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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 793 records · Page 44Linked to original sources

[A case of cervical teratoma in adult].

Cervical teratomas are rare neoplasms in adults. A 21-year-old male was admitted to our hospital for evaluation of a cervical tumor. CT scan and MRI showed the tumor extended into the mediastinum and not invaded to surrounding tissue. 201T1 scintigram showed increased uptake in the tumor. The tumor was resected with coller incision and median sternotomy. Histological examination revealed mature teratoma. The patient remains free of disease one year and seven months after operation.

Adult↗

[Arterial infusion chemotherapy of 5-FU and leucovorin for patients with liver metastases from colorectal cancer].

Fifteen patients with liver metastases from colorectal cancer were treated by arterial infusion of 5-FU and leucovorin. Two regimens were performed. One was weekly bolus infusion of leucovorin following bolus infusion of 5-FU (bolus group), the other was 5 days continuous infusion of 5-FU and leucovorin in 3 weeks (continuous group). One PR was obtained both in the bolus group and in the continuous groups. The objective response rate was 11% in the bolus group and 20% in the continuous group. The one- and 2-year survival rates for these patients were 40% and 0% in the bolus group, and 80% and 60% in the continuous group, respectively. These results suggest that continuous arterial infusion of 5-FU and leucovorin was more effective than individual bolus arterial infusion of leucovorin and 5-FU for patients with liver metastases from colorectal cancer.

Adult↗

[Cooperative Study of Surgical Adjuvant Chemotherapy for Colorectal Cancer (third report): five-year results after surgery].

Beginning in January 1984, in collaboration with 357 institutions nationwide, comparative studies on curative resection cases of colorectal cancer and a control group were conducted for 2 years. The following method of administration was employed; Group A received 12 mg/m2 of MMC on the day of operation, followed by 6 mg/m2 every 2 months 6 times. From the 2nd week after the operation, 800 mg/body/day of Futraful was administered for one year. Group B received no treatment. Altogether 2786 cases were collected and, excluding ineligible cases, 2477 evaluable cases were analyzed. There was no difference in either survival rate or disease free rate, but after the bias of background factors was corrected by the hazard model, the disease free rate was better with Group A, and there was a significant difference with the rectum. According to the Dukes classification, in the Dukes C cases with the rectum Group A had higher rate of survival, disease free rate and lower rate of metastasis to the liver and local recurrence of cancer.

Administration, Oral↗

[Cooperative Study of Surgical Adjuvant Chemotherapy for Colorectal Cancer (fourth report): five-year results after surgery].

In collaboration with 428 institutions nation-wide, comparative studies on the optimal daily dosage of UFT were carried out for non-curative resection cases of colorectal cancer for two years from January 1984 to December 1985. The administration method employed was as follows. Group C received 12 mg/m2 of MMC on the day of operation, followed by 6 mg/m2 every 2 months 6 times, and from the 2nd week after the operation 600 mg/body of UFT was continuously administered every day for 1 year. Group D received 400 mg/body of UFT every day and the same amount of MMC as Group C. Analysis was made of 556 evaluable cases. There was no difference in the survival rate between the two groups. With respect to the dosage per body weight (kg), 8-12 mg/kg of UFT produced good prognoses and less side effects than the group which received more than 12 mg/kg. It seems necessary to administer UFT at its optimal dosage for colorectal cancers.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of chest wall abscess due to Salmonella newport].

A 18-year-old female with a history of precordial pain was admitted. There was a mass (3.5 x 2.5 cm) in the right inframammary region which was suspected to be chest wall tumor on the basis of CT scan and Ga scintigraphy findings. Exploratory surgery, consisting of total resection of the tumor without removing the ribs, was performed and revealed an abscess. Culture of pus from the abscess grew Salmonella newport (0 antigen 8, H antigen eh; 1.2). Focal infection with Salmonellosis is discussed. Surgical treatment is necessary in addition to chemotherapy.

Abscess↗

[A case of Buerger's disease solitary involved in the left subclavian and axillary artery].

A 26-year-old male with about a ten-year history of smoking was admitted to our hospital for evaluation of ischemic symptoms including numbness, easy fatigability on exercise and lack of pulse in his left arm. His left axillary, brachial and radial pulse could not be palpated and a needle reaction was negative on physical examination. Laboratory data showed no diabetes mellitus or hyperlipidemia. C-reactive protein, Wassermann's reaction, rheumatoid reaction, anti-nuclear factor, anti-DNA antibody, hypocomplementemia and circulating immune complex were negative. Invasive arteriography using contrast medium revealed segmental occlusion with multiple collateral arteries showing a typical "corkscrew" appearance at the left subclavian artery. However, no stenotic and aneurysm-like lesions suggesting aortitis syndrome, vasculo-Beçhet disease and giant arteritis were found on the aorta or other arteries including the pulmonary artery. Although no pathological study could be carried out, the angiographic and laboratory findings strongly suggested Buerger's disease as a possible cause of solitary stenosis of the left subclavian artery in this patient.

Adult↗

[A case of slowly-growing localized malignant mesothelioma].

We report a case of localized malignant mesothelioma. The patient was a 37-year-old male, admitted to our hospital because of a solitary nodular shadow in the right middle lung field noted on chest X-ray. Five years prior to admission, a solitary nodular shadow had been seen in the same area on chest X-ray, and the diameter of the tumor had gradually increased. A transbronchial biopsy specimen revealed proliferation of spindle-shaped tumor cells, suggesting fibrosarcoma. No other lesions were identified as primary foci, so we made the tentative diagnosis of primary pulmonary sarcoma prior performing right upper lobectomy. The resected specimen revealed that the tumor, which partially touched the pleura, contained a number of large and small cystic spaces, and was composed of numerous spindle-shaped tumor cells. Some of the tumor cells were immunohistochemically positive for cytokeratin and epithelial membrane antigen, and many mitotic figures were noted. Thus, we made the histopathological diagnosis of localized malignant mesothelioma.

Adult↗

Chromatin changes accompany the developmental activation of insulin-like growth factor I gene transcription.

Insulin-like growth factor I (IGF-I) is a potent regulator of postnatal growth in mammals, yet little is known about the developmental control of IGF-I synthesis. We have investigated the regulation of IGF-I expression in the rat in order to gain insight into the mechanisms of growth factor induction during early postnatal life. Steady-state levels of liver IGF-I mRNA increased by more than 15-fold during the period from fetal day 18 to postnatal day 7 and reached 50% of adult values by day 14. Transcription run-on experiments using isolated hepatic nuclei and direct analysis of nuclear RNA each demonstrated a comparable rise in nascent IGF-I mRNA over the same time period. Over 90% of transcripts were directed by promoter 1, the more 5' of the two IGF-I gene promoters. By contrast IGF-II gene transcription rates and mRNA levels fell during the first 3 weeks after birth, and albumin expression rose slightly. Analysis of chromatin structure around the IGF-I gene revealed 15 DNase I-hypersensitive sites in adult rat liver in the 120 kilobases (kb) comprising the 6 exon gene and its flanking regions (8 sites within 10 kb at the 5'-end including exons 1-3, 5 sites in the 50-kb third intron, and 2 sites in the 15-kb fifth intron). During development there was a progressive appearance of DNase I-hypersensitive sites that coincided with activation of IGF-I gene expression. One site that became fully hypersensitive by postnatal day 7 was mapped by in vivo DNAse I footprinting to the proximal 200 nucleotides of promoter 1. Since serum IGF-I values rose from 10 to 120 micrograms/liter during the initial postnatal week, these results indicate that transcriptional mechanisms are principally responsible for the stimulation of IGF-I synthesis that occurs shortly after birth. Because discrete changes in chromatin organization coincided with induction of IGF-I gene transcription, it is likely that a series of developmentally modulated transcription factors are involved the activation process.

Animals↗

In vitro proliferation and the cytotoxic specificity of a cryopreserved cytotoxic T cell clone reacting against human autologous tumor cells.

Proliferation and functional maintenance of CTL after cell cryopreservation often proves to be quite difficult. We developed an improved method for proliferating cryopreserved CTL, and for gaining their specific cytotoxic function. T cells were cryopreserved at -180 degrees C in RPMI 1640 containing 50% FCS and 10% DMSO. The cryopreserved T cells were well recovered by culturing in a medium containing the supernatant of primary cultures with TIL and autologous tumor cells, in addition to a high concentration (350 U/ml) of rIL-2. Furthermore, these cells were proliferated more efficiently when MMC-treated autologous tumor cells were used in vitro as a feeder and an antigenic stimulant. However, such a high dose IL-2 cultivation resulted in the loss of cytotoxic reactivity of CTL clone. In contrast, the withdrawal of rIL-2 from in vitro cultivation for 24 h prior to the cytotoxic assays conferred the specificity of cytotoxicity on CTL. By these methods, one can obtain a large number of CTL, and pursue the physiologic detail of the specific cytotoxic mechanism of CTL against autologous human tumor cells.

Antigens, Surface↗

An abasic site analogue activates a c-Ha-ras gene by a point mutation at modified and adjacent positions.

Synthetic c-Ha-ras genes with an analogue of an abasic site in the first or the second position of codon 12, or in the second position of codon 61 were constructed and transfected into NIH3T3 cells. The genes with the lesions in codon 12 exhibited more focus formation than a normal c-Ha-ras gene, while the gene with the lesion in codon 61 did not. Transformed cells were isolated from the foci, and the c-Ha-ras genes present in the transformants were analysed. A point mutation to A in the modified position was found most frequently in the cases of ras genes modified in codon 12. Surprisingly, point mutations in the adjacent position were also detected. These results indicate that dTMP, and not dAMP, was mainly incorporated into the sites opposite to the abasic site analogue, and that incorrect deoxynucleotides were incorporated in the position adjacent to the abasic site analogue.

3T3 Cells↗

Direct demonstration of transcriptional activation of collagen gene expression in systemic sclerosis fibroblasts: insensitivity to TGF beta 1 stimulation.

Lesional fibroblasts propagated from the skin of patients with scleroderma, when compared to normal fibroblasts, show increased synthesis of several collagens and increased levels of their corresponding mRNAs. Using constructs (COL1A2/CAT) containing the promoter for the alpha 2 (I) collagen gene in transient transfection assays with matched pairs of scleroderma and normal skin fibroblasts, we observed higher transcriptional activity of the COL1A2 gene in scleroderma fibroblasts and, in contrast to normal fibroblasts, no further expression was observed in the presence of TGF beta 1. Analysis of the expression of COL1A2 promoter deletion constructs indicates that the TGF beta responsive element functional in normal fibroblasts and the sequence involved in intrinsic upregulation of COL1A2 gene expression in scleroderma fibroblasts are both located between bp-376 (Bgl II) and bp-108 (Sma I) sites. These data may indicate that intrinsic upregulation of extracellular matrix genes in scleroderma fibroblasts utilizes a TGF beta dependent pathway.

Base Sequence↗

Cell cycle dependent gene expressions and activities of protein phosphatases PP1 and PP2A in mouse NIH3T3 fibroblasts.

We determined the mRNA levels and the activities in nuclear and non-nuclear fractions of protein phosphatase type 1 (PP1) and type 2A (PP2A) through the cell cycle in synchronized mouse NIH3T3 fibroblasts. The mRNA level for PP1 alpha was gradually elevated in late G1 phase, began to decrease in M phase, and reached the control level with entering into the next G1 phase. The mRNA level for PP2A was rapidly increased in early G1 phase, kept at the high level, and decreased after S phase. In nuclear fractions of cells, spontaneous activities of both PP1 and PP2A were gradually increased until M phase and rapidly decreased with entering the next G1 phase, while in non-nuclear fraction such dramatic alterations were not observed. Potential activities of PP1 in both fractions revealed by Co(2+)-trypsin treatment showed an oscillaion patterns similar to those of the spontaneous activities. These results strongly suggest that cell cycle dependent gene expressions and activities of PP1 and PP2A play roles in DNA synthesis and mitosis during the cell cycle.

Animals↗

[The role of insulin on renal sodium handling and sympathetic nerve activity in overweight normotensive subjects].

Recently, it was suggested that the role of hyperinsulinemia on the hypertensive mechanism of essential hypertension might be related to renal sodium handling and sympathetic nerve activity, especially in obese hypertensive patients. However, the interrelationship between insulin, obesity, renal sodium metabolism and sympathetic nerve activity in normotensive subjects (NT) still remains unclear. The present study, therefore, was undertaken to clarify the role of insulin on renal sodium handling and sympatho-adrenal function in overweight NT. The study consisted of 24NT, who were divided into two groups of twelve non-obese (NNT) and twelve obese (ONT) subjects. NNT was categorized as a body mass index (BMI) less than, and ONT as a BMI equal to or more than 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance test. During the two-hour clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance(CCr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma immunoreactive insulin (IRI), plasma norepinephrine concentration (pNE), and plasma epinephrine concentration (pE) were determined. Although no significant difference was found in age, MAP, HR, pE, CCr or UNaV between the two groups, a significantly higher IRI (p less than 0.05) and lower FENa (p less than 0.05) were observed in ONT than in NNT. There was no significant correlation between IRI and UNaV, FENa or pE in ONT or in NNT. In addition, no significant correlation was shown between FENa and pNE or pE in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

Gene expressions and activities of protein phosphatases PP1 and PP2A in rat liver regeneration after partial hepatectomy.

We have examined the levels of gene expressions and activities of protein phosphatases, PP1 and PP2A, in rat regenerating livers. PP1 alpha mRNA started to increase from 6 h after partial hepatectomy (PH) and showed two peaks at 12 and 48 h. PP2A mRNA level showed two peaks at 6 and 10-12 h. Protein phosphatase activities were determined both in non-nuclear fraction and in nuclei. While spontaneous PP1 activity in non-nuclear fraction was nearly constant, potential PP1 activity revealed by Co(2+)-trypsin treatment showed a small peak between 7 and 12 h. In nuclei, both spontaneous and potential PP1 activity began to increase from 4-7 h after PH, reached a maximum (about 2.5-fold over control levels) at 12 h, the time which corresponds to the G1 to S transition in the cell cycle, and then declined back to control levels by 7 days. PP2A activity in non-nuclear fraction was nearly constant in both spontaneous and potential forms. PP2A activity in both forms in nuclei was very low throughout. These results suggest the possibility that PP1 in nuclei plays some role in the G1 to S transition in the cell cycle of hepatocyte proliferation.

Animals↗

Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts.

Transforming growth factor beta (TGF-beta), a multifunctional cytokine, is an indirect mitogen for human fibroblasts through platelet-derived growth factor (PDGF), particularly the A ligand-alpha receptor arm of that system. TGF-beta effects on PDGF alpha receptor expression were studied in vitro using ligand binding techniques in three human dermal fibroblast strains: newborn foreskin, adult skin, and scleroderma (systemic sclerosis, SSc). Each cell strain responded differently to TGF-beta. In newborn foreskin fibroblasts, PDGF alpha receptor number decreased in a dose-dependent manner after exposure to low concentrations of TGF-beta (0.1-1 ng/ml). Responses of normal skin fibroblasts were varied, and mean net receptor number was unchanged. Increases in PDGF alpha receptor number by TGF-beta occurred consistently with SSc fibroblasts and low concentrations of TGF-beta (0.1-1 ng/ml) were particularly stimulatory. Increased surface expression of alpha receptor subunit by TGF-beta in SSc fibroblasts correlated with increased new PDGF alpha receptor synthesis as demonstrated by radioimmunoprecipitation analysis of metabolically labeled cells and with increased steady-state levels of corresponding mRNAs. In normal adult skin fibroblasts, TGF-beta had no effect on either synthesis or mRNA expression of alpha receptor subunits. Proliferative responses to PDGF-AA after pretreatment with TGF-beta correlated positively with effects of TGF-beta on expression of alpha receptor subunit. Decreased mitogenic responses to PDGF-AA were observed in foreskin fibroblasts, small changes in responses in adult fibroblasts, and significant increases in SSc fibroblasts. Thus, costimulation with PDGF-AA and TGF-beta selectively enhanced proliferation of fibroblasts with the SSc phenotype. Immunohistochemical examination of SSc and control skin biopsies revealed the presence of PDGF-AA in SSc skin. Data obtained by ligand binding, immunoprecipitation, mRNA, and mitogenic techniques are consistent with the hypothesis that activation of the PDGF-AA ligand/alpha receptor pathway is a characteristic of the SSc fibroblast and may contribute to the expansion of fibroblasts in SSc.

Adult↗