Why do old men have big ears? Correlation of ear length with age in Japan.
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Adult↗
Biomedical subjects
M Yoshimura
Publications and source records attributed to M Yoshimura.
Bisecting N-acetylglucosamine on K562 cells suppresses natural killer cytotoxicity and promotes spleen colonization.
beta 1-4 N-acetylglucosaminyltransferase (GnT-III) catalyzes the formation of bisecting N-acetylglucosamine (GlcNAc) in the biosynthesis of N-linked oligosaccharides. To examine the effect of bisecting GlcNAc on the natural killer (NK) cytotoxicity, the GnT-111 gene was introduced into NK-sensitive K562 cells that have no detectable GnT-III activity. We obtained three clones stably expressing high GnT-III (positive transfectants). Introduction of the GnT-III gene resulted in an increase of bisecting GlcNAc and a decrease of external sialic acid as well as tri- and tetraantennary sugars, as judged by flow cytometry. Compared to controls, the NK cytotoxicity was completely blocked against positive transfectants. The binding of effector cells to positive transfectants was also decreased. After s.c. injection into nude mice, positive transfectants produced spleen colonization, although no spleen lesions were formed by control cells. In nude mice depleted of NK cells by anti-asialo GM1 antibody, both positive transfectants and controls produced spleen colonization equally. These results indicate that K562 cells expressing GnT-III are resistant to NK cytotoxicity, resulting in spleen colonization in nude mice.
Acetylglucosamine↗
Modulation of L-type Ca current by denopamine, a nonparenteral partial beta 1 stimulant, in rabbit ventricular cells.
The effects of denopamine, a nonparenteral partial beta agonist which is used clinically in Japan, on the L-type Ca2+ current (ICa) were examined in rabbit ventricular cells. Denopamine stimulated basal ICa with a maximum response of +33.2% and a concentration for half-maximal response (EC50) of 0.039 microM. The maximum response of ICa was only a quarter of that induced by isoprenaline (ISO), while 10 microM denopamine elicited 70-75% of the maximum inotropic response in the papillary muscle preparations. The denopamine stimulation of ICa was abolished by selective beta 1 antagonists (atenolol or bisoprolol). Pretreatment with forskolin or dialysis with cAMP also abolished the stimulation. Denopamine, in turn, inhibited ISO-stimulated ICa. This inhibition was not affected by pretreatment with pertussis toxin or prazosin. The presence of denopamine at various concentrations caused a rightward shift in the concentration/response curve for ISO stimulation of ICa. The Schild plot for this effect had a slope of 0.99 and Kp of 0.20 microM. In the presence of guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) (0.5 mM) in the pipette, denopamine (10 microM) stimulated the ICa to 86 +/- 5% of the maximum response induced by ISO. These findings indicate that denopamine modulates ICa exclusively through the beta 1 adrenoceptor-adenylate cyclase pathway, that the stimulatory GTP-binding protein regulates the agonistic potency of denopamine, and that the signal from the beta 1 adrenoceptors is amplified between ICa and the tension development, which would contribute to the spare capacity of beta adrenoceptors.
Adenylyl Cyclases↗
Skip metastasis and hidden N2 disease in lung cancer: how successful is mediastinal dissection?
Out of 703 consecutive patients who underwent lung cancer surgery from 1986 to 1994, 562 were studied with an emphasis on lymph node metastasis. Skip metastasis was defined as metastasis to the upper mediastinum without involvement of the carinal, hilar, or intrapulmonary nodes. Twenty-nine patients had skip metastasis, accounting for 17% of the 175 with N2 disease. Except for one patient with a huge tumor, there was no lower-lobe disease. Patients with N2 disease nodes were categorized into the following groups: (1) 32 with false negative N2 that could not be detected macroscopically on the specimen; (2) 64 with true positive N2, detected macroscopically on the specimen; and (3) 79 patients with obvious N2. Positive carinal nodes were found in 12 of 70 N2 patients who underwent upper lobectomy, and in 60 of the (105) remaining N2 patients who had other types of surgery. We conclude that upper mediastinal dissection should be carried out in patients with adenocarcinoma in the upper lobe, because skip and undetectable metastasis are not rare. However, dissection of the carinal nodes with upper-lobe tumors, and of the upper mediastinum with lower-lobe tumors, can be omitted when the gross and frozen section findings are negative in the upper mediastinum and both the carinal and hilar nodes.
Carcinoma, Non-Small-Cell Lung↗
Thyroid hormone-free albumin: charcoal treatment or resin treatment.
Free thyroid hormone measurement by means of immunoassay kits is greatly influenced by the altered serum albumin and free fatty acid (FFA) levels. In the evaluation of these kits, it is therefore essential to study the interferences due to these factors by adding FFA or thyroid hormone-free human serum albumin (HSA) to the assay mixture, but little attention has been paid to the selection of albumin. In the present study, FFA content in various preparations of thyroid hormone-free HSA was compared. Charcoal-treated HSA was free from both thyroid hormone and FFA, whereas anion exchange resin-treated HSA was only free from thyroid hormone. Commercially available "FFA-free HSA" was also free from thyroid hormone. Our results suggest that attention must be paid to the nature of albumin when studying the interference by albumin in free thyroid hormone measurement and that commercially available "FFA-free HSA" is a ready-to-use thyroid hormone-free HSA when HSA free from both FFA and thyroid hormone is desired.
Artifacts↗
Property of receptor for vasoactive intestinal contractor (VIC) expressed in Xenopus oocytes injected with mRNA from rat intestine.
Property of receptor for vasoactive intestinal contractor (VIC), a peptide related to the endothelin family, expressed in Xenopus oocytes by injecting mRNA obtained from the intestine of rat, were studied using the voltage-clamp method. Inward-current responses to VIC (1 nM-100 nM) were evoked in a concentration-dependent manner in mRNA-injected oocytes. Non-injected and water-injected oocytes failed to respond to VIC. The reversal potential for the VIC response was around -20 mV and the depolarizing shift was approximately 18 mV, when the external concentration of Cl-was halved, in agreement with the Nernst equation. The response to VIC was suppressed either by the external application to BAPTA/AM (10 microM) or by pertussis toxin 0.5 microgram/ml). These results indicate that the receptor for VIC, functionally expressed in Xenopus oocytes injected with rat intestinal mRNA, is coupled to pertussis toxin-sensitive G-protein and its activation leads to mobilization of intracellular Ca2+.
Animals↗
Processing and mechanical properties of hydroxyapatite reinforced with hydroxyapatite whiskers.
Hydrothermally synthesized HAp fine crystals/HAp whiskers mixtures have been used for the preparation of HAp/0-30% (whiskers) composites. The composites have been fabricated by pressureless sintering and hot-pressing. The best mechanical properties and the highest densities have been achieved for composites hot pressed at 1000 degrees C (2 h, 30 MPa in flowing Ar). Their density was in the range of 90-97% of the theoretical density. Fracture toughness (Klc) of the composites reflected their microstructure and had the value of 1.4 MPa m1/2 (as compared with Klc = 1.0 MPa m1/2 for the non-reinforced HAp matrix). Compressive prestressing of the HAp matrix and crack deflection (both derived from the residual stress field) contributed to the increase of fracture toughness. Other toughening mechanisms have not been observed. HAp/HAp (whiskers) composites exhibited improved toughness without degradation of biocompatibility, because the HAp whiskers acted both as a reinforcement and as a biocompatible phase. Problems related to biocompatibility and mechanical properties of available HAp-based composites were also discussed.
Biocompatible Materials↗
Increased plasma levels of B-type natriuretic peptide in patients with unstable angina.
This study was designed to examine the plasma levels of B-type or brain natriuretic peptide (BNP), as well as A-type or atrial natriuretic peptide (ANP) in patients with unstable angina as compared with those in patients with stable exertional angina and control subjects. We measured the plasma levels of BNP and ANP in 33 patients with unstable angina, 20 patients with stable exertional angina, and 20 control subjects. The plasma levels of BNP were significantly increased in patients with unstable angina compared with those in patients with stable exertional angina and control subjects, respectively (39.5 +/- 29.4 pg/ml vs 15.1 +/- 8.0 pg/ml; p < 0.01 and 39.5 +/- 29.4 pg/ml vs 10.3 +/- 6.4 pg/ml; p < 0.01, respectively). On the other hand, there was no significant difference in the plasma levels of ANP among the three groups. Furthermore, in patients with unstable angina, the plasma levels of BNP decreased significantly after the medical treatment (from 39.5 +/- 29.4 pg/ml to 15.8 +/- 11.0 pg/ ml; p < 0.01), whereas the plasma levels of ANP did not change. We conclude that the plasma levels of BNP are increased in the majority of patients with unstable angina and that the increased levels decrease toward normal after treatment.
Adult↗
Natriuretic peptides in the treatment of heart failure.
BACKGROUND: This study was designed to examine the hemodynamic, renal, and hormonal effects of infusion of A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with congestive heart failure (CHF). METHODS AND RESULTS: We infused synthetic human ANP or BNP at a rate of 0.1 microgram/kg/ min in patients with CHF and control subjects. ANP and BNP infusion decreased pulmonary capillary wedge pressure (ANP: from 24 +/- 1 to 12 +/- 2 mmHg; BNP: from 21 +/- 3 to 14 +/- 4 mmHg, P < .01, respectively) and systemic vascular resistance (ANP: from 2,129 +/- 293 to 1,737 +/- 293 dyne.sec.cm-5; BNP: from 2,485 +/- 379 to 1,771 +/- 195 dyne.sec.cm-5, P < .01, respectively), and increased stroke volume index (ANP: from 26 +/- 4 to 32 +/- 4 mL/m2; BNP: from 26 +/- 4 to 32 +/- 4 mL/m2, P < .01, respectively) in patients with CHF. ANP and BNP infusion increased urine volume (ANP: from 0.7 +/- 0.3 to 4.5 +/- 3.3 mL/min, BNP; 0.8 +/- 0.2 to 5.3 +/- 1.0 mL/min, P < .01, respectively). excretion of sodium (ANP: from 53 +/- 26 to 478 +/- 389 microEq/min, P = NS; BNP: from 77 +/- 21 to 754 +/- 108 microEq/min, P < .01) and chloride (ANP: from 61 +/- 31 to 470 +/- 369 microEq/min, P = NS, BNP; from 74 +/- 20 to 709 +/- 103 microEq/min, P < .01) in patients with CHF. In the hormonal analysis, ANP and BNP infusion had inhibitory effects on reninangiotensin aldosterone system and the sympathetic nervous system. CONCLUSION: We conclude that ANP and BNP infusion improves left ventricular function in patients with CHF by vasodilation and prominent natriuretic action.
Aged↗
In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product.
The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo anti-tumour effects of a humanised antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its murine counterpart, mu4D5, for the direct antiproliferative activity against the c-erbB-2-overexpressing SK-BR-3 cell line. In vivo treatment of severe combined immunodeficient (SCID) mice carrying the c-erbB-2-overexpressing 4-1ST human gastric carcinoma xenograft with 4hu4D5 revealed that the recombinant protein had potent anti-tumour activity. Furthermore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was significantly augmented with rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might perform better in patients than predicted from preclinical studies.
Animals↗
P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo.
We examined whether the increased expression of P-glycoprotein (P-gp) encoded by the human multidrug resistance gene MDR1 is related to the acquired multidrug resistance of lung cancer in vivo. We estimated the chemosensitivity of lung cancer xenografts (LC-6, adenocarcinoma; Lu-24, small-cell cancer) by calculation of relative tumour growth (T/C%, treated/control) in vivo, based on statistical significance determined by the Mann-Whitney U test (P < 0.01, one-sided). MDR1 gene expression levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) assay. P-gp production and P-gp localisation were examined by Western blotting and by immunohistochemical analysis respectively. LC-6 and Lu-24 were initially sensitive to both vincristine (VCR, 1.6 mg kg-1: LC-6, 45%; Lu-24, 39%) and doxorubicin (DOX, 12 mg kg-1: LC-6, 26%; Lu-24, 27%) in vivo. VCR-resistant variants (LC-6R, 66% and Lu-24R, 68%) selected with VCR (0.4 mg kg-1, x 9) significantly acquired cross-resistance to DOX (LC-6R, 55% and Lu-24R, 55% respectively). RT-PCR assay showed increased levels of MDR1 expression in LC-6R and Lu-24R with stable MDR1 expression levels. P-gp expression levels were elevated, and the percentage of P-gp-positive tumour cells increased in both LC-6R and Lu-24R. These results suggest that P-gp/MDR1 overexpression is related to acquired multidrug resistance in lung cancer in vivo.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Remodeling of cell surface glycoproteins by N-acetylglucosaminyltransferase III gene transfection: modulation of metastatic potentials and down regulation of hepatitis B virus replication.
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Animals↗
Localization of endothelin ETB receptors on the myenteric plexus of guinea-pig ileum and the receptor-mediated release of acetylcholine.
1. The type of endothelin (ET) receptor located on the myenteric neurones of guinea-pig ileum was determined by receptor autoradiography and function of the receptor was examined by release experiments of acetylcholine (ACh) from the longitudinal muscle myenteric plexus (LM-MP) preparations. 2. Specific [125I]-ET-1 binding sites were distributed in muscle layers, myenteric and submucous plexuses, and mucosa layers. High-grain densities were detected in both myenteric and submucous plexuses. 3. Binding in the myenteric plexus was abolished by incubation with either IRL 1620 (endothelin ETB receptor agonist) or BQ 788 (endothelin ETB receptor antagonist), but not with BQ 123 (endothelin ETA receptor antagonist). The [125I]-IRL 1620 binding sites were evident in the myenteric plexus. Thus, the endothelin receptor located on the myenteric neurones is of the ETB type. 4. ET-1 (10(-10)-3 x 10(-8) M) and ET-3 (10(-10)-3 x 10(-8) M) evoked 3H outflow from LM-MP preparations of ileum preloaded with [3H]-choline, in a concentration-dependent manner. There was no significant difference between maximum amounts of ET-1-evoked and ET-3-evoked 3H outflow. 5. ET-1 and ET-3 evoked outflow of 3H was BQ 788-sensitive, but BQ 123-insensitive. Both evoked outflows of 3H were Ca(2+)-dependent and tetrodotoxin-sensitive. 6. These results indicate that the endothelin ETB receptor is located on the enteric cholinergic neurones and that stimulation evokes the release of ACh.
Acetylcholine↗
Comparative study of regional cerebral blood flow values measured by Xe CT and Xe SPECT.
The regional cerebral blood flow (rBCF) values measured by stable xenon-enhanced computed tomography (Xe XT) and by radioactive xenon-133 single photon emission computed tomography (Xe SPECT) were compared in 16 patients with cerebral infarct. On the non-lesion side Xe SPECT recorded 10.7% higher rCBF values than Xe CT in the anterior cerebral artery territory, while Xe CT recorded 9.6% higher values than Xe SPECT in the middle cerebral artery territory. These differences were not statistically significant. Although the rCBF values were almost the same, no correlation was found between the two methods in the posterior cerebral artery territory and the basal ganglia. Only hemispheric CBF on the non-lesion side showed the same value and a good correlation between the Xe CT and the Xe SPECT. There was a good correlation in the hemispheric CBF values on the lesion side, too. The difference of rCBF between the non-lesion side and the lesion side was expressed smaller in the Xe SPECT than in the Xe CT. This is in agreement with the previous reports that Xe SPECT overestimates the flow in the low flow areas. The higher rCBF values in the anterior cerebral artery territory measured by the Xe SPECT was ascribed to the artifact from the radioactivities in the inhalation mask and the air passages as reported previously. In conclusion, there is no good correlation between the rCBF values measured by the Xe CT and by the Xe SPECT. Only hemispheric CBF shows a good correlation between the two methods.
Adult↗
Regulation by acetylcholine of Ca2+ current in rabbit atrioventricular node cells.
Effects of acetylcholine (ACh) on L-type Ca2+ current (ICa) were examined in isolated atrioventricular (AV) node cells exhibiting spontaneous contractions and pacemaker current (If). ACh at a saturating concentration of 10 microM reduced basal ICa by 48 +/- 6%. The ACh effect was abolished by dialysis with 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase inhibitor, or guanosine-5'-O-(2-thiodiphosphate). Dialysis with guanosine 3',5'-cyclic monophosphate (cGMP) or NG-monomethyl-L-arginine (L-NMMA) and application of the cGMP-dependent protein kinase inhibitor KT-5823 (1 microM) did not affect ACh inhibition of ICa. Nitric oxide donor 3-morpholinosydnonimine (100 microM) and type III phosphodiesterase (PDE) inhibitor trequinsin (10 nM) enhanced basal ICa by 10-20%, whereas type IV PDE inhibitor Ro-20-1724 (30 microM) together with trequinsin caused a large ICa stimulation comparable to that by 3-isobutyl-1-methylxanthine (IBMX). These findings indicate that ACh inhibits basal ICa primarily by suppressing cAMP synthesis and that these cells have a potent type III and IV PDE activity to determine the basal cAMP concentration. When ICa was stimulated by IBMX (100 microM), the inhibitory effect of ACh was slightly reduced by L-NMMA, cGMP, and methylene blue but not by KT-5823 or Ro-20-1724. ACh hardly inhibited, or even enhanced, IBMX-stimulated Ica when forskolin (3 microM) was coapplied or the IBMX concentration was increased to 500 microM. These findings suggest that cAMP is degraded in the presence of 100 microM IBMX to some extent. Type II PDE, for which IBMX has a relatively high inhibitor constant, seems to contribute partially to the cAMP degradation.
1-Methyl-3-isobutylxanthine↗
Proliferating cell nuclear antigen (PCNA) expressed in human leptomeninges.
Here we report on the presence of proliferating cell nuclear antigen (PCNA) in human leptomeninges from 35 normal subjects with ages ranging from 57 to 94 years. Strong immunoreactivity with PC10 (a monoclonal antibody to PCNA) was detected in the nuclei of meningothelial cells, smooth muscle cells of leptomeningeal vessels, and ependymal cells. An immunoblot of leptomeningeal homogenate with PC10 showed the presence of a single band at 35 KD, the expected molecular mass of PCNA. Ki-67, another marker for cell proliferation, was undetectable in human leptomeninges. These observations point to isolated PCNA expression in tissue in which cells are not actively proliferating.
Aged↗
Thyroid cell proliferation-inhibiting activity in serum of patients with chronic renal failure on hemodialysis.
To investigate the possible humoral factor(s) influencing thyroid cell activity in chronic renal failure, we measured serum activity which stimulates or inhibits the [3H]thymidine incorporation by using a cultured functioning rat thyroid cell line (FRTL-5 cells) in 17 patients on hemodialysis and 19 healthy controls. Polyethylene glycol-treated serum was centrifuged and FRTL-5 cells were cultured with the supernatant. Thyroid stimulating activity was determined by [3H]thymidine incorporation after incubation for 72 h. There was no significant difference in [3H]thymidine incorporation between cultures incubated with patient and normal serum, suggesting the absence of the stimulating activity. But when patient serum was added to cultures together with 20 or 50 microU/ml of TSH, the TSH-stimulated increase in [3H]thymidine incorporation was significantly decreased, indicating the presence of thyroid inhibiting activity, which possibly inhibits the thyroid cell growth. This activity was not significantly altered by hemodialysis. No significant correlation was observed between this activity and serum levels of thyroid hormones or the iodine concentration. Patients on hemodialysis therefore have serum thyroid inhibiting activity which is nondialysable, differs from iodine, and could influence the thyroid cell growth.
Adult↗
Plasma free thyroxine (FT4) concentrations during hemodialysis in patients with chronic renal failure: effects of plasma non-esterified fatty acids on FT4 measurement.
Plasma free T4 (FT4) concentrations could be increased during hemodialysis in patients with chronic renal failure (CRF) because an increase in non-esterified fatty acids (NEFA) could interfere with the binding of T4 to thyroxine-binding globulin. To evaluate the effect of hemodialysis on the FT4 concentration in patients with CRF, we measured the FT4 in 39 patients with CRF by four assay methods including equilibrium dialysis, the 125I-T4 analog method and enzyme immunoassay. The addition of the fatty acid sodium oleate to normal pooled sera led to a marked increase in FT4 as measured by equilibrium dialysis (Model FT4). A moderate increase in the serum FT4 concentration also was observed with an IMX enzyme immunoassay kit, whereas the Coat-A-Count analog method demonstrated no interference by sodium oleate. The mean serum FT4 prior to hemodialysis measured by equilibrium dialysis did not differ significantly from that in the normal control, although those measured by analog methods (Coat-A-Count and Amerlex) and IMX were subnormal. The FT4 by IMX were albumin-dependent, and the values decreased as the samples were serially diluted, but Model FT4 was not affected by the albumin level or the serial dilution. FT4 by Model FT4 showed a marked increase beginning 10 min after the start of dialysis, and it correlated well with the plasma concentration of NEFA and the NEFA/albumin molar ratio. The other three assay methods, including one which is not affected by NEFA, did not show a change in FT4 at 10 min, but a significant increase of 11 to 17% was observed by the end of dialysis. The TSH concentration decreased significantly during hemodialysis. These data suggest that (1) the low serum FT4 in hemodialysis patients measured by some immunoassay methods may be an underestimation due to the low albumin level; (2) FT4 actually increases during hemodialysis due to the actual increase in NEFA, although the marked increase in FT4 during hemodialysis as measured by equilibrium dialysis is an overestimation due to the in vitro generation of NEFA; and (3) one should beware of aberrations in thyroid hormone parameters during hemodialysis and potential complications.
Dialysis↗