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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 217 records · Page 12Linked to original sources

Ophthalmomyiasis caused by Sarcophaga crassipalpis (Diptera: Sarcophagidae) in a hospital patient.

Nine sarcophagid larvae were found on the right eyelid, cornea, and bulbar conjunctiva of a debilitated patient in a hospital in Osaka, Japan. Inflammation of the right eyelid and conjunctival congestion, probably initiated or aggravated by the larvae, were found. The larvae were removed and reared for accurate identification, and, on the basis of the characteristics of the 3rd instar and adult flies, the species was identified as Sarcophaga crassipalpis Macquart. This is a report of ophthalmomyiasis caused by this facultative parasite in a human. Patients with diminished consciousness in hospitals need protection from flies.

Aged↗

The acidic domain and first immunoglobulin-like loop of fibroblast growth factor receptor 2 modulate downstream signaling through glycosaminoglycan modification.

Fibroblast growth factor receptors (FGFRs) are membrane-spanning tyrosine kinases that have been implicated in a variety of biological processes including mitogenesis, cell migration, development, and differentiation. We identified a unique isoform of FGFR2 expressed as a diffuse band with an unusually large molecular mass. This receptor is modified by glycosaminoglycan at a Ser residue located immediately N terminal to the acidic box, a stretch of acidic amino acids. The acidic box and the glycosaminoglycan modification site are encoded by an alternative exon of the FGFR2 gene. The acidic box appears to play an important role in glycosaminoglycan modification, and the presence of this domain is required for modification by heparan sulfate glycosaminoglycan. Moreover, the presence of the first immunoglobulin-like domain encoded by another alternative exon abrogated the modification. The high-affinity receptor with heparan sulfate modification enhanced receptor autophosphorylation, substrate phosphorylation, and ternary complex factor-independent gene expression. It also sustained mitogen-activated protein kinase activity and increased eventual DNA synthesis, a long-term response to fibroblast growth factor stimulation, at physiological ligand concentrations. We propose a novel regulation mechanism of FGFR2 signal transduction through glycosaminoglycan modification.

Alternative Splicing↗

Indocyanine green angiographic features prognostic of visual outcome in the natural course of patients with age related macular degeneration.

AIMS: To determine indocyanine green (ICG) angiographic features prognostic of visual acuity loss in eyes following a natural course of exudative age related macular degeneration (AMD). METHODS: 89 eyes of 72 patients (48 men, 24 women) aged between 50 and 87 years old (mean 69.5 (SD 8.8) years) with classic and/or occult choroidal neovascularisation (CNV) were reviewed. ICG angiographic features were classified as follows: type 1, well demarcated hyperfluorescence with late ICG leakage; type 2, well demarcated hyperfluorescence with no late dye leakage; type 3, poorly demarcated hyperfluorescence; type 4, no hyperfluorescence. Follow up ranged from 6 to 67 months (mean 19.2 (11.5) months). Logistic regression analyses were performed using change of visual acuity (worse or not) as the dependent variable, and patient age, sex, characteristics of fluorescein angiography (classic or occult CNV), location of CNV, and each ICG type as the independent variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Type 1 CNV was associated with the highest risk for visual acuity loss (OR: 7.50, CI: 1.42-39.55, p = 0.018) among the present variables. In contrast, CNV having no ICG leakage (type 2, 3, and 4), represented no significantly increased risk. CONCLUSION: Well demarcated hyperfluorescence with late ICG leakage appears to be predictive of visual acuity loss in eyes with CNV. Thus, ICG angiography may offer a useful means of predicting visual outcomes in AMD.

Aged↗

Subtraction ICG angiography in Harada's disease.

BACKGROUND/AIM: The significance of indocyanine green (ICG) angiography (ICGA) in Harada's disease still awaits clarification in many respects. This study investigates the details of choroidal lesions observed in Harada's disease by the subtraction method. METHODS: Eight patients with Harada's disease were followed with ICGA. ICG angiograms were obtained with a Topcon high resolution digital fundus camera and processed with a Topcon IMAGEnet computer system. Image subtraction was conducted for analysing serial angiograms taken at about 2 second intervals during the dye transit phase and those taken in the early and middle phases of angiography. RESULTS: Standard ICG images of acute stage disease showed delayed choroidal filling in the early phase. Mid phase angiograms showed areas with bright fluorescence of variable intensity, indicating intrachoroidal ICG leakage. With image subtraction of angiograms with an interval of seconds the choroidal vessels could be imaged sequentially, with the choroidal arteries visualised first, followed by the definition of the choriocapillaris and then the choroidal veins. The choroidal veins with delayed filling were visualised as positive images in serial subtraction angiograms. Subtraction with an interval of minutes showed uneven background fluorescence and bright fluorescence corresponding to the areas of intrachoroidal ICG leakage. After the disease subsided with steroid therapy, angiography revealed an improvement in delayed choroidal filling. Image subtraction by the second allowed a clear visualisation of improved choroidal venous filling, while subtraction by the minute showed homogeneous background fluorescence, eliminating brighter areas. CONCLUSION: Subtraction ICGA demonstrated that delayed filling of the choroidal veins of varying severity occurs in association with hyperpermeability of the choroidal vessels in the course of Harada's disease.

Adult↗

Effect of retinoic acid on proliferation and polyamine metabolism in cultured bovine retinal pigment epithelial cells.

Reports regarding the effect of all-trans-retinoic acid (RA) on the cell growth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells and to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 microM RA significantly increased both cell number and [3H]thymidine incorporation. RPE cells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activity and spermidine/spermine N1-acetyltransferase (SAT) activity of RA-treated RPE cells were significantly greater until 8 and 16 h after incubation, respectively. The putrescine content was significantly increased in RA-treated RPE cells up until 24 h, while spermidine, spermine and N1-acetylspermidine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of RPE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.

Adenosylmethionine Decarboxylase↗

Clinical study of brain metastasis of renal cell carcinoma.

OBJECTIVES: To evaluate the natural history and the efficacy of treatments for renal cell carcinoma (RCC) with brain metastasis, we reviewed 18 patients with this disease. METHODS: Out of 325 cases with RCC treated at Osaka University Hospital from 1957 to 1993, 18 (5.5%, male:female ratio 16:2) cases developed brain metastases. Median follow-up was 44 months after the initial treatment of the primary lesion. Twelve patients had surgical resection of brain metastases (surgical group), and 7 of them received adjuvant radiotherapy. Six patients with poor performance status were treated with supportive therapy alone (nonsurgical group). RESULTS: Of 18 RCC patients with brain metastasis, 16 were male and 2 female. All brain metastases except for 1 case were symptomatic. Median interval between the initial treatment of the primary lesion and the diagnosis of brain metastasis was 19 months. The most frequent metastatic site prior to brain was the lung, which was detected in 7 cases (38.9%). Median survival of the entire group, measured from the onset of brain metastasis, was 9.5 months. One-year survival rate after the diagnosis of brain metastasis was 43.2% (64.8% in surgical group, 0% in nonsurgical group), 3-year 18.5% and 5-year 0%. Among 109 metastatic RCC, 14 patients were treated by lymphokine-activated killer (LAK) therapy. Out of 14 metastatic RCC patients treated by LAK therapy, 3 (21.4%) developed brain metastases. On the other hand, out of 95 metastatic RCC patients without LAK therapy, 15 (15.8%) had brain metastases. There was no significant difference in the rate of brain metastases between these two groups. CONCLUSION: There was a trend for prognosis of the surgical group to be better compared to that of the nonsurgical group, although it is not statistically significant. The optimum treatment for brain metastasis of RCC remains undefined, but our data suggested surgical resection in selected patients might contribute to prolonged survival of patients with brain metastasis. LAK therapy was not necessarily the risk factor of the brain metastasis.

Adult↗

The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells.

ATP-sensitive K+ channels (KATP channels) play important roles in many cellular functions by coupling cell metabolism to electrical activity. The KATP channels in pancreatic beta-cells are thought to be critical in the regulation of glucose-induced and sulfonylurea-induced insulin secretion. Until recently, however, the molecular structure of the KATP channel was not known. Cloning members of the novel inwardly rectifying K+ channel subfamily Kir6.0 (Kir6.1 and Kir6.2) and the sulfonylurea receptors (SUR1 and SUR2) has clarified the molecular structure of KATP channels. The pancreatic beta-cell KATP channel comprises two subunits: a Kir6.2 subunit and an SUR1 subunit. Molecular biological and molecular genetic studies have provided insights into the physiological and pathophysiological roles of the pancreatic beta-cell KATP channel in insulin secretion.

ATP-Binding Cassette Transporters↗

Unresponsiveness to glibenclamide during chronic treatment induced by reduction of ATP-sensitive K+ channel activity.

The insulin response to the sulfonylurea glibenclamide was markedly impaired in pancreatic beta-cell line MIN6 cells with chronic glibenclamide treatment (MIN6-Glib). The intracellular calcium concentration increased only slightly in response to glibenclamide in MIN6-Glib. While the properties of the voltage-dependent calcium channels were not altered, the conductance of the K(ATP) channels, the primary target of glibenclamide, was significantly reduced in MIN6-Glib. The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits. MIN6 cells have both high- and low-affinity binding sites for glibenclamide. The binding affinities at these two sites were unchanged, but the maximum binding capacities at both sites were similarly increased by chronic glibenclamide treatment. Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib. In addition, electron microscopic examination revealed a majority of the SUR1 to be present in a cluster near the plasma membrane in control MIN6, while it tends to be distributed in the cytoplasm in MIN6-Glib. These data suggest that chronic glibenclamide treatment causes the defect in acute glibenclamide-induced insulin secretion by reducing the number of functional K(ATP) channels on the plasma membrane of the beta-cells.

ATP-Binding Cassette Transporters↗

[An analysis of questionnaires about geriatric medicine/medical education sent to members of the Japanese Society of General Medicine].

Geriatric medical care can be viewed as general medical care for the elderly. We conducted a survey of members of the Japanese Society of General Medicine who belong to a university hospital, on their views of geriatric medicine/medical education. The questionnaires consisted of six categories of items about: (1) the physician's career; (2) whether the physician performs geriatric research in his/her laboratory; (3) whether the physician has an interest in geriatric medicine or medical education; (4) the physician's views on geriatric medicine or medical education; (5) of what pre- and post-graduate medical education on geriatric medicine should consist, from the physician's point of view: and (6) the physician's ideas about geriatric medicine/medical education in view of general medicine. Out of the 181 questionnaires sent, 96 (53%) people replied, of whom 51 (53.1%) were members of a Department of General Medicine, 57 (60%) were teaching staff, 46 (48.4%) had experience in home medical care such as home visits, and 17 (18.1%) belonged to the Japanese Society of Geriatric Medicine. Seventy-six respondents (85.4%) had an interest in geriatric medicine/medical education. Of the respondents, 96.8% recognized the need for pre- and post-graduate medical education concerning geriatrics. Some members of the Japanese Society of General Medicine who answered the questionnaire see geriatric medicine as entirely general medicine, and also that geriatric medicine is important, necessary and special. In addition, they see that the field of geriatric medicine is not yet developed in regard to geriatric medical care and education. Most respondents could not specify which section in a medical university is responsible for teaching the fields of basic and social medicine. This result shows that it may be difficult to incorporate pre-graduate geriatric medical education into the curriculum. As part of the pre-graduate curriculum of medical education on geriatrics, a practical exercise such as inspection of a geriatric hospital and geriatric home was considered most desirable by the respondents. Out of nine items, the top three most important aspects of post-graduate medical education on geriatrics for clinical and social medicine, were (1) studying the medical care and welfare of the elderly, (2) assessing the impaired life function of the elderly, and (3) studying pharmaco- therapy. Out of 6 items, the top three most important aspects of a practical exercise in post-graduate medical education in geriatrics were (1) providing general care to the elderly, (2) giving rehabilitation guidance and (3) providing psychological support for the elderly. Furthermore, 20 of the respondents (22.5%) have performed geriatric medical research on either the activities of daily life of the elderly or living wills, both of which seem to reflect the health and life of elderly people.

Attitude of Health Personnel↗

[The investigation of age-specific PSA reference range as the cut-off values in the mass screening for prostatic cancer].

BACKGROUND: The objective of this study is to determine age-specific PSA reference ranges in Japanese healthy men and investigate the effectiveness of these ranges as the cut-off values in the mas screening for prostatic cancer. METHODS: The study included a total of 5,206 male aged from 55 to 89 years old who wished to submit the mass screening for prostatic cancer in an urban area of Kyoto in 1995-1997, but had no evident prostatic cancer. We measured serum PSA levels by the filter paper method (Delfia PSA kit). RESULTS: We found the increase in serum PSA levels with the advancing age. With the 95th percentile for serum PSA as the upper limit, the age-specific PSA reference ranges were determined to be 2.1 ng/ml for patients aged 55 to 59 years old, 3.2 ng/ml for 60 to 69 years old, 4.4 ng/ml for 70 to 79 years old, 6.5 ng/ml for 80 to 89 years old. If we used these ranges as the cut-off values in the mass screening this time, five cases from 76 to 89 years old of prostatic cancer were overlooked. CONCLUSIONS: We found the increase in serum PSA levels with advancing age. But the positive proof of using this range to a mass screening for prostatic cancer was not certified, because time incidence of prostatic cancer in the examinees was uncertain and there is a possibility of overlooking some cases.

Age Factors↗

[Genomic instability and neurodegenerative disease].

The discovery of unstable DNA sequences as the cause of genetic disease is a fascinating new area in human genetics, raising a number of important questions addressing the understanding of both the mechanisms and the effects of this new type of mutation. Trinucleotide repeat expansion mutations have been identified in a number of neurodegenerative diseases, including spinal and bulbar muscular atrophy (SBMA), fragile X syndrome (FRAXA and FRAXE), myotonic dystrophy (DM), Huntington's disease (HD), spinocerebellar ataxia types 1, 2, 3, 6, 7 (SCA1, SCA2, SCA3, SCA6, SCA7), dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich's ataxia (FRDA) and autosomal dominant pure spastic paraplegia (ADPSP). They have been traced to genetic variation in the length of (CTG)n/(CAG)n, (CGG)n/(CCG)n, or (GAA)n/(TTC)n triplet repeats in DNA. In normal individuals these loci contain a short length of triplet repeats (usually 5-40), which is polymorphic within the population. Increases in the lengths of the translated triplet repeats to 40-100 are associated with disease symptoms, whereas the untranslated triplet repeats to 200-3000 are associated with the disease. We concentrated on repeat expansions in myotonic dystrophy. In this symposium, we outline the molecular aspects of myotonic dystrophy including DNA diagnosis and anticipation, and review the similarities and differences among these triplet repeat diseases.

Humans↗

[ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH): a case report].

We report a case of adrenocorticotropic hormone (ACTH)-independent macronodular adrenocortical hyperplasia (AIMAH). A 54-year-old Japanese man was admitted to our hospital for further examination of obesity and hypertension. Endocrinological studies showed that plasma cortisol was high (22.5 micrograms/dl) without diurnal rhythm, and plasma ACTH was low. Two or 8 mg of dexamethasone did not suppress the plasma cortisol levels. Abdominal computed tomography revealed nodular hyperplasia of bilateral adrenal glands. Adrenal scintigraphy showed the positive uptake of 131I-adosterol to bilateral adrenal glands. Brain magnetic resonance imaging revealed no abnormalities. He was diagnosed as having Cushing's syndrome with bilateral adrenal hyperplasia, and bilateral adrenalectomy was performed. Left and right adrenal glands were 52 g and 35 g, respectively, and were occupied by yellow nodular lesions. Histologically, hyperplastic lesions were composed of clear cells. Finally he was diagnosed with AIMAH.

Adrenal Cortex↗

Synergistic cytotoxicity and apoptosis by Apo-2 ligand and adriamycin against bladder cancer cells.

Resistance to conventional anticancer chemotherapeutic agents remains one of the major problems in the treatment of bladder cancer. Hence, new therapeutic modalities are necessary to treat the drug-resistant cancers. Apo-2 ligand (Apo-2L) is member of the tumor necrosis factor ligand family, and it induces apoptosis in cancer cells. Several cytotoxic anticancer drugs, including Adriamycin (ADR), also mediate apoptosis and may share the common intracellular pathways leading to cell death. We reasoned that combination treatment of the drug-resistant cancer cells with Apo-2L and drugs might overcome their resistance. Here, we examined whether bladder cancer cells are sensitive to Apo-2L-mediated cytotoxicity and whether Apo-2L can synergize with ADR in cytotoxicity and apoptosis against bladder cancer cells. Recombinant human soluble Apo-2L (sApo-2L), which carries the extracellular domain of Apo-2L, was used as a ligand. Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. Human T24 bladder cancer line was relatively resistant to sApo-2L. Treatment of T24 line with combination of sApo-2L and ADR resulted in a synergistic cytotoxic effect. Synergy was also achieved in the ADR-resistant T24 line (T24/ADR), two other bladder cancer lines, and three freshly derived human bladder cancer cell samples. In addition, T24 cells were sensitive to treatment with sApo-2L combined with epirubicin or pirarubicin. The synergy achieved in cytotoxicity with sApo-2L and ADR was also achieved in apoptosis. Intracellular accumulation of ADR was not affected by sApo-2L. Incubation of T24 cells with sApo-2L down-regulated the expression of glutathione S-transferase-pi mRNA. This study demonstrates that combination treatment of bladder cancer cells with sApo-2L and ADR overcomes their resistance. The sensitization obtained with established ADR-resistant bladder cancer cells and freshly isolated bladder cancer cells required low subtoxic concentrations of ADR, thus supporting the in vivo potential application of combination of sApo-2L and ADR in the treatment of ADR-resistant bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[The role of power Doppler-guided prostatic biopsy in the diagnosis of prostate cancer].

Between March 1997 and December 1998, a total of 170 cases with an abnormal serum prostate specific antigen (PSA) level (range: 4.1-200, mean: 20.5 +/- 31.0) were chosen for this study. Following the evaluation of the prostate using power Doppler imaging (PDI) with a 7.5 MHz transrectal probe, the hypervascular lesion (HVL) was biopsied transperineally under PDI real-time guidance. Thereafter, when gray-scale transrectal sonography revealed a hypoechoic lesion, additional samples were taken from them. Finally, sextant systematic biopsy was performed in all cases. Prostatic biopsy was positive for cancer in 41 cases (24%). The positive biopsy rate was 59% (40/68) in cases with HVL, compared to 1% (1/102) in cases with no HVL (p < 0.0001). In 107 patients with serum PSA 4.1 to 10.0 ng/ml, biopsy was positive in 13 cases (12%). The positive biopsy rate was 38% (12/32) in cases with HVL, compared to 1% (1/75) in cases with no HVL (p < 0.0001). These results imply that HVL represents the neovascularity or increased perfusion of blood in the cancer lesion. Power Doppler-guided prostatic biopsy could be promising as a new biopsy technique in patients with abnormal PSA levels including moderately elevated PSA levels (4.1-10.0 ng/ml).

Aged↗

[Chiari malformation (type I) associated with bilateral abducens nerve palsy: case report].

There are still many questions concerning the pathology and therapeutic strategy for Chiari malformation. We recently encountered a case of Chiari malformation associated with only bilateral abducens nerve palsy which was successfully treated by foramen magnum decompression. The pathology and mechanisms of Chiari malformation (type I) were evaluated in this case. The patient was a 12-year-old girl who had visited our institute 1 month previously complaining of diplopia. She had no particular past or family history and her general appearance was also normal. Bilateral abducens nerve palsy was the only neurological deficit. Her cerebrospinal pressure was 9 cm H2O. Neuroradiological findings revealed basilar impression, C4-6 syringomyelia and Chiari malformation (type I), but no hydrocephalus or meningocele. Foramen magnum decompression with lateral extension, upper cervical laminectomy and open duraplasty were performed. The position of both eyes recovered fully shortly after surgery, and diplopia occurred only when the patient looked sideways. Eye movements also returned completely to normal 3 months after surgery. MRI showed no syringomyelia 4 months after surgery, the upward shift of the pendulous portion of the cerebellar tonsil, and the expansion of the subarachnoidal space of the pons-oblongata junction. In conclusion, it was thought that the mechanism of bilateral abducens nerve palsy in this case was due to the strangulation and the downward traction of the pons-oblongata junction. The nerve was relieved from this traction by foramen magnum decompression.

Abducens Nerve Diseases↗

[Renal angiomyolipoma with marked extrarenal development: a case report].

A 28-year-old female complained of minimal fever elevation. Computed tomography (CT) revealed a left renal tumor of 10 cm in diameter. Ultrasonogram and CT, magnetic resonance imaging and angiography suggested a renal angiomyolipoma (AML) with marked extrarenal development. Partial nephrectomy was performed using a microwave tissue coagulater without clamping of the renal artery. The tumor weight was 800 g and the pathological diagnosis was AML. The management of large AML is reviewed in the literature. Nephron sparing surgery should be performed even in patients who have a larger tumor with extrarenal development.

Adult↗