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Biomedical subjects

S Shintani

Publications and source records attributed to S Shintani.

At least 37 records · Page 2Linked to original sources

A case of disseminated extrahepatic hepatocellular carcinoma after US-guided biopsy and percutaneous ethanol injection therapy.

A case of disseminated extrahepatic hepatocellular carcinoma (HCC) occurring after ultrasound (US)-guided biopsy and percutaneous ethanol injection therapy is presented. A 72-year-old man with hepatitis-C-virus-related cirrhosis underwent percutanous ethanol injection therapy (PEIT) two times with complete remission: the first for moderately-differentiated HCC in segment six (S6), and the second for well-differentiated HCC in another part of S6. Imaging studies including carbon dioxide (CO(2))-US angiography, incremental computed tomography, and dynamic magnet resonance imaging showed that both HCCs were hypovascular. Twenty-one months after the first PEIT and 7 months after the second, a 5.5x4.5 cm extrahepatic mass interfaced with S6 of the liver was detected by imaging studies. The patient underwent surgery for extrahepatic HCC. Grossly, the main tumor was 5.5x4.5 cm with capsule and septum; the disseminated tumors were detected on the surface of the liver, including the right diaphragm and the falx ligamentosa. Histologically, it was moderately- to poorly-differentiated HCC, which, although not attributed to direct track seeding, was suspected of being induced by the percutaneous US-guided biopsy procedure or by PEIT, irrespective of a hypovascular tumor. Further studies may provide insight into the risk factor engendered by these procedures.

Journal Article↗

The usefulness of intraoral ultrasonography in the evaluation of oral cancer.

Many studies focused on the tumour thickness in oral squamous cell carcinomas, suggesting a relationship with the occurrence of cervical metastasis. Accurate preoperative assessment of the tumour thickness of oral cancer would provide useful information for targeting those patients who need elective treatment of the neck. Some useful diagnostic aids to evaluate oral cancer are computed tomography (CT), magnetic resonance imaging (MRI), and intraoral ultrasonography. The purpose of the present study is to compare intraoral ultrasonography with CT and MRI in delineating the disease extent and in measuring the tumour thickness of oral carcinoma. Thirty-nine patients with oral cancer were preoperatively evaluated with intraoral ultrasonography, and CT, and in 26 of them MRI was carried out. High-quality ultrasonographic images were obtained and the tumour thickness was measured within 1 mm. However, in most tumours less than 5.0 mm in thickness, CT and MRI could not detect a sufficient density difference from the normal tissue to accurately delineate the extent of the tumour. There was a significant correlation between measurements by intraoral ultrasonography and the histological sections. The present study shows that ultrasonography is superior to CT and MRI in assessment of the primary lesion of oral carcinoma.

Adult↗

Overexpression of CDK2 is a prognostic indicator of oral cancer progression.

Cyclins and cyclin-dependent kinases (CDKs) play key roles in cell cycle regulation, a process of which dysregulation can lead to uncontrolled cell growth and hence to cancer. We have already reported the alteration of CDK4 and cyclin D1 expression in oral cancer. In this study, we examined by immunohistochemistry the expression of CDK2, and cyclins A and E in 20 normal oral mucosa, 42 dysplastic epithelia, and 103 oral squamous cell carcinomas (SCCs). The expressions of CDK2, and cyclins A and E were not detected in the normal epithelium and significantly altered from epithelial dysplasia to SCC. While there were no significant correlations between the expression of cyclins A, E and the patients' survival, CDK2 expression was significantly correlated with lymph node involvement (P = 0.025), tumor differentiation (P = 0.032), mode of tumor invasion (P = 0.017), and shorter survival period (P = 0.0173). These results suggest that the elevated expression of CDK2 is a critical factor in oral cancer progression and can be used as a negative predictive marker of the patients' prognosis.

Adult↗

Long-term smoking causes nitroglycerin resistance in platelets by depletion of intraplatelet glutathione.

We investigated whether platelet responsiveness to nitroglycerin (NTG) is maintained in long-term smokers and if not, the mechanism. In the absence or presence of NTG, intraplatelet reduced glutathione (GSH) levels and ADP-induced platelet aggregation and intraplatelet cGMP levels were measured in 10 long-term smokers and 10 age-matched nonsmokers. The intraplatelet GSH level was significantly lower in smokers than in nonsmokers (P<0.05). Platelet aggregation was dose-dependently inhibited by NTG in both groups; however, inhibition was significantly weaker in smokers. N-acetylcysteine (1 mmol/L), an exogenous thiol agent, significantly potentiated NTG-induced platelet inhibition in nonsmokers but not in smokers. The ADP-induced intraplatelet cGMP level was significantly greater in the presence of NTG in nonsmokers but not so in smokers. Because the effects of long-term smoking are multifactorial, a rabbit model was made by chronic administration of buthionine sulfoximine (BSO, n=6) to decrease intraplatelet GSH. The intraplatelet GSH level was significantly lower in BSO-treated rabbits than in saline-treated rabbits (P<0.001). The NTG-induced inhibition of platelet aggregation was significantly weaker in BSO rabbits. N-acetylcysteine-induced potentiation was not observed in BSO rabbits, whereas significant potentiation was found in saline rabbits. These findings were similar to those of long-term smokers. In contrast, the intraplatelet GSH-to-oxidized glutathione ratio, which represents the redox state of glutathione, was significantly lower in smokers than in nonsmokers, whereas no difference was found between saline rabbits and BSO rabbits. In conclusion, long-term smoking causes NTG resistance to aggregation in platelets, possibly through the depletion of intraplatelet GSH.

Animals↗

Dentin matrix protein 1 is predominantly expressed in chicken and rat osteocytes but not in osteoblasts.

Although osteocytes are the most abundant cells in bone, little is known about their function, and no specific marker protein for osteocytes has been described. Dentin matrix protein 1 (DMP1) is an acidic phosphoprotein expressed in tooth organ and bone. Our previous work showed that in the chicken, which is not capable of forming tooth, DMPI messenger RNA (mRNA) is highly expressed in bone by Northern blot analysis. To clarify the significance of DMP1 expression in bone, the expression of DMP1 mRNA and its protein was examined in the chicken and rat. In the chicken, DMPI mRNA was detected only in bone tissues and was localized in osteocytes and preosteocytes but not in osteoblasts. Similarly, in the rat, DMPI mRNA was predominantly expressed in osteocytes and preosteocytes in bone matrix but not in osteoblasts located at the bone surface. Antiserum was raised against the peptide from rat DMP1, and the localization of DMP1 was examined by immunohistochemistry. In the development of bone, DMP1 was first detected in newly formed bone matrix after osteoblastic cells had been embedded within it. After the appearance of typical osteocytes, DMP1 was localized in the pericellular bone matrix of osteocytes, including their processes. These data show that DMP1 is a bone matrix protein specifically expressed in osteocytes and preosteocytes and suggest that DMP1 plays a role in bone homeostasis because of its high calcium ion-binding capacity.

Animals↗

Autoimmune hepatitis concomitant with hypergammaglobulinemic purpura, immune thrombocytopenia, and Sjögren's syndrome.

Sjögren's syndrome occurs as an occasional complication of autoimmune hepatitis, and purpura or thrombocytopenia develops in some patients with this syndrome. This report describes a 62-year-old woman with a 6-year history of autoimmune hepatitis who concurrently had hypergammaglobulinemic purpura, immune thrombocytopenia and Sjögren's syndrome. Treatment with prednisolone resulted in marked improvement of biochemical, hematological and dermatological abnormalities. This case emphasizes the manifestation of purpura or thrombocytopenia as an associated disorder during the course of autoimmune hepatitis concomitant with Sjögren's syndrome.

Anti-Inflammatory Agents↗

Reduction of p12DOC-1 expression is a negative prognostic indicator in patients with surgically resected oral squamous cell carcinoma.

PURPOSE: p12DOC-1 is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. Expression of p12DOC-1 is reduced and/or lost in tumor tissues. The purpose of this study is to correlate in vivo the expression of p12DOC-1 in oral cancer tissues by immunohistochemistry with clinical and pathological parameters. EXPERIMENTAL DESIGN: Twenty-five cases of normal oral mucosa and 127 cases of oral squamous cell carcinomas were evaluated. Patients' charts were reviewed for clinical, pathological, and 10-year survival data. Because p12DOC-1 is a growth suppressor and associates with CDK2, parallel immunostaining was done for proliferating cell nuclear antigen and CDK2 to evaluate cell proliferation and potential correlation with CDK2. RESULTS: Our results showed that strong p12DOC-1 staining was uniformly seen in normal oral mucosa. p12DOC-1 staining was reduced or absent in 81 cases (63.8%) of oral squamous cell carcinomas. Decreased p12DOC-1 staining (<25% of cells stained) correlated with tumor mode of invasion (P = 0.001) and higher proliferating cell nuclear antigen (P = 0.0028) and CDK2 (P = 0.0020) expression. Survival analysis showed significant correlation of low p12DOC-1 expression with the risk of cervical lymph node metastasis (P = 0.001) and patients' 10-year survival status (P = 0.0214). CONCLUSIONS: These results allow us to conclude that reduction of p12DOC-1 protein expression is a frequent event in oral cancers. Intratumor immunohistochemical evaluation of p12DOC-1 expression can be an adjunctive prognostic indicator for patients with oral cancer.

Adult↗

[Feeding methods for long-term bedridden patients with dysphagia under home health care--percutaneous endoscopic gastrostomy (PEG) and intravenous hyperalimentation (IVH)].

We began home health care in our hospital in 1992, and the total number of patients under home health care has reached 380 so far. We report 12 bedridden patients with dysphagia, who have obtained nutrition using two feeding methods. The patients are 7 men and 5 women, with a mean age of 81.4 +/- 8.8 years. The diseases in these patients include cerebrovascular diseases, Parkinson's disease, and senile dementia of the Alzheimer type. The feeding methods include swallowing after swallowing training, percutaneous endoscopic gastrostomy (PEG), and intravenous hyperalimentation (IVH). We have fed these patients by combinating these three methods. The patients fed by swallowing and PEG, swallowing and IVH, and PEG and IVH are five, five and two, respectively. It is very important for bedridden patients to eat and swallow food by themselves, even if the amount is extremely small. Although swallowing training has been performed, the amount of food is not sufficient for life support. Therefore, additional feeding by PEG or IVH is necessary. Sufficient nutrition through a variety of feeding methods is important for patients under home health care.

Aged↗

Carotid-cavernous fistula with brainstem congestion mimicking tumor on MRI.

Article abstract-A 65-year-old woman presented with a left abduction deficit and "red eye," mild proptosis, chemosis, arterialization of the conjunctival vessels, intention tremor, and bilateral pyramidal signs. MRI showed significant left-sided brainstem involvement that mimicked a tumor. Right hemiplegia ensued 1 week later. Venous congestion of the brainstem with hemiplegia resulting from shunting of blood flow from both carotid arteries is an extremely rare complication of carotid-cavernous fistula.

Aged↗

Kinetic alteration of a human dihydrodiol/3alpha-hydroxysteroid dehydrogenase isoenzyme, AKR1C4, by replacement of histidine-216 with tyrosine or phenylalanine.

Human dihydrodiol dehydrogenase with 3alpha-hydroxysteroid dehydrogenase activity exists in four forms (AKR1C1-1C4) that belong to the aldo-keto reductase (AKR) family. Recent crystallographic studies on the other proteins in this family have indicated a role for a tyrosine residue (corresponding to position 216 in these isoenzymes) in stacking the nicotinamide ring of the coenzyme. This tyrosine residue is conserved in most AKR family members including AKR1C1-1C3, but is replaced with histidine in AKR1C4 and phenylalanine in some AKR members. In the present study we prepared mutant enzymes of AKR1C4 in which His-216 was replaced with tyrosine or phenylalanine. The two mutations decreased 3-fold the K(m) for NADP(+) and differently influenced the K(m) and k(cat) for substrates depending on their structures. The kinetic constants for bile acids with a 12alpha-hydroxy group were decreased 1.5-7-fold and those for the other substrates were increased 1.3-9-fold. The mutation also yielded different changes in sensitivity to competitive inhibitors such as hexoestrol analogues, 17beta-oestradiol, phenolphthalein and flufenamic acid and 3,5,3', 5'-tetraiodothyropropionic acid analogues. Furthermore, the mutation decreased the stimulatory effects of the enzyme activity by sulphobromophthalein, clofibric acid and thyroxine, which increased the K(m) for the coenzyme and substrate of the mutant enzymes more highly than those of the wild-type enzyme. These results indicate the importance of this histidine residue in creating the cavity of the substrate-binding site of AKR1C4 through the orientation of the nicotinamide ring of the coenzyme, as well as its involvement in the conformational change by binding non-essential activators.

3-Hydroxysteroid Dehydrogenases↗

Expression of a truncated epidermal growth factor receptor in oral squamous cell carcinomas.

Epidermal growth factor receptor (EGFR) frequently overexpresses in cancers, including oral squamous cell carcinomas (OSCC). We previously identified a truncated EGFR (tEGFR) in human oral keratinocytes. In this study, we evaluated the prognostic value of tEGFR in 45 cases of OSCC. tEGFR expression inversely correlated with EGFR expression (r=-0.83, P<0.01), decreased with T-stage progression and lymph-node metastasis (P<0.05). The EGFR/tEGFR ratio correlated with the lymph-node metastasis (P<0.05) and survival outcome (hazard ratio =3.601; P<0.05). These results suggest that tEGFR may play an important roles in oral carcinogenesis and that the EGFR/tEGFR ratio may be a prognostic factor for OSCC.

Adult↗

Alterations of Rb, p16(INK4A) and cyclin D1 in the tumorigenesis of oral squamous cell carcinomas.

Immunohistochemical analysis of Rb, p16(INK4A) and cyclin D1 expression was performed on 78 oral squamous cell carcinoma (SCC), 46 leukoplakia, and 20 normal mucosa. Rb and p16(INK4A) expression were observed in all normal mucosa and most of leukoplakia. Lack of Rb and p16(INK4A) was observed in 56.4 and 67.9% of SCC, respectively. The overexpression of cyclin D1 was not observed in normal mucosa and was observed in 35.9% of SCC. A strong reciprocal relationship between Rb and p16(INK4A) expression was observed in oral SCC, and all these SCC cases have at least one of the alterations in the Rb pathway.

Carcinoma, Squamous Cell↗

Hypercholesterolemia inhibits angiogenesis in response to hindlimb ischemia: nitric oxide-dependent mechanism.

BACKGROUND: Endothelium-derived nitric oxide (EDNO) plays an important role in the regulation of angiogenesis, whereas hypercholesterolemia (HC) impairs EDNO release. We examined the hypothesis that HC may inhibit ischemia-induced angiogenesis by inhibition of EDNO in a rat model of unilateral hindlimb ischemia and that oral L-arginine supplementation, a substrate for NO synthase, may prevent HC-related impairment of angiogenesis. METHODS AND RESULTS: Male Sprague-Dawley rats were fed (A) standard diet (control), (B) 2% high-cholesterol diet (HC group), or (C) high-cholesterol diet with oral L-arginine (2.25% in drinking water) (HC+L-arg group). At 2 weeks of the dietary intervention, unilateral limb ischemia was surgically induced in all animals. Dietary HC groups (B and C) revealed elevated total and LDL cholesterol levels compared with control animals. Laser Doppler blood flow analyses showed significant decreases in the ischemic/normal limb blood flow ratio in the HC group compared with controls (P:<0.05) when followed up until 4 weeks after surgery. Selective angiography and immunohistochemical analyses in the ischemic limb at postoperative day 14 revealed significantly lower angiographic scores (P:<0.01) and capillary densities (P:<0.01) in the HC group than controls, which were associated with decreased tissue contents of NO(x) and cGMP. Oral L-arginine supplementation (HC+L-arg) significantly improved all parameters of the laser Doppler blood perfusion ratio, angiographic scores, and capillary densities (P:<0.01 versus HC group), which were accompanied by significant elevations in serum L-arginine levels and tissue NO(x) and cGMP contents. CONCLUSIONS: Collateral vessel formation and angiogenesis in response to hindlimb ischemia were significantly attenuated in rats with dietary HC. The mechanism may be related to the reduced NO bioactivity in the ischemic tissues. Augmentation of the tissue NO activity by oral L-arginine supplementation restored the impaired angiogenesis in HC.

Administration, Oral↗

Cloning and characterization of the human ameloblastin gene.

We isolated the full-length human ameloblastin (AMBN) cDNA clone using reverse transcription-polymerase chain reaction (RT-PCR) methods. Sequence analysis of the AMBN cDNA revealed an open reading frame of 1341bp encoding a 447-amino-acid protein. Comparison with pig, cattle, rat, and mouse AMBN sequences showed a high amino acid sequence similarity and led to the identification of a novel 78bp (26 amino acids) insert resulting from internal sequence duplication. By DNA analysis of a human genomic clones, the AMBN gene was shown to consist of 13 exons and a novel 78bp segment, which proved to comprise two small exons. Human ameloblastomas express AMBN transcripts that contain some mutations.

Ameloblastoma↗

Do lampreys have lymphocytes? The Spi evidence.

It is generally accepted that living jawless vertebrates (lampreys and hagfishes) lack the capability of mounting an adaptive immune response. At the same time, however, there are reports describing histological evidence for the presence in agnathan tissues of lymphocytes, the key players in adaptive immunity. The question therefore arises whether the cells identified morphologically as lymphocytes are true lymphocytes in terms of their genetic developmental program. In this study, evidence is provided that the lampreys express a member of the purine box 1 (PU.1)/spleen focus-forming virus integration B (Spi-B) gene family known to be critically and specifically involved in the differentiation of lymphocytes in jawed vertebrates. The lamprey gene is expressed in the lymphocyte-like cells of the digestive tract and inexplicably also in the ovary.

Amino Acid Sequence↗

Apoptosis and p53 are associated with effect of preoperative radiation in oral squamous cell carcinomas.

This study was carried out to elucidate whether apoptosis and p53 can be used to stratify oral cancer patients into groups with a favorable or unfavorable response to preoperative radiation therapy. Thirty-two patients were evaluated. The apoptosis index was 1.7+/-0. 9% in the ineffective cases, and it was significantly lower than effective cases (3.2+/-1.2%). While 14 of 16 effective cases (86.7%) did not express p53, 13 of 16 ineffective cases (81.3%) overexpressed p53. These results suggest that mutated p53 in tumors is associated with a poor response to radiation which may be related to evasion of apoptosis in oral cancer.

Aged↗

Serial positron emission tomography (PET) in gliomatosis cerebri treated with radiotherapy: a case report.

Results of serial positron emission tomography (PET) in a biopsy-proven case of gliomatosis cerebri (GC) are reported. Computed tomography (CT) with and without contrast failed to detect focal abnormalities, but magnetic resonance (MR) revealed iso-intensity or low-intensity lesions in T1-weighted images and high-intensity lesions in T2-weighted images. Lesions were seen in the left thalamus, right temporal lobe and claustrum, and pons. Radiotherapy remarkably improved clinical and imaging findings. Both before and shortly after radiotherapy, 11C-methionine PET images showed hypermetabolism while 15O-water PET images showed a marked increase in cerebral blood flow in GC lesions. However, 6 months later PET images had remarkably improved, appearing nearly normal.

Adult↗