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T Teramoto

Publications and source records attributed to T Teramoto.

At least 91 records · Page 5Linked to original sources
PubMed1998

Functional characterization of ion permeation pathway in the N-type Ca2+ channel.

Multiple types of high-voltage-activated Ca2+ channels, including L-, N-, P-, Q- and R-types have been distinguished from each other mainly employing pharmacological agents that selectively block particular types of Ca2+ channels. Except for the dihydropyridine-sensitive L-type Ca2+ channels, electrophysiological characterization has yet to be conducted thoroughly enough to biophysically distinguish the remaining Ca2+ channel types. In particular, the ion permeation properties of N-type Ca2+ channels have not been clarified, although the kinetic properties of both the L- and N-type Ca2+ channels are relatively well described. To establish ion conducting properties of the N-type Ca2+ channel, we examined a homogeneous population of recombinant N-type Ca2+ channels expressed in baby hamster kidney cells, using a conventional whole cell patch-clamp technique. The recombinant N-type Ca2+ channel, composed of the alpha1B, alpha2a, and beta1a subunits, displayed high-voltage-activated Ba2+ currents elicited by a test pulse more positive than -30 mV, and were strongly blocked by the N-type channel blocker omega-conotoxin-GVIA. In the presence of 110 mM Ba2+, the unitary current showed a slope conductance of 18.2 pS, characteristic of N-type channels. Ca2+ and Sr2+ resulted in smaller ion fluxes than Ba2+, with the ratio 1.0:0. 72:0.75 of maximum conductance in current-voltage relationships of Ba2+, Ca2+, and Sr2+ currents, respectively. In mixtures of Ba2+ and Ca2+, where the Ca2+ concentration was steadily increased in place of Ba2+, with the total concentration of Ba2+ and Ca2+ held constant at 3 mM, the current amplitude went through a clear minimum when 20% of the external Ba2+ was replaced by Ca+2. This anomalous mole fraction effect suggests an ion-binding site where two or more permeant ions can sit simultaneously. By using an external solution containing 110 mM Na+ without polyvalent cations, inward Na+ currents were evoked by test potentials more positive than -50 mV. These currents were activated and inactivated in a kinetic manner similar to that of Ba2+ currents. Application of inorganic Ca2+ antagonists blocked Ba2+ currents through N-type channels in a concentration-dependent manner. The rank order of inhibition was La3+ >/= Cd2+ >> Zn2+ > Ni2+ >/= Co2+. When a short strong depolarization was applied before test pulses of moderate depolarizing potentials, relief from channel blockade by La3+ and Cd2+ and subsequent channel reblocking was observed. The measured rate (2 x 10(8) M-1 s-1) of reblocking approached the diffusion-controlled limit. These results suggest that N-type Ca2+ channels share general features of a high affinity ion-binding site with the L-type Ca2+ channel, and that this site is easily accessible from the outside of the channel pore.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Genetic analysis enables definite and rapid diagnosis of cerebrotendinous xanthomatosis.

Mutations in the sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis (CTX). Early diagnosis of CTX is crucial because treatment with chenodeoxycholic acid can prevent or reverse some of the neurologic disability associated with the disease. We report the identification of three types of mutations (Arg441Trp, Arg372Gln, and Arg441Gln) in the CYP27 gene in five patients with suspected CTX from four unrelated families by restriction endonuclease analysis.

Adult↗
PubMed1998

Effect of combination treatment with a vitamin D analog (OCT) and a bisphosphonate (AHPrBP) in a nude mouse model of cancer-associated hypercalcemia.

Hypercalcemia represents one of the important paraneoplastic syndromes affecting morbidity and mortality of cancer patients. We and others have demonstrated that vitamin D analogs with little calcemic activities suppress the transcription of the parathyroid hormone-related peptide (PTHrP) gene, a major humor responsible for cancer hypercalcemia, and thereby prevent the development of hypercalcemic syndrome. The present study was undertaken: to compare the therapeutic efficacy of a vitamin D analog, 22-oxa-1,25-dihydroxyvitamin D3 (OCT), and a bisphosphonate (disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate [AHPrBP]), an inhibitor of osteoclastic bone resorption, on cancer-induced hypercalcemia; and to see if the effect could be enhanced by combination treatment, using a nude mouse model implanted with a human pancreas carcinoma (FA-6). After a single intravenous administration, OCT (5 microg/kg of body weight [BW]) was as effective as AHPrBP (10 mg/kg of BW) in lowering blood ionized calcium levels in tumor-bearing nude mice, and their combination further enhanced the therapeutic effect. Although AHPrBP lost its efficacy after repeated injections, OCT was still effective after the third administration. The therapeutic effect of OCT in cancer hypercalcemia was observed in four other human tumors, including another pancreas carcinoma (PAN-7), two squamous cell carcinomas of the lung (KCC-C1 and LC-6), and a squamous carcinoma of the pharynx (PHA-1), all of which elaborated PTHrP into the circulation. Treatment with OCT resulted in a decrease in circulating PTHrP levels by approximately 50% in two representative models. However, the mechanism underlying the antihypercalcemic effect of OCT seemed complex, involving inhibition of PTHrP production, suppression of excessive bone resorption, and an antitumor activity. OCT also markedly inhibited the body weight loss with tumor growth, while AHPrBP, which exhibited a similar antihypercalcemic effect, was less effective than OCT in preventing cachexia. The anticachectic activity of their combination did not exceed that of OCT alone, suggesting a hypercalcemia-dependent as well as an independent mechanism of cancer cachexia. It is concluded that OCT may be useful, either as a single agent or in combination with bisphosphonates, for the treatment of cancer-associated hypercalcemia and cachexia.

Animals↗
PubMed1998

[Successful treatment of hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan].

Satisfactory therapeutic effects are rarely obtained with oral chemotherapy for gastric cancer. We have experienced successful treatment for synchronous hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan. The patient was a 78-year-old female, diagnosed as having gastric cancer with multiple hepatic metastases, who underwent gastrectomy. Immunohistochemistry of the resected specimens with anti-thymidine phosphorylase (dThdPase) antibody yielded positive results for dThdPase in the primary tumor as well as the hepatic metastases. Two months after surgery, administration of 400 mg of 5'-DFUR per day and 2 mg i.v. of Lentinan every other week was started. Four months after discharge, carcinoembryonic antigen (CEA) in plasma showed an abrupt logarithmic decline. Furthermore, a 99% reduction in hepatic metastases was demonstrated by abdominal CT. At present, 22 months after surgery, the patient is managed on an outpatient basis with no complaints of any side effects. Immunochemotherapy using 5'-DFUR and Lentinan may be effective against gastric malignancies expressing dThdPase activity.

Adenocarcinoma↗
PubMed1998

Interleukin-1beta and interleukin-6 increase levels of apolipoprotein B mRNA and decrease accumulation of its protein in culture medium of HepG2 cells.

The purpose of the present study was to examine the regulation of levels of apolipoprotein B (apoB) mRNA and its protein by cytokines in HepG2 cells. A dose-dependent increase in apoB mRNA levels was observed in the presence of either interleukin-1beta (IL-1beta) or IL-6 alone. This increase occurred as early as 1 h after IL-1beta or IL-6 stimulation. Exogenous addition of IL-1beta (5 ng/ml) and IL-6 (50 ng/ml) induced 2.8- and 2.1-fold increases as a result of 18 h of culture, respectively. Co-stimulation with IL-1beta and IL-6 significantly enhanced the increase in apoB mRNA levels stimulated with either cytokine alone. Treatment with cycloheximide prevented the induction of apoB mRNA by IL-1beta, but not by IL-6. These findings suggest that enhancement of apoB mRNA levels by these cytokines is mediated through different pathways. Conversely, IL-1beta and IL-6 lowered the accumulation of apoB protein levels in the culture medium. The pulse-chase study showed that addition of N-acetyl leucyl leucyl norleucinal to the medium induced a decrease in newly synthesized apoB in the cell lysate in response to IL-1beta (P < 0.05) or IL-6 (not to a significant extent) compared with control. These findings demonstrated that the lower level of apoB in the medium was caused by the enhanced intracellular degradation. In addition, IL-1beta increased LDL receptor mRNA levels as well as protein activity, although IL-6 did not, suggesting that the more marked decrease in apoB accumulation in the medium induced by IL-1beta compared with that induced by IL-6 may reflect an increased uptake of apoB from the medium by IL-1beta. The present study demonstrates that a cytokine network may be involved in the metabolism of apoB under certain conditions such as inflammation.

Apolipoproteins B↗
PubMed1998

[Evaluation of peritoneal lavage smears and intraperitoneal administration of anti-neoplastic agents in stage III and IV gastric cancer].

Examinations of peritoneal lavage smears (cy) in gastric cancer surgical stages III and IV are very important for determining the disease stage. We have been carrying out these examinations for 8 years. One hundred sixty patients with gastric cancer were examined. The incidence of cy positivity was higher in T4 than in T3, and higher in P1,2,3 than in P0. We performed intraperitoneal administration of CDDP in 10 patients with gastric cancer using a reservoir (Infuse-A-Port) implanted in the abdominal wall once a week. No difference in survival was observed between patients who received chemotherapy via i.p. and those who received it i.v.

Adenocarcinoma↗
PubMed1998

[Ischemic disease of the intestine].

With the remarkable progress in diagnostic techniques, the recent increase in the incidence of arteriosclerosis and the gradually aging population, a great deal of attention is now being focused on intestinal ischemia and this disease has come to be regarded as one of the clinically important pathological conditions. From the clinic aspect, special attention should be directed to the artery which is involved in intestinal ischemia. Furthermore acute superior mesenteric arterial ischemia (SMA ischemia), ischemic colitis, non-occlusive mesenteric ischemia (NOMI) require serious attentions. Few specific findings of these pathological conditions can be obtained in general examinations, therefore angiography is the most useful technique for making difinitive diagnoses. SMA ischemia and NOMI are progressive diseases and their prognoses are poor. The progress of ischemic colitis is gradual and the conservative therapy consisting of fasting, drip infusion and antibiotic administration is generally effective in treating this disease.

Acute Disease↗
PubMed1997

A novel type of calcium channel sensitive to omega-agatoxin-TK in cultured rat cerebral cortical neurons.

We characterized the electrophysiological properties of calcium channels in cultured rat cerebral cortical neurons using omega-agatoxin-TK (omega-Aga-TK) by a patch-clamp technique. Two types of slowly inactivating calcium channels sensitive to omega-Aga-TK were detected. The first type showed high sensitivity to omega-Aga-TK and low recovery from the omega-Aga-TK-induced blockade during washout, corresponding to the P-type channel. The second type showed low sensitivity to omega-Aga-TK and high recovery, resembling the Q-type channel, although it was distinct from the Q-type in terms of slower inactivation kinetics. We designate this channel as Q(L)-type (long-lasting Q channel). The omega-Aga-TK-sensitive calcium channels involved in the glutamatergic synaptic transmission were also divided into two types based on the sensitivity to omega-Aga-TK and reversibility of omega-Aga-TK-induced blockade. We conclude that the Q(L)-type is a novel type of channel, and that both P-type and Q(L)-type channels play a significant role in the cerebral cortical synaptic transmission.

Agatoxins↗
PubMed1997

Purification and characterization of low density lipoprotein containing apolipoprotein B-48 from the plasma of an apoE-deficient patient.

The plasma low density lipoprotein (LDL) of an apolipoprotein (apo) E-deficient patient was reported to contain apoB-48 (D. Kurosaka et al., Atherosclerosis 1988;88:15), which is a structural protein of chylomicrons and is not present in the fasting plasma LDL of normal subjects. We separated the LDLs containing apoB-48 (apoB-48 LDL) and apoB-100 (apoB-100 LDL) from the plasma of this patient using heparin-sepharose column chromatography. The apoB-48 LDL contained apoA-I, apoA-IV, and apoCs besides apoB-48. There were no differences in size and lipid composition of the apoB-48 and the apoB-100 LDLs, both of which contained more triglyceride than LDL from normal subjects. After incubation with apoE, the apoB-48 LDL contained twice the amount of apoE than the apoB-100 LDL and showed a marked decrease in apoA-I and apoA-IV content. These results suggest that lipoproteins containing apoB-48 in normal subjects can be quickly taken up through an apoE-mediated receptor mechanism after receiving apoE in exchange for apoA-I and A-IV.

Apolipoprotein B-100↗
PubMed1997

CA19-9 as a predictor of recurrence in patients with colorectal cancer.

BACKGROUND AND OBJECTIVES: CA19-9 is a cancer-associated carbohydrate antigen that plays a role in the process of tumor progression as an adhesion molecule. METHODS: We evaluated the prognostic value of CA19-9 tumor expression and CA19-9 preoperative and postoperative serum levels in colorectal cancer patients treated by complete resection. The most powerful discrimination was achieved using the three CA19-9 markers in combination. RESULTS: CA19-9 tumor expression was identified by immunostaining in 71.0% (86/121) of primary carcinomas. Positive CA19-9 serum levels (> or = 37 U/ml) were restricted to cases with positive tumor expression, and CA19-9 was detected more frequently in preoperative serum (20.6%, 25/121) than in 1-month postoperative serum (6.6%, 8/121). Positive tumor expression, positive preoperative serum level, and positive postoperative serum level were all predictive of increased cancer mortality. Patients with three negative parameters had no recurrences and 97.1% 5-year survival, whereas patients with three positive parameters had 62.5% recurrence and 42.8% 5-year survival. CONCLUSIONS: CA19-9 detection in tumor tissue and serum identified patients at high risk of cancer recurrence and death and may be useful in selecting patients for adjuvant therapy.

Adult↗
PubMed1997

Partial cloning of rat CD34 cDNA and expression during stem cell-dependent liver regeneration in the adult rat.

The sialomucin CD34 is expressed on human and mouse hematopoietic stem cells and is used as an important marker for isolating the hematopoietic stem/progenitor cells. The involvement of hepatic stem cells in liver regeneration under certain conditions in adult rats is now well supported. The objective of the present research was to explore the idea that CD34 might also be expressed on hepatic stem cell progeny. Polymerase chain reaction (PCR)-based cloning of rat CD34 was partially accomplished. During the hepatic stem cell activation (2-acetylaminofluorene/partial hepatectomy [AAF/PH] model), the CD34 transcripts were increased and reached the peak level between 9 and 12 days after partial hepatectomy when the progenitor cells (e.g., oval cells, early hepatocytes in basophilic foci, and intestinal type of cells) are most abundant. Both in situ hybridization and immunohistochemistry, using anti-mouse CD34 antibody, which recognizes the cytoplasmic domain, clearly showed the expression of CD34 on oval cells as well as on endothelial cells of large hepatic vessels. In addition, bile ductular epithelial (BDE) cells both in the AAF/PH model and in normal liver expressed CD34, suggesting a close relationship between BDE cells and the hepatic stem-cell compartment. Taken together, the data indicate that CD34 would, similar to its role in the hematopoietic system, be an important probe for characterizing the cellular biology of the hepatic stem-cell compartment.

2-Acetylaminofluorene↗
PubMed1997

Per anum intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer: the ultimate sphincter-preserving operation.

PURPOSE: The most important goal of sphincter-preserving operations for rectal cancer is to secure a distal surgical margin of safety and the anal sphincter. However, it is not always easy to transect the rectum and to secure a distal surgical margin of safety through the abdominal approach for tumors situated extremely low in the rectum. The aim of this study was to describe and to evaluate a new technique of per anum intersphincteric rectal dissection and coloanal anastomosis. METHODS: The rectum, including the entire width of the internal anal sphincter, is transected circumferentially via the anal route to secure the surgical margin of safety under direct vision and is mobilized proximally as far as possible through the intersphincteric plane. Per anum coloanal anastomosis is performed following transabdominal resection of the rectum. RESULTS: This technique has been used in 12 patients. There have been no instances of short-term or long-term anastomotic complications. CONCLUSIONS: This technique is safe when anastomosis must be performed at the dentate line. It is the best sphincter-preserving operation for lower rectal cancer and does not result in serious postoperative anal dysfunction.

Anal Canal↗
PubMed1997

Reduced expression of the interferon-gamma messenger RNA in IgG2 deficiency.

The specific defect that causes IgG2 deficiency, which is one of the primary immunodeficiencies, is unknown. Recently, it was shown that interferon-gamma (IFN-gamma) induces synthesis of human germline C gamma 2 transcripts. In the authors' previous study and the present one, peripheral blood lymphocytes (PBLs) of all five tested patients with IgG2 deficiency failed to produce enough IFN-gamma when stimulated with phytohaemagglutinin or concanavalin A although they produced a sufficient amount of interleukin-2 (IL-2). The low level of IgG2 production in pokeweed mitogen-stimulated PBLs of four tested patients was improved by the addition of recombinant IFN-gamma. In this study, the amount of IFN-gamma messenger RNA showed various degrees of reduction in all five tested patients. Sequence analysis of the IFN-gamma coding regions and flanking regions revealed neither a point mutation nor a deletion for any of the patients. Thus the results suggest that the reduced expression of IFN-gamma messenger RNA may play an important role in the IgG2 deficiency of these patients.

Antigens, CD↗
PubMed1997

Skipping of exon 14 and possible instability of both the mRNA and the resultant truncated protein underlie a common cholesteryl ester transfer protein deficiency in Japan.

Among the Japanese population, a G-to-A mutation at the beginning of intron 14 of the human cholesteryl ester transfer protein (CETP) gene is a frequent cause of CETP deficiency characterized by markedly increased HDL cholesterol. The resulting abnormalities responsible for null CETP deficiency were studied in detail. The CETP mRNA transcripts amplified by polymerase chain reaction from the monocyte-derived macrophages of two homozygous patients were both found to be normal except for the whole deletion of exon 14. The deletion causes a shift of reading frame and introduces a premature termination codon downstream. Examination of the macrophage RNA from heterozygotes suggested the increased instability of the abnormal mRNA in the cytoplasm, because the amount of the aberrant transcript was nearly one third that of a normal transcript in the cytoplasm, while they were equal in the nucleus. Although this indicated the synthesis of a mutant CETP that lacks about 15% at its carboxy terminus, immunoblot analysis demonstrated that the abnormal CETP was virtually absent in both the media and cell lysates of transfected COS-1 cells, which massively expressed the mutant CETP mRNA. These results elucidate the primary abnormality due to the common CETP splicing mutation to be the exon skipping of mRNA, which decreases the level of mRNA and produces a truncated protein that should be rapidly degraded intracellularly.

Alternative Splicing↗
PubMed1997

Two Japanese siblings with Bloom syndrome gene mutation and B-cell lymphoma.

Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by lupus-like erythematous telangiectasia of the face, sun sensitivity, infertility and stunted growth. Upper respiratory tract and gastrointestinal infections are commonly associated with the decreased immunoglobulin levels found in BS patients. Chromosomal abnormalities are hallmarks of the disorder, and high frequencies of sister chromatid exchanges and quadriradial configurations in lymphocytes and fibroblasts are virtually diagnostic. Recently, the causative gene for BS (BLM) has been identified. We encountered and defined a family with a nonsense mutation in BLM. The brother and sister were homozygous for the mutation and both developed B-cell malignant lymphoma in their twenties. These findings indicate the importance of prenatal diagnosis and the detection of BS carriers based on molecular genetic analysis.

Adenosine Triphosphatases↗