Transgenic mice in renal research.
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Animals↗
Biomedical subjects
T Doi
Publications and source records attributed to T Doi.
Bunazosin induces use-dependent slowing of conduction in guinea-pig ventricular myocardium.
The use-dependent effects of bunazosin on the maximal rate of rise (Vmax) of the action potential and conduction velocity were studied in isolated papillary muscles of guinea-pig. Standard microelectrode techniques were used to monitor the conduction and action potential of the muscles. In the presence of 30 microM bunazosin, the time constants for the start of the use-dependent inhibition of Vmax during a 0.2, 1, 2 and 3 Hz stimulation were (means +/- S.E.M. in s) 30.9 +/- 8.0, 15.0 +/- 1.6, 7.4 +/- 0.9 and 3.9 +/- 0.7 (n = 4) and those for conduction velocity were 17.3 +/- 2.3, 17.3 +/- 5.2, 6.5 +/- 0.9 and 3.4 +/- 0.2, respectively. These results showed that in the cardiac ventricular muscle of the guinea-pigs, bunazosin produces use-dependent changes in conduction velocity with onset kinetics comparable to those measured simultaneously using Vmax. The characteristics of the use-dependent inhibition of conduction velocity induced by bunazosin are similar to those found with slow kinetic drugs such as disopyramide rather than with fast ones.
Action Potentials↗
The ram: a novel low molecular weight GTP-binding protein cDNA from a rat megakaryocyte library.
A novel low Mr GTP-binding protein cDNA was isolated from a rat megakaryocyte cDNA library with a synthetic oligonucleotide probe corresponding to an 8-amino acid sequence specific for c25KG, a GTP-binding protein previously isolated from human platelet cytosol fraction [(1989) J. Biol. Chem. 264, 17000-17005]. The cDNA has an open reading frame encoding a protein of 221 amino acids with a calculated Mr of 25068. The protein is designated as ram (ras-related gene from megakaryocyte) protein (ram p25). The amino acid sequence deduced from the ram cDNA contains the consensus sequences for GTP-binding and GTPase domains. ram p25 shares about 23%, 39% and 80% amino acid homology with the H-ras, smg25A and c25KG proteins, respectively. The 3.5-kb ram mRNA was detected abundantly in spleen cells.
Amino Acid Sequence↗
Characterization of the heterodimeric complex of human IL-2 receptor alpha.beta chains reconstituted in a mouse fibroblast cell line, L929.
The receptor for IL-2 has been known to exist in three forms on the basis of their affinities to IL-2: high, intermediate, and low affinity forms. Two IL-2R components have been identified as IL-2R alpha (p55, Tac Ag) and IL-2R beta (p70-75) chains, both bind IL-2 with low and intermediate affinities, respectively. Recently, we cloned human IL-2R beta chain cDNA and demonstrated that the cDNA product binds IL-2 with intermediate affinity and forms high affinity IL-2R with coexpressed IL-2R alpha chain in a human T cell line, Jurkat. In this study, we report the establishment of the mouse fibroblast transformants expressing either the IL-2R beta chain alone or both the IL-2R alpha and IL-2R beta chains. In contrast to lymphoid cells, significant IL-2 binding was not detected in the transformants expressing the IL-2R beta chain alone at IL-2 concentrations (50 pM to 10 nM) generally utilized. Nonetheless, the transformants expressing both IL-2R alpha and IL-2R beta chains displayed two forms of the IL-2R with high and low affinities to IL-2. However, neither IL-2 internalization nor signal transduction via the high affinity IL-2R complex were observed in the L929 transformants. Those findings suggest that the interaction of the IL-2R beta chain with the IL-2R alpha chain occurs in the absence of additional lymphoid specific component(s) to form high affinity IL-2R, but that this interaction is insufficient for IL-2 internalization and signal transduction just as observed in lymphoid cells. The experimental approach described here may allow further dissection of the molecular architecture of the IL-2R complex in the ligand binding, internalization, and signal transduction.
Animals↗
The human interleukin-2 receptor beta-chain gene: genomic organization, promoter analysis and chromosomal assignment.
The chromosomal gene for the human interleukin-2 receptor beta-chain (IL-2R beta) was isolated and characterized. The entire IL-2R beta gene is composed of ten exons spanning about 24.3 kilobases, in which the protein is encoded by the exons 2-10. The cysteine rich extracellular region which displays a significant evolutionary resemblance to other cytokine receptors, as well as growth hormone and prolactin receptors, is encoded primarily by exons 3 and 4, whereas the membrane proximal, cysteine poor domain showing a homology with type III modules of fibronectin is encoded by exon 7. Sequence analysis of the 5'-flanking region revealed the presence of potential binding sites for transcription factors such as Octamer binding factors, AP-1, AP-2 as well as the 'GC-clusters'. At least five potential cap sites were identified by S1 mapping analysis. The 850 bp DNA sequence of the 5'-flanking region exhibited constitutive promoter activity when it was linked upstream of the HSV-tk reporter gene and then transfected into YT cells, a human leukemic cell line. By applying the RFLP linkage analysis, the IL-2R beta gene has been assigned to chromosome 22q12-13.
Base Sequence↗
[Analysis of factors associated with the occurrence of low birth weight infants].
The relationship between low birth weight infants (LBW) and 3 perinatal factors; pre-pregnant maternal Body Mass Index (BMI: Quetelet's index), maternal height and parity was investigated by the log-linear analysis, using the birth records of an obstetric facility at Naha city. In this facility there were 4,894 deliveries from Jan. 1978 to Dec. 1987. Of the 4,894 infants, 4,142 were live singletons with available data for the analysis. The odds ratio of each risk factor was calculated by the log-linear model. Women with lower pre-pregnant BMI (less than 20) had an increased LBW risk by 1.80 (95% CI: 1.32-2.43) compared to women with higher pre-pregnant BMI (20 less than). Lower maternal height (150 cm greater than) was associated with significant LBW risk (1.47; 95% CI: 1.03-2.12). Primiparae had higher LBW risk than multiparae (1.68; 95% CI: 1.25-2.28). In this analysis we evaluated the interaction effects on LBW occurrence of the three factors and found no interaction effects among them.
Body Height↗
Favourable associations between the myosin heavy-chain and light-chain isoforms in human skeletal muscle.
Histochemical and biochemical analyses were performed in order to examine the relationship between myosin light-chain (LC) isoforms and fibre-type distributions in whole human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis muscle in six healthy men, and analysed for the relative area occupied by each fibre type (percentage of fibre type area) and the molar ratio of each LC isoform. The percentage of type I fibre area was positively correlated with the molar ratio of slow LC (LC1s and LC2s) to total LC. The regression line was located below the line of unity. Also, the ratio of percentage of type IIa fibre area to that of type II fibre area was positively correlated with the molar ratio of the fast alkali LC LC1f to fast alkali LCs LC1f and LC3f. These results support previous study, having shown that in human skeletal muscle some type I fibres express various amounts of fast LC in addition to slow LC and suggest that fast myosin heavy-chain HCIIa is favourably associated with LC1f, whereas HCIIb is favourably associated with LC3f.
Adult↗
An electrophysiological study of 9-amino-1,2,3,4-tetrahydroacridine (THA) on sino-atrial node preparations of rabbits.
1. The electrophysiological effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on the rabbit sino-atrial node was studied using double-microelectrode voltage clamp methods. 2. THA (above 10 microM) caused statistically significant decreases in the maximum rate of rise, the action potential amplitude, the rate of diastolic depolarization, and increases in the spontaneous cycle length, the action potential duration at 50% repolarization. 3. On the current systems, THA obviously depressed the time-dependent outward K+ current. The compound also decreased the slow inward Ca2+ current and the hyperpolarization-activated inward current. 4. These findings indicate that THA exerts an inhibitory action on the automaticity of sino-atrial node via effects on both outward and inward current systems.
Action Potentials↗
Role of the intradiscal domain in rhodopsin assembly and function.
The role of the intradiscal polypeptide loops in bovine rhodopsin has been investigated by deletions in the N-terminal tail and in loops B-C, D-E, and E-F as well as by single amino acid substitutions in the D-E loop. Mutants with three types of phenotypes were observed. Type I mutants showed a rhodopsin-like chromophore and glycosylation. Type II mutants did not regenerate the chromophore and showed abnormal glycosylation. Type III mutants showed poor chromophore regeneration and abnormal glycosylation. Reduced transducin activation was shown by some type I and III mutants. Single amino acid substitutions in the D-E loop gave mostly type I mutants. Deletions in loops B-C, D-E, and F-G gave type II mutants, whereas deletions in the N-terminal tail produced type III mutants. Systematic deletions of two adjacent amino acids in loop D-E indicated that the amino acid sequences 171-182 and 189-192 were essential to rhodopsin structure. Immunofluorescence double-staining and transmission electron microscopy of one type II mutant (with residues 189 and 190 deleted) showed that it was mostly in the endoplasmic reticulum, whereas the wild-type protein was in the plasma membrane. We conclude that the first step in the assembly of the rhodopsin molecule is the formation of a three-dimensional structure in the intradiscal domain involving the bulk of the out-of-the-membrane polypeptide segments followed by the linkage of Cys-110 and Cys-187 through a disulfide bond.
Amino Acid Sequence↗
Expression of the archaebacterial bacterio-opsin gene with and without signal sequences in Escherichia coli: the expressed proteins are located in the membrane but bind retinal poorly.
In a further effort to obtain functional expression of the bacterio-opsin gene (bop) in Escherichia coli, the bop gene with E. coli signal sequences as well as the bop gene with the native presequence were expressed in E. coli. The location of the expressed products in the E. coli cell and their processing and folding to a structure that binds retinal as in Halobacterium halobium were investigated. All the expressed proteins were in the membrane. The proteins were largely unprocessed, and they were distributed between the outer and the inner membrane. The processed fractions, which were minor, were exclusively in the inner membrane. The processed proteins bound exogenously added all-trans-retinal but only partially, indicating that these proteins were present in at least two folded states.
Amino Acid Sequence↗
Murine interleukin 2 receptor beta chain: dysregulated gene expression in lymphoma line EL-4 caused by a promoter insertion.
The functional, high-affinity interleukin 2 receptor (IL-2R) consists of at least two receptor components, IL-2R alpha (p55) and IL-2R beta (p70-75). The cDNA encoding the murine IL-2R beta has been isolated by using the previously cloned cDNA for human IL-2R beta as a probe. Analysis of the cDNA revealed that the murine IL-2R beta shows a marked homology with the human IL-2R beta and that it is also structurally related to other cytokine receptors such as erythropoietin receptor. The cDNA-directed murine IL-2R beta formed high-affinity IL-2R in conjunction with the endogenous IL-2R alpha in a murine pro-B-cell line and could transduce IL-2-induced growth signal. In mouse lymphoma line EL-4, the IL-2R beta gene was found to be rearranged by the insertion of the long terminal repeat sequence of an intracisternal A particle, giving rise to constitutive expression of the IL-2R beta mRNA.
Amino Acid Sequence↗
Effects of acutely impaired regional function on remote myocardial wall motion and blood flow in the canine left ventricle studied by coronary occlusion and hypoxic perfusion.
STUDY OBJECTIVE: The aim was to examine whether regional myocardial dysfunction has a significant effect on the wall motion and blood flow in remote non-ischaemic regions. DESIGN: Two different severities of regional dysfunction were produced by occluding the left anterior descending coronary artery and perfusing it with a hypoxic solution. Haemodynamic variables were otherwise identical in the two conditions. The relationship of regional dysfunction in the left anterior descending artery region to regional wall motion and regional myocardial blood flow in the left circumflex artery region were examined. EXPERIMENTAL MATERIAL: 22 anaesthetised mongrel dogs, 9-16 kg, were used for the studies: 14 for the regional wall motion studies, and eight for the regional myocardial blood flow studies. MEASUREMENTS AND MAIN RESULTS: Segment shortening in the left anterior descending artery region was impaired differently in the two conditions: arterial occlusion caused a bulge, while hypoxic perfusion caused only mild hypokinesis. Segment shortening and the myocardial blood flow in the left circumflex artery region were augmented similarly in the two conditions. Left ventricular end diastolic pressure and end diastolic segment length in the left circumflex region were increased and aortic pressure was slightly decreased by left anterior descending artery occlusion and hypoxic perfusion, but there was no significant difference between the two conditions. Heart rate was not affected. CONCLUSION: The augmentation of wall motion and blood flow of the remote myocardium does not depend on the magnitude of acutely induced regional dysfunction per se. The augmented wall motion in the remote region is unlikely to be due to mechanical unloading of the remote myocardium due to an intraventricular regional interaction, but rather to the Frank-Starling mechanism and left ventricular afterload reduction following acute ischaemia.
Animals↗
Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice.
We evaluated various biochemical parameters in influenza virus-infected mice and focused on adenosine catabolism in the supernatant of bronchoalveolar lavage fluid (s-BALF), lung tissue, and serum (plasma). The activities of adenosine deaminase (ADA) and xanthine oxidase (XO), which generates O2-, were elevated in the s-BALF, lung tissue homogenate, and serum (plasma). The elevations were most remarkable in s-BALF and in lung tissue: We found a 170-fold increase in ADA activity and a 400-fold increase in XO activity as measured per volume of alveolar lavage fluid. The ratio of activity of XO to activity of xanthine dehydrogenase in s-BALF increased from 0.15 +/- 0.05 (control; no infection) to 1.06 +/- 0.13 on day 6 after viral infection. Increased levels of various adenosine catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) in serum and s-BALF were confirmed. We also identified O2- generation from XO in s-BALF obtained on days 6 and 8 after infection, and the generation of O2- was enhanced remarkably in the presence of adenosine. Lastly, treatment with allopurinol (an inhibitor of XO) and with chemically modified superoxide dismutase (a scavenger of O2-) improved the survival rate of influenza virus-infected mice. These results indicate that generation of oxygen-free radicals by XO, coupled with catabolic supply of hypoxanthine from adenosine catabolism, is a pathogenic principle in influenza virus infection in mice and that a therapeutic approach by elimination of oxygen radicals thus seems possible.
Adenosine↗
[Secular changes of the mean birth weight and the mean gestational day at an obstetric clinic in Naha].
In our previous study we reported that the secular change of the mean birth weight (MBW) of Okinawa was different from that of Japan as a whole, that is, the MBW of Okinawa was lower, but the annual increase rate of the MBW of Okinawa was larger than that of Japan as a whole. Through analyses using birth records of several obstetric facilities in Naha, we concluded that this phenomenon must be due to the remarkable improvement of the socioeconomical environment of Okinawa. In this report we analyzed secular changes of mean birth weight (MBW) and mean gestational day (MGD) of 15,847 singleton babies born at an obstetric clinic in the city of Naha for the 33 years from 1955 to 1987. To avoid fluctuations of annual changes in MBW and MGD caused by a small number of babies born in a single year, we also used the moving average of three years. In analyzing birth weight we stratified birth weight by sex, parity and the number of gestational weeks. It is considered that birth weight stratified by the number of gestational weeks reflects the intrauterine growth rate of infants. According to our results, both the MBW of infants with 40 gestational weeks, which reflects the intrauterine growth rate, and the MGD increased during the period from the 1950s to the early 1970s in this clinic. On the basis of these results we concluded that the increase of birth weight in this clinic until the early 1970s was due to increases in both the intrauterine growth rate and the gestational period. Our results also show that the mean height of mothers who delivered at this clinic also increased, which might reflect the development of the socioeconomical environment during their childhood. During the period when MBW increased, the economic growth rate of Okinawa was higher than that of other prefectures. From these results we concluded that the MBW can be used as a community health indicator reflecting the total health condition in a given community.
Birth Weight↗
Glomerular lesions in nonobese diabetic mouse: before and after the onset of hyperglycemia.
The natural history of renal lesions in nonobese diabetic mice was assessed. This strain develops a spontaneous overt insulin-dependent diabetes that has a female predominance and an autoimmune pathogenesis. We compared mice that had a normal glucose tolerance test with mice that had a diabetes of 2 to 15 weeks' duration. The glomerular surface area was increased in all diabetic mice regardless of the duration of hyperglycemia. There was an increase in the albumin/creatinine ratio in the urine of diabetic mice. Finally, nonobese diabetic mice all showed mesangial sclerosis that was more pronounced in the diabetic mice. This suggests that this strain is susceptible to glomerulosclerosis and that the occurrence of hyperglycemia results in an increase of glomerular size, mesangial sclerosis, and proteinuria, soon after glycosuria is first demonstrated.
Animals↗
[Macrophage scavenger receptor].
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Amino Acid Sequence↗
Introducing the concept of amae.
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Emotions↗
[Castleman disease in the pelvic retroperitoneum].
About 50% of the cases with Castleman disease firstly described by Castleman in 1956 occur in the thoracic cavity. The pelvic cavity is a rare location affected by the disease; there are only 7 reports. Herein, a case of Castleman disease of the pelvic cavity is reported. A 41-year-old man complaining of microscopic hematuria consulted us. Drip intravenous pyelography and computerized tomography showed a solitary mass at the pelvic retroperitoneum. Abnormal laboratory findings were as follows; glucose tolerance test (GTT), erythrocyte sedimentation rate, alpha 2-globulin level, CRP titer and hematuria. With the diagnosis of a pelvic retroperitoneal tumor, pelvic exploration was performed. The resected tumor was encapsulated, elastic hard and 4x3x2 cm in size. The cut surface was homogeneously granular and yellowish white in color. Histological diagnosis was the plasma cell type of Castleman disease. Within three weeks after the operation, laboratory abnormalities diminished except for GTT and microscopic hematuria. The patient is free from the disease with no signs of recurrence for 2 years postoperatively.
Adult↗