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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 1,045 records · Page 58Linked to original sources
PubMedDate not supplied

A new simple test for evaluation of intestinal bacteria.

We investigated a newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) to determine its suitability to evaluate enteric bacteria. This compound, PABA-UDCA, is deconjugated by cholylglycine hydrolase to release free PABA whereas it is completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriological experiments, almost all of the microorganisms which split glycocholic acid deconjugated this compound. In animal experiments, urinary excretions of PABA were measured for 6 hours following oral administration of 10 mg PABA-UDCA. Ten control rats excreted 338.5 +/- 43.8 micrograms (mean +/- SD) of PABA; 10 rats with intestinal bacterial overgrowth due to enteric stagnant loops excreted more (673.6 +/- 222.1 micrograms; p less than 0.01), whereas 10 rats in each of 8 groups with intestinal antisepsis by oral administration of various antibiotics excreted significantly less (p less than 0.001) (ampicillin + doxycycline + fradiomycin: 18.3 +/- 16.7, polymixin B + tinidazole: 14.0 +/- 8.0, polymixin B: 224.9 +/- 74.3, tinidazole: 42.7 +/- 27.3, kanamycin: 50.3 +/- 18.2, clindamycin: 57.4 +/- 23.3, vancomycin: 70.4 +/- 27.0, and paromomycin: 160.4 +/- 51.9 micrograms). These observations indicate that this compound is likely to offer a simple and rapid method for evaluation of intestinal microorganisms without the use of radioisotopes or expensive, special apparatus.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Characterization of immunosuppressive factors expressed in serum by rat tolerogenic liver transplantation.

BACKGROUND: In a rat tolerogenic model of orthotopic liver transplantation (OLT), recipient serum after OLT (post-OLT serum) possesses strong immunosuppressive activity. This study aimed to identify immunosuppressive factors present in early post-OLT serum. METHODS: Immunosuppressive activity was evaluated in vitro by inhibition of the mixed-lymphocyte reaction (MLR). Autoantigens recognized by MLR-inhibitory IgG were identified by the internal protein sequencing. RESULTS: Recipient post-OLT serum inhibited MLR, and OLT-inducible IgG was the major immunosuppressive factor. IgG from post-OLT sera (2 to 3 weeks) specifically reacted to 31; 34; and 73-kd autoantigens on spleen cells. The internal sequences of the 31- and 34-kd antigens coincided completely with those of histone H1 molecules. Immunodepletion of anti-histone H1 antibodies (Abs) from early post-OLT serum abolished the MLR-inhibitory activity. Furthermore, rabbit polyclonal Ab-directed histone H1 not only significantly suppressed rat and human MLR but also prolonged survival of heart allografts. Flow-cytometric analysis revealed that some live PVG splenocytes were stained with antihistone H1 Abs, and that these positive cells increased on Con A stimulation. Western blot analysis indicated that several cross-reactive antigens against anti-histone H1 Abs were found in their membrane fraction. CONCLUSIONS: In this study we provide evidence that autoreactive Abs, against histone H1 are a major OLT-induced graft survival factor, and may play at least a part in overcoming the acute rejection phase to establish solid allograft tolerance.

Animals↗
PubMedDate not supplied

Postoperative acute respiratory failure following thoracotomy in a patient with Charcot-Marie-Tooth disease.

We present the case of a patient with Charcot-Marie-Tooth (CMT) disease who required prolonged ventilatory support following a thoracotomy due to respiratory muscle weakness. Although CMT was traditionally believed to affect only skeletal muscles, recent evidence suggests that respiratory involvement is relatively common, even in the absence of pulmonary symptoms. Assessment of respiratory muscle strength using measurements of vital capacity and negative inspiratory force is helpful in evaluating pulmonary reserve in patients with CMT.

Adult↗
PubMedDate not supplied

The life-cycle of human immunodeficiency virus type 1.

The life-cycle of human immunodeficiency virus type 1 (HIV-1) has been studied using several techniques including immunoelectron microscopy and cryomicroscopy. The HIV-1 particle consists of an envelope, a core and the region between the core and the envelope (matrix). Virus particles in the extracellular space are observed as having various profiles: a central or an eccentric round electron-dense core, a bar-shaped electron-dense core, and immature doughnut-shaped particle. HIV-1 particles in the hydrated state were observed by high-resolution electron cryomicroscopy to be spherical and the lipid membrane was clearly resolved as a bilayer. Projections around the circumference were seen to be knob-like. The shapes and sizes of the projections, especially the head parts, were found to vary with each projection. HIV-1 cores were isolated with a mixture of Nonidet P40 and glutaraldehyde, and were confirmed to consist of HIV-1 Gag p24 protein by immunogold labelling. On infection, the HIV-1 virus was found to enter the cell in two ways: membrane fusion and endocytosis. After viral entry, no structures resembling virus particles could be seen in the cytoplasm. In the infected cells, positive reactions by immunolabelling suggest that HIV-1 Gag is produced in membrane-bound structures and transported to the cell surface by the cytoskeletons. A crescent electron-dense layer is then formed underneath the cell membrane. Finally, the virus particle is released from the cell surface and found extracellularly to be a complete virus particle with an electron-dense core. However, several cell clones producing defective mature, doughnut-shaped (immature) or teardrop-shaped particles were found to be produced in the extracellular space. In the doughnut-shaped particles, Gag p17 and p24 proteins exist facing each other against an inner electron-dense ring, suggesting that the inner ring consists of a precursor Gag protein showing a defect at the viral proteinase.

Cell Line↗
PubMedDate not supplied

Properties of Aspergillus tamarii, A. caelatus and related species from acidic tea field soils in Japan.

Fungi in Aspergillus section Flavi include both aflatoxin producers and non-producers. Aspergillus caelatus is a recently described non-aflatoxigenic species in this section, which has some common characteristics with A. tamarii, such as yellowish brown color and double walled spores. In contrast to the morphological similarities, all of the A. caelatus isolates tested produced no cyclopiazonic acid whereas most isolates of A. tamarii produce this compound. There are six nucleotide differences that distinguish the DNA sequences of these two species in the regions of ITS1, ITS2, 5.8S rDNA and 28S rDNA and this is a consistent difference. Both species were isolated from acidified field soils, but A. tamarii isolates were more common than A. caelatus in highly acidic soils.

Aflatoxins↗
PubMedDate not supplied

Production and activation of hepatocyte growth factor in acute renal failure.

Hepatocyte growth factor (HGF) facilitates the regeneration of injured kidney in acute renal failure (ARF). HGF is produced as a single-chain precursor by cells of mesenchymal origin and is converted to a biologically active, heterodimeric molecule by proteolytic processing. We studied HGF mRNA and protein levels in systemic organs of glycerol-induced ARF rats, a model of crush syndrome. HGF protein concentration of tissue homogenate was measured by ELISA. Both mRNA and protein levels were increased in liver and spleen at 24 hours after the glycerol injection whereas HGF protein level was decreased in the injured kidney. Expression of HGF receptor/c-met mRNA was elevated only in the kidney. These results suggest that HGF supplied in an endocrine manner may play an important role in the regenerating process following ARF. Next, we measured serum HGF concentration by ELISA in 8 ARF patients caused by crush syndrome and the molecular size of serum HGF was determined by immunoblotting. Although serum HGF levels elevated in all patients, the HGF levels did not associate with their prognoses. While a single-chain molecule was predominantly observed in sera from chronic renal failure patients and healthy subjects, the majority of serum HGF was a heterodimeric form in 7 ARF patients. In one patient who developed disseminated intravascular coagulation syndrome and had a poor prognosis, a single-chain molecule was predominant although the serum HGF concentration was equivalent. These data suggest that the activity of proteolytic processing may be also an important factor for the expression of the biological function of HGF.

Acute Kidney Injury↗
PubMedDate not supplied

Platelet adhesion to heparin coated oxygenator fibers under in vitro static conditions: impact of temperature.

Heparin coating of cardiopulmonary bypass (CPB) circuitry may attenuate the platelet consumption associated with CPB. We investigated the effect of temperature on the interaction between platelet and heparin coated surfaces under in vitro static conditions. Heparin coated and non coated oxygenator fibers were incubated with heparinized whole blood at 37 degrees C and 22 degrees C. The incubation time was set at 30, 60, 180, and 300 minutes. The number of platelets adhering to each fiber was assessed with enzyme immunoassay using monoclonal antibody against platelet receptor protein CD 61(GPIIbIIIa). As an index of platelet activation, plasma soluble(s) P-selectin levels were measured by enzyme-linked immunosorbent assay. Under normothermia, the number of adherent platelets on the non coated surface increased significantly after 300 min of incubation. Platelet adhesion was reduced significantly by heparin coating of the surface and was kept constant after 300 min. Under hypothermia, heparin coating was also associated with significant reduction of platelet adhesion. The levels of sP-selectin did not correlate with the extent of platelet adhesion. Our results suggest that heparin coating is effective in decreasing platelet adhesion to the synthetic surface tested regardless of the temperature under static conditions. Inhibition of platelet activation on the heparin coated surface may be masked by standard dose heparinization.

Anticoagulants↗
PubMedDate not supplied

The mechanism underlying the vasodilator action of bunitrolol: contribution of alpha 1-adrenoceptor blocking action.

The mechanism of the vasodilator action of bunitrolol was investigated in pentobarbital-anesthetized dogs. When injected intraarterially, bunitrolol increased blood flow through the femoral arterial bed more effectively than that through the vascular bed of the left anterior descending coronary artery (LAD). The former is rich in alpha-adrenoceptors and tonically controlled by the sympathetic nerves, whereas the latter is not. Intraarterial prazosin increased femoral flow but not LAD flow, whereas intraarterial nitrendipine increased equieffectively both femoral and LAD flows. In the saphenous arterial bed of dogs that also underwent spinal anesthesia and received atropine and nadolol, intravenous bunitrolol suppressed more effectively vasoconstrictor responses to saphenous nerve stimulation than those to intraarterial norepinephrine. These effects of bunitrolol were similar to those of prazosin and dissimilar to those of yohimbine. In similarly treated dogs, bunitrolol suppressed more effectively increases in mean systemic arterial pressure in response to methoxamine than those to B-HT 920. From these results, it was concluded that an alpha 1-adrenoceptor blocking action is mainly involved in the acute vasodilator effect of bunitrolol. This action may also contribute to the decrease in total peripheral resistance seen in hypertensive patients treated chronically with bunitrolol.

Anesthesia, Spinal↗
PubMedDate not supplied

Plasma abnormal prothrombin (PIVKA-II): a new and reliable marker for the detection of hepatocellular carcinoma.

We evaluated the clinical usefulness of a protein induced by vitamin K absence, antagonist-prothrombin (PIVKA-II), in detecting hepatocellular carcinoma (HCC) specifically in patients with liver cirrhosis, and the possible correlation between levels of PIVKA-II and pathological features of HCC. Plasma levels of PIVKA-II and alpha-fetoprotein (AFP) were measured in 628 patients with various diseases, including 253 with liver cirrhosis and 116 with HCC. PIVKA-II was detected (greater than or equal to 0.1 arbitrary unit/mL) in 54.3% of HCC and the concentration showed a positive correlation with the tumour size. As a screening test for the detection of HCC, PIVKA-II produced values comparable with those of AFP with a sensitivity, specificity and validity of 52.8, 98.8 and 51.6% respectively. Sixteen of 45 patients (37%) with HCC who had low AFP (less than 100 ng/mL) levels were positive for PIVKA-II. No apparent relationship, however, could be found between the levels of PIVKA-II and the aetiology or pathological findings of HCC. These results suggest that PIVKA-II can be a reliable marker for detecting HCC in patients with liver cirrhosis.

Biomarkers↗
PubMedDate not supplied

Two pathways in the biosynthesis of cadystins (gamma EC)nG in the cell-free system of the fission yeast.

Small metal-binding peptides, cadystins, with the general structure of (gamma-Glu-Cys)n-Gly ((gamma EC)nG), were synthesized in a cell-free system of fission yeast to examine the in vivo synthetic pathway. The crude enzyme for cadystin synthesis was prepared by ammonium sulfate precipitation (75% saturation) from the 120,000 x g supernatant of the cell extract, and the excess salt in the enzyme fraction was removed by Sephadex gel filtration. Using this crude enzyme fraction, it was shown that there were two pathways for cadystin biosynthesis. One pathway is gamma-Glu-Cys (gamma EC) dipeptidyl transfer from both glutathione (gamma ECG) and cadystins to glutathione and cadystins. The other one is gamma EC polymerization from (gamma EC)n and glutathione to (gamma EC)n + i, followed by glycine addition with glutathione synthetase.

Amino Acid Sequence↗
PubMedDate not supplied

Attenuation of pressor responses to norepinephrine and pitressin and potentiation of pressor response to angiotensin II by captopril in human subjects.

The present study was conducted to investigate the influence of captopril on cardiochemodynamic responses in 38 normal volunteers (20- to 35-year-old men) to exogenously administered vasopressor substances. Norepinephrine (NE), 0.05, 0.1, and 0.2 micrograms/kg min-1; angiotensin II (AII), 5, 10, and 20 ng/kg min-1; and pitressin (2 mU/kg min-1) were infused for 10 minutes. Each infusion was reported twice, and the responses were reproducible. Captopril (50 mg by mouth) significantly attenuated the pressor responses to NE and pitressin, but the decrease in heart rate in response to NE and pitressin was almost the same before and after captopril treatment, suggesting that captopril potentiates reflex slowing of the heart. Captopril significantly potentiated the pressor response to AII. Attenuation of pressor response and potentiation of reflex slowing of the heart, in response to NE and pitressin, disappeared when a subdepressor dose of AII (1 ng/kg min-1) was infused in addition to captopril. Infusion of a subdepressor dose of bradykinin (BK), 0.1 microgram/kg min-1, had no influence on the pressor response to NE. In the subjects treated with indomethacin (225 mg/54 hrs), captopril still attenuated the pressor response to NE. These results suggest that captopril attenuates the pressor responses to NE and pitressin primarily by depletion of endogenous AII; decreased AII may desensitize the contraction of arterial smooth muscle and may potentiate the compensatory reflex mechanism.

Adult↗
PubMedDate not supplied

Sonic detection of intracranial aneurysm and AVM.

This paper describes a method of detecting intracranial aneurysm and arteriovenous malformation (AVM) by analysing weak sounds produced by the blood circulation at the affected part. There is thought to be no turbulence in the normal cerebrovascular system, whereas abnormalities such as aneurysm and AVM sometimes cause turbulence in the blood flow. Thus, a small fraction of the flow energy might be converted into an acoustically detectable noise. For the detection of the sound, sensitive detectors must be applied close to the head since the sound is very weak, and, as in cerebrovascular diseases, the origin of the sound is usually concealed deep inside the hard shelter of the skull. The detection system we used had a gain of 40 to 50 dB greater than that of an ordinary stethoscope. The detection points were the teeth or forehead. Usually the sound started about 160 msec after the ventricular contraction and lasted for 100 to 400 msec. Its frequency component mostly ranged from 400 to 2000 Hz, but the spectrum profile changed according to the position and degree of abnormalities. The uttered sound was very random, which facilitated detection of the position of the sound origin by means of cross correlation methods using a pair of detectors. This method is completely noninvasive, causes no pain to the patient, and might be used even in mass examinations.

Adolescent↗
PubMedDate not supplied

Molecular size of the diapause hormone of the silkworm Bombyx mori.

The diapause hormone (DH) responsible for arrested development of the silkworm Bombix mori consists of two active principles of peptide (A and B). Since both hormones form aggregates in aqueous phases, the molecular weights were determined by gel permeation chromatography of Merckogel OR 6000 using methanol-dichloromethane mixture as the developing agent. Gramicidins and modified peptides soluble in the organic solvents were used as the standard markers for the molecular weight measurements of the hormones. The molecular weights of DH-A and -B are estimated to be 3300 +/- 400 and 2000 +/- 200, respectively.

Animals↗
PubMedDate not supplied

Exploratory study of effective chemotherapy to clear cell carcinoma of the ovary.

Although clear cell carcinoma of the ovary is considered to be a tumor with poor prognosis, the clinical characteristics has not been defined. The aim of this study was to evaluate the response of clear cell carcinoma of the ovary to first and second-line chemotherapy and explore effective chemotherapy. Fifty-three patients with clear cell carcinoma of the ovary were enrolled between 1988 and 1997 at our department. Since taxol was not available in Japan at that time, cisplatin-based combination chemotherapy has been exclusively used as a standard first-line chemotherapy. Retrospective analyses of clinical characteristics and the response to first or second-line chemotherapy were performed. Median age was 52 years (range 27-71 years). Tumors were 34% (18/53) stage I, 19% (5/53) stage II, 38% (20/53) stage III, and 9% (5/53) stage IV. All patients with I or II stage disease had optimal cytoreduction. Out of 25 patients with III or IV stage disease 20% (5/25) had negative residual tumor, 36% (9/25) had <2 cm residual tumor, and 44% (11/25) had >/=2 cm residual tumor. All patients received postoperative platinum-based chemotherapy. Of 23 patients with measurable residual tumor 8.7% (2/23) completely and 13% (3/23) partially responded to first-line chemotherapy consisting of cisplatin, adriamycin and cyclophosphamide (CAP) or cisplatin and cyclophosphamide (CP) by CT scan or second look laparotomy. Presence of endometriosis was 55% (29/53) but was not a prognostic factor. Although overall response rate of ovarian clear cell carcinoma to first-line chemotherapy by CAP or CP was about 22%, EP or EJ consisting of etoposide and cisplatin or carboplatin used as a second-line chemotherapy showed 29% response rate, while CPT-P consisting of CPT-11 and cisplatin showed 40% response rate. Clear cell carcinomas were frequently present at early stage, with association of endometriosis and with poor overall prognosis. Although patients with advanced ovarian clear cell carcinoma seemed to have better response to CPT-P than conventional platinum-based chemotherapy, further studies are required with larger number of patients to draw firm conclusions.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome in nude mice bearing human melanomas G361 and SEKI.

Our recent study has demonstrated that ponalrestat, an aldose reductase inhibitor, activates lipoprotein lipase (LPL) activity in the adipose tissue and alleviates the cachectic symptoms induced by B16 melanoma in mice. In this study, the effect of ponalrestat on cachexia symptoms in nude mice bearing human melanomas G361 and SEKI was investigated because it has been suggested that the suppression of LPL has an important role in cachexia induction by these two melanomas in nude mice. Mice bearing G361 subcutaneously did not gain weight and became cachectic, associated with the tumor growth. Tumor growth was not affected by ponalrestat, nevertheless treatment with ponalrestat resulted in an amelioration of the reduction in the weight of body mass, epididymal fat, gastrocnemius muscle, carcass and whole body lipid induced by the presence of G361. A severe weight loss observed in nude mice bearing SEKI was also partially attenuated by ponalrestat treatment. Overall, this study showed that ponalrestat is effective in the attenuation of the cachectic symptoms induced by human melanomas G361 and SEKI in nude mice, suggesting that ponalrestat has a potential usefulness for the treatment of cancer cachexia.

Aldehyde Reductase↗