Myeloma cells produce sialyl salivary-type amylase.
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Aged↗
Biomedical subjects
Hitoshi Shibuya
Publications and source records attributed to Hitoshi Shibuya.
Triple-phase dynamic MRI of intratumoral vessel density and hyalinization grade in uterine leiomyomas.
OBJECTIVE: Our purpose was to clarify the relationship between the tissue vascularity shown on triple-phase dynamic MRI and the number of intratumoral vessels and degree of hyalinization, which are two histopathologic changes in leiomyoma. SUBJECTS AND METHODS. The subjects were 10 premenopausal patients with 20 leiomyomas who had undergone surgery without preoperative gonadotropin-releasing hormone analogue treatment. Intratumoral vessel density was determined by the mean number of intratumoral vessels with at least one smooth-muscle layer in the optic fields magnified 100 times. Hyalinization grade was determined by the severity of hyalinization, histopathologically classified in three grades. The enhancement index (EI) of the leiomyoma was calculated using the formula EI(t) = [S(t) - S(0)] / S(0), where S(0) is the signal intensity on pre-enhanced T1-weighted images and S(t) is the signal intensity on each dynamic phase image (t = 20, 60, and 180 sec) [corrected]. The histopathologic parameters of intratumoral vessel density and hyalinization grade were compared with the enhancement indexes obtained from the triple-phase dynamic MRI. RESULTS: We found positive correlations between intratumoral vessel density and EI(60) and between intratumoral vessel density and EI(180) (in both cases, p = 0.0028 and r = 0.69). We found significant differences among the mean enhancement indexes for each hyalinization grade at all dynamic phases (p < 0.01). The leiomyomas with lower intratumoral vessel densities tended to show greater hyalinization. CONCLUSION: Our results showed that leiomyomas with only slight hyalinization or with abundant vessels were well enhanced, but the leiomyomas with severe hyalinization enhanced poorly.
Adult↗
[A case of advanced gastric cancer with bulky N2 lymph node metastases resected after successful treatment with TS-1].
We report a case of advanced gastric cancer with bulky N2 lymph node metastases resected after successful treatment with novel oral anticancer drug TS-1 as a neoadjuvant chemotherapy (NAC). A 62-year-old man was admitted to our hospital complaining of epigastralgia and dysphagia. Endoscopic examination revealed type 3 advanced gastric cancer in the upper gastric body. Computed tomography (CT) showed bulky N2 lymph node metastases. He was treated with a daily dose of 120 mg of TS-1 for 4 consecutive weeks, followed by 2 weeks of rest. No serious adverse reaction was observed. After 1 course of treatment, the primary tumor and metastatic lymph nodes were reduced. Therefore, a total gastrectomy combined with splenectomy and D2 lymph node dissection was performed. Histopathologically, a few viable cancer cells remained in the resected stomach and metastatic lymph nodes were found. The histological effect of NAC was judged to be grade 2. The patient's postoperative course was uneventful, and he has been well for 11 months following surgery. TS-1 as NAC is considered to be effective for advanced gastric cancer.
Adenocarcinoma↗
Roles of the insulin-like growth factor I receptor C-terminus in cellular radioresistance.
Available evidence suggests that insulin-like growth factor I receptor (IGF-IR) expression leads to increased cellular radioresistance. The most direct explanation of these findings predicts that IGF-IR is the source of survival signals in resistant cells. Mutational analysis revealed that protein truncated at amino acid 1245 in the C-terminus retained the ability of IGF-IR to confer radioresistance whereas point mutations at both Tyr-1250 and Tyr-1251 abrogated this effect using IGF-IR-deficient mouse embryo fibroblasts (R-) as a recipient. In cells expressing the latter mutant receptors, both phosphatidylinositol-3(') kinase (PI3-K) and mitogen-activated protein kinase (MAPK) signaling pathways remained intact, and addition of exogenous IGF-I could not change the radiosensitivity of these cells. Further analysis indicated that the abrogation of radioresistance required the presence of His-1293 and Lys-1294. These results suggest a novel regulatory role of the C-terminus of IGF-IR in mediating cellular radioresistance that may be independent of survival signals transmitted through this receptor.
Amino Acid Sequence↗
Increase of KL-6 in sera of uveitis patients with sarcoidosis.
BACKGROUND: KL-6 is a human glycoprotein secreted by type II alveolar cells in lung, and its serum levels increase in pneumonia of various causes. KL-6 is a member of the MUC-1 family, which is expressed in lung, cornea, and conjunctiva. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for diagnosing sarcoidosis in patients with uveitis. METHODS: Sera were obtained from 24 uveitis patients diagnosed with sarcoidosis, 37 uveitis patients with other etiologies, and 138 healthy control subjects. Serum concentration of KL-6 was determined by a human KL-6 electrochemiluminescence immunoassay. RESULTS: The average level of KL-6 in the sera of uveitis patients with sarcoidosis was 387 U/ml. This was significantly higher than in healthy subjects and uveitis patients with other etiologies. The KL-6 measurements identified 45.8% of sarcoidosis-positive patients. When the KL-6 results were combined with serum angiotensin-converting enzyme (ACE) concentrations, 87.5% of sarcoidosis patients were identified, compared to 66.7% using ACE results alone. The combined measurement identified 10.8% of the non-sarcoid patients and 0.72% of healthy subjects as positive (false positive). CONCLUSION: Combined measurements of serum KL-6 and ACE may be useful as a screening for sarcoidosis in uveitis patients.
Antigens↗
Oral pseudotumor: benign polypoid masses following radiation therapy.
BACKGROUND: The current study evaluated postirradiation pseudotumor in the oral cavity to investigate clinical and pathologic characteristics and incidence rates. METHODS: Between 1960 and 1999, 2719 patients with squamous cell carcinoma of the oral cavity were treated with radiation therapy at Tokyo Medical and Dental University Hospital. Of these, six patients developed clinically polypoid tumors pathologically diagnosed as pseudotumors. Histopathology, immunohistology, and the clinical courses of these lesions were investigated. RESULTS: Spindled fibroblastic cells arranged in whorled patterns were common pathologic features. Immunohistochemical results showed reactivity for vimentin and smooth muscle actin and nonreactivity for cytokeratin. The latent period from the initial radiation therapy to the development of the pseudotumor ranged from 45 to 145 months (median, 79 months). The overall cumulative incidence of pseudotumor was 0.22% during the 40 year period. All six patients were cured with simple excisions. CONCLUSIONS: Oral carcinoma patients treated with radiation therapy may develop pseudotumor in a low frequency with a shorter period than that of radiation induced carcinoma/sarcoma. Pseudotumor was curable with surgery. Pseudotumor should be added to the list of differential diagnosis for postirradiation oral polypoid masses.
Adult↗
Regional cerebral blood flow in depressed patients with white matter magnetic resonance hyperintensity.
BACKGROUND: Functional neuroimaging studies have consistently demonstrated decreased regional cerebral blood flow (rCBF) or metabolism in the frontal lobe, temporal lobe, or anterior cingulate gyrus of depressed patients. On the other hand, white matter hyperintensity as defined by magnetic resonance imaging (MRI) has been the most consistently replicated finding in structural neuroimaging studies on depression; however, these functional and structural neuroimaging findings of depression have not been well integrated. We aimed to clarify the possible associations of MRI-defined subcortical hyperintensities with rCBF changes in depressed patients. METHODS: Twelve depressed patients with subcortical hyperintensities defined by MRI, 11 depressed patients without MRI hyperintensities, and 25 healthy volunteers underwent 99mTc ECD SPECT. Group comparisons of their rCBF and correlation analysis between MRI hyperintensity and rCBF in patients were performed with a voxel-based analysis using statistical parametric mapping (SPM) software. RESULTS: Depressed patients showed decreased rCBF compared with control subjects in the frontal lobe, temporal lobe, and anterior cingulate gyrus whether subcortical hyperintensity existed or not; however, the patients with MRI hyperintensity showed decreased rCBF in the thalamus, basal ganglia, and brainstem in addition to cortical areas. Further, the score for white matter hyperintensity correlated negatively with rCBF in subcortical brain structures, including the thalamus and right basal ganglia. CONCLUSION: Our study indicates that depressed patients with MRI hyperintensities may have dysfunction in subcortical brain structures in addition to dysfunction in the fronto-temporal cortical structures.
Adult↗
MR imaging of the thyroid: correlation between apparent diffusion coefficient and thyroid gland scintigraphy.
PURPOSE: To evaluate the usefulness of echo-planar MR imaging for assessing the thyroid function and confirm the clinical use of MR imaging for thyroid diseases. MATERIALS AND METHODS: Thirty-four patients with a variety of thyroid disorders (24 Graves disease; five subacute thyroiditis; five Hashimoto thyroiditis) were examined using T1-, T2-, and diffusion-weighted magnetic resonance (MR) imaging and thyroid scintigraphy with Tc-99m pertechnetate. RESULTS: The ADC values obtained from the diffusion-weighted images of the patients with Graves disease were significantly higher than those of patients with subacute hyroiditis and Hashimoto thyroiditis, though no difference among those disorders was observed on T1- and T2-weighted images. Based on the ADC value, anisotropy was not observed in the thyroid gland. An ADC value of 1.82 x 10(-3) mm(2)/second or higher indicated the presence of Graves disease (sensitivity 75%, specificity 80%). CONCLUSION: Diffusion-weighted MR images may be of value for the diagnosis of thyroid diseases and could be clinically important in the evaluation of thyroid function.
Diffusion Magnetic Resonance Imaging↗
Brain perfusion SPECT in patients with corticobasal degeneration: analysis using statistical parametric mapping.
We sought to determine the characteristics of brain perfusion in patients with corticobasal degeneration (CBD) using single photon emission computed tomography (SPECT) and statistical parametric mapping (SPM). Thirteen patients with CBD and 10 age-matched healthy volunteers were examined using brain perfusion SPECT and (99m)Tc-ethyl cysteinate dimer (ECD). Regional cerebral blood flow (rCBF) measurements were performed noninvasively using a graphic analysis method. Both the absolute rCBF data (raw data) and the adjusted rCBF data (global CBF normalized to 50 ml/100 g/min) were used in the SPM analysis. A significant decrease in the absolute rCBF was observed in extended areas of the brain in CBD patients compared to the control group. These areas included the frontal, parietal, and temporal cortices; basal ganglia; thalamus; and pontocerebellar regions. Our results suggest that the extent of the reduced rCBF region in CBD patients is more widespread than previously reported.
Aged↗
Neck node metastasis after successful brachytherapy for early stage tongue carcinoma.
BACKGROUND AND PURPOSE: The accuracy of factors for predicting lymph node metastasis in patients with early-stage (stage I and II) mobile tongue carcinoma and prognostic factors associated with the clinical and pathological findings of lymph node metastasis were examined. MATERIAL AND METHODS: Between 1971 and 1998, 616 patients with early stage mobile tongue carcinoma were treated by brachytherapy with or without external irradiation. Neck lymph node metastasis occurred in a total of 237 cases, and 191 of them were not associated with primary failure. Neck dissection was performed in 169 of these 191 cases, and 16 cases were treated by radiotherapy. A pathological analysis was possible in 159 of the 169 neck dissection cases. RESULTS: There were 88 tongue cancer recurrences, and the incidence of neck metastasis was 38% (191/528) in the cases of primary controlled early tongue carcinoma, and 25% (38/151) and 41% (153/377), in stage-I and -II carcinoma, respectively. Neck metastasis was diagnosed within 12 months in 80% of cases, and within 24 months in 95%. Macroscopic appearance, tumor thickness and tumor length were identified as significant risk factors by a univariate analysis, but macroscopic appearance was the only significant risk factor identified by a multivariate analysis (P<0.001). The incidence of cervical lymph node metastasis was 62% among the invasive/ulcerative type tongue carcinomas, and was lower among the superficial type and exophytic/nodular type (20 and 35%, respectively). Regional and/or distant failure occurred in 75 of the 169 neck dissection cases (44%). The incidence of regional/distant failure was extremely high (49/68=72%) in the extra-nodal invasion group, and extra-nodal invasion was found even in small metastatic node less than 1 cm in length (20%). CONCLUSIONS: The macroscopic appearance of the primary tongue carcinoma has a major impact on the incidence of lymph node metastasis in patients with early tongue cancer, and extra-nodal invasion was the dominant risk factor for regional and distant failure. Treatment policy for clinically negative neck metastasis in early tongue cancer patients should be determined after considering the possibility of neck metastases and the morbidity associated with elective neck dissection.
Adult↗
Redundancy of radioresistant signaling pathways originating from insulin-like growth factor I receptor.
The insulin-like growth factor I receptor (IGF-IR) has the ability to confer clonogenic radioresistance following ionizing irradiation. We attempted to determine the downstream pathways involved in IGF-IR-mediated radioresistance and used mouse embryo fibroblasts deficient in endogenous IGF-IR (R-) as recipients for a number of mutant IGF-IRs. Mutational analysis revealed that the tyrosine at residue 950 (Tyr-950) of IGF-IR, as well as the C-terminal domain, are required for radioresistance and that both domains must be mutated to abrogate the phenotype. Furthermore, the contribution of downstream pathways was analyzed by combining the use of wild-type or Tyr-950 and C-terminal mutants with specific inhibitors of phosphatidylinositol 3'-kinase (PI3-K) or mitogen-activated protein extracellular signal-regulated kinase (ERK) kinase (MEK). Radioresistance could be induced by IGF-IR as long as the ability of the receptor to stimulate the MEK/ERK pathway was retained. This was confirmed by the expression of constitutively active MEK in R- cells. The ability to stimulate the PI3-K pathway alone was not sufficient, but PI3-K activation coupled with MEK/ERK pathway-independent signals from the C terminus was able to induce radioresistance. Taken together, these results indicate that the IGF-IR-mediated radioresistant signaling mechanism progresses through redundant downstream pathways.
Animals↗
Insulin-like growth factor I receptor is expressed at normal levels in Nijmegen breakage syndrome cells.
Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder sharing a pleiotropic phenotype with ataxia-telangiectasia (A-T), including increased radiosensitivity and cancer disposition. Insulin-like growth factor I receptor (IGF-IR) expression is reportedly decreased in A-T cells, which is thought to contribute to its increased radiosensitivity. In this study, we investigated whether the same mechanism underlies the radiosensitivity of NBS cells. GM7166VA7 cells lacking NBS1 protein displayed a phenotype of increased radiosensitivity, while the introduction of NBS1 cDNA conferred radioresistance comparable to normal cells. IGF-IR expression levels were essentially the same among normal, NBS, and NBS1-complemented NBS cells. There was no significant difference between NBS and NBS1-complemented cells in activation of major downstream pathways of IGF-IR upon IGF-I stimulation, including phosphatidylinositol-3(') kinase (PI3-K) and mitogen-activated protein kinase (MAPK). Collectively, IGF-IR-related events are unlikely to be disrupted in NBS cells, and therefore, defects in IGF-IR signaling do not explain the increased radiosensitivity of NBS cells.
Cell Line, Transformed↗
Trimodal combination therapy for maxillary sinus carcinoma.
PURPOSE: This study was conducted to evaluate the effectiveness of trimodal combination therapy (radiotherapy, intra-arterial chemotherapy, antrotomy) for the treatment of primary maxillary sinus carcinoma. METHODS AND MATERIALS: Between 1977 and 1996, 110 patients with maxillary squamous cell carcinoma were treated with trimodal combination therapy at Tokyo Medical and Dental University Hospital. All tumors were classified according to the 1997 UICC TNM staging system. Eighty percent of patients had T3 or T4 tumors. The T3 and T4 tumors were also classified into three groups according to their location, as visualized using computed tomography: the posterior-lateral (P) group, the medial (M) group, and the upper (U) group. Eight patients received additional radiotherapy, and 37 patients underwent a second surgical procedure, in addition to the trimodal combination therapy. RESULTS: The 5-year cause-specific survival and local control rates were 71% and 65%, respectively. The 5-year local control rate was 80% for the T1+2 tumors, 64% for the T3 tumors, and 52% for the T4 tumors (p = 0.06). Patients in the P+M group who received a 5-fluorouracil (5-FU) dosage of more than 3500 mg had a better 5-year local control rate than patients who received a 5-FU dosage of less than 3500 mg (p = 0.01). No improvement in the local control rate after a second surgical procedure or additional irradiation treatment was observed in any of the groups. CONCLUSION: Trimodal combination therapy provides good local control, with the final outcome depending on the T stage of the tumor and the dosage of 5-FU.
Adult↗
Site specific dependency of second primary cancer in early stage head and neck squamous cell carcinoma.
BACKGROUND: A study was conducted to determine the site specificity of second primary cancer (SPC) following early (Stage I and II) squamous cell carcinoma of the head and neck (SCH) and its impact on prognosis. METHODS: Between 1956 and 1999, 1,639 early stage SCHs in 1,609 patients were treated by radiotherapy at the authors' institution. The risk of additional respiratory and upper digestive tract (RUDT) carcinoma and the treatment outcome were reviewed for each SCH site. Second primary RUDT carcinomas were the second most common cause of death (113 cases) after death from primary SCH carcinomas (350 cases). RESULTS: Among the 1,609 early stage SCH patients, 333 second primary cancers were documented in 258 patients, 235 (71%) of which were RUDT carcinomas. The risk of SPCs was 3.2% per year, and the risk of SPCs in the RUDT region was 2.3% per year. The risk of SPCs was almost two times higher in males (3.7% per year) than in females (2.2% per year). The highest risk of SPC was observed in the oro-hypopharynx index cancer group (8.5% per year), and the lowest risks were observed in the epipharynx group (0% per year) and the maxillary sinus group (1.4% per year). CONCLUSIONS: Different SPC risks according to the SCH site result in a different prognosis for each site of early stage SCH. Long-term follow-up care after the initial treatment for early SCH should be continued according to the site of the initial SCH.
Adult↗
Decreased thyroid uptake of Tc-99m pertechnetate in patients with advanced-stage Sjögren syndrome: evaluation using salivary gland scintigraphy.
PURPOSE: The authors assessed the uptake of Tc-99m pertechnetate in the thyroid using salivary gland scintigraphy in patients with Sjögren syndrome and in healthy controls. MATERIALS AND METHODS: Salivary gland scintigraphy and a labial biopsy were performed in 73 patients with Sjögren syndrome. Based on the labial biopsy findings, 32 patients with a histopathologic grade of 1 or 2 were regarded as having early-stage Sjögren syndrome and 41 patients with a grade of 3 or 4 were regarded as having an advanced stage. After the administration of 370 MBq (10 mCi) Tc-99m pertechnetate, dynamic salivary gland scintigraphy was performed for 50 minutes. Lemon juice was used to stimulate the salivary glands, and the thyroid gland was included in the imaging area. Scintigraphy was also performed in an age- and sex-matched control group of 25 healthy persons. The thyroid uptake ratio was calculated for the scintigraphic images and compared among the three groups: healthy controls, patients with early-stage Sjögren syndrome, and those with advanced-stage Sjögren syndrome. RESULTS: When compared with the control group, the thyroid uptake ratio of the early-stage Sjögren syndrome group was not significantly different, whereas that of the advanced-stage group was significantly lower. CONCLUSIONS: Thyroid uptake of Tc-99m pertechnetate was less in patients with advanced-stage Sjögren syndrome than in patients with early-stage Sjögren syndrome or in healthy controls. Measuring the thyroid uptake of Tc-99m pertechnetate using salivary gland scintigraphy is an easy and useful method for assessing thyroid disorders in Sjögren syndrome and thus should be performed routinely.
Adolescent↗
Effect of ageing on plasma lipoprotein(a) levels.
BACKGROUND: Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerosis and increases with age. The purpose of this study was to determine the effect of ageing on Lp(a) for three different apo(a) phenotypes. METHODS: We measured plasma Lp(a) concentrations in 551 unrelated Japanese subjects (20-88 years of age). We performed statistical analyses separately for three apo(a) phenotypes: the low-molecular-weight (LMW) phenotype with the F, B or S1 isoform, the intermediate-molecular-weight (IMW) phenotype with the S2 isoform and the high-molecular-weight (HMW) phenotype with the S3 or S4 isoform. RESULTS: For each phenotype, the mean plasma Lp(a) concentration and the frequency of Lp(a) concentrations > or = 250 mg/L increased with age. Further, a statistically significant difference was always found between the younger subjects (20-39 years of age) and the elderly (over 60 years). The frequency of coronary heart disease increased with age, particularly for the LMW and IMW phenotypes. CONCLUSIONS: We conclude that ageing elevates plasma Lp(a) concentrations, which may have a role in the prevalence of coronary heart disease in the elderly, especially those with the LMW or IMW phenotypes.
Adult↗
The phosphatidylinositol-3 kinase pathway is not essential for insulin-like growth factor I receptor-mediated clonogenic radioresistance.
The insulin-like growth factor I receptor (IGF-IR) is known to induce clonogenic radioresistance in cells following ionizing irradiation. To explore the downstream signaling pathways, we focused on the phosphatidylinositol-3 kinase (PI3-K) pathway, which is thought to be the primary cell survival signal originating from the receptor. For this purpose, R- cells deficient in the endogenous IGF-IR were used as a recipient of the human IGF-IR with or without mutations at potential PI3-K activation sites: NPXY950 and Y1316XXM. Mutants with double mutation at Y950/Y1316 exhibited not abrogated, but reduced activation of IRS-1, PI3-K, and Akt upon IGF-I stimulation. However, the mutants had the same clonogenic radioresistance as cells with wild type (WT) receptors. Neither wortmannin nor LY294002, specific inhibitors of PI3-K, affected the radioresistance of cells with WT receptors at concentrations specific for PI3-K. Collectively, these results indicate that the PI3-K pathway is not essential for IGF-IR-mediated clonogenic radioresistance.
Animals↗