Biomedical subjects

N Kobayashi

Publications and source records attributed to N Kobayashi.

At least 253 records · Page 14Linked to original sources

PubMed1999

A standardized protocol for assessing regulators of pigmentation.

Varied effects of chemical or biological compounds on mammalian pigmentation have been reported by many groups, but to date, no standardized method has established necessary and/or optimal parameters for testing such agents. A standardized method has been developed to screen compounds with potential effects on pigmentation. The protocol comprises basic parameters to analyze melanogenic effects and allows for further characterization of candidate compounds, providing important insights into their mechanism of action. In this protocol (termed STOPR, for standardized testing of pigmentation regulators), compounds are initially screened using purified tyrosinase and are then tested on melanocytes in culture. After treatment of melanocytes with potentially bioactive compounds, cell proliferation and viability, total melanin accumulated, and melanogenic potential are measured. This protocol is an important first step in characterizing chemical regulation of effects on melanogenesis. When bioactive candidate compounds are identified, testing may proceed for pharmacological or otherwise commercial applications in coculture and/or organ culture models followed by in vivo testing. As an application of this method, results for compounds known to stimulate and/or inhibit melanogenesis (including arbutin, hydroquinone, kojic acid, melanocyte-stimulating hormone, and thymidine dimers) as well as some commercial skin whiteners are reported.

Animals↗

PubMed1999

Multifunctional laryngeal motoneurons: an intracellular study in the cat.

We studied the patterns of membrane potential changes in laryngeal motoneurons (LMs) during vocalization, coughing, swallowing, sneezing, and the aspiration reflex in decerebrate paralyzed cats. LMs, identified by antidromic activation from the recurrent laryngeal nerve, were expiratory (ELMs) or inspiratory (ILMs) cells that depolarized during their respective phases in eupnea. During vocalization, most ELMs depolarized and most ILMs hyperpolarized. Some ILMs depolarized slightly during vocalization. During coughing, ELMs depolarized abruptly at the transition from the inspiratory to the expiratory phase. In one-third of ELMs, this depolarization persisted throughout the abdominal burst. In the remainder ("type A"), it was interrupted by a transient repolarization. ILMs exhibited a membrane potential trajectory opposite to that of type A ELMs during coughing. During swallowing, the membrane potential of ELMs decreased transiently at the onset of the hypoglossal burst and then depolarized strongly during the burst. ILMs hyperpolarized sharply at the onset of the burst and depolarized as hypoglossal activity ceased. During sneezing, ELMs and ILMs exhibited membrane potential changes similar to those of type A ELMs and ILMs during coughing. During the aspiration reflex, ELMs and ILMs exhibited bell-shaped hyperpolarization and depolarization trajectories, respectively. We conclude that central drives to LMs, consisting of complex combinations of excitation and inhibition, vary during vocalization and upper airway defensive reflexes. This study provides data for analysis of the neuronal networks that produce these various behaviors and analysis of network reorganization caused by changes in dynamic connections between the respiratory and nonrespiratory neuronal networks.

Animals↗

PubMed1999

Fragment reconstitution of a small protein: disulfide mutant of a short C-terminal fragment derived from streptococcal protein G.

Hierarchical studies on the folding of protein G B1 domain have shown that the C-terminal fragment (C16) has a considerable amount of beta-hairpin structure that exchanges between the folded and unfolded states at room temperature, and that the C16 fragment binds noncovalently to an N-terminal fragment (N40) under physiological conditions. Those studies have led us to the hypothesis that the amphipathic beta-hairpin structure of C16 initiates folding of the domain. To obtain a more detailed understanding of the folding mechanism of the domain, we designed a mutant of C16 (SS16ox) with a disulfide bond between residues 41 and 56, and then examined the interaction of the mutant with N40 by surface plasmon resonance (SPR) and by thermal denaturation studies using circular dichroism. SS16ox strongly interacted with N40, with an equilibrium constant, KD, that was 7-fold higher than wild-type. The association rate constant, kon, of SS16ox was 8.7-fold higher than that of wild-type. This strong interaction can be explained by the entropic effect of the disulfide bond. The introduction of the disulfide bond into C16 stabilizes the beta-hairpin structure of C16, accelerates the association rate with N40, and then stabilizes the whole complex. These results support a hypothetical folding mechanism of protein G where the amphipathic beta-hairpin structure of C16 acts as a nucleus and accelerates folding of the whole molecule.

Amino Acid Sequence↗

PubMed1999

Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40.

CD40 signaling modulates the immune response at least in part by activation of nuclear factor kappaB (NFkappaB). It has been shown that two distinct domains in the CD40 cytoplasmic tail (cyt), namely cyt-N and cyt-C, independently activate NFkappaB. Although four members of the tumor necrosis factor receptor-associated factor (TRAF) family, including TRAF2, TRAF3, TRAF5, and TRAF6, bind to the CD40 cyt, how each TRAF protein contributes to the NFkappaB activation by CD40 is not clear. Here we report that TRAF2, TRAF3, and TRAF5 bind cyt-C, whereas TRAF6 binds cyt-N. cyt-N is conserved poorly between human and mouse CD40, while cyt-C is highly conserved. However, single aa substitution of Glu-235 in cyt-N of human CD40 with Ala abolishes the binding of TRAF6 to cyt-N and NFkappaB activation by cyt-N. Conservation of this Glu between mouse and human CD40 strongly suggests that TRAF6 could link cyt-N to signals essential for CD40-mediated immune response. Furthermore, NFkappaB activation by cyt-C is inhibited by a kinase-negative form of NFkappaB-inducing kinase more efficiently than that by cyt-N, consistent with the result that NFkappaB activation by TRAF2 and TRAF5 is inhibited by a kinase-negative form of NFkappaB-inducing kinase more efficiently than that by TRAF6. These results indicate that NFkappaB activating signals emanating from cyt-N and cyt-C are mediated by the different members of the TRAF family and could be regulated in a distinct manner.

Amino Acid Sequence↗

PubMed1999

Inhibition of replication of HIV-1 at both early and late stages of the viral life cycle by single-chain antibody against viral integrase.

Retroviruses including HIV-1 integrates a DNA copy of their RNA genome into cellular DNA of the infected cell. This reaction, essential and unique to replication of retroviruses, is mediated by the viral enzyme, integrase (IN). We constructed a recombinant gene encoding a single-chain, antigen-binding peptide (scAb2-19), which interacted with a carboxyl terminal part of HIV-1 IN. HeLa CD4 cells expressing scAb2-19 localized in either cytoplasmic or nuclear compartment were resistant to HIV-1 infection at an multiplicity of infection (MOI) of 0.25 or 0.063, but the resistance was overcome when MOI was increased to 1. To determine whether this resistance was due to inhibition of the early events, transduction experiments were performed with a replication-incompetent HIV-1 vector carrying bacterial lacZ driven by an internal Tat-independent cytomegalovirus immediate early promoter. Both cytoplasmic and nuclear expressions of scAb2-19 resulted in decrease in the transduction efficiency on HeLa CD4 cells. This implies that an early step of replication--before or during integration--was affected by the scAb2-19. Furthermore, cytoplasmic expression of scAb2-19 did not affect the viral amount released from the cells transfected with HIV-1 infectious clone DNA (pLAI). However, infectivity relative to reverse transcriptase activity was lower for virions released from the 293T cells cotransfected with pLAI and the cytoplasmic scAb2-19 expression plasmid than for those released from the 293T cells transfected with pLAI alone. This implies that scAb2-19 reduced infectivity of released virions by interfering a late step of the viral replication. The single-chain, antigen-binding peptide molecule may prove useful not only for studies of the functions of IN and its role in the viral life cycle but also for developing a gene therapy strategy against AIDS.

Amino Acid Sequence↗

PubMed1999

Fragment reconstitution of a small protein: folding energetics of the reconstituted immunoglobulin binding domain B1 of streptococcal protein G.

To elucidate early stages in protein folding, we have adopted a fragment reconstitution method for small proteins. This approach is expected to provide nuclei for protein folding and to allow us to investigate folding mechanisms. In previous work [Kobayashi, N., et al. (1995) FEBS Lett. 366, 99-103.] we demonstrated the association of two complementary fragments, derived from the immunoglobulin G-binding domain B1 of streptococcal Protein G, and showed the structural similarity between the reconstituted domain and the uncleaved wild-type domain. In this work we have further characterized the reconstituted domain as well as the uncleaved domain thermodynamically by means of differential scanning calorimetry (DSC) and circular dichroism (CD) measurements. Although composed of short peptide fragments not linked by covalent bonds, the reconstituted domain showed a typical folding/unfolding curve in both DSC and CD melting measurements and behaved like a globular protein. The domain was not very stable, and the small value of the Gibbs free energy corresponded to the class of the weakest protein-protein binding systems. The denaturation temperature of 0. 78 mM solution was 313 K at pH 5.9 as measured by DSC, which was more than 40 degrees lower than the uncleaved domain. This apparent instability was primarily caused by entropic disadvantage attributed to a bimolecular reaction. The temperature dependence of the enthalpy change from the folded to the unfolded state was almost identical for the reconstituted domain and the uncleaved one. This indicates that most of the noncovalent intramolecular interactions stabilizing the native structure, such as hydrogen bonding and hydrophobic interactions, are regenerated in the reconstituted domain. By comparing the equilibrium constants of the reconstituted and uncleaved domains, we determined the effective concentration to be approximately 6 M at 298 K. Structure-based estimation of the thermodynamic properties from the values of accessible surface areas showed that approximately 35% of the total heat capacity change and approximately 25% of the total enthalpy change can be attributed to the interchain interaction at 298 K. Furthermore, the folding/unfolding equilibrium of beta-hairpin structure of the fragment 41-56 alone was also characterized. These analyses allow us to envision the microdomain folding mechanism of the Protein G B1 domain, in which segment 41-56 first forms a stable beta-hairpin structure and then collides with segment 1-40, followed by spontaneous folding of the whole molecule.

Antigens, Bacterial↗

PubMed1999

Epidemiological study of the G serotype distribution of group A rotaviruses in Kenya from 1991 to 1994.

An epidemiological study on the G serotype distribution of group A rotaviruses (GARV) isolated in Kenya was carried out in one urban hospital in Nairobi and in two rural hospitals in Nanyuki and Kitui to clarify the prevalent G serotypes before future introduction of the ready licensed rotavirus vaccine in Kenya. A total of 1,431 stool specimens were collected from children, who were mainly outpatients, aged from 0 to 6 years old with acute gastroenteritis from August 1991 to July 1994. Samples positive for GARV by conventional ELISA were then analyzed by subgrouping and serotyping ELISA and by PAGE. To ascertain the G serotypes of viruses in samples that were unable to be typed by serotyping ELISA, polymerase chain reaction was also attempted. The prevalence of GARV was 28.4% in the urban hospital, 22.5% in Nanyuki, and 13.7% in Kitui. Among rotavirus-positive samples, subgroup II rotaviruses were detected in 63.1%, and subgroup I rotaviruses were 25.9%. Serotype G4 was most prevalent, accounting for 41.6% followed by 23.3% of serotype G1, 17.0% of serotype G2, and serotype G3 was rarely isolated. Seven strains of serotype G8/P1B rotavirus was detected for the first time in Kenya by RT-PCR. Eleven specimens with an unusual composition of subgroup, serotype, and electropherotype were atypical GARV in which the P-serotype was P1A, P1B, or P2. Although uncommon GARV serotype G8/P1B and atypical GARV were detected, the four major GARV serotypes, G1 through G4, should be targeted at this moment for vaccination to control this diarrheal disease in Kenya. Continuous monitoring of the G- and P-serotype distribution of GARV should provide important information about the impact of rotavirus vaccination in Kenya.

Child↗

PubMed1999

Lower restenosis rate with stenting following aggressive versus less aggressive rotational atherectomy.

The present study evaluated the acute and follow-up results of stenting following aggressive rotational atherectomy compared with stenting following less aggressive rotational atherectomy. Recent work has demonstrated that stenting following rotational atherectomy is a promising strategy for complex and calcified lesions. However, there is little information available regarding the optimal procedural technique of rotational atherectomy to be employed before stent implantation. Between May 1995 and February 1997, 162 lesions in 126 patients were stented following rotational atherectomy because of the presence of severe calcification on fluoroscopy or intravascular ultrasound (95%). The lesions were divided as to whether aggressive rotational atherectomy was performed or not. Aggressive rotational atherectomy, defined as the use of a final burr size > or =2.25 mm and/or final burr/vessel ratio > or =0.8, was performed in 56 lesions. A less aggressive rotational atherectomy strategy was performed in 106 lesions. Procedural Q-wave (8.9% vs. 1.9%, P<0.05) and non-Q-wave (11% vs. 1.9%, P<0.05) myocardial infarctions were observed more frequently after aggressive rotational atherectomy; there was no significant difference in the incidence of other procedural complications. Although there was no significant difference in minimal lumen diameter after the procedure (3.11+/-0.68 vs. 2.99+/-0.48 mm, NS), at follow-up a greater minimal lumen diameter was observed in the lesions treated with aggressive rotational atherectomy compared to those treated with less aggressive rotational atherectomy (2.12+/-1.31 vs. 1.56+/-0.89 mm, P<0.01). Restenosis rates were 50.0% in the lesions treated without aggressive rotational atherectomy and 30.9% in those treated with aggressive rotational atherectomy (P<0.05). There was no significant difference in the incidence of restenosis with a focal pattern between the two groups (25.0% vs. 21.4%, NS). In contrast, restenosis with a diffuse pattern was lower in lesions treated with aggressive rotational atherectomy than in those without aggressive rotational atherectomy (9.5% vs. 25.0%, P<0.05). Aggressive rotational atherectomy followed by stenting is a promising strategy to reduce the restenosis rate in calcified lesions. However, the aggressive strategy is associated with an increased risk of procedural myocardial infarction.

Calcinosis↗

PubMed1999

Basic fibroblast growth factor induces osteoclast formation by reciprocally regulating the production of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in mouse osteoblastic cells.

Basic fibroblast growth factor (bFGF) induced osteoclast formation in co-cultures of mouse spleen cells and osteoblasts. Osteoclastogenesis inhibitory factor (OCIF) and a selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, abolished bFGF-induced osteoclast formation. bFGF did not affect spleen cells, but it did affect osteoblasts, to stimulate osteoclast formation. Northern blot analysis revealed that bFGF up-regulated the expression of osteoclast differentiation factor (ODF) and COX-2 and down-regulated the expression of OCIF in primary osteoblastic cells. NS-398 abolished the increase of ODF mRNA, but it had no effect on the decrease of OCIF mRNA. NS-398 suppressed the binding of (125)I-labeled OCIF to osteoblastic cells treated with bFGF. Enzyme-linked immunosorbent assay showed that bFGF inhibited OCIF production by osteoblastic cells, and the inhibition was not affected by NS-398. We conclude that bFGF induces osteoclast formation by stimulating ODF production through COX-2-mediated prostaglandin synthesis and by suppressing OCIF production through a mechanism independent of prostaglandin synthesis.

Animals↗

PubMed1999

Basic fibroblast growth factor inhibits osteoclast formation induced by 1alpha,25-dihydroxyvitamin D(3) through suppressing the production of osteoclast differentiation factor.

Basic fibroblast growth factor (bFGF) inhibited osteoclast-like cell (OCL) formation in cocultures of mouse spleen cells with either osteoblasts or a stromal cell line, ST2, in the presence of 1alpha, 25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. bFGF directly acted on osteoblasts/stromal cells, but not osteoclast progenitors, to inhibit 1,25(OH)(2)D(3)-induced OCL formation. bFGF suppressed the mRNA expression of osteoclast differentiation factor (ODF) but did not affect that of osteoclastogenesis inhibitory factor (OCIF) in ST2 cells treated with 1,25(OH)(2)D(3) and dexamethasone. Enzyme-linked immunosorbent assay showed that bFGF hardly affected OCIF production in the treated ST2 cells. A genetically engineered soluble form of ODF, but not anti-OCIF neutralizing antibody, abolished bFGF-mediated inhibition of OCL formation. bFGF suppressed the binding of (125)I-labeled OCIF to both ST2 cells and osteoblasts treated with 1,25(OH)(2)D(3). These findings indicate that bFGF inhibits 1,25(OH)(2)D(3)-induced OCL formation via suppression of ODF production by osteoblasts/stromal cells.

Animals↗

PubMed1999

Changes of GABA metabolic enzymes in acute retinal ischemia.

It is reported that GABA accumulates in Müller cells in ischemic and diabetic rat retina. To investigate the mechanism of GABA accumulation in Müller cells, we localized GABA and glutamate in ischemic rat retina and measured the activity of GAD and GABA-T, enzymes involved in GABA metabolism. Using general anesthesia, we incised the bulbar conjunctiva of the rat around the limbus and clamped the left optic nerve. A sham operation was performed on the right eyes. Ocular ischemia was sustained for 30, 60 and 90 minutes. Rat eyes were enucleated immediately after ischemia and prepared for immunohistochemistry and enzyme activity measurement. Glutamate-like immunoreactivity (Glu-IR) in the sham-operated rat retina was observed in all retinal layers, showing intense staining in the nerve fiber layer (NFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Glu-IR increased in the outer plexiform layer (OPL) and outer nuclear layer (ONL) in an ischemic time-dependent manner. GABA-like immunoreactivity (GABA-IR) in sham-operated rat retina was observed in NFL, GCL, IPL and inner nuclear layer (INL). When the ischemic time was extended, GABA-IR intensely stained Müller cells. GAD activity was not changed in ischemic rat retina as compared to normal rat retina, but GABA-T activity was significantly decreased in ischemic rat retina. These results suggested that glutamate was induced by ischemia and was converted to GABA by GAD activity. Increased GABA was not metabolized because GABA-T activity was decreased. GABA accumulation in Müller cells progressed during the change in activity of these metabolic enzymes.

4-Aminobutyrate Transaminase↗

PubMed1999

Preoperative chemotherapy for advanced esophageal cancer and relation with histological effect.

The results of surgical treatment for advanced esophageal cancer remain extremely poor. Irradiation and chemotherapy are not superior to surgery. Perioperative morbidity and the influence on long-term survival of a combination of surgery and preoperative chemotherapy were investigated in patients with advanced esophageal cancer. Forty-nine patients with advanced esophageal squamous cell carcinoma were subjected to preoperative chemotherapy of cisplatin-5-fluorouracil. Fifty-seven patients were chosen as a historical control group who had not undergone chemotherapy before surgery but had the same histological stages as the chemotherapy group. The response to chemotherapy was assessed by histological studies of surgical specimens. The survival rates noted no significant difference between preoperative chemotherapy plus surgery and a resection alone. However, subclassification according to the grading of chemotherapeutic effectiveness showed that, compared with control, preoperative chemotherapy was beneficial to high responders (P = 0.01), ineffective in low responders (P = 0.61), and detrimental to nonresponders (P = 0.03). Postoperative morbidity was significantly higher in the chemotherapy group than in the control group (P = 0.02). These findings suggest that preoperative chemotherapy is necessary only for high responders and we therefore need to reliably identify non-, low, and high responders before chemotherapy to improve the survival and quality of life of patients with advanced esophageal cancer.

Actuarial Analysis↗

PubMed1999

Assessment of outcome by EC/IC bypass with 123I-iomazenil brain SPECT.

We report two patients with occlusive cerebrovascular disease who were examined by means of benzodiazepine receptor SPECT(BZR-SPECT) with 123I-iomazenil (IMZ) before extracranial-intracranial bypass surgery (EC/IC bypass). Preoperative low perfusion areas detected by cerebral blood flow SPECT (CBF-SPECT) were divided into two parts on BZR-SPECT images. In the low perfusion areas where the BZR were preserved, regional cerebral blood flow (rCBF) increased on postoperative CBF-SPECT, but where the BZR were not preserved, rCBF did not increase on postoperative CBF-SPECT. On visual inspection, the SPECT images of postoperative CBF-SPECT appeared similar to those of preoperative BZR-SPECT. For evaluation of the ischemic brain condition itself, instead of the cerebral metabolism, the distribution and activity of cerebral neurons indicated by BZR-SPECT with IMZ might be utilized.

Aged↗

PubMed1999

Analysis on reassortment of rotavirus NSP1 genes lacking coding region for cysteine-rich zinc finger motif.

Rotavirus clones A5-10 and A5-16 isolated from a bovine rotavirus strain A5 possess NSP1 gene which has a point mutation generating a nonsense codon and a 500 base-deletion, respectively. As a result, the two A5 clones encode truncated NSP1 product which lacks cysteine-rich region forming zinc finger motif. In order to analyze reassortment of these mutated NSP1 gene with RNA segments from heterologous strains, we investigated a number of reassortant clones derived from coinfection with either A5-10, A5-16 or a reference strain A5-13 (possessing intact NSP1 gene) and either simian rotavirus SA11 or human rotavirus KU. In coinfection with SA11 and A5-13, selection rates of A5-13 segments in reassortants ranged approximately from 20 to 70% (46% for NSP1 gene). In contrast, in the reassortment between SA11 and A5-10 or between SA11 and A5-16, selection rates of NSP1 gene from A5-10 and A5-16 were only 1% (one clone) and 0%, respectively. In reassortants from crosses KU x A5-clones, selection rate of A5-13 NSP1 gene decreased to 15%, while 11 reassortants with A5-10 NSP1 gene (31%) and one reassortant with A5-16 NSP1 gene (2%) were isolated. Reassortants with A5-10 NSP1 possessed a single gene (segment 9 or 11) from KU in the genetic background of A5-10. One reassortant clone (cl-55) with A5-16 NSP1 gene possessed KU gene segments 3, 4, and 8-11. When single-step growth curves were compared, the reassortant cl-55 showed almost identical growth curve to that of KU, while KU showed a better replication than A5-16. These results indicated that although A5-10 or A5-16 NSP1 gene encoding the truncated NSP1 is selected into reassortants much less efficiently than normal NSP1 gene, the reassortants with the mutated NSP1 gene and RNA segments from heterologous strains normally replicated in cultured cells. Thus, cysteine-rich region of NSP1 was not considered essential for genome segment reassortment with heterologous virus.

Animals↗

PubMed1999

Functional analysis of the heterologous NSP1 genes in the genetic background of simian rotavirus SA11.

Function of rotavirus NSP1 was analyzed by using single-NSP1 gene-substitution reassortants, SKF, SDF, and SNF which have the NSP1 gene derived from human rotaviruses KU, DS-1, and canine rotavirus K9, respectively, in the genetic background of simian rotavirus SA11. The NSP1 genes from KU, DS-1, K9, and SA11 exhibited 58-76% nucleotide sequence identity to one another. No substantial difference in viral growth was observed among the reassortants and SA11. However, production of NSP1 was not detected in SNF when viral proteins were labelled with 35S-methionine during replication in MA104 cells, in contrast to SA11, SKF and SDF which exhibited evident expression of NSP1. Difference in reassortant formation was examined among the reassortant clones generated between human rotavirus strain 69M and either of SA11, SKF or SNF. Although reassortant formation rate was significantly lower in the cross 69M x SNF than the other crosses, selection rates of RNA segments from parent strain 69M in the resultant reassortants was similar among the crosses. Selectivity of homologous and heterologous NSP1 genes in SA11 background was also analyzed by mixed infection and multiple passages among the single-NSP1 gene-reassortants and/or SA11, KU NSP1 gene was selected most frequently, whereas homologous (SA11) NSP1 gene was least efficiently segregated. These results indicated that viral growth and genome segment reassortment with other viruses may not be influenced by the presence of heterologous NSP1 and its expression level, while genomic diversity of NSP1 genes might have been associated with the relative adaptability to the genetic background of SA11.

Animals↗

PubMed1999

Effects of imidapril on NOS expression and myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats.

OBJECTIVES: To elucidate the relationship between renin-angiotensin system and nitric oxide in hypertensive heart failure, we evaluated the effects of long-term treatment with imidapril, angiotensin-converting enzyme inhibitor, on endothelial-cell nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in the left ventricle (LV) and its relation to myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats (DS) fed a high-salt diet. METHODS: In DS rats fed an 8% NaCl diet after the age of 6 weeks, a stage of concentric left ventricular hypertrophy at 11 weeks (DSLVH) was followed by a distinct stage of fatal left ventricular failure with chamber dilatation at 18 weeks (DSCHF). Imidapril (DSCHF-I, n = 7, 1 mg/kg/day, subdepressor dose) or vehicle (DSCHF-V, n = 7) were given from DSLVH to DSCHF stage for 7 weeks, and age-matched (18 weeks) Dahl salt-resistant rats fed the same diet were served as control group (DR-C, n = 7). RESULTS: Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSCHF-V was significantly ameliorated in DSCHF-I using transthoracic echocardiography. The level of eNOS mRNA and protein in the LV was significantly suppressed in DSCHF-V compared with DR-C, and significantly increased in DSCHF-I compared with DR-C and DSCHF-V. The iNOS mRNA and protein and the fibrosis factor expression of type I collagen mRNA were significantly increased in DSCHF-V compared with DR-C, and significantly decreased in DSCHF-I compared with DSCHF-V. DSCHF-V demonstrated a significant increase in wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis. These changes in the microvasculature were improved significantly by imidapril. CONCLUSIONS: Subdepressor dose of imidapril may ameliorate the endothelial damage not only by inhibiting production of angiotensin II but also by promoting eNOS and inhibiting iNOS mRNA and protein expression in the LV, and this increased eNOS mRNA and protein level may have a role in the improvement of congestive heart failure and myocardial remodelling.

Analysis of Variance↗

PubMed1999

Severe stenosis of the internal carotid artery presenting as loss of consciousness due to the presence of a primitive hypoglossal artery: a case report.

BACKGROUND: Symptoms of ischemic attacks in the internal carotid system usually involve focal cerebral dysfunction, i.e., hemiparesis or aphasia. However, an ischemic attack in the vertebrobasilar artery system usually presents with combined symptoms. The variety of manifestations included in the vertebrobasilar profile makes the potential pattern of symptoms considerably more variable and complex than that in the carotid system. Manifestations can include syncope and also vertigo. METHOD AND RESULTS: A 42-year-old woman experienced frequent attacks of faintness with vertigo. Angiography demonstrated severe stenosis of the left internal carotid artery with a persistent primitive hypoglossal artery just distal to the stenosis. The right internal carotid artery was normal and cross circulation through the anterior communicating artery was not well developed. Both vertebral arteries were hypoplastic. The patient underwent carotid endarterectomy and, thereafter the episodes of syncope completely disappeared. CONCLUSION: It was supposed that global ischemia including the brain stem occurred because of stenosis of the left internal carotid artery attributable to the presence of a primitive hypoglossal artery.

Adult↗

PubMed1999

Aneurysm of the distal anterior inferior cerebellar artery at the medial branch: a case report and review of the literature.

BACKGROUND: Distal aneurysms of the anterior inferior cerebellar artery (AICA) are rare. Most have been located at the cerebellopontine angle. Only three cases, including ours, located in the medial branch of the AICA have been reported in the literature. METHODS: A 55-year-old female presented with epilepsy that she experienced for the first time. Computed tomography and magnetic resonance imaging revealed no abnormality. Digital subtraction angiography (DSA) disclosed a rare aneurysm at the medial branch of the distal anterior inferior cerebellar artery. In the blood workup on her admission, a mild inflammatory sign was found, and bacterial aneurysm was suggested as the presumptive differential diagnosis. Repeated DSA was performed 3 months after admission, but the aneurysm did not disappear. She then underwent a suboccipital craniotomy in the prone position. RESULTS: The aneurysm was clipped and partially resected for the pathological examination. Histologic examination revealed a true aneurysm. She was discharged without neurological deficit. CONCLUSIONS: In this report, we summarize the previous cases and discuss the location and clinical manifestations of aneurysms of the AICA through a review of the literature.

Angiography, Digital Subtraction↗