggregates formed prostatic acinus-like structures, which consisted of a small intercellular lumen enclosed by one layer of cuboidal epithelial cells. The epithelial cells were connected together by junctional complexes, had microvilli at the luminal surface, and the basal side was surrounded by a distinct basal lamina. In the lumina of acinus-like structures, secretory products were often found. CONCLUSIONS: Prostatic acinus-like structures were reconstructed from dissociated prostatic epithelial cells in three-dimensional collagen gel matrix culture. The reconstructed acinus-like structures are similar to prostatic acini in vivo in structure and function. This three-dimensional collagen gel matrix culture model may provide a useful means for investigating prostatic diseases and influences that hormones and growth factors exert on prostatic epithelial cells.

Acid Phosphatase↗

Transforming growth factor-beta1 induces a mesenchyme-like cell shape without epithelial polarization in thyrocytes and inhibits thyroid folliculogenesis in collagen gel culture.

Transforming growth factor-beta1 (TGFbeta1) induces a mesenchyme-like cell shape in some epithelial cell types. To clarify the role of TGFbeta1 in the morphological regulation of thyrocytes, we performed collagen gel culture of porcine thyrocytes with serum-free medium. TGFbeta1-nontreated cells organized follicles. In contrast, the cells treated with 10 ng/ml TGFbeta1 became spindle shaped, i.e. they resembled mesenchymal fibroblasts, and did not form follicles. To characterize the spindle-shaped cells, we examined the fine structures and expression of thyroglobulin (Tg) and cytoskeletal proteins using electron microscopy, immunohistochemistry, and immunoblotting. TGFbeta1-nontreated cells had microvilli at the apical side facing follicle lumen and had basal lamina at the basal side in contact with collagen gel. TGFbeta1-treated cells showed both microvilli and basal lamina at the basal side. TGFbeta1-nontreated cells expressed Tg, whereas TGFbeta1-treated cells showed no expression. TGFbeta1-nontreated cells barely expressed vimentin, but they expressed enough cytokeratin. TGFbeta1-treated cells extensively displayed vimentin along with the change in shape to become spindle-like and retained a decreased expression of cytokeratin. TSH (10 mU/ml) did not essentially influence any TGFbeta1 effects on the cells. These results indicate that TGFbeta1 induces a mesenchyme-like cell shape accompanied by cytoskeletal molecular change and the loss of both epithelial polarization and a function in thyrocytes, and that it results in inhibiting thyroid folliculogenesis with or without TSH.

Animals↗

Reconstruction culture system simulating human synovium: a three-dimensional collagen gel culture of synoviocytes.

We developed a reconstruction culture system simulating human synovium to investigate the synoviocytes in a more physiological condition. This system with two types of dishes provided the two separated spaces corresponding to the joint cavity and nutrient vessels. The isolated normal synoviocytes were cultured in type-I collagen gel with a layer-seeded on top in a smaller inner dish with a porous bottom, which was placed in a larger outer dish. We added hyaluronic acid solution to the space on the gel to make an environment close to the physiological joint cavity. The space between the inner and outer dishes was filled with a complete medium to nourish the synoviocytes through the porous filter (Experiment 1). In addition, to examine cell-to-cell interaction, we created a co-culture model by mixing synoviocytes and peripheral blood mononuclear cells in the collagen gel matrix (Experiment 2). In this way we could reconstruct the synovium in vitro. The synoviocytes could survive and maintain their characteristics for four weeks of culture. In Experiment 1, almost all the cells were similar to type B synovial cells by histological, immunohistochemical and electron microscopic observations. In Experiment 2, the spherical cells in abundance of lysosomes like type A synovial cells appeared sporadically in the lining layer. Immunohistochemically, the majority of cultured cells expressed CD68 and matrix metalloproteinase 3. This culture system promises to be of use in investigating the pathogenesis of various joint diseases.

Adolescent↗

Microinjection of rat GH but not human IGF-I into a defined area of the hypothalamus inhibits endogenous GH secretion in rats.

It has been surmised that GH exerts feedback action on the hypothalamus and thereby regulates its own secretion. Our previous studies suggested that GH acts on somatostatin neurons in the hypothalamic periventricular nucleus (PeV) and neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC). However, there remains uncertainty whether GH acts directly or indirectly through the generation of IGFs on the hypothalamus to regulate its own secretion. To examine this, rat GH (rGH) or human IGF-I was injected directly into a defined area of the hypothalamus, and the blood GH profile was observed in conscious male rats. In the rats given 0.5 microgram rGH into the ARC or PeV bilaterally, GH secretion was inhibited, and the inhibition lasted for 12 h. During the period of inhibition, the duration and amplitude of GH pulses were significantly decreased and the episodic secretion of GH appeared irregularly compared with the vehicle-injected control rats. In control rats given the vehicle or those given rGH into the lateral hypothalamus, the blood GH profile did not change and pulsatile GH secretion was produced every 3 h. When 0.1 microgram IGF-I was injected into the ARC or PeV bilaterally, the blood GH secretory pattern was not affected. Together with the results of our previous studies showing that c-fos gene expression was induced by systemic administration of GH and that GH receptor mRNA was contained in somatostatin neurons in the PeV and NPY neurons in the ARC, the data of the present study indicate that GH, but not IGF-I, acts on the cells in the ARC and the PeV or in their vicinity to inhibit its own secretion, presumably by activating the somatostatin and NPY neurons.

Animals↗

Cushing's syndrome due to bilateral adrenocortical adenomas with different pathological features.

A 48-year-old woman with Cushing's syndrome due to bilateral adrenocortical adenomas is reported. The patient presented with a typical Cushingoid appearance. The serum cortisol level was elevated with loss of the diurnal rhythm and the plasma adrenocorticotropic hormone (ACTH) level was undetectable. Dynamic testing showed no suppression of urinary 17-OHCS by high-dose dexamethasone and no stimulation by metyrapone. An abdominal computed tomography (CT) scan showed bilateral adrenal tumors. Bilateral adrenalectomy was performed. The right adrenal gland contained a tumor that was encapsulated and consisted mainly of compact cells. The surrounding cortex was atrophic. The left adrenal gland contained an encapsulated tumor composed predominantly of clear cells. There were numerous small adrenocortical nodules in the surrounding cortex. Immunohistochemical analysis of steroidogenic enzymes (P450scc, 3beta-HSD, P450c21, P450c17 and P450c11) was performed. Immunoreactivity of all the enzymes was intense in the compact cells of the right adrenocortical adenoma, while the adjacent non-neoplastic cortex was negative for the enzymes. In the left adrenal tumor, the immunoreactivity of 3beta-HSD was intense, while that of P450c17 was weak. In the adrenocortical nodules, 3beta-HSD activity was sporadically observed. G protein genes encoding Gs alpha and Gi2 were examined for activating mutations at codons 201 and 227 (Gs alpha) and codons 179 and 205 (Gi2 alpha) in the bilateral adrenal tumors, but no mutations were found. The bilateral adenomas of this patient showed marked differences in microscopic and immunohistochemical studies, suggesting that the capacity of steroidogenesis differs between the right and left tumors.

Adrenal Cortex Neoplasms↗

Acute lymphoblastic leukemia with isolated adrenocorticotropic hormone deficiency.

A 57-year-old female was admitted to our hospital because of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). On admission, disturbance of consciousness and hyponatremia were recognized. The patient's endocrinological data showed low levels of adrenocorticotropic hormone (ACTH) (less than 5 pg/ml) and cortisol (5.9 microg/dl). Other anterior pituitary hormones were normal. Plasma ACTH and cortisol did not respond to the corticotropin releasing factor (CRF) test. A diagnosis of isolated ACTH deficiency was made. This is a rare case of isolated ACTH deficiency complicated with hematological malignancies.

Adrenocorticotropic Hormone↗

[A calculation of an index of the coronary flow reserve using exercise and rest myocardial SPECT with 99mTc-tetrofosmin].

We designed a new method to evaluate the rate of change of myocardial 99mTc-tetrofosmin (TF) uptake between exercise and rest images with a 1-day protocol. Fifteen normal cases were studied. A 370 MBq of TF was injected at peak exercise. Initial (TF1) and delayed (TF2) exercise SPECT images were acquired 30 min and 3 hr after the injection. A 740 MBq of TF was reinjected soon after TF2 acquisition, and rest SPECT images (TF3) were obtained 30 min after the reinjection. Myocardial counts of TF1, TF2 and TF3 were defined C1, C2 and C3 respectively. Then, the rate of change of myocardial TF uptake between exercise and rest (delta MTU: delta myocardial TF uptake) was determined by the following formula. delta MTU = [(C1/(C3-C2)] x R-1] x 100 (%) (R: dose ratio). delta MTU was 57.8 +/- 9.9% in normal cases and roughly correlated with maximal heart rates and double product. If the extraction fraction of TF is not changed under the exercise and resting condition, delta MTU may have some relation with the coronary flow/cardiac output ratio at exercise. In conclusion, delta MTU is a useful index to evaluate coronary flow reserve non-invasively.

Adult↗

[Angle of defect on 123I-MIBG myocardial SPECT].

The quantitative assessment of infero-posterior defect on 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was studied in 150 patients with non-ischemic heart diseases at rest. The bull's eye map, obtained from the SPECT images at 4 hours after MIBG injection, was evaluated by generating the blacked out map which exhibits regions with reduced % uptake under mean-2 SD of 13 normal controls. The blacked out regions involved infero-posterior segments and were closely resembled to the sector form. The central angle of this sector, which was named as angle of defect (AOD), significantly correlated with both the heart-to-mediastinum activity ratio (H/M) and the myocardial clearance of MIBG. Because H/M and clearance are widely used as quantitative indices in MIBG myocardial scintigraphy, these results indicate that AOD can also be used as a quantitative index of abnormal cardiac sympathetic nervous function, which is likely to appear in infero-posterior regions in non-ischemic cardiac diseases.

3-Iodobenzylguanidine↗

Septal perfusion and wall thickening in patients with left bundle branch block assessed by technetium-99m-sestamibi gated tomography.

UNLABELLED: Septal hypoperfusion is often observed in patients with complete left bundle branch block (LBBB) in myocardial perfusion imaging. Abnormal wall motion in the septal region may potentially cause artifactual perfusion abnormalities. To assess the effect of abnormal wall thickening on myocardial perfusion images, ECG-gated sestamibi SPECT was performed on 12 patients with LBBB and 10 normal subjects used as controls. METHODS: After administration of 740 MBq 99mTc-sestamibi injection at rest, ECG-gated SPECT was obtained 60 min later with division of the cardiac cycle into eight frames. RESULTS: Septal hypoperfusion was noted in 10 patients on nongated images and 11 patients on end-systolic (ES) images, whereas only two patients showed abnormalities on end-diastolic (ED) images. The septal to lateral wall count ratio in the LBBB group was lower (0.72 +/- 0.09) than in the control group (0.84 +/- 0.09) (p < 0.01) at nongated images, while it was similar at ED images (0.84 +/- 0.11 versus 0.86 +/- 0.12; ns). In addition, the count increase from ED to ES during a cardiac cycle in the septal region was smaller compared with the lateral region in the LBBB patients (25% +/- 19% in the septal region, versus 48% +/- 14% in the lateral region; p < 0.01), indicating less wall thickening in the septal region. CONCLUSION: Smaller count increase due to reduced wall thickening in the septal region may mimic hypoperfusion in patients with LBBB. This artifact can be eliminated with ECG-gated 99mTc-sestamibi SPECT, particularly with ED images.

Aged↗

Metabolism substrate with negative myocardial uptake of iodine-123-BMIPP.

UNLABELLED: Iodine-123-BMIPP is an iodinated methyl-branched-chain fatty acid. Low uptake of BMIPP relative to thallium or other perfusion tracer indicates metabolically damaged but viable myocardium (for example, ischemic but viable myocardium). In some cases, however, negative myocardial uptake of BMIPP is observed. The main purposes of this study were to assess the frequency of such BMIPP findings and to clarify metabolism of such cases by using PET. METHODS: Among the 1258 patients who underwent BMIPP scintigraphy, 11 patients (0.9%) showed negative myocardial uptake of BMIPP. Under fasting condition, PET using [11C]palmitate, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [11C]acetate was performed in nine of these 11 patients. RESULTS: Global myocardial uptake of [11C]palmitate, expressed as the standardized uptake value, was significantly lower in the patients than in control (3.62 +/- 0.44 versus 5.49 +/- 1.62; p < 0.01). However, the early phase clearance rate of [11C]palmitate and oxidative metabolism was not significantly different. In the fasting state, PET studies showed increased FDG accumulation in seven of nine patients (high group) and decreased accumulation in two patients (low group). In the high group patients, glucose metabolism in the fasting state was similar to that in the normal volunteers after glucose loading (Kcomplex: 0.050 +/- 0.016 versus 0.038 +/- 0.015; p = ns). However, low glucose metabolism was noted in the low group patients (Kcomplex: 0.007 and 0.005). CONCLUSION: Negative myocardial uptake of BMIPP is occasionally, but not often, observed. Global uptake of [11C]palmitate was decreased in these patient. The majority of these patients showed "metabolic switching" from normal free fatty acid metabolism to abnormally enhanced glucose metabolism in the fasting state. However, some patients showed decreases in both exogenous glucose utilization and free fatty acid uptake in the fasting state.

Acetates↗

[Importance of the delayed 123I-BMIPP image for detecting myocardial metabolic abnormality induced by transient myocardial ischemia: a case of vasospastic angina].

We experienced a case of 64-year-old man with stunned myocardium caused by vasospasm. Without enzymatic evidence of an acute myocardial infarction, the patient developed a prolonged chest pain with ST elevation in the electrocardiogram in the midnight before the day of coronary angiography. Coronary angiogram revealed no significant stenosis and left ventriculography demonstrated akinesis in the apico-anteroseptal region. Although initial images of 123I-BMIPP myocardium SPECT showed no significant decrease of uptake, delayed images revealed marked decrease of tracer uptake in the apico-anteroseptal region in which left ventriculography showed abnormal wall motion. After 3 months of medication, left ventriculography disclosed a marked improvement, and coronary spasm was evoked in the proximal portion of left anterior descending artery after intracoronary ergonovine provocations. At the same time, both initial and delayed images of 123I-BMIPP myocardial SPECT showed no significant decrease of tracer uptake. This patients was considered as a noteworthy case to understand the kinetics and metabolism of 123I-BMIPP in stunned myocardium.

Angina Pectoris↗

[Analysis of microsatellite regions and DNA ploidy pattern in signet ring cell carcinomas of the stomach].

We examined microsatellite instability (MSI) and loss of heterozygosity (LOH) in regions of several important genes in 25 signet-ring cell carcinomas of the stomach. The relationship between microsatellite analysis and DNA ploidy pattern was also investigated. MSI was observed in 15% (2/13) of early carcinomas and in 17% (2/12) of advanced carcinomas. Although LOH in the region of APC gene was found in 16% (4/25) and LOH of p53 was found in 12% (3/25), 15% (2/13) of early carcinomas and 33% (4/12) of advanced carcinomas showed LOH in regions of E-cadherin gene. Cyto-fluorometrical study revealed that 85% (11/13) of early carcinomas were diploid pattern, and aneuploid components were demonstrated in 50% (6/12) of advanced carcinomas. However, no MSI-positive cases contained aneuploid components, and in contrast, all p53-LOH cases contained aneuploid components. Our results suggest that gene abnormalities which have been frequently reported in differentiated adenocarcinomas are rare events in signet-ring cell carcinomas other than those associated with cell adhesion, and that MSI is not related to the occurrence of aneuploid cells.

Adult↗

[Quantification of brain perfusion SPECT with N-isopropyl-p-iodoamphetamine using noninvasive microsphere method: estimation of arterial input by dynamic imaging].

We have developed a noninvasive method to quantify brain perfusion SPECT with 123I-N-isopropyl-p-iodoamphetamine (IMP) using serial dynamic planar imaging of the initial transit phase. The method is based on the microsphere model, but does not require arterial sampling. Serial dynamic planar imaging was performed for 6 min after the bolus injection of IMP (167 MBq in 1.5 ml), followed by additional planar imaging at 20 min and SPECT scan thereafter. The total arterial input to the brain during the initial 5 min after injection was estimated by the injected dose, with the correction of the lung retention, divided by cardiac output (CO). CO was estimated from the initial transit of IMP in the right heart. Cardiac output index (COI), obtained from the integral of the first transit of IMP in the right heart divided by the injected dose, was calibrated by CO measured by Doppler ultrasonography. Regional cerebral blood flow (rCBF) obtained by this method in normal subjects was acceptable. However, the results may be influenced by the injection technique, and careful attention should be considered for clinical application of this method.

Adult↗

[An autopsy case of amyotrophic lateral screlosis (ALS): magnetic resonance imaging and pathological findings of the pyramidal tract].

A 59-year-old woman was diagnosed as amyotrophic lateral screlosis (ALS) on the basis of neurological and electromyographical findings, and died after about 4 years course. Magnetic resonance imaging (MRI) on coronal planes through the internal capsule revealed high signal area almost limited to the pyramidal tract; the high signal area was more restricted in proton weighted imaging than in T2 weighted imaging. Histological lesion of the precentral gyrus was slight, while loss of myelinated fibers in the posterior limb of the internal capsule was remarkable. Extent of the pathological lesion in the posterior limb of the internal capsule well corresponded to the high signal area in proton weighted imaging. Comparison of the pyramidal tract pathology in the corona radiata and the internal capsule in Klüver-Barrera preparations with the MRI findings obtained 2 years and 8 months before the autopsy suggests us that the T2 weighted imaging of ALS brains may detect involvement of the pyramidal tract as early as or even earlier than histological changes become manifest.

Amyotrophic Lateral Sclerosis↗

[Usefulness of 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT in a congestive heart failure patient with isolated coronary ostial stenosis].

We reported a 47-year-old female with congestive heart failure (CHF) of unknown origin. In this case, it was suggested that 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT images were useful in the diagnosis of CHF of unknown origin. She had complained of easy fatigability and dyspnea on effort since Sep. 1995. She was admitted to our hospital because of worsening of symptoms in Dec. 1995. Slightly decreased uptake in anterior, lateral and apical walls was recognized in 99mTc-tetrofosmin SPECT images, meanwhile 123I-BMIPP SPECT images showed markedly reduced uptake in the same areas. This discordance in the distribution between 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT suggested that CHF was not due to dilated cardiomyopathy, but ischemic myocardial disease. Coronary angiography revealed 90% stenosis at the just proximal of left coronary artery. This case was diagnosed an isolated coronary ostial stenosis with CHF, because she was menstruated middle aged woman and did not have a history of aortitis syndrome, syphilis and coronary risk factor before.

Coronary Disease↗