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Biomedical subjects

H Takeuchi

Publications and source records attributed to H Takeuchi.

At least 505 records · Page 28Linked to original sources

Modulation of neuropeptide effects by achatin-I, an Achatina endogenous tetrapeptide.

Achatin-I (Gly-D-Phe-L-Ala-L-Asp), an endogenous tetrapeptide in the ganglia of Achatina fulica Férussac, at 3 x 10(-6) M suppressed both the inward current (Iin) of an Achatina giant neurone, PON (periodically oscillating neurone), caused by locally ejected oxytocin, and the outward current (Iout) of v-RCDN (ventral-right cerebral distinct neurone) induced by APGW-amide. Dose (pressure duration)-response studies with oxytocin and APGW-amide showed that their ED50 values were not affected by achatin-I, whereas the Emax values were suppressed. The v-RCDN Iout caused by FMRF-amide was enhanced by achatin-I, but the same current induced by [Ser2]Mytilus inhibitory peptide ([Ser2]MIP) was not affected. Achatin-I suppressed the Iout of TAN (tonically autoactive neurone) caused by acetylcholine, but did not affect the Iin of v-RCDN elicited by acetylcholine. The Iout caused by gamma-aminobutyric acid, threo-beta-hydroxy-L-glutamic acid and dopamine was not affected by achatin-I. It is considered that achatin-I acts as a neuromodulator and has both suppressing and enhancing actions on the effects of various neurotransmitters, including peptides, in Achatina giant neurones.

Acetylcholine↗

Modulatory effects of achatin-I, an Achatina endogenous neuroactive peptide, on responses to 5-hydroxytryptamine.

Achatin-I (Gly-D-Phe-L-Ala-L-Asp) was found in the ganglia of an African giant snail (Achatina fulica Férussac), and proposed as an excitatory neurotransmitter of Achatina neurones. At 3 x 10(-6) the peptide markedly enhanced the fast inward current (Iin) of an Achatina neurone type, TAN (tonically autoactive neurone), produced by the pneumatic pressure ejection of 5-HT. This Iin was facilitated immediately by the achatin-I perfusion, and the facilitation decreased gradually even with the peptide present. The dose (duration)-response curves of the TAN fast Iin on pressure ejection in the absence (control) and presence of achatin-I at 3 x 10(-6) M (n = 8) were analyzed as follows. The ED50 (95% confidence limit) were 59.3 ms (13.9-95.3 ms) for the control, and 36.5 ms (19.5-52.6 ms) for achatin-I. The Emax were 1.06 +/- 0.11 nA for the control, and 1.74 +/- 0.26 nA for achatin-I (P < 0.01 for paired data). Among achatin-I derivatives, achatin-II (Gly-L-Phe-L-Ala-L-Asp) enhanced the TAN fast response to 5-HT, but was ten times weaker than achatin-I. [L-Glu4]achatin-I (Gly-D-Phe-L-Ala-L-Glu) and achatin-I amide (Gly-D-Phe-Ala-L-Asp-NH2) had no facilitatory effect. We propose that achatin-I is a neuromodulator as well as a neurotransmitter for Achatina giant neurones.

Amino Acid Sequence↗

AJ-2615, a long-acting Ca2+ channel antagonist with a novel structure.

AJ-2615, a dihydrodibenzothiepin derivative, at 10(-4) M inhibited the peak ICa amplitude of an identifiable Achatina neurone, PON (periodically oscillating neurone), by nearly a half of the control response 30 min after the start of perfusion (ED50: 0.96 x 10(-4) M). The ICa inhibition was still sustained 30 min after washout, indicating that AJ-2615 has long-lasting activity. The compound inhibited the ICa over a wide range of membrane potentials depolarized by the voltage pulse (Vd), but did not change the membrane potential required to produce the maximal ICa (Vd = 0 mV). The additional decrease in ICa amplitude caused by changing from low-frequency (1/5 min) depolarizing pulses to high-frequency (3/min) depolarizing pulses in the presence of AJ-2615 at 10(-4) M was 39.2 +/- 4.5% (mean+S.E.M.; n = 5), indicating use dependence. The steady state inactivation curves were measured in the presence or absence of AJ-2615 at 10(-4) M with a depolarizing prepulse (Vd = varied, duration = 30 s) followed by a depolarizing test pulse (Vd = +10 mV, duration 80 ms), with 2 ms intervals (n = 3): the ratio of AJ-2615 dissociation constant in the resting Ca2+ channel (Kr) and in the inactivated Ca2+ channel (Ki), Kr/Ki, was calculated to be 9.6:1, indicating voltage dependence.

Animals↗

Identification of a universal B cell epitope on DNA topoisomerase I, an autoantigen associated with scleroderma.

OBJECTIVE: To investigate the distribution of B cell autoepitopes of human DNA topoisomerase I (topo I), an autoantigen associated with scleroderma. METHODS: A complementary DNA clone, T1B, was used to produce recombinant proteins of topo I as beta-galactosidase fusion proteins. Immunoreactivity to these fusion proteins was then tested in 35 anti-topo I-positive sera from patients with scleroderma, by immunoblotting, enzyme-linked immunosorbent assay, and double immunodiffusion. RESULTS: One epitope was found to be universally recognized by all sera tested. Thirty-two of the samples recognized multiple antigenic regions, but sera from the remaining 3 patients recognized only this universal epitope, and in longitudinal studies of 1 of these 3 patients, the serum recognized only this epitope for more than 2 years, even though multiple, potent, antigenic regions were found on topo I. CONCLUSION: Recognition of multiple epitopes in most patients suggests that the topo I molecule itself would drive the autoimmunity on topo I. However, antigen-driven autoimmunity could not explain the production of the monoreactive anti-topo I antibody seen in the 3 patients. We thus hypothesize that there is a process whereby recognition of the universal epitope by cross-reaction develops into antigen-driven autoimmunity.

Autoantibodies↗

Postoperative PSK and OK-432 immunochemotherapy for patients with gastric cancer.

We evaluated the effects of chemotherapy given postoperatively with and without immunomodulators on the survival of patients who had undergone resection for gastric cancer. We conducted a retrospective survey of data on 963 Japanese patients treated at our department of surgery between 1965 and 1987. Data related to the duration of postoperative survival were calculated for those who received chemotherapy, i.e. an individualized combination of various agents given with or without the immunomodulators PSK, a protein extract of the fungus Coriolus versicolor, and/or OK-432, a preparation of an attenuated strain of Streptococcus (immunochemotherapy). Postoperative immunochemotherapy was more often prescribed for patients with advanced disease. The survival of patients who received immunochemotherapy was shorter than that of patients who received only chemotherapy. In a subgroup of patients adjusted for disease stage, the survival of those on chemotherapy versus immunochemotherapy did not differ significantly at any stage. For optimal results, a protocol for postoperative immunochemotherapy needs to be designed and investigated prospectively and according to the stage of gastric cancer. The stage III gastric cancers seem amenable to a favorable response.

Adjuvants, Immunologic↗

Reconstruction of the posterior cruciate ligament with LAD-augmented semitendinosus and gracilis tendons: a preliminary report.

We present our technique for reconstruction of the posterior cruciate ligament (PCL) using the semitendinosus and gracilis tendons with the Kennedy ligament augmentation device (LAD). The safe and excellent exposure of the posterior aspect of the knee allowed us to identify the most isometric position in the intercondylar notch of the femur. In addition to this advantage, firm fixation of the LAD-augmented tendons with staples prevented the tibia from sagging posteriorly during early protected motion of the knee. Evaluation of 12 patients followed for more than 2 years showed 9 (75%) good results. In this small series no correlation was found between clinical results and the number of major structures injured, indicating that postoperative care is as important as isometric placement of the PCL in obtaining satisfactory results.

Adolescent↗

Application of polymerase chain reaction-single strand conformation polymorphism analysis to the diagnosis and screening of adenine phosphoribosyltransferase deficiency.

Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis is a rapid and sensitive method used to identify point mutations in a given sequence of genomic DNA. We applied this method to the diagnosis of adenine phosphoribosyltransferase (APRT) deficiency, which is an autosomal recessive hereditary disease leading to 2,8-dihydroxyadenine urolithiasis. Genomic APRT genes were amplified and labeled simultaneously with [alpha-32P]dCTP (cytidine triphosphate) by PCR. When run in a 6% polyacrylamide gel containing 10% glycerol, two types of mutant genes-APRT*QO and APRT*J-gave bands clearly distinct from those of the equivalent normal APRT genes. Using this method we diagnosed both homozygotes and heterozygotes for defective APRT genes. On screening 80 Japanese individuals for polymorphism or mutations by PCR-SSCP we did not find any alterations leading to a false positive diagnosis. These findings suggest that PCR-SSCP, in addition to being rapid and sensitive, is a useful diagnostic method which is highly specific in detecting mutant APRT genes in the Japanese population.

Adenine↗

Restriction fragment length polymorphisms of the CYP11B1 gene in the Japanese population.

Restriction fragment length polymorphisms (RFLPs) of the CYP11B1 gene were studied in Japanese using cDNA clone P450c11 as a probe. Genomic DNAs from 60 unrelated Japanese individuals were digested with 8 different restriction enzymes and analyzed by Southern blot hybridization. Two RFLPs were detected in MspI digests of the DNA. One (A) was characterized by polymorphic bands at 3.4 and 2.5 kilobase-pairs (kb) and the other (B) by polymorphic bands at 1.7 and 1.2 kb. The third RFLP was observed in PvuII-digested samples and was polymorphic at 5.8 and 4.0 kb bands. Two of the three RFLPs found, RFLP (A) and (C), have not been described in the only previous report which was based on Caucasian samples. We also examined the RFLPs of a 3 generation family of 11 beta-hydroxylase deficiency caused by an abnormality of the CYP11B1 gene. All the family members were homozygous in all three RFLPs and was thus not informative.

Adrenal Hyperplasia, Congenital↗

A case of Goldenhar syndrome associated with growth hormone deficiency.

We have experienced the case of a 10-year-old boy who had Goldenhar syndrome accompanied by growth hormone (GH) deficiency. His height increased after treatment with growth hormone was administered. We found no untoward effects of the hormone and we consider that treatment with GH is useful for patients who present with Goldenhar syndrome associated with growth hormone deficiency.

Child↗

Spinal xanthogranuloma in a child: case report.

A case of a patient with a xanthogranuloma in the thoracic spine is presented. Magnetic resonance imaging revealed an intradural extramedullary tumor between T6 and T9 as a low-intensity mass on both T1- and T2-weighted images. Total removal of this tumor was achieved through a laminoplastic laminectomy. Differentiation of this disease from other xanthogranulomas in the central nervous system is discussed.

Diagnosis, Differential↗

Four calcium phosphate ceramics as bone substitutes for non-weight-bearing.

Calcium phosphate ceramics, beta-calcium pyrophosphate (Ca2P2O7), beta-tricalcium phosphate (Ca3(PO4)2), hydroxyapatite (Ca10(PO4)6(OH)2) and tetracalcium phosphate (Ca4(PO4)2O), were prepared. The calcium:phosphorus ratios and microporosities were 1 (31.6%), 1.5 (1.6%), 1.66 (1%) and 2 (34.6%) respectively. Samples (15 mm x 10 mm x 2 mm), abraded with No. 2000 alumina powder, were implanted into the tibial metaphysis of mature male rabbits. Failure load, when an implant detached from the bone or the bone itself broke, was measured. At 10 wk after implantation, the failure loads in beta-calcium pyrophosphate, beta-tricalcium phosphate, hydroxyapatite and tetracalcium phosphate were 31.65 +/- 9.90 N, 72.81 +/- 19.01 N, 49.49 +/- 17.25 N and 43.22 +/- 14.99 N respectively. At 25 wk after implantation, the values were 47.04 +/- 14.90 N, 71.34 +/- 19.50 N, 69.09 +/- 16.17 N and 62.03 +/- 18.62 N respectively. Histologically, bone bonding behaviour of calcium phosphate ceramics did not vary with the calcium:phosphorus ratio, as observed by contact microradiogram, Giemsa surface staining and scanning electron micrograph-electron probe micro analysis. There was no intervening soft tissue at the interface of bone and ceramics. Hydroxyapatite or tricalcium phosphate are used as bone substitutes. However, their mechanical strength is insufficient for weight-bearing and they are used as bone filler. This study showed that the apparent insignificance of strict calcium:phosphorus ratio with respect to the biological results greatly simplifies processing of calcium phosphate ceramics for clinical application. In clinical application, calcium phosphate ceramics with different Ca:P can be used as bone fillers for bone defects or bone cavities under non-weight-bearing conditions.

Animals↗

Influence of the drugs for membrane excitability modification on the excitation caused by achatin-I.

1. The pneumatic pressure ejection of achatin-I (Gly-D-Phe-L-Ala-L-Asp), an endogenous tetrapeptide having a D-phenylalanine residue, produced an inward current (Iin) in an identifiable giant neuron, PON (periodically oscillating neuron), of an African giant snail, Achatina fulica Férussac. The influence of the drugs for membrane excitability modification, applied by perfusion, on the PON excitation caused by achatin-I was examined under voltage clamp. 2. The four channel blocking drugs, tetrodotoxin (TTX), tetraethylammonium chloride (TEA), verapamil and picrotoxin, at 10(-4) M did not affect significantly the PON excitation caused by the peptide. 3. N-beta-phenylpropionyl-L-tyrosine (BPLT), a membrane hyperpolarizant, at 10(-6) M and concanavalin A (Con A), which altered the response to L-glutamate, at 100 micrograms/ml-1 were considered to hardly influence the PON excitation caused by achatin-I.

Amino Acid Sequence↗

A reliable operative procedure for preparing a sufficiently nourished gastric tube for esophageal reconstruction.

We developed a reliable procedure for obtaining sufficient blood flow at the anastomotic site of the gastric tube for esophageal reconstruction. By utilizing the junction between the left gastroepiploic and short gastric vessels via the splenic hilar vascular arcade, the distal portion of the gastric tube could be sufficiently nourished. The application of this technique resulted in a complete prevention of postoperative anastomotic leakage after antesternal esophageal reconstruction.

Aged↗

Long-term followup of the Kock and Indiana pouch procedures.

Between 1984 and 1991, 115 consecutive patients underwent cutaneous continent urinary diversion comprising 76 Kock and 39 Indiana pouch procedures. The 2 different forms of achieving continent urinary diversion were subsequently compared in a long-term followup that evaluated complications, including pouch function and the need for revisions. In the Kock pouch group there were 14 (18.4%) early postoperative complications (3 months), which required 4 subsequent reoperations (5.3%). The Indiana pouch group had a similar incidence of early complications (17.9%) but there were no reservoir related problems. The long-term study group comprised 68 Kock and 37 Indiana pouch patients who were observed for 12 months or longer (mean followup 53 and 34 months, respectively). Of 9 efferent nipple valve malfunctions observed in the Kock pouch group 5 required surgical revision. Of 16 complications related to afferent limb function 15 were caused by the use of polyester fiber fabric for the anchoring collar and 8 of these 15 complications required surgical revision. The first 2 Indiana pouch patients had pouch deformities due to incomplete detubularization of the cecum that required surgical repair. Overall, surgical revisions, including minor repairs, were performed on 15 Kock pouch patients (22.1%) and 4 Indiana pouch patients (10.8%). Both forms of the procedure preserved continence to a satisfactory degree. Urinary tract stones developed in 18 patients (26.5%) from the Kock pouch group, usually on the exposed staples or the eroded, nonabsorbable collar used to construct the nipple valves. Stone formation was rare (5.4%) in the Indiana pouch group. The incidence of ureteral implantation stricture was low in both procedures. There was no significant difference in the incidence of bacteriuria between the 2 methods of urinary diversion. These data demonstrate that the Kock pouch and Indiana pouch procedures can be accomplished with the same early postoperative complication rate. Our 8-year experience showed a high incidence of Kock afferent nipple valve malfunction. However, most of these malfunctions were due to the use of a nonabsorbable collar and can be avoided. When taking this into account, therefore, it can be concluded that the Indiana pouch functions as well as the Kock pouch with roughly the same incidence of late complications and the same reoperation rate but with a lower incidence of stone formation.

Adult↗

A case of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine urolithiasis: review of the reported cases with 2,8-dihydroxyadenine stones in Japan.

We report a case of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine urolithiasis. Polymerase chain reaction-single strand conformation polymorphism analysis demonstrated that APRT*J and APRT*Q0 alleles from the father and mother, respectively, had been transmitted to the patient. We also reviewed the literature regarding Japanese patients with 2,8-dihydroxyadenine urolithiasis. There seemed to be little difference in clinical course between type 2 homozygotes and compound heterozygotes. However, hemolysate APRT activities of compound heterozygotes were lower than those of type 2 homozygotes.

Adenine↗

Low-substituted hydroxypropylcellulose as a sustained-drug release matrix base or disintegrant depending on its particle size and loading in formulation.

Tablets of acetaminophen as a model drug were prepared with low-substituted hydroxypropylcellulose (L-HPC) of various particle sizes at various loadings in the formulation. Drug release into an aqueous dissolution medium (pH 1.2) was remarkably sustained from tablets prepared with fine L-HPC (LH41) at loadings of more than 20%. Tablets prepared with less than 20% LH41 or with coarse L-HPCs (LH11, LH21, and LH31) disintegrated in the medium, resulting in rapid release of the drug. The difference in behavior could not be explained in terms of differences in tablet strength, but in swelling and water uptake abilities of the tablet's polymer. Swelling work (swelling force), water penetration speed, and water uptake of LH41 (4.4-microns average particle size) were much smaller than those of coarse L-HPCs. The formation of a continuous gel-like layer on the surface of tablets containing more than 20% LH41 was another factor to sustain the drug release rate.

Acetaminophen↗

A novel cytochrome P-450IID6 mutant gene associated with Parkinson's disease.

Genetic polymorphism of the CYP2D6 gene [phenotypically individuals are either poor metabolizers (PM) or extensive metabolizers (EM)] has been reported to be associated with susceptibility to Parkinson's disease. We analyzed CYP2D6 genes from Japanese patients and controls, and found that EM/PM polymorphism is not a suitable marker for populations with a low PM frequency. However, a novel mutant highly associated with Parkinson's disease was discovered. The mutation was located at the HhaI site in exon 6 and changed a conserved amino acid residue, Arg296, to Cys296. The risk factor for the mutant homozygote was 5.56 (95% CI, 1.30-23.82). These results suggest that the HhaI polymorphism in the CYP2D6 gene is a part of the molecular basis of Parkinson's disease.

Arginine↗