Change in the circadian rhythm of blood pressure in pseudo-hypoaldosteronism type 2 in response to thiazide diuretics.
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Adult↗
Biomedical subjects
K Takahara
Publications and source records attributed to K Takahara.
Esophageal hernia in dementia: surgeon's role for mixed-type esophageal hernia in an elderly woman with dementia.
The mixed-type esophageal hernia is an indication for operation to prevent stomach volvulus and perforation. However, preventive operation is meaningful depending on the physical status. We encountered an 84-year-old, demented, bed-ridden woman of mixed-type esophageal hernia complicated with severe reflux esophagitis. First, the patient was conservatively treated by intravenous hyperalimentation and H2 blocker but, with onset of delirium, she removed the venous route twice. Subsequently, she was tightly restrained to the bed to avoid removing the line. Ethical deliberation for the patient tightly fixed to the bed and intravenous alimentation for her life prompted us to reconsider hernia operation after discussion with surrogate decision makers. The patient recovered uneventfully after operation, and movement without intravenous route or without any restraints was maintained by oral feeding assisted by gastrostomy feeding. In the coming decade, when senior patients are expected to increase, such operations can be forwarded to respect the patients' quality of life.
Aged↗
Tie-2 and angiopoietin-1 expression in human thyroid tumors.
Tie-2 is an endothelial cell-specific receptor tyrosine kinase involved in vascular maturation and remodeling. Although its expression is considered to be restricted to vascular endothelial cells and hematopoietic progenitors, our immunohistochemical and in situ hybridization studies showed that Tie-2 and its ligand, angiopoietin (Ang)-l were expressed not only in benign and malignant human thyroid tumor cells but also in hyperplastic regions of adenomatous goiter. To confirm the expression in these tissues further, we used a laser capture microdissection system to isolate epithelial tumor cells from tissue specimens selectively, and demonstrated the expression of Tie-2 and Ang-1 mRNAs in tumor cells by RT-PCR analysis. Furthermore, Tie-2 and Ang-1 mRNAs and proteins were also detected in rat thyroid cell lines, FRTL-5 and PCCL-3. Our results suggest that Ang-1/Tie-2 signaling may be involved in the proliferation of thyroid epithelial cells.
Adenocarcinoma, Follicular↗
Metastases to the penis from carcinoma of the prostate.
A 58-year-old man presented with dysuria at the Osaka Medical College Hospital in November 1996. Laboratory examination revealed elevated serum prostate-specific antigen (PSA) to > 100 ng/mL. Adenocarcinoma of the prostate with metastasis to the bone was diagnosed after a biopsy of the prostate and bone scintigraphy; hormonal therapy was administered. Although bone metastasis was well controlled and the serum PSA level declined to within normal levels (2.0 ng/mL), several painless nodules were found on the penile glans. Biopsy of the nodules showed that the penile tumor was a metastasis from the prostate cancer. The patient underwent partial penectomy for relief from penile pain. The serum PSA level showed no elevation 3 months after the partial penectomy, suggesting that careful observation of prostate cancer patients is necessary, even when oseous metastasis is well controlled and serum PSA levels are kept within normal ranges by hormonal therapy. The case also indicates that urologists should consider the possibility of metastasis to the penis from prostate cancer.
Adenocarcinoma↗
Mutational analysis of the BMP-1 gene in patients with gastroschisis.
BACKGROUND: Gastroschisis is a rare abdominal wall defect. Although the pathogenesis of gastroschisis is unknown, there is some evidence of the genetic etiology of gastroschisis. Recently, a functionally null deletion of the mouse bone morphogenic protein-1 (BMP-1) gene resulted in a phenotype that resembled a human neonate with gastroschisis. BMP-1 thus became the first potential candidate gene for gastroschisis. METHODS: To explore this possibility the authors collected blood samples from 11 patients who had gastroschisis. Mutational analysis of exons 2 to 15 of the human BMP-1 gene was performed using genomic polymerase chain reaction, single-strand conformation polymorphism analysis and direct sequencing methods. RESULTS: No mutation of the human BMP-1 gene was observed in any of these patients. CONCLUSION: Although heterogeneous etiologies might be proposed for gastroschisis, our results provide further evidence of a nongenetic etiology for gastroschisis. J Pediatr Surg 36:885-887.
Bone Morphogenetic Protein 1↗
Five mouse homologues of the human dendritic cell C-type lectin, DC-SIGN.
DC-SIGN, a human C-type lectin, is expressed on the surface of dendritic cells (DC), while a closely related human gene, DC-SIGNR or L-SIGN, is found on sinusoidal endothelial cells of liver and lymph node. Both DC-SIGN and DC-SIGNR/L-SIGN can bind ICAM-3 and HIV gp120, and transmit HIV to susceptible cells in trans. Here, we report the cloning of five mouse genes homologous to human DC-SIGN and DC-SIGNR/L-SIGN. Only one gene, named mouse DC-SIGN, is highly expressed in DC, and is not found in a panel of mouse macrophage and lymphocyte cell lines. The other four genes, named mouse SIGNR1 (SIGN-Related gene 1), SIGNR2, SIGNR3 and SIGNR4, are expressed at lower levels in various cells according to RT-PCR and Northern blot analyses on RNA. All the genes of mouse DC-SIGN and SIGNRs map to adjacent regions of chromosome 8 A1.2-1.3. However, like human DC-SIGN, only the mouse DC-SIGN gene is closely juxtaposed to the CD23 gene, while the other four SIGNR genes are located close to each other in a neighboring region. mRNAs of mouse DC-SIGN and three SIGNR genes encode type II transmembrane proteins (DC-SIGN, 238 amino acids; SIGNR1, 325 amino acids; SIGNR3, 237 amino acids; SIGNR4, 208 amino acids), but the SIGNR2 gene only encodes a carbohydrate recognition domain (CRD) without a cytosolic domain and a transmembrane domain (SIGNR2, 178 amino acids). Amino acid sequence similarities between the CRD of human DC-SIGN and the mouse homologues are 67% for DC-SIGN, 69% for SIGNR1, 65% for SIGNR2, 68% for SIGNR3 and 70% for SIGNR4 respectively. However, the membrane proximal neck domains in the mouse genes are much shorter than their counterparts in human DC-SIGN and DC-SIGNR/L-SIGN. This family of mouse C-type lectins is therefore complex, but only one of the new genes, DC-SIGN, is juxtaposed to CD23 and is expressed at high levels in DC.
Amino Acid Sequence↗
Minimal-change nephrotic syndrome associated with mixed connective-tissue disease.
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Adult↗
Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain.
Epithelial cells maintained in culture medium containing low calcium proteolytically process laminin 5 (alpha3beta3gamma2) within the alpha3 and gamma2 chains (). Experiments were designed to identify the enzyme(s) responsible for the laminin 5 processing and the sites of proteolytic cleavage. To characterize the nature of laminin 5 processing, we determined the N-terminal amino acid sequences of the proteolytic fragments produced by the processing events. The results indicate that the first alpha3 chain cleavage (200-l65 kDa alpha3) occurs within subdomain G4 of the G domain. The second cleavage (l65-l45 kDa alpha3) occurs within the lIla domain, 11 residues N-terminal to the start of domain II. The gamma chain is cleaved within the second epidermal growth factor-like repeat of domain Ill. The sequence cleaved within the gamma2 chain matches the consensus sequence for the cleavage of type I, II, and III procollagens by bone morphogenetic protein-1 (BMP-1), also known as type I procollagen C-proteinase (). Recombinant BMP-1 cleaves gamma2 in vitro, both within intact laminin 5 and at the predicted site of a recombinant gamma2 short arm. alpha3 is also cleaved by BMP-1 in vitro, but the cleavage site is yet to be determined. These results show the laminin alpha3 and gamma2 chains to be substrates for BMP-1 in vitro. We speculate that gamma2 cleavage is required for formation of the laminin 5-6 complex and that this complex is directly involved in assembly of the interhemidesmosomal basement membrane. This further suggests that BMP-1 activity facilitates basement membrane assembly, but not hemidesmosome assembly, in the laminin 5-rich dermal-epidermal junction basement membrane in vivo.
Animals↗
Post-translational proteolytic processing of procollagen C-terminal proteinase enhancer releases a metalloproteinase inhibitor.
Activity of matrix metalloproteinases (MMP) is regulated by a family of proteins called tissue inhibitors of metalloproteinases (TIMP). Four TIMPs have been cloned, and their molecular weights range from 29,000 to 20,000. By reverse zymography, we have observed a metalloproteinase inhibitor with an apparent molecular weight of 16, 500 from medium conditioned by human brain tumor cells. Antibodies directed against TIMPs failed to react with the 16,500 molecular weight inhibitor, indicating that it was not a truncated form of a known TIMP. The inhibitor was isolated from conditioned medium using affinity and ion exchange chromatography. N-terminal sequences of the inhibitor matched amino acid sequences within the C-terminal domain of a protein known as procollagen C-terminal proteinase enhancer (PCPE). Thus, the inhibitor was named CT-PCPE. Comparison of the N-terminal domain of TIMP with CT-PCPE revealed that both contained six cysteine residues. As in the case of TIMP, reduction and alkylation abolished the inhibitory activity of CT-PCPE. Purified CT-PCPE inhibited MMP-2 with an IC(50) value much greater than that of TIMP-2. This implies that MMPs may not be the physiologic targets for CT-PCPE inhibition. However, these results suggest that CT-PCPE may constitute a new class of metalloproteinase inhibitor.
Amino Acid Sequence↗
Physical training augments plasma catecholamines and natural killer cell activity.
To elucidate the effects of a 10-week exercise training period on physical fitness and plasma catecholamine concentration at rest, and on natural killer cell activity in young healthy untrained females, subjects (20-22 years old. N = 16) carried out physical training by a protocol which consisted of treadmill jogging at a work-intensity of 50% of their VO2max, two hours a day three times a week for ten weeks. VO2max was increased significantly from 33.1 +/- 3.4 ml/kg/min to 38.3 +/- 6.6 ml/kg/min by the ten weeks of physical training (P < 0.005), and natural killer cell activity was also increased significantly from 31.9 +/- 14.3% to 46.4 +/- 18.4% (P < 0.05). The concentrations of epinephrine and norepinephrine before and after physical training were 18.3 +/- 8.7 pg/ml and 20.4 +/- 8.9 pg/ml, and 134.1 +/- 52.2 pg/ml and 248.1 +/- 106.8 pg/ml (P < 0.005), respectively. Changes in norepinephrine and epinephrine correlated with the change in VO2max (r = 0.780, P < 0.005; r = 0.556, P < 0.05). While the change in natural killer cell activity correlated with the change in epinephrine (r = 0.623, P < 0.01), the correlation of the change in natural killer cell activity with change in norepinephrine did not reach statistical significance (r = 0.497, P = 0.0503). From these results we concluded that physical training augments plasma catecholamine levels and natural killer cell activity at rest in young healthy females.
Adult↗
Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis.
Vertebrate bone morphogenetic protein 1 (BMP-1) and Drosophila Tolloid (TLD) are prototypes of a family of metalloproteases with important roles in various developmental events. BMP-1 affects morphogenesis, at least partly, via biosynthetic processing of fibrillar collagens, while TLD affects dorsal-ventral patterning by releasing TGFbeta-like ligands from latent complexes with the secreted protein Short Gastrulation (SOG). Here, in a screen for additional mammalian members of this family of developmental proteases, we identify novel family member mammalian Tolloid-like 2 (mTLL-2) and compare enzymatic activities and expression domains of all four known mammalian BMP-1/TLD-like proteases [BMP-1, mammalian Tolloid (mTLD), mammalian Tolloid-like 1 (mTLL-1), and mTLL-2]. Despite high sequence similarities, distinct differences are shown in ability to process fibrillar collagen precursors and to cleave Chordin, the vertebrate orthologue of SOG. As previously demonstrated for BMP-1 and mTLD, mTLL-1 is shown to specifically process procollagen C-propeptides at the physiologically relevant site, while mTLL-2 is shown to lack this activity. BMP-1 and mTLL-1 are shown to cleave Chordin, at sites similar to procollagen C-propeptide cleavage sites, and to counteract dorsalizing effects of Chordin upon overexpression in Xenopus embryos. Proteases mTLD and mTLL-2 do not cleave Chordin. Differences in enzymatic activities and expression domains of the four proteases suggest BMP-1 as the major Chordin antagonist in early mammalian embryogenesis and in pre- and postnatal skeletogenesis.
Amino Acid Sequence↗
Structural organization and expression patterns of the human and mouse genes for the type I procollagen COOH-terminal proteinase enhancer protein.
The procollagen C-proteinase enhancer (PCPE) is a glycoprotein that potentiates enzymatic cleavage of the type I procollagen C-propeptide by bone morphogenetic protein-1 (BMP-1). The human PCPE gene (PCOLCE) was previously mapped to 7q22, an area frequently disrupted in uterine leiomyomata, while disruption of the rat PCPE gene leads to anchorage-independent growth and loss of contact inhibition in rat fibroblasts. Here we describe the entire intron/exon organizations of PCOLCE and the mouse PCPE gene (Pcolce) and analyze expression of PCOLCE RNA in various human adult and fetal tissues and of Pcolce RNA at various stages of mouse development. PCOLCE and Pcolce are shown to be small genes 6.0 and 6.5 kb, respectively, with a conserved intron/exon structure comprising 9 exons. A notable difference between the two genes derives from insertion of multiple Alu sequences immediately upstream and downstream and within PCOLCE. Temporal expression of PCPE mRNA is shown to differ from that of BMP-1 and type I procollagen during mouse development, consistent with possible additional functions for PCPE beyond enhancement of C-proteinase activity. Consistent with a possible role in leiomyomata, PCOLCE is shown to be expressed at relatively high levels in uterus.
Adult↗
Assignment of TLL1 and TLL2, which encode human BMP-1/Tolloid-related metalloproteases, to chromosomes 4q32-->q33 and 10q23-->q24 and assignment of murine Tll2 to chromosome 19.
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Animals↗
[Autonomic nerve function expressed by the baroreflex sensitivity (BRS) in elderly adults].
We examined 24 hour heart rate variability (HRV) components and baroreflex sensitivity (BRS) in elderly adults. Forty-eight subjects, aged 65-69 years old (24 men, 24 women) were examined in this study. BRS was measured in the morning (8:00-9:00) using noninvasive cross spectral analysis. There were significant correlations between BRS and low-frequency (LF) power (r = 0.593, p < 0.001) of HRV, and between BRS and high-frequency (HF) power (r = 0.402, p < 0.005). BRS values were lower in women compared with men (p < 0.01), and LF/HF was significantly lower in women than in men (p < 0.05).
Aged↗
Changes in cyclin B during oocyte maturation and early embryonic cell cycle in the newt, Cynops pyrrhogaster: requirement of germinal vesicle for MPF activation.
When full-grown oocytes of the newt Cynops pyrrhogaster were treated with progesterone in O-R2 solution containing antibiotics, approximately 85% of the oocytes completed meiosis synchronously. Maturation-promoting factor (MPF) activity appeared just before germinal vesicle breakdown (GVBD) and the oocytes maintained high MPF activity throughout metaphase I and metaphase II of meiosis. A slight decrease of MPF activity was observed at the first polar body emission. The distribution of cyclin B1 was investigated with anti-cyclin B1 antibody. No cyclin B1 was found in the oocytes before progesterone treatment. Cyclin B1 appeared in the cortex of animal hemispheres, especially around and inside germinal vesicle just before GVBD. A large amount of cyclin B1 accumulated at metaphase I, approximately half disappeared at the first polar body emission, and then cyclin B1 accumulated again at metaphase II. An inactive form of cdc2 kinase was observed in both the germinal vesicles and the oocyte cytoplasm, while an active form appeared at the M phase. No MPF was observed in the oocytes from which the germinal vesicle had been removed. A cdk7-like molecule was localized in the germinal vesicle, but not in oocyte cytoplasm, indicating that inactive cdc2 kinase associated with cyclin B1 derived from cytoplasm is activated by phosphorylation in the germinal vesicle. The changes in the amount of cyclin B1 were synchronous with the first cell cycle after fertilization. Cyclin B1 was primarily localized in the cortex of the animal hemisphere. A shift in band mobility upon electrophoresis of cyclin B1 was observed from samples taken during the cell cycle; this shift was probably due to the protein's phosphorylation state.
Animals↗
Transforming growth factor-beta regulation of bone morphogenetic protein-1/procollagen C-proteinase and related proteins in fibrogenic cells and keratinocytes.
Transforming growth factor-beta1 (TGF-beta1) induces increased extracellular matrix deposition. Bone morphogenetic protein-1 (BMP-1) also plays key roles in regulating vertebrate matrix deposition; it is the procollagen C-proteinase (PCP) that processes procollagen types I-III, and it may also mediate biosynthetic processing of lysyl oxidase and laminin 5. Here we show that BMP-1 is itself up-regulated by TGF-beta1 and that secreted BMP-1, induced by TGF-beta1, is either processed to an active form or remains as unprocessed proenzyme, in a cell type-dependent manner. In MG-63 osteosacrcoma cells, TGF-beta1 elevated levels of BMP-1 mRNA approximately 7-fold and elevated levels of mRNA for mammalian tolloid (mTld), an alternatively spliced product of the BMP1 gene, to a lesser extent. Induction of RNA was dose- and time-dependent and cycloheximide-inhibitable. Secreted BMP-1 and mTld, induced by TGF-beta1 in MG-63 and other fibrogenic cell cultures, were predominantly in forms in which proregions had been removed to yield activated enzyme. TGF-beta1 treatment also induced procollagen N-proteinase activity in fibrogenic cultures, while expression of the procollagen C-proteinase enhancer (PCPE), a glycoprotein that stimulates PCP activity, was unaffected. In contrast to fibrogenic cells, keratinocytes lacked detectable PCPE under any culture conditions and were induced by TGF-beta1 to secrete BMP-1 and mTld predominantly as unprocessed proenzymes.
Amino Acid Sequence↗
Effects of nisoldipine on cytosolic calcium, platelet aggregation, and coagulation/fibrinolysis in patients with coronary artery disease.
The effect of nisoldipine, a dihydropyridine Ca2+ antagonist, on the platelet cytosolic Ca2+ concentration ([Ca2+]i), platelet aggregation, and various coagulation and fibrinolysis parameters was assessed in normotensive patients with coronary artery disease (CAD). Eleven patients with angiographically confirmed CAD (4 men, 7 women aged 67.3 +/- 5.4 years) were administered nisoldipine at 10 mg/day for two weeks. The [Ca2+]i was determined by use of fura2-loaded platelets, platelet aggregation was measured with an aggregometer, and coagulation/fibrinolysis parameters were measured by standard methods. Nisoldipine did not significantly affect blood pressure or heart rate. However, the [Ca2+]i decreased significantly (P<0.05) and platelet aggregation was also significantly inhibited. Plasma D-dimer levels decreased significantly (P<0.01). Thus, nisoldipine not only suppressed platelet activation but also affected the coagulation system, suggesting that it is not only a vasodilator and platelet inhibitor but also an antithrombotic agent.
6-Ketoprostaglandin F1 alpha↗
Characterization of a novel gene product (mammalian tolloid-like) with high sequence similarity to mammalian tolloid/bone morphogenetic protein-1.
Bone morphogenetic protein-1 (BMP-1), a metalloprotease isolated from osteogenic extracts of demineralized bone, is capable of cleaving the C-propeptides of procollagen types I, II, and III. A single mammalian gene produces alternatively spliced RNA transcripts for BMP-1 and for a second longer protein, designated mammalian tolloid (mTld) due to a domain structure identical to that of the Drosophila dorsal-ventral patterning gene product tolloid (Tld). Here we report the use of a cDNA library, prepared from BMP-1/mTld-null mouse embryos, to isolate cDNA clones for a novel mammalian protein with a domain structure identical to that of mTld. The new protein, designated mammalian tolloid-like (mTll), has 76% identity with mTld for amino acid residues in all domains downstream of, and including, the protease domain. In contrast, the N-terminal activation domains of the two proteins show little similarity. In situ hybridizations show the distribution of mTll RNA to overlap extensively that previously shown for the BMP-1 and mTld RNA forms. However, mTll shows additional strong expression in structures of the developing, neonatal, and adult brain in which expression of BMP-1 and mTld has not been observed. The murine mTll gene (Tll) is mapped to central chromosome 8, which is a different chromosomal location than that of the BMP-1/mTld gene. Loci for some developmental abnormalities map to the same general chromosomal location as Tll.
Alternative Splicing↗