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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 577 records · Page 32Linked to original sources

Altered transcriptional regulation of the insulin-like growth factor 2 gene in human hepatocellular carcinoma.

The insulin-like growth factor 2 (IGF2) gene is regulated in a complex manner, involving developmentally regulated use of four different promoters as well as transcriptional repression of the maternal allele due to genomic imprinting. It has been well documented that liver is an exceptional organ in which overall transcription from the four IGF2 promoters is markedly imbalanced towards preferential paternal expression only in fetal life, this being relaxed during the postnatal period, resulting in biallelic expression thereafter. We previously reported a marked allelic-expression imbalance in the overall transcription of IGF2 in hepatocellular carcinoma (HCC), leading to preferential expression nonrandomly from the paternal allele. The study presented here, using 18 HCC specimens taken directly from patients, showed that this molecular change often reflects promoters switching from the adult P1 promoter to the fetal P2, P3, and P4 promoters. Interestingly, however, we found that restoration of allele-specific expression of the P1 promoter nonrandomly from the paternal allele was also frequent in HCC suggesting retention of an imprint for paternal expression from the P1 promoter of IGF2 in adult normal liver and altered availability of its modifying factor or factors in HCC. Further studies of the molecular mechanisms involved in the fluctuation of promoter usage and genomic imprinting of IGF2 are warranted to gain an insight into the biology of the liver in terms of development and oncogenesis.

Adult↗

[A case of sarcoidosis with proliferative retinopathy].

A 19-year-old female manifested severe bilateral panuveitis with neovascularization in the iris, optic disc, and retina. Fluorescein fundus angiography showed dye leakage from the optic disc and retinal blood vessels, and a large non-perfused area was present in the peripheral retina of the right eye. Sarcoidosis was diagnosed histologically by conjunctival and skin biopsy. Although the patient was given a large dose of a corticosteroid systemically and received panretinal photocoagulation, a dense vitreous hemorrhage and cataract were apparent in the right eye. The right visual acuity decreased to hand motions. A pars plana lensectomy and vitrectomy were performed. After vitrectomy, inflammation and neovascularization regressed and the visual acuity improved to 20/100. Proliferative membrane obtained during vitrectomy was histopathologically studied by light and electron microscopy. Many new vessels containing neutrophils were observed. A direct effect of inflammation as well as ischemia in the retina may have been the stimulus for the proliferative changes.

Adult↗

Inhibition of syncytium formation by antisense oligonucleotide phosphorothioates complementary to tax mRNA of human T-cell leukemia virus type 1 (HTLV-1).

HTLV-1 infection is known as the factor to cause adult T-cell leukemia (ATL). Antisense oligonucleotide phosphorothioates against tax gene and control oligonucleotide phosphorothioates were synthesized. Antisense oligonucleotide was complementary to the region of initiation codon of tax gene. Two control oligonucleotides were tax sense and random. HTLV-1-positive human T-cell line, C91/PL and HTLV-1 non-infected human glioma cell line, U251-MG were co-cultured in the presence of antisense or control oligonucleotides for 24 hours. Oligonucleotides used in this study were not toxic at 10 microM concentration. Antisense oligonucleotide against tax gene inhibited 59% the syncytium formation assay at 10 microM concentration.

Adult↗

Pathogenesis and prevention of HTLV-1-associated diseases.

HTLV-1 is an important factor involved in various diseases including adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis. Amount of HTLV-1 provirus integrated in human peripheral blood mononuclear cells might be a candidate for a risk factor in the manifestation of HTLV-1 associated diseases. Experimental animal models would be useful to dissect the pathogenesis of HTLV-1 associated diseases. We present rat and mouse models of HTLV-1 infection. Using these animal models, we could clarify the intrauterine transmission of HTLV-1, and have found that both genetic background and HTLV-1 infection are important in pathogenesis of HAM/TSP-like rats. We also discuss the preventive measures of HTLV-1 transmission by use of antisense oligonucleotides.

Adult↗

Establishment of HTLV-1 carrier mice by injection with HTLV-1-producing T cells.

We injected with HTLV-1-producing T-cells, MT-2, into C3H/HeJ and Balb/c mice intraperitoneally within 24 hours after birth and at one week old. At 3 months old, HTLV-1 provirus was detected in peripheral blood mononuclear cells in both mice. It was also detected in lymph nodes, thymus, spleen and liver of those mice. The antibody response against HTLV-1 Gag antigen was detected in some of Balb/c mice. These findings suggest that the C3H/HeJ and Balb/c mice were infected with HTLV-1 persistently. The HTLV-1-infected mice should be helpful for studying the pathological state of HTLV-1 carriers and for an establishment of a small animal model of HTLV-1 related diseases including ATL.

Animals↗

[Assessment of quality of life in long-term results of patients over 75 years old after emergent cardiovascular surgery].

Long-term results in QOL of patients over 75 years old after emergent cardiovascular surgery were examined. From January 1991 to June 1996, 46 patients underwent cardiovascular surgery. 22 patients who had elective surgery (elective group) and 15 patients who had emergency surgery (emergency group) tolerated with the operation: Two-year survival rate after surgery was 80.7% in the elective group and 78% in the emergency group, and relative survival rate was 0.89 in the elective group and 0.86 in the emergency group. As regards to the ability to live independently, 89% of elective group and 75% of emergency group showed good improvement, and there was no significant difference between two groups. The rate of patients who did not feel anxiety for disease at all was 61.1% in the elective group and 41.7% in the emergency group. The relationship between the patient and his family was good in both groups. For physical condition, the emergency group was superior to the elective group with no significant difference. Although QOL was relatively good after emergency surgery, some items were inferior compared with elective surgery. To improve the long-term results, elective surgery is required to avoid emergency surgery.

Age Factors↗

[Surgery for acute aortic dissection extending to the aortic root using gelatine-resorcine-formol biological glue--a case report].

A 73-year-old woman was admitted with chest pain of sudden onset and hypotension. Enhanced CT showed the dilated ascending aorta with an intimal flap. Emergency surgery was performed under a diagnosis of type A acute aortic dissection and cardiac tamponade. Replacement of the ascending aorta was planned, but during the operation we found that the dissection had extended to the aortic root and that the laceration of the adventitia was located just distal to the aortic annulus. Since the laceration was closer to the aortic annulus than the coronary ostium, it was impossible to reconstruct the aortic stump by classical techniques using Teflon felt strips. Gelatine-Resorcine-Formol (GRF) glue was therefore used to reinforce the proximal aortic stump. We then curved the suture line of the proximal anastomosis so as to resect the laceration while preserving the ostia of the coronary arteries. We were thus able to perform simple replacement of the ascending aorta successfully and the postoperative course was uneventful. By using GRF glue, replacement of the aortic root can be avoided in such cases.

Acute Disease↗

[Prognosis of renal cell carcinoma and detection of numerical chromosome aberration].

Identification of numerical abberations of chromosome #3, #7, #11, #17, #18, X and Y were evaluated using biotinylated probes specific for the alpha satellite region on paraffin embedded sections from formalin-fixed materials of renal cell carcinoma utilizing in situ hybridization (ISH). The copy number of each chromosome did not show any correlation with tumor grade, clinical (Robson) stage, pT, pN, pV or the presence of metastasis. Copy numbers of #3 chromosome were highly correlated with the patient prognosis (p < 0.01). Since numerical abberations of #3 chromosome are suggested to be correlated with the prognosis of renal cell carcinoma, this technique can now be applied to the detection of biological activity in renal cell carcinoma.

Adult↗

[Quantitative evaluation of pulmonary perfusion volume using 99mTc-MAA SPECT: a comparison of COPD patients and healthy volunteers].

99mTc-MAA pulmonary perfusion single-photon emission computed tomography was performed on 18 patients with chronic obstructive pulmonary disease (COPD) and 41 healthy male volunteers. We quantified the extent of pulmonary perfusion with the Application Visualization System. We measured the pulmonary perfusion volume (PV) at 8 threshold levels encompassing 10 percentage points each from 21-100%. We also calculated the ratio of perfusion volume to total perfusion volume (TPV) at each threshold. Pulmonary perfusion volume in healthy volunteers remained relatively constant at levels of 31-70% and decreased gradually at levels of 71-100%. There was no significant difference in perfusion volume between smokers and non-smokers. Perfusion volume in COPD patients gradually decreased at levels of 31-60% and markedly decreased at levels greater than 60%. Perfusion volume differed significantly between COPD patients and healthy volunteers at levels of 41-100%. The mean PV/TPV value of COPD patients was significantly higher than that of healthy volunteers at levels of 21-40% and significantly lower than that of healthy volunteers at levels of more than 50%. This finding demonstrates that lung volume at high levels of pulmonary perfusion is decreased in COPD patients. The pulmonary perfusion volume at levels of more than 60% is an efficient means of distinguishing COPD patients from healthy subjects.

Adult↗

Effect of oral administration of Lactobacillus casei on alloxan-induced diabetes in mice.

The effect of Lactobacillus casei (LC) on the onset of alloxan (AXN)-induced diabetes in 7-week-old BALB/c mice were examined. It was observed that the mice given a diet containing 0.1% or 0.05% LC or orally administered LC showed significantly decreased incidence of diabetes induced by intravenous injection of AXN and that the plasma glucose level was slightly lower than that in the control group. The body weight in the LC-treated groups was higher than that in the control group, although the food intake weights were almost the same. Pathological analysis revealed that the AXN-induced disappearance of insulin-secreting beta-cells in the islets of Langerhans was strongly inhibited in the LC-treated groups. It was also shown that the serum nitric oxide level was maintained at a normal level in LC-treated mice, whereas the level in the control group was increased by AXN administration. Taken together, these findings suggest that oral administration of LC to AXN-treated BALB/c mice contributed to the reduction of diabetes and the increase in plasma glucose level.

Alloxan↗

[Bladder cancer associated with von Recklinghausen's disease: a case report].

A 53-year-old man was admitted to our hospital with urinary frequency and miction pain. He had von Recklinghausen's disease with multiple café-au-lait spots and neurofibromatosis. Computed tomography scan and magnetic resonance imaging revealed an invasive bladder tumor 10 cm in diameter, and not metastasis. He was diagnosed as having a bladder tumor (T3a N0 M0 with von Recklinghausen's disease. After balloon occluded arterial infusion (BOAI) chemotherapy, total cystectomy was performed. Pathological diagnosis was transitional cell carcinoma, G3, pT3aN0M0. We reviewed and discussed 97 cases of carcinoma associated with von Recklinghausen's disease reported in the Japanese literature. Only 5 cases of bladder cancer have been reported, including the present case.

Antineoplastic Combined Chemotherapy Protocols↗

[Survey of sensitivities of clinical isolates to antibacterial agents (annual report)].

Research groups were formed in 20 institutions nationwide to investigate carbapenem resistance of clinical isolates. Activities of various antibacterial agents, principally carbapenems, were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of 17 antibacterial agents for 1,326 strains of 11 bacterial species isolated at the institutions between October and December 1994. The results are as follows: 1. Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae. Their activities against Enterococcus faecalis were comparable to that of ABPC. Carbapenems showed low activities against MRSA. 2. OFLX exhibited the greatest antibacterial activity against Haemophilus influenzae, followed by MEPM. Antibacterial activities of the other carbapenems were comparable to those of FMOX, CTM, and ABPC. 3. The carbapenems showed high activities against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Bacteroides fragilis group. Their activities were greater than those exhibited by other beta-lactam antibacterial agents. The carbapenems also exhibited stronger antibacterial activities against Serratia marcescens than the other beta-lactam antibacterial agents, but some resistant strains were detected. 4. The antibacterial activities of carbapenems against Pseudomonas aeruginosa were comparable to those of CAZ, AZT, AMK.

4-Quinolones↗

Studies on the antifungal activity of the new imidazole antimycotic lanoconazole in infected sites. Distribution in the skin and in vitro activity in the presence of stratum corneum.

To answer the question why topically applied lanoconazole (CAS 101530-10-3, NND-318) is so highly effective in the treatment of dermatomycoses in both animal models and human patients, the antifungal activity of lanoconazole in infected sites was investigated. 1. Distribution of lanoconazole in rat skin: The distribution of lanoconazole within the dorsal skin of rats was examined by measurement of radioactivity and microscopic autoradiography. 24 h after dermal application of 14C-lanoconazole cream formulation, 83% of the total radioactivity in the skin was recovered from the stratum corneum, and thereafter the radioactivity decreased gradually up to 96 h. Metabolite analysis showed that more than 94% of the extractable radioactivity was lanoconazole itself after 24 and 48 h. Microautoradiograms of the skin also supported the radioactivity distribution. 2. In vitro antifungal activity in stratum corneum-containing medium: Candida albicans TIMM 2640 was incubated for 10 days at 27 degrees C in a vitamin-supplemented yeast carbon base medium containing 5 mg/ml of human stratum corneum and different concentrations of lanoconazole or bifonazole (CAS 60628-96-8, reference agent). Compared with the control culture, lanoconazole strongly inhibited fungal growth in a concentration dependent manner at concentration above 0.1 microgram/ml, resulting in a reduction of viable cell recovery to less than 50% after 10 days. The inhibitory activity of bifonazole was clearly weaker than that of lanoconazole. At concentrations of 0.1-10 micrograms/ml lanoconazole reduced keratinolytic acid proteinase activity in the culture-supernate to 40-70% of the control value, while bifonazole showed 50% reduction of the activity at a concentration of 10 micrograms/ml. These results indicate that lanoconazole is mainly distributed and retained in the stratum corneum after topical application where it exerts strong antifungal activity.

Administration, Topical↗

Clinical, morphologic, and biochemical characteristics of Chediak-Higashi syndrome in fifty-six Japanese black cattle.

OBJECTIVE: To characterize Chediak-Higashi syndrome (C-HS) in Japanese Black cattle. ANIMALS: 56 of 200 cattle with a bleeding disorder and giant granules in leukocytes. PROCEDURE: Clinical observation, CBC, hemostatic screening test, platelet aggregometry, electron microscopy, platelet constituent analysis, and ophthalmoscopic examination were done. RESULTS: Affected Japanese Black cattle had increased bleeding tendency and abnormal granules in their leukocytes. Susceptibility to infection was not increased. Cutaneous albinism was evident in 6 new-born calves, but not in most affected cattle. In all affected cattle, the tapetal fundus was pale and the nontapetal fundus was almost devoid of pigment. By electron microscopy, a remarkable decrease in the number of dense granules in platelets was observed. Functionally, collagen-induced platelet aggregation was markedly reduced. CONCLUSIONS: This bleeding disorder was diagnosed as C-HS. With regard to susceptibility to infection, albinism, and mortality, clinical manifestations of C-HS in Japanese Black cattle were moderate, compared with C-HS in human beings and Hereford cattle. CLINICAL RELEVANCE: Because an autosomal recessive mode of inheritance was documented and recessive homozygotes could be easily detected, C-HS in Japanese Black cattle can be controlled.

Adenosine Diphosphate↗

[Acute eosinophilic pneumonia associated with aspirin].

A 21-year-old man was admitted to our hospital with acute progressive dyspnea and a high fever. He had started smoking 6 weeks before admission. A chest radiograph showed diffuse infiltrates with Kerley B lines and bilateral pleural effusions. There was no evidence of infection. His condition improved rapidly and without medication. On admission the concentrations of interleukin-5 in bronchoalveolar lavage fluid and in blood were high, but they were normal one week later. Acute eosinophilic pneumonia was diagnosed. A positive result of a lymphocyte stimulation test indicated that the development of symptoms was closely associated with ingestion of aspirin. We know of no previous report of acute eosinophilic pneumonia associated with aspirin.

Acute Disease↗

[The in vitro antifungal activities of fluconazole against pathogenic yeasts recently isolated from clinical specimens].

The emergence of Candida albicans resistance to azole antifungal agents have been reported in the U. S. and Europe. We examined the in vitro antifungal activities of fluconazole against clinical isolates collected by seven investigators in three years to examine if a tendency existed toward the development of azole-resistance among fungal isolates in Japan. The following results were obtained: 1. Sensitivities to fluconazole (FLCZ) were determined for yeast-like fungi, including 113 strains isolated in 1993, 149 strains isolated in 1994 and 205 strains isolated in 1995. No significant differences in sensitivities in the three years were detected. 2. Minimum inhibitory concentrations of FLCZ were 0.1-0.78 microgram/ml for C. albicans and 3.13-25 micrograms/ml for C. glabrata. Strains with 25 micrograms/ml of FLCZ's MIC were detected; two strains of C. krusei and one strain each of C. krusei, Trichospron beigelii and Hansenula anomala. No strains with higher than 50 micrograms/ml MIC of FLCZ were detected. 3. In vitro activities of FLCZ were compared between clinical strains isolated between 1993 and 1995 and clinical strains isolated before the marketing of FLCZ (up to December 1987) or clinical yeasts isolated between 1991 and 1992. No significant differences were observed, suggesting that no tendency existed toward azole resistance among fungal strains examined.

Antifungal Agents↗