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Biomedical subjects

S Taniguchi

Publications and source records attributed to S Taniguchi.

At least 217 records · Page 12Linked to original sources

Different electrophysiological character of I-, ClO4-, and SCN- in the transport by Na+/I- symporter.

The electrophysiological characteristics of the Na+/I- symporter were examined using the Chinese hamster ovary (CHO) cell line, which was transfected with the rat Na+/I- symporter gene and stably expressed the Na+/I- symporter. In this cell line, iodide uptake was dependent on Na+, and kinetic studies revealed that the K(m) for iodide was 35 microM, similar to that of FRTL-5 cells. The maximal velocity at the cell protein level was 6- to 10-fold higher than in FRTL-5 cells. ClO-4 and SCN- dose-dependently inhibited iodide uptake in a competitive manner. Electrophysiological characteristics were examined using the whole-cell patch-clamp technique. The holding current at-40 mV rapidly shifted inwardly when the cells were perfused with 1 mEq I- or SCN-. The inward current induced by 1 mEq I- did not increase when bathing solution was replaced with a Tyrode solution with 10 mEq I-, indicating that 1 mEq I- was a saturating amount. The inward current induced by 1 mEq I- increased 1.5-fold by changing the bathing solution to a Tyrode solution containing 1 mEq I- and 1 mEq SCN-. The inward current induced by 0.5 mEq SCN- decreased when the bathing solution was changed to a Tyrode solution containing 0.5 mEq SCN- and 10 mEq I-. These findings indicated that the I- ion and the SCN- ion were carried by the NA+/ I- symporter with at least two Na+ ions. The current induced by the transport of SCN- was larger than that induced by the transport of I-, possibly because the number of Na+ ions that was carried with one SCN- ion was larger than the number of Na+ ions carried with one I- ion. Surprisingly, the perfusion of ClO-4 did not induce an inward current, indicating that ClO-4 bound to the Na+/I- symporter, but was not carried by it, or that one ClO-4 ion was carried with one Na+ ion.

Animals↗

Transformation-related expression of a low-molecular-mass tropomyosin isoform TM5/TM30nm in transformed rat fibroblastic cell lines.

We cloned a full-length rat TM5/TM30nm cDNA. Using this cDNA as a probe, we demonstrated that expression of TM5/TM30nm mRNA was higher in the tumorigenic rat fibroblastic cell lines SR-3Y1-2 and fos-SR-3Y1-202 than in the normal cell line 3Y1. High expression of TM5/TM30nm protein in SR-3Y1-2 and fos-SR-3Y1-202 cells was also detected by Western blot analysis using anti-TM5/TM30nm antiserum. In addition, the cellular localization of this protein differed between 3Y1 cells and tumorigenic ones. These findings suggest that TM5/TM30nm is involved in malignant transformation of rat fibroblastic cells.

Amino Acid Sequence↗

Successful treatment of intraoperative pulmonary tumor embolism from renal cell carcinoma.

During left nephrectomy in a 35-year-old woman with a left renal cell carcinoma extending into the inferior vena cava (IVC) and right atrium, cardiac arrest occurred. Immediate transesophageal echocardiography demonstrated that the event was caused by a pulmonary tumor embolism. Emergent cardiopulmonary bypass (CPB) was established and the tumors in the pulmonary arteries were successfully removed. The left nephrectomy was completed. The patient recovered in the intensive care unit without any neurological deficit. A postoperative pulmonary perfusion scintigram showed no defect in the pulmonary circulation. Transesophageal echocardiography was useful for making a rapid diagnosis of an intraoperative pulmonary embolism originating from a tumor of the IVC or right atrium.

Adult↗

Primary bronchogenic carcinoma in recipients of heart transplants.

With the exception of carcinomas of the skin and lip, carcinoma of the bronchus is the most common carcinoma that afflicts recipients of solid organ grafts. Of 859 tumors occurring in 830 recipients of thoracic organs reported to the Cincinnati Tumor Transplant Registry, 242 were carcinomas and 68 of these were bronchogenic carcinomas, which therefore made up 8% of the overall total. There are, however, relatively few reports of heart transplant patients with bronchogenic carcinoma in the literature. We present details of four patients who developed this malignancy out of a total of 196 patients who survived and have been followed up for more than 3 months at our center, an incidence of 2%. The mean period from the time of transplant to diagnosis of malignancy was 58 months (range 11-82 months). The histology was squamous or anaplastic in three cases, and adenocarcinoma in one. Immunosuppressive therapy was reduced in all cases. Resection was carried out in two patients (both of whom died 6 and 11 months later, respectively), resection was combined with chemotherapy and radiation in one patient (alive 15 months later), and therapy consisting of radiation alone was given to one patient (died within 1 month). We conclude that bronchogenic carcinoma is relatively common in patients with heart transplants and that it has a poor prognosis.

Adult↗

Comparative rest and exercise hemodynamics of allograft and prosthetic valves in the aortic position.

BACKGROUND: Allograft aortic valve replacement has gained widespread acceptance. However, there is little information about in vivo allograft valve function at rest and during exercise. METHODS: Cardiac catheterization was performed to measure hemodynamic variables at rest and during supine bicycle exercise in 44 patients who had had aortic valve replacement using allograft valves or Bicer or St. Jude Medical prosthetic valves 19 to 27 mm in diameter. Sixteen patients received an allograft valve; 17, a Bicer valve; and 11, a St. Jude Medical valve. There were no significant differences between the three groups in age, body surface area, left ventricular end-systolic and end-diastolic volume indices, exercise cardiac index, exercise heart rate, or work load achieved. Left ventricular and ascending aortic pressures were measured simultaneously according to the transseptal method. RESULTS: The mean pressure gradient was generally higher for the Bicer and St. Jude Medical valves than for the allograft valves, both at rest and during exercise. Significant differences were obtained in patients with small-sized valves (21 and 23 mm); pressure gradients were higher in the prosthetic valve groups. In patients with large-sized prosthetic valves (25 mm), there were no significant differences between the three groups at rest and during exercise. However, there was no pressure gradient at all for allograft valves. CONCLUSIONS: Exercise cardiac catheterization confirms that the allograft aortic valve is an ideal substitute from the hemodynamic aspect, particularly in patients with a small aortic root and in those who perform strenuous exercise.

Aortic Valve↗

Granulocyte colony-stimulating factor-combined marrow-ablative chemotherapy and autologous blood cell transplantation for the treatment of patients with acute myelogenous leukemia in first remission. The Fukouka Bone Marrow Transplant Group.

We conducted a clinical trial to increase the chemosensitivity of residual leukemic cells by combining G-CSF to marrow-ablative chemotherapy, including cytosine arabinoside (Ara-C), and facilitated by autologous blood cell transplantation (ABCT) for treatment of acute myelogenous leukemia (AML) in first complete remission. A total of 16 patients were consecutively treated with granulocyte colony-stimulating factor (G-CSF)-combined high-dose chemotherapy (busulfan, etoposide and Ara-C) followed by autotransplantation of peripheral blood progenitor cells, which had been collected after the consolidation chemotherapy. At a median follow-up time of 44.5 months, the probability of 5-year event-free survival was 74.5% with only three leukemic relapses. This preliminary observation suggests the effectiveness of G-CSF-combined conditioning and ABCT as a post-remission therapy for AML.

Adolescent↗

Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia.

The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stem cell transplantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients. Peripheral blood stem cells (PBSC) were collected during recovery after consolidation chemotherapy. High-dose chemotherapy consisting of busulfan (16 mg/kg), etoposide (40 mg/kg), and cytosine arabinoside (3 g/m2 x 4) (BEA regimen) was used for pretransplant conditioning in 13 patients. For the remaining 47 patients, granulocyte colony-stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning. Unpurged, cryopreserved PBSC containing a median number of 5.4 x 10(8) MNC/kg or 12 x 10(4) CFU-GM/kg were reinfused at transplantation. The median number of days to granulocytes exceeding 500/microl and last platelet transfusion were 15 (8-44) and 24 (0->180), respectively. The 3-year probabilities of disease-free survival (DFS) and relapse were 78.6 and 21.4% for patients transplanted in first remission, 29.6 and 64.4% for those in second or third remission, and 11.1 and 77.8% for those in relapse, respectively. There were no transplant-related deaths within 100 days of transplantation. Age, disease status at transplantation, and number of induction chemotherapies to first complete remission were risk factors affecting the outcome of ABSCT. These results of ABSCT for AML in first remission warrant a prospective study of ABSCT as post-remission therapy.

Acute Disease↗

A novel mutation causing complete deficiency of thyroxine binding globulin.

OBJECTIVE: Thyroxine binding globulin (TBG) is a serum protein that transports thyroxine. Three naturally occurring mutations have been reported to produce complete deficiency of TBG (TBG-CD). The first to be reported was TBG-CD5 in caucasian families of French-Canadian origin and consists of substitutions in exons 2 and 3. TBG-CD of English ethnic origin (TBG-CD6) is characterized by a thymine deletion in codon 165 (exon 1). In Japanese families with TBG-CD (TBG-CDJ), a variant has been characterized with a deletion of the first base of the codon for amino acid 352 (exon 4) in the common type TBG. In this communication we report a new type of TBG-CD in a family of Japanese ethnic origin that is characterized by a single nucleotide substitution in place of two nucleotides in exon 1. This is an uncommon mutation which we have been unable to find in other genes. DESIGN: Exons of the TBG gene amplified by the polymerase chain reaction (PCR) were subcloned and sequenced. To examine for the presence of the same mutation in potentially affected individuals, we performed PCR using primer-directed mutagenesis or allele-specific amplification. PATIENTS: The index case was of Japanese ethnic origin, and was diagnosed as having TBG deficiency on the basis of undetectable serum TBG. The patient consented to this evaluation and the protocol was in accordance with IRB standards. MEASUREMENTS: Serum thyroid hormones, thyrotrophin binding inhibitory immunoglobulin and TBG concentrations were measured by conventional radio-immunoassay. Genomic DNA was extracted from white blood cells. RESULTS: In the index case exons 2, 3 and 4 were normal, but nucleotides 144 (cytosine) and 145 (thymine) in exon 1 were substituted with a single base (adenine) which induced a frame shift in the reading frame, resulting in an early stop codon at codon 51. The patient and his daughters were confirmed as having this mutation using primer-directed mutagenesis or allele-specific amplification. CONCLUSIONS: We have described a novel mutation in the TBG gene in a Japanese family. This results in a frame shift and premature stop codon, and was associated with undetectable serum TBG in the index case.

Exons↗

Pertechnetate thyroid uptake is not always suppressed in patients with subacute thyroiditis.

The authors studied the clinical courses and immunologic aspects in 15 patients (age range, 32-69 years old; 14 women) with clinical features that were similar to subacute thyroiditis (SAT). In 2 patients (group A) whose thyrotropin-binding inhibitory immunoglobulins (TBII) and thyroid stimulating antibody (TSAb) showed strongly positive activity at the initial visit, Tc-99m pertechnetate thyroid uptake (Tc-99m uptake) was elevated (5.6% and 3.8%, respectively, normal; 0.7-3.0%). In 6 (group B) of 13 other patients, Tc-99m uptake was not completely suppressed (2 normal, 4 near normal) and imaging showed uptake in one lobe. In 7 (group C), however, there was no evidence of uptake in either lobe. Inflammatory process was localized in one lobe in all group B patients, and was in both lobes in all group C patients but one. Serum TSH levels were detectable in at least 4 patients (2 group B, 2 group C) low in all. There were no patients in both groups B and C in whom TBII and/or TSAb were detected at the initial visit. In SAT, marked suppression of Tc-99m uptake may be ascribed mainly to inflammatory follicular cell damage, but it is not always suppressed, owing to an association similar to Graves' disease and other unknown mechanism(s).

Adult↗

Mechanism of anion permeation in the basolateral membrane of isolated rabbit renal proximal tubule S3 segment.

Conventional and double-barreled microelectrodes were used to examine the anion selectivity of Cl- conductance in the basolateral membrane of rabbit renal proximal tubule S3 segment. The permeability sequence determined by anion replacements in the presence of K+ channel blocker quinine was SCN- > I- > Br- > Cl- > gluconate in both nonperfused and luminally perfused tubules. The anion-selective microelectrodes with higher sensitivity to I- enabled us to measure intracellular I- activities. With these electrodes, we could compare the conductive movements of Cl- and I- in response to the increase in bath K+ concentrations and confirmed that the conductance sequence was also I- > Cl-. Although the basolateral potential changes generated by Cl- and Br- currents were stimulated by adenosine 3',5'-cyclic monophosphate (cAMP), the potential changes by SCN- and I- currents were somewhat inhibited by cAMP. In addition, the conductive uptake of I- was, in contrast to that of Cl-, inhibited by cAMP These results are consistent with the existence of at least two distinct anion conductances in this membrane, which are differently regulated by cAMP.

Animals↗

Prostaglandins induce proliferation of rat hepatocytes through a prostaglandin E2 receptor EP3 subtype.

We characterized the proliferative action of prostaglandins (PGs) in relation to their membrane receptors on rat hepatocytes in primary culture. PGs in the order 16,16-dimethyl PGE2 > PGE2 > PGF2alpha >> PGD2 augmented epidermal growth factor (EGF)/insulin-induced DNA synthesis, assessed by [(3)H]thymidine incorporation, in a concentration-dependent manner, whereas PGs alone did not stimulate basal DNA synthesis without EGF and insulin. The cells exhibited [(3)H]PGE2 binding sites that were displaced by unlabeled PGs in the order PGE1 = PGE2 > PGF2alpha > PGD2. PGE2 inhibited glucagon-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation concentration dependently. The mean effective concentration for DNA synthesis, median inhibitory concentration for cAMP accumulation, and dissociation constant for [(3)H]PGE2 binding at 25 degrees C were almost identical (approximately 70 nM). Treatment of the cells with pertussis toxin (100 ng/ml), which ADP-ribosylated most of the 41-kDa substrate, abolished the proliferative effects of PGs. We detected the expression of mRNA of the EP3 subtype PGE2 receptor using reverse transcription-polymerase chain reaction. Moreover, an EP3 agonist, enprostil, but not the EP1 agonist 17-phenyl-trinor-PGE2 or the EP2/EP4 agonist 11-deoxy-PGE1, stimulated EGF/insulin-induced DNA synthesis. These results indicate that PGs act as comitogenic growth factors through the EP3 subtype PGE2 receptor coupled with G(i) protein in cultured rat hepatocytes.

Animals↗

cAMP mediates homologous downregulation of PAF receptor mRNA expression in mesangial cells.

To clarify the molecular mechanism and significance of homologous desensitization of platelet-activating factor (PAF) signaling, we examined the effect of PAF on PAF receptor mRNA expression in rat mesangial cells by Northern blot analysis. Treatment of the cells with PAF (10(-7)-10(-8) M) reduced the expression of PAF receptor mRNA in 1 h, and this reduction was recovered by pretreatment of mesangial cells with a specific PAF receptor antagonist, WEB-2086 (10(-6) M), or a cyclooxygenase inhibitor, indomethacin (10(-6) M), for 10 min. PAF-stimulated prostaglandin E2 (PGE2) and adenosine 3',5'-cyclic monophosphate (cAMP) formation was measured by radioimmunoassays specific for each substance. Reduction of PAF receptor mRNA expression was mimicked by treatment of the cells with PGE2 (10(-6) M) or dibutyryl-cAMP (10(-3) M), a cell-permeable analog of cAMP. These results, taken together, suggest that PAF receptor mRNA expression is downregulated by exposure to PAF in cultured mesangial cells. This homologous downregulation is mediated by cAMP production through PGE2 synthesis.

Animals↗

Capnometry as a tool to unmask silent pulmonary embolism.

Because pulmonary embolism is often silent, simple clinical procedures are desirable to identify patients with a low to intermediate probability of pulmonary embolism. Among 19,467 patients managed under general anesthesia, we had one bile tract surgery case and three neurosurgical cases whose silent pulmonary embolism was initially suggested by an increase in the arterial to end-tidal CO2 gradient (from 17 to 27 mmHg) after general anesthesia was induced or their trachea was intubated. During the preoperative assessment, the patients presented no clinical manifestations suggestive of pulmonary embolism. Our initial diagnosis was confirmed by scintigraphy and/or angiography done immediately after the operations. Because capnometry has been shown to be applicable to non-intubated, spontaneously breathing patients, we suggest that measuring the gradient may serve as an additional method for unmasking silent pulmonary embolism in patients at risk or with disturbed consciousness, whether they are scheduled for operations or not.

Aged↗

Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung.

We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury.

Animals↗

National survey on accidental low back pain in workplace.

Out of the "Report on Workers" Casualties" presented by the employers in the entire nation in 1986 and 1988 to the Labor Standards Inspection Offices, 13,166 cases diagnosed as low back pain (5,820 cases in 1986 and 7,346 cases in 1988) were sampled and studied. This survey revealed that its incidence in men was about 4 times greater than that in women, being noted uniformely in all age groups except the 50 or older age group in men. As to types of industry, it was seen to be high in those working in the mining and cargo industries, as well as those working in the transport, traffic, forestry and agriculture, livestock, and fishing industries. As to the types of occupation, the incidence of low back pain was high in those working in transportation and construction. Onset was noted every month throughout the year, but a little less in December. It was pronounced at the beginning of the week, and seemed to peak immediately after starting the day's work, at 9 a.m. followed by 10 a.m. There was a trend toward accidental low back pain being caused frequently when one worked in an unnatural posture, especially in regular work when acting single-handed.

Accidents, Occupational↗

Clinical xenotransplantation: past, present and future.

The ability to use animal organs, such as from the pig, for the purposes of transplantation in humans, would clearly overcome the major shortage of human organs that greatly restricts transplantation programmes worldwide. Recent experimental advances have raised the possibility of renewed attempts at organ xenotransplantation in humans within the near future. Previous clinical experience, dating back to 1906, is briefly reviewed. The problems that still require resolution include the immunological barrier, the risk of transferring infectious agents with the transplanted organ, and uncertainty as to whether the transplanted animal organ will function satisfactorily in the human environment. Ironically, the answers to some of these problems may only be provided when clinical xenotransplantation is undertaken.

Animals↗