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Biomedical subjects

A Uemura

Publications and source records attributed to A Uemura.

At least 19 recordsLinked to original sources

Visual outcome after surgical removal of choroidal neovascularization in pediatric patients.

OBJECTIVE: To assess the visual outcome after surgical removal of choroidal neovascularization (CNV) in pediatric patients. METHODS: A retrospective, noncomparative, consecutive case series of 17 eyes undergoing surgical removal of CNV of various causes in patients aged 18 years and younger. RESULTS: The cause of the CNV was presumed ocular histoplasmosis syndrome in 11 eyes, idiopathic in 3, and optic nerve coloboma, ocular toxoplasmosis, and trauma in 1 eye each. Two eyes had CNV within 100 microm of the center of the foveal avascular zone (juxtafoveal CNV) and 1 eye had peripapillary CNV, while 14 eyes had CNV beneath the geometric center of the foveal avascular zone (subfoveal CNV). In eyes with subfoveal CNV, median preoperative Snellen visual acuity was 20/200 (range, 20/80-3/200). With a median follow-up of 27 months (range, 6-45 months), median final visual acuity was 20/50 (range, 20/20-2/200); 10 (72%) had improvement of 2 or more Snellen lines after surgery, and 6 eyes (43%) had final visual acuity of 20/40 or better. In 3 eyes with juxtafoveal CNV or peripapillary CNV, all eyes had improvement of 4 or more Snellen lines. Postoperative recurrent CNV developed in 6 (35%) of 17 patients; 2 of the eyes underwent a second vitrectomy and 4 received laser treatment for the recurrences. CONCLUSIONS: Pediatric patients may have good recovery of vision after surgical removal of CNV, and the removal of these membranes may be a viable alternative to laser photocoagulation in pediatric patients.

Adolescent↗

Subretinal surgery for choroidal neovascularization in patients with high myopia.

OBJECTIVE: To analyze the visual outcome in patients undergoing surgical removal of subfoveal choroidal neovascularization (CNV) in eyes with high myopia. METHODS: We retrospectively reviewed the medical records of 48 consecutive patients with high myopia (> or =6 diopters [D]) who underwent vitrectomy with surgical removal of subfoveal CNV. The patient population consisted of 2 groups. Group 1 included 23 patients with findings only of myopic degeneration, and group 2 included 25 patients with presumed ocular histoplasmosis syndrome and myopia of 6 D or more. RESULTS: In group 1, the visual acuity improved by 2 or more Snellen lines in 9 eyes (39%), decreased in 8 eyes (35%), and remained unchanged in 6 (26%), with a mean follow-up of 24 months (range, 8-60 months). The preoperative visual acuity was 20/40 or better in only 1 eye (4%), but 8 (35%) achieved a final visual acuity of 20/40 or better. In group 2, the visual acuity improved in 16 eyes (64%), was stable in 4 (16%), and deteriorated in 5 (20%), with a mean follow-up of 18 months (range, 6-44 months). Only 3 eyes (12%) had a preoperative visual acuity of 20/40 or better, but 11 (44%) achieved a final visual acuity of 20/40 or better. Recurrence occurred in 13 (57%) of the 23 eyes in group 1 and in 9 (36%) of the 25 eyes in group 2. Univariate analysis demonstrated a significant relation between younger patient age (group 1) and absence of postoperative CNV recurrence (group 2) and an improvement of visual acuity (P<.01). CONCLUSIONS: Surgical removal of CNV may provide visual benefit in selected cases of subfoveal CNV associated with high myopia. The determination of whether surgical intervention is appropriate in these cases requires a prospective, randomized, clinical trial.

Adolescent↗

[Subretinal surgery for choroidal neovascularization].

BACKGROUND: Ten years have passed since subretinal surgery for choroidal neovascularization (CNV) was developed. Many reports regarding the visual outcome after subretinal surgery have been published, which have revealed the role of the subretinal surgery, including long-term visual outcome and surgical complications. METHOD: Reports associated with subretinal surgery published in the past decade were used to clarify the indication for surgery, visual outcome, and surgical complications. RESULTS: The visual prognosis for patients with surgically excited CNV is variable, depending on the underlying disease. Patients with widespread defects of Bruch's membrane and retinal pigment epithelium (RPE), such as age-related macular degeneration, are probably not good candidates for surgery from the standpoint of recovering good visual acuity. On the other hand, patients with focal abnormalities in Bruch's membrane and the RPE, such as presumed ocular histoplasmosis or idiopathic CNV, may be good candidates for surgery. However, it has not been proved that subretinal surgery is superior to photocoagulation or observation. CONCLUSIONS: For the time being, we have to select patients for subretinal surgery on the basis of published reports. The Submacular Surgery Trial now being held in the United States will evaluate the role of subretinal surgery in the management of patients with choroidal neovascularization.

Choroidal Neovascularization↗

Histologic diagnostic rate of cardiac sarcoidosis: evaluation of endomyocardial biopsies.

BACKGROUND: An early diagnosis of cardiac sarcoidosis is important, particularly when considering the need for administering corticosteroid therapy. However, no reports are available on the success rate of diagnosis on the basis of biopsy findings in patients with cardiac sarcoidosis. This study investigated the diagnostic success rate of histologic evaluation of endomyocardial biopsy specimens in patients with this disease. METHODS AND RESULTS: Right ventricular endomyocardial biopsy was performed in 26 patients in whom cardiac sarcoidosis was strongly suspected according to the Diagnostic Criteria of Sarcoidosis, plus abnormalities on the electrocardiogram, cardiac radionuclide images, or in left ventricular wall motion. A mean of 4.0 sites were sampled per patient. In each case we determined whether a definitive diagnosis of cardiac sarcoidosis could be made histologically. Noncaseating granulomas were found in only 5 (19.2%) of the 26 cases, thus permitting a histologic diagnosis of cardiac sarcoidosis. A histologic diagnosis was made in 4 (36.4%) of 11 patients who exhibited a dilated cardiomyopathy-like clinical picture, in contrast to only 1 (6.7%) of 15 patients in whom conduction disturbances were the major clinical feature and whose left ventricular ejection fraction was within normal limits. CONCLUSIONS: The diagnostic rate achieved with biopsy in cardiac sarcoidosis is low; the patients with sarcoidosis and evidence of significant cardiac involvement should be treated for cardiac sarcoidosis despite negative myocardial biopsies for this disease.

Adult↗

Therapeutic effects of a calcium antagonist, lacidipine, on stroke-prone spontaneously hypertensive rats with cerebrovascular lesions.

The aim of this study was to investigate the therapeutic effectiveness of lacidipine in stroke-prone spontaneously hypertensive rat (SHRSP) with cerebrovascular lesions in comparison with nicardipine. SHRSP were fed 1% saline as drinking water. After the onset of stroke, saline was replaced with water and each drug was administered orally once a day for 3 weeks. In the drug-untreated group, recurrence of stroke was repeated, deterioration and amelioration of neurological deficits (ND) were repeated, and histological examination and measurement of regional blood flow (rBF) using nonradioactive colored microspheres performed at the end of treatment revealed severe damages and significantly decreased rBF in brain and kidney, respectively. In kidney, not only lacidipine (1 mg/kg) but also nicardipine (30 mg/kg) decreased vascular lesions and ameliorated low-rBF significantly. Both drugs also inhibited the recurrence of stroke completely even at a low dose that did not ameliorate severe hypertension. Neuronal damages and ND in each lacidipine-treated group were ameliorated significantly, whereas those in each nicardipine-treated group were slightly improved. Lacidipine at 1 mg/kg alone ameliorated the cerebral low-rBF significantly even at 24 hr after administration. These results suggest that a long-lasting improvement of low-rBF after stroke may be useful in the treatment of SHRSP with cerebrovascular lesions.

Animals↗

Demonstration of a Ca2+/calmodulin dependent protein kinase cascade in the hog heart.

Members of the Ca2+/calmodulin dependent protein kinase (CaMK) family and a CaMK cascade have been identified and well characterized in the brain, but little is known about their equivalents in the heart. Thus only CaMKII and its function have been reported so far. Therefore, we purified and characterized CaMKI and CaMK kinase (CaMKK) as an associated activator from the hog heart for the first time. The heart CaMKI was revealed to be the alpha isoform of brain CaMKI with a molecular weight of 41 kDa to phosphorylate cardiac phospholamban peptide, and to exhibit autophosphorylation requiring CaMKK. Heart CaMKK was found as a 67 kDa band and proved to be a different kinase from that in brain. These data indicate the existence of a heart specific CaMK cascade, consisting of CaMKI and CaMKK, along with CaMKII, which should be taken into account in any consideration of Ca2+ signal transduction.

Amino Acid Sequence↗

Oral-mucosal administration of IFN-alpha potentiates immune response in mice.

We studied the effects of oral-mucosal administration of murine interferon-alpha (Mu-IFN-alpha) on immune responses and infection with vaccinia virus (VV) in mice. When Mu-IFN-alpha was administered to sheep red blood cell (SRBC)-sensitized mice for 4 or 5 days, Mu-IFN-alpha significantly enhanced delayed-type hypersensitivity (DTH) and antibody production, with maximum enhancement of each at 1 IU/body. To investigate the antiviral effect of oral-mucosal Mu-IFN-alpha, mice were infected with VV, and Mu-IFN-alpha was administered for 15 days. Pocks were observed in the tail skin of infected mice, and Mu-IFN-alpha at doses of 1, 10, and 100 IU/body significantly suppressed pock formation. Also, VV-specific cytotoxic T cells (CTL) were observed in the spleen from the same mice at 7 days after infection, and Mu-IFN-alpha enhanced CTL activity at doses above 1 IU/body. These results suggest that the oral-mucosal Mu-IFN-alpha may have potentiating effects on cellular and humoral immune responses, which may contribute to its effects against VV.

Administration, Oral↗

Gene expression of the two heavy chains and one light chain forming the inter-alpha-trypsin-inhibitor in human tissues.

Human inter-alpha-trypsin-inhibitor (ITI) is a serine proteinase inhibitor with a molecular weight of 220 kDa which consists of 3 different polypeptides. The constitutive components are 2 heavy chains (H1 and H2 chains) and 1 light chain (L chain), and its inhibitory activity is considered to be derived from this L chain. It has also been reported that this L chain is almost identical to the trypsin inhibitor (UTI) occurring in human urine. We examined the gene expression of the ITI constitutive peptides in human tissues using the reverse transcription (RT) -PCR technique. As a result, the genes of the H1 chain were found to be expressed in various tissues, particularly strongly in the liver. On the other hand, the genes of the H2 chain were found to be strongly expressed in the adrenal glands, brain, kidneys, and lungs, as well as the liver. Further, the PCR amplification product of the L chain was strongly detected not only in the liver but also in the pancreas, kidneys, lungs, stomach and testes. These results suggest the possibility that the major tissue which produces ITI is the liver, and the H chains and L chain (UTI) are produced as a component of ITI- related proteins in other tissues as well as in the liver.

Alpha-Globulins↗

Human neutrophil elastase degrades inter-alpha-trypsin inhibitor to liberate urinary trypsin inhibitor related proteins.

Urinary trypsin inhibitor (UTI) is a physiological protease inhibitor and inter-alpha-trypsin inhibitor (ITI) is regarded as a precursor of UTI. The purpose of this study is to determine the mechanism of the UTI release from ITI. To examine this, ITI was digested by human neutrophil elastase at various concentrations, and UTI-related proteins which were of the same size as UTI were obtained. The amino acid sequence of the 15 amino acid residues at the N-terminal of UTI-related proteins, corresponded to that of UTI. The amino acid sequences of the small amount of peptides detected corresponded to those of peptides from the heavy chain1 (H1) and the heavy chain2 (H2) of ITI, suggesting that most UTI-related proteins do not combine with peptides from the H1 and H2 of ITI. It was also revealed that UTI-related proteins have several physiological activities similar to those of UTI, i.e., human trypsin inhibitory activity, human neutrophil elastase inhibitory activity, inhibition of tumor necrosis factor-alpha (TNF-alpha) production from rat macrophages and of superoxide production from rabbit leukocytes. These results demonstrated that ITI is a precursor of UTI which is digested by human neutrophil elastase to release UTI, and that its elastase inhibitory activity is derived from UTI.

Alpha-Globulins↗

National survey of the use of endomyocardial biopsy in Japan.

A national survey of endomyocardial biopsy procedures was conducted in Japan. Questionnaires were mailed to 852 institutions and statistical analysis of the 213 completed questionnaires (25.0% of the total) was performed. Cardiac biopsies were being performed at 134 of these institutions (62.9%), representing a 5.5-fold increase over 1980. A total of 19,964 cardiac biopsies have been performed in Japan. Specimens were obtained from the right ventricle at 113 institutions, and from the left ventricle at 76 centers. The Konno-Sakakibara bioptome was used at 32 institutions, whereas the long sheath method was used at 98 institutions. Sixty of the institutions (44.8%) had encountered ventricular wall perforation. The perforation rate of the two ventricles combined was 0.7% (147 of 19,964 cases), with a mortality rate of 0.05% (10 of 19,964 cases). Endomyocardial biopsy has become widespread in Japan, and its safety was ascertained by this national survey.

Adult↗

Feasibility of diagnosing chronic myocarditis by endomyocardial biopsy.

In studies of all the layers of autopsied hearts from patients with chronic myocarditis, local clusters of lymphocytes are frequently noted, in contrast with hearts obtained from patients with acute myocarditis. Myocardial biopsy specimens, however are no larger than about 2mm x 3mm. With this in mind, the present study was undertaken to determine whether chronic myocarditis can be diagnosed by endomyocardial biopsy. Specimens were obtained from seven patients in whom chronic myocarditis was confirmed by the clinical course and by autopsy findings. In H&E stained specimens, sites corresponding to the biopsy sites in both ventricles (right ventricular free wall, right ventricular side of the ventricular septum, left ventricular lateral wall) were selected at random (five sites each from the right and left ventricles in each patient) and examined under a light microscope. A mean of 5 or more lymphocytes per visual field (by light microscopy at 400-fold magnification), a proposed quantitative diagnostic criterion of myocarditis, was noted in the right ventricle in three patients (5 lymphocytes in two patients and 6 in one patient) and in the left ventricle in one patient (5 lymphocytes). Also, when the presence of lymphocyte clusters, considered to be a characteristic feature of chronic myocarditis, was determined, clusters of 20 or more lymphocytes per visual field were found in the same patients as those mentioned above, namely, in three patients (42.8%) in the right ventricle, as mentioned above, and in one patient (14.3%) in the left ventricle. At the sites of these lymphocyte clusters. findings such as degenerative changes of the myocardial cells and interstitial fibrosis were also associated, making possible a diagnosis of myocarditis. Therefore, in chronic myocarditis, even if five specimens are obtained by right ventricular biopsy, in approximately one half of patients the diagnosis of chronic myocarditis will be missed because of sampling errors.

Adolescent↗

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↗

Effects of a calcium antagonist, lacidipine, on experimental focal cerebral ischemia in rats.

We investigated the effects of lacidipine on focal cerebral ischemia in rats, and these effects were compared with those of nicardipine. Drugs were administered orally 5 min after middle cerebral artery occlusion (MCAO). Neurological scores as described by Bederson et al. (Stroke 17, 472-476, 1986) and cerebral infarct size (CIS) determined by the 2,3,5-triphenyltetrazolium chloride staining method were measured 24 hr after MCAO. Cerebral blood flow (CBF) and energy metabolites were determined by the hydrogen clearance method and an enzymatic method, respectively. In the drug-untreated group, we observed low-CBF of approximate 13 ml/100 g/min during 0.5-6 hr of occlusion and extensive cerebral infarction associated with severe neurologic deficits (ND). Lacidipine at 1 and 3 mg/kg, although it lowered blood pressure, improved low-CBF to approximate 20 ml/100 g/min during 1.5-6 hr of occlusion and increased tissue levels of ATP 6 hr after MCAO in a dose-dependent manner. Nicardipine at 30 mg/kg also improved low-CBF and increased tissue levels of ATP significantly. However, the improvement of low-CBF by nicardipine was transient. Lacidipine at 3 mg/kg reduced CIS and ameliorated ND significantly. In contrast, nicardipine at 30 mg/kg could not ameliorate ND in spite of a significant reduction of CIS similar to that of lacidipine (3 mg/kg). These results suggest that the improvement of focal cerebral ischemia by lacidipine may be partly due to long-lasting improvement of collateral blood supply to the ischemic area.

Adenosine Triphosphate↗

Spatial memory disturbance after focal cerebral ischemia in rats.

We investigated the impairment of retention of spatial memory in rats with chronic focal cerebral ischemia, and examined the correlation between this impairment and pathological outcomes. A preoperative acquisition trial of the Morris water-maze task was performed twice a day for 14 successive days, and then the middle cerebral artery (MCA) was occluded. A retention trial was performed 8 weeks after MCA occlusion. Escape latency and swimming path length to the platform were significantly increased in MCA-occluded rats compared with those of sham-operated rats, and these deficits significantly correlated with massive shrinkage of the brain. Retention latency of a passive avoidance task, which was trained preoperatively, was also significantly shortened in MCA-occluded rats compared with that in sham-operated rats. These results suggest that chronic focal cerebral ischemia causes prolonged spatial memory disturbance in rats and is associated with pathological changes, and that this rat model may be useful for assessing not only anterograde but also retrograde amnesia caused by focal cerebral ischemia.

Animals↗