Search PubMed⌕ Search

Biomedical subjects

Y Hara

Publications and source records attributed to Y Hara.

At least 55 records · Page 3Linked to original sources
PubMed2001

Effect of tetra-peptide isolated from interleukin 1 (IL-1) on corneal epithelial wound healing in the rabbit.

To develop a new method for wound healing in case of injured corneal epithelium, the effects of the tetrapeptide (Val-Leu-Leu-Lys), showing the consensus sequence between human interleukin (IL)-1alpha and bovine parotid protein (parotin) on epithelial cell proliferation and elongation were analysed in vitro cell culture experiments on epithelial cells obtained from rabbit cornea. The peptide showed dose-dependent stimulatory effects on epithelial cell proliferation and elongation at 10-100 microg ml(-1)compared with the control experiments. Furthermore, the peptide also exhibited a significant wound healing activity for the epithelial cells in an in situ experiment using mechanically injured rabbit cornea, while the higher concentration of the peptide (100 microg ml(-1)) showed greater efficient results than a previously known agent, sodium hyaluronate (0.3%). In addition, no pyrogenic activity of this peptide was detected by the previously established pyrogenicity test using rabbits. These results suggest that the tetrapeptide (Val-Leu-Leu-Lys) is a promising agent for wound healing in the case of injured corneal epithelium.

Amino Acid Sequence↗
PubMed2001

Localization of gelatinolytic activity can be detected in breast cancer tissues by film in situ zymography.

BACKGROUND: Extracellular matrix-degrading proteinases secreted by malignant tumor cells have been thought to play an essential role in the processes of invasion and metastasis. However, existence and localization of gelatinase activity in breast cancer tissues have not been clarified. METHODS: We developed a novel film for highly reproducible detection and the localization of gelatinolytic activity. This film has a gelatin layer with a constant thickness 7 microm, and adequate crosslinking to control the speed of degradation by proteases. Cryosections of several breast cancer tissues were put on this gelatin film and incubated for 16 hrs at 37 degrees C. After staining with ponceau 3R dye, the digested area was evaluated under light microscopy. RESULTS: Digestion of gelatin was detected in more than 90%of breast cancer specimens, although it varied in degree and area for each case. In most cases, the gelatinolytic activity was located within cancer nests, and was not detected in stromal cells surrounding cancer cells. The gelatinolytic activity was inhibited by 1,10-phenanthroline, an inhibitor of matrix metalloproteinases (MMPs). CONCLUSIONS: In this study, the localization of net MMP activity was confirmed in breast cancer nest using film in situ zymography. Detailed analysis on the relationship between the strength or distribution of MMP activity and malignancy are anticipated in the future.

Azo Compounds↗
PubMed2001

Telomerase activity levels for evaluating the surgical margin in breast-conserving surgery.

To evaluate the efficiency of measuring telomerase activity levels in clinical diagnosis, we performed a semiquantitative analysis of telomerase activity in breast tumors and compared the results with the histological findings. Breast tissue adjacent to areas of cancer were also serially resected and checked for telomerase activity. The amount of telomerase activity in the breast cancers ranged widely, from 0.36 to 1180 units/microg, with 31 of the 34 (91.2%) showing a value above 1.0unit/microg. None of the normal breast tissues including mastopathy, and only 4 (23.5%) of 17 benign breast masses had values above 1.0unit/microg. Telomerase activity was detectable in serial sections of adjacent tissues as far as 10mm from the macroscopic tumor margin with histologically detectable cancer cells. Furthermore, telomerase activity was detectable in the scrape specimens obtained from the stump of the surgical margins for breast-conserving surgery, and this activity was in accordance with the histological findings. These findings show that conducting a semiquantitative assay of telomerase activity is useful for evaluating the surgical margin in breast-conserving surgery.

Biomarkers, Tumor↗
PubMed2001

Successful management of breast cancer with liver metastases with medroxyprogesterone acetate treatment.

A 38-year-old woman with cancer in the left breast underwent standard radical mastectomy. The estrogen receptor and progesterone receptor status of the primary tumor was unknown. Ten years after the surgery, a metastatic liver tumor was detected, and chemoendocrine therapy, consisting of cyclophosphamide, epirubicin, 5-fluorouracil (CEF) and medroxyprogesterone acetate (MPA) was initiated. The metastatic liver tumor showed a partial response after 11 cycles of such chemoendocrine therapy. Subsequently, MPA alone was given daily as maintenance therapy, and the disease has remained stable for 6 years. For women with metastatic breast cancer, complete remission is uncommon, and stable disease is a reasonable goal of successful therapy. In this respect, chemoendocrine therapy with CEF and MPA, followed by MPA alone as maintenance therapy, was successful in the patient reported here. Importantly, the patient's quality of life has remained favorable for several years after the partial response was achieved.

Adult↗
PubMed2001

Inhibition by epigallocatechin gallate (EGCg) of conjugative R plasmid transfer in Escherichia coli.

Epigallocatechin gallate (EGCg) in tea catechins blocked or significantly diminished the transfer of conjugative R plasmid between Escherichia coli C600 with plasmid R-222 (donor) and E. coli K-12 RC85 (recipient) in a dose-dependent manner. The inhibition rates of R plasmid transfer by EGCg were 42%-67% at 50-200 microg/ml, and up to 99% at 800 microg/ml. Nevertheless, EGCg, even at the concentration of 1600 microg/ml, was not sufficient to kill E. coli cells in 1 h, as confirmed by determining viable cells after incubation with various concentrations of EGCg. The result indicates that the bactericidal activity of EGCg against the two strains was not the main factor responsible for the inhibition of R plasmid transfer. This observation suggests the possibility that tea consumption may be effective in preventing R plasmid transfer in enteric bacteria.

Catechin↗
PubMed2001

A histopathological study of the role of periodontal ligament tissue in root resorption in the rat.

Whether periodontal ligament (PDL) tissue is capable of inducing root resorption was examined. The distal root of the rat molar was sectioned at the furcation and the PDL tissue removed from the root (non-PDL group, n=40). The distal root with the PDL intact was also prepared (PDL-intact group, n=40). The roots were transplanted into the dorsal skin of the rat. On the 1st, 3rd, 5th, 7th, 10th, 14th, 21st or 28th day after transplantation, the roots were removed together with surrounding dorsal subcutaneous tissue and were fixed, demineralized and embedded in paraffin. Serial sections from each block were stained with haematoxylin and eosin or by the tartrate-resistant acid phosphatase (TRAP) method to observe root-resorbing cell formation. Cyclo-oxygenase-2 (COX2) was also detected immunohistologically to examine prostaglandin E(2) production. On the 7th day after transplantation, multinucleated root-resorbing cells with TRAP were observed in the PDL-intact group. The number of TRAP-positive cells peaked on the 10th day after transplantation. COX2-positive cells were observed in PDL during the early experimental stages. No root resorption was seen in the non-PDL group. These results suggest that PDL tissue is involved in the formation of root-resorbing cells and root resorption.

Acid Phosphatase↗
PubMed2001

Immunohistological study of interferon-gamma- and interleukin-4-bearing cells in human periodontitis gingiva.

The purpose was to investigate the balance between interferon (IFN)-gamma- and interleukin (IL)-4-bearing cells in various human inflamed gingiva by immunohistochemistry. Gingival tissues obtained from patients with gingivitis or periodontitis were divided into three groups based on the degree of histopathological inflammation, mild, moderate and severe. The tissues were also divided into four groups according to the clinical probing depth (PD). IFN-gamma- and IL-4-bearing cells in gingival tissues were stained immunohistologically and counted. The ratio of IL-4-bearing cells to IFN-gamma-bearing cells was calculated for each section. IFN-gamma-bearing cells were widespread in the connective tissue and their number increased significantly with the severity of inflammation and an increase of PD. IL-4-bearing cells were located beneath the pocket epithelium and their number showed no significant differences among the inflammation or PD groups. The ratios of IL-4-bearing cells to IFN-gamma-bearing cells in the severe inflammation or deep PD groups were significantly lower than those in the moderate inflammation or shallow PD groups. These results suggest that a low ratio of IL-4-bearing cells to IFN-gamma-bearing cells might be involved in the destruction of periodontal tissue.

Adult↗
PubMed2001

Risk factors for the development of diabetic retinopathy in Japanese type 2 diabetic patients.

This study investigated the risk factors for development of diabetic retinopathy (DR) in 787 type 2 diabetic patients with no retinopathy at the first visit. The subjects were followed up for at least 3 years (mean, 6.7 years). Among the baseline factors, significant correlations were observed between the development of DR and HbA1c (P < 0.0001), the method of therapy (P < 0.005), the duration of diabetes at the first visit (P < 0.005) and the past maximal body mass index (BMI) (P < 0.01). No significant correlation was found with the blood pressure, age, gender, TC or BMI. Among the follow-up variables, the mean HbA1c (P < 0.0001) and duration of diabetes (P < 0.001) correlated significantly with DR development, whereas the blood pressure and age did not. We found that a 1% decrease in HbA1c led to a 35% reduction in the risk of development of DR during the follow-up. The patients whose HbA1c at the first visit was higher than the median value of 8.2% showed a higher probability of development of DR during the next 3 years even when the same blood glucose control was maintained during the follow-up. In conclusion, our study demonstrated that the most important risk factor influencing the development of DR was the blood glucose control. Moreover, we found that the glycemic level at the first visit also influenced the development of DR.

Adolescent↗
PubMed2001

Action sites of adrenomedullin in the rat brain: functional mapping by Fos expression.

The effects of intracerebroventricular (icv) administration of adrenomedullin (AM) and proadrenomedullin NH2-terminal 20 peptide (PAMP) on the expression of Fos in the central nervous system (CNS) were examined in conscious rats, using immunohistochemistry. Fos-like immunoreactivity (LI) was detected in various brain areas of the rats, including the supraoptic nucleus, the paraventricular nucleus, the locus coeruleus, the area postrema and the nucleus of the tractus solitarius 90 min after icv administration of AM. Few cells with Fos-LI were found in the CNS 90 min after icv administration of saline. Fos-LI was also detected in the various hypothalamic areas after icv administration of PAMP. These results suggest that centrally administered AM and PAMP may cause physiological responses through the activation of a neural network in the hypothalamus and the brainstem.

Adrenomedullin↗
PubMed2001

Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy.

OBJECTIVES: This study was designed to evaluate the beneficial effect of beta-blockers on circulating cytokine levels in patients with dilated cardiomyopathy (DCM). BACKGROUND: Elevated circulating levels of inflammatory cytokines have been reported in patients with DCM. However, alterations of the levels of inflammatory and anti-inflammatory cytokines in association with beta-blocker therapy are unknown. METHODS: We studied 32 patients with idiopathic DCM who had been treated with digitalis, diuretics and angiotensin-converting enzyme inhibitors. In addition to this combination therapy, beta-blockers were started in all patients. Serum levels of interleukin (IL)-10, tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNF-R1 and R2) were measured at baseline and 12 weeks after the initiation of beta-blocker therapy. We also measured plasma levels of neurohumoral factors, as well as left ventricular (LV) size and function. Ten age-matched subjects with no cardiac disease served as the control group. RESULTS: Baseline levels of IL-10, TNF-alpha and sTNF-R2 were significantly higher in patients with DCM than in control subjects (p < 0.05). There was a significant positive correlation between IL-10 and TNF-alpha levels (r = 0.545, p = 0.029). The TNF-alpha/IL-10 ratio correlated well with plasma epinephrine levels (r = 0.677, p = 0.025), and the level of sTNF-R2 was closely related to LV size. Serum levels of IL-10, TNF-alpha and sTNF-R2 were significantly decreased during beta-blocker therapy (p < 0.005). CONCLUSIONS: Our findings indicate that beta-blockers have an important immunoregulatory role in modifying the dysregulated cytokine network in DCM. This effect of beta-blockers may be partly responsible for the efficacy of therapeutic drugs for heart failure.

Adrenergic beta-Antagonists↗
PubMed2001

Investigation of commercial Mitolife as an antioxidant and antimutagen.

Coronary heart disease and many types of cancer are important diseases in the world and especially in Western countries. There are biochemical activation processes for low-density lipoprotein cholesterol and genotoxic carcinogens to reactive products. In part, these also involve the generation of active oxygen and reactive oxygen species. We investigated the effect of a natural product, MitoLife, which contains a mixture of fruit and tea extracts, on the oxidation of low-density lipoprotein cholesterol and the mutagenicity of five genotoxic carcinogens, specifically, 2-acetylaminofluorene, 2-aminoanthracene, 2-amino-3-methylimidazo[4,5-f]quinoline, aflatoxin B(1), and benzo[a]pyrene. A positive antioxidant control, polyphenon 60, a concentrate of green-tea polyphenols, was used to compare the effect of MitoLife with that of polyphenon. MitoLife displayed inhibiting effects in all series of tests at slightly lower effectiveness but with the same order of magnitude as the green-tea polyphenol product. Thus, MitoLife represents another means to decrease adverse effects associated with the oxidation of low-density lipoprotein cholesterol or of a series of carcinogens, some of which are in the human environment.

Antimutagenic Agents↗
PubMed2001

Synthesis of (-)-[4-3H]epigallocatechin gallate and its metabolic fate in rats after intravenous administration.

Because a great deal of attention has been focused on the metabolism of (-)-epigallocatechin gallate (EGCg), quantitative analysis of this compound is required. For this purpose we developed a method of chemical synthesis of [4-(3)H]EGCg. Synthesized [4-(3)H]EGCg showed 99.5% radiochemical purity and a specific activity of 13 Ci/mmol. To clarify the excretion route of EGCg, the radioactivity levels of bile and urine were quantified after intravenous administration of [4-(3)H]EGCg to bile-duct-cannulated rats. Results showed that the radioactivity of the bile sample excreted within 48 h accounted for 77.0% of the dose, whereas only 2.0% of the dose was recovered in the urine. The excretion ratio of bile to urine was calculated to be about 97:3. These results clearly showed that bile was the major excretion route of EGCg. Time-course analysis of the radioactivity in blood was also performed to estimate the pharmacokinetic parameters following intravenous administration of [4-(3)H]EGCg. In addition, EGCg metabolites excreted in the bile within 4 h after the intravenous dose of [4-(3)H]EGCg were analyzed by HPLC. The results showed that 4',4"-di-O-methyl-EGCg was present in the conjugated form and made up about 14.7% of the administered radioactivity.

Animals↗
PubMed2001

Metabolic fate of (-)-[4-(3)H]epigallocatechin gallate in rats after oral administration.

After oral administration of [4-(3)H]EGCg to rats, the radioactivity in blood, major tissues, urine, and feces was measured over time. The radioactivity in blood and most tissues remained low for 4 h postdose, began to increase after 8 h, peaked at 24 h, and then decreased. Major urinary excretion of radioactivity occurred in the 8-24 h period, and the cumulative radioactivity excreted by 72 h was 32.1% of the dose. The radioactivity in the feces was 35.2% of the dose within 72 h postdose. In the case of rats pretreated with antibiotics (antibiotic-pretreated rats), the radioactivity levels of the blood and urine were definitely lower than those in rats not pretreated with antibiotics (normal rats). The radioactivity recovered in the antibiotic-pretreated rat urine was estimated to be only (1)/(100) of that in the normal rat urine. These results clearly demonstrated that the radioactivity detected in the blood and urine of normal rats mostly originated from degradation products of EGCg produced by intestinal bacteria. Furthermore, a main metabolite in the normal rats was purified and identified as 5-(5'-hydroxyphenyl)-gamma-valerolactone 3'-O-beta-glucuronide (M-2). In feces of the normal rats, EGC (40.8% of the fecal radioactivity) and 5-(3',5'-dihydroxyphenyl)-gamma-valerolactone (M-1, 16.8%) were detected. These results suggested that M-1 was absorbed in the body after degradation of EGCg by intestinal bacteria, yielding M-1 with EGC as an intermediate. Furthermore, M-2 was thought to be formed from M-1 in the intestinal mucosa and/or liver, then to enter the systemic circulation, and finally to be excreted in the urine. Taking into account all of the above findings, a possible metabolic route of EGCg orally administered to rats is proposed.

Administration, Oral↗
PubMed2001

Bone resorption and local interleukin-1alpha and interleukin-1beta synthesis induced by Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis lipopolysaccharide.

Different types of periodontopathic bacterial lipopolysaccharide (LPS) exert various biological activities in vitro. However, whether or not these activities also occur in vivo remains unclear. Thus the present study investigates bone resorption, as well as local IL-1alpha and IL-1beta synthesis induced by Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis LPS in the periodontal tissue of mice. Both types of LPS were injected into mouse gingiva every 48 h and the animals were sacrificed 6 h after the 1st. 4th, 7th, 10th, 13th, 16th, 20th, or 24th injection. Bone resorption in the injected gingiva was histopathologically and histomorphometrically investigated and local concentrations of IL-1alpha and IL-1beta were detected using an enzyme-linked immunosorbent assay. The active resorption ratio was significantly higher in the group given the 10th injection of LPS from A. actinomycetemcomitans than in the group given P. gingivalis LPS. Furthermore, A. actinomycetemcomitans LPS stimulated significantly more synthesis of IL-1alpha than P. gingivalis LPS after the 4th and 10th injections. and of IL-1beta after the 4th, 7th, 10th, 13th, 16th and 20th injections. These results suggest that A. actinomycetemcomitans LPS is a more potent inducer of bone resorption and synthesis of IL-1alpha and IL-1beta in the short term than P. gingivalis LPS.

Aggregatibacter actinomycetemcomitans↗
PubMed2001

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive and -negative diffuse large B cell lymphoma.

We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was estimated from the number of further single base-substitutions, expressed as a percentage of the total number of nucleotides in 10 cloned PCR products for each case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases) and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024). These data may indicate that the cell origin of CD5+ DLBCL is different from that of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived from this unique subset.

Adult↗
PubMed2001

Angled rigid neuroendoscope for continuous intraoperative visual monitoring: technical note.

We developed and tested a new, angled rigid endoscope as a tool for performing continuous visual monitoring during microsurgery. The shaft of the scope is angled 110 degrees at its midportion using a prism. We used the scope continuously in 30 cases including 15 pituitary tumours, 7 brain tumours, 7 cerebral aneurysms, and one hemifacial spasm. For pituitary tumours the tip of the scope was positioned in the sphenoid sinus or in the cavity formed by tumour removal; for cerebral aneurysms it was placed behind the parent artery or the aneurysmal neck. Image quality was acceptable for intraoperative monitoring. In no case did the neuroendoscope have a deleterious impact on th e proper function of the microscope or surgical instruments. This angled rigid scope was more effective for intraoperative monitoring than conventional straight scopes.

Endoscopes↗
PubMed2001

A new technique for intraoperative visual monitoring during spinal surgery: angiofiber and endoscopic ultrasonography.

PURPOSE: This paper is focused on our clinical use of endoscopic ultrasonography (EUS) and angiofiber (AF) for spinal microsurgery. METHODS: EUS and AF were used in seven operations for syringomyelia and spinal tumor. We used EUS for extradural observation, and AF for extra and intra-dural, subarachnoid and intraluminal visual evaluation of the lesions. RESULTS: EUS images of the spinal cord, roots and lesions were clear, providing precise evaluation of the lesion and the course of the shunt tube in real time during surgery. AF could provide clear vision of the syrinx lumen or subarachnoid space. Because these fine instruments could be advanced under the unresected laminae, sonographic and endoscopic images were obtained from beyond the extent of laminotomy, where the microscope could not reach. CONCLUSION: Combined together, EUS and AF contributed to accurate and safe spinal surgery while minimising the laminotomy.

Adolescent↗