Search PubMed⌕ Search

Biomedical subjects

S Yagihashi

Publications and source records attributed to S Yagihashi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Rectal adenocarcinoid with lymph node metastasis.

We describe a case of a rare variant of a rectal carcinoid tumor that showed mucous gland differentiation accompanied by a lymph node metastasis with a histological appearance similar to that of the primary site. The tumor consisted of a typical argyrophilic carcinoid component and of goblet cell glands. The carcinoid component was positive for neuron-specific enolase, chromogranin A and synaptophysin. The goblet cells stained positively with periodic acid-Schiff (PAS) and alcian blue, and expressed carcinoembryonic antigen, but were negative for neuroendocrine markers. This case suggests that carcinoid tumor can differentiate towards mucus glands, which can also be found in the metastatic site.

Adenocarcinoma↗
PubMed1999

Expression of tumor necrosis factor-alpha and interleukin-6 in oral squamous cell carcinoma.

To explore the role of cytokines in tumor development and clinical manifestations, we examined the expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in tumor tissues obtained from 57 patients with oral squamous cell carcinoma (OSCC) and their relationships to pathological grade and staging. Enzyme-linked immunosorbent assay on the tumor tissues demonstrated elevated concentrations of TNF-alpha and IL-6 proteins and upregulated mRNA levels were detected by the reverse transcription-polymerase chain reaction method when compared to those in normal control tissues. These cytokines and their transcripts were localized in stromal macrophages and in the tumor cells in particular of the front area of tumor tissues, possibly indicating active synthesis of these cytokines by tumor cells. Larger-sized tumors (T3, 4) contained significantly greater levels of IL-6 proteins than small-sized tumors (T1, 2) (P<0.05). The levels of these cytokines were significantly reduced in cases with effective pre-treatment with radiation or anti-cancer agents compared to those in the less effective group (P<0.05, grade IIa vs. grade IV for both TNF-alpha and IL-6). The present study thus demonstrated enhanced expression of cytokines in OSCC tissues.

Carcinoma, Squamous Cell↗
PubMed1998

Accelerated loss of islet beta cells in sucrose-fed Goto-Kakizaki rats, a genetic model of non-insulin-dependent diabetes mellitus.

The Goto-Kakizaki (GK) rat is a spontaneously diabetic animal model of non-insulin-dependent diabetes mellitus, which is characterized by progressive loss of beta cells in the pancreatic islets with fibrosis. In the present study, we examined the effects of sucrose feeding on the islet pathology in this model. Six-week-old GK rats were fed with 30% sucrose for 6 weeks to induce severe hyperglycemia, and their condition was compared with that of nontreated rats. Age-matched normal Wistar rats were also given sucrose for the same periods and used for comparison. The sucrose-treated GK rats showed elevated blood glucose levels on oral glucose tolerance tests at 60 minutes and 120 minutes, representing 123% and 127% of values in untreated GK rats, respectively. At the end of the study, the mean beta-cell volume density in GK rats was 50% less than that in untreated Wistar rats. Sucrose feeding further reduced the volume densities of beta cells to only 50% of the levels of age-matched GK rats. Apoptotic cells were found in islet beta cells only in GK rats fed sucrose (mean 0.067%). There appeared to be more islets that immunohistochemically stained strongly positive with 8-hydroxy-deoxyguanosine as a marker of oxidative damage of DNA in GK rats fed sucrose compared with those not given sucrose. GK rats not fed sucrose showed significantly lower proliferative activity of beta cells measured by 5-bromo-2'-deoxyuridine uptake and intensified expression of Bcl-2 immunoreactivities at 6 weeks of age compared with those in age-matched Wistar rats. These two indices were reduced in both GK and Wistar rats with increasing age and were not affected by sucrose feeding in either group. The present study thus indicated that sucrose feeding promoted the apoptosis of beta cells in GK rats through increased oxidative stress without altering their proliferative activity.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Rerupture of coil-embolized aneurysm during long-term observation. Case report.

The authors describe the histopathological findings in a case involving rerupture of a recanalized aneurysm of the internal carotid artery 8 months after partial (95%) embolization with interlocking detachable coils. The aneurysm was filled with poorly organized thrombus, and its orifice was devoid of endothelial cells. It appears likely that a long period of observation may be required to confirm the complete thrombotic organization of coil-embolized aneurysms. This indicates that caution is needed because rupture may follow recanalization of the aneurysm.

Aged↗
PubMed1997

Effects of aminoguanidine on structural alterations of microvessels in peripheral nerve of streptozotocin diabetic rats.

This study was designed to explore the effect of aminoguanidine (AG) on the structural abnormalities of microvessels in the sural nerve of streptozotocin-induced diabetic rats. Diabetic rats were treated with AG (25 mg/ kg, sc) for 16 weeks, a dose high enough to prevent glycation but also inhibit inducible nitric oxide synthase. Non-treated diabetic rats and normal Wistar rats were used for comparison. Morphometric analysis disclosed an expansion of vascular and luminal areas of endoneurial microvessels in diabetic rats, particularly of large size, compared to control rats. These changes were partially but significantly corrected by AG treatment. There was no closure of microvessels in diabetic rats. The mean ratio of basement membrane area to vascular area was significantly smaller in diabetic rats than that in normal control rats and basement membrane was not thickened in diabetic rats. The mean ratio of endothelial cell area to vascular area was smaller in diabetic rats than that in nondiabetic control rats, and it was not influenced by AG treatment. Numbers of microvessels per unit endoneurial area in diabetic rats were not different from those of control rats. These findings in conjunction with previous reports suggest that alterations of nerve blood flow detected in diabetic peripheral nerve may be relevant to structural alterations of endoneurial microvessels, which may be an early sign of endoneurial microangiopathy. We also consider that AG treatment is beneficial for experimental diabetic neuropathy, partially through the correction of endoneurial microcirculation.

Animals↗
PubMed1997

Localization in human diabetic peripheral nerve of N(epsilon)-carboxymethyllysine-protein adducts, an advanced glycation endproduct.

The present study was designed to elucidate in situ distribution of advanced glycation endproducts (AGE) in human peripheral nerve and whether the reaction products were excessive in the diabetic condition. For the detection of AGE, immunoperoxidase staining was undertaken on peripheral nerve samples obtained from 5 non-insulin-dependent diabetic patients and 5 non-diabetic control subjects. The anti-AGE antibody used in this study contained an epitope against N(epsilon)-carboxymethyllysine. Light microscopically, AGE localized in the perineurium, endothelial cells and pericytes of endoneurial microvessels as well as myelinated and unmyelinated fibers. At the submicroscopic level, AGE deposition appeared focally as irregular aggregates in the cytoplasm of endothelial cells, pericytes, axoplasm and Schwann cells of both myelinated and unmyelinated fibers. Interstitial collagens, basement membranes of the perineurium also reacted with this antibody. The AGE depositions were detected in both control and diabetic nerves, but were more intense in the latter. The excessive AGE deposition correlated with a reduction in myelinated fiber density. However, the localization of AGE was not directly associated with degeneration of nerve fibers and the link between AGE deposition and nerve fiber degeneration is yet to be determined. The present study thus demonstrated the excessive deposition of intra- and extracellular AGE in human diabetic peripheral nerve and strengthened the contention that the enhanced glycation may play a role in the development of diabetic neuropathy.

Aged↗
PubMed1997

Crystalloid formation in gastrointestinal schwannoma.

We found intracytoplasmic crystalloids in two of six cases (33.3%) of gastrointestinal (GI) schwannomas. The crystalloid inclusions were periodic acid-Schiff (PAS) positive with diastase-resistance and stained blue with Masson's trichrome. They were needle-shaped and about 1 to 15 microm in length at microscopic levels. They had varying electron density revealed by electron microscopy and some of them showed distinct lattice structure with periodicity of about 9 nm. Survey of soft tissue schwannomas (n = 20) and S-100-negative GI stromal tumors (n = 41) did not detect such crystalloids. Although the origin and differentiation of GI stromal tumors (GISTs) have been a source of controversy, these intracytoplasmic crystalloids may be a marker for Schwann cell differentiation in some GIST.

Adult↗
PubMed1997

Immunohistochemical assessment of proliferative activity in mammary adenomyoepithelioma.

AIMS: Two cases of adenomyoepithelioma of the breast were examined by immunohistochemistry to evaluate proliferative activity of epithelial and myoepithelial components. METHODS AND RESULTS: The tumours showed a bicellular pattern of gland-forming epithelial cells and proliferative myoepithelial cells with clear cytoplasm. They showed foci of monotonous growth of myoepithelial cells devoid of glands with low mitotic rate (1-2/10 high-power fields) and mild cytological atypia. Immunohistochemically, the glandular cells were positive for epithelial membrane antigen, cytokeratin (KL-1 and CAM5.2) and carcinoembryonic antigen, whereas tumour cells with clear cytoplasm were reactive with muscle-specific actin (MSA), alpha smooth muscle actin, vimentin, and S100 protein but negative for desmin. Proliferative activities assessed by MIB-1 (Ki-67)/MSA positive cell index were greater in myoepithelial cells in both cases (19.2% and 17.7%) as compared to those in epithelial cells (MIB-1/CAM5.2 index: 10.2% and 9.5%). CONCLUSIONS: These results might account for the previous findings that myoepithelial components predominate over the epithelial ones in an advanced stage of this tumour as well as in recurrent or metastatic lesions.

Aged↗
PubMed1997

c-myc, c-erbB-1 and c-erbB-2 expressions in urothelial carcinoma.

The expression of c-myc, c-erbB-1 and c-erbB-2 in 24 cases of urothelial carcinoma by Southern and northern blot analysis, and immunohistochemistry was examined. The results were compared with the pathological grade and stage. We found elevated mRNA expressions of c-myc and c-erbB-1 in 19 and 11 of 21 cases, respectively, but there was no apparent amplification or rearrangement of these oncogenes in any of the cases examined. By immunohistochemistry using anti-epidermal growth factor receptor antibody, most of the cases showed positive immunoreactivity on the cancer cell membranes, and cancers of higher pathological grade and stage showed more intense staining. By contrast, amplification of c-erbB-2 was detected in four of 24 cases, all of which were assigned to a high pathological grade (G3). Elevated c-erbB-2 mRNA levels appeared to correlate with the pathological grade of the cancers. Positive immunohistochemical reactions to c-erbB-2 were found in the cancer cell membranes in three of 24 cases, which were accompanied by amplification and elevated mRNA levels of c-erbB-2. In conclusion, expressions of c-myc, c-erbB-1 and c-erbB-2 were all elevated in the majority of urothelial carcinomas, but the amplification was not universal.

Blotting, Northern↗
PubMed1996

P53 protein expression in pancreatic tumors and its relationship to clinicopathological factors and prognosis.

We examined the expression of p53 protein by immunohistochemical method in a series of pancreatic tumors and evaluated its relationships to the clinicopathological factors and prognosis. The study involved 108 cases of pancreatic tumors (79 ductal carcinomas, 1 acinar cell carcinoma, 14 endocrine tumors, 6 solid cystic tumors, 8 benign ductal tumors) and 8 chronic pancreatitides. Thirty-nine cases of pancreatic ductal carcinoma (49.4%) were positive for p53 protein. Analysis of the Cox hazards model identified p53 positivity and stage at the initial operation as an independent prognostic factor. Patients with p53 positive ductal carcinomas had a greater risk of death compared to p53 negative cases (P < 0.05). There was, however, no statistically significant correlation between p53 protein expression and other clinicopathological factors. Cases of stage III and IVb with positive p53 showed a bleak prognosis compared to p53 negative cases (P < 0.05). Our results suggest that p53 expression is common in invasive pancreatic ductal carcinomas and may have a prognostic value.

Adult↗
PubMed1996

Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.

Acetylcysteine↗
PubMed1996

Expression of nitric oxide synthase in macula densa in streptozotocin diabetic rats.

Renal haemodynamic changes are suggested to be an early sign of diabetic glomerulopathy. The juxtaglomerular apparatus relevant to the renin angiotensin system, known to be the site of nitric oxide (NO) production, is considered to play a role in the regulation of glomerular blood flow. This study was therefore designed to clarify whether in situ expression of nitric oxide synthase (NOS) is altered in the kidney of diabetic rats. Streptozotocin-induced diabetic rats with 6, 8, 12 and 32 weeks diabetes duration and age-matched normal control rats were used. The expression of a constitutive form of NOS (cNOS, neural type) and NADPH diaphorase activity in the renal cortex were studied immunohistochemically and histochemically. Diabetic rats had lower body weight and heavier kidney mass compared to control rats at each time point examined. Mean glomerular surface area was greater in 6, 8 and 12-week diabetic rats compared to age-matched control rats. cNOS reaction was localized in the macula densa and appeared less intense in diabetic rats compared to age-matched control rats. The mean number of macula densa cells positive for cNOS in each glomerulus and in each glomerular area was significantly lower in diabetic rats compared to control rats at any time examined. In contrast, NADPH diaphorase activity was detected in both juxtaglomerular arterioles and macula densa cells. The staining reaction of NADPH diaphorase in the arterioles remained positive but appeared less intense in macula densa cells in diabetic rats. These results suggest that NO production in macula densa cells may be reduced in diabetic rats, modulating the vasodilatory function of afferent arterioles. Further investigation on the changes in inducible NOS as well as endothelial cNOS are necessary to clarify mechanisms of haemodynamic changes in the diabetic kidney.

Animals↗
PubMed1996

Peripheral nerve pathology in rats with streptozotocin-induced insulinoma.

Peripheral nerve structure was systematically examined in rats with insulinoma induced by streptozotocin (STZ). Normal Wistar rats, aged 3 months (n = 10), were treated with intravenous injections of STZ (20 mg/kg) and housed in plastic cages with free access to water and chow until 24 months of age. Three rats with insulinoma survived and were examined pathologically. Age-matched normal Wistar rats (n = 6) were used for comparison. The insulinoma-bearing rats showed a marked increase in body weight and decrease in blood glucose. In a teased nerve fiber study of the sciatic nerve, the percentage of abnormal fibers undergoing axonal degeneration and de- and remyelination in age-matched normal control rats was 3.9 +/- 2.5% (means +/- SD), whereas in the three insulinoma-bearing rats 49%, 50%, and 24%, respectively, of the fibers showed such changes. Regenerating fibers were also numerous in each insulinoma-bearing rat (36%, 42% and 27%, respectively). Morphometric analysis revealed smaller mean myelinated fiber and axonal areas in all the nerves examined (sciatic, tibial and sural) in insulinoma-bearing rats as compared to those in age-matched normal rats. Fiber area frequency histograms showed a decrease in large myelinated fibers and an increase in small regenerated fibers in insulinoma-bearing rats. Ultrastructurally, endoneurial microvessels exhibited a narrowed vascular lumen with swollen endothelial cells and vacuolar degeneration of pericytes, suggesting an involvement of vascular changes in the neuropathic development. The present study demonstrated marked structural changes in both motor and sensory peripheral nerves of rats bearing experimentally induced insulinoma. We consider that axonal degeneration, regeneration and demyelination constitute the main pathology in the peripheral nerves of insulinoma-bearing rats, although no particular difference in severity of the lesions between sensory and motor and between proximal and distal nerves was apparent.

Animals↗
PubMed1996

Galactosemic neuropathy in transgenic mice for human aldose reductase.

We studied the functional consequences of an enhanced polyol pathway activity, elicited with galactose feeding, on the peripheral nerve of transgenic mice expressing human aldose reductase. Nontransgenic littermate mice were used as controls. With a quantitative immunoassay, the expression level of human aldose reductase in the sciatic nerve was 791 +/- 44 ng/mg protein (mean +/- SE), about 25% of that in human sural nerve. When the transgenic mice were fed food containing 30% galactose, significant levels of galactitol accumulated in the sciatic nerve. Galactose feeding of nontransgenic littermate mice led to a 10-fold lower accumulation of galactitol. Galactose feeding for 16 weeks caused a significant and progressive decrease in motor nerve conduction velocity in transgenic mice to 80% of the level of galactose-fed littermate mice, which was not significantly different from that of galactose-free littermate mice. A morphometric analysis of sciatic nerve detected > 10% reduction of mean myelinated fiber size but no alterations of myelinated fiber density in galactose-fed transgenic mice compared with other groups. The functional and structural changes that develop in galactose-fed transgenic mice are similar to those previously reported in diabetic animals. The results of these studies suggest that transgenic mice expressing human aldose reductase may be a useful model not only for defining the role of the polyol pathway in diabetic neuropathy but also for identifying and characterizing effective inhibitors specific for human aldose reductase.

Aldehyde Reductase↗