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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 109 records · Page 6Linked to original sources
PubMed2001

En bloc laminoplasty performed with threadwire saw.

OBJECTIVE: To introduce a method for a simple, nonexpansive laminoplasty that can be performed with a threadwire saw (T-saw) after en bloc laminotomy has been performed. The method can be applied along the entire spinal region, including the thoracic and lumbar spine. METHODS: An en bloc laminotomy of trapezoid shape at the cross section is performed bilaterally at the junctional area of the lamina and facet joint with a thin, flexible T-saw, while preserving the supraspinous, interspinous, and interlaminar ligaments. After the intradural procedure has been performed, the laminar flap is replaced in its original site and fixed with 1-0 nylon sutures, resulting in the complete reconstruction of the posterior supporting elements of the spinal column. RESULTS: En bloc laminoplasty was performed on 16 patients via a T-saw; most of the patients had intradural spinal tumors. The patients did not need their spinal canals to be enlarged after the intradural procedure had been performed. The follow-up period ranged from 2 to 40 months (mean +/- standard error, 22.6 +/- 3.4 mo). The laminoplasty was performed from the upper cervical to the sacral regions, although the most frequently operated level was the lower thoracic level. Two-level laminoplasty was performed in 12 patients, and three-level laminoplasty was performed in four. The laminoplasty was done safely and without any complications, except in one patient, who experienced thoracic root injury from a T-saw that was accidentally inserted anterior to the roots. No spinal column deformity or sinking of the replaced laminar flap was noted during the follow-up period; patients were assessed at follow-up via radiographs or computed tomographic scans. Computed tomographic scans obtained later indicated that bony fusion occurred at the cutting edges 1.0 to 4.0 months after surgery (mean, 1.90 +/- 0.34 mo). CONCLUSION: Simple en bloc laminoplasty performed with a T-saw is a useful, safe procedure that can be used to reconstruct the posterior spinal elements throughout the whole spinal region after the intradural procedure has been performed.

Adult↗
PubMed2001

Inhibitory effects of sodium butyrate on proliferation and invasiveness of human glioma cells.

OBJECTIVE: Sodium butyrate (SB), a differentiation-inducing agent, has been demonstrated to inhibit cellular proliferation in a number of human cell lines. Its precise mechanisms remain to be clarified, however. We investigated molecular mechanisms of SB-induced growth suppression as well as the effects of SB on the invasiveness of human glioma cells. METHODS: Human glioma U87MG and U251MG cells were treated with 1 or 2 mmol/L SB for 48 hours, and the inhibition of cell growth was assessed by spectrophotometric analysis. Cell cycle analysis was carried out by the 5-bromo-2'-deoxyuridine incorporation method, and expression of cell cycle-regulatory proteins was determined by immunoblotting. In addition, invasiveness was assessed using a Transwell chamber (Iwaki, Tokyo, Japan) with extracellular matrix substrate fibronectin or laminin (Iwaki). RESULTS: SB treatment resulted in significantly suppressed proliferation of both U87MG and U251MG cells in a dose-dependent manner. It inhibited the G1-S transition, which was associated with increased expression of p21 and cyclin D1 and reduced pRb phosphorylation. Treatment with antisense oligonucleotide for Rb abrogated SB-induced G1 arrest. p21 up-regulation was independent of the p53 status of the glioma cells. SB treatment also inhibited invasiveness on fibronectin and laminin. CONCLUSION: Our results indicate that SB may suppress the growth of human glioma cells through modulation of cell cycle progression and also may affect their invasiveness on extracellular matrix substrates, which suggests that SB may be a useful therapeutic agent in treating multiple aspects of malignant gliomas.

Brain Neoplasms↗
PubMed2001

Genetic analysis reveals different functions for the products of the thyroid hormone receptor alpha locus.

Thyroid hormone receptors are encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) loci. These genes are transcribed into multiple variants whose functions are unclear. Analysis by gene inactivation in mice has provided new insights into the functional complexity of these products. Different strategies designed to modify the TRalpha locus have led to strikingly different phenotypes. In order to analyze the molecular basis for these alterations, we generated mice devoid of all known isoforms produced from the TRalpha locus (TRalpha(0/0)). These mice are viable and exhibit reduced linear growth, bone maturation delay, moderate hypothermia, and reduced thickness of the intestinal mucosa. Compounding TRalpha(0) and TRbeta(-) mutations produces viable TRalpha(0/0)beta(-/-) mice, which display a more severe linear growth reduction and a more profound hypothermia as well as impaired hearing. A striking phenotypic difference is observed between TRalpha(0/0) and the previously described TRalpha(-/-) mice, which retain truncated TRDeltaalpha isoforms arising from a newly described promoter in intron 7. The lethality and severe impairment of the intestinal maturation in TRalpha(-/-) mice are rescued in TRalpha(0/0) animals. We demonstrate that the TRDeltaalpha protein isoforms, which are natural products of the TRalpha locus, are the key determinants of these phenotypical differences. These data reveal the functional importance of the non-T3-binding variants encoded by the TRalpha locus in vertebrate postnatal development and homeostasis.

Animals↗
PubMed2001

Development of a new method for assessing the cardiac baroreflex: response to downward tilting in patients with diabetes mellitus.

OBJECTIVE: To investigate the clinical value of a new non-invasive method for assessing baroreflex sensitivity using downward tilting. PATIENTS: 34 patients with diabetes mellitus, mean (SD) age, 53.6 (11.8) years. DESIGN: Arterial blood pressure and ECG were recorded simultaneously while the patients were on a tilt table. After 20 minutes at a 70 degrees upright tilt, the patients were returned to the supine position at a speed of 3.2 degrees /s (downward tilting baroreflex sensitivity test, DT-BRS). A beat to beat systolic blood pressure increase associated with a corresponding lengthening of the RR interval was noted during downward tilting. Baroreflex sensitivity was also assessed using the conventional method of an intravenous injection of phenylephrine (Phe-BRS). Heart rate variability was analysed during rest and tilting. RESULTS: The slope of the regression line for systolic blood pressure v RR interval during downward tilting was highly correlated with Phe-BRS (r = 0.83, p < 0.0001). Both DT-BRS and Phe-BRS were correlated with the high frequency (HF) component of resting heart rate variability (p < 0.005) and with the ratio of the low frequency to the high frequency component (LF/HF) during upright tilting (p < 0.005). DT-BRS and Phe-BRS were also correlated with the difference between rest and tilting values of HF and LF/HF (p < 0.005). CONCLUSIONS: DT-BRS provides a physiological, non-invasive method for determining baroreflex sensitivity and may be a useful index of reflex cardiac vagal and sympathetic function in patients with diabetes mellitus.

Adult↗
PubMed2001

Urinary podocytes in primary focal segmental glomerulosclerosis.

BACKGROUND/AIM: Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome. Although the pathogenesis is not known, recent studies suggest that FSGS may be a podocyte disease. The aim of this study was to look for podocyte injury in this disease, using measurements of urinary podocytes. METHODS: We examined the first morning urine of the day collected from 71 patients (45 men and 26 women, median age and range 11.2 and 3-29 years) diagnosed as having nephrotic syndrome. Freshly voided urine samples were examined by immunofluorescence labeling using monoclonal antibodies against human podocalyxin. Renal histological examinations were performed in 58 of the 71 patients: 28 had minimal-change disease, 20 had FSGS, and 10 had membranous nephropathy. RESULTS: Median and range of urinary podocytes measured were 0.2 and 0-40.8 cells/ml for 71 patients with nephrotic syndrome and 0 and 0-0.8 cells/ml for normal healthy control subjects (n = 200). Patients with FSGS had significantly higher levels of urinary podocytes (median and range 1.3 and 0-40.8 cells/ml) than those with minimal-change disease (median and range 0 and 0-6.9 cells/m; p = 0.003) or membranous nephropathy (median and range 0 and 0-1.4 cells/ml; p = 0.02). CONCLUSIONS: The urinary excretion of podocytes is significantly higher in patients with FSGS as compared with those having membranous nephropathy or minimal-change disease. These findings suggest that podocyte injury and loss in the urine may have an important role in the pathogenesis of FSGS.

Adolescent↗
PubMed2001

Development of lumbosacral spina bifida: three-dimensional computer graphic study of human embryos at Carnegie stage twelve.

There is still some controversy as to whether sacral spina bifida in humans is the result of a defect of the primary or secondary neural tube. As somites are related to the development of vertebrae and the primary neural tube is related to the development of the spinal cord in embryos, it is very important to determine the number of somites in normal human embryos at the time of closure of the primary neural tube to understand the contribution of primary neural tube defects to the development of spina bifida. However, in the literature, the number of somites in stage 12 human embryos is still controversial. The aim of this study is to find the number of somites in human embryos at Carnegie stage 12. Four human embryos at Carnegie stage 12 were selected from the laboratory of the Congenital Anomaly Research Center in Japan. The neural tube and somites were reconstructed from their slices by a three-dimensional computer graphic reconstruction technique. The reconstructed embryos were examined from multidirectional magnified images. Thirty-three pairs of somites were present in all these reconstructed embryos. As the 33rd pair of somites corresponds to the fifth sacral segment, the presence of 33 pairs of somites at Carnegie stage 12 suggests that spina bifida develops from defects of the primary neural tube.

Computer Graphics↗
PubMed2001

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis.

Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the Na(+)-HCO(3)(-) cotransporter (NBC-1). However, the mechanism by which NBC-1 inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters are present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium. In the human lens epithelial (HLE) cells, RT-PCR detected mRNAs of both kNBC-1 and pNBC-1. Although a Na(+)-HCO(3)-cotransport activity has not been detected in mammalian lens epithelia, cell pH (pH(i)) measurements revealed the presence of Cl(-)-independent, electrogenic Na(+)-HCO(3)-cotransport activity in HLE cells. In addition, up to 80% of amiloride-insensitive pH(i) recovery from acid load in the presence of HCO(3)(-)/CO(2) was inhibited by adenovirus-mediated transfer of a specific hammerhead ribozyme against NBC-1, consistent with a major role of NBC-1 in overall HCO(3)-transport by the lens epithelium. These results indicate that the normal transport activity of NBC-1 is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2001

Immunohistochemical analyses of cell cycle-related proteins, apoptosis, and proliferation in pituitary adenomas.

To analyze the cell cycle regulatory mechanisms in the growth of pituitary adenomas, we investigated immunohistochemically the expression of the cell cycle-related proteins cyclin A and p27 in 48 pituitary adenomas. The frequency of apoptosis and the proliferative potential were also examined. The percentage of apoptotic cells was evaluated by immunohistochemical analysis using the anti-single-strand DNA antibody. The proliferative potential was assessed using the anti-Ki-67 antibody. The mean cyclin A labeling index (LI) for the non-recurrent group was 1.03% and for the recurrent group 2.31%. A positive linear correlation between cyclin A LI and Ki-67 LI was found. The mean p27 LI for the non-recurrent group was 67.4% and for the recurrent group 47.0%. There were significant differences in cyclin A LI and p27 LI between the non-recurrent group and the recurrent group. The mean apoptotic rate for the non-recurrent group was 0.87% and for the recurrent group 1.05%. There was no significant difference. Multivariate regression analysis revealed that high cyclin A LI and high Ki-67 LI were significant factors for shorter progression-free survival. The results suggest that the cyclin A LI is a useful prognostic factor in pituitary adenomas. (J Histochem Cytochem 49:1193-1194, 2001)

Adenoma↗
PubMed2001

Prevalence of virulent Rhodococcus equi in soil from five R. equi-endemic horse-breeding farms and restriction fragment length polymorphisms of virulence plasmids in isolates from soil and infected foals in Texas.

Rhodococcus equi isolates (462) obtained from 64 soil samples collected on 5 R. equi-endemic horse-breeding farms and isolates from 100 infected foals in Texas were examined to determine the prevalence and genotypic diversity of virulence-associated plasmids. Isolates were tested for the presence of 15-17-kDa virulence-associated protein antigens (VapA) by immunoblotting and virulence-associated plasmids by PCR. Plasmid DNAs were isolated and analyzed by digestion with restriction endonucleases for estimation of size and comparison of polymorphisims. Rhodococcus equi were isolated from soil of all 5 farms; however, virulent R. equi were only isolated from 3 of the 5 farms and represented 18.8% (87 of 462) of total isolates. Of the 87 virulent soil isolates, 56 (64.5%) contained an 85-kb type I plasmid, 23 (26.4%) an 87-kb type I plasmid, 7 (8%) a newly defined 85-kb type III plasmid (Tx 43), and 1 (1.1%) a newly defined 85-kb type IV plasmid (Tx 47). Of the 100 isolates from infected foals, 96 were virulent. Of the 96 virulent isolates, 51 (53.1%) contained an 85-kb type I plasmid, 39 (40.6%) an 87-kb type I plasmid, 4 (4.2%) an 85-kb type III plasmid (Tx 43), and 2 (2.1%) an 85-kb type IV plasmid (Tx 47). There are at least 4 different R. equi virulence-associated plasmids in Texas, 2 of which have not previously been described. Based upon virulence plasmid typing, there is geographic diversity among isolates of R. equi from clinical and environmental samples on horse-breeding farms in Texas. There is not a strong correlation between the presence of virulent R. equi in farm soils and the R. equi disease status of those farms.

Actinomycetales Infections↗
PubMed2001

Activation of mitochondrial ATP-dependent protease by peptides and proteins.

We examined the effect of peptides or protein on the proteolytic and ATPase activities of mitochondrial ATP-dependent LON protease purified from bovine adrenal cortex. Peptides/proteins including angiotensin I which stimulated ATPase activity without hydrolysis of any peptide bonds stimulated proteolysis of 125I-labeled substrates at low concentrations; whereas at high concentrations they competitively inhibited proteolysis, thus displaying a biphasic activity profile. All peptides and proteins thus examined stimulated degradation of 125I-labeled substrates. When an ATP analog was substituted for ATP, only inhibition; i.e., no stimulation, of proteolysis by unlabeled peptides was observed. Without activator peptides, degradation of [125I] peptides was higher in the presence of an ATP analog than that in the presence of ATP. ADP, a product of the ATPase reaction, inhibited the proteolytic activity in the absence of an activator peptide but not in its presence. From analogy to E. coli ATP-dependent protease La (LON), we suggest that the activator peptides stimulated the proteolysis by releasing enzyme-bound ADP.

ATP-Dependent Proteases↗
PubMed2001

Progressive interstitial renal fibrosis due to Chinese herbs in a patient with calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome.

A 58-year-old woman with calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome presented with slowly progressive renal dysfunction. She was normotensive with normal plasma renin activity and lacking symptoms of vasculitis. Mild proteinuria was of tubular origin, but serological tests and an absence of sicca symptoms excluded the possibility of Sjögren's syndrome. Light microscopic study of renal biopsy showed interstitial fibrosis with ectasia and degeneration of proximal tubule and lymphocyte infiltration. There were no remarkable changes in the glomeruli. Chromatographic analysis of the Chinese herbs regimen that she had been taking for several years demonstrated aristolochic acid. She was diagnosed as Chinese herbs nephropathy. Therapy with oral prednisolone was markedly effective in improving renal function and anemia. To our knowledge, this is the first report of Chinese herbs nephropathy complicating connective tissue disease. It is important to consider the possibility of Chinese herbs nephropathy when patients treated with Chinese herbs develop renal dysfunction.

Aristolochic Acids↗
PubMed2001

IgA-kappa type multiple myeloma affecting proximal and distal renal tubules.

A 45-year-old male was admitted because of chest pain, lumbago, and bilateral ankle pain. Examination disclosed hypophosphatemic osteomalacia, acquired Fanconi syndrome, and abnormalities in distal nephron such as distal renal tubular acidosis and renal diabetes insipidus. Further exploration revealed IgA kappa multiple myeloma excreting urinary Bence Jones protein (kappa-light chain). Renal biopsy revealed thick basement membranes and elec-tron-dense crystals in proximal tubular epithelial cells. Immunofluorescent studies revealed deposition of kappa-light chain in renal tubular epithelial cells that caused the renal tubular damage. Although the osteomalacia was relieved by medical treatment, the urinary Bence Jones protein and the renal tubular defects were not improved by the chemotherapy for the myeloma. The patient died of exacerbation of multiple myeloma at 50 years of age.

Biopsy↗
PubMed2001

Primitive trigeminal artery variant aneurysm treated with Guglielmi detachable coils--case report.

A 69-year-old woman had suffered from diplopia on right lateral gaze for the last 4 months due to right abducens nerve paresis. Right carotid angiography showed a cavernous internal carotid artery (ICA) aneurysm of 17 x 16 x 14 mm size and a primitive trigeminal artery (PTA) variant supplying the territory of the posterior inferior cerebellar artery. Intraluminal occlusion of the aneurysm was performed with 15 Guglielmi detachable coils. The flow of the PTA variant and the ICA was preserved. Right abducens nerve paresis improved partially. PTA variant is a primitive artery originating from the cavernous ICA supplying the cerebellum without opacification of the basilar artery. Only four of the 67 cases of PTA variant were associated with an aneurysm of the PTA variant. The possibility of this rare association should be considered when treating cavernous portion aneurysm because of the risk of cerebellar ischemia.

Abducens Nerve Diseases↗
PubMed2001

A case of ileus caused by implantation of cancer after surgical treatment of bile duct carcinoma.

We encountered a patient with an ileus caused by implantation of cancer cells after surgical treatment of bile duct carcinoma. The patient was a 55-year-old male diagnosed as having cancer in the lower bile duct who underwent pancreatoduodenectomy in March 1996. The comprehensive curability was B. The patient experienced nausea and vomiting and was diagnosed as having ileus in October 1998. The symptoms were alleviated by medical treatment. Because ileus symptoms recurred in December 1998 but were not alleviated by medical treatment, the patient was hospitalized in Kurume University Hospital for surgery. A mirror reflection was observed by plain radiography of the abdomen. Ultrasonography (US) revealed dilation of the intestinal duct and hypertrophy of the intestinal wall. An ileus tube was inserted but the symptoms did not improve, and therefore, the patient underwent surgery in February 1999. Upon laparotomy, a node of milk white color about 2 cm in size was found in the region coinciding with the enhancement on CT images, and part of the intestinal duct was found to be folded and adhered to the lower surface of the liver. No recurrence was observed in the liver, peritoneum, and lymph nodes. The tumor was excised together with part of the intestinal duct and liver to remove the ileus. At present, the patient is alive without recurrence. Because recurrence of cancer by implantation of cancer cells is often localized in a limited region, early diagnosis and excision are important.

Bile Duct Neoplasms↗
PubMed2001

Evaluation of simultaneous excision of pancreatic cancer and the surrounding blood vessels.

Of the 139 patients who underwent excision for invasive cancer in the pancreatic duct at Kurume University Hospital between January 1965 and December 1998, the subjects were 38 patients in whom blood vessels around the cancer were simultaneously excised. The surgical methods were pancreatoduodenectomy (PD) in 31 patients, distal pancreatectomy (DP) in 5, and total pancreatectomy (TP) in 2. The excised blood vessels were the portal vein alone in 32 patients, the artery alone in 1, and both portal vein and artery in 5. Excision of the portal vein was performed by circumcision in 25 patients and by segmentectomy in 12. The range of circumcision was 1.0-7.0 cm (mean, 3.5 +/- 1.4 cm), and the blocking time of the portal vein was 8-36 min (mean, 19.5 +/- 8.8 min). Of the 25 patients who underwent circumcision, reconstruction was performed by end-to-end anastomosis in 23 and by transplantation of the autologous vein between the ends in 2. Of the 12 patients who underwent segmentectomy, direct suture was performed in 10, and transplantation of an autologous vein patch was performed in 2. Postoperative complications occurred in 14 of the 32 patients. In 5 of the 6 patients who underwent excision of the artery, reconstruction was performed by end-to-end anastomosis in 3 and by transplantation of the autologous vein between the ends in 2. Postoperative complications did not occur in the patient who had undergone excision of the artery alone, but 4 of the 5 patients who had undergone simultaneous excision of the portal vein and artery had postoperative complications, of whom 2 died during the period of hospitalization. Three patients with pv0, pv1 or pv2 survived for more than 3 years. Because some of the patients who had undergone excision of the portal vein alone survived for a long time and this method is relatively safe, this surgery can be generally applied, but simultaneous excision of the portal vein and artery should be carefully applied because the incidences of postoperative complications and death during the period of hospitalization are high. With the development of surgical techniques and postoperative control, simultaneous excision of pancreatic cancer and the surrounding blood vessels has become safe, but this method should only be applied to patients who have the potential to recover completely.

Hepatic Artery↗