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Biomedical subjects

M Nakatani

Publications and source records attributed to M Nakatani.

At least 19 recordsLinked to original sources

PACAP stimulates the release of interleukin-6 in cultured rat Müller cells.

We have investigated the in vivo effect of PACAP on rat Müller cells that are the predominant glial element in the retina. Müller cells were treated with PACAP38, either alone or in the presence of the PACAP-selective antagonist, PACAP6-38. Cellular proliferation was determined by measuring the incorporation of bromodeoxyuridine, while interleukin-6 (IL-6) levels in the culture medium were examined using a B9 cell bioassay. In cultured rat Müller cells, the expression of PACAP receptor (PAC1-R) was assessed with immunohistochemistry using a PAC1-R-specific antiserum. PACAP stimulated IL-6 production in Müller cells at a concentration as low as 10(-12) M, which was not sufficient to induce cell proliferation. This elevation of IL-6 production was significantly inhibited by PACAP6-38. These data suggest that Müller cells are one of the target cells for PACAP, stimulating the release of IL-6, and providing a mechanism whereby PACAP exerts a significant neuroprotective effect in the retina.

Animals↗

Inhibitors of the TGF-beta superfamily and their clinical applications.

The transforming growth factor-beta (TGF-beta) superfamily includes TGF-betas, activin, myostatin and bone morphogenetic proteins. Misregulation of the activity of TGF-beta family members is involved in pathogenesis of cancer, muscular dystrophy, obesity and bone and tooth remodeling. Natural inhibitors for the TGF-beta superfamily regulate fine-tuning of activity of TGF-beta family in vivo. In addition to natural inhibitors for the TGF-beta family, soluble forms of receptors for the TGF-beta family, blocking monoclonal antibodies and small chemical TGF-beta inhibitors have been developed. In this review, we summarize recent advances in our understanding of inhibitors for the TGF-beta superfamily and their medical applications.

Animals↗

The involvement of vascular endothelial growth factor and flt-1 in the process of neointimal proliferation in pig coronary arteries following stent implantation.

To clarify the role of vascular endothelial growth factor (VEGF) in the process of restenosis, a Palmaz-Schatz stent was implanted in the left anterior descending coronary artery of male pigs at 2 weeks after balloon injury (balloon/artery ratio 1.2:1). The animals were euthanized at 1, 2, and 4 weeks after stenting, and western blot and immunohistochemical analysis were performed using VEGF, fms-like tyrosine kinase (flt)-1, and platelet-derived growth factor (PDGF) antibodies. The expressions of VEGF and flt-1 protein in the neointima were observed as early as 1 week after stenting and remained for up to 4 weeks, while re-endothelialization was complete at 2 weeks. These protein expressions were demonstrated in proliferated smooth muscle cells throughout the entire period after stenting and, in addition, they were observed in the macrophages and endothelial cells of microvessels around stent struts at 4 weeks. The expression pattern of VEGF corresponded with that of PDGF, a growth factor well-known to induce neointimal proliferation. The cell proliferative activity, measured by the proliferating cell nuclear antigen index, around the struts remained high until 4 weeks after stenting, while that in the other areas declined at 4 weeks. These results suggest that VEGF is involved in the process of restenosis not only through its angiogenic properties and induction of monocyte chemotaxis, but also by a synergistic effect with PDGF.

Animals↗

Studies toward the total synthesis of popolohuanone E: enantioselective synthesis of 8-O-methylpopolohuanone E.

[structure: see text]. 8-O-methylpopolohuanone E (2) was synthesized in a highly convergent manner starting from the cis-fused decalin derivative accessible from the (-)-Wieland-Miescher ketone analogue. The synthetic method features a biogenetic-type annulation of the phenolic and quinone segments to regioselectively construct the central tricyclic ring system as the key step.

Enzyme Inhibitors↗

Diterpenoids from Euphorbia paralias.

Two segatane diterpenoids containing a bicyclic [4,3,1] ring system were isolated, together with 11 known diterpenoids, four segetanes, five jatrophanes and two paralianes, from the aerial parts of Euphorbia paralias. The structures of the new compounds were established by spectroscopic means, including by 2D NMR and CD spectroscopic analyses. The antifeedant and antiviral activities of the isolated compounds are also described.

Animals↗

Antifeedant rings B and D opened limonoids from Khaya senegalensis.

Three new rings B and D opened limonoids, two mexicanolides named khayanone (1) and 2-hydroxyseneganolide (2) and one rearranged phragmalin limonoid of 1-O-acetylkhayanolide A (3), were isolated together with six known B,D-seco compounds from the acetone extract of the stem bark of Khaya senegalensis. Structures of new compounds were elucidated by spectroscopic means, and the absolute stereochemistry of 1 was established by CD study of the dibenzoate derivative. The insect antifeedant and antiviral activities of the new compounds were also determined.

Animals↗

Successful use of a defined antigen/GM-CSF adjuvant vaccine to treat mucosal Leishmaniasis refractory to antimony: A case report.

Immunotherapy has been proposed as a method to treat mucosal leishmaniasis for many years, but the approach has been hampered by poor definition and variability of antigens used, and results have been inconclusive. We report here a case of antimonial-refractory mucosal leishmaniasis in a 45 year old male who was treated with three single injections (one per month) with a cocktail of four Leishmania recombinant antigens selected after documented hypo-responsiveness of the patient to these antigens, plus 50 microg of GM-CSF as vaccine adjuvant. Three months after treatment, all lesions had resolved completely and the patient remains without relapse after two years. Side effects of the treatment included only moderate erythema and induration at the injection site after the second and third injections. We conclude that carefully selected microbial antigens and cytokine adjuvant can be successful as immunotherapy for patients with antimonial-refractory mucosal leishmaniasis.

Adjuvants, Immunologic↗

Hyperperfusion phenomenon after percutaneous transluminal angioplasty for atherosclerotic stenosis of the intracranial vertebral artery. Case report.

The authors report on a patient who underwent percutaneous transluminal angioplasty (PTA) for stenosis of the intracranial vertebral artery (VA). This 67-year-old man's dizziness while walking was caused by infarction of the left cerebellar peduncle. On angiograms, his left VA manifested 90% stenosis at the intracranial portion and his right VA ended at the posterior inferior cerebellar artery. Because single-photon emission computerized tomography (SPECT) showed low perfusion and poor perfusion reserve in the posterior circulation, the authors performed PTA of the left VA, which was only 35% dilated due to stenosis. Although the patient's postoperative course was uneventful, postoperative hemodynamic studies (SPECT and transcranial Doppler [TCD] ultrasonography) revealed the hyperperfusion phenomenon. A 100% increase of regional cerebral blood flow in the posterior circulation was demonstrated on SPECT studies and TCD ultrasonography revealed a doubling of blood flow velocity in the VA compared with preoperative values. Careful control of the patient's blood pressure resulted in resolution of the hyperperfusion phenomenon within I week post-PTA. Although hyperperfusion syndrome following carotid endarterectomy is not rare, it is seldom seen after reconstruction of the posterior circulation, and the possibility of its occurrence must be kept in mind when the posterior circulation is reconstructed.

Aged↗

Treatment of chronic suppurative otitis media with Broncasma Berna.

Broncasma Berna, an inactivated bacterial vaccine, has been safely used throughout the world for 30 years for the prevention or treatment of various infectious processes. Until now, there has been no published report regarding its use as a treatment for chronic suppurative otitis media. In this small study, five such patients (median age: 57 years) underwent a series of seven 0.05-ml injections of Broncasma Berna. In all cases, their otorrhea diminished markedly and their tympanic membranes were almost completely dry. The cost of treatment was extremely low.

Bacterial Vaccines↗

[Effects of home oxygen therapy on patients with chronic heart failure].

OBJECTIVES: Dyspnea on exertion and/or hypoxemia due to nocturnal respiratory disturbance may occur in patients with stable chronic congestive heart failure. Such patients with respiratory disorder during sleep have a poor prognosis. The effects of treatment with home oxygen therapy on patients with congestive heart failure are unclear when symptoms are stable at rest. This study investigated the effects of home oxygen therapy on patients with stable chronic congestive heart failure. METHODS: Thirty-three patients with stable chronic congestive heart failure(New York Heart Association functional class II-IV) and hypoxemia during exercise or sleep were treated with oxygen above the level of 90% SaO2. The following factors were compared before and after home oxygen therapy: Subjective minimal capacity on exercise(metabolic equivalents: METs) before and 1 month after patients first became aware of dyspnea on effort using the specific activity scale(SAS); SaO2 at rest before and 1 month after; and frequency of admission during 1 year due to deterioration of heart failure. RESULTS: After home oxygen therapy, SAS improved from 2.5 +/- 0.9 to 3.3 +/- 1.0 METs(p < 0.0001), and SaO2 at rest improved from 92.8 +/- 2.5% to 96.3 +/- 1.6%(p < 0.0001). The frequency of admission was decreased from 1.3 +/- 1.2 to 0.8 +/- 1.2 times(p = 0.03). CONCLUSIONS: Home oxygen therapy is effective for improving the symptoms and activity of daily life in patients with chronic heart failure. Home oxygen therapy may prevent the deterioration of heart failure.

Aged↗

[Usefulness of three-dimensional color Doppler sonography for the differential diagnosis of subpleural lesions].

The purpose of our investigation was to assess the usefulness of three-dimensional color Doppler sonography (velocity mode and power mode) for the differential diagnosis of subpleural lesions. Thirty lesions (11 pneumonias, 5 lung abscesses, 11 primary lung cancers, 3 metastatic lung cancers) were examined. Three-dimensional images were reconstructed by a maximum intensity projection method. Three-dimensional representations of intralesional blood flow became available for all lesions approximately 11 seconds after scanning. In every case, the entire vasculature of the tumor, the pneumonia, the abscess, or the inflamed region of the lung was appreciated more easily from three-dimensional images than from two-dimensional images. We classified the color flow pattern of subpleural lesions depicted by color flow imaging into seven groups. Color flow was depicted better by the three-dimensional color Doppler power mode than the velocity mode. Three-dimensional color flow patterns observed in power mode, patterns of the pneumonias and the lung cancers differed significantly. Our results suggest that the three-dimensional color Doppler power mode is useful for the differential diagnosis of subpleural lesions.

Adult↗

[Morphological and histological studies of in-stent restenosis in seven types of stents implanted in porcine coronary arteries].

OBJECTIVES: Differences in the mechanism of restenosis after stenting between coil and tubular stents were examined in porcine coronary arteries using histological and immunohistochemical methods. METHODS: Twenty-four pigs underwent balloon-induced injury in the left anterior descending coronary artery. Two weeks later, seven different stents clinically available in Japan (Coil stents: GR I, GR II, Wiktor, Cordis; Tubular stents: gfx, Multilink, Palmaz-Schatz) were implanted in the injured site. Four weeks after the stent implantation, the pigs were sacrificed for histological examination and for morphometrical analysis of the lumen, neointima, media and adventitia. Immunohistochemical studies using anti-proliferating cell nuclear antigen (PCNA), anti-alpha-smooth muscle actin and anti-macrophage antibody were also performed. RESULTS: The coil stents formed eccentric, and the tubular stents formed concentric neointimal proliferation. Although there was no difference in the area of neointima between the stents, the area of lumen in the tubular stents was bigger than that in the coil stents (p < 0.01), because the vascular area was bigger in the tubular stents (p < 0.05). Immunohistochemical examination found many PCNA-positive cells in the proliferated neointima, especially in the area around the stent strut. Many of these cells around the stent strut were positively stained by anti-macrophage antibody. Other cells positively stained for PCNA were confirmed as smooth muscle cells. CONCLUSIONS: Tubular stents maintained a wider lumen than coil stents, because negative remodeling after stenting was less in the tubular stents. Implantation of stents with less negative remodeling is very important to prevent restenosis after stenting.

Actins↗

Anthocyanins in callus induced from purple storage root of Ipomoea batatas L.

Two anthocyanins were isolated from the highly pigmented callus derived from the storage root of purple sweet potato (Ipomoea batatas L.) cultivar 'Ayamurasaki'. One was identified as cyanidin 3-O-sophoroside-5-O-glucoside, and the other as cyanidin 3-O-(2-O-(6-O-(E)-p-coumaroyl-beta-D-glucopyranosyl)-beta-D-glucop yranoside)-5-O-beta-D-glucopyranoside, by chemical and spectroscopic analysis.

Anthocyanins↗

Studies on defatted seed removal efficiency for organochlorine compounds.

Defatted seeds were evaluated for effective adsorption of organochlorine compounds such as chloroform, dichloromethane, and trichloroethylene. The amounts of these compounds adsorbed were plotted against the equilibrium concentration of substances in solution on a logarithmic scale. A linear relationship was obtained, indicating that the adsorption reactions were of the Freundlich type. The removal of these organochlorine compounds by defatted seed was attributed to the uptake by intracellular particles called spherosomes.

Dose-Response Relationship, Drug↗

A DNA ligase from a hyperthermophilic archaeon with unique cofactor specificity.

A gene encoding DNA ligase (lig(Tk)) from a hyperthermophilic archaeon, Thermococcus kodakaraensis KOD1, has been cloned and sequenced, and its protein product has been characterized. lig(Tk) consists of 1,686 bp, corresponding to a polypeptide of 562 amino acids with a predicted molecular mass of 64,079 Da. Sequence comparison with previously reported DNA ligases and the presence of conserved motifs suggested that Lig(Tk) was an ATP-dependent DNA ligase. Phylogenetic analysis indicated that Lig(Tk) was closely related to the ATP-dependent DNA ligase from Methanobacterium thermoautotrophicum DeltaH, a moderate thermophilic archaeon, along with putative DNA ligases from Euryarchaeota and Crenarchaeota. We expressed lig(Tk) in Escherichia coli and purified the recombinant protein. Recombinant Lig(Tk) was monomeric, as is the case for other DNA ligases. The protein displayed DNA ligase activity in the presence of ATP and Mg(2+). The optimum pH of Lig(Tk) was 8.0, the optimum concentration of Mg(2+), which was indispensable for the enzyme activity, was 14 to 18 mM, and the optimum concentration of K(+) was 10 to 30 mM. Lig(Tk) did not display single-stranded DNA ligase activity. At enzyme concentrations of 200 nM, we observed significant DNA ligase activity even at 100 degrees C. Unexpectedly, Lig(Tk) displayed a relatively small, but significant, DNA ligase activity when NAD(+) was added as the cofactor. Treatment of NAD(+) with hexokinase did not affect this activity, excluding the possibility of contaminant ATP in the NAD(+) solution. This unique cofactor specificity was also supported by the observation of adenylation of Lig(Tk) with NAD(+). This is the first biochemical study of a DNA ligase from a hyperthermophilic archaeon.

Adenosine Triphosphate↗

[Changes of serum hepatocyte growth factor in coronary artery disease].

Hepatocyte growth factor (HGF) is an endothelial cell specific growth factor involved in the repair of endothelial cells and collateral formation, however, the role for coronary artery disease is still unknown. We measured serum HGF level in various coronary artery diseases to examine the clinical significance. Serum HGF level was measured using the enzyme-linked immunosorbent assay method in patients with stable effort angina pectoris (n = 26), old myocardial infarction (n = 18), unstable angina pectoris (UAP; n = 10) and acute myocardial infarction (AMI; n = 21). As a control group, we selected 11 patients with neurocirculatory asthenia. Blood samples from peripheral veins were collected at cardiac catheterization before heparin administration. In the AMI group, blood samples were also collected at 48, 72 hr, 1, 2, 3 and 4 weeks from the peripheral veins and 48 and 72 hr after reperfusion from the coronary sinus. Serum HGF level was significantly higher in the UAP (0.41 +/- 0.12 ng/ml, p < 0.001) and AMI groups (0.38 +/- 0.26 ng/ml, p < 0.05) compared to the control group (0.19 +/- 0.09 ng/ml). Serum HGF level peaked 48 hr after reperfusion in both the peripheral veins (0.42 +/- 0.16 ng/ml) and coronary sinus (0.58 +/- 0.23 ng/ml) in the AMI group, with a significantly higher level in the coronary sinus than the peripheral veins (p < 0.05). No significant correlation between peak HGF level in the peripheral veins and peak creatine kinase (CK), CK-MB, ejection fraction and cardiac index was observed. Serum HGF was elevated in acute coronary syndrome, indicating advanced endothelial cell damage. HGF is produced, at least partially, in the heart in patients with AMI. Serum HGF level may be useful to detect endothelial cell damage rather than myocardial cell damage.

Angina Pectoris↗