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K Nakano

Publications and source records attributed to K Nakano.

At least 271 records · Page 15Linked to original sources

Stimulative effect of transforming growth factor-beta on collagen synthesis by human prostatic stromal cells in vitro.

BACKGROUND: Expression of transforming growth factor-beta (TGF-beta) in the prostate has been reported. The purpose of this study was to evaluate the effect of TGF-beta on collagen synthesis by stromal cells isolated from a patient with benign prostatic hyperplasia (BPH). METHODS: Human prostatic stromal cells (HPSC) derived from BPH tissue were cultured in serum-free medium. After incubation with TGF-beta1, the concentration of procollagen type I C-peptide (PIP) in the HPSC-conditioned medium was measured by enzyme immunoassay while the concentration of procollagen type III N-peptide (PIIIP) was measured by radioimmunoassay. Per-cell production of each type of collagen was calculated by multiplying the measured concentration by the volume of medium and dividing by the number of harvested cells. RESULTS: One ng/mL of TGF-beta1 significantly (P < 0.05) increased collagen production by HPSC, to 220% and 120% of control for types I and III, respectively. Increasing the amount of TGF-beta1 to 10 ng/mL had no further effect. TGF-beta1 did not significantly affect HPSC number at concentrations of either 1 or 10 ng/mL. There was a strong correlation between PIP and PIIIP production (r = 0.929, P < 0.001). CONCLUSION: These findings suggest that TGF-beta1 stimulates accumulation of extracellular matrix in stromal BPH tissue without affecting proliferation of stromal cells.

Aged↗

Oral sustained-release cisplatin preparation for rats and mice.

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II): cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin-ethylcellulose-stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg-1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg-1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 +/- 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 +/- 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL-1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10-16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL-1 in mice serum in which the total cisplatin concentration was 0.30 mg mL-1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.

Administration, Oral↗

GLP-I(7-36) amide augments Ba2+ current through L-type Ca2+ channel of rat pancreatic beta-cell in a cAMP-dependent manner.

The whole-cell patch-clamp method was used to examine the effect of glucagon-like peptide I (GLP-I)(7-36) amide on the activation process of L-type Ca2+ channels of rat pancreatic beta-cells. After depolarization, GLP-I (1-100 nmol/l) caused action potentials in cells exposed to a glucose-free solution for 10 min. The percentage of cells producing action potential depended on the concentration of GLP-I. In some cells, GLP-I caused action potentials without the prior depolarization of the membrane. In cells exposed to the glucose-free solution for longer than 30 min, or in cells that were deprived of ATP by a means of the conventional whole-cell configuration, GLP-I (20 nmol/l) did not cause the electrical excitation. Application of GLP-I augmented the maximum Ba2+ current (IBa) through L-type Ca2+ channels and shifted the current voltage curve to the left. Values of changes in the maximum IBa depended on GLP-I concentration. Application of dibutyryl cAMP (dbcAMP, 1 mmol/l) also augmented IBa. In cells pretreated with Rp-cAMP, dbcAMP did not change the magnitude of IBa. Also in cells pretreated with Rp-cAMP, GLP-I failed to augment IBa. These results suggest that in pancreatic beta-cells, GLP-I, by a cAMP-dependent mechanism, increases opening of L-type Ca2+ channels. cAMP-dependent augmentation of Ca2+ entry as well as cAMP production itself by GLP-I plays a crucial role in controlling insulin secretion.

Action Potentials↗

Serum autoantibodies against sulfatide and phospholipid in NIDDM patients with diabetic neuropathy.

OBJECTIVE: We investigated the presence of antisulfatide and antiphospholipid antibodies and the relationship between these antibodies and the results of quantitative tests of nerve function in NIDDM patients with diabetic neuropathy. RESEARCH DESIGN AND METHODS: Antisulfatide and antiphospholipid antibodies were measured in serum samples obtained from 68 NIDDM patients with diabetic neuropathy by an enzyme-linked immunosorbent assay (ELISA). Each patient was classified into one of three groups based on the combined neuropathy score (determined by the symptom score, the results of autonomic nerve function tests, and the vibration perception test), as follows: mild (n = 26), moderate (n = 22), and severe (n = 20). Nerve conduction studies were performed in a subgroup of 37 patients. RESULTS: The antisulfatide antibody was detected in 1 (4%) of 26 patients in the mild group, 4 (18%) of 22 patients in the moderate group, and 8 (40%) of 20 patients in the severe group (P < 0.01 vs. mild group). The antiphospholipid antibody was detected in none of the patients in the mild group, 8 (36%) of 22 patients in the moderate group (P < 0.001 vs. mild group), and 6 (30%) of 20 patients in the severe group (P < 0.01 vs. mild group). The threshold amplitude, determined by the vibration perception test, was significantly higher in antibody-positive patients than in antibody-negative patients: antisulfatide antibody, 55.9 +/- 46.8 microns (n = 13) vs. 22.9 +/- 13.7 microns (n = 55), P < 0.001; antiphospholipid antibody, 47.2 +/- 32.5 microns (n = 14) vs. 24.5 +/- 23.2 microns (n = 54), P < 0.01. The conduction velocity of the sural nerve was slower in the antisulfatide antibody-positive group (37.9 +/- 11.1 m/s, n = 12) than in the antisulfatide antibody-negative group (45.2 +/- 6.0 m/s, n = 19) (P < 0.05). CONCLUSIONS: These results suggest that autoimmune nerve destruction may be involved in diabetic neuropathy in NIDDM patients.

Aged↗

Huge aneurysm of the sinus of Valsalva following infective endocarditis in Behçet's disease.

A huge aneurysm of the sinus of Valsalva with conduction disturbance as a consequence of infective endocarditis in Behçet's disease is reported. The aneurysm extended not only into the ventricular septum but also to the right atrium and ventricle, with a complicated cavity formation. We speculate that complete atrioventricular block occurred due to an enlargement of the aneurysm into the ventricular septum, leading to a direct conduction system injury. Preoperative echocardiography and aortography were insufficient to recognize the extent of the lesion; subsequent operative examination revealed the true size. At operation, it is important to understand the lesion dimensions fully in order that appropriate surgical procedures be performed.

Aortic Aneurysm↗

[Ultrastructural study of lens in rat hereditary cataract by quick-freezing and deep-etching].

The cytoskeleton of lens fiber cells in rats with hereditary cataract (ICR/f) was studied by quick-freezing and deep-etching. Two kinds of filamentous structure with diameters of 5 and 10 approximately 15 nm were observed in the cortical fiber cells. They showed meshwork structures which were buried in globular particles. These filamentous structures were mostly absent in the nucleus fiber cells, but aggregated and fused globular particles with diameters of 10 approximately 20 nm were observed. Small cavities were sometimes observed in their cytoplasm. Between lens fiber cells, many globular structures were also seen. These changes might represent the degeneration of the lens fiber cells in cataract lenses.

Animals↗

[Aortic valve replacement with stentless porcine aortic valve].

The Toronto stentless porcine valve (TSPV) is a stentless porcine aortic valve, preserved with glutaraldehyde solution, which has been designed to maintain natural laminar blood flow and improve hemodynamic performance and enhance durability. Aortic valve replacement with TSPV was performed in seven patients. The reason for this indication was advanced age (65 years or more) in six patients and connective tissue disease in another patient. One patient required reoperation because of prosthetic valve endocarditis 4 months after implantation. There were no other valve-related complications. Echocardiographic examination of prosthetic valve function one month after surgery showed no aortic regurgitation in any patient. Transprosthetic gradient was 15.1 +/- 5.0 mmHg. Technical know-how is required for the implantation. The hemodynamic characteristics of the TSPV were excellent. Further follow-up is required to determine durability, but further extensive indication of this valve is expected as a bioprosthesis.

Adult↗

Choice of replacement valve in the elderly.

BACKGROUND AND AIMS OF THE STUDY: Little comparative information exists on the outcome of the valve replacement with bioprostheses or mechanical valves in the elderly. This study was carried out to make such a comparison. METHODS: Follow up data were examined from 219 patients aged > or = 65 years who underwent aortic and/or mitral valve replacement using bioprosthetic (n = 67) or mechanical valve (n = 152) between April 1979 and December 1993. The mean follow up periods were 6.3 +/- 2.8 years after bioprosthesis and 4.9 +/- 2.1 years after mechanical valve implantation. RESULTS: Although the actuarial rate of structural deterioration was higher in patients with bioprosthetic valves than in those with mechanical valves (58% versus 100% freedom at 10 years after surgery, p < 0.01), no such prosthesis-related difference was seen in the subgroup of patients aged > or = 70 (100% versus 100% at nine years, p = N.S.). The actuarial rate of major bleeding was higher after mechanical valve implantation than after bioprosthetic valve placement (90% versus 100% freedom at 10 years, p < 0.05); this lower rate with bioprosthetic valves was maintained in patients aged > or = 70 (78% versus 100% at nine years, p < 0.05). There were no significant differences in the incidences of thromboembolism and bacterial endocarditis between the two valve types. CONCLUSIONS: Structural degeneration of bioprosthetic devices was a major problem in patients aged 65-70 years, but it was essentially negligible in those aged > or = 70 years. Anticoagulant-related bleeding was a major problem with mechanical valves in both age groups. Therefore, for patients older than 70 years, valve replacement with a bioprosthesis appears to be the method of choice.

Age Factors↗

[Extensive indication of mitral valvuloplasty for non-rheumatic mitral regurgitation and postoperative QOL].

Between January 1993 and June 1996, 108 patients with non-rheumatic mitral regurgitation (MR) underwent surgical treatment. Mitral valvuloplasty (MVP) was performed in 94 patients (87%) and mitral valve replacement (MVR) was performed in 14 patients. The patients were reviewed based on the location of the prolapse, active endocarditis, and re-valvuloplasty. The proportion of MVP patients to the total number of cases was 92%, 96% and 94% for prolapse of the anterior mitral leaflet (MVP: n = 22), the posterior mitral leaflet (n = 47) and of both leaflets (n = 15), respectively; it was 60% and 33% in the patients with active infective endocarditis (n = 3) and in reoperation cases (n = 3). Reoperation was required in 2 patients. Other than reoperation cases, 3/4 grade MR was detected by color Doppler echocardiography in 6 patients although they were asymptomatic. Thromboembolism occurred in 3 patients. The event-free rate at 42 months was 80.4%. Concomitant maze procedure was performed in 36 of 39 patients with atrial fibrillation and normal sinus rhythm was obtained in 25 of the 36 patients. Only 6 patients received warfarin anticoagulation after MVP. In current cases with non-rheumatic MR, the MVP could be performed in 87% of all patients and in 94% of the patients with simple prolapse, regardless of the prolapse area. Concomitant maze procedure might provide a better quality of life after MVP.

Adult↗

Surgical treatment for prolapse of the anterior mitral leaflet.

BACKGROUND AND AIMS OF THE STUDY: Mitral valvuloplasty (MVP) for the prolapse of the anterior mitral leaflet (AML) is more difficult than that for the posterior mitral leaflet. The introduction of artificial chordae (November, 1986) and the concomitant maze operation (November, 1992) were surgical 'turning points' in our 17 years' experience. METHODS: In total, 163 surgical cases of AML prolapse based on the above turning points, and carried out between 1979 and 1996, were reviewed. These included 110 MVP and 53 mitral valve replacements. MVP was performed in only 46% (29/63) of patients before October 1986 (Group I); in 72% (42/58) of patients between November 1986 and October 1992 (Group II); and in 93% (39/42) of patients after November 1992 (Group III). RESULTS: Reoperation was required in nine patients. The reoperation-free rate after MVP was 79% at 17 years in all cases, 82% at 17 years in Group I, 86% at 10 years in Group II and 97% at four years in Group III. Besides reoperation cases, grade 3/4 mitral regurgitation (MR), assessed by color Doppler echocardiography, was detected in seven patients. The event-free (reoperation, MR, thromboembolism) rate was 69% at 17 years in all cases, 78% at 17 years in Group I, 71% at 10 years in Group II and 92% at 4 years in Group III. A concomitant maze operation was performed in 19 of 20 current patients with atrial fibrillation. The percentage of sinus rhythm after operation in Group I, II and III was 53%, 60% and 84%, respectively. CONCLUSIONS: During 17 years' experience, mortality and morbidity after MVP for AML prolapse were satisfactory. With the use of artificial chordae, we have been able to perform MVP in more than 90% of current patients with AML prolapse. Further, a concomitant maze procedure could provide a higher incidence of postoperative sinus rhythm.

Actuarial Analysis↗

Long-term results of artificial chordae implantation in patients with mitral valve prolapse.

BACKGROUND AND AIMS OF THE STUDY: In terms of valve-related complication and ventricular function, mitral valve repair (MVR) is superior to valve replacement. To date, chordae shortening and transposition have been used for diffuse prolapses. We have used artificial chordae implantation for MVR since 1986, and here review our long-term results. METHODS: Pericardial strips were used in nine patients, and e-PTFE (Gore-Tex) sutures in 58. A degenerative lesion was present in 69% of cases, endocarditis in 16% and rheumatic valvulitis in 7%. Implantation of artificial chordae was indicated for treatment of diffuse prolapse. Annuloplasty was performed in patients with or without prosthetic ring. RESULTS: Actuarial survival rate was 78% for the pericardial chordae group at nine years, and 94% for the Gore-Tex chordae group at eight years. Thromboembolic events occurred in two pericardial chordae patients, and three Gore-Tex chordae patients required reoperation. Freedom from reoperation was 100% for pericardial chordae after nine years and 96% for Gore-Tex chordae after eight years. Quality of life among survivors is good: 83% are in NYHA class I, 89% are free from anticoagulation, and 60% require no medication. Mitral valve orifice area, estimated echocardiographically, was similar in both groups at discharge and at follow up. CONCLUSIONS: MVR with artificial chordae provided satisfactory valve function for up to nine years. Gore-Tex chordae are less prone to deterioration than pericardial chordae. Follow up observations support the use e-PTFE chordae to correct diffuse leaflet prolapse.

Chordae Tendineae↗

[Acarbose].

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Acarbose↗

Direct projections from the medial vestibular nucleus to the posterior hypothalamic area in the monkey (Macaca fuscata).

Direct projections from the medial vestibular nucleus to the posterior hypothalamic area was found in the macaque monkey by the anterograde and the retrograde tract-tracing methods. After injection of biotinylated dextran amine (BDA) into the ventrolateral part of the medial vestibular nucleus, anterogradely labeled axon terminals were seen bilaterally in the posterior hypothalamic area. After injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the posterior hypothalamic area, retrogradely labeled neuronal cell bodies were observed bilaterally in the ventral part of the medial vestibular nucleus with a contralateral predominance.

Animals↗

Factors affecting rhythm after the maze procedure for atrial fibrillation.

BACKGROUND: The maze procedure failed to abolish atrial fibrillation (AF) in 14% of patients with underlying organic cardiac lesions. Identification of contributing risk factors will improve results either by treatment of such factors or by avoidance of high-risk patients. METHODS AND RESULTS: We analyzed 192 consecutive patients with AF undergoing three variations of the maze procedure performed simultaneously with correction of valvular diseases (n = 165), congenital anomalies (n = 19), isolated AF (n = 7), and ischemic disease (n = 1). Twenty-six preoperative factors and two postoperative cardiac size parameters were analyzed by multivariate analyses between patients with successfully ablated AF (n = 165) and those who remained in AF (n = 27) after the maze procedure. Among all factors, postoperative left atrial dimension was the most potent in predisposing patients to persistent AF. Duration of AF left atrial dimension, and cardiothoracic ratio were identified as preoperative risk factors, whereas modifications of the maze procedure and pathogenesis and location of underlying disease failed to have a significant prognostic impact on rhythm after surgery. Individual risk analysis using the three preoperative variables revealed that left atrial size reduction to normalize its dimension played a pivotal role in determining rhythm after the maze procedure. CONCLUSIONS: Results favor earlier performance of the procedure before these risk factors develop, after which omission of the procedure or extensive left atrial plication may be appropriate. This requires further study.

Adolescent↗

Increase in histamine synthesis by liver macrophages in CCl4-injured mast cell-deficient W/Wv mice.

This study set out to examine the possible role of liver macrophages in histamine synthesis in the injured liver. The effects of the hepatotoxins Escherichia coli lipopolysaccharide (LPS) and CCl4 on histamine synthesis in the liver of mice were evaluated. C3H/HeJ mice were resistant to LPS in including histidine decarboxylase (HDC) in the liver compared with C3H/HeN mice and mast cell-deficient W/Wv mice. However, C3H/HeJ mice did respond strongly to another hepatotoxin, CCl4, leading to a significant increase in HDC activity. CCl4 also caused a marked increase in HDC activity and histamine levels in the liver of W/Wv mice. In addition, injection of CCl4 produced a large increase in the activity of HDC in the spleen and lung of W/Wv mice. HDC activity was confined to the nonparenchymal cells, with parenchymal cells expressing essentially no HDC activity. The CCl4-induced increase in HDC activity was confined, at least in part, to the liver macrophages. These results indicate that the macrophages are responsible for the increase in HDC-dependent histamine production in the liver caused by the injection of hepatotoxins. The possible role of histamine in liver regeneration after injury is discussed.

Animals↗

Formation of crossline as a fluorescent advanced glycation end product in vitro and in vivo.

Crossline is one of the major advanced glycation end products resulting the reaction mixture of free amino group(s) such as epsilon-one in lysine with D-glucose in vitro. To study crossline formation on proteins in vitro and in vivo, polyclonal antiserum to the crossline hapten was prepared. This antiserum reacted with bovine and human serum albumin that had been modified by prolonged incubation with glucose as well as with crossline itself. Antisera did not react with unmodified serum albumin or the other Maillard-related compounds. Crossline was formed in a time-dependent manner when a mixture of six different proteins was incubated with glucose at pH 7.2 or 9.0. Crossline levels could be measured in rat lens proteins and the levels increased with age. The crossline content of lens proteins in diabetic rats was more than two-fold higher than that of age-matched controls. Results of this study suggest that most proteins containing advanced glycation end products have crossline-like structures. Measurement of crossline-like structures in biological specimens may provide an index of aging and of the development of diabetic complications.

Animals↗