Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 127 records · Page 7Linked to original sources

PubMed2001

[The significance of early detection for prostate cancer in mass screening].

PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.

Aged↗

PubMed2001

[Age-related changes in lower urinary tract symptoms and urodynamic parameters in patients with benign prostatic hyperplasia treated by transurethral resection of the prostate].

PURPOSE: To characterize age-related clinical and urodynamic features of patients with benign prostatic hyperplasia (BPH) treated by transurethral resection of the prostate (TUR-P). MATERIALS AND METHODS: Between July 1994 and March 2000, a total number of 451 patients underwent TUR-P in Nagoya Urology Hospital. Out of these 451 patients, 15 (3.3%) were diagnosed as having an incidental prostate cancer on pathological examination of resected prostate tissue. The remaining 436 patients (48-92 years, 69.8 +/- 7.4 years), in whom 196 (45.0%), 208 (47.7%) and 32 (7.3%) were < or = 69, 70-79 and > or = 80 years, respectively, were subjects for the present study. Their clinical features before and after TUR-P and the therapeutic effects of the treatment were evaluated in terms of aging. RESULTS: Among preoperative variables evaluated, IPSS in patients aged < or = 69 years was significantly higher than in those aged 70-79 years (p < 0.05). The QOL index was significantly higher in patients aged > or = 80 years than in those aged 70-79 years (p < 0.05). The maximum bladder capacity decreased with age from 276 ml in patients aged < or = 69 years to 211 ml in those aged > or = 80 years. Postoperatively, both maximum and mean flow rates were significantly lower in patients aged 70-79 and > or = 80 years compared to those aged < or = 69 years. There was, however, no significant age-related difference in IPSS and QOL index. The assessment of treatment effects at 3 months following TUR-P revealed that the outcomes in function as evaluated by uroflowmetry, anatomy and ultrasonic measurement of prostate volume were significantly worse in patients aged > or = 80 years compared to those in younger patients. However, there was no significant age-related difference in outcomes in subjective symptoms and QOL. CONCLUSIONS: TUR-P could be performed safely even in patients aged > or = 80 years. It is concluded that although postoperative urinary condition might be worse in older patients, they would nevertheless be satisfied with the results of TUR-P in the same way as less aged patients. As long as subjects are selected properly based on the correct diagnosis of BPH and a sufficient evaluation of operation risks, TUR-P can be expected to be performed safely and be followed by satisfaction with the treatment effects.

Aged↗

PubMed2001

[Acute ultraviolet B induced lens epithelial cell photo-damage and its repair process].

PURPOSE: To clarify the process of acute lens epithelial cell photo-damage induced by ultraviolet B (UV-B) exposure and its repair. METHODS: Pigmented rabbits were exposed to UV-B (300 mJ/cm2). The time course of lens epithelial cell photo-damage was evaluated by light microscopy of lens epithelial cell flat mounts. The flat mounted lens epithelial cells were stained with Mayer's hematoxylin or by immunohistochemistry with anti-proliferating cell nuclear antigen (PCNA) monoclonal antibodies. RESULTS: The lens epithelial cells were irregularly arranged and there were debris and pycnotic nuclei, small nuclei, existence of large cells, and phagocytosis of neighboring cells in the pupillary area. A repair process was seen in the injured areas within a week after UV-B exposure. PCNA positive cells were seen and it was confirmed that the healing of the photo-injured part was due to epithelial cell proliferation. CONCLUSIONS: The acute lens epithelial cell photo-damage induced by UV-B exposure was repaired within a week by cell proliferation.

Animals↗

PubMed2001

Pharmacological characterization of KUR-1246, a selective uterine relaxant.

The aim of the present study was to evaluate the efficacy and beta 2-adrenoceptor (AR) selectivity of KUR-1246, a new uterine relaxant. Inhibition of spontaneous or drug-induced uterine contractions by KUR-1246 was evaluated in pregnant rats and rabbits by an organ bath method or by a balloon method. The selectivity of KUR-1246 was assessed simultaneously in organs isolated from late-pregnant rats. The affinity of KUR-1246 for human beta 1-, beta 2-, and beta 3-ARs was determined using two radioligands. KUR-1246 suppressed both spontaneous and drug-induced contractions in isolated uteri, the rank order of potency being isoproterenol > KUR-1246 > terbutaline > ritodrine. ICI-118551 (selective beta 2-AR antagonist) competitively antagonized the KUR-1246-induced inhibition of spontaneous uterine contractions, but CGP-20712A (selective beta 1-AR antagonist) and SR-58894A (selective beta 3-AR antagonist) did not. All beta-AR agonists tested produced significant inhibition of spontaneous uterine contractions in vivo: ED(30) value for KUR-1246 was 0.13 microg/kg/min, a potency about 6 times and 400 times greater than that of terbutaline and ritodrine, respectively. In contrast, the positive chronotropic effect was minimal in KUR-1246-treated rats. KUR-1246 displaced radioligand binding to beta 1-, beta 2-, and beta 3-ARs, the pK(i) values being 5.75 +/- 0.03, 7.59 +/- 0.08, and 4.75 +/- 0.03 for beta 1-, beta 2-, and beta 3-ARs, respectively. For the selectivity of KUR-1246 for human beta 2-AR, we obtained values of 39.2 ([IC(50) for beta 1-AR]/[IC(50) for beta 2-AR]) and 198.2 ([IC(50) for beta 3-AR]/[IC(50) for beta 2-AR]), indicating an apparently higher affinity for human beta 2-AR than for other beta-AR subtypes. The present study clearly demonstrated that KUR-1246 is a more selective beta 2-AR agonist than the drugs presently used for relaxing uterine muscle.

Acetamides↗

PubMed2001

[A case of infravesical obstruction caused by prostatic stones as diagnosed by transrectal ultrasonography at voiding].

A 69-year-old patient, who had been treated using alpha 1-blocker for benign prostatic hyperplasia (BPH) at another clinic, visited our clinic due to persistent difficulty in urination. Total International Prostate Symptom Score (IPSS) was 32 points and quality of life (QOL) index was 5. Uroflowmetry demonstrated maximum urinary flow rate and average urinary flow rate to be 9.2 ml/sec and 5.1 ml/sec, respectively, with 3 ml of residual urine volume. Transrectal ultrasonography (TRUS) revealed prostatic stones but not BPH. Retrograde urethrography demonstrated nothing abnormal other than prostatic stones. TRUS at voiding phase using linear probe (voiding TRUS) revealed poor opening of the urethra surrounded by prostatic stones. As a result, the cause of urinary disturbance was diagnosed to be due to urethral obstruction caused by prostatic stones, and transurethral resection of prostatic tissue with stones was performed. Postoperatively, IPSS decreased to 10 points and QOL index to 2. Maximum urinary flow rate also improved to 18.1 ml/sec and mean urinary flow to 8.4 ml/sec. Thus, voiding TRUS is likely the best urodynamic test for clinical use in determining the etiology of obstruction at posterior urethra.

Aged↗

PubMed2001

[Ghrelin: a novel growth-hormone releasing peptide].

Growth hormone secretagogues are small synthetic molecules that act through an orphan G-protein coupled receptor(GPCR) called GHS-R. We purified its endogenous ligand from rat stomach and named it 'ghrelin'. Ghrelin is a 28-amino-acid peptide with an essential n-octanoyl modification at Ser3. The discovery of ghrelin indicates that the release of GH from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin from the stomach and hypothalamus. Moreover, ghrelin induces appetite-stimulating effect and adiposity in rat. These facts indicate that ghrelin is a natural leptin antagonist.

Animals↗

PubMed2001

Surgical and molecular approaches to the sentinel lymph nodes.

Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) provides a unique opportunity for assessing potential immunologic interactions between the primary tumor and regional lymph node basin. We performed LM/SL in 24 patients with early-stage melanoma and resected an additional nonsentinel node (non-SN) in each case. Sentinel nodes (SNs) and non-SNs were evaluated by routine pathologic analysis, and a portion of each node was processed for expression of three dendritic markers of activation (CD80, CD86, CD40) and their corresponding T-cell receptors (CTLA-4 and CD28). Twenty (83%) patients had matched SNs and non-SNs. A total of 26 nodal pairs were obtained because one patient had three pairs and two other patients each had two pairs. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of paired SNs and non-SNs demonstrated a marked reduction in semiquantitative expression of CD80 (77%), CD86 (77%), and CD40 (85%), as well as CTLA-4 (88%) and CD28 (85%) in SNs. The diminished expression appeared to be unrelated to B-cell (CD20) and T-cell (CD2) expression. A quantitative reduction in dendritic cell markers in SNs may be important in the immunologic interaction between the primary site and regional lymph node basin and may also provide useful criteria for identifying SNs.

Antigens, CD↗

PubMed2000

Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue.

Ghrelin, a novel peptide purified from stomach, is the endogenous ligand for the growth hormone secretagogue receptor and has potent growth hormone-releasing activity. The Ser3 residue of ghrelin is modified by n-octanoic acid, a modification necessary for hormonal activity. We established two ghrelin-specific radioimmunoassays; one recognizes the octanoyl-modified portion and another the C-terminal portion of ghrelin. Using these radioimmunoassay systems, we found that two major molecular forms exist-ghrelin and des-n-octanoyl ghrelin. While ghrelin activates growth-hormone secretagogue (GHS) receptor-expressing cells, the nonmodified des-n-octanyl form of ghrelin, designated as des-acyl ghrelin, does not. In addition to these findings, our radioimmunoassay systems also revealed high concentrations of ghrelin in the stomach and small intestine.

Amino Acid Sequence↗

PubMed2000

Kidney produces a novel acylated peptide, ghrelin.

Ghrelin is a novel growth hormone-releasing peptide with a unique acylated structure. Here we reveal that prepro-ghrelin gene is expressed in the mouse kidney and glomerulus. We also show by reverse-phase high performance liquid chromatography coupled with radioimmunoassay that the mouse kidney does produce ghrelin. The ghrelin immunoreactivity in the mouse kidney is 6.79+/-0.48 fmol/mg (n=5), which is much more abundant than that in the mouse plasma of 0.339+/-0.029 fmol/microl (n=6). Furthermore, prepro-ghrelin gene is expressed in cultured rat mesangial cells, fibroblast-like NRK-49F cells and mouse podocytes, but not in rat epithelial cell-like NRK-52E cells. Ghrelin receptor gene is also expressed in the rat kidney. These findings demonstrate that the kidney, glomerulus and renal cells express prepro-ghrelin gene and ghrelin is produced locally in the kidney, and suggest the endocrine and/or paracrine roles of ghrelin in the kidney.

Acylation↗

PubMed2000

Detection and characterization of a 36-kDa peptide in C-terminal region of a 24-kDa vacuolar protein (VP24) precursor in anthocyanin-producing sweet potato cells in suspension culture.

A 24-kDa vacuolar protein (VP24) was found to accumulate in anthocyanin-producing sweet potato cells (Ipomoea batatas Lam.) in suspension culture [Nozue et al., Plant Physiol. 115 (1997) 1065]. VP24 cDNA (accession No. AB025531) encodes a 96.3-kDa large precursor protein with a C-terminal propeptide which contains the eight putative transmembrane domains. The mature VP24 is probably involved in the formation of intravacuolar pigmented globules (cyanoplasts) in highly anthocyanin-containing vacuoles, but the biological function of the C-terminal region including the putative transmembrane domains is unknown. To confirm the expression and characterize the C-terminal region in the VP24 protein precursor in the anthocyanin-producing cells, polyclonal antibodies were developed against the fusion protein, including the C-terminal region, expressed in Escherichia coli. Western blot analysis showed that a 36-kDa peptide (VP36) localized in anthocyanin-containing vacuoles was expressed under continuous illumination, but not in darkness. The expression pattern of VP36 showed high similarity to VP24. These results suggested that VP36 may be derived from the large VP24 protein precursor; it includes several of the hydrophobic domains in the C-terminal region.

Journal Article↗

PubMed2000

Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype.

Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P <.0001), lower serum lactate dehydrogenase level (P =.01), better performance status (P =.03), less frequent extranodal involvement (P =.01), lower international prognostic index (IPI) categories (P =.002), and superior survival (P =.0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56(+) cases showed a significantly poor prognosis overall (P =.002) as well as in both ALK-positive and ALK-negative subgroups (P =.02 and P =.04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56(+) cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56(+) and CD56(-) groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.

Adolescent↗

PubMed2000

Central effects of neuromedin U in the regulation of energy homeostasis.

Neuromedin U (NMU) is a brain-gut peptide whose peripheral activities are well-understood but whose central actions have yet to be clarified. The recent identification of two NMU receptors in rat brain has provided a springboard for further investigation into its role in the central nervous system. Intracerebroventricular administration of NMU to free-feeding rats decreased food intake and body weight. Conversely, NMU increased gross locomotor activity, body temperature, and heat production. NMU, a potent endogenous anorectic peptide, serves as a catabolic signaling molecule in the brain. Further investigation of the biochemical and physiological functions of NMU will help our better understanding of the mechanisms of energy homeostasis.

Animals↗

PubMed2000

Ghrelin stimulates gastric acid secretion and motility in rats.

Ghrelin, a novel growth-hormone-releasing peptide, was discovered in rat and human stomach tissues. However, its physiological and pharmacological actions in the gastric function remain to be determined. Therefore, we studied the effects of rat ghrelin on gastric functions in urethane-anesthetized rats. Intravenous administrations of rat ghrelin at 0.8 to 20 microgram/kg dose-dependently increased not only gastric acid secretion measured by a lumen-perfused method, but also gastric motility measured by a miniature balloon method. The maximum response in gastric acid secretion was almost equipotent to that of histamine (3 mg/kg, i.v.). Moreover, these actions were abolished by pretreatment with either atropine (1 mg/kg, s.c.) or bilateral cervical vagotomy, but not by a histamine H(2)-receptor antagonist (famotidine, 1 mg/kg, s.c.). These results taken together suggest that ghrelin may play a physiological role in the vagal control of gastric function in rats.

Animals↗

PubMed2000

Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3).

GPR66 is an orphan G-protein-coupled receptor (GPCR) whose structure is similar to the ghrelin and motilin receptors. We have tried to purify a natural ligand for GPR66 in rat tissues and identified a 23-amino-acid peptide as the endogenous ligand. Sequence analysis revealed the peptide as neuromedin U (NMU), a smooth-muscle-contracting peptide that was first purified from porcine spinal cord by our group. NMU binds to GPR66-expressing cells with high specificity to induce intracellular calcium mobilization. When NMU was injected intracerebroventricularly (ICV) into rats, it potently suppressed food intake. In contrast, ICV injection of NMU-antibody increased food intake. These results suggest that NMU is a potent endogenous anorexic peptide.

Amino Acid Sequence↗

PubMed2000

Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats.

Ghrelin, a novel growth-hormone-releasing acylated peptide, was recently isolated from rat stomach by the search of an endogenous ligand to an "orphan" G-protein-coupled-receptor. Ghrelin neuron is present in the arcuate nucleus of rat hypothalamus, but its central effect on growth hormone (GH) release has yet to be clarified. We determined the plasma GH concentration and GH mRNA level in the pituitary in response to central administration of ghrelin. A single intracerebroventricular (ICV) administration of ghrelin to rats increased the plasma GH concentration dose-dependently. A continuous ICV administration of ghrelin via osmotic pump for 12 days increased the plasma GH concentration on day 6, but did not keep the high GH concentration on day 12. The GH mRNA levels in both groups of single and continuous administration of ghrelin were not significantly different from those of controls. A single administration of growth-hormone secretagogue also did not stimulate GH synthesis. Central ghrelin stimulated GH release but did not augment GH synthesis. In addition to gastric ghrelin, hypothalamic ghrelin functions to regulate GH release.

Animals↗

PubMed2000

Identification of a glutamic acid and an aspartic acid residue essential for catalytic activity of aspergillopepsin II, a non-pepsin type acid proteinase.

Aspergillopepsin II from Aspergillus niger var. macrosporus is a non-pepsin type or pepstatin-insensitive acid proteinase. To identify the catalytic residues of the enzyme, all acidic residues that are conserved in the homologous proteinases of family A4 were replaced with Asn, Gln, or Ala using site-directed mutagenesis. The wild-type and mutant pro-enzymes were heterologously expressed in Escherichia coli and refolded in vitro. The wild-type pro-enzyme was shown to be processed into a two-chain active enzyme under acidic conditions. Most of the recombinant mutant pro-enzymes showed significant activity under acidic conditions because of autocatalytic activation except for the D123N, D123A, E219Q, and E219A mutants. The D123A, E219Q, and E219A mutants showed neither enzymatic activity nor autoprocessing activity under acidic conditions. The circular dichroism spectra of the mutant pro- and mature enzymes were essentially the same as those of the wild-type pro- and mature enzyme, respectively, indicating that the mutant pro-enzymes were correctly folded. In addition, two single and one double mutant pro-enzyme, D123E, E219D, and D123E/E219D, did not show enzymatic activity under acidic conditions. Taken together, Glu-219 and Asp-123 are deduced to be the catalytic residues of aspergillopepsin II.

Amino Acid Sequence↗

PubMed2000

Jumonji is a nuclear protein that participates in the negative regulation of cell growth.

The jumonji (jmj) gene, obtained by a gene trap strategy, is essential for mouse embryogenesis and is suggested to play important roles in cell growth during development. The amino acid sequence of the Jmj protein includes a nuclear localization signal and a DNA binding motif called the AT-rich interaction domain (ARID). To investigate the biological functions of the Jmj protein, we prepared specific antibodies. Using these antibodies, we showed that the Jmj protein is a 160-kDa protein and localizes in the nuclei of COS-7 cells transfected with jmj cDNA and megakaryocytes from fetal liver which show strong endogenous expression of the jmj gene. Moreover, overexpression of the Jmj protein in COS-7 and NIH3T3 cells remarkably reduced cell proliferation compared with control cells transfected with vector alone. These results show that the Jmj protein acts in cell nuclei and participates in the negative regulation of cell proliferation signaling.

3T3 Cells↗

PubMed2000

Synthesis, characterization, and spontaneous resolution of chiral nickel(II) complexes with the tripod ligand tris[2-(((2-phenylimidazol-4-yl)methylidene)amino)ethyl]amine.

The chiral nickel(II) complexes of a tripod-type ligand with the chemical formulas [Ni(H3L)](NO3)2.MeOH (1), [Ni(H3L)](ClO4)2.MeOH (2), and [Ni(H3L)](C6H5COO)2.6H2O (3) were synthesized and characterized (H3L = tris[2-(((2-phenylimidazol-4-yl)methylidene)amino)ethyl]amine). The crystal structures of 1-3 were determined by their single-crystal X-ray analyses. 1, C37H40N12O7Ni: orthorhombic, P2(1)2(1)2(1); a = 14.198(2) A, b = 22.422(2) A, c = 12.019(2) A, Z = 4. 2, C37H40N10O9Cl2Ni: orthorhombic, P2(1)2(1)2(1); a = 14.206(2) A, b = 22.735(3) A, c = 12.696(3) A, Z = 4. 3, C50H58N10O10Ni: triclinic, P1; a = 14.191(5) A, b = 16.048(4) A, c = 13.692(4) A, alpha = 115.25(2) degrees, beta = 111.07(3) degrees, gamma = 64.75(2) degrees, Z = 2. Each complex has an octahedral coordination environment for the nickel(II) ion, formed by the six nitrogen donor atoms, and is either a delta (clockwise) or a lambda (anticlockwise) enantiomorph, depending on the screw arrangement of the tripod-type ligand around the nickel(II) ion. The circular dichroism (CD) spectrum of a powdered sample of a crystal of 1 showed a positive and a negative peak at 915 and 630 nm, respectively, and that of another crystal showed an enantiomeric pattern. The observation of the Cotton effect and the crystal structure provided evidence for spontaneous resolution of the chiral complex molecule.

Journal Article↗