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Biomedical subjects

K Itoh

Publications and source records attributed to K Itoh.

At least 127 records · Page 7Linked to original sources

The effect of myocardial bridging of the coronary artery on vasoactive agents and atherosclerosis localization.

The relationship between alterations in the immunohistochemical expression of three vasoactive agents [endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), and angiotensin-converting enzyme (ACE)] and the occurrence human atherosclerosis was investigated in relation to the myocardial bridge (MB) of the left anterior descending coronary artery (LAD), an anatomical site that experiences increased shear stress. Five millimetre cross-sections of LADs with MB from 22 autopsied cases were taken from the left coronary ostium to the cardiac apex and were immunohistochemically stained with antibodies against eNOS, ET-1, and ACE. The extent of atherosclerosis in each section was calculated using the atherosclerosis ratio (intimal cross-sectional area/medial cross-sectional area) determined by histomorphometry. The results were analysed according to their anatomical location relative to the MB, either proximal, beneath, or distal. The extent of atherosclerosis was significantly lower beneath the MB, compared with proximal and distal segments. The expression of eNOS, ET-1, and ACE was also significantly lower beneath the MB. The expression of these agents correlated significantly with the extent of atherosclerosis. Because nitric oxide, after its production by eNOS, is believed to be degraded by superoxide radicals, the effect of eNOS expression on atherosclerosis remains controversial. However, the present findings clearly indicate that the expression of ET-1 and ACE is directly related to the development of human coronary atherosclerosis in vivo through shear stress.

Adult↗

Sonographic findings in Shigella colitis.

We present a case of colitis caused by Shigella sonnei in which abdominal sonography helped in the early diagnosis, leading to successful conservative management. Sonography showed diffuse wall thickening and layer stratification in the descending and sigmoid colon. Although Shigella colitis is relatively rare, the possibility must be considered when patients have diffuse wall thickening with distinct layer stratification in the left colon.

Aged↗

Recognition of the Lck tyrosine kinase as a tumor antigen by cytotoxic T lymphocytes of cancer patients with distant metastases.

The Lck protein (p56(lck)), a src family tyrosine kinase that is essential for T cell development and function, is aberrantly expressed in metastatic colon cancers. p56(lck) seems to facilitate the malignant transformation of epithelial cells through initiation of anchorage-independent proliferation. We demonstrate that the lck gene encodes antigenic epitopes recognized by the HLA class I-restricted and tumor-specific CTL of metastatic cancer patients. Lck peptides augmented CTL activity in peripheral blood mononuclear cells (PBMC) of colon and other epithelial cancer patients with distant metastases, but not those without distant metastases. CTL precursors recognizing the Lck peptide were identified in freshly prepared PBMC of patients with distant metastases, and their frequency was significantly augmented by stimulation with the peptide. Thus, Lck peptides could be useful in developing a specific immunotherapy for cancer patients with distant metastases.

Antigens, Neoplasm↗

Malignant hepatic tumor detection with ferumoxides-enhanced MR imaging with a 1.5-T system: comparison of four imaging pulse sequences.

The purpose of our study was to compare observer performance in the detection of malignant hepatic tumors with ferumoxides-enhanced magnetic resonance (MR) images obtained with proton density-weighted spin-echo (SE), T2-weighted fast SE, T2*-weighted gradient-recalled-echo (GRE), and proton density-weighted echo-planar (EP) sequences. Ferumoxides-enhanced MR images obtained with the four sequences in 50 patients with 92 solid malignant and 64 nonsolid benign lesions were retrospectively analyzed. Image review was conducted on a segment-by-segment basis; a total of 397 liver segments was reviewed separately for solid and nonsolid lesions by three independent readers. Observer performance was evaluated with receiver operating characteristic analysis. Lesion-to-liver contrast-to-noise ratio was higher with SE and EP than with GRE and fast SE images for solid lesions (P < 0.05), and higher with fast SE and SE than with GRE images for nonsolid lesions (P < 0.01). Proton density-weighted SE and T2-weighted fast-SE images were superior to T2*-weighted GRE and proton density-weighted EP images for detection of malignant hepatic tumors. T2-weighted fast SE images were the best for detection of nonsolid lesions. T2-weighted fast SE images that were comparable to proton density-weighted SE images for solid tumor detection, that were the best for nonsolid lesion detection, and that had an acquisition time of one third to half of that of SE imaging may be able to replace SE images for ferumoxides-enhanced liver imaging.

Aged↗

Possible involvement of protein kinases and Smad2 signaling pathways on osteoclast differentiation enhanced by activin A.

Bone tissues reportedly contain considerable amounts of activin A and follistatin, an activin A-binding protein. In the present study, we found that follistatin strongly inhibited osteoclast formation in cocultures of mouse bone marrow cells and primary osteoblasts induced by 1alpha,25 dihydroxyvitamin D(3), prostaglandin E(2), and interleukin-1alpha. Antibody aganist activin A also inhibited the osteoclast formation. Furthermore, activin A synergistically stimulated osteoclast differentiation mediated by receptor activator NF-kappaB ligand (RANKL). RT-PCR analysis revealed that osteoblasts produced not only activin A but also follistatin. Western blot analysis of a panel of phosphorylated proteins revealed that activin A stimulated the phosphorylation of p44/42 mitogen activated protein (MAP) kinase (ERK1/2) and p38 MAP kinase in macrophage colony-stimulating factor-dependent bone marrow macrophages (M-BMMPhis). In addition, phosphorylation of Smad2 was observed in M-BMMPhis stimulated with activin A. These findings indicate that the phosphorylation of p44/42 MAP kinase, p38 MAP kinase, and Smad2 is involved in activin A-enhanced osteoclast differentiation induced by RANKL. Taken together, these results suggest that both activin A and follistatin produced by osteoblasts may play an important role in osteoclast differentiation through MAP kinases and Smad2 signaling pathways.

Activin Receptors↗

Power Doppler sonography of the kidney: effect of Valsalva's maneuver.

PURPOSE: It has been reported that an intra-abdominal pressure (IAP) above 15 mm Hg may cause oliguria and that an IAP above 25 mm Hg may cause anuria. Because Valsalva's maneuver yields an IAP exceeding 180 mm Hg, it is presumed to affect renal perfusion. We evaluated the ability of power Doppler sonography to depict the changes in renal blood flow during Valsalva's maneuver. METHODS: Seven healthy men aged 21-24 years and 1 50-year-old man with massive ascites participated in the study. With each healthy subject lying in a supine position, longitudinal power Doppler sonograms of the kidney were obtained and analyzed semiquantitatively during Valsalva's maneuver. Also, in the patient with massive ascites, power Doppler sonography was performed before and after paracentesis. RESULTS: Along with an increase in IAP, monitored as expiratory pressure during Valsalva's maneuver, power Doppler signals decreased as indicated by both visual impression and computer scores. In the patient with massive ascites, signal intensity increased after paracentesis. CONCLUSIONS: Our results demonstrated that an increase in IAP within the physiologic range affects renal perfusion and that power Doppler sonography depicts semiquantitatively the change in renal blood flow.

Adult↗

Pelvic floor disturbance after childbirth: vaginal delivery damages the upper levels of sphincter innervation.

PURPOSE: Vaginal delivery disturbs pelvic floor innervation, which has previously been studied as a single mechanism. The effects of childbirth on innervation at different levels of the anal sphincter system were studied after childbirth. METHODS: Both anal manometry and motor latencies were measured in 67 females. Twenty-nine females (30.8 +/- 4.4 years) were examined four days after vaginal delivery. Eleven of these 29 females were re-examined five months after vaginal delivery. Nineteen females (33.6 +/- 4.6 years) who were examined five to nine days after undergoing an elective cesarean section and 19 asymptomatic, nonpregnant females (26.8 +/- 6.9 years) served as controls. Motor latencies were bilaterally measured within the anal sphincter system at 5, 3.8, 2.6, and 1.5 cm from the perineal skin by using a concentric needle electrode after sacral magnetic stimulation. Means of the bilateral latencies were analyzed. RESULTS: In postpartum females who gave birth vaginally, motor latencies at 5 and 3.8 cm, although not those at 2.6 and 1.5 cm, from the perineal skin were significantly prolonged, and anal pressure monitored by maximum resting and squeeze pressures was significantly decreased compared with that in control females. The decreased anal pressure normalized spontaneously. The prolonged motor latencies at the upper two levels of the anal sphincter system persisted in these females for five months after vaginal delivery. CONCLUSIONS: The disturbance of innervation of the upper anal sphincter system after vaginal delivery may last for a long time, whereas the decreased anal pressure normalizes in a short time. The protracted disturbance of innervation of the upper anal sphincter system may be associated with later development of fecal incontinence.

Adult↗

A case of spindle cell carcinoma of the breast--long survival achieved by multiple surgical treatment.

Spindle cell carcinoma of the breast was formerly called carcinosarcoma, and is relatively rare. We report a case of spindle cell carcinoma of the breast. The patient was treated with multiple surgeries and achieved long-term survival. The patient was a 52-year-old woman, in whom small induration developed at the areola of the nipple of the right breast. The lesion was resected, and benign tumor was diagnosed pathologically. Four years later, she had recurrence at the scar, and a typical mastectomy was performed. A tumor developed again 5 years later; the lesional focus was at the scar of the right chest wall and invasion of the ribs and the sternum was noted. The sternum and the right costal cartilage of ribs 3-9 were dissected together. The right chest wall was reconstructed and adjuvant radiation therapy performed. Four years after this operation, tumor recurred near the scar and chest wall resection including part of the pericardial cavity and the left lung was performed. However, 6 months later, invasion of the mediastinum, heart and lung were noted. The patient died 16 years after the first surgery. Dermatofibrosarcoma protuberance of the breast was diagnosed at the second operation. However, the diagnosis was changed to spindle cell carcinoma of the breast following immunohistochemical studies. Spindle cell carcinoma of the breast is rare, and definitive histopathological diagnosis is often difficult. When spindle cell carcinoma is suspected, comprehensive diagnostic studies including immunohistochemical examinations should be performed. Even in case with multiple recurrences correctly performed operations may contribute to prolongation of survival.

Bone Neoplasms↗

99mTc-MAG3: review of pharmacokinetics, clinical application to renal diseases and quantification of renal function.

About 14 years have passed since Fritzberg et al. developed 99mTc-MAG3 in 1986. The biological properties of this radiopharmaceutical are somewhat different from radioiodine labeled hippurate: it exhibits higher protein binding, slower blood clearance, higher extraction efficiency by tubular cells and larger excretion into the bile than the latter. Nonetheless, it has been widely used as the agent of choice for renal scintigraphy, diuresis renography, captopril augmented renography, and renal transplant. Renal scintigraphy with 99mTc-MAG3 can provide excellent image quality even in the presence of severely decreased renal function. 99mTc-MAG3 is also used as an alternative to radio-hippurate for quantitative measurement of effective renal plasma flow. In this review, I focused on its pharmacokinetics, simplified quantitative methods and clinical application in renal diseases.

Humans↗

Cerebellar blood flow in methylmercury poisoning (Minamata disease).

We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part.

Aged↗

Apoptosis in the basal ganglia of the developing human nervous system.

Programmed cell death (PCD) plays a crucial role in the development of the central nervous system through controlling neuronal numbers and adequate synaptic connections. PCD has been considered to occur in the form of apoptosis. To examine how apoptosis occurs in the developing human brain, we performed a morphometric TUNEL study, using a commercially available kit (ApopTag Kit, Oncor Inc.). We examined apoptotic cells in the basal ganglia of 47 fetuses and newborns without macroscopical and microscopical evident congenital anomalies. Gestational age ranged from 12 to 40 weeks. The numerical density as well as the labeling index of TUNEL-positively labeled nuclei were evaluated. In the caudate nucleus and putamen, TUNEL-labeled cells were observed around the 12th week of gestation. The numerical density of total cells was significantly decreased, whereas the labeling index of apoptotic cells was significantly increased with advanced gestational age. In the globus pallidus, the numerical density of total cells decreased with advancing gestational age, while the labeling index of apoptotic cells increased between the 20th and 28th week, followed by a decrease until the 40th week. The analysis of TUNEL-positive cells revealed a different reaction pattern for the various basal ganglia with regard to the timing and degree of the apoptotic process in regulating cell numbers.

Age Factors↗

Thymic carcinoid in a patient with multiple endocrine neoplasia type 1: report of a case.

We report herein the rare case of a 33-year-old man found to have a multiple endocrine neoplasia type 1 (MEN1)-associated carcinoid tumor in the thymus. A chest roentgenogram demonstrated an asymptomatic anterior mediastinal mass, 7 cm in diameter, and ultrasound-guided percutaneous Tru-Cut biopsy revealed a carcinoid tumor of the thymus. An extended thymectomy was performed through a median sternotomy and pathological examination confirmed the diagnosis of a thymic carcinoid tumor, which was mainly encapsulated with locally invasive growth into the pleura. Despite the absence of a family history of MEN1, he was treated for two pancreatic islet cell tumors, hyperparathyroidism, an adrenal tumor, and a retroperitoneal lipoma. MEN1 mutations were detected both in blood samples and pancreatic tumor tissues. He is now well without any evidence of tumor recurrence 27 months after the operation for the thymic carcinoid. MEN1 mutations were screened by direct nucleotide sequencing of all protein-coding regions of exons 2-10 of the MEN1 gene. Heterozygous germline mutation was detected in the blood sample analyses. Moreover, fresh-frozen pancreatic tumor tissues showed a loss of heterozygosity in the MEN1 region.

Adult↗

Chum salmon trypsin-catalyzed preferential formation of peptides containing D-amino acid.

Chum salmon trypsin-catalyzed peptide synthesis has been studied by using nine series of "inverse substrates," i.e., p-amidinophenyl, p- and m-guanidinophenyl, p- and m-(guanidinomethyl)phenyl, and four position isomers of guanidinonaphthyl esters derived from Nalpha-(tertbutyloxycarbonyl)amino acid as acyl donor components. They were found to couple with an acyl acceptor such as L-alanine p-nitroanilide to produce dipeptide in the presence of trypsin. All substrates tested in this study undergo less enantioselective coupling reaction, and the coupling product was the favorably obtained D-series rather than L-series (in the present case; Nalpha-Boc-D-Ala and Nalpha-Boc-L-Ala). The optimum condition for the coupling reaction was studied by changing the organic solvent, buffer solution, pH, and acyl acceptor concentration. It was found that the enzymatic hydrolysis of the resulting product was negligible.

Amino Acids↗

Treatment of ruptured hepatocellular carcinoma.

BACKGROUND: The problem of whether surgical or conservative treatment is indicated for ruptured hepatocellular carcinoma (HCC) has not been analyzed from the viewpoint of long-term development of hepatitis viral infection from liver fibrosis to liver cirrhosis. Although transcatheter arterial embolization (TAE) for hemostasis followed by two-stage hepatectomy has been established as the best treatment for ruptured HCC, there still remain difficulties in the treatment of some patients. METHODS: Twelve patients with ruptured HCC who were surgically or conservatively treated were retrospectively analyzed in terms of modality of treatment, liver function, extension of HCC, complications, survival rate, and cause of death. RESULTS: Tumor rupture can occur either in the early phase or in the terminal phase during the development from liver fibrosis to liver cirrhosis, while tumor rupture occurs at the advanced stage in terms of HCC extension. TAE for emergent hemostasis or prevention of re-bleeding was performed in ten patients, while TAE was contraindicated in one patient and emergent laparotomy for hemostasis was performed in one patient. In four patients, elective extended surgical resection was performed, because liver function was evaluated as clinical stage 1 according to the General rules for the clinical and pathological study of primary liver cancer of the Liver Cancer Study Group of Japan. In seven patients, conservative or medical treatment was selected, because liver function was evaluated as poor. The surgically treated group, who could tolerate extensive operation, survived longer than the conservatively treated group. CONCLUSIONS: While TAE remains the best method to employ for hemostasis, it still has limitations. Hence, we should be mindful of other possible modalities for hemostasis and their outcomes. Rupture of HCC at an early phase in the development of liver fibrosis is a good indication for elective surgical treatment and should be distinguished from rupture in the terminal phase of liver cirrhosis, which should be treated conservatively. Although elective surgical treatment can be performed in selected patients, tumor size and location of HCC, in addition to liver function, should be taken into consideration.

Aged↗

Different neural systems for recognizing plants, animals, and artifacts.

The purpose of this study was to investigate functional organization in the human brain involved in the representation of knowledge regarding plants. We measured the brain activity of eight male volunteers during the recognition of visual stimuli representing plants, animals and artifacts, using positron emission tomography. The participants were presented with and were required to name silently two different images each of 15 entities belonging to three ontological categories, and 30 series of four to six digits. Marked increases in regional cerebral blood flow were found in the hippocampus and the parahippocampal areas bilaterally and the right lateral occipital cortex during the silent naming of all three categories, compared with that during the silent reading of digits. The right lateral occipital cortex was specifically activated in association with the naming of plants, and the right fusiform cortex was specifically activated in association with the naming of animals. In addition, the right temporo-occipital cortex was activated only during animals and plants, not artifacts. Our results indicate that there were a few characteristic activations for the different categories, and that entities belonging to the different categories are not necessarily represented in different locations of the brain.

Cerebral Cortex↗

Expression of a newly defined tumor-rejection antigen SART3 in musculoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytes by SART3-derived peptides.

We recently reported that a SART3 tumor-rejection antigen possessing tumor epitopes is capable of inducing HLA class 1-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients. We studied the expression of the SART3 protein in musculoskeletal tumors to find a molecule for potential use in tumor-specific immunotherapy. The SART3 was detected at protein levels in 100% of the osteosarcoma cell lines (n = 20), in 50% of the musculoskeletal tumor tissue specimens (n = 32), and at notable levels in 67% of osteosarcoma tissues (n = 9) and malignant fibrous histiocytosis tissues (n = 9), respectively. SART3-derived peptides at positions 109-118 and 315-323 induced HLA-A24-restricted tumor-specific cytoxic T lymphocytes from peripheral blood mononuclear cells of patients with osteosarcoma or malignant fibrous histiocytosis. These peptide-induced cytotoxic T lymphocytes recognized HLA-A24+ SART3+ osteosarcoma cells but not HLA-A24 or SART3 cells. These results suggest that the SART3 protein and its derived peptides could be molecules appropriate for use in specific immunotherapies for approximately 60% of HLA-A24+ patients with osteosarcoma or malignant fibrous histiocytosis.

Antigens, Neoplasm↗

Rapid detection of mutations associated with resistance to erythromycin in Campylobacter jejuni/coli by PCR and line probe assay.

Mutation of 23S rDNA is one of the mechanisms of erythromycin resistance. PCR and line probe assay (PCR-LiPA) with ten oligonucleotide probes were developed to detect the mutations associated with macrolide resistance at positions of 2072, 2073 and 2074 in 23S rDNA of Campylobacter jejuni/coli. A2074-->G mutation was detected in 12 of 25 isolates, which were resistant to erythromycin. No other mutations in 23S rDNA were detected. The rest of the strains were susceptible to erythromycin and no mutation in 23S rDNA was detected. Six laboratory induced erythromycin resistant mutants had no mutations in 23S rDNA. PCR-LiPA is a useful and rapid method to detect mutations in 23S rDNA associated with erythromycin resistance in C. jejuni/coli.

Base Sequence↗

Factors affecting the pharmacokinetics of CPT-11: the body mass index, age and sex are independent predictors of pharmacokinetic parameters of CPT-11.

This study was conducted to describe the relationship between pharmacokinetics of CPT-11 and its active metabolite SN-38, and clinical values with special emphasis on the influence of relative weight referring to the appropriateness of a conventional dose adjustment method by body surface area (BSA). Thirty-six patients received 100 mg/m2 of CPT-11 intravenously over 90 min. Body Mass Index (BMI) was used as a measure of relative weight which is calculated from the equation: BMI=weight(kg)/[height(m)]2. The area under the concentration-time curve (AUC) of CPT-11 was significantly correlated with sex, age, poorer creatinine clearance and indocyanine green retention test (ICG). The peak plasma concentration (Cmax) of CPT-11 was significantly correlated with sex a larger BMI, BSA and age. The AUC of SN-38 was significantly correlated with ICG. The volume of distribution at steady state of CPT-11 inversely correlated with BMI. Multiple regression analysis revealed that the best fitting model with significant independent predictors for AUC of CPT-11 included age and sex (F=6.93, R2=0.29). That of Cmax of CPT-11 included sex and BMI (F=8.96, R2=0.35). The only independent predictor of AUC of SN-38 was ICG (F=7.75, R2=0.19). These results indicated that several factors affect pharmacological behaviors of CPT-11 even in patients with normal organ functions. The dose modification method based solely on BSA is not sufficient to reduce interpatient variability of cancer chemotherapy. The influence of relative weight, sex and age on pharmacokinetics/pharmacodynamics should be taken into consideration in every pharmacological approach to establish the ideal dose modification method.

Adult↗