Biomedical subjects

S Ichihara

Publications and source records attributed to S Ichihara.

At least 55 records · Page 3Linked to original sources

PubMed1996

Neoadjuvant chemotherapy in scirrhous cancer of the stomach using uracil and tegafur and cisplatin.

We administered a mixture of uracil and tegafur (UFT)/cisplatin (CDDP) chemotherapy in 28 patients with scirrhous gastric cancer. In the regimen, UFT was orally administered at a dose of 200 mg/m2 twice a day. The CDDP was administered at a dose of 90 mg/m2 by 24-hour continuous infusion every 4 weeks. As a result, antitumor effects for primary gastric foci were achieved in 14 of the 28 patients (50%). Ascites from peritoneal dissemination disappeared completely in eight of 13 patients (62%). Total gastrectomy was performed in ten patients after 2 to 3 courses of chemotherapy. Histological response grades assessed on the resected specimen were Grade 2 in four, Grade 1b in three, Grade 1a in one and Grade 0 in two patients. Neoadjuvant chemotherapy is feasible against scirrhous gastric cancer and a subsequent prospective randomized trial should be prepared to clarify the survival benefit of the treatment.

Adenocarcinoma, Scirrhous↗

PubMed1995

Cerebellar diaschisis in pontine infarctions: a report of five cases.

We evaluate regional cerebral and cerebellar perfusion to prove the occurrence and follow the persistence of crossed cerebellar diaschisis in infratentorial pontine infarction. Six consecutive patients exhibiting mild hemiparetic symptoms or a heavy feeling in the head (mean age 65 years; four women, two men) and diagnosed as having pontine infarction by magnetic resonance imaging were subjected to evaluation. Lesions due to infarction were located at the upper basis pontis in five patients and the upper tegmentum pontis in one, and medially at the paramedian portion in four and laterally in two. Regional cerebral and cerebellar perfusion was evaluated semiquantitatively by iodine-123 N-isopropyl-p-iodoamphetamine (IMP) single-photon emission tomography (SPET); this was done during the acute stage in five cases (mean time after onset: 0.7 months) and during the chronic stage in three (mean time after onset: 14.8 months). Four patients had two examinations during their clinical courses. For semiquantitative evaluation of perfusion, an asymmetry index was calculated for each region of interest, set symmetrically in regions of the cerebral cortex and cerebellum in both hemispheres. Significant asymmetry (P < 0.01) in cerebellar perfusion, which was reduced in the contralateral (n = 4) or ipsilateral (n = 1) cerebellar hemisphere, was demonstrated semiquantitatively in four cases during the acute stage and in one during the chronic stage, as compared with normal controls (n = 5, mean age 61 years). This asymmetry continued to the chronic stage (6.5 and 33.0 months) in two cases, while no patient showed any significant asymmetries in cerebral perfusion in any region of interest in either SPET study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

The dithiane Ro 44-5912 enhances vinblastine sensitivity of drug resistant and parental KB lines in vivo.

The multidrug resistance modifying activity of a dithiane analogue of tiapamil, Ro 44-5912, was examined in vivo. Results of acute toxicity studies in mice indicated that lethal toxicity occurred with doses greater than 1 mmol/kg of body weight. In a preliminary pharmacokinetic investigation, Ro 44-5912 appeared to have a longer half-life in mice than did its (R) enantiomer Ro 44-5911 (3.15 +/- 0.02 h versus 2.15 +/- 0.14 h) as measured by total radiolabel in plasma. In non-tumour bearing mice, Ro 44-5912 enhanced the toxicity of vinblastine in a manner that was dependent on the dose of both drugs. Vinblastine did not have a significant effect on tumour growth when given to nude mice bearing the parental cell line KB-3-1 at a dose of 1.5 mg/kg once per week for 3 weeks. Combination treatment with Ro 44-5912 markedly enhanced the antitumour activity of vinblastine. Similar results were seen when KB-3-1 tumours were treated with the combination of vinblastine plus cyclosporin A. Another tiapamil analogue, Ro 11-2933, had no enhancing activity with this tumour when used at an equitoxic combination dose. Ro 44-5912 also significantly enhanced vinblastine activity with P-glycoprotein-expressing KB-8-5 tumours. In three independent experiments, Ro 44-5912 enhanced the growth inhibiting activity of vinblastine by a mean of approximately 40%. Neither Ro-11-2933 nor cyclosporin A, at the maximal tolerated doses in combination with vinblastine, led to significant inhibition of KB-8-5 tumour growth compared to treatment with the two vehicles alone. These results show that Ro 44-5912 is an active modulator of drug resistance in vivo.

Animals↗

PubMed1995

Temporal-discontinuity detection with contrast-modulated gratings.

Three experiments on temporal-discontinuity detection were carried out. In experiment 1, temporal-discontinuity thresholds were measured for sinusoidal gratings by the use of the double-staircase method. A sinusoidal grating was presented twice successively. The subject judged whether or not an interval was present. The temporal-discontinuity threshold increased as the spatial frequency of the grating increased, but decreased as the contrast of the grating increased. In experiment 2, contrast-modulated gratings were used instead of the sinusoidal grating. The temporal-discontinuity threshold increased as the carrier frequency increased, and the threshold for each contrast-modulated grating was similar to that for the no-modulation (sinusoidal) grating whose contrast was the same as the maximum local contrast of the contrast-modulated grating. In experiment 3, temporal-discontinuity thresholds were measured for low-contrast (3%) sinusoidal gratings. The thresholds were very low, even for such low-contrast gratings. These results suggest that the low-spatial-frequency channels are not involved in detecting the modulation frequency of the contrast-modulated grating. Rather, the local contrast seems to be the determinant of the detection of the contrast-modulated grating itself.

Attention↗

PubMed1995

Decreasing accumulation of acetate in a rich medium by Escherichia coli on introduction of genes on a multicopy plasmid.

Escherichia coli excretes acetate during aerobic growth in a rich medium, L-broth containing 0.4% glucose, and growth ceases before depletion of glucose because of the decrease in pH caused by the accumulation of acetate. The addition of sodium phosphate buffer to the medium allows cells to reuse the acetate accumulated. Reuse of the acetate, however, does not occur in the presence of remaining glucose. A gene on a multicopy plasmid was found to significantly decrease the accumulation of acetate by the transformant and the growth did not cease until depletion of both the glucose and acetate in the medium. The gene was tentatively named mlc (making large colonies). The putative Mlc protein has high hology with the NagC protein, which is a regulator protein in the nag operon responsible for the use of N-acetylglucosamine. The nagC gene on a multicopy plasmid also decreased the accumulation of acetate. Although the function of the genes in the phenomenon described is still unclear, transformants harboring the mlc gene or nagC gene on a multicopy plasmid will be useful for condensed cultivations involving glucose.

Acetates↗

PubMed1994

Intraductal carcinoma of the breast associated with high levels of circulating tumor-associated antigens (CA 15-3 and NCC-ST-439).

BACKGROUND: A remarkable elevation of serum tumor-associated antigen levels usually occurs in advanced or metastatic cancer and has not been reported previously in the setting of noninvasive carcinoma of the breast. METHODS: An immunohistochemical and histopathologic study is presented on a specimen taken from a 43-year-old Japanese woman with micropapillary intraductal carcinoma of the breast with significantly high levels of preoperative circulating tumor-associated antigens, CA 15-3 (198.5 U/ml) and NCC-ST-439 (1400 U/ml). RESULTS: A histologic specimen consisted of numerous cysts lined by slightly stratified, monotonous columnar cells producing foci of micropapillary intraductal carcinoma. Extensive sampling of the specimen demonstrated no invasive foci although faintly eosinophilic secretory material occasionally leaked from disrupted cysts into the surrounding stroma. The cancerous and normal epithelium showed intense apical reactivity with monoclonal antibodies 115D8, DF3, and NCC-ST-439; intraluminal and spilled secretion also showed positive reaction with these antibodies. Serum levels of CA 15-3 and NCC-ST-439 were within normal limits after subcutaneous mastectomy. No carcinoembryonic antigen was demonstrated either in the sera, the neoplastic epithelium, or the secretory material. CONCLUSIONS: These histopathologic and immunohistochemical studies showed that the leaked secretion from the disrupted cysts into the surrounding connective tissue stroma may be responsible for the marked elevation of circulating tumor-associated antigen levels in this micropapillary intraductal carcinoma.

Adult↗

PubMed1994

Point mutations at glycine-121 of Escherichia coli dihydrofolate reductase: important roles of a flexible loop in the stability and function.

To elucidate the role of a flexible loop in the stability and function of Escherichia coli dihydrofolate reductase, glycine-121 in a flexible loop (residues 117-131), separated by 19 A from active site Asp27, was substituted by site-directed mutagenesis with eight amino acids (Ala, Val, Leu, Asp, Ser, Cys, Tyr, and His). The free energy change of unfolding decreased in the order of G121A > G121D > G121C > G121S, wild-type > G121H > G121Y > G121L > G121V. The thermal denaturation temperature decreased with all mutations, accompanied by a decrease in the calorimetric enthalpy of denaturation. The steady-state kinetic parameter for the enzyme reaction, Km, was only slightly influenced, but kcat was significantly decreased by the mutations, there being 3- (G121C) to 42-fold (G121L) decreases in kcat/Km compared to that of the wild-type enzyme. The effects of mutations on the stability and enzyme activity were statistically examined as a function of the hydrophobicity and volume of amino acids introduced. The diminished stability and activity with increases in the hydrophobicity and volume of amino acids suggest that the main effect of the mutations would be modification of the flexibility of the loop due to overcrowding of the bulky side chains, overcoming the enhancement of the hydrophobic interaction.

Base Sequence↗

PubMed1994

Identification and characterization of the ackA (acetate kinase A)-pta (phosphotransacetylase) operon and complementation analysis of acetate utilization by an ackA-pta deletion mutant of Escherichia coli.

The pta gene encoding phosphotransacetylase was cloned on a high copy plasmid with or without the ackA gene encoding acetate kinase in Escherichia coli. The acetate kinase and phosphotransacetylase were overproduced in cells harboring the plasmid possessing both genes. Nucleotide sequencing of the pta gene revealed that it is able to produce a polypeptide comprising 714 amino acid residues, which starts at 70 base pairs downstream from the stop codon of the ackA gene. The 77-kDa protein band of overproduced phosphotransacetylase was observed on SDS-polyacrylamide gel electrophoresis, of which the amino terminal sequence corresponds to that of the deduced polypeptide without the amino terminal methionine. Two transcripts of pta of different sizes were found in the cells. A 3,700 nucleotide transcript, which covers the ackA and pta genes, seemed to be produced by the first promoter in the operon and a 2,300 nucleotide transcript, which covers just pta, seemed to be produced by the second promoter. In a synthetic medium containing acetate as the sole carbon source, the growth of an ackA-pta double mutant was greatly impaired. Complementation analyses revealed that both the acetate kinase and phosphotransacetylase were required for the rapid growth in the acetate medium.

Acetate Kinase↗

PubMed1994

Infarction of breast fibroadenoma in a postmenopausal woman.

Infarction of a breast fibroadenoma usually occurs in young females during pregnancy or lactation. This report describes a rare case of the total infarction of a fibroadenoma in a 58 year old postmenopausal woman. The chief complaint was a rapidly enlarged, slightly painful lump. Medullary carcinoma was suspected on palpation and mammography. Microscopically, the tumor was composed of a coarsely lobulated necrotic mass invaginated into an epithelial lined cyst. This was interpreted as an infarcted intracanalicular fibroadenoma, although the possibility of an infarcted phyllodes tumor cannot be entirely excluded. The significance of this rare event is the possible confusion with carcinoma. Extensive search for viable tissue is essential for the confirmation of the diagnosis.

Breast Neoplasms↗

PubMed1994

Intraductal carcinoma of the breast arising in sclerosing adenosis.

An unusual case of intraductal carcinoma of the breast arising in sclerosing adenosis is reported. A 49 year old Japanese woman noticed a lump in her right breast 3 years before she sought medical advice. Histologic examination of the lumpectomy specimen showed, adjacent to intraductal papilloma, sclerosing adenosis involved in a neoplastic cellular proliferation with cribriform pattern and comedo necrosis. Immunohistochemical study with anti-actin antibodies discriminated intraductal carcinoma from adjacent sclerosing adenosis by highlighting myoepithelial components in the latter. Extensive sampling revealed no carcinoma outside the sclerosing adenosis, implying that the intraductal carcinoma did originate in the tubules of sclerosing adenosis. A review of the literature indicated that the ductal to lobular ratio among carcinoma in situ concurring with sclerosing adenosis is about 1:2. The average age of patients with ductal and lobular carcinoma in situ in sclerosing adenosis is 39 and 43.7, respectively. It is suggested that carcinoma in situ arising in sclerosing adenosis and fibroadenoma have a similar biological basis.

Adenofibroma↗

PubMed1994

Construction of Pta-Ack pathway deletion mutants of Escherichia coli and characteristic growth profiles of the mutants in a rich medium.

Escherichia coli grown in a rich medium excreted acetate and reused the acetate. Using cloned genes and a plasmid with a temperature-sensitive replication origin, three kinds of Pta-Ack pathway deletion mutants were constructed. Acetate production and reuse by wild-type cells grown in the rich medium was confirmed to largely occur through the Pta-Ack pathway. The deletion mutants of the gene encoding phosphotransacetylase secreted pyruvate before the secretion of acetate into the medium. A deletion mutant of the gene encoding acetate kinase grew at a slow rate, but its secretion and use of acetate were rapid. These results indicated that a pathway(s), other than the Pta-Ack pathway, functions in the control of excess carbon flow in the mutants.

Acetate Kinase↗

PubMed1994

Successful treatment of primary sclerosing cholangitis with cyclosporine and corticosteroid.

A case of primary sclerosing cholangitis (PSC) successfully treated with cyclosporine is described. A 65-year-old man who presented with jaundice and anemia was diagnosed as having PSC, accompanied by pancreatic duct abnormalities. Cholangiography and pancreatography showed marked improvements following combined therapy with cyclosporine and methylprednisolone. Cyclosporine seems to be a promising drug for the treatment of patients with PSC. This report reasons that the same disease process affects both the pancreatic ducts and the bile ducts, and that stagnation of pancreatic juice may have a role to play in the pancreatic duct abnormalities.

Aged↗

PubMed1993

Effects of point mutation in a flexible loop on the stability and enzymatic function of Escherichia coli dihydrofolate reductase.

To elucidate the role of a flexible loop in the stability and function of Escherichia coli dihydrofolate reductase, glycine-121 in the flexible loop (117-131) was substituted to valine and leucine by site-directed mutagenesis. Despite the increased hydrophobicity of the side chains, the free energy changes of unfolding of the two mutants (G121V and G121L) determined by urea denaturation at 15 degrees C were decreased by 1.22 and 0.38 kcal/mol, respectively, compared with that of the wild-type. Thermal denaturation temperature, as monitored by differential scanning calorimetry, was decreased by 2.4 and 5.2 degrees C for G121V and G121L, respectively, accompanying the decrease in enthalpy change of denaturation. These findings indicate that the structure of DHFR is destabilized by the mutations, predominantly due to the large decrease in enthalpy change of denaturation relative to entropy change of denaturation. The steady-state kinetic parameter in the enzyme reaction, Km, was not influenced but kcat was greatly decreased by these mutations, resulting in 240- and 52-fold decreases in kcat/Km for G121V and G121L, respectively. The main effect of the mutations appeared to be modification of the flexibility of the loop due to overcrowding of the bulky side chains, overcoming the enhancement of hydrophobic interaction.

Base Sequence↗

PubMed1993

Molecular cloning, sequencing, and mapping of the gene encoding protease I and characterization of proteinase and proteinase-defective Escherichia coli mutants.

Clones carrying the gene encoding a proteinase were isolated from Clarke and Carbon's collection, using a chromogenic substrate, N-benzyloxycarbonyl-L-phenylalanine beta-naphthyl ester. The three clones isolated, pLC6-33, pLC13-1, and pLC36-46, shared the same chromosomal DNA region. A 0.9-kb Sau3AI fragment within this region was found to be responsible for the overproduction of the proteinase, and the nucleotide sequence of the region was then determined. The proteinase was purified to homogeneity from the soluble fraction of an overproducing strain possessing the cloned gene. N-terminal amino acid sequencing of the purified protein revealed that the cloned gene is the structural gene for the protein, with the protein being synthesized in precursor form with a signal peptide. On the basis of its molecular mass (20 kDa), periplasmic localization, and substrate specificity, we conclude this protein to be protease I. By using the gene cloned on a plasmid, a deletion mutant was constructed in which the gene was replaced by the kanamycin resistance gene (Kmr) on the chromosome. The Kmr gene was mapped at 11.8 min, the gene order being dnaZ-adk-ush-Kmr-purE, which is consistent with the map position of apeA, the gene encoding protease I in Salmonella typhimurium. Therefore, the gene was named apeA. Deletion of the apeA gene, either with or without deletion of other proteinases (protease IV and aminopeptidase N), did not have any effect on cell growth in the various media tested.

Amino Acid Sequence↗

PubMed1993

Effect of medication with pravastatin sodium on hemorheological parameters in patients with hyperlipoproteinemia.

Pravastatin sodium, a newly developed potent synthesis inhibitor of HMG-CoA (beta-hydroxy-beta-methylglutaryl-cocarboxylase-A) reductase (Sankyo Co., Ltd., Japan) was medicated, 10 approximately 15 mg/day (mean: 11.1 mg/day) for 10.2 weeks in mean, in 14 patients with primary hyperlipoproteinemia of more than 230 mg/dl of serum cholesterol levels (mean age: 56.9 y.o.). The values of serum cholesterol decreased (from 242 +/- 12 to 207 +/- 22; mg/dl), and of high density lipoprotein (HDL) increased (from 42.3 +/- 8.8 to 45.3 +/- 9.2; mg/dl) significantly (p < 0.05, respectively) 10.2 weeks in mean after medication with pravastatin sodium. The whole blood viscosity, at every shear rate examined, corrected blood viscosity, for the standard hematocrit level of 45%, and plasma fibrinogen decreased significantly (p < 0.05, respectively) at the same time, without showing significant differences any more 10.2 weeks in mean after medication with those in 14 elderly normal subjects (mean age: 56.7 y.o.), which suggested that the hemorheological parameters in patients with primary hyperlipoproteinemia had improved significantly by medication with pravastatin sodium.

Cholesterol↗

PubMed1992

Prevalence of pancreatitis in liver diseases of various etiologies: an analysis of 107,754 adult autopsies in Japan.

The frequency of acute and chronic pancreatitis is 3.3 and 2.1%, respectively, in 107,754 adult autopsies in Japan. Acute pancreatitis is highly associated with liver diseases of various etiologies such as subacute hepatitis (16.1%), fulminant hepatitis (13.5%), biliary cirrhosis (10.5%), cholangiocarcinoma (8.6%) and postnecrotic cirrhosis (7.1%). Chronic pancreatitis is also closely related to various liver diseases. It is suggested that the portal venous stasis in liver diseases may predispose the patients to develop pancreatitis regardless of the etiology of liver diseases.

Acute Disease↗

PubMed1991

The behavior of remaining enzyme activity in a suicidal enzyme system.

We derived an equation which describes the plot of the remaining enzyme activity versus ratio of initial concentration of suicide substrate to that of enzyme to obtain a partition ratio from the time-course of remaining enzyme activity. The simulation data calculated from the representative kinetic model for a suicide substrate were used to verify this equation, which approximated steady state kinetics. Although the time-dependent loss of enzyme activity is usually characterized by pseudo-first-order kinetics, the present results show that pseudo-first-order kinetics are followed only when the ratio of initial concentration of suicide substrate to that of enzyme is greater than the partition ratio. Our results also show that the present method can be used to obtain the partition ratio of a suicide substrate from the time-course of the remaining enzyme activity when the suicide substrate is given an arbitrary concentration of one, where the ratio of initial concentration of suicide substrate to that of enzyme is less than the partition ratio. The theoretically verified equation was also checked against reported experimental data for a microsomal enzyme system.

Enzyme Inhibitors↗

PubMed1990

Thymic carcinoid--a case report and review of the literature.

We report herein a case of a patient with thymic carcinoid who was operated on twice and has been followed for 9 years. In 1979, the original tumor was removed through an emergency left thoracotomy incision done for a hemothorax caused by an anterior mediastinal biopsy. Tumor recurrence was found 6 years later and removal carried out through a median sternotomy. The patient has been working and enjoying life following radiation and chemotherapy for a total of 9 years after his first operation. Recurrent thymic carcinoid has been thought to carry a poor prognosis, but this successfully treated case has been followed up for a long time after the removal of his recurrent tumor. We present this case and discuss other such cases reported in the Japanese literature.

Carcinoid Tumor↗