Biomedical subjects

T Fujiwara

Publications and source records attributed to T Fujiwara.

At least 397 records · Page 22Linked to original sources

PubMed1997

Performance evaluation of a large axial field-of-view PET scanner: SET-2400W.

The SET-2400W is a newly designed whole-body PET scanner with a large axial field of view (20 cm). Its physical performance was investigated and evaluated. The scanner consists of four rings of 112 BGO detector units (22.8 mm in-plane x 50 mm axial x 30 mm depth). Each detector unit has a 6 (in-plane) x 8 (axial) matrix of BGO crystals coupled to two dual photomultiplier tubes. They are arranged in 32 rings giving 63 two-dimensional image planes. Sensitivity for a 20-cm cylindrical phantom was 6.1 kcps/kBq/ml (224 kcps/microCi/ml) in the 2D clinical mode, and to 48.6 kcps/kBq/ml (1.8 Mcps/microCi/ml) in the 3D mode after scatter correction. In-plane spatial resolution was 3.9 mm FWHM at the center of the field-of-view, and 4.4 mm FWHM tangentially, and 5.4 mm FWHM radially at 100 mm from the center. Average axial resolution was 4.5 mm FWHM at the center and 5.8 mm FWHM at a radial position 100 mm from the center. Average scatter fraction was 8% for the 2D mode and 40% for the 3D mode. The maximum count rate was 230 kcps in the 2D mode and 350 kcps in the 3D mode. Clinical images demonstrate the utility of an enlarged axial field-of-view scanner in brain study and whole-body PET imaging.

Bone Neoplasms↗

PubMed1997

Purification and characterization of a glutamic-acid-specific endopeptidase from Bacillus subtilis ATCC 6051; application to the recovery of bioactive peptides from fusion proteins by sequence-specific digestion.

Screening cultures of nonpathogenic microorganisms led us to a glutamic-acid-specific endopeptidase from Bacillus subtilis ATCC 6051, which we purified and named BSase. The nucleotide sequence encoding BSase, with a molecular mass of 23,894 Da, completely agreed with that of the mpr gene, which had been reported by Rufo Jr. and Sloma et al. to encode a metalloprotease [J Bacteriol (1990) 172: 1019-1023 and 1024-1029 respectively]. However, enzymatic characterization revealed it to have the catalytic triad of a serine protease and not the consensus sequence of a metalloprotease, and it was inhibited by diisopropylfluorophosphate. We therefore consider BSase (mpr) to be a serine protease. In the alignment of the acidic-amino-acid-specific proteases, the proteases from bacilli have a highly conserved histidine residue, which is most important in the histidine triad in the proteases from streptomycetes. Furthermore, Ca2+ was necessary for its activity and stability. BSase cleaved the C-terminal glutamic acid with high specificity and was very stable over a wide pH range. On the basis of these properties, we tried to retrieve a bioactive peptide from a fusion protein by sequence-specific digestion, and succeeded in obtaining the bioactive peptide. BSase was found to be very useful as a tool for selective cleavage.

Amino Acid Sequence↗

PubMed1997

Surfactant proteins and stable microbubbles in tracheal aspirates of infants with respiratory distress syndrome: relation to the degree of respiratory failure and response to exogenous surfactant.

UNLABELLED: Surfactant proteins (SP-A and SP-BC), albumin (ALB), and stable microbubble (SM) count were measured in tracheal aspirates from infants with respiratory distress syndrome (RDS) receiving single-dose Surfactant-TA (surfactant group, n = 32) or no surfactant (control group, n = 12), and those without RDS (non-RDS group, n = 8) to determine biochemical and biophysical status of surfactant in the course of RDS after surfactant replacement. Surfactant therapy resulted in immediate and sustained elevations of SP-BC/ALB and SM count with a rapid fall in ventilatory index to levels measured in the non-RDS group, whereas these indices improved slowly in the control group. The SP-A/ ALB was initially low in both RDS groups and increased to levels measured in the non-RDS group by age 48 h. Multiple regression analysis showed that SP-BC/ALB, postnatal age, SM count, SM count/SP-A plus SP-BC, and surfactant therapy were independently associated with the severity of RDS as assessed by ventilatory index (r = 0.75, P < 0.0001; number of samples = 256). Infants with a relapse response to surfactant (n = 9) had levels of SP-A/ALB and SP-BC/ALB similar to those measured in the sustained group (n = 23), but had significantly lower SM count and SM count/SP-A plus SP-BC between 24 and 96 h of age. CONCLUSION: Surfactant therapy normalizes the surfactant and respiratory status of infants with RDS. Surfactant dysfunction rather than depletion may explain the relapse response seen in some surfactant recipients.

Albumins↗

PubMed1997

Acute disseminated demyelination due to primary human herpesvirus-6 infection.

UNLABELLED: A previously healthy 19-month-old boy developed acute encephalopathy, thrombocytopenia and hepatic dysfunction. Human herpesvirus-6 (HHV-6) DNA was found in his CSF during the acute stage of the disease by means of the polymerase chain reaction. T2-weighted MRI revealed high signal intensity in the left thalamus and left parieto-occipital deep white matter. The myelin basic protein concentration in the CSF was elevated suggesting acute demyelination. The patient is now 2.5 years old and has no sequelae. CONCLUSION: Since clinical course and neuroimaging after HHV-6 infection are similar to those in acute disseminated encephalomyelitis, clinicians must pay attention to primary HHV-6 infection in patients under 2 years old with white matter lesions.

Acute Disease↗

PubMed1997

Physiological and psychological assessment of sound.

The psycho-physiological effects of several sound stimulations were investigated to evaluate the relationship between a psychological parameter, such as subjective perception, and a physiological parameter, such as the heart rate variability (HRV). Eight female students aged 21-22 years old were tested. Electrocardiogram (ECG) and the movement of the chest-wall for estimating respiratory rate were recorded during three different sound stimulations; (1) music provided by a synethesizer (condition A); (2) birds twitters (condition B); and (3) mechanical sounds (condition C). The percentage power of the low-frequency (LF; 0.05 < or = 0.15 Hz) and high-frequency (HF; 0.15 < or = 0.40 Hz) components in the HRV (LF%, HF%) were assessed by a frequency analysis of time-series data for 5 min obtained from R-R intervals in the ECG. Quantitative assessment of subjective perception was also described by a visual analog scale (VAS). The HF% and VAS value for comfort in C were significantly lower than in either A and/or B. The respiratory rate and VAS value for awakening in C were significantly higher than in A and/or B. There was a significant correlation between the HF% and the value of the VAS, and between the respiratory rate and the value of the VAS. These results indicate that mechanical sounds similar to C inhibit the para-sympathetic nervous system and promote a feeling that is unpleasant but alert, also suggesting that the HRV reflects subjective perception.

Acoustic Stimulation↗

PubMed1997

Contribution of hypoxia to the development of cardiomyopathy in hamsters.

OBJECTIVE: It has been hypothesized that microvascular spasms cause cardiomyopathy. To elucidate the contribution of hypoxia to the development of cardiomyopathy, the newly-developed hypoxia tracer, Tc-99m nitroimidazole, was applied to detect myocardial hypoxia in a hamster model. METHODS: Tc-99m nitroimidazole (180 MBq) and I-125 iodoantipyrine (370 kBq) were injected into cardiomyopathic Syrian hamsters or control hamsters at age 10, 25, and 40 weeks (n = 6 in each group). The myocardial uptake of Tc-99m nitroimidazole was measured and dual tracer autoradiography was performed. RESULTS: Histologic study revealed that the cardiomyopathic hamsters at age 10, 25 and 40 weeks were in the myocytolytic stage, the fibrotic and healing stage, and the hypertrophy and dilatation stage, respectively. Tc-99m nitroimidazole uptake was significantly greater in the cardiomyopathic hamsters than in the controls at age 25 weeks (cardiomyopathic hamsters, 33.3 +/- 4.7% g dose/g; control, 25.2 +/- 3.1), whereas there were no significant differences between both strains at age 10 and 40 weeks. The quantified concentration of I-125 iodoantipyrine in the cardiomyopathic hamster at age 40 weeks was significantly lower than that in the controls. When the Tc-99m nitroimidazole uptake was normalized by I-125 iodoantipyrine concentrations, the cardiomyopathic hamsters at age 25 and 40 weeks showed significantly greater uptake than the controls. CONCLUSION: The myocardium in cardiomyopathic hamsters was hypoxic at the fibrotic and healing stage and may be hypoxic at the hypertrophy and dilatation stage. This may contribute to the development of cardiomyopathy.

Animals↗

PubMed1997

Modified Boerema technique for the closure of congenital abdominal wall defects to prevent incisional herniation and infection.

Tension and infection often cause wound dehiscence or incisional herniation after the fascial closure of congenital abdominal wall defects in neonates. To overcome these problems, a modification of the Boerema technique (a method for repairing large incisional hernia in adults) was applied to repair abdominal wall defects in 14 neonates. The efficacy of this technique is discussed in this report.

Abdominal Muscles↗

PubMed1997

Intestinal pacemaker C-KIT+ cells and synapses in allied Hirschsprung's disorders.

The cause of bowel dysmotility in allied Hirschsprung's disorders (AHDs) such as hypoganglionosis (HYPG), immature ganglia (IMG) and neuronal intestinal dysplasia (NID) remains unexplained. Recent experimental studies in mice have shown that c-kit gene product positive (C-KIT+) cells are responsible for intestinal pacemaker activity and that c-kit is also closely involved in synapse formation. To further understand the pathophysiology of AHDs, the authors used immunohistochemistry to study the distribution of C-KIT+ cells and synapses in the muscle layers of normal bowel from controls (12 cases) and bowel from patients with AHDs (10 patients; mean age, 3.0 years; 5 HYPG, 3 NID, 2 IMG). Anti-human C-KIT serum and monoclonal antibody 171B5 (a novel marker of synapses) were used for visualization of C-KIT+ cells and 171B5+ synapses, respectively. In normal bowel from controls and patients with AHDs, moderate to many C-KIT immunoreactive (C-KIT-IR+) cells were observed in the muscle layers. Myenteric plexuses were clearly demarcated by C-KIT-IR+ cells. 171B5 immunoreactive (171B5-IR+) synapses were abundant in the muscle layers and within the myenteric plexuses. In contrast, the number of C-KIT-IR+ cells or 171 B5-IR+ synapses was reduced in the muscle layers of bowel affected by AHDs, except within the myenteric plexuses, where there was a moderate to large number of 171B5-IR+ synapses identified. A lack of intestinal pacemaker C-KIT+ cells may be of great significance with respect to the bowel dysmotility associated with AHDs and also to the abnormal synapse formation seen in the muscle layers of bowel affected by these disorders.

Adolescent↗

PubMed1997

Complications after cyst excision with hepaticoenterostomy for choledochal cysts and their surgical management in children versus adults.

The aim of this study was to review the cases 200 children and 40 adults who had cyst excision combined with hepaticoenterostomy (CEHE) for choledochal cyst, with particular emphasis on post-CEHE complications and their surgical management. Patients who had CEHE at the age of 15 years or less were defined as children, and those aged 16 years or older were defined as adults. The mean age when patients became initially symptomatic was 3 years in children and 26 years in adults. Eleven adults became symptomatic as children (< or = 15 years of age). The mean age of CEHE in children and adults was 4.2 years and 35 years, respectively. The time interval between the onset of initial symptoms and CEHE was significantly less in children than in adults (P < .0001). Of the 200 children, 176 had primary CEHE, and 24 had secondary CEHE converted from cystoenterostomy or other biliary surgery. Seventy children had intraoperative cyst endoscopy, which enabled us to examine the proximal intrahepatic bile ducts for stenosis and debris, and to wash out debris, protein plugs, and stones from the intrapancreatic ducts. Of the 40 adults, 22 had primary CEHE, 18 had secondary CEHE. The mean follow-up period was 10.9 years in children and 10.7 years in adults. The number of patients with post-CEHE complications in children and adults was 18 (9.0%) and 17 (42.5%), respectively. The post-CEHE complication rate in children was significantly lower than in adults (P < .0001). The 18 children had 25 post-CEHE complications such as cholangitis, intrahepatic bile duct stones, pancreatitis, stone formation in the intrapancreatic terminal choledochus or pancreatic duct, and bowel obstruction. Twenty-seven post-CEHE complications developed in the 17 adults including 2 cases of cholangiocarcinoma. There were no post-CEHE complications in the 70 children who had intraoperative cyst endoscopy. No stone formation was seen in the 145 children who had CEHE at the age of 5 years or less. Eight stone formations were seen in seven (12.7%) of the remaining 55 children aged over 5 years. Stones developed in seven (17.5%) adults. The incidence of post-CEHE stone formation in children aged 5 years or less was significantly lower than in other children and adults (P < .0001). Reoperation was required in 15 children: revision of hepaticoenterostomy in 4, percutaneous transhepatic cholangioscopic lithotomy (PTCSL) in 1, excision of intrapancreatic terminal choledochus in 2, endoscopic sphincterotomy of the papilla of Vater in 1, pancreaticojejunostomy in 1, and laparotomy for bowel obstruction in 6. Ten adults required reoperations: revision of hepaticoenterostomy in 2, PTCSL in 2, left hepatic lobectomy in 1, endoscopic sphincterotomy in 2, exploratory laparotomy in 2, and adhesiolysis in 1. The authors conclude that early diagnosis followed by CEHE is the treatment of choice for choledochal cyst, and intraoperative cyst endoscopy is recommended as a valuable adjunct to CEHE.

Adolescent↗

PubMed1997

Acute effect of troglitazone on glucose metabolism in the absence or presence of insulin in perfused rat hindlimb.

Troglitazone (CS-045) is a new type of antidiabetic agent that decreases plasma glucose by enhancing insulin action in insulin-resistant diabetic animals and non-insulin-dependent diabetes mellitus (NIDDM) patients. To examine the direct effect of troglitazone on glucose metabolism and insulin action in skeletal muscle, we infused troglitazone solution into perfused rat hindlimbs in the presence of 6 mmol/L glucose and in the absence or presence of insulin. In the absence of insulin, even 50 mumol/L troglitazone did not elicit glucose uptake. Troglitazone did increase lactate and pyruvate release at concentrations of 20 mumol/L and higher; however, it decreased the ratio of lactate to pyruvate (L/P ratio) and increased oxygen consumption at concentrations higher than 5 and 20 mumol/L, respectively. In hindlimb muscle, 20 mumol/L troglitazone decreased glycogen content without changing fructose 2,6-bisphosphate (F2,6P2) content in the absence of insulin. Insulin infusion with 250 microU/mL obtained half-maximal effects, causing a 2.8-fold increase in glucose uptake and a 1.5-fold increase in lactate and pyruvate release. When 20 mumol/L troglitazone was infused for 30 minutes together with 250 microU/mL insulin, insulin-induced glucose uptake significantly increased 30 minutes after troglitazone infusion, and this increase was further augmented after withdrawal of troglitazone. In insulin plus troglitazone infusion at 30 minutes after troglitazone removal, glycogen content in hindlimb muscle was significantly decreased compared with that obtained with insulin infusion alone. In summary, in the absence of insulin, troglitazone does not elicit glucose uptake, but causes an increase in glycolysis accompanied by a decrease in muscle glycogen content and L/P ratio and an increase in oxygen consumption. In the presence of insulin, troglitazone increases insulin-induced glucose uptake, and this increase is further augmented after troglitazone removal. Addition of troglitazone to insulin infusion decreased the glycogen content in hindlimb muscle. This decrease in muscle glycogen content may trigger an enhancement of insulin-induced glucose uptake similar to that observed during muscle contraction or epinephrine treatment.

Animals↗

PubMed1997

Effects of vinconate on age-related alterations in [3H]MK-801, [3H]glycine, sodium-dependent D-[3H]aspartate, [3H]FK-506 and [3H]PN200-110 binding in rats.

We investigated the effects of age and (+/-)-methyl-3-ethyl-2,3,3a,4-tetrahydro-1 H-in-dolo[3,2,1-de] [1,5] naphthyridine-6-carboxylate hydrochloride (vinconate), an indolonaphthyridine derivative, on calcium channels, neurotransmitter receptor systems and immunophilin in Fischer rat brain using quantitative receptor autoradiography. [3H]MK-801, [3H]glycine, sodium-dependent D-[3H]aspartate, [3H]FK-506 and [3H]PN200-110 were used to label N-methyl-D-aspartate (NMDA) receptors, glycine receptors, excitatory amino acid transport sites, FK-506 binding proteins (FKBP) and voltage-dependent L-type calcium channels, respectively. [3H]Glycine and sodium-dependent D-[3H]aspartate binding significantly decreased in the frontal cortex, parietal cortex, striatum, nucleus accumbens, hippocampus, thalamus, substantia nigra and cerebellum of 24 month old rats in comparison with 6 month old animals. In contrast, [3H]MK-801, [3H]FK-506 and [3H]PN200-110 binding showed no significant changes in the brain of 24 month old rats. Intraperitoneal chronic treatment with vinconate (10 and 30 mg/kg, once a day for 4 weeks) dose-dependently ameliorated the significant reduction in [3H]glycine and sodium-dependent D-[3H]aspartate binding in the brain of 24 month old rats. These results demonstrate that glycine receptors and excitatory amino acid transport sites are more susceptible to aging processes than NMDA receptors, immunophilin and voltage-dependent L-type calcium channels. Furthermore, our findings suggest that vinconate may have a beneficial effect on age-related changes in glycine receptors and excitatory amino acid transport sites.

Aging↗

PubMed1997

Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on spatial memory and central cholinergic neurons in aged rats.

The effects of a novel prolyl endopeptidase inhibitor (PEP), (S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)- 1-pyrrolidinecar-boxamide (JTP-4819), on performance of the Morris water maze task and on central cholinergic function were investigated in aged rats. Spatial memory (escape latency, path length, and swimming speed to the platform) was impaired in aged rats performing the Morris water maze task when compared to young rats. Administration of JTP-4819 (1 mg/kg, p.o.) for 14 days improved this memory deficit in aged rats, as shown by the decrease in escape latency and path length. In addition, when JTP-4819 (at doses of 1 and 3 mg/kg, p.o.) was administered for 3 wk, it reversed the age-related increase of ChAT activity in the cerebral cortex and the decrease of 3H-choline uptake in the hippocampus. These data suggest that JTP-4819 ameliorates age-related impairment of spatial memory and partly reverses central cholinergic dysfunction, possibly due to the enhancement of neuropeptide function by inhibition of PEP mediated degradation of substance P, arginine-vasopressin, and thyrotropin-releasing hormone.

Acetylcholine↗

PubMed1997

A novel prolyl endopeptidase inhibitor, JTP-4819, with potential for treating Alzheimer's disease.

The pharmacological actions of JTP-4819, a new prolyl endopeptidase (PEP) inhibitor targeted for the treatment of Alzheimer's disease, are reviewed with respect to its effects on PEP activity, brain neurotransmitters, and memory-related behaviour in rats. JTP-4819 was shown to be a very potent and specific inhibitor of PEP. At nanomolar concentration, JTP-4819 inhibited the degradation of substance P, arginine-vasopressin, and thyrotropin-releasing hormone by PEP in supernatants of the rat cerebral cortex and hippocampus. Repeated administration of JTP-4819 reversed the aging-induced decrease in brain substance P-like and thyrotropin-releasing hormone-like immunoreactivity, suggesting that this drug may be able to improve the imbalance of peptidergic neuronal systems that develops with senescense by inhibiting PEP activity. JTP-4819 increased acetylcholine release from the frontal cortex and hippocampus, regions closely associated with memory, in both young and aged rats. In addition, it improved performance in several memory and learning-related tests (e.g., the Morris water maze task in aged or MCA-occluded rats and the passive avoidance test). This memory-enhancing effect of JTP-4819 may result from prevention of the metabolic degradation of brain neuropeptides by PEP as well as from the enhancement of acetylcholine release. Taken together, these unique and potent pharmacological actions of JTP-4819 suggest that it may have the potential to be used for treating Alzheimer's disease.

Alzheimer Disease↗

PubMed1997

Transient decrease of HPC-1/syntaxin-1A mRNA in the rat hippocampus by kainic acid.

HPC-1/syntaxin-1A is a neuronal protein of which the mRNA has an immediate early gene-like structure in its 3'-untranslated region. Whereas HPC-1/syntaxin-1A protein plays a crucial role in neurotransmitter release, little is known about HPC-1 gene expression. We demonstrate here that HPC-1 mRNA expression in rat hippocampal neurons in vivo decreased 8 h after kainic acid (KA) administration, but was restored thereafter. The transient decrease of HPC-1 mRNA upon KA administration suggests that the HPC-1 mRNA expression in neurons could be altered by excitation by trans-synaptic stimulation.

Animals↗

PubMed1997

Two different pathological conditions of photoparoxysmal responses in hereditary dentatorubral-pallidoluysian atrophy.

In order to reveal the pathophysiology of photoparoxysmal responses (PPRs) in photosensitive patients with hereditary dentatorubral-pallidoluysian atrophy (DRPLA) who had expansion of the CAG repeat in the DRPLA gene, we studied the characteristics of PPRs using optical filters with specific wavelength transmission. In two patients, the wavelength spectrum around 700 nm (670-720 nm) was apparently the only visible range essential for eliciting PPRs, and flash lights containing the essential wavelength elicited PPRs. In another patient, PPRs were elicited by flash lights above certain quantity of light and independent of the wavelength composition of the lights. These data suggest that two different pathological conditions contribute to PPRs in DRPLA patients; one condition depends on the essential wavelength spectrum around 700 nm, and the other not on the wavelength, but on the quantity of light. The condition contributing to PPRs in all three patients was not determined directly by the level of the CAG repeat expansion in the DRPLA gene.

Adult↗

PubMed1997

Effect of cerebral ischemia on dopamine receptors and uptake sites in the gerbil hippocampus.

Dopamine D1 and D2 receptors and uptake sites were studied in the gerbil hippocampus, parietal cortex and thalamus 1 h to 7 days after 10 min of cerebral ischemia using the occlusion of bilateral common carotid arteries. [3H]SCH23390 ([N-methyl-3H]R[+]-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-7-ol-be nzazepine) and [3H]mazindol were used as markers of dopamine D1 receptors and uptake sites, respectively. [3H]Nemonapride was used to label dopamine D2 receptors. No obvious alteration in [3H]SCH23390 and [3H]mazindol binding was found in the hippocampus up to 48 h after ischemia. These bindings showed a significant reduction in the hippocampus after 7 days of recirculation. In contrast, [3H]nemonapride binding was unaffected in the hippocampus during the recirculation periods. The parietal cortex and thalamus also exhibited no significant changes in [3H]SCH23390, [3H]nemonapride and [3H]mazindol binding after ischemia. MAP2 (microtubule-associated protein 2) immunoreactivity was unchanged in all regions up to 48 h after ischemia. Thereafter, a marked loss of MAP2-immunoreactive neurons was observed in the hippocampal CA1 and CA3 neurons 7 days after recirculation. These findings were consistent with histological observations with cresyl violet staining. Our results demonstrate that dopamine D1 receptors and dopamine uptake sites in the hippocampus are susceptible to cerebral ischemia, whereas dopamine D2 receptors in this region are particularly resistant. Furthermore, these findings suggest that dopamine transmission may not be major factor in producing ischemic hippocampal damage.

Animals↗

PubMed1997

Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: application of PET to drug pharmacokinetic study.

Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [11C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [11C]MAP using positron emission tomography (PET). A significant increase of [11C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization.

Animals↗

PubMed1997

Up-regulated expression of angiotensin II type 1 receptor gene in human pathologic hearts.

BACKGROUND: An accumulation of evidence suggests that the local renin-angiotensin system plays a role in the development of cardiac hypertrophy in vivo; however, it remains unknown how the expression of angiotensin II type 1 receptor (AT1), which mediates most of the cardiovascular effects of angiotensin II, is regulated in the left ventricles of human pathologic hearts. METHODS AND RESULTS: Expression of AT1 gene in the left ventricle wall of 14 autopsied human hearts was examined by reverse transcription polymerase chain reaction. The levels of AT1 messenger RNA relative to those of beta-actin messenger RNA in the left ventricle wall were increased 3.8-fold in the hearts with dilated cardiomyopathy (n = 4, P < .05) and 6.2-fold in the noninfarcted areas of hearts with old myocardial infarction (n = 4, P < .05), compared with the control hearts without any cardiac disease (n = 6). The increases in the relative AT1 messenger RNA level showed a positive correlation with myocyte diameter in the adjacent tissue (r = .927, P < .001 for dilated cardiomyopathy and r = .934, P < .005 for old myocardial infarctions) and with the extent of fibrosis (r = .880, P < .005 for dilated cardiomyopathy and r = .690, P < .05 for old myocardial infarction). CONCLUSIONS: Expression of AT1 in these human pathologic hearts was associated with myocardial cell hypertrophy and extent of fibrosis, a finding that further emphasizes the importance of the local renin-angiotensin system in the remodeling of human hearts with dilated cardiomyopathy and old myocardial infarction.

Adolescent↗