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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 109 records · Page 6Linked to original sources

Thresholds of ischemia salvageable with intravenous tissue plasminogen activator therapy: evaluation with cerebral blood flow single-photon emission computed tomographic measurements.

OBJECTIVE: This study investigated the cerebral blood flow (CBF) thresholds of ischemic cortices that were salvageable with intravenous tissue plasminogen activator (t-PA) infusion therapy. METHODS: We retrospectively reviewed data for 20 patients who were treated with intravenous low-dose (7.2 mg) native t-PA infusion therapy for distal embolic occlusions of middle cerebral artery divisions or branches, without early computed tomographic ischemic changes. All patients underwent pretreatment single-photon emission computed tomographic CBF measurements using (99m)Tc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethylester. Intravenous t-PA infusion was initiated within 6 hours (average, 3 h) after symptom onset for 14 patients and 6 to 14 hours (average, 8.8 h) after the last time the patient was noted to be in normal condition for the other 6 patients. Pretreatment single-photon emission computed tomographic and 3-month post-treatment computed tomographic scans were compared using computerized coregistration. Ischemic cortices in single-photon emission computed tomographic scans were divided into areas of reversible and irreversible ischemia. The degree of hypoperfusion was analyzed with an asymmetry index (AI). The AI was calculated as C(a)/C(b) x 100%, where C(a) represents the mean reconstructed counts for the ipsilateral ischemic area and C(b) represents the mean reconstructed counts for the corresponding contralateral area. RESULTS: Partial recanalization, with clinical improvement, at 60 minutes was confirmed by angiography for 14 of the 20 patients (70%). Seventeen of the 20 patients (85%) exhibited major neurological improvements (defined as decreases in National Institutes of Health Stroke Scale scores of > or =4 points) at 24 hours, suggesting that recanalization occurred within 24 hours for almost all patients. AIs for the 25 irreversible lesions ranged from 15.0 to 53.4% (37.3 +/- 11.6%), whereas AIs for the 38 reversible lesions ranged from 45.0 to 83.1% (69.3 +/- 8.6%). There was a significant difference in the AIs for these two groups (P < 0.0001). The ischemia in tissue with AIs of more than 53.4% was reversible. In contrast, ischemic tissue with AIs of less than 45.0% could not escape cerebral infarction with our treatment. The ischemia in tissue with AIs between 45.0 and 53.4% was reversible in some patients and irreversible in others. CONCLUSION: To save ischemic tissue with our intravenous t-PA infusion therapy, residual CBF should be at least 45% of the contralateral presumed normal CBF value. CBF thresholds for ischemia that would be surely salvageable with our intravenous t-PA infusion therapy might be approximately 50 to 55% of the contralateral presumed normal CBF values.

Acute Disease↗

Comparison of 99Tcm-tetrofosmin with 201Tl and 131I in the detection of differentiated thyroid cancer metastases.

The purpose of this study was to assess the detectability of metastatic lesions by 99Tcm-tetrofosmin in differentiated thyroid cancer, and to compare the results with those obtained using 201Tl-chloride and tracer doses of 131I. Twenty-four thyroidectomized patients with metastases were studied. There were 34 metastases, including 16 lung, nine lymph node and nine bone. Radiological studies (chest X-ray, computed tomography and magnetic resonance imaging), serum thyroglobulin assays and histopathological examinations were performed to verify the presence of metastases with positive uptake of the three radionuclides. Increased accumulation of 99Tcm-tetrofosmin was observed in 11 of 16 (68.8%) lung metastases, eight of nine (88.9%) lymph node metastases and eight of nine (88.9%) bone metastases. Increased accumulation of 201Tl and 131I was observed in 11 of 16 (both) (68.8%) lung metastases, eight (88.9%) and three (33.3%), respectively, of lymph node metastases and eight (88.9%) and nine (100%), respectively, of bone metastases. The detectability of thyroid cancer metastases using 99Tcm-tetrofosmin, 201Tl and 131I was 79.4%, 79.4% and 67.6%, respectively. The combined detectabilities of 99Tcm-tetrofosmin and 131I and of 201Tl and 131I were both 88.2%. 99Tcm-tetrofosmin and 201Tl imaging were found to be more sensitive than 131I for the detection of differentiated thyroid cancer metastases, particularly for regional lymph node. The combination of 99Tcm-tetrofosmin and 131I imaging may be a more sensitive and effective method for detecting metastases in differentiated thyroid cancer.

Adenocarcinoma, Follicular↗

The use of double-straight needle device in laparoscopic incisional and ventral hernia repair.

Incisional and ventral hernias are good indications for laparoscopic hernia repair. A successful repair requires complete covering of the hernia defect, adequate tension of the prosthesis, and secure stapling by a hernia stapler. The authors introduce their technique using a double-straight needle device. This technique is easy and quick and achieves adequate fixation between the prosthesis and the abdominal wall, which reduces operating time and provides cosmetic benefit.

Hernia, Ventral↗

Involvement of tyrosine kinase in citrate-stimulated aldosterone production in bovine glomerulosa cells.

The present study was designed to assess whether citrate stimulates aldosterone production by isolated bovine adrenal glomerulosa cells in vitro. When the cells were incubated with graded concentrations of citrate up to 4.0 mM, basal aldosterone production was significantly elevated, with a gradual reduction of extracellular ionized calcium concentration. Without citrate, however, adding increasing amounts of calcium chloride to a calcium-free medium did not reproduce the citrate's effect on basal aldosterone production. Genistein, an inhibitor of tyrosine kinases, inhibited the citrate (4 mM)-induced aldosterone production in a dose-dependent manner, with 89.8% of inhibition at a concentration of 10 microM. When the cells were exposed to citrate (4 mM) for 5, 10, and 30 min, tyrosine in Mr 105,000 endogenous protein was dominantly phosphorylated. This study demonstrates for the first time that citrate stimulates aldosterone production in bovine adrenal glomerulosa cells in vitro and also suggests a crucial involvement of protein tyrosine kinase in the steroidogenic action of citrate in the cells.

Aldosterone↗

Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group.

PURPOSE: To assess the efficacy and safety of S-1, a novel oral fluoropyrimidine derivative, we conducted a multicenter late phase II study in patients with advanced gastric cancer. PATIENTS AND METHODS: Fifty-one patients who had received no previous chemotherapy were enrolled. Fifty patients were eligible for efficacy and safety analyses. The overall response was evaluated for the 43 patients who had metastatic lesions. S-1 was administered orally after breakfast and dinner for 28 days, followed by a 14-day break. The dosages were assigned according to the patients' body surface area (BSA): BSA <1.25 m(2), 40 mg; 1.25-1.5 m(2), 50 mg, and BSA > or =1.5 m(2), 60 mg, twice daily. RESULTS: The overall response to treatment was evaluated as partial response in 19 of the 43 patients (44%; 95% confidence interval 30-59%). The median survival time in all patients was 207 days with 1- and 2-year survival rates of 36.0 and 14.0%, respectively. Grade 3 adverse reactions included decreased hemoglobin values in 2 patients, leukopenia, neutropenia and diarrhea in 1 patient each. No other grade 4 or unexpected adverse reactions were seen. CONCLUSIONS: S-1 is effective against advanced gastric cancer. This oral treatment is suitable for outpatients because of its mild toxicity. Further therapeutic benefits are likely to be obtained by combining S-1 with other chemotherapeutic agents.

Administration, Oral↗

Drug interaction between cimetidine and timolol ophthalmic solution: effect on heart rate and intraocular pressure in healthy Japanese volunteers.

Systemic adverse effects of timolol ophthalmic solution given at usual therapeutic doses have been well characterized. Timolol is partially metabolized by cytochrome P450 (CYP) 2D6. Cimetidine inhibits the activity of cytochrome P450, including CYP2D6, leading to reduced systemic clearance of concomitant drugs. Coadministration of cimetidine has been speculated to affect the pharmacological effects of timolol ophthalmic solution, resulting in increased blood concentration. To evaluate whether administration of cimetidine with timolol ophthalmic solution increased the degree of beta-blockade, 12 healthy Japanese male volunteers ages 19 to 26 received cimetidine (400 mg), on oral placebo, timolol maleate 0.5% (0.05 mL to each eye), or placebo eye drops in a randomized, double-blind, Latin-square design. The oral drug alone was given for 3 days, and on the 4th day, eye drops were applied after oral drug administration. At baseline and 1, 3, and 6 hours after eye drop administration, blood pressure and heart rate (HR) were measured before and after exercise. Intraocular pressure (IOP) was measured at rest. A visual analog scale (VAS) was used to assess subjective bodily feelings in exercise tolerance after every physical exercise. The exercise HR, exercise systolic blood pressure (SBP), and resting SBP were reduced following timolol with and without cimetidine compared with the placebo (p < 0.01, respectively). Administration of cimetidine with timolol ophthalmic solution resulted in additional reductions of the resting HR and IOP. VAS detected a significant reduction in exercise tolerance from timolol ophthalmic solution (p < .05). In conclusion, administration of cimetidine with timolol ophthalmic solution increased the degree of beta-blockade.

Adrenergic beta-Antagonists↗

Treatment of renovascular hypertension using stent implantation in an elderly patient with NIDDM.

A 70-year-old man with NIDDM was diagnosed as having renovascular hypertension (RVH), based on a stenosis of the ostial portion of the left renal artery with markedly elevated plasma renin activity (PRA) in both the left renal vein and the peripheral blood, and positive captopril tests. After percutaneous transluminal renal angioplasty (PTRA), his blood pressure (BP) and PRA normalized. However, since restenosis occurred three months later, stent therapy was applied, and consequently BP and PRA normalized immediately after this procedure. During the one-year follow-up, side effects have not been noted. We propose that stent therapy may be feasible for ostial renal artery stenosis in elderly diabetic patients.

Age Factors↗

Unilateral middle cerebral artery stenosis in an adult with Down's syndrome--case report.

A 29-year-old male with Down's syndrome presented with severe headache and vomiting. Computed tomography demonstrated subarachnoid hemorrhage. Left carotid angiography showed severe stenosis of the middle cerebral artery 2 cm distal to its origin, as well as abnormal hyper-vascularization near the stenosis site similar to that seen in moyamoya disease. Right carotid angiography showed no abnormalities. However, slight stenosis of the distal part of the bilateral vertebral arteries was noted. There was no aneurysm. We judged that the subarachnoid hemorrhage had been caused by rupture of the moyamoya-like vessel. Some patients with Down's syndrome have anatomical vascular abnormality and vascular fragility. The cerebral vascular abnormality found in this case may be part of the systemic vascular abnormalities associated with Down's syndrome. The vascular changes in some adult patients with Down's syndrome may be a sign of premature aging, and long-term studies with periodic vascular examination of patients with Down's syndrome need to be performed.

Adult↗

[Effects of healthy aging on the regional cerebral blood flow measurements using 99mTc-ECD SPECT assessed with statistical parametric mapping].

To clarify the effects of normal aging on the cerebral blood flow, regional cerebral blood flow measurements++ using a Patlak Plot method of 99mTc-ECD were performed in 53 normal volunteers aged 18 to 87 years old (mean = 47.9 years). The subjects, 29 men and 24 women, were normal on clinical examination, and had neither a history of neurological nor psychiatric disease and no abnormal CT or MRI images. Statistical parametric mapping (SPM) was used for automatching and an objective approach to analysis of SPECT image data. Global cerebral blood flow showed a significant decline with age (r = 0.406). The SPM analysis (voxel height; p < 0.001, Bonferroni correction; p < 0.05) demonstrated significant age-related decrease of relative rCBF in prefrontal cortices, anterior cingulate giri, and insular cortices-temporal poles bilaterally, these affected areas belonged to limbic or association cortices. Therefore, these decreases in rCBF may suggest cognitive changes that occur during normal aging.

Adolescent↗

Surface composition and structure of titanium polished with aqueous slurry of ferric oxide.

Cast plates were prepared from commercial titanium. The plates were polished with a slurry of fine ferric oxide powder. The surface composition and structure were investigated by electron probe microanalysis (EPMA) and X-ray photoelectron spectroscopy (XPS). In the high pressure-polished surface, iron was non-uniformly distributed but oxygen was mostly uniformly distributed, while in a light pressure-polished surface, iron and oxygen were uniformly distributed though at lower and higher concentrations, respectively. EPMA state analysis and XPS suggested that the iron might exist as Fe2+ in the outermost surface, while it might be in a metallic state in the inner surface layer.

Copper↗

New partition technique for two-chamber pressure casting unit for titanium.

Although titanium has been widely used in prosthetic appliances, such as cast removable partial denture frameworks, high quality castings are still difficult to obtain. This study proposes a new partition technique using a metal foil for improving castability of a two-chamber pressure casting unit. The metal foil was formed beforehand to bring it in contact with the mold crucible wall so that no clearance was left behind it. Using this formed foil, the mold cavity can be completely isolated from the upper chamber and can be maintained in a vacuum even after the rupture of the foil. Accordingly, a large casting force is generated very quickly, and as a result, castability is expected to be significantly improved. This expectation was confirmed by the experiments using wax patterns including thin plate and mesh plate.

Aluminum↗

The spectrum of mutations causing end-plate acetylcholinesterase deficiency.

The end-plate species of acetylcholinesterase (AChE) is an asymmetric enzyme consisting of a collagenic tail subunit composed of three collagenic strands (ColQ), each attached to a tetramer of the T isoform of the catalytic subunit (AChE(T)) via a proline-rich attachment domain. The principal function of the tail subunit is to anchor asymmetric AChE in the synaptic basal lamina. Human end-plate AChE deficiency was recently shown to be caused by mutations in COLQ. We here report nine novel COLQ mutations in 7 patients with end-plate AChE deficiency. We examine the effects of the mutations on the assembly of asymmetric AChE by coexpressing each genetically engineered COLQ mutant with ACHE(T) in COS cells. We classify the newly recognized and previously reported COLQ mutations into four classes according to their position in ColQ and their effect on AChE expression. We find that missense mutations in the proline-rich attachment domain abrogate attachment of catalytic subunits, that truncation mutations in the ColQ collagen domain prevent the assembly of asymmetric AChE, that hydrophobic missense residues in the C-terminal domain prevent triple helical assembly of the ColQ collagen domain, and that other mutations in the C-terminal region produce asymmetric species of AChE that are likely insertion incompetent.

Acetylcholinesterase↗

Cathepsins B and L in synovial fluids from patients with rheumatoid arthritis and the effect of cathepsin B on the activation of pro-urokinase.

To clarify the pathophysiological role of cathepsins in rheumatoid arthritis (RA), we investigated whether cathepsin B or cathepsin L was increased in synovial fluid (SF) of RA joints, and whether the cathepsin isolated from SF of RA patients activated pro-urokinase or not. Thus, we estimated the content of cathepsins in SF of RA patients by measuring their activities by fluorospectrometry, using Z-Phe-Arg-MCA as the substrate. Cathepsin activity was approximately 4-fold higher in the SF of RA patients than in those of patients with osteoarthritis. Cathepsin B and cathepsin L were separated by cation-exchange column chromatography. As a result, a large peak corresponding to cathepsin B and a very small peak corresponding to cathepsin L were detected. Biochemical sequential fractionation of the cathepsin purified from the SF showed that the large peak was mainly composed of cathepsin B. This purified enzyme induced conversion of pro-urokinase to urokinase, and the Km for pro-urokinase was approximately 8.27 microM. These findings indicated that an imbalance between cathepsin B and its inhibitors occurred due to increased concentrations of active cathepsin B in RA articular lesions, and that cathepsin B might be related to the degradation of cartilage in RA by activating the fibrinolytic cascade.

Adult↗

[Remodeling of basement membrane in association with cancer invasion].

Type IV collagen the major component of basement membrane (BM), is composed of six genetically distinct alpha chains. In normal breast tissue, benign breast tumors, and in the intraductal components of invasive ductal carcinoma, alpha 1 (IV) and alpha 2 (IV) chains were stained in all BM, whereas alpha 5 (IV) and alpha 6 (IV) chains were restrictively localized in a linear pattern in the epithelial BM. However, in invasive ductal carcinoma, alpha 1 (IV) and alpha 2 (IV) chains were discontinuously or negatively stained in the cancer cell nest, and the assembly of alpha 5 (IV) and alpha 6 (IV) chains into the BM was completely inhibited. The results indicate that the mammary gland forms a second network of BM composed of alpha 5 (IV)/alpha 6 (IV) chains, in addition to the classic network of alpha 1 (IV)/alpha 2 (IV) chains. Remodeling of type IV collagen alpha chains during the development of invasive breast cancer seems to be differentially regulated, and to be associated with modification of histopathological findings.

Basement Membrane↗

Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT.

UNLABELLED: The aim of this SPECT study was to determine the initial abnormality and longitudinal changes in regional cerebral blood flow (rCBF) in early Alzheimer's disease (AD) using statistical parametric mapping (SPM). METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer SPECT in 32 patients complaining of mild cognitive impairment, with a Mini-Mental State Examination score more than 24 at the initial study, and 45 age-matched healthy volunteers. All patients satisfied the diagnostic criteria of AD during the follow-up period of at least 2 y. Follow-up SPECT studies were performed on the patients at a mean interval of 15 mo. We used the raw data (absolute rCBF parametric maps) and the adjusted rCBF images of relative flow distribution (normalization of global cerebral blood flow [CBF] for each subject to 50 mL/100 g/min with proportional scaling) to compare these groups with SPM. RESULTS: In the baseline study, the adjusted rCBF was significantly and bilaterally decreased in the posterior cingulate gyri and precunei of patients compared with healthy volunteers. In the follow-up study, selected reduction of the adjusted rCBF was observed in the left hippocampus and parahippocampal gyrus. These areas showed the most prominent reduction in absolute rCBF on each occasion. Moreover, further decline of the absolute rCBF was longitudinally observed in extensive areas of the cerebral association cortex. CONCLUSION: SPM analysis showed the characteristic early-AD rCBF pattern of selective decrease and longitudinal decline, which may be overlooked by a conventional region-of-interest technique with observer a priori choice and hypothesis. This alteration in rCBF may closely relate to the pathophysiologic process of this disease.

Aged↗

[Evaluation of lung lobar ventilation dynamics with magnetic resonance imaging: a comparison of interstitial pneumonia patients with normal subjects].

Magnetic resonance imaging (MRI) was utilized to study lung lobar dynamic ventilation in 11 patients with interstitial pneumonia (IP) and 10 non-smoking men. The IP patients included 7 with interstitial lung disease associated with collagen vascular disease, 3 with idiopathic interstitial pneumonia, and 1 with lung cancer who was excluded from statistical analysis. We calculated lung lobar volumes in each phase from each dynamic image and constructed time-volume curves(TVCs). Lung lobar volume rates(%), fluctuation rates(%), lobar fluctuation rate/total lung fluctuation rate (%), and time lag (sec.) for the IP patients and normal subjects were calculated and compared. In the former, the mean volume rate for the right upper lobe was larger (p < 0.01) than that in normal subjects. The mean volume rate for the left lower lobe in the IP patients was smaller(p < 0.01) than that in the normal subjects. In IP patients, peak TVC for the right middle lobe appeared later (p < 0.01) than that in normal subjects. Although the fluctuation rates and fluctuation rate/total lung fluctuation rate for the lower lobes tended to be higher than those for the upper and middle lobes in normal subjects, this tendency was not distinct in IP patients. The quantitative evaluation of pulmonary ventilation dynamics with MRI may be a useful noninvasive technique for the assessment of lung lobar ventilation in patients with IP.

Adult↗