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Biomedical subjects

I Toda

Publications and source records attributed to I Toda.

At least 19 recordsLinked to original sources
PubMed2001

Laser in situ keratomileusis: association with increased width of palpebral fissure.

PURPOSE: To report the preoperative and postoperative palpebral fissure width in eyes undergoing laser in situ keratomileusis. METHODS: In a prospective study, 165 consecutive eyes of 87 patients (41 men and 46 women with a mean +/- standard deviation age of 32.9 (+/-9.5) years) had laser in situ keratomileusis using a Summit (Waltham, MA) APEX PLUS excimer laser and a Moria (Antony, France) LSK microkeratome. The width of palpebral fissure was measured preoperatively, 3 months or 6 months after laser in situ keratomileusis. Patients were classified into three groups as follows: hard contact lens users group (n = 61), soft contact lens users group (n = 63), and non-contact lens users group (n = 41). RESULTS: The average width of palpebral fissure increased after laser in situ keratomileusis in all three groups. The hard contact lens users group increased from 7.6 (+/-1.6) mm to 8.7 (+/-1.2) mm (P <.0001) and non-contact lens users group increased from 7.7 (+/-1.9) mm to 8.9 (+/-1.9) mm (P <.0001). CONCLUSION: These results suggest that laser in situ keratomileusis may be associated with an increase in the width of the palpebral fissure.

Adult↗
PubMed2001

Effect of laser in situ keratomileusis correction on contrast visual acuity.

PURPOSE: To evaluate the changes in contrast visual acuity (CVA) based on the amount of myopic correction with laser in situ keratomileusis (LASIK). METHODS: In this prospective study, patients with myopia ranging from -2.0 to -14.0 diopters (D) were divided into 2 groups: those with myopia less than -6.0 D (n = 20) and those with myopia greater than -6.0 D (n = 13). The CVA was measured preoperatively and 1 week and 1 and 3 months postoperatively using Variable Contrast Visual Acuity Charts. RESULTS: The patients with less than -6.0 D of myopia had a CVA decrease of 15% 1 week postoperatively, which recovered by 1 month, and a decrease of 2.5% 1 week and 1 month postoperatively, which recovered by 3 months. The patients with more than -6.0 D of myopia had a decrease of 15% and 2.5% at all postoperative times. CONCLUSIONS: After LASIK to correct myopia of greater than -6.0 D, there may be a persistent decrease in intermediate and low CVA. Patients should be informed preoperatively of this possible decrease in CVA.

Adult↗
PubMed2001

Lack of evidence for an increased microchimerism in the circulation of patients with Sjögren's syndrome.

OBJECTIVE: To examine the hypothesis that fetal microchimerism plays a part in the pathogenic process of Sjögren's syndrome (SS). METHODS: Genomic DNA samples were extracted from peripheral blood whole nucleated cells and the CD34+ cell enriched fraction of patients with SS and healthy women who had male offspring as well as nulliparous women. A Y chromosome-specific sequence was detected as a marker for fetal cells by a nested polymerase chain reaction (PCR) and by DNA hybridisation combined with PCR using specific primers and probes. All procedures were performed with great care to avoid the contamination of male DNA. RESULTS: A nested PCR and DNA hybridisation combined with PCR was established that can detect a single male cell out of 1.67x10(5) female cells. It was not possible to increase the sensitivity further because the amount of template DNA held in the PCR was limited. When these methods were used, no fetal cells were detected in any samples from patients with SS, though they were detected in whole nucleated cells from two healthy women who had delivered sons previously. CONCLUSIONS: The findings indicate that circulating fetal cells in patients with SS are uncommon (<1 in 1.67x10(5)), if they exist. With the conventional PCR based methods that were used, it is difficult to evaluate the quantitative difference in circulating fetal cells between patients with SS and healthy women.

Adult↗
PubMed2001

A significant role of stromal fibroblasts in rapidly progressive dry eye in patients with chronic GVHD.

PURPOSE: To elucidate histopathologic features of the lacrimal gland in chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. METHODS: Lacrimal gland specimens from five patients who had dry eye as part of the symptoms of chronic GVHD were examined by immunohistochemistry and transmission electron microscopy. Lacrimal gland specimens from five patients with Sjögren's syndrome (SS) were used as control samples. RESULTS: Lymphocytes, predominantly T cells, were found primarily in the periductal areas of the lacrimal gland from patients with chronic GVHD, whereas B cells were the dominant infiltrating cells in the acinar areas of the lacrimal gland from patients with SS. Notable findings in the lacrimal gland from patients with chronic GVHD were marked fibrosis of the glandular interstitium and an increase in the number of CD34(+) stromal fibroblasts. These findings were more prominent in patients with severe dry eye than in those with mild dry eye. Electron microscopic observations of the lacrimal gland from patients with chronic GVHD revealed that stromal fibroblasts were attached to various inflammatory cells, especially T cells, through primitive or rudimentary contacts. In addition, the presence of a well-developed rough endoplasmic reticulum in the fibroblasts and newly synthesized collagen fibrils in the extracellular matrix indicated an active production of extracellular matrix components. Electron micrographs revealed multilayered and thickened basal laminae of blood vessels, ducts, and lobules in the lacrimal gland of patients with chronic GVHD; however, these observations were infrequently observed in the lacrimal glands of patients with SS. CONCLUSIONS: The results suggest substantial differences in the lacrimal gland histopathology of patients with chronic GVHD and SS. In addition, it is likely that stromal fibroblasts are actively involved in the pathogenic process of chronic GVHD in the lacrimal gland by producing excessive extracellular matrix components.

Adult↗
PubMed2000

Angiotensin blockade inhibits SIF DNA binding activities via STAT3 after myocardial infarction.

The in vivo activation of transcription factors, which is important for cell regulation by gene expression, has not been well examined in myocardial infarcted heart. The purpose of this study was to determine whether myocardial signal transducer and activator of transcription (STAT) pathway is activated as sis-inducing factor (SIF) in infarcted heart, and to assess the angiotensin blockade on SIF activity in ischemic and non-ischemic myocardium of rat. Myocardial infarction was made by ligation of the coronary artery in Wistar rats. In electrophoretic mobility shift assay, myocardial SIF DNA binding activities gradually increased and reached to peak at 1 week in infarcted and non-infarcted regions after myocardial infarction. Imidapril and candesartan cilexitil significantly prevented the increase in SIF DNA binding activity in infarcted and non-infarcted regions. This increased SIF DNA complex was supershifted by specific anti-STAT3 antibody, indicating that increased SIF complex at least contained activated STAT3 proteins in myocardial infarcted heart. Furthermore, immunoprecipitation-Western blot analysis revealed that STAT3 of infarcted and non-infarcted regions were tyrosine-phosphorylated at 1 week after myocardial infarction. Imidapril and candesartan cilexitil prevented the increase in phosphorylated STAT3. Thus, the transcriptional activation of STAT3 through AT1 receptor may be partially involved in cardiac remodeling after myocardial infarction.

Angiotensin Receptor Antagonists↗
PubMed2000

Prognostic value of Doppler transmittal flow patterns and cardiac natriuretic peptides in patients with chronic congestive heart failure admitted for episodes of acute decompensation.

This study was designed to determine whether the restrictive filling transmitral flow velocity pattern is associated with increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It was also designed to evaluate the prognostic value of these parameters from patients with chronic congestive heart failure (CHF) admitted for episodes of acute decompensation. We performed Doppler echocardiography, measured plasma levels of ANP and BNP in 33 patients at the time of admission, and assessed the subsequent cardiac mortality for 3 months. Eleven patients (33%) had a restrictive filling pattern of deceleration time (DcT) < 120ms. Plasma ANP and BNP levels were markedly increased in all patients to 189 +/- 145 pg/ml and 865 +/- 559 pg/ml, respectively. Seventeen patients (52%) showed more than 700 pg/ml of plasma levels of BNP. There was a significant correlation of DcT with the plasma ANP level (r = -0.41, P = 0.017), and a better correlation of DcT with the plasma BNP level (r =-0.50, P = 0.003). The combined index of both shorter DcT (< 120 ms) and higher plasma BNP levels (>700 pg/ml) was the best predictor of cardiac mortality by Cox univariate analysis (chi2 = 5.87, P = 0.015). Furthermore, the sensitivity and specificity of this index for the detection of cardiac mortality were 80% and 86%, respectively. In conclusion, the combined analysis of the Doppler transmitral flow velocity pattern and measurement of the plasma BNP level is noteworthy since it is noninvasive and convenient. Moreover, it is extremely useful in predicting the prognosis for patients with chronic CHF admitted for episodes of acute decompensation.

Acute Disease↗
PubMed2000

Identification of androgen, estrogen and progesterone receptor mRNAs in the eye.

PURPOSE: Previous research has demonstrated that sex steroids exert a significant influence on the structure and function of numerous ocular tissues. To begin to explore the underlying basis of this hormone action, we examined whether various anterior and posterior tissues of the eye contain androgen, estrogen and progesterone receptor mRNAs. METHODS: Tissue samples were obtained from adult male and female rats, rabbits and humans, processed for the isolation of total RNA and analyzed by RT-PCR, agarose gel electrophoresis and Southern blot hybridization. All PCR amplifications included positive and negative controls. RESULTS: Our findings showed that androgen, estrogen and/or progesterone receptor mRNAs are present in the lacrimal gland, lacrimal gland acinar epithelial cells, meibomian gland, lid, palpebral and bulbar conjunctivae, cornea, iris/ciliary body, lens, retina/uvea, retina/choroid and retinal pigment epithelial cells of rats, rabbits or humans. CONCLUSIONS: Our findings demonstrate that sex steroid receptor mRNAs exist in a variety of ocular tissues and suggest that these sites may represent target organs for androgens, estrogens and/or progestins.

Animals↗
PubMed2000

Identification of androgen receptor protein and 5alpha-reductase mRNA in human ocular tissues.

BACKGROUND/AIMS: Androgens have been reported to influence the structural organisation, functional activity, and/or pathological features of many ocular tissues. In addition, these hormones have been proposed as a topical therapy for such conditions as dry eye syndromes, corneal wound healing, and high intraocular pressure. To advance our understanding of androgen action in the eye, the purpose of the present study was twofold: firstly, to determine whether tissues of the anterior and posterior segments contain androgen receptor protein, which might make them susceptible to hormone effects following topical application; and, secondly, to examine whether these tissues contain the mRNA for types 1 and/or 2 5alpha-reductase, an enzyme that converts testosterone to the very potent metabolite, dihydrotestosterone. METHODS: Human ocular tissues and cells were obtained and processed for histochemical and molecular biological procedures. Androgen receptor protein was identified by utilising specific immunoperoxidase techniques. The analysis of type 1 and type 2 5alpha-reductase mRNAs was performed by the use of RT-PCR, agarose gel electrophoresis, and DNA sequence analysis. All immunohistochemical evaluations and PCR amplifications included positive and negative controls. RESULTS: These findings show that androgen receptor protein exists in the human lacrimal gland, meibomian gland, cornea, bulbar and forniceal conjunctivae, lens epithelial cells, and retinal pigment epithelial cells. In addition, our results demonstrate that the mRNAs for types 1 and 2 5alpha-reductase occur in the human lacrimal gland, meibomian gland, bulbar conjunctiva, cornea, and RPE cells. CONCLUSION: These combined results indicate that multiple ocular tissues may be target sites for androgen action.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2000

Effects of metabolically ischemic, but viable, myocardium on QT dispersion in patients with acute myocardial infarction: a study with resting I-123-BMIPP/thallium-201 myocardial single-photon emission computed tomography.

In chronic Q-wave myocardial infarction, QT dispersion is closely correlated with infarct size, but this correlation has not been evaluated for acute myocardial infarction (AMI). The effects of abnormal fatty acid metabolism on QT dispersion were examined in 123 patients with AMI who underwent resting iodine-123-15-iodophenyl 3-methyl pentadecanoic acid (BMIPP)/thallium-201(201Tl) myocardial single photon emission computed tomography (SPECT) and electrocardiographic analysis in the subacute phase. The relationship between BMIPP and 201Tl was defined as match when the total defect score for BMIPP was equal to or smaller than that for 201Tl, and as mismatch when the total defect score for BMIPP was larger than that for 201Tl. Twenty-six patients (21%) demonstrated BMIPP-201Tl match and 97 (79%) demonstrated mismatch. Infarct size was closely correlated with QT dispersion (r=0.67, p<0.001) in patients with BMIPP-201Tl match, but weakly correlated (r=0.30, p<0.005) in patients with BMIPP-201Tl mismatch. For small infarctions, QT dispersion was significantly larger in patients with BMIPP-201Tl mismatch than in those with BMIPP-201Tl match (62+/-24 ms vs 41+/-18 ms, p=0.03), but did not differ between the 2 groups for large infarctions. This study shows that QT dispersion is influenced by infarct size and by the presence of metabolically ischemic but viable myocardium in patients with AMI.

Adult↗
PubMed2000

A reverse flow-metabolism mismatch pattern: a new marker of viable myocardium with greater contractility during dobutamine stress than myocardium with a flow-metabolism mismatch pattern.

Few studies have investigated the contractility of myocardium with a reverse flow-metabolism pattern; that is, greater uptake of nitrogen- 13-ammonia (NH3) than fluorine- 18-fluorodeoxyglucose (FDG) on positron emission tomography (PET). This study examined the contraction thickening represented by count increase in ECG-gated FDG-PET of myocardium with a reverse flow-metabolism pattern during low-dose dobutamine stress. Fifty-four patients with myocardial infarction were studied. Relative NH3 and FDG uptake (%NH3, %FDG) and %count increase were measured in 216 apical and 216 lateral segments on ECG-gated FDG-PET. The %count increase during low-dose dobutamine stress was greater in myocardium with a reverse flow-metabolism mismatch pattern than in myocardium with a flow-metabolism mismatch pattern (35.9+/-25.7% vs 24.6+/-15.9%, p=0.0221 in apical segments, and 38.4+/-22.6% vs 27.6+/-18.4%, p=0.0040 in lateral segments) despite smaller %FDG. A reverse flow-metabolism mismatch pattern should be noted as a new marker of viable myocardium with greater contractility during dobutamine stress than myocardium with a flow-metabolism mismatch pattern.

Aged↗
PubMed2000

[Prediction of restenosis after percutaneous transluminal coronary angioplasty using coronary flow reserve. Kansai Doppler Guide Wire Study Group].

This multi-center prospective study attempted to predict restenosis after percutaneous transluminal coronary angioplasty(PTCA) using coronary flow reserve. Intracoronary blood flow velocity was measured in 47 patients(37 males, 10 females, mean age 66 +/- 9 years) with a Doppler guide wire, following successful PTCA. Twenty-four patients had prior myocardial infarction. After successful PTCA, a Doppler guide wire was placed at the distal portion of the target lesion, and coronary blood flow velocity was measured before and during intravenous administration of adenosine triphosphate. Follow-up coronary angiography was performed 154 +/- 69 days after PTCA, and the diameter stenosis of the target lesion was measured using quantitative coronary angiography. Follow-up angiography showed restenosis in 13 patients(28%). Sensitivity and specificity for predicting restenosis were low(50%, 45%, respectively) with a post-PTCA% diameter stenosis cut-off point of 27%. Sensitivity and specificity were 67% and 61% with a minimal lumen diameter cut-off of 1.8 mm. The reference coronary artery diameter(cut-off point 2.5 mm) was better for predicting restenosis(sensitivity 78% and specificity 76%). Sensitivity and specificity were 62% and 67%, respectively, using coronary flow reserve(cut-off point 2.0). The restenosis rate of patients with a reference diameter of more than 2.5 mm was 10%, but 54% for those with less than 2.5 mm(p < 0.05). In patients with a reference diameter of less than 2.5 mm, coronary flow reserve was useful for predicting restenosis(cut-off point 1.9, sensitivity 71% and specificity 83%). Coronary flow reserve is useful for predicting restenosis after PTCA, when combined with reference coronary artery diameter.

Aged↗
PubMed2000

Effects of preinfarction angina on myocardial injury in patients with acute myocardial infarction: a study with resting 123I-BMIPP and 201T1 myocardial SPECT.

METHODS: Recent studies have suggested that patients with preinfarction angina have smaller infarcts and a better in-hospital outcome than those without angina. The mechanisms responsible for limitation of infarct size in the presence of preinfarction angina are unclear. We examined the effects of preinfarction angina on myocardial injury in patients with the first acute myocardial infarction with resting 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) 201TI myocardial scanning performed within 1 mo of infarction. RESULTS: Of 136 patients tested, 48 (35%) had preinfarction angina within 72 h before infarction, whereas 88 (65%) did not. BMIPP and 201TI defects were scored in 9 segments of the left ventricle (0 = normal, 1 = mild defect, 2 = moderate defect, 3 = severe defect, and 4 = no uptake). The total defect score was defined as the sum of the defect scores. There was no significant difference in percentage diameters of stenoses of infarct-related arteries, collateral circulation, total defect scores for BMIPP, or 201TI between the groups with and without preinfarction angina. However, the ratio of total defect score for 201TI to that for BMIPP was significantly smaller for patients with than for those without preinfarction angina (0.64 +/- 0.21 versus 0.74 +/- 0.25, respectively; P = 0.007). CONCLUSION: Preinfarction angina did not affect the areas at risk in acute myocardial infarction, as shown by BMIPP defect, but decreased necrotic myocardium in the areas at risk, as shown by 201TI defect, and increased metabolically damaged but viable myocardium, as shown by BMIPP and 201TI mismatch through unidentified mechanisms other than collateral circulation (e.g., ischemic preconditioning).

Angina, Unstable↗
PubMed2000

Androgen influence on the meibomian gland.

PURPOSE: The hypothesis in the study was that androgens control meibomian gland function, regulate the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer. To test this hypothesis, a study was conducted to determine whether androgen receptor protein exists in the epithelial cell nuclei of rat meibomian glands and, in addition, whether androgen deficiency and/or treatment influences the gross morphology, neutral lipid content, and fatty acid profile of the rabbit meibomian gland, as well as the appearance of the tear film lipid layer. METHODS: Rat lids were obtained and processed for immunohistochemistry. Meibomian glands from intact, androgen- and/or placebo-treated rabbits were analyzed by histology, and glandular lipids were evaluated by gas chromatography, high-performance liquid chromatography (HPLC), and mass spectrometry. The rabbit tear film lipid layer was assessed by interferometry. RESULTS: In the current study androgen receptor protein existed within acinar epithelial cell nuclei of rat meibomian glands; androgen deficiency was associated with alterations in the lipid content of the rabbit meibomian gland; 19-nortestosterone treatment modulated the fatty acid profile in the total and neutral lipid fractions of the rabbit meibomian gland; and androgens did not appear to influence the gross morphology of meibomian tissue or to exert a demonstrable effect on the rabbit tear film lipid layer. CONCLUSIONS: The findings show that the meibomian gland is an androgen target organ and that androgens influence the lipid profile within this tissue. However, the extent to which androgens regulate the production of these lipids and whether this action may impact tear film stability remain to be determined.

Androgens↗
PubMed1999

Androgens and dry eye in Sjögren's syndrome.

Sjögren's syndrome is an extremely complex and currently incurable autoimmune disorder, which occurs primarily in females, and is associated with lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye. We hypothesize that androgen deficiency, which reportedly occurs in primary and secondary Sjögren's syndrome (e.g., systemic lupus erythematosus, rheumatoid arthritis), is a critical etiologic factor in the pathogenesis of dry eye syndromes. We further hypothesize that androgen treatment to the ocular surface will promote both lacrimal and meibomian gland function and alleviate both "aqueous-deficient" and "evaporative" dry eye. Our results demonstrate that androgens regulate both lacrimal and meibomian gland function, and suggest that topical androgen administration may serve as a safe and effective therapy for the treatment of dry eye in Sjögren's syndrome.

Androgens↗
PubMed1999

Expression of transcripts for cysteine-rich secretory proteins (CRISPs) in the murine lacrimal gland.

Cysteine-rich secretory proteins (CRISPs) represent a family of evolutionarily conserved proteins which may play a role in the innate immune system and are transcriptionally regulated by androgens in several tissues. Transcripts for all three members of the CRISP family have now been identified in the murine lacrimal gland. RT-PCR using primers able to discriminate between the related CRISP forms allowed the amplification of fragments with the expected length. DNA sequencing revealed a complete identity with the hitherto characterized epididymal CRISP-1, testicular CRISP-2, and salivary gland CRISP-3. An analysis of several mouse strains indicated that all expressed the three CRISP forms, but in differing amounts. RT-PCR analysis of RNA isolated from acinar cells of lacrimal glands revealed that they expressed CRISP-1 and CRISP-2. Semiquantitative and quantitative analyses furthermore showed higher CRISP-1 and CRISP-3 mRNA levels in the lacrimal glands of male BALB/c and NOD mice when compared to females. Testosterone treatment of C3H/HeJ female mice was followed by an upregulation of the steady-state CRISP-1 but not CRISP-2 transcript levels. A comparable stimulation was observed for the mRNAs coding for parotid secretory protein (PSP), a factor previously shown to exhibit sexual dimorphism in the murine lacrimal gland. The expression of CRISP transcripts in the lacrimal gland is consistent with a function in the innate immune system.

Animals↗
PubMed1999

Impact of gender on exocrine gland inflammation in mouse models of Sjögren's syndrome.

Sjögren's syndrome is a complex autoimmune disorder, that occurs almost exclusively in females, induces extensive lymphocyte accumulation in lacrimal and salivary glands, and represents one of the leading causes of dry eye and mouth in the world. The purpose of this study was to determine whether the profound, gender-related differences observed in the magnitude of exocrine gland inflammation in Sjögren's syndrome may also be found in tissues of mouse models of this disorder. Lacrimal and submandibular glands were obtained from adult MRL/lpr, MRL+/+ (MRL+), NZB/NZW F1 (F1), C3H/lpr, C3H/gld (gld), C57BL/6-lpr/lpr [B6/lpr; with (bcl-2(+)/lpr) or without (bcl-2(-)/lpr) bcl-2 transgene insertion] and nonobese diabetic (NOD) mice after the onset of autoimmune disease, and processed for microscopy and image analysis. Our results showed that: (1) the extent of inflammation was significantly greater in lacrimal glands of female MRL/lpr, MRL+, F1, C3H/lpr and gld mice, and salivary glands of female MRL+, F1 and gld mice, relative to those of males; (2) the severity of inflammation in NOD mice showed a tissue-specific pattern: inflammation was far worse in lacrimal glands of males, whereas immune pathology was far greater in salivary tissues in females; and (3) no gender-related variations were present in the degree of inflammation in lacrimal glands of bcl-2(+)/lpr and bcl-2(-)/lpr mice or in submandibular tissues of MRL/lpr, C3H/lpr, bcl-2(+)/lpr and bcl-2(-)/lpr mice. Our findings demonstrate that gender-, strain- and tissue-related differences exist in the extent of inflammation in several mouse models of Sjögren's syndrome.

Animals↗
PubMed1999

Endomyocardial biopsy findings in patients with atrioventricular block in the absence of apparent heart disease.

The purpose of this study was to examine the histopathological findings of right ventricular endomyocardial biopsies from ten patients less than 60 years of age (47 +/- 9.8 (mean +/- SD) years) with documented atrioventricular block but without apparent heart disease. They underwent electrophysiological testing, echocardiography, coronary angiography, and right ventricular endomyocardial biopsy. Biopsy specimens were assessed for morphologic changes in myocyte diameter, fibrosis, disarray, and degeneration. Electrophysiological testing demonstrated atrioventricular nodal block in 2, intra-His bundle block in 2, and infra-His bundle block in 6 patients. Histology revealed evidence of myocardial fibrosis with either myocyte hypertrophy or disarray in 7 of the 10 patients. The results of electrophysiological testing did not correlate with the histopathological findings or severity. In one patient, heart failure appeared during the follow-up period. We conclude that patients with atrioventricular block of unknown etiology have histological abnormalities of the ventricular endomyocardium in addition to the conduction system disturbances. We consider such cases as constituting one of the disease groups of cardiomyopathy, and suggest that it is necessary to follow up the clinical course in these patients.

Adult↗