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Biomedical subjects

H Shinohara

Publications and source records attributed to H Shinohara.

At least 91 records · Page 5Linked to original sources

Epidural compression of the cauda equina caused by vertebral osteoblastic metastasis of prostatic carcinoma: resolution by hormonal therapy.

A 59 year old man with prostatic carcinoma developed epidural compression of the cauda equina caused by bony expansion from a vertebral osteoblastic metastasis. For medical reasons he could not undergo radiation or surgery. Hormonal therapy alone relieved his low back pain and restored ambulation and urinary function. Postmyelography CT showed that the bony expansion from the vertebra had completely disappeared after treatment. This is the first report of remarkable improvement due to hormonal therapy alone.

Bone Neoplasms↗

Serial changes in serum VEGF and HGF in patients with acute myocardial infarction.

The time course of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) release in patients with acute myocardial infarction (AMI) is unknown. Blood samples were obtained at the time of admission and 3, 7, 14 and 21 days later in 32 patients with AMI and 30 control patients. Serum VEGF and HGF, as well as C-reactive protein (CRP) and amyloid A protein (SAA), were determined. Both serum VEGF and HGF levels on admission in patients with AMI were higher than control values and peaked on day 7. VEGF levels in patients with preinfarction angina were higher than in patients with no preinfarction angina, whereas the HGF level did not differ. Both CRP and SAA levels peaked on day 3, and the CRP level on day 3 correlate with both VEGF and HGF levels on day 7. We hypothesized that the serum VEGF level is associated with preinfarction ischemia and the increase in VEGF and HGF on day 7 of AMI may represent a response to acute inflammation.

Aged↗

Milk-borne epidermal growth factor modulates intestinal transforming growth factor-alpha levels in neonatal rats.

Epidermal growth factor (EGF) is present in milk from various mammalian species, but its physiologic function in neonatal development remains unclear. Transforming growth factor-alpha (TGF-alpha) is a peptide structurally related to EGF, and its presence is detected in the developing small intestine of rats. The purpose of the present study was to examine the effect of milk-borne EGF on endogenous production of EGF and TGF-alpha in the small intestine of suckling rats. Neonatal rats were fed via gastrostomy either growth factor-free rat milk substitute (RMS) or RMS supplemented with EGF (100 ng/mL of RMS) from 8 to 12 d of age. Artificially reared rats were then compared with their dam-fed littermates. Animals fed the EGF-deficient diet RMS had markedly increased EGF and TGF-alpha mRNA levels in duodenum and ileum compared with dam-fed controls and significantly elevated total intestinal content of TGF-alpha peptide. Intestinal EGF content and EGF serum levels were significantly decreased in the RMS group compared with controls. The addition of EGF to the RMS diet normalized TGF-alpha mRNA levels in the duodenum and ileum, EGF mRNA levels in the ileum, and total intestinal TGF-alpha content and EGF serum levels to the levels measured in dam-fed littermates. Motility studies showed that enteral administration of EGF did not affect stomach emptying and intestinal transit. These studies indicate that exogenous milk-borne EGF modulates endogenous production of TGF-alpha in developing small intestine. It is likely that neither TGF-alpha nor EGF are solely responsible for small intestinal overgrowth of artificially reared neonatal rats.

Animals↗

Conformational effects on photophysical characteristics of C5-C5'-linked dihydrothymine dimers in solution.

Photophysical characteristics of N-substituted C5-C5'-linked dihydrothymine dimers (1a,b[meso], meso compounds of [5R,5'S]-bi-5,6-dihydrothymines; 1a,b[rac], racemic compounds of [5R,5'R]-bi-5,6-dihydrothymines and [5S,5'S]-bi-5,6-dihydrothymines) in aqueous solution with varying contents of less-polar aprotic solvent such as tetrahydrofuran or dioxane have been investigated by UV-absorption, and steady-state and time-resolved fluorescence spectroscopies. Among the C5-C5'-linked dimers, (5R,5'S)-bi-5,6-dihydro-1-methylthymine (1a[meso]) showed a red-shifted weak UV-absorption band at 270-350 nm and excimer fluorescence emission at lambda max = 370 nm with a quantum yield (phi F) of approximately 0.1 in phosphate buffer (pH < 10) at 293 K. Racemic compound of 5,6-dihydro-1-methylthymine dimer (1a[rac]), meso and racemic compounds of 5,6-dihydro-1,3-dimethylthymine dimers (1b[meso] and 1b[rac]) in phosphate buffer were nonfluorescent under similar conditions. The UV-absorption and fluorescence spectral characteristics of 1a[meso] in aqueous solution were interpreted in terms of intramolecular stacking interactions between the dihydropyrimidine chromophores leading to a preferential "closed-shell" conformation both in the ground state and the excited singlet state. In basic solutions at pH > pKa = 11.7, the fluorescence quantum yield of 1a[meso] decreased due to a dominant "open-shell" conformation resulting from the electrostatic repulsion between the deprotonated dihydrothymine chromophores of 1a[meso] in a dianion form.

Journal Article↗

Anatomy and histology of the lacrimal fluid drainage system.

Five human specimens of the lacrimal canaliculus and sac were examined by light and scanning electron microscopy. The superior and inferior lacrimal canaliculi are lined with stratified squamous epithelium that is non-keratinized and non-mucin-producing. The common canaliculus is also lined with stratified squamous epithelium, but its lumen is much narrower than the lumen of the superior and inferior canaliculi. The common canaliculus opens into an ample space called the vestibule, where the epithelium changes to high pseudostratified columnar and then low pseudostratified columnar. The vestibule continues to the infundibulum of the lacrimal sac. The infundibulum is formed by several epithelial folds that radiate from the vestibular opening to the lacrimal sac. The vestibule and infundibulum are consistent transitional structures from the common canaliculus to the lacrimal sac. The connective tissue of the lamina propria from the common canaliculus to the lacrimal sac has two histological characteristics: numerous free cell aggregates (= lymphoid structure) and numerous venules and capillaries (= cavernous structure).

Aged↗

Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin.

We determined the efficacy of HB21(Fv)PE40, a single-chain immunotoxin made by fusing the variable regions of a monoclonal antibody directed at the human transferrin receptor (TfR) with a truncated mutant of Pseudomonas exotoxin (PE), against metastatic human colon carcinoma KM12L4 cells growing in the liver or subcutis of nude mice. Organ-specific modulation of TfR expression was examined by immunohistochemistry and flow cytometry using anti-human CD71 antibody. KM12L4 cells expressed human TfR and were lysed in vitro by HB21(Fv)PE40 but not LMB-7 (a control immunotoxin specific for a Lewis Y-related carbohydrate antigen). KM12L4 cells growing in the liver expressed higher levels of TfR than cells growing s.c. Systemic administration of HB21(Fv)PE40 eliminated KM12L4 liver metastasis, whereas administration of LMB-7 did not. Treatment of mice with HB21(Fv)PE40 only delayed the growth of s.c. tumors. KM12L4 cells recovered from liver metastases, expressed higher levels of TfR, and were more sensitive to lysis by HB21(Fv)PE40 than KM12L4 cells recovered from s.c. tumors. Indeed, collectively, the data show that the expression level of the TfR by human colon cancer cells is modulated by the organ microenvironment which can be advantageous for the use of therapeutic immunotoxins.

Animals↗

Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation.

Malignant pleural effusion (PE) is associated with advanced human lung cancer. We found recently, using a nude mouse model, that vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is responsible for PE induced by non-small cell human lung carcinoma cells. The purpose of this study was to determine the therapeutic potential of a VEGF/VPF receptor tyrosine kinase phosphorylation inhibitor, PTK 787, against PE formed by human lung adenocarcinoma (PC14PE6) cells. PTK 787 did not affect the in vitro proliferation of PC14PE6 cells, whereas it specifically inhibited proliferation of human dermal microvascular endothelial cells stimulated by VEGF/VPF. A specific platelet-derived growth factor receptor tyrosine kinase inhibitor, CGP57148 (used as a control because PTK 787 also inhibits platelet-derived growth factor receptor tyrosine kinases), had no effect on proliferation of PC14PE6 or human dermal microvascular endothelial cells. i.v. injection of PC14PE6 cells into nude mice produced lung lesions and a large volume of PE containing a high level of VEGF/VPF. Oral treatment with CGP57148 had no effect on PE or lung metastasis. In contrast, oral treatment with PTK 787 significantly reduced the formation of PE but not the number of lung lesions. Furthermore, treatment with PTK 787 significantly suppressed vascular hyperpermeability of PE-bearing mice but did not affect the VEGF/VPF level in PE or expression of VEGF/VPF protein and mRNA in the lung tumors of PC14PE6 cells in vivo. These findings indicate that PTK 787 reduced PE formation mainly by inhibiting vascular permeability, suggesting that this VEGF/VPF receptor tyrosine kinase inhibitor could be useful for the control of malignant PE.

Adenocarcinoma↗

[Comparison of scatter and attenuation correction methods in single photon emission CT--simulation study].

Quantitative SPECT requires an accurate and appropriate attenuation correction and scatter correction. This paper compares scatter corrected images combined with attenuation correction. The scatter correction methods used here were the deconvolution method, dual energy window subtraction method, triple energy window method, and dual photopeak window method. The attenuation correction methods used were Sorenson's method, iterative Chang's method, and Bellini's method. The numerical phantoms used were the cold spot, hot spot, star, and MCAT phantom. These correction methods were assessed by using profiles and images, contrast values, and linearity of SPECT values.

Computer Simulation↗

[Quantitative evaluation for scatter and attenuation correction in 99mTc SPECT--multicenter cooperation phantom study].

A multicenter cooperation phantom study was conducted to evaluate the accuracy of a triple energy window scatter correction technique in combination with various attenuation correction methods for 99mTc single photon emission computed tomography (SPECT) imaging. Six centers participated in this research and the data obtained with seven SPECT instruments were analyzed. The phantom used in the experiment was a 20 x 10 cm cylinder filled with homogeneous 99mTc solution, containing two kinds of cold spots (cold rod phantoms). One had a water-filled cylinder 5.5 cm in diameter positioned 2.5 cm from the center. The other contained 6 water-filled cylinders of various sizes. Contrasts of cold regions were in the range from 74% to 120% (true 100%). Another phantom had the shape of a pie-chart divided into six chambers symmetrically positioned in a cylinder 20 cm in diameter and 10 cm in height. Each chamber had volume of 480 ml and contained homogeneous 99mTc solution of different concentrations. This phantom was used to test for linearity between the radio activity concentration and reconstructed count density (linearity phantom). The intercept of the regression line obtained from the linearity phantom was 8.4 kBq ml-1 without scatter correction and -6.8 kBq ml-1 with scatter correction. Contrast was in the range from 78% to 132% (true 100%). The mean relative error for the measured activity concentration was 4.9% +/- 3.5% (mean +/- sd).

Phantoms, Imaging↗

A rare case of lung cancer associated with renal cell cancer and benign histiocytoma of bone.

Lung cancer often metastasizes to organs outside the thorax, and consequently radiological evaluation of distant metastasis has become standard procedure prior to surgery. Although positive radiological findings generally suggest distant metastasis, the possibility of the co-existence of a benign tumor and primary malignancies must be considered. Herein we report a case of surgical resection of histologically confirmed lung cancer associated with renal cell cancer and benign histiocytoma of the humerus.

Adenocarcinoma↗

Group V phospholipase A(2)-dependent induction of cyclooxygenase-2 in macrophages.

When exposed for prolonged periods of time (up to 20 h) to bacterial lipopolysaccharide (LPS) murine P388D(1) macrophages exhibit a delayed prostaglandin biosynthetic response that is entirely mediated by cyclooxygenase-2 (COX-2). Both the constitutive Group IV cytosolic phospholipase A(2) (cPLA(2)) and the inducible Group V secretory phospholipase A(2) (sPLA(2)) are involved in the cyclooxygenase-2-dependent generation of prostaglandins in response to LPS. Using the selective sPLA(2) inhibitor 3-(3-acetamide-1-benzyl-2-ethylindolyl-5-oxy)propane sulfonic acid (LY311727) and an antisense oligonucleotide specific for Group V sPLA(2), we found that induction of COX-2 expression is strikingly dependent on Group V sPLA(2), which was further confirmed by experiments in which exogenous Group V sPLA(2) was added to the cells. Exogenous Group V sPLA(2) was able to induce significant arachidonate mobilization on its own and to induce expression of the COX-2. None of these effects was observed if inactive Group V sPLA(2) was utilized, implying that enzyme activity is crucial for these effects to take place. Therefore, not only delayed prostaglandin production but also COX-2 gene induction are dependent on a catalytically active Group V sPLA(2). COX-2 expression was also found to be blunted by the Group IV cPLA(2) inhibitor methyl arachidonyl fluorophosphonate, which we have previously found to block Group V sPLA(2) induction as well. Collectively, the results support a model whereby Group IV cPLA(2) activation regulates the expression of Group V sPLA(2), which in turn is responsible for delayed prostaglandin production by regulating COX-2 expression.

Animals↗

Regulation of delayed prostaglandin production in activated P388D1 macrophages by group IV cytosolic and group V secretory phospholipase A2s.

Group V secretory phospholipase A2 (sPLA2) rather than Group IIA sPLA2 is involved in short term, immediate arachidonic acid mobilization and prostaglandin E2 (PGE2) production in the macrophage-like cell line P388D1. When a new clone of these cells, P388D1/MAB, selected on the basis of high responsivity to lipopolysaccharide plus platelet-activating factor, was studied, delayed PGE2 production (6-24 h) in response to lipopolysaccharide alone occurred in parallel with the induction of Group V sPLA2 and cyclooxygenase-2 (COX-2). No changes in the level of cytosolic phospholipase A2 (cPLA2) or COX-1 were observed, and Group IIA sPLA2 was not detectable. Use of a potent and selective sPLA2 inhibitor, 3-(3-acetamide 1-benzyl-2-ethylindolyl-5-oxy)propanesulfonic acid (LY311727), and an antisense oligonucleotide specific for Group V sPLA2 revealed that delayed PGE2 was largely dependent on the induction of Group V sPLA2. Also, COX-2, not COX-1, was found to mediate delayed PGE2 production because the response was completely blocked by the specific COX-2 inhibitor NS-398. Delayed PGE2 production and Group V sPLA2 expression were also found to be blunted by the inhibitor methylarachidonyl fluorophosphonate. Because inhibition of Ca2+-independent PLA2 by an antisense technique did not have any effect on the arachidonic acid release, the data using methylarachidonyl fluorophosphonate suggest a key role for the cPLA2 in the response as well. Collectively, the results suggest a model whereby cPLA2 activation regulates Group V sPLA2 expression, which in turn is responsible for delayed PGE2 production via COX-2.

Animals↗

New simple technique for hepatic parenchymal resection using a Cavitron Ultrasonic Surgical Aspirator and bipolar cautery equipped with a channel for water dripping.

We have developed a new technique to resect hepatic parenchyma without inflow occlusion by using the Cavitron Ultrasonic Surgical Aspirator (CUSA) and bipolar cautery with a saline irrigation system. The significance of this method in hepatectomy was analyzed in comparison with historical control of hepatectomy using Pringle's maneuver. An ordinary bipolar cautery was remodeled with an infusion line to bring saline droplets down the inner surface of one arm of the tweezers through an opening about 1.5 cm proximal to its tip. The optimal flow rate of saline was approximately one drop per second. The power of bipolar cautery was adjusted to 50 watts. When the tweezer blades were approximated to 1 or 2 mm, saline droplets were directed to the tip of tweezers and could be immediately evaporated. After sonicating parenchymal cells, the tissue of small branches of Glisson's tree or small tributaries of the hepatic vein were coagulated by bipolar cautery. The coagulated cords were then easily cut by scissors. The impact of this technique on ordinary liver resections was evaluated by analyzing the postoperative clinical course in relation to the hepatic functional reserve necessary for major hepatectomy, duration of hepatectomy, and intraoperative blood loss. Hepatic resection without vascular occlusion using this technique could decrease the morbidity in patients who have less hepatic functional reserve. It could also decrease intraoperative blood loss. This new technique effectively decreased the surgical load of the remnant liver during parenchymal resection by avoiding ischemic stress. Consequently it extends the safety limits of major hepatectomy.

Electrocoagulation↗

Changes in optic nerve head blood flow and retrobular hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma.

BACKGROUND: Because calcium channel blockers reduce vascular resistance, they may have a clinical application in the treatment of normal-tension glaucoma (NTG). This study investigates changes in both the optic disc blood flow and the hemodynamics of retrobulbar vessels in NTG patients after the systemic administration of a calcium channel blocker. METHODS: Twelve eyes of 12 NTG patients (mean age 57.6 +/- 15.3 years) were examined before and after a 4-week treatment with 2 mg b.i.d. oral nilvadipine, an L-typc calcium channel blocker. By scanning laser-Doppler flowmetry (SLDF), we obtained the velocity, flow, and volume from within a 10 x 10 pixel window placed on the temporal rim region of the optic disc perfusion map. By ultrasound color Doppler imaging (CDI), we measured the peak systolic velocity (PSV) and the end diastolic velocity (EDV) of the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA), and temporal posterior ciliary artery (TPCA). We then calculated a resistance index (RI) for each vessel. RESULTS: After treatment, the flow and velocity of the optic disc blood flow significantly increased (P < 0.05). Nilvadipine also significantly reduced RIs of the CRA, NPCA, and TPCA (P < 0.05), and increased both the PSV of the NPCA and the EDVs of the CRA, NPCA, and TPCA. The percent change in velocity correlated significantly with the percent changes of the CRA RI and NPCA RI. CONCLUSIONS: Oral nilvadipine appears to reduce orbital vascular resistance, which consequently increases the optic disc blood flow.

Adult↗

Disc hemorrhage and peripapillary atrophy in apparently healthy subjects.

PURPOSE: We estimated the prevalence of disc hemorrhage and peripapillary atrophy in apparently healthy subjects. METHODS: We reviewed consecutive plain color fundus photographs of 12,140 eyes of 6,070 subjects (male/female=4,079/1,991) who visited a health consultation center. RESULTS: We analyzed 11,934 eyes of 5,967 subjects with good quality of photographs. Disc hemorrhage was found in 36 eyes of 35 subjects (0.6%). The prevalence of disc hemorrhage was significantly greater in women 60 years of age or older (Fisher's exact test, p=0.0004). The prevalence of peripapillary atrophy (zone Beta, zone Alpha), and suspected glaucomatous excavation in eyes with disc hemorrhage was 66.7%, 86.1% and 25.0%, respectively, and significantly greater than that (29.1%, 52.9% and 1.7%) in eyes without disc hemorrhage (Fisher's exact test, p<0.0001). CONCLUSIONS: Disc hemorrhage is more frequent in women over 60 years of age and is significantly associated with peripapillary atrophy in otherwise apparently healthy Japanese people.

Adult↗

High expression of the gamma5 isoform of G protein in neuroepithelial cells and its replacement of the gamma2 isoform during neuronal differentiation in the rat brain.

High concentrations of G proteins, which include multiple isoforms of each subunit, alpha, beta, and gamma, are expressed in the adult brain. In this study, we concentrated attention on changes of these isoforms during embryonic development in the rat brain. Concentrations of gamma2 as well as GoAalpha, GoBalpha, and beta2 were low in early embryogenesis and then increased, whereas expression of gamma5, in contrast, was initially high followed by a drop, with only very low levels observed throughout postnatal development. Among the other isoforms, Gi1alpha, G(s)alpha-short, G12alpha, G13alpha, beta4, gamma3, gamma7, and gamma12 were present in the embryonic brain at low levels, but their levels markedly increased after birth. In contrast, the levels of Gi2alpha, G(s)alpha-long, Gq/11alpha, and beta1 were essentially constant throughout. Immunohistochemical staining of the brain vesicles in the embryos showed gamma5 to be specifically expressed in the proliferative region of the ventricular zone, whereas gamma2 was mainly present in differentiated neuronal cells of the marginal zone. Furthermore, differentiation of P19 mouse embryonal carcinoma cells to neuronal cells with retinoic acid induced the expression of gamma2 and a decrease of gamma5, the major isoform in the undifferentiated state. These results suggest that neuronal differentiation is responsible for the on/off switch of the expression of gamma2 and gamma5 subunits.

Animals↗

Implementation and quantitative evaluation of analytical methods for attenuation correction in SPECT: a phantom study.

Three differing exact methods of inverting the two-dimensional (2D) exponential Radon transform were implemented and evaluated quantitatively with a phantom study. The phantom had the shape of a pie-chart divided into six cavities, each 480 ml in volume and 10 cm in height, that were symmetrically positioned in a cylinder that was 20 cm in diameter and 10 cm in height. This phantom tests for linearity between true activity concentration and measured activity concentration, and it is denoted as a linearity phantom in the present study. Each cavity contained a different concentration of a homogeneous solution of 99mTc (74, 148, 222, 296, 370 and 444 kBq ml(-1)). Data acquisition was performed with two energy windows: a 20% photopeak energy window set symmetrically over the 140 keV of 99mTc and a secondary 5% energy window set over the 122 keV peak. We optimized a triple-energy window scatter correction method for a gamma camera-collimator system to obtain accurate scatter-corrected projections. A circular ROI 3 cm in diameter was identified over each cavity region, and count density (counts per pixel) was calculated. This value was converted to activity concentration (kBq ml(-1)) using a cross-calibration coefficient between SPECT counts and the gamma well counter. The relation between true activity (x) and measured activity concentration (y) was fitted to a line using the least-squares method. Regression lines were y = 0.63 + 1.0255x (R2 = 0.9987), y = -2.62 + 1.0278x (R2 = 0.9995), and y = 0.092 + 1.0241x (R2 = 0.9989) for the Bellini, Inouye and Metz-Pan methods respectively. In another phantom study using two different types of phantoms, contrast of a cold region in the two was 96% and 101% for all three methods. Combined optimized scatter correction and analytical attenuation correction methods achieve good accuracy in quantification of activity distribution with a uniform attenuating medium.

Humans↗