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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 559 records · Page 31Linked to original sources
PubMed1994

Synthetic dipeptide, N-stearoyl-D-Ser-L-Pro-OEt, induces release of tissue-type plasminogen activator in cultured cells and in experimental animals.

The tissue-type plasminogen activator (t-PA)-releasing action of synthetic dipeptides containing Gly, Ser or Pro was investigated. Among 10 dipeptides, Boc-L-Ser-L-Pro-OH and H-L-Ser-L-Pro-OH induced t-PA release in vitro, but the others were inactive. Since Boc-L-Ser-L-Pro-OH was more effective than H-L-Ser-L-Pro-OH, 7 related dipeptides with N-acylation were synthesized. Five of them enhanced the release of t-PA; N-stearoyl-L-Ser-L-Pro-OH (FK-5) had the greatest effect. Four compounds were further examined for activity to enhance the release of t-PA in rats. FK-5 produced a two-fold increase in fibrinolytic activity, and N-palmitoyl-L-Ser-L-Pro-OH (FK-4) also markedly enhanced the release of t-PA. Since FK-5 caused severe hemolysis, 7 analogues of FK-5 were synthesized. All of them enhanced the release of t-PA from melanoma (Bowes) cells. In rats, FK-5, N-stearoyl-D-Ser-L-Pro-OH (FK-8) and N-stearoyl-D-Ser-L-Pro-OEt (FK-10) enhanced the fibrinolytic activity two-fold. FK-5 and FK-8 also exhibited strong hemolytic activity, but FK-10 did not induce hemolysis. Therefore, FK-10 was examined in rabbits. After the injection of this compound, the fibrinolytic activity in the euglobulin fraction was markedly enhanced without accompanying hemolysis. Thus, FK-10 potently enhances fibrinolytic activity both in vitro and in vivo.

Amino Acid Sequence↗
PubMed1994

Renin inhibitors. III. Synthesis and structure-activity relationships of transition-state inhibitors containing dihydroxyethylene isostere at the P1-P1 site.

The design, synthesis and structure-activity relationships of transition-state inhibitors containing the dihydroxyethylene isostere at the scissile site are described. The compounds with (2S,3R,4S)-4-amino-5-cyclohexyl-1-morpholino-2,3-pentanediol at the P1-P1 site are potent renin inhibitors. (2S,3R,4S)-4-[N-[(2S)-3-Ethylsulfonyl-2-(1-naphthylmethyl)propiony l]-L- norleucyl]amino-5-cyclohexyl-1-morpholino-2,3-pentanediol (2) (BW-175), which is the most potent inhibitor (IC50: 3.3 nM against human renin) in this series, poorly inhibits cathepsin D (IC50: 26000 nM) and pepsin (IC50: > 100000 nM), and thus it is specific for renin. Compound 2 contains only one amino acid and showed an oral bioavailability of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. The interaction between renin and inhibitor 2 is discussed on the basis of molecular modeling studies.

Animals↗
PubMed1994

Intrapulmonary lymph nodes.

We report two cases of intrapulmonary lymph nodes detected by a chest roentgenogram or CT scan. The first patient was a 61-year-old fisherman referred complaining of cough and hemosputum. Chest roentgenogram showed a subpleural small nodular shadow at the superior segment of the right lower lobe. Thoracotomy showed a small anthracotic lymph node. The other case was a 68-year-old female patient admitted for further examination of a subpleural small nodular shadow at the latero-basal segment of the left lower lobe detected on a chest CT scan. Thoracoscopic surgery revealed that the black nodule was an anthracotic lymph node. The appearance of an intrapulmonary lymph node on radiological examination is rare, however, it should be considered in the differential diagnosis of a solitary or multiple peripheral pulmonary nodules in adults. A small nodular shadow should be resected if malignancy is suspected though not proven. Subpleural intrapulmonary lymph node warrants thoracoscopic surgery.

Aged↗
PubMed1994

Significance of VLA-4 and LFA-1 expressions in neoplastic follicle formation and its deterioration in B-cell non-Hodgkin's lymphomas.

In an attempt to determine the roles of adhesion molecules in the formation and deterioration of neoplastic follicles, we used flow cytometry to investigate how strongly neoplastic B-cells express VLA-4 alpha and LFA-1 alpha on their surfaces. Neoplastic and normal B-cells were taken from 24 patients with B-cell non-Hodgkin's lymphomas (B-NHL) and 6 with B-cell chronic lymphocytic leukemia (B-CLL). The expression intensities of the adhesion molecules were graded as follows: (-), (+), (+2) and (+3). Normal B-cells expressed those molecules with an intensity of (+2). The data for VLA-4 alpha expression were as follows: follicular B-NHL [10/11; (+2) and 1/11; (+)], partially follicular [5/5; (+)], diffuse [8/8; (+)] and B-CLL [6/6; (-)]. Those for LFA-1 alpha were as follows: follicular B-NHL [7/11; (+2), 4/11; (+)], partially follicular [3/5; (+2), 2/5; (+)], diffuse [3/8; (+2), 5/8; (+)] and B-CLL [3/6; (+), 3/6; (-)]. These results suggest that VLA-4 molecules expressed on neoplastic B-cells may be involved closely in the formation and deterioration of neoplastic follicles, although the expression of LFA-1 molecules seems to play only a minor part in such events.

Antibodies, Monoclonal↗
PubMed1994

[Prophylactic oral antibiotics in urethral instrumentation].

Between July 1990 and December 1992, the incidence of infection after 1,249 urethral manipulations on patients, who had no urinary infection before the manipulation, was studied. Infections developed in 21 patients (1.7%). The prophylactic 3-day antimicrobial medication reduced the development of infection to 5/790 (0.6%), in contrast to 16/459 (3.5%) among patients who did not take the prophylactic antimicrobial (P = 0.0004). Of the procedures studied, urethral dilation with sounds and retrograde urethrography were not so dangerous as cystoscopic examination. After cystoscopic examinations, 5 (1.4%) out of 347 males with prophylactic antimicrobial developed infection, although none of the prophylacted 135 females developed infection. Elderly persons had greater risk of developing the infection. The most disastrous bacteria was P. aeruginosa.

Administration, Oral↗
PubMed1994

[Effects of amrinone on left ventricular function following open heart surgery--analysis with left ventricular pressure volume loops].

The effects of Amrinone on cardiac function soon after extracorporeal circulation (ECC) were studied in 5 patients including mitral valvuloplasty, VSD closure, Fontan operation and coronary AV fistel closure. In all patients, left ventricular volume load decreased postoperatively. To evaluate the efficacy, we obtained left ventricular pressure-volume loops (P-V loop) before and after ECC and after intravenous administration of Amrinone (1 mg/kg) following ECC. P-V loops were produced by measuring left ventricular pressure using a Miller catheter which was retrogradely advanced from the ascending aorta into the left ventricle and by measuring left ventricular diameter to calculate left ventricular volume with Teichholtz' formula. Although no apparent difference of Emax was recognized before and after ECC, Emax increased from 3.2 +/- 2.5 mmHg/cm3 to 5.9 +/- 4.7 mmHg/cm3 after the administration of Amrinone. The left ventricular "systolic" pressure-volume area (PVA) which is the sum of stroke work (SW) and elastic potential energy decreased from 34.4 +/- 16.4 gm to 30.9 +/- 17.8 gm after Amrinone. No difference was also recognized in left ventricular end-diastolic pressure. Ejection fraction increased from 50 +/- 17.5% to 56.1 +/- 17.3%. These results suggested that Amrinone could improve the left ventricular function without prominent change in myocardial oxygen consumption immediately after open heart surgery.

Adult↗
PubMed1994

Isolation of intact transition protein 4 from boar late spermatid nuclei.

Boar transition protein 4 was extracted with acid from the late spermatid nuclei, and separated from the transition protein-degrading proteases by ion-exchange chromatography on Fractogel EMD SO3- 650 (M). The transition protein was further purified by HPLCs on Nucleosil 300 7C18 and Diol-200. The circular dichroic spectra of the protein with and without dithiothreitol showed that the protein had beta-form predominantly. Although sodium dodecyl sulfate affected the tertially structure of the protein, the beta-form was well retained. These indicate that the protein has a structure-forming potential for the beta-structure.

Animals↗
PubMed1994

Establishment of a human thymic stromal cell line (R-3-4) and its adhesive capacity with T cells in vitro.

T cells are considered to be activated in the thymus, and it has been emphasized recently that the thymic stromal cells play an important role in the process of T-cell maturation. To clarify how the stromal cells interact with T cells a cloned stromal cell line from human thymus was established and its adhesive capacity with T cells was studied. A recombinant plasmid, pSV3gpt containing SV40 large T antigen was introduced to human thymic stroma by the calcium phosphate co-precipitation method, and the thymic stromal cell line R-3-4 was obtained. Immunohistochemical examination showed that R-3-4 possessed with HLA-class 1 antigen, laminin, fibronectin, and keratin. To determine if the R-3-4 interacts with T cells, the binding activity of R-3-4 with T cells examined by using rosette formation technique. The R-3-4 formed rosette only with the T cells, but both B cells and myeloid cells did not bind to the R-3-4. This rosette formation between R-3-4 and T cells was inhibited when T cells were pretreated with anti-CD2 antibodies, suggesting that some mechanism involving CD2 participates in this binding. Our novel established thymic stromal cell line might be useful for studying the interactions between thymic stroma and T cells in vitro.

Antibodies, Monoclonal↗
PubMed1994

Genetic instability of human cells with DNA related to human retrovirus.

To elucidate the role of HTLV-I in human neoplasia, DNA was extracted from tumor tissues, cultured cells, and/or sera from 20 HTLV-I seropositive and from 10 seronegative cancer patients, subjected to PCR-PAGE, and analyzed by Southern hybridization. HTLV-I related sequences were detected in tumors of the seropositives with different types of cancer. In the seronegatives, gag related sequences were detected in some tumors, whereas LTR related sequences were detected in only uterus carcinoma and tax related sequences in none of tumors examined. These sequences were detected in tumor cells as well as lymphoid cells by in situ hybridization. Some of these sequences were also detected in cultured fibroblasts derived from ATL patients. Cultured normal human lymphocytes grew continuously in conditioned media following HTLV-I infection, and transformed on exposure to carcinogens. Chromosome changes in transformed cells appeared clustering to chromosomes abnormalized on HTLV-I infection. The frequency of abnormal chromosomes in lymphocytes was significantly higher in the seropositives and in their family members than in seronegative normal donors. The frequency increased with advancement of host age in the seropositives but not in the seronegatives. These findings indicate that some individuals carry HTLV-I related sequences that may be derepressed by host aging and resulted in increasing genetic instability of host cells rendering them increasingly susceptible to carcinogens.

Adult↗
PubMed1994

[Immunoregulatory cells in patients with monoclonal gammopathies].

The authors detected immunoregulatory cells by two-color cytometric analysis in the peripheral blood of 21 patients with multiple myeloma (MM) and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). CD3-CD56+ cells increased in both MGUS and IgG, IgA type MM in clinical stage (CS) I & II, whereas CD3+ cells decreased. On the other hand, the CD4/8 ratio, the proportions of CD45RA+ cells and CD29++ cells in CD4+ cells, and S6F1++ cells in CD8++ cells remained normal. In CS III MM of IgG and IgA type, CD3-CD56+ cells did not increase, although CD3+ cells decreased. Additionally, both CD4/8 and CD4+ CD45RA+/CD4+ ratios were low, while the proportions of CD29++ cells in CD4 cells and S6F1++ cells in CD8++ cells were high. However, this type of change in the T-cell subset balance was not observed in CS III MM of the Bence-Jones type, which showed no significant elevation of serum M-protein. These findings suggest that serum monoclonal idiotypes could affect immunoregulatory cells, especially T cells.

Flow Cytometry↗
PubMed1994

[Clinical study of neoadjuvant intraarterial chemotherapy (I A-MAC) for advanced bladder cancer].

The clinical efficacy of intraarterial neoadjuvant chemotherapy with MTX, ADR and CDDP in 88 patients with advanced bladder cancer (> or = T2 or TCC G3) was evaluated. The intraarterial chemotherapy was performed using Seldinger's method. The three drugs were administered at the same time among 60 patients. In sixteen patients MTX was administered intravenously before intraarterial infusion of ADR and CDDP. In twelve patients, a high dose of CDDP (more than 100 mg/m2) was administered. The mean regression rate was 70%. That of the high-dose CDDP group was rather superior to the other two groups. However, the adverse reaction and duration of recovery were inferior to those of the other two groups. When intraarterial chemotherapy is performed as a neoadjuvant chemotherapy, care must be taken to determine the suitable dose.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Use of the 21-mm Björk-Shiley Monostrut valve in patients with a narrow aortic root.

Technical considerations regarding the insertion of 21-mm Björk-Shiley Monostrut valves, particularly regarding decalcification of a calcified annulus with an ultrasonic surgical dissector, in patients with aortic stenosis and a narrow aortic root are described. Short-term follow-up (mean(s.d.) 37(10) months) is also presented. Ten adults whose body surface area ranged from 1.26 to 1.47 m2 underwent implantation of a 21-mm valve without outflow patch or annuloplasty. One operative death occurred; there were no other complications. The New York Heart Association functional class decreased from a mean of 3.2 before surgery to 1 in all cases. The mean(s.d.) end-diastolic volume decreased from 129(44) ml to 80(21) ml, and the end-systolic volume from 41(21) ml to 27(10) ml (P < 0.01). The mean(s.d.) maximum velocity, as measured by Doppler echocardiography in the aortic position, decreased from 4.35(0.55) m/s to 2.42(0.59) m/s (P < 0.01). This degree of improvement was not meaningfully different from that of the 23-mm valve. However, there was a negative correlation between the reduction in left ventricular mass and body surface area (r = -0.72, P < 0.03). It is concluded that the 21-mm Björk-Shiley Monostrut valve can be inserted using a modified technique in most patients with a narrow aortic root. This size valve is satisfactory when the patient's body surface area is < 1.45 m2.

Aortic Valve↗
PubMed1994

[A clinicopathological study of renal hemodynamics in patients with systemic lupus erythematosus].

We evaluated the clinical value of the glomerular filtration rate (GFR) and renal plasma flow (RPF) in patients with systemic lupus erythematosus (SLE). All of the patients fulfilled the criteria for SLE of the American Rheumatism Association and were divided into two groups by the criteria for disease activity. GFR and RPF were simultaneously measured by the standard clearance technique using sodium thiosulfate and sodium paraaminohippurate, respectively. Ninety-six clinically active patients and 60 inactive patients underwent one clearance study. In 36 other patients, repeated clearance studies were undertaken on two occasions during the period from the active to inactive phase. The mean RPF was 590.3 +/- 213.7 ml/min in 132 active patients and 485.7 +/- 184.0 ml/min in 96 patients without disease activity (p < 0.01), whereas the mean GFR was comparable between the two groups. In active SLE, the mean GFR in 76 patients with proteinuria was 76.0 +/- 38.2 ml/min as compared with 104.8 +/- 34.3 ml/min in 56 patients without proteinuria (p < 0.01); however, there was no significant difference in the mean RPF between the two groups. A fall in GFR was frequently observed in patients with class IV lupus nephritis. In contrast, there was no significant difference in the mean RPF between class IV patients and the patients in the other classes. As a result, a marked decrease in the filtration fraction (FF) was frequently observed in class IV lupus nephritis, irrespective of the use of diuretics or antihypertensive agents. Semiquantitative histological analyses revealed that mesangial proliferative changes were more responsible than glomerular sclerotic changes for these hemodynamic features.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[A clinical study of renal hemodynamics in patients with lupus nephritis].

This study was designed to evaluate the clinical significance of glomerular filtration rate (GFR) and renal plasma flow (RPF) in 122 patients with lupus nephritis. All patients had definite clinical evidence of active lupus nephritis, including urinary and immunological abnormalities. The average RPF was 634.5 +/- 171.4 ml/min in systemic lupus erythematosus patients and 537.4 +/- 141.9 ml/min in 37 age-and sex-matched patients with primary glomerular disease (PGD) (p < 0.01). A fall in GFR, accompanied by massive proteinuria and hypocomplementemia, was observed frequently in patients with class IV lupus nephritis (diffuse proliferative GN). In contrast, RPF did not change in most patients except in some with increased RPF. No correlation was noticed between RPF and proteinuria or immunological abnormalities. As a result, a marked fall in filtration fraction (FF) was observed frequently in class IV lupus nephritis, and was correlated significantly with urinary and immunological abnormalities. Follow-up data during treatment in the active to inactive phases (average 7.8 months) were available for 39 patients. The average GFR increased significantly from 56.9 +/- 31.4 ml/min in the pre-treatment stage to 74.5 +/- 26.9 ml/min in the post-treatment stage, accompanied by an improvement in proteinuria and hypocomplementemia. On the other hand, RPF decreased significantly from 521.3 +/- 217.1 to 437.6 +/- 156.2 ml/min, so that FF increased significantly as the renal and immunological parameters normalized. Additionally, the renal function was evaluated in 11 patients during the exacerbation of lupus nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Early phase II clinical study of RP56976 (docetaxel) in patients with primary pulmonary cancer. Docetaxel Cooperative Study Group for Lung Cancer].

An early phase II clinical study of RP56976 (Docetaxel), a new anticancer agent of plant origin, was conducted in patients with primary pulmonary cancer as a multicentered study involving 28 Japanese institutions. Docetaxel was administered at an intravenous dose of 60 mg/m2 based on the results of a phase I clinical study, and efficacy and safety were examined. Of the 65 patients enrolled, 57 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. The antitumor effect in patients with non-small cell lung cancer was 21.4% (9/42). In patients not previously treated, the antitumor effect was 30.0% (6/20), in patients previously treated the antitumor effect was 13.6% (3/22), and in 13.3% (2/15) of patients with small cell lung cancer. This shows that docetaxel had an efficacy for non-small cell lung cancer. Hematological adverse reactions included leukopenia and neutropenia of Grade III or more as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy in 53.3% (32/60) and 78.3% (47/60) patients, respectively. Other major adverse reactions included alopecia and anorexia. Neurological symptoms developed at a low frequency and were mild in severity.

Adult↗
PubMed1994

[A technique of successfully performing an annuloplasty for narrowed aortic valvular annulus in aortic valve replacement].

We previously reported that a significant reduction in both myocardial weight and left ventricular end-diastolic volume weight and left ventricular end-diastolic volume was achieved with the use of an artificial valve of 21 mm size in aortic valve replacement (AVR) performed on aortic stenosis patients with a body surface area of less than 1.4 m2. In those patients with a narrower valvular annulus on a unit body surface area basis, however, we have aggressively performed an operation of enlarging the valvular annulus in conjunction with AVR with a similar satisfactory hemodynamic improvement invariably in all cases, including 3 without autologous blood transfusion. In this paper mention is made, based on our experiences gained so far, of some points of critical technical importance for the successful performance of AVR involving annuloplasty, specification by the Manouguian's and Konno's procedure.

Adolescent↗
PubMed1994

The amino acid sequence and phosphorylation sites of a boar transition protein 1.

Boar transition protein 1 was extracted with acid from the testes, purified by chromatographies on CM-Sephadex C-25 and Sephadex G-50, and reduced and carboxymethylated. The modified protein was purified by HPLC on Nucleosil 300 7C18. The primary structure of the protein was determined by automated Edman degradation of the C-terminal peptide of the BrCN-cleaved protein and of the whole protein, and by carboxypeptidase digestion of it. The study of phosphorylation sites showed that Ser36 and Ser39 in the very conserved sequence 29-42 were partly phosphorylated, suggesting the involvement of this region in the interaction with DNA.

Amino Acid Sequence↗