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Biomedical subjects

K Mikami

Publications and source records attributed to K Mikami.

At least 91 records · Page 5Linked to original sources

Non-Mendelian inheritance of macronuclear mutations is gene specific in Paramecium tetraurelia.

Paramecium tetraurelia contains two types of nuclei, a diploid germinal micronucleus and a large transcriptionally active macronucleus. The macronuclear genome is formed from the micronuclear DNA during sexual reproduction. Previous studies have shown that the processing of the A-type variable surface protein gene during formation of a new macronucleus is dependent on the presence of the A gene in the old macronucleus. It is not clear if this is a general feature that controls the formation of the Paramecium macronuclear genome or a unique feature of the A locus. Using micronuclear transplantation, we have constructed a strain that has a wild-type micronucleus but has macronuclear deletions of the A- and B-type surface protein genes. Neither the A nor the B gene is incorporated into the new macronucleus after sexual reproduction. Macronuclear transformation of this strain with the B gene rescues the B-gene deletion after formation of the next macronucleus but has not effect on the A deletion. Similarly, transformation with the A gene shows gene-specific rescue for A but not B. The effect of the old macronucleus on the processing of the new macronucleus results in a pattern of non-Mendelian inheritance of both macronuclear deletions. Progeny from the wild-type exconjugant are all wild type, and progeny from the A- B- exconjugant are mutant. The features of this A- B- non-Mendelian mutant demonstrate that the regulation of macronuclear DNA processing is gene specific, and our results open the possibility that this type of regulation affects many regions of the Paramecium genome.

Animals↗

[The role of repeat transurethral resection in stage A1 carcinoma of the prostate].

In order to evaluate the significance of repeat transurethral resection (TUR) in differentiating stage A1 prostatic adenocarcinoma from those with stage A2, we performed repeat TUR in 34 patients with an initial diagnosis of stage A1 prostatic adenocarcinoma. It was found that residual adenocarcinoma was present in five cases (14.7%), but the diagnosis was changed from stage A1 to stage A2 in only one case (2.9%). In one patient with final diagnosis of stage A1 carcinoma, bone metastases were detected seven months after the repeat TUR. It was concluded that repeat TUR for stage A1 prostatic adenocarcinoma did not yield clinically significant information.

Adenocarcinoma↗

[Successful collection of peripheral blood stem cells mobilized by high-dose etoposide for patients with chemotherapy-resistant and/or poor prognostic testicular cancer].

Clinical effects of peripheral blood stem cell autotransplantation (PBSCT) after ultra high-dose chemotherapy were evaluated in patients with chemotherapy-resistant and/or poor prognostic testicular cancer. Four patients with testicular cancer, who had high-risk malignancy, were treated with high-dose etoposide (500 mg/m2 x 4 days) in order to collect peripheral blood stem cells. After the administration of high-dose etoposide, rG-CSF (250 micrograms/body) was administered from nadir state. Blood mononuclear cells were collected using a Fenwall CS-3000 blood cell separator. Fractions enriched for stem cells were obtained by discontinuous Percoll gradient centrifugation and were stored in liquid nitrogen using patient's sera and DMSO. The mean number of peripheral blood granulocyte-macrophage-colony-forming units (CFU-GM) collected by one apheresis was 22.3 x 10(5)/kg body weight. In addition, CFU-GM more than 2.0 x 10(5)/kg body weight could be collected in each apheresis, which was though to be sufficient dosis to perform PBSCT in safe, based upon our previous studies. All the patients were treated by a combination of cisplatin (20 mg/m2 x 5 days), etoposide (100 mg/m2 x 5 days) and bleomycin (15 mg x 3 days). Three patients responded to BEP therapy and obtained a CR, however, remaining 1 patient failed to achieve CR, who was later treated by ultrahigh-dose chemotherapy including carboplatin (200 mg/m2 x 4 days), etoposide (250 mg/m2 x 4 days) and cyclophosphamide (50 mg/kg x 2 days) followed by PBSCT. He responded to this therapy and obtained a CR for 10 months. The results suggested the method was promising for patients with chemotherapy-resistant and/or poor prognostic testicular cancer.

Adult↗

[Laparoscopic pelvic lymphadenectomy for localized prostate cancer].

Between April 1992 and May 1993, 13 patients (age, 66-79) with localized prostate cancer underwent laparoscopic pelvic lymphadenectomy at Asahi General Hospital. Clinical stage comprised A2 for 3 patients, B1 for 1 and C for 9. Lymphadenectomy covered inner half of external iliac nodes and obturator nodes, from pubic bone to proximal end of umbilical ligament. Operating time ranged from 70 minutes to 133 minutes with median of 102 minutes. The number of total lymph nodes dissected ranged from 3 to 17 nodes with median of 7. Lymph nodal involvement was detected in one patient. Two patients needed laparotomy due to bleeding; from abdominal wall caused at insertion of trocar in one, and oozing of blood for 10 hours after procedure in the other. Other serious complications were not observed. In conclusion, laparoscopic pelvic lymphadenectomy was a good staging procedure for localized prostate cancer.

Aged↗

[Ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer].

This is a report of 45-year-old man with advanced nonseminomatous germ cell tumor (stage IIIB2: embryonal carcinoma, yolk sac tumor, seminoma), who had relapse after PVB (cisplatin, vinblastine, bleomycin) chemotherapy. Peripheral blood stem cells (PBSCs) were taken by two consecutive apheresis using a CS-3000 blood separator after high-dose chemotherapy of cytarabine and mitoxantrone. In total, 6.4 x 10(5)/kg of granulocytic cells (CFU-GM) was collected. He was treated with ultra high-dose chemotherapy consisting of carboplatin (800 mg/m2), etoposide (1,000 mg/m2) and cyclophosphamide (100 mg/kg) from day 1, followed by peripheral blood stem cell autotransplantation (PBSCT) on day 9. We transfused 2.4 x 10(5)/kg CFU-GM, which was enough number of stem cells for safe PBSCT. No serious side effects or complications were encountered. The patient achieved partial remission for more than two months. However, he died of respiratory dysfunction caused by metastatic lung cancer 5 months later. It was thought that ultra high-dose chemotherapy with PBSCT might be a new therapy for refractory testicular cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[A resected case of esophageal leiomyoma with 15 cm in long diameter, diagnosed by transesophageal ultrasonic endoscopy].

A 28-year-old man whose chest X-ray film showed a mass on the right upper mediastinum was admitted. Preoperative examination, including CT, MRI, esophagogram, did not make it possible to determine clinically from which organ the tumor originated. On diagnosing with transesophageal ultrasonic endoscopy (TUE) the tumor was found to originate in the esophageal submucosa, with no involvement of the mediastinal organ apparent. Esophageal sub-mucosal tumor enucleation was performed. The resected tumor was 15 cm in long diameter and weighed 125 g. We therefore believe that TUE is clinically useful in diagnosing the tumor originating in the esophageal wall or adjoining esophageal wall.

Adult↗

Enhanced expression by the brain matrix of P-glycoprotein in brain capillary endothelial cells.

P-glycoprotein (PGP), an active efflux pump of antitumor agents in multidrug-resistant tumor cells, exists in brain capillary endothelium and could be functionally involved in the blood-brain barrier. To study the regulatory mechanism of PGP expression in brain capillary endothelium, various mouse tissue matrices were tested for their abilities to enhance the expression of PGP in mouse brain capillary endothelial cells (MBEC), which express relatively small amounts of PGP. Of the four tissue matrices we examined, PGP expression in MBEC cultured on the brain matrix increased 2.0-fold. The PGP-inducing activity was similarly detected in bovine brain matrix, and the activity was enriched in the fraction of pl 9.0 by isoelectric focusing. The fraction, named PIC-fraction (PGP-inducing component), increased the PGP expression in MBEC 3.5-fold. By Northern blot analysis, a 3.3-fold enhancement of mdr gene expression was observed in MBEC cultured on the PIC-fraction. The PGP-inducing activity of the PIC-fraction was reduced by the treatment with trypsin but not with collagenase, suggesting that a proteinaceous factor distinct from type I collagen might be responsible for the PGP-inducing activity of PIC-fraction. Although the PIC-fraction increased the PGP expression in other mouse brain capillary endothelial cells, the PIC-fraction did not increase PGP expression in mouse aortic endothelial cells and KB carcinoma cell lines expressing various amounts of PGP. These observations suggest that PGP expression in brain capillary endothelium is specifically regulated by a tissue-specific factor in the brain matrix.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Microheterogeneity of PSI-E subunit of photosystem I in Nicotiana sylvestris.

Microheterogeneity of a photosystem I (PSI) subunit encoded by a nuclear gene psaE was examined in Nicotiana sylvestris, with the aid of cDNA cloning, peptide mapping analysis and protein sequencing. The psaE product of this plant has four isoforms whose mobilities in PAGE are slightly different from each other. We isolated two types of psaE cDNAs from a N. sylvestris cDNA library, and designated the corresponding genes as psaEa and psaEb, respectively. The psaEa and psaEb genes are 77% homologous at DNA level, and their translation products share 80.4% homology for the precursor proteins and 89.1% for the mature forms. Comparative analysis of the four isoproteins and the putative products of the two psaE genes revealed that two isoproteins out of four are derived from psaEa gene, and the difference between these two isoproteins lies in the respective presence or absence of N-terminal alanine. Likewise, the other two proteins are derived from psaEb with similar N-terminal heterogeneity. These results indicate that multi-gene organization and heterogeneous N-terminal formation at post-translational level are two possible causes for PSI subunit polymorphism in isogenic plant lines.

Amino Acid Sequence↗

[Clinical evaluation on renal pelvic and ureteral tumors].

We report 82 patients with renal pelvic and ureteral tumors admitted to Kyoto Prefectural University of Medicine, Kyoto Second Red Cross Hospital and Shakai-Hoken Kyoto Hospital between January, 1981 and December, 1991. Sixty two were males and 24 were females, and they were between 47 and 93 years old (average: 68.2 years). The tumor occurred on the right side in 34 patients, on the left side in 51 patients and on both sides in one patient. There were 43 renal pelvic tumors, 37 ureteral tumors and 6 renal pelvic with ureteral tumors. The most frequent symptom was macrohematuria, which was seen in 54 patients (62.8%). Urinary cytology was performed in 76 patients and a positive result was obtained in 44 patients (57.9%). We performed surgical treatment on 71 patients. The most frequently adopted method was total nephroureterectomy with partial cystectomy which was performed on 51 patients (71.8%). Of the 73 specimens diagnosed histopathologically, 71 specimens were transitional cell carcinoma (TCC), one was a squamous cell carcinoma (SCC) and one was a mixed type of TCC and adenocarcinoma. As to grading, 6 specimens were G1, 28 G2, 38 G3 and one GX. As to staging, 8 specimens were pTa, 17 pT1, 21 pT2, 18 pT3, 8 pT4 and one pTX. The overall survival rate (by Kaplan-Meier's method) at 3 and 5 years was 47.0% and 39.5%, respectively. The patients with high grade tumors and those who had ureter preservation, the survival rate was lower than in the other patients.

Aged↗

[Clinical evaluation of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy for advanced urothelial cancer].

M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy was performed on 27 patients with advanced urothelial cancer. The patients included 20 with bladder cancer, 4 with upper urinary tract cancer and 3 with both lesions. Complete response (CR) was observed in 2 (7.4 +/- 9.9%) patients and partial response (PR) in 10 (37.0 +/- 18.2%) patients after the treatment, i.e., the overall objective response rate was 44.4 +/- 18.7%. The rate of relapse or recurrence in the patients with CR and PR was 100% and 90.0%, respectively. The mean duration of the response was 18.5 +/- 13.4 months and 10.7 +/- 10.9 months for CR and PR, respectively. The overall survival rate after one year was 30.2%. Bone marrow suppression was the most serious side effect. The white blood cell count became below 1,000/microliters in 10 patients (36.7%). Among them, 4 patients suffered from sepsis. In conclusion, M-VAC chemotherapy was effective for induction therapy against advanced urothelial cancer, although the effective duration was short. Further maintenance therapy should be established.

Adult↗

Ethanol-elicited structural and biochemical alterations in mitochondrial ATPase in cultured myocardial cells.

The effects of ethanol (12.5-500 mM for up to 24 h) on mitochondrial structure including that of ATPase particles in cultured ventricular myocardial cells were studied using negative-stain electron microscopy. The activity of mitochondrial ATPase after ethanol treatment was also examined cytochemically and biochemically. At 5 min after the addition of all the concentrations of ethanol examined, some mitochondrial cristae were expanded and the arrangement of mitochondrial ATPase particles on these cristae was disordered. At and after 30 min the cristae decreased in number and some were expanded, vesiculated or fragmented. ATPase particles also decreased in number, particularly after the application of ethanol in concentrations of more than 50 mM. All the mitochondria had broadened and translucent cristae, and lacked ATPase particles with 200 and 500 mM ethanol at 24 h, although with 12.5 and 50 mM ethanol some mitochondria had similar negatively stained images but others had ATPase particles on broadened cristae. The enzymatic activity of the mitochondrial ATPase was unchanged with 200 and 500 mM ethanol at 24 h, compared with controls. The cytochemical technique also detected enzyme activity with all the concentrations of ethanol examined at 24 h. The discrepancy between the structural and biochemical alterations in mitochondrial ATPase induced by ethanol is discussed.

Adenosine Triphosphatases↗

Molecular heterogeneity of photosystem I. psaD, psaE, psaF, psaH, and psaL are all present in isoforms in Nicotiana spp.

The protein composition of photosystem I (PSI) was examined in Nicotiana spp. by high-resolution polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and immunoblot analysis. Five PSI proteins show polymorphism in an amphidiploid species, Nicotiana tabacum, but not in its ancestral diploid species, Nicotiana sylvestris and Nicotiana tomentosiformis. These Nicotiana spp. appear to have at least 18 PSI proteins per genome that range in molecular mass from 3 to 20 kD. They include the products of nuclear genes psaD, psaE, psaF, psaG, psaH, psaK, and psaL, the product of chloroplast gene psaC, N-terminally blocked proteins of 4.5 and 3.0 kD, and an unidentified protein of 12.5 kD. The psaD, psaF, psaH, and psaL products have two isoforms each that are distinguished by different mobilities in polyacrylamide gel electrophoresis, and the psaE product has four isoforms. The two isoforms of the psaD product have distinct amino acid sequences, indicating that they are encoded by different genes within the genome. Four isoforms of the psaE products can be classified into two groups by N-terminal amino acid sequence, indicating that at least two psaE genes are present in the genome. To examine whether the polymorphic nature of PSI is peculiar to Nicotiana spp., we carried out immunoblot analysis of the psaD and psaE products in isogenic lines of tomato (Lycopersicon esculentum), Arabidopsis thaliana, red bean (Vigna angularis), and corn (Zea mays). Two electrophoretically distinct isoforms were found for the psaD products of tomato, A. thaliana, and corn, and two isoforms of psaE products were detected in tomato, A. thaliana, and red bean. These results suggest that the nuclear-encoded subunits of PSI, except for the psaG and psaK products, generally have two isoforms.

Amino Acid Sequence↗

Inhibition of the induction and activity of hepatic P450IA isozymes by in vivo administration of carbon tetrachloride to rats.

The effect of carbon tetrachloride (CCl4) on the induction and activity of 3-methylcholanthrene (MC)-inducible P450IA isozymes (P450IA1 and P450IA2) in the liver was examined by treating male Sprague-Dawley rats with simultaneous i.p. injections of MC and CCl4. Following the treatment, the quantities of P450IA mRNAs determined by Northern blotting and P450IA proteins by Western blotting were significantly reduced as compared with those in rats treated with MC alone. As determined by a bacterial mutation test using carcinogenic aromatic amines are P450IA enzyme substrates, CCl4 treatment selectively inhibited the activity of P450IA2 in the MC-induced isozymes. These results indicate that CCl4 exerts on inhibitory effect on the induction of P4501A isozymes and that it selectively inhibits P450IA2 activity.

Animals↗

Regulation of cholesterol metabolism in adrenal cortex: effects of apoproteins on cholesterol esterase in rat adrenal glands.

We have investigated the effects of apoproteins on cholesterol esterase (CEase) in rat adrenal glands in order to clarify the mechanism of synthesis of free cholesterol which is the most important substrate for steroidogenesis. We prepared lipid mixtures containing cholesteryl oleate plus apoproteins with and without phosphatidylcholine as a substrate for CEase in order to investigate the effect of the substrate state on CEase. The substrate containing only cholesteryl oleate and apo-HDL increased both acid and alkaline CEase activities. Both acid and alkaline CEase activities were also increased by a substrate containing apo-HDL plus cholesteryl oleate and phosphatidylcholine more than by a substrate containing cholesteryl oleate plus apo-LDL with phosphatidylcholine or cholesteryl oleate with phosphatidylcholine. We have already reported that phosphatidylcholine is an important factor for the regulation of adrenal CEase. Therefore, the present studies show that apoproteins as well as phosphatidylcholine may be important factors for the regulation of adrenal CEase.

Adrenal Cortex↗

Regulation of cholesterol metabolism in adrenal cortex: comparative studies on cholesterol esterase in human adrenal glands.

We have studied the nature and characteristics of cholesterol esterase (CEase) in human adrenal adenoma and hyperplasia tissues showing Cushing's syndrome, comparing with those in normal tissue. Each tissue demonstrated that two pH optima were found at around 4.5 and 8.0. The results of a subcellular distribution study show that acid and alkaline CEase are mainly located in lysosomes and microsomes, respectively. Our previous data suggested that phosphatidylcholine which was sonicated with cholesteryl oleate as a substrate may play a crucial role in the regulation of CEase in rat adrenal. The effect of phosphatidylcholine was therefore investigated in the present study. Acid CEase in normal tissue was increased in a dose-dependent manner by phosphatidylcholine, but not in the adenoma or hyperplasia tissues. None of those tissues showed any enhancement in alkaline CEase activity when phosphatidylcholine was added to the substrates. It is therefore suggested that the mechanism of regulation of CEase among three different kinds of human adrenals may be different from the data for the effect of phosphatidylcholine. Basal activity of acid CEase in adenoma and hyperplasia was significantly higher than that in normal tissue, and also that of alkaline CEase in hyperplasia tissue was significantly higher than that in normal tissue. Thus it is suggested that such an adrenocortical disorder as Cushing's syndrome due to adenoma and diffuse hyperplasia of the adrenal cortex may possess the nature and characteristics of autonomy of steroidogenesis which seems to be induced by the active metabolism of cholesterol, when compared with normal tissue.

Adenoma↗

[Characteristic features of the atrophic border of gastric ulcers in elderly].

We studied the characteristic features of gastric ulcers in 50 elderly cases (over 60 years old) concerning 2 points. Initially, we compared the clinical features of the elderly patients with those of the non-elderly (under 60 years old) patients. Secondly, we compared the endoscopic appearance of the atrophic border of elderly patients with that of elderly persons without gastric ulcer, using the Takemoto and Kimura's classification of endoscopic atrophic borders. The results were that elderly patients with gastric ulcer had few symptoms. The symptoms associated with bleeding, however, were recognized. Many of them had some complications. There was no difference in the healing rate at 8 weeks from the beginning of the treatment by histamine H2-receptor blocker (H2 blocker) between the elderly and non-elderly with gastric ulcer. Concerning the endoscopic atrophic border of the elderly persons without ulcers, the number of the open type cases was significantly greater than that of the closed type. On the contrary, in elderly persons with gastric ulcer, the number of the closed type was significantly greater than that of the open type, especially the number of C-2 type was the greatest. The healing rate of the elderly with closed type border was higher than that of elderly cases with open type border in 4 and 8 weeks from the beginning of the treatment.

Aged↗

[Renal functions of the patients with long-term catheterization in upper urinary tract].

In order to investigate long-term effects of indwelling urinary catheters on renal functions, in 46 patients (27 male and 19 female) with ureterostomy or nephrostomy serum creatinine values were measured periodically. Average age of the patients was 60.6 years old. Duration of catheterization was more than 3 years (average 8.1 years). Renal dysfunction was defined as an elevation of serum creatinine more than 2 mg/dl. It was found that catheterization used more than 15 years evoked renal insufficiency over 50% of such patients. This period, however, was shorten to 11 years in patients with nephrolithiasis or frequent fever. It was concluded that urolithiasis and symptomatic urinary tract infections were two remarkable risk factors for the deterioration of renal functions, and that these risk factors must be avoided in patients on long-term catheterization in the upper urinary tract.

Aged↗

[A clinical study of 17 cases of penile cancer].

A clinical evaluation of 17 patients with penile cancer treated in our hospital from 1965 to 1991 were surveyed. They were between 34 and 74 years old with a mean age of 63.8 years. The average interval between the onset and the first visit was 22.8 months. Fourteen patients (83%) complained of the manifestation of a tumor and 14 patients (83%) were phimotic. The stage classified according to Jackson was Stage I for 6, Stage II for 6, Stage III for 4 and Stage IV for 1 patient. At the first visit, the inguinal lymph nodes were palpated in 8 patients and metastasis was confirmed in 5 (63%) of them. Surgical treatment was given to 15 patients (88%) (radical or partial penectomy was performed in most cases). Chemotherapy was given to 9 patients (60%) (main chemotherapeutic agent was bleomycin) and irradiation to 5 patients (30%). The overall 3-year survival rate was 71%, and 5-year survival rate was 56%. The 5-year survival rate in the low stage group (Stage I, II) was 75%, while that in the high stage group (Stage III, IV) was 0%, showing a significant difference.

Adult↗