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Biomedical subjects

Hiroyuki Kato

Publications and source records attributed to Hiroyuki Kato.

At least 109 records · Page 6Linked to original sources

Decreased Smad4 expression in the transforming growth factor-beta signaling pathway during progression of esophageal squamous cell carcinoma.

BACKGROUND: Transforming growth factor-beta (TGF-beta) has antiproliferative effects in various cells, and inactivation of the TGF-beta signaling pathway contributes to tumor progression or development. Smad4, a tumor suppressor gene, is a central mediator in the signaling pathways of the TGF-beta superfamily. This study was undertaken to clarify the correlation between Smad4 expression and the clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). The authors also investigated the expression of components of the TGF-beta signaling pathway in seven established cell lines derived from esophageal SCC. METHODS: Immunohistochemistry for Smad4 using monoclonal anti-Smad4 antibody was performed on surgical specimens obtained from 80 patients with esophageal SCC. In seven cell lines, the authors examined the expression of components of the TGF-beta signaling pathway using Western and Northern blot analyses. RESULTS: There was a significant inverse correlation between Smad4 expression and both depth of invasion (P = 0.0008) and pathologic stage (P = 0.0079). The expression of Smad4 proteins could be detected in five of seven cell lines. The expression of TGF-beta type II receptor protein was decreased in two of seven cell lines, and the expression of both Smad2 and Smad3 proteins was decreased in only one cell line. The level of expression of Smad4 mRNA did not differ dramatically between cell lines and was not correlated with the quantity of Smad4 protein. CONCLUSIONS: In this study, the expression of Smad4 protein appeared to be correlated with the depth of invasion of esophageal SCC. The loss of Smad4 expression was not regulated at the level of transcription.

DNA-Binding Proteins↗

G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis.

Covalent modification of histone tails is crucial for transcriptional regulation, mitotic chromosomal condensation, and heterochromatin formation. Histone H3 lysine 9 (H3-K9) methylation catalyzed by the Suv39h family proteins is essential for establishing the architecture of pericentric heterochromatin. We recently identified a mammalian histone methyltransferase (HMTase), G9a, which has strong HMTase activity towards H3-K9 in vitro. To investigate the in vivo functions of G9a, we generated G9a-deficient mice and embryonic stem (ES) cells. We found that H3-K9 methylation was drastically decreased in G9a-deficient embryos, which displayed severe growth retardation and early lethality. G9a-deficient ES cells also exhibited reduced H3-K9 methylation compared to wild-type cells, indicating that G9a is a dominant H3-K9 HMTase in vivo. Importantly, the loss of G9a abolished methylated H3-K9 mostly in euchromatic regions. Finally, G9a exerted a transcriptionally suppressive function that depended on its HMTase activity. Our results indicate that euchromatic H3-K9 methylation regulated by G9a is essential for early embryogenesis and is involved in the transcriptional repression of developmental genes.

Acetylation↗

A putative nuclear receptor coactivator (TMF/ARA160) associates with hbrm/hSNF2 alpha and BRG-1/hSNF2 beta and localizes in the Golgi apparatus.

An ATP-dependent chromatin remodeling factor, SNF/SWI complex, acts as a coactivator for numerous transcriptional factors. One of the best-documented examples is nuclear receptors, although the molecular mechanism for this coactivation has not been sufficiently elucidated. Here we show that hbrm/hSNF2 alpha and BRG-1/hSNF2 beta, the ATPase subunits of the human SNF/SWI complexes, specifically associate in vitro and in vivo with TATA element modulatory factor (TMF)/ARA160, which has been described as a binding protein to and coactivator for the androgen receptor. This interaction requires highly conserved N-terminal regions of hbrm/hSNF2 alpha and BRG-1/hSNF2 beta and a C-terminal region of TMF/ARA160. Immunofluorescence and Western blot studies revealed that the TMF isoforms differentially localize in the Golgi apparatus and the nucleus.

Adenosine Triphosphatases↗

A dyad oct-binding sequence functions as a maintenance sequence for the unmethylated state within the H19/Igf2-imprinted control region.

DNA methylation of an imprinted control region (ICR) directs the allele-specific and reciprocal expression of the mouse H19 and the insulin-like growth factor 2 (Igf2) genes, mediated by controlling enhancer access. The ICR shows enhancer blocking activity through CTCF binding to an unmethylated sequence. The unmethylated state of the maternal ICR is maintained throughout development after establishment in the germ line; however, little is known of the molecular mechanisms that regulate DNA methylation. Hence, in this study we show that a dyad Oct-binding sequence (DOS) in the ICR mediates the demethylation of low-density methylation but not hypermethylation and is required to maintain the unmethylated state against the tendency for de novo methylation within the ICR in the embryonic carcinoma cell line P19. Furthermore, we also reveal that the unmethylated state of at least one CTCF-binding site within the ICR is under the control of DOS. Our results suggest that the ICR, as a CTCF-dependent insulator, requires DOS as well as CTCF-binding sites and that DOS maintains the maternal specific unmethylated state of the ICR at postimplantation stages.

Animals↗

Significant correlation between expression of heat shock proteins 27, 70 and lymphocyte infiltration in esophageal squamous cell carcinoma.

The objective of this study was to clarify the clinicopathologic and prognostic significance of heat shock proteins (HSP) 27 and 70 expression in esophageal squamous cell carcinoma (SCC). Immunohistochemical staining for HSPs 27 and 70 was performed on surgical specimens obtained from 62 patients with esophageal SCC. The expression of both HSPs 27 and 70 correlated inversely with depth of invasion (P<0.05) and pathologic stage (P<0.05), and correlated positively with lymphocyte infiltration (P<0.05). Reduction of HSP 70 expression was significantly correlated with poor prognosis (P<0.05). Patients with HSP 27-negative tumors tended to have a poor prognosis compared with patients with HSP 27-positive tumors. The present findings suggest that HSPs 27 and 70 are significant prognostic factors for esophageal SCC.

Adult↗

Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma.

BACKGROUND: The role and potential value of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. The authors retrospectively assessed the performance of 18-F-fluorodeoxyglucose (FDG)-PET in the assessment of esophageal squamous cell carcinoma (SCC). METHODS: The results using PET were compared with those using computed tomography (CT), and these were correlated with the pathologic findings. The authors studied 32 patients with thoracic esophageal SCC who had undergone radical esophagectomy. RESULTS: Uptake of FDG in the primary tumor was found in 25 of the 32 (78.1%) cases. Comparison of the FDG uptake and the clinicopathologic findings showed that there was a significant association between the FDG uptake and each of the depth of tumor invasion (P < 0.05), occurrence of lymph node metastasis (P < 0.01), and lymphatic invasion (P < 0.01). The survival rate in cases with high FDG uptake (standardized uptake value [SUV], >3) was significantly lower than that in cases with low FDG uptake (SUV, < 3; P < 0.05). In the evaluation of lymph node staging by the detection of lymph node metastasis, FDG-PET showed 77.8% sensitivity, 92.9% specificity, and 84.4% accuracy, and CT scanning showed 61.1% sensitivity, 71.4% specificity, and 65.6% accuracy. Positron emission tomography scanning showed a high degree of accuracy in the neck, upper thoracic, and abdominal regions. However, in the mid- and lower thoracic regions, the sensitivity was very low. The smallest lymph node metastasis that was detected by FDG-PET imaging was 6 mm. The average size of lymph node metastasis that was undetected by FDG-PET scanning was 7.3 mm (range, 1-17 mm). CONCLUSIONS: In conclusion, FDG-PET may be used as a noninvasive diagnostic technique in assessing the aggressiveness of the tumor and the prognosis in patients with esophageal SCC. During the preoperative diagnostic procedures, the sensitivity, specificity, and accuracy of lymph node staging is higher with FDG-PET than with CT imaging. In view of the high specificity of FDG-PET, it also gives useful information to guide the choice of treatment of esophageal carcinoma.

Adult↗

Gastrectomy in combination with a distal splenorenal shunt in a patient with gastric cancer and portal hypertension: report of a case.

We describe the case of a patient with gastric cancer complicated by portal hypertension due to liver cirrhosis. Endoscopy showed esophageal varices in the lower third of the esophagus and a superficially depressed lesion in the middle third of the stomach, while a biopsy suggested signet-ring cell carcinoma. Laboratory data showed pancytopenia, the indocyanine green fraction after 15 min was 29%, and the symptoms corresponded to the Child B criteria. A preoperative arteriogram revealed a remarkably dilated left gastric vein and the development of collateral pathways. We performed a distal subtotal gastrectomy with a reconstruction by the Billroth I method combined with a distal splenorenal shunt (DSRS) and a splenopancreatic disconnection (SPD). The endoscopic findings of the esophageal varices 15 months after surgery showed only a few white veins and the red color sign had disappeared. Now 7 years have passed since surgery, the risk of variceal hemorrhage has disappeared, and the patient is ambulatory and well. These results seems to be attributable to the long-term maintenance of the shunt selectivity and good portal hemodynamics. In patients with gastric cancer complicated with esophageal and/or gastric varices, it is recommended that DSRS with SPD be performed after a reconstruction using the Billroth I method.

Carcinoma, Signet Ring Cell↗

Inflammatory malignant fibrous histiocytoma of the gallbladder: report of a case.

We describe herein a case of inflammatory malignant fibrous histiocytoma (IMFH) of the gallbladder that subsequently metastasized to the ascending colon and later to the stomach. A 70-year-old Japanese man with a palpable mass in the right upper quadrant of the abdomen was referred to our hospital for investigation and treatment. Laboratory data showed severe leukocytosis and elevated serum granulocyte colony-stimulating factor (G-CSF) concentrations. A laparotomy was performed, and the tumor was excised en bloc with the gallbladder and part of the liver bed. Histopathologically, the tumor was composed of ordinary malignant fibrous histiocytoma (MFH) components characterized by pleomorphic tumor cells, bizarre giant cells, and conventional spindle cells in a storiform growth pattern, as well as a xanthogranulomatous component, including inflammatory cells, foamy histiocytes, and plasma cells. Immunohistochemical study revealed that the pleomorphic tumor cells and bizarre giant cells were positive for antibodies against alpha1-antitrypsin and alpha1-antichymotrypsin. The final pathologic diagnosis was IMFH. The tumor cells were diffusely positive for anti-G-CSF monoclonal antibody, and the inflammatory reaction subsided immediately after tumor resection, strongly suggesting that the primary tumor cells produced G-CSF. This patient is still alive with no signs of recurrence more than 3 years after his primary operation, which to our knowledge is the longest survival period ever reported. Therefore, visceral IMFH is manageable in some cases by resecting the primary and isolated metastatic lesions.

Aged↗

Gastropyloric motor activity and the effects of erythromycin given orally after esophagectomy.

BACKGROUND: The motor activity of the gastric tube as an esophageal replacement after esophagectomy is poorly understood. The aims of the present study were to examine the gastropyloric motility of the gastric tube and the effects of erythromycin given orally. METHODS: Interdigestive gastropyloric motility was recorded by manometry with a sleeve sensor in 23 esophagectomized patients. The 23 patients were classified into 3-, 12-, and 24-month groups according to postoperative follow-up time. Radiopaque markers were used in 8 patients to assess gastric emptying. The effects of erythromycin were studied after the patients received 600 mg during fasting and 1 g postprandially. RESULTS: Compared with the 3-month group, the 12-month group and the 24-month group showed significantly increased pyloric and antral motility, respectively. During a fast, erythromycin induced phase III in 44.4% of the patients with more than 12 months of follow-up. In contrast to the normal subjects, esophagectomized patients showed delayed gastric emptying at 3 and 4 hours. However, erythromycin significantly accelerated gastric emptying at 1, 2, 3, and 4 hours. CONCLUSIONS: The motor activity of the gastric tube returns towards normal in a progression over time from the pylorus cephalad. Erythromycin given orally might be used as a prokinetic agent in patients after esophagectomy.

Administration, Oral↗

Usefulness of positron emission tomography for assessing the response of neoadjuvant chemoradiotherapy in patients with esophageal cancer.

BACKGROUND: In this study, we retrospectively assessed the performance of 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) compared with computed tomography (CT) and esophagography for assessing the response of advanced esophageal squamous cell carcinoma (SCC) to neoadjuvant chemoradiotherapy. METHODS: We studied 10 patients with thoracic esophageal SCC who received neoadjuvant chemoradiotherapy followed by surgery. Tumor response was assessed by CT, endoscopy, esophagography and FDG-PET before and after neoadjuvant treatment. RESULTS: Assessment of the rate of decrease in standardized uptake value (SUV) revealed a partial response (more than 50% decrease) in 5 (50%) of the patients, and assessment of length decrease of FDG uptake showed a partial response in 9 (90%) of the patients. Comparison of the histological response and the rate of decrease of various parameters revealed significant associations between histological response and tumor length (P <0.05), SUV after neoadjuvant therapy (P <0.05), and reduction in the extent of FDG uptake (P <0.01). However histological response was not significantly correlated with the rate of reduction of SUV, for both CT and esophagography. CONCLUSIONS: FDG-PET may be of considerable value for predicting the pathologic response of esophageal SCC to neoadjuvant therapy. Despite assessment of SUV before neoadjuvant therapy, low FDG uptake after therapy and reduction in the extent of FDG uptake may provide a reliable assessment of the response to therapy.

Adult↗

The subepithelial extension of esophageal carcinoma for determining the resection margin during esophagectomy: a serial histopathologic investigation.

BACKGROUND: An evaluation of the safe resection margin in esophagectomy or esophageal endoscopic mucosal resection for carcinoma, based on serial histologic investigations by measuring the length of subepithelial extension of the lesion beneath the noncancerous epithelium, has not been reported. METHODS: Forty-eight patients with esophageal carcinoma restricted to within the esophageal wall including 67 lesions (27 mucosal, 27 submucosal cancer, and 13 lesions of cancer invading to proper muscular layer) were histopathologically examined. The length of subepithelial extension (SEE) beneath the noncancerous epithelium of each lesion was measured and the clinicopathologic significance of SEE was discussed. RESULTS: Among these 67 lesions in 48 cases, there were 17 (25.4%) lesions with SEE. The rates of coexistence of SEE were 3.7, 37.0, and 46.2% in mucosal and submucosal cancer, and cancer invading the proper muscular layer, respectively. When the positive rate was more than 50% for the factors of SEE--lymphatic permeation, blood vessel permeation, and intramural metastasis--the prognosis was significantly poorer in the patients with esophageal cancer. CONCLUSIONS: When the lesion was restricted to within the mucosal layer, SEE was almost negligible at resection. The coexistence of SEE was thus found to be one of the prognostic factors predicting a poor prognosis.

Aged↗

Vascularized fibular graft after excision of giant-cell tumor of the distal radius: wrist arthroplasty versus partial wrist arthrodesis.

Several reconstructive procedures have been described for the complete defect of the distal radius that is created after a wide excision of a giant-cell tumor of bone, including hemiarthroplasty using the vascularized fibular head and partial wrist arthrodesis between a vascularized fibula and the scapholunate portion of the proximal carpal row. The objectives of this study are to compare clinical and radiographic results between the partial wrist arthrodesis and the wrist arthroplasty, and to discuss which procedure is superior. Four patients with giant-cell tumors involving the distal end of the radius were treated with en bloc resection and reconstruction with a free vascularized fibular graft. The wrists in two patients were reconstructed with an articular fibular head graft and the remaining two patients underwent partial wrist arthrodesis using a fibular shaft transfer. There was radiographic evidence of bone union at the host-graft junctions in all cases. In the newly reconstructed wrist joint, there was palmar subluxation of the carpal bones and degenerative changes in both patients. Local recurrence was seen in one patient. According to the functional results described by Enneking et al., the mean functional score was 67 percent. The functional scores including wrist/forearm range of motion in the cases with partial wrist arthrodesis were superior to those with wrist arthroplasty. A partial wrist arthrodesis using a vascularized fibular shaft graft appears a more useful and reliable procedure for reconstruction of the wrist after excision of the giant-cell tumor of the distal end of the radius than a wrist arthroplasty using the vascularized fibular head, although our study includes only a small number of patients.

Adult↗

Factors influencing prognosis after direct repair of the flexor pollicis longus tendon: multivariate regression model analysis.

Few studies have focused on the relevance of early motion exercise on repair of the flexor pollicis longus tendon. We evaluated 29 patients with flexor pollicis longus tendon lacerations treated by direct end-to-end suture, and statistically assessed the clinical factors that influenced the results by using a multivariate logistic regression model. Association with age, vascular damage and timing of repair did not affect the results. Patients with flexor pollicis longus tendon lacerations in zone II or with the tendon stumps retracted proximally had a significantly high risk of unsatisfactory results. Postoperative passive flexion and active extension exercise using rubber bands significantly decreased the risk of unsatisfactory results in these conditions. Results of this study indicate that early postoperative motion is useful after every FPL tendon repair, particularly in patients with zone II laceration or retraction of the proximal tendon stump.

Adolescent↗

Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis.

BACKGROUND AND PURPOSE: Gradient-echo T2*-weighted MRI is uniquely sensitive to detect silent, old hemosiderin deposits, but the clinical significance of such "microbleeds" remains to be determined. Therefore, we investigated the incidence and the number of microbleeds among different stroke subtypes and the correlation with stroke recurrence and the severity of leukoaraiosis. METHODS: This study consisted of 213 patients (73.5+/-9.1 years old, 104 men and 109 women), who were classified according to stroke subtypes into atherothrombotic infarction (24 patients), cardioembolic infarction (23 patients), lacunar infarction (66 patients), intracerebral hemorrhage (35 patients), and control (65 patients) groups. Gradient-echo T2*-weighted MRI was performed with a 1.5 T system, and asymptomatic microbleeds were located and counted. RESULTS: The incidence and the number of microbleeds were significantly greater in patients with intracerebral hemorrhage (71.4% and 9.1+/-13.8, respectively) and lacunar infarction (62.1% and 7.4+/-16.1) compared with patients with cardioembolic infarction (30.4% and 2.5+/-5.6), atherothrombotic infarction (20.8% and 0.63+/-1.53), and controls (7.7% and 0.09+/-0.34). There was a correlation between the number of microbleeds and the severity of periventricular hyperintensity (r=0.626, P<0.0001). There was also a correlation between the number of microbleeds and the number of intracerebral hemorrhages (r=0.689, P<0.0001) or lacunar infarctions (r=0.514, P<0.0001). The locations of microbleeds were subcortical white matter (31.8%), thalamus (24.8%), basal ganglia (19.8%), brain stem (12.0%), and cerebellum (11.7%). CONCLUSIONS: The findings suggest that microbleeds on T2*-weighted MRI are an indicator of advanced small artery disease of the brain with an increased risk for bleeding. This result should be taken into consideration when treating patients with stroke, and further studies are required.

Aged↗

Near-infrared spectroscopic topography as a tool to monitor motor reorganization after hemiparetic stroke: a comparison with functional MRI.

BACKGROUND AND PURPOSE: Motor functional recovery from stroke can occur, but the mechanisms underlying this restorative process remain to be elucidated. We used near-infrared spectroscopic (NIRS) topography in comparison with functional MRI (fMRI) to evaluate the compensatory motor activation of cortical regions in patients who recovered from hemiparesis after cortical cerebral infarction. METHODS: We examined 6 right-handed patients who suffered cerebral infarction of the middle cerebral artery territory with minimal or mild residual contralateral hemiparesis (4 men and 2 women, 59 to 79 years old, all had left hemiparesis). Both fMRI and NIRS were studied during a hand movement task at chronic stages. Five right-handed, normal subjects (3 men and 2 women, 44 to 81 years old) served as controls. RESULTS: fMRI and NIRS detected very similar cerebral cortical activation, although NIRS detected only superficial activation. The spatial resolution of NIRS was less than that of fMRI, but NIRS provided a dynamic profile of activation. Normal subjects activated predominantly the contralateral primary sensorimotor cortex and supplementary motor areas during each hand movement. All the stroke patients exhibited the normal activation pattern during normal hand movement. On affected hand movement, the stroke patients showed extended activation not only in the contralateral motor cortex but also in the ipsilateral motor cortex (primary motor cortex and supplementary motor areas). CONCLUSIONS: Both fMRI and NIRS studies provided evidence for the contribution of ipsilateral motor cortical compensation or reorganization to the recovery from poststroke hemiparesis. The result demonstrated that NIRS was a unique tool to monitor poststroke alterations in cortical motor functions.

Adaptation, Physiological↗

Cubital tunnel syndrome associated with medial elbow Ganglia and osteoarthritis of the elbow.

BACKGROUND: Medial elbow ganglia have been reported in association with cubital tunnel syndrome. This lesion is thought to occur rarely and has not been emphasized in the literature. The purposes of the present study are to report our experience with this lesion in order to elucidate its prevalence as well as its clinical and radiographic features, to describe our operative findings, and to present the results of surgical treatment. METHODS: Four hundred and eighty-seven elbows in 472 patients were treated for cubital tunnel syndrome between 1980 and 1999. We performed a retrospective study of the thirty-eight patients who had a medial ganglion. All of the ganglia were excised, and the ulnar nerve was translocated subcutaneously. Thirty-two patients were followed for a mean of thirty-seven months. RESULTS: Medial elbow ganglion was the third most common causative factor associated with cubital tunnel syndrome, with an overall prevalence of 8%. Resting pain in the medial aspect of the elbow was reported by twenty-five of the thirty-eight patients, and a sudden onset of numbness in the ring and little fingers or of medial elbow pain without prior symptoms was reported by twenty-nine patients. The symptoms lasted two months or less in thirty-one patients. All ganglia originated from the medial aspect of the ulnohumeral joint, and radiographs of that joint showed degenerative changes in thirty-seven patients. At the time of follow-up, all measurements of sensory and motor function of the ulnar nerve had improved and no recurrence of nerve palsy was found. CONCLUSIONS: Although uncommon, medial elbow ganglia have a strong association with osteoarthritis of the elbow and can cause a relatively acute onset of cubital tunnel syndrome. A patient with cubital tunnel syndrome associated with elbow osteoarthritis who complains of medial elbow pain or severe numbness within two months after the onset of the syndrome should be strongly suspected of having a ganglion. Most ganglia are occult, and ultrasonography and magnetic resonance imaging can assist in the preoperative diagnosis. Careful excision of the ganglion performed concurrently with subcutaneous anterior transposition of the ulnar nerve can produce satisfactory results.

Adult↗