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Biomedical subjects

H Kobayashi

Publications and source records attributed to H Kobayashi.

At least 325 records · Page 18Linked to original sources
PubMed2000

Localization of Smad6 and Smad7 in the rat kidney and their regulated expression in the anti-Thy-1 nephritis.

Under normal conditions, kidney expresses Smad6 and Smad7 most abundantly among the organs of the body. To understand the physiological roles of these Smad expressions in the kidney, we first identified the sites of Smad6 and Smad7 expression in the rat kidney by in situ hybridization. The expression of Smad7 in the rat kidney was only observed in the glomeruli, while Smad6 was expressed in both the glomeruli and thick ascending limb of Henle's loop. In order to investigate whether Smad6 and 7 are also involved in the negative feedback loop of TGF-beta signaling in vivo, we examined the changes of mRNA levels of these Smads in the glomeruli of rat anti-Thy1 (1-22-3) nephritis, a model where the expression of TGF-beta in the glomeruli has been shown to be most up-regulated from day 4 to 14 after the antibody injection. Unexpectedly, 7 days after injection, the levels of Smad6 and Smad7 did not increase but rather decreased to approximately 70% of the levels on day 0. During that period, Smad7 immunostaining was observed in the glomerular endothelial cells (GEN) where Smad3 immunostaining was also observed. This suggested that Smad7 expression was not augmented by the TGF-beta signal in GEN in vivo in anti-Thy-1 nephritis. The absence of up-regulation of these inhibitory Smads may be involved in the pathogenesis of anti-Thy-1 nephritis.

Animals↗
PubMed2000

Readministration of tamoxifen after adjuvant therapy for recurrent breast cancer.

BACKGROUND: Previous series concerning tamoxifen (TAM) rechallenge did not obtain satisfactory results. Using stricter criteria, we now assess the usefulness of readministration of TAM as an initial therapy for patients with recurrent breast cancer. METHOD: The eligibility criteria were postmenopausal, estrogen receptor (ER) positive or unknown, at least 12 months of adjuvant TAM, a 6-month or longer drug-free period and no previous therapy after recurrence. A total of 10 patients were enrolled. TAM was administered in daily doses of 20 or 30 mg. RESULTS: The mean age of the patients at the time of recurrence was 64.8 years. The receptor status was positive in 8 patients and unknown in 2. The median disease-free interval (DFI) after mastectomy was 71.7 months. A complete response was observed in one patient, a partial response in 6, stable disease in 2, and progression in one. The response rate was thus 70%, with an additional two patients showing no progression over 6 months. Although only one patient with a DFI of less than 48 months showed a positive response, all patients with a DFI longer than 48 months showed a clinical response. The duration of response was less than 12 months in 3 patients and longer in 4. CONCLUSION: The post-adjuvant readministration of tamoxifen is a useful first choice therapy for postmenopausal recurrent breast cancer patients with positive ER and longer DFI.

Aged↗
PubMed2000

Regional cardiac sympathetic reinnervation in transplanted human hearts detected by 123I-MIBG SPECT imaging.

The purpose of this study was to assess the regional cardiac sympathetic reinnervation late (> or = 1 year) after heart transplantation (HTX) by means of 123I-MIBG (MIBG) scintigraphy. Eight patients with a pretransplantation diagnosis of idiopathic dilated cardiomyopathy underwent MIBG scintigraphy more than one year after HTX. The presence or absence of regional MIBG uptake was evaluated in each SPECT image, and global MIBG uptake was semi-quantitatively assessed by the heart to mediastinum ratio (H/M). Five of 8 patients had visible MIBG uptake in both planar and SPECT images (PU group), whereas 3 of 8 patients had no uptake, 2 of them after a period of 2 years, and one of them as long as 5 years after HTX, respectively (NU group). Positive regional MIBG uptake involved the basal anterior region in all 5 patients, the basal septal region in 4 patients, the basal lateral region in 3 patients and the basal posterior region in 1 patient. The H/M value was 1.24+/-0.10 in the PU group and 1.09+/-0.03 in the NU group. In conclusion, MIBG SPECT can detect regional sympathetic reinnervation, indicating that basal septal and lateral regions next to the basal anterior are more likely to be reinnervated, but reinnervation is much less likely to occur in the midventricular and apical regions.

3-Iodobenzylguanidine↗
PubMed2000

The development of an elevated lesion associated with colitis cystica profunda in the transverse colonic mucosa during the course of ulcerative colitis: report of a case.

We report the case of a 53-year-old man with a long history of ulcerative colitis in whom an elevated lesion in the epithelium of the affected transverse colon was initially diagnosed as a benign inflammatory polyp by endoscopic biopsies. After 4 years of follow-up, because the tumor had enlarged and villous components were endoscopically observed on the surface, a colonic resection was performed. The tumor was found to consist of hyperplastic colonic epithelium associated with multiple mucinous cysts lined with dysplastic colonic epithelial cells. Moreover, the mucinous cysts were primarily located beneath the submucosal layer and appeared to intrude into the muscularis propria of the colonic wall. This lesion had a unique pathological feature, presumably indicating neither benign inflammatory epithelium nor a neoplastic lesion of the colonic epithelium. Mucinous cysts lined with colonic epithelial components in the muscularis propria suggest a loss of normal integrity of the colonic wall. Areas of the epithelial cell lining of the mucinous cysts showed apparent structural and nuclear atypia and positive expression for p53, suggesting that this portion of the specimen was dysplastic epithelium. These pathological findings may indicate one longitudinal aspect of tumor development which could provide evidence of premalignant change or initial pathological features during the long-standing course of ulcerative colitis.

Colitis↗
PubMed2000

Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity.

For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high specific activity is often necessary, especially when using a radionuclide with a shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric molecules with large numbers of amine residues on their spherical surface. In order to bind large numbers of radiometals to single antibody molecules, the generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of 2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M), a derivative of DTPA. This product [G4-(1B4M)43] was then conjugated with OST7, a murine monoclonal IgG1. We evaluated the achievable specific activity for 111In labeling, immunoreactivity, biodistribution, and tumor targeting in mice of the 111In- or 153Gd-OST7-G4-(1B4M)43 as compared with radiolabeled OST7-1B4M or 56C-1B4M. The maximum specific activity of 111In-OST7-G4-(1B4M)43 and 111In-OST7-1B4M was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of radiolabeled OST7-G4-(1B4M)43 and OST7-1B4M, as determined by the binding to KT005 cells expressing the antigen, was respectively 91% and 84% of that of 125I-labelled OST7. Biodistribution studies for preparations with maximum specific activity in normal mice 3 h after injection showed that 111In- or 153Gd-OST7-G4-(1B4M)43 cleared faster from the blood and accumulated more in the liver than did 111In- or 153Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M)64] itself showed similar saturation effects with metals. The radioactivity in all the other organs reflected the rapid clearance of radioactivity from the blood. 153Gd-OST7-G4-(1B4M)43 showed specific accumulation in the KT005 tumor. In conclusion, we could successfully bind 49 times as many metal atoms to an antibody molecule as is possible with conventional metal labeling for indium and gadolinium, and did so with minimal loss of immunoreactivity. When we achieved radiolabeling with maximum specific activity, Gd conjugate showed better biodistribution than In conjugate.

Animals↗
PubMed2000

Change in regional pulmonary perfusion as a result of posture and lung volume assessed using technetium-99m macroaggregated albumin SPET.

The purpose of this study was to evaluate the effects of gravity and lung volume on regional pulmonary perfusion using technetium-99m macroaggregated albumin (99mTc MAA) single-photon emission tomography (SPET). Twenty-five subjects were classified into three groups according to their position during the injection of the tracer [11 subjects sitting, six supine and eight both supine and prone (S+P) positions]. All of these subjects were injected with the tracer during normal tidal breathing. In the S+P group, half of the tracer was injected while the subject was in each position. The remaining 11 subjects were classified into two groups according to their lung volume during the injection. Supine patients were instructed to hold their breath at residual volume (RV) (five subjects) or total lung capacity (TLC) (six subjects) while receiving the tracer injection. A region of interest with a ventrodorsal axis was defined in the centre of each lung. Profile curves were produced by plotting and normalizing the perfusion values as a percentage of the maximum value. The perfusion distributions for the sitting and S+P positions and at RV were relatively uniform. However, the distributions for the supine position and at TLC showed a gravitational influence [sitting vs. TLC: 87.8%+/-10.4% vs. 67.3%+/-8.7% for % maximum perfusion at +5 pixels from the midpoint of the upper lobe (P<0.00002)]. The gravity-related perfusion inhomogeneity was more prominent in the lower lobe than in the upper lobe. It is concluded that the physiological vertical gravitational gradient should be taken into consideration during the interpretation of lung SPET images. Preferably, patients should be injected with the tracer twice, once in the supine position and once in the prone position, while breathing normally. Alternatively, they may be injected with the tracer once while in the supine position and holding their breath at RV. Either of these protocols should ensure a uniform distribution of tracer.

Adult↗
PubMed2000

Adnexal torsion: MR imaging findings of viable ovary.

We report a case of torsed ovarian cystic tumor, in which contrast-enhanced high-resolution MR images accurately contributed to the diagnosis of torsion despite the lack of symptoms and to the preoperative evaluation of viability of the edematous ovary. Accurate preoperative assessment by MR images and prompt conservative surgical approach succeeded in salvaging the involved ovary.

Adult↗
PubMed2000

alpha-Glutathione-s-transferase as a new sensitive marker of hepatocellular damage in biliary atresia.

Early identification of patients likely to deteriorate post-hepatic portoenterostomy for biliary atresia (BA) would be beneficial. alpha-Glutathione-s-transferase (alpha-GST) is a serologic marker of reactive hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosol concentration, and short half-life. We evaluated whether serum alpha-GST in post-surgical BA patients correlates with liver function (LF) and investigated its potential as a medium- to long-term marker of prognosis. Postoperative BA patients (n = 30; mean age: 11.8 +/- 3.7 years) were divided into three groups based on average LF over the 3 months prior to this study. Group I (n = 8) were jaundice-free and had normal LF. Group II (n = 12) had moderate liver dysfunction, and group III (n = 10) had severe liver dysfunction. Serum alpha-GST was determined using a specific ELISA. Tissue alpha-GST was determined immunohistochemically, using liver needle-biopsy specimens. Bile lakes were found in 5 group II patients and 5 group III patients. Serum alpha-GST was significantly higher in group II (20.7 +/- 8.4 ng/ml) than in groups I (4.7 +/- 1.3 ng/ml) and III (8.0 +/- 1.2 ng/ml) (P < 0.0001) and was highest in group II subjects with bile lakes. In control liver specimens alpha-GST distribution was weak but uniform throughout normal liver lobule hepatocytes. In group II there was strong staining in centrilobular hepatocytes, and in group III alpha-GST was only found in regenerative nodules. We conclude that alpha-GST may be a more sensitive indicator of hepatocellular damage in BA because its distribution is correlated to the proportion of functioning liver tissue present. This is the first report of this relationship, which has great implications for group II subjects because a sudden shift in concentration of alpha-GST may be a better predictor of impending hepatic dysfunction than conventional LF tests.

Adolescent↗
PubMed2000

Quantitative measurements of changes of idiopathic stage 3 macular holes after vitrectomy using confocal scanning laser tomography.

PURPOSE: To perform quantitative three-dimensional analysis of changes of idiopathic full-thickness stage 3 macular holes following vitrectomy and gas tamponade using confocal scanning laser tomography to study the mechanism of repairing the holes and to correlate with visual recovery. METHODS: We studied 44 patients, 10 men and 34 women, aged between 40 and 76 years (mean 65.5 years) with stage 3 macular holes with symptoms of 1-4 months' duration (mean 2.7 months). Using the Heidelberg Retina Tomograph, we measured the macular area within 1 week before surgery (3.5+/-1.6 days), and between 2 and 4 weeks (2.4+/-0.6 weeks) and at least 3 months (3.8+/-00.8 months) after surgery. RESULTS: All 44 eyes showed closure of the holes and flattening of cuff and retinal striae after vitrectomy and gas tamponade. All the eyes showed small flat depressions that corresponded to each macular hole with the area of 0.027-0.184 mm2 (0. 110+/-0.042 mm2). Thirty-nine (89%) of 44 eyes showed large concave depressions that appeared to correspond to the preoperative retinal striae, with areas of 0.844 to 5.563 mm2 (3.688+/-1.263 mm2). The areas of the postoperative small depressions and large depressions were significantly correlated with the area, volume, and depth of the macular holes and the area of the cuff and retinal striae prior to treatment. Postoperative visual acuity showed significant correlations with the areas of the postoperative small depressions and large depressions. CONCLUSIONS: Confocal scanning laser tomography is potentially useful as a noninvasive diagnostic technique for quantitative measurements of changes of macular holes by vitrectomy and gas tamponade. Postoperative small depressions corresponding to the healed macular holes appeared to be caused by gliosis involving sealing of the holes. The large depressions and their concave shape may result from postoperative changes of the retina, including swelling of ganglion cells and loss of outer and inner segments of photoreceptor cells in regions of preoperative cuff and retinal striae.

Adult↗
PubMed2000

Isolation and characterisation of a mutation in the PMR1 gene encoding a Golgi membrane ATPase, which causes hypersensitivity to over-expression of Clb3 in Saccharomyces cerevisiae.

We screened for mutant strains of Saccharomyces cerevisiae that are sensitive to overexpression of specific cyclins, and identified mutations in two genes that caused growth inhibition in response to mild overexpression of Clb3. One was the ANP1 gene, which encodes a glycosyltransferase previously identified by a similar strategy using Clb2 instead of Clb3. This paper describes the second strain of S. cerevisiae that is hypersensitive to Clb3 expression. The gene mutated in this strain was identified as PMR1, which encodes a Ca2+-ATPase located in the Golgi membrane. The protein product of pmr1-1 was truncated at residue 409 and thus lacked the C-terminal ATPase domain. The pmr1-1 strain was hypersensitive to over-expression of Clb3, but not Cln2, Clb5 or Clb2. The lethality due to Clb3 expression in pmr1-1 could be suppressed by adding Ca2+ ions to the medium. The pmr1-1 strain proved to be defective in glycosylation, and the defects in glycosylation were exacerbated by high levels of Clb3. On induction of Clb3 expression in the pmr1-1 strain, the cells arrested at anaphase with an elongated daughter bud. We discuss possible interpretations of this synthetic lethal phenotype.

Calcium↗
PubMed2000

Sites of expression of mRNA for lysenin, a protein isolated from the coelomic fluid of the earthworm Eisenia foetida.

Lysenin is a 33-kDa protein of 297 amino acids that was originally purified from the coelomic fluid of the earthworm Eisenia foetida. It binds specifically to sphingomyelin. In this study, we attempted to identify the site of synthesis of lysenin in the earthworm. We detected the expression of mRNA for lysenin and the presence of immunoreactive lysenin in the large coelomocytes and in the free large chloragocytes present in the lumen of the typhlosole, a depression in the dorsal wall of the intestine. These coelomocytes and chloragocytes seemed to be mature and separate from the chloragogen tissue that lined the typhlosole. The free large chloragocytes in the typhlosole contained numerous vacuoles. The nuclei were small and irregular in shape, and glycogen granules and mitochondria were occasionally found between vacuoles. The chloragocytes of the chloragogen tissue that surrounded the coelomic side of the intestine and the dorsal blood vessel did not react with the lysenin antiserum and no expression of lysenin mRNA was detected in these cells. Furthermore, no evidence of the protein or of the mRNA was found in the cells of the pharyngeal gland. Our findings suggest that lysenin is produced in the free large chloragocytes in the lumen of the typhlosole.

Animals↗
PubMed2000

Intra-abdominal metastases in musculoskeletal sarcomas.

This study examined the incidence, histological type, clinical symptoms, and prognosis in patients with intra-abdominal metastases of musculoskeletal sarcomas. The medical records of 505 patients with musculoskeletal sarcomas were reviewed for examples of intra-abdominal metastases. The incidence of intra-abdominal metastases (excluding lung) was: 4% in the liver (20 patients), 1.2% in gastrointestine (6 patients), 0.8% in pancreas (4 patients), and 0.8% on the peritoneal surface (4 patients). Patients with a previous hisory of lung metastases and those with high-grade liposarcoma tended to show metastasis in the intra-abdominal organs. Most patients with liver metastasis had no symptoms. Patients with gastrointestinal metastasis had abdominal pain, anemia, and melena. Patients with pancreatic metastasis had diabetes and jaundice. Six patients underwent surgical treatment, and two of them survived for more than 2 years. Metastases within the abdomen must be considered as a possible site for dissemination of musculoskeletal sarcomas, especially in patients with advanced disease and those with liposarcoma.

Adolescent↗
PubMed2000

Influence of macrolides on guanosine diphospho-D-mannose dehydrogenase activity in Pseudomonas biofilm.

The formation of biofilm is regarded as a major cause of intractable infectious disease. Our studies were done to elucidate the action of a 14-membered-ring macrolide (erythromycin; EM) and a 16-membered-ring macrolide (midecamycin; MDM) on guanosine diphospho-d-mannose dehydrogenase (GDP-mannose dehydrogenase; GMD), one of the constituents of bacterial biofilm that is known to produce alginate. The mucoid type of Pseudomonas aeruginosa PT-1578 and the non-mucoid type of P. aeruginosa PAO1 were grown with nutrient-rich and nutrient-poor media. Comparative measurements were made of their GMD enzyme activities, with glucose-6-phosphate dehydrogenase (G6PDH), a cell membrane enzyme, used as a control. It was found that the GMD enzyme activity of mucoid type of Pseudomonas bacteria increased when they were grown on nutrient-poor media. Measurements were also made to determine the effects of EM and MDM against GMD and G6PDH enzyme activities. In media with either EM or MDM added, the production of G6PDH was not inhibited, irrespective of the concentration of EM or MDM. However, EM was effective against the production of GMD, showing a concentration-dependent effect. Scanning electron microscopy studies were also carried out to determine the effects of both macrolides on bacterial alginate production. It was found that reduction of alginate content occurred after the addition of EM. When environmental conditions for bacteria deteriorate, GMD enzyme is activated, production of alginate is initiated, and then biofilm is formed. Our results suggest that EM may have an inhibitory effect on the GMD production cycle, hence inhibiting the formation of biofilm. This may explain the differences in the clinical usefulness of 14-membered-and 16-membered-ring macrolides against biofilm disease.

Anti-Bacterial Agents↗
PubMed2000

Clinical assessment of long-term safety and efficacy of a widely implanted polyacrylic intraocular lens material.

PURPOSE: To evaluate the long-term safety and efficacy, in a large series of patients, of polyacrylic intraocular lens implants 1 and 3 years after surgery, compared with polymethylmethacrylate intraocular lens implants. METHODS: This was a randomized, prospective study of 1,514 eyes of 1,202 patients that were examined for a 1-year follow-up study and 1,264 eyes of 990 patients that were examined for a 3-year follow-up study. All the patients were prospectively randomized to receive a polyacrylic or polymethylmethacrylate intraocular lens implant. A standardized surgical protocol was performed using a phacoemulsification technique and capsulorhexis. Any surgical complications were excluded, and all patients had standard postoperative medication and follow-up. Postoperative measurements included spectacle-corrected visual acuity, occurrence of postoperative sight-threatening or lens-related complications, and adverse reactions. Results were compared between the polyacrylic intraocular lens and polymethylmethacrylate intraocular lens groups. Results were also compared with standards for polymethylmethacrylate intraocular lens that were established by the US Food and Drug Administration and a previous study for silicone lens. RESULTS: The overall complete follow-up rates were 79.9% for 1-year follow-up and 69.5% for 3-year follow-up. At 1 year, the mean logarithm of the minimum angle of resolution (logMAR) of visual acuity was 0.037 +/- 0.150 and 0.042 +/- 0.154 in best case patients of the polyacrylic intraocular lens group and polymethylmethacrylate intraocular lens group, respectively. At 3 years, the mean logMAR visual acuity was 0.038 +/- 0.155 and 0.054 +/- 0.181 in best case patients in the polyacrylic intraocular lens group and polymethylmethacrylate intraocular lens group. There was no significant difference between groups at 1 and 3 years. At 1 year, 96.8% of best case patients in the polyacrylic intraocular lens group and 95.8% of those in the polymethylmethacrylate intraocular lens group achieved corrected visual acuity of 0.5 or better. At 3 years, 96.4% of best case patients in the polyacrylic intraocular lens group and 94.9% of those in the polymethylmethacrylate group achieved a corrected visual acuity of 0.5 or better; no significant difference was found at 1 and 3 years. The rate of sight-threatening complications was 1. 2% for the polyacrylic intraocular lens group of all patients and 1. 5% for the polymethylmethacrylate intraocular lens group at 1 year, and 1.6% for the polyacrylic intraocular lens group and 1.4% for the polymethylmethacrylate intraocular lens group at 3 years. No significant difference was found between the groups. The cumulative rate of Nd:YAG capsulotomy for the polyacrylic intraocular lens group (7.1%) was significantly lower than that for the polymethylmethacrylate intraocular lens group (38.1%) through 3 years (P <.0001). CONCLUSIONS: Polyacrylic intraocular lenses demonstrated safe and effective performance through long-term follow-up at a level equal to or better than polymethylmethacrylate intraocular lenses. Patients undergoing polyacrylic intraocular lens implantation achieved excellent postoperative visual acuity and experienced a low rate of postoperative complications, adverse reactions, and Nd:YAG capsulotomy. These long-term clinical results are an important outcome database for the ongoing use of this foldable optic material.

Acrylic Resins↗
PubMed2000

Age-related macular degeneration: long-term results of radiotherapy for subfoveal neovascular membranes.

PURPOSE: To study results of 2-year follow-up of radiotherapy for subfoveal choroidal neovascular membrane associated with age-related macular degeneration. METHODS: In a randomized prospective clinical study, 101 patients received a low-dose radiotherapy or no treatment. In the treatment group, subfoveal choroidal neovascular membranes were treated with 20 Gy of 6-MV photons to the macula of the affected eye. RESULTS: The overall complete follow-up rate was 84.2% (85/101). No measurable treatment-related morbidity was seen during or after treatment. Mean changes in log of minimal angle of resolution (logMAR) of visual acuity and area of choroidal neovascular membrane for 2-year follow-up were +0.226 +/- 0.373 and 143.5 +/- 53.1% in the treatment group, and +0.563 +/- 0.370 and 190. 3 +/- 81.4% in the control group; a significant difference was found (P <.0001; P =.0008). In patients with smaller choroidal neovascular membrane (</=1.5 mm(2)) or better visual acuity (>/=60/200) at baseline, the treatment group showed a significantly smaller increase in area of choroidal neovascular membrane and a significantly smaller decrease in LogMAR visual acuity for 2 years, whereas there was no significant difference in patients with larger choroidal neovascular membrane (>1.5 mm(2)) or poorer visual acuity (<60/200). CONCLUSIONS: Radiotherapy appeared to have a favorable treatment effect in eyes with subfoveal neovascular membrane associated with AMD. Favorable factors for radiotherapy were a smaller area of choroidal neovascular membrane and better visual acuity.

Aged↗