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Biomedical subjects

S Aoki

Publications and source records attributed to S Aoki.

At least 19 recordsLinked to original sources

Hepatocyte growth factor plays a dual role in regulating skeletal muscle satellite cell proliferation and differentiation.

The role of hepatocyte growth factor (HGF) and its receptor, c-met, in proliferation and differentiation of satellite cells was studied in primary cultures of chicken skeletal muscle satellite cells and a myogenic C2 cell line. HGF mRNA was expressed mainly in the myotubes of both cultures. The addition of conditioned medium derived from those cultures had a scattering effect on the canine kidney epithelial cell line, MDCK. In contrast, c-met mRNA levels decreased during cell differentiation of C2 and primary satellite cells. Application of exogenous HGF to chicken myoblasts resulted in their enhanced DNA synthesis. Among several growth factors, HGF was the first to induce DNA synthesis in quiescent satellite cells, thereby driving them into the cell cycle. Ectopic expression of chicken HGF in primary satellite cells suppressed the activation of muscle-regulatory gene reporter constructs MCK-CAT, MRF4-CAT, MEF2-CAT and 4Rtk-CAT, as well as the gene expression of MyoD and myogenin, and MHC protein expression. Ectopic MyoD reversed HGF's inhibitory effect on MCK transactivation. These data suggest that HGF inhibits cell differentiation by inhibiting the activity of basic helix-loop-helix (bHLH)/E protein heterodimers, thus inhibiting myogenic determination factor activity and subsequent muscle-specific protein expression. During muscle growth and regeneration, HGF plays a dual role in satellite-cell myogenesis, affecting both the proliferation and differentiation of these cells in a paracrine fashion.

Animals

Clinicopathological features of chronic inflammatory demyelinating polyradiculoneuropathy in childhood.

The clinical, electrophysiological, and pathological findings, and the therapeutic characteristics in ten children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), whose onset age was less than 16 years, were evaluated. The clinical progression pattern of the initial phase divided the patients into two groups. One group (six patients) showed a subacute progression for up to 2 months after onset and a subsided progression over 3 months. Three patients in this group had a preceding febrile episode. The other group (four patients) showed a chronic insidious progression for more than 3 months. The former group of patients revealed a favourable response to corticosteroid therapy as compared with the latter group. However, other clinical and laboratory features at the peak impairment were not distinguishable between these two groups. Motor dominant neuropathy was common to all patients, and only three cases showed sensory disturbance on the distal limbs. No cases revealed cranial nerve involvement. Motor and sensory nerve conduction and sural nerve biopsy studies revealed the demyelinating nature of the neuropathy. These clinicopathological features suggest that the subacute progression form frequently associated with prodromal episode and rather favourable corticosteroid response is characteristic in childhood CIDP, while the chronic insidious progression form is indistinguishable from the common adult CIDP.

Adolescent

Three-dimensional ultrasonographic assessments of fetal development.

OBJECTIVE: To visualize fetal surface anatomic structures in advancing gestation by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. METHODS: One hundred six normal fetuses from 9 to 40 weeks' gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and also can generate within seconds high-quality three-dimensional images in the surface and transparent modes with no need for an external workstation. We determined percentage of surface anatomic structures visualized at each trimester using two-dimensional and three-dimensional ultrasonography. RESULTS: The number and the clarity of surface anatomic structures increased from the first to the third trimester of pregnancy. The image quality was less distinct in the first trimester because of the small fetal size. The ability to view the fetal face, hands, and feet was better with three-dimensional ultrasonography than with two-dimensional ultrasonography in the first trimester (P < .05), whereas fetal genitals were viewed better with two-dimensional ultrasonography than with three-dimensional ultrasonography in the second and third trimesters (P < .05). CONCLUSION: Three-dimensional ultrasonography provides a new means of visualizing surface anatomic structures of the fetus in utero. Our results suggest that three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and should be useful in evaluating fetal abnormalities in high-risk pregnancies.

Embryonic and Fetal Development

Three-dimensional intrauterine sonography in the early first-trimester of human pregnancy: preliminary study.

Our purpose was to visualize normal embryonal surface anatomic structures using three-dimensional (3D) intrauterine sonography with a 20 MHz flexible catheter-based high-resolution real-time miniature transducer in the early first trimester of pregnancy. A total of 15 women about to undergo therapeutic abortion at 7-9.9 weeks gestational age were studied by means of 3D intrauterine sonography with a specially developed catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer (20 MHz). This imaging system can provide conventional 2D intrauterine sonographic images and can also generate within seconds high-quality 3D images in the surface and transparent mode. At week 8, prominent forehead was evident, and upper and lower limbs and midgut herniation were clearly depicted. At week 9, fingers and toes were depicted as small digital rays, and the sacral tail protruded caudally. The midline cranial ectodermal cleft was also identified. At week 10, embryonic face and fingers were clearly shown. 3D intrauterine sonography provides a novel means for visualizing of surface anatomic structures of the human embryo in utero. These results suggest that 3D intrauterine sonography can become an important modality in future embryological research and in detection of embryonic developmental disorders in the early first-trimester pregnancy.

Embryo, Mammalian

Familial occurrence of congenital bile duct cysts.

Congenital bile duct cysts are now a well-documented anomaly of the biliary tree, and have become more common in Japan. Familial occurrence of congenital bile duct cysts, however, is extremely rare, with only six reported cases in the literature. We report a familial pattern of congenital bile duct cysts in a mother and her daughter. A 33-year-old female was admitted for evaluation of right upper quadrant abdominal pain and fever 6 days after an uneventful delivery of her second child. A computed tomography (CT) and ultrasound scan (US) revealed an obstructed biliary tract. Percutaneous transhepatic biliary drainage was then performed, and a cholangiogram revealed a Scholtz type B choledochocele without an anomalous connection of the pancreaticobiliary ducts. Endoscopic US demonstrated that the choledochocele was associated with a stone in the cyst. A pylorus-preserving pancreatoduodenal resection was performed, and a histological study revealed that the choledochocele was lined by biliary mucosa without evidence of malignancy. The newborn infant had an abdominal tumour. An US and CT revealed a congenital bile duct cyst. An operation was performed and the intraoperative cholangiogram showed an Alonso-Lej type I congenital bile duct cyst with an anomalous connection of the pancreaticobiliary ducts. Whether congenital bile duct cysts are hereditary remains to be elucidated.

Adult

Power Doppler enhancement of the placenta by dehydroepiandrosterone sulphate in term pregnancy.

We studied the effect of dehydroepiandrosterone sulphate (DHAS) on placental blood flow in 11 women with an uncomplicated pregnancy between 37 and 39 weeks of gestation. Power Doppler enhancement of the placenta was performed before and 60 minutes after the administration of a 200 mg intravenous dose of DHAS dissolved in 20 mL of 5% dextrose. Increased power Doppler enhancements of the placenta after DHAS injection were evident in each case studied. The power Doppler enhancement returned to the baseline imaging within 60 minutes. This DHAS loading test, assessed by means of power Doppler imaging, may be a useful technique when attempting to assess fetoplacental function in normal and high risk pregnancies.

Acetone

A period-extender gene, pex, that extends the period of the circadian clock in the cyanobacterium Synechococcus sp. strain PCC 7942.

We cloned the pS1K1 plasmid in the process of apparently "complementing" a circadian clock mutant of cyanobacterium Synechococcus sp. strain PCC 7942, SP22, which has a 22-h period (T. Kondo, N. F. Tsinoremas, S. S. Golden, C. H. Johnson, S. Kutsuna, and M. Ishiura, Science 266:1233-1236, 1994). Sequence analysis revealed that SP22 did not have a mutation in the genomic DNA segment carried on pS1K1, and the sp22 mutation was later found in a recently cloned new clock gene, kaiC. Therefore, the period-extender gene pex that was carried on pS1K1 was a suppressor gene for the sp22 mutation. The pex gene encoded a protein of 148 amino acid residues. No meaningful homologs were found in DNA or protein databases including the Synechocystis genome database. The pex gene was transcribed from 129 and 164 bp upstream of the translation initiation codon as 0.6-kb transcripts. The Pex protein was detected as a fusion protein with a molecular mass of 15 kDa by the epitope tag fusion method using a c-Myc epitope tag. Disruption of the pex gene in wild-type cells shortened the period of the rhythms by 1 h, although it did not affect other properties of the rhythms, whereas its overexpression extended the period by 3 h with a concomitant reduction in the amplitude of the rhythms. In various clock mutants examined, overexpression caused arrhythmicity. Thus, Pex is likely to function as a modifier of the circadian clock in Synechococcus.

Amino Acid Sequence

Three-dimensional ultrasonographic assessment of the umbilical cord during the 2nd and 3rd trimesters of pregnancy.

OBJECTIVE: To evaluate the umbilical cord and its abnormalities by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. PATIENTS AND METHODS: Ninety-five pregnancies (92 normal, 2 with hydrops fetalis, and 1 with omphalocele) from 14 to 40 weeks of gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This system can provide conventional two-dimensional ultrasonography images and can also generate within seconds high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. A proportion of the umbilical cords (coiled or noncoiled free loop, abdominal insertion, and placental insertion) visualized at each gestational age interval is presented. RESULTS: The proportion of the umbilical cords visualized during pregnancy except for between 24 and 27 weeks of gestation was about 70% (range 64-83%). Optimal visualization of the umbilical cord was achieved between 24 and 27 weeks of gestation. During this period it was possible to adequately depict the umbilical cord in 93% of the cases. The proportions of the noncoiled umbilical cord depicted during pregnancy ranged from 8 to 45%. The detection rate of abdominal insertion of the umbilical cord visualized at 14-19 weeks was 44%; the detection rate decreased thereafter. Placental insertion of the umbilical cord could not be identified after 28 weeks of gestation. In 2 cases with hydrops fetalis, edematous umbilical cord was evident. In 1 fetus, omphalocele was clearly depicted. CONCLUSIONS: The new three-dimensional ultrasound technology generates within seconds high-quality three-dimensional images of the umbilical cord, although limitation of viewing direction exists. These results suggest that the new three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and might be useful in identifying abnormal umbilical cords in utero.

Edema

Three-dimensional sonographic visualization of the fetal face.

OBJECTIVE: This study was done to show the potential of using three dimensional (3D) sonography to reveal fetal facial anomalies. SUBJECTS AND METHODS: Ninety-four healthy fetuses from 15 to 40 weeks' gestation were studied with a specially developed 3.5-MHz abdominal 3D transducer. This imaging system provided conventional two-dimensional (2D) sonographic images and also generated within seconds high-quality 3D images in the surface and transparent modes with no need for an external workstation. RESULTS: Using this imaging system, we obtained 2D and 3D images of fetal faces (forehead, eyes, nose, lips, and chin) at six gestational ages. At less than 24 weeks' gestation, 65% of facial structures were visualized. The image quality was slightly degraded because of the small fetal size. At or after 24 weeks' gestation, 84% of facial structures were revealed. We found no significant difference in image quality of the fetal face between 2D and 3D sonography. CONCLUSION: The new 3D sonographic technology can generate within seconds high-quality 3D images of the fetal face. The 3D technology seems to perform at least as well as conventional 2D sonography. Our results suggest that 3D sonography has the potential to supplement 2D sonography and might be useful in identifying malformations of the fetal face and chromosomal abnormalities in utero.

Face

[Intracranial aneurysms in autosomal dominant polycystic kidney disease detected by MR angiography: screening and treatment].

The association of intracranial aneurysm with ADPKD is well-known, and patients with ADPKD are at increased risk of subarachnoid hemorrhage from rupture of intracranial aneurysms. We prospectively performed three-dimensional time-of-flight magnetic resonance angiography (MRA) in 30 nonselective adult patients with ADPKD. Sixteen were women and 14 were men with a mean age of 51 yr (range 24 to 79 yr). The diagnosis of ADPKD was made on the basis of abdominal ultrasound or computed tomographic studies. Three patients were on maintenance hemodialysis, 8 patients were nondialysed patients with chronic renal failure (serum creatinine > or = mg/dl) and 25 patients had hypertension (BP > or = 140/90 mmHg). None of these patients have a previous diagnosis of intracranial aneurysm. Unruptured intracranial aneurysms were suspected in 5 patients by MRA, and 8 aneurysms were confirmed in 4 (13.3%) of 30 patients by conventional arteriography. These aneurysms were 3 approximately 10 mm in diameter and 3 aneurysms (3 approximately 4 mm in diameter) were newly detected by cerebral arteriography. After informed consent was obtained, neck clipping of the intracranial aneurysms were performed successfully in all the patients. These results suggest that the prevalence of intracranial aneurysms is about 13% in ADPKD, and that MRA is useful in screening for occult intracranial aneurysms in patients with ADPKD.

Adult

Velocity-coded color MR angiography.

We developed a method of velocity-coded color MR angiography using a color code from the data obtained from velocity-phase images of phase-contrast MR angiography in order to add flow direction information to MR angiograms. Phase-contrast MR angiography with reconstruction of velocity-phase images was performed in 30 patients. Two projection images from velocity-phase images of each phase-contrast MR angiogram were obtained and assigned color according to flow direction. We then superimposed the two color images onto the maximum intensity projection image of the MR angiogram. The velocity-coded color MR angiogram clearly showed flow direction from the data on the phase-contrast MR angiogram of the neck. Veins were readily distinguishable from arteries, and flow changes, such as a subclavian steal, were also identified.

Blood Flow Velocity

Activation of Met tyrosine kinase by hepatocyte growth factor is essential for internal organogenesis in Xenopus embryo.

Hepatocyte growth factor (HGF) specifically activates Met tyrosine kinase receptor, leading to mitogenic, motogenic, and morphogenic responses in a wide variety of cells. To know a role of HGF in Xenopus embryogenesis, loss-of-function mutation was introduced by dominant expression of truncated tyrosine kinase-negative Met. When tyrosine kinase-negative Met mRNA was micro-injected into two-cell to eight-cell stages Xenopus embryos, the liver development was mostly impaired and structures of pronephros and the gut were grossly underdeveloped in the restricted, late stage of development. These results strongly suggest that functional coupling between HGF and Met is essential for the development of internal organs originated from primitive gut and possibly involved in embryonic skeletogenesis. Together with developmental abnormality in mice mutated with HGF or Met gene, essential role of HGF for liver development is highly conserved from amphibian to mammalian species.

Animals

Circadian rhythms in rapidly dividing cyanobacteria.

The long-standing supposition that the biological clock cannot function in cells that divide more rapidly than the circadian cycle was investigated. During exponential growth in which the generation time was 10 hours, the profile of bioluminescence from a reporter strain of the cyanobacterium Synechococcus (species PCC 7942) matched a model based on the assumption that cells proliferate exponentially and the bioluminescence of each cell oscillates in a cosine fashion. Some messenger RNAs showed a circadian rhythm in abundance during continuous exponential growth with a doubling time of 5 to 6 hours. Thus, the cyanobacterial circadian clock functions in cells that divide three or more times during one circadian cycle.

Cell Division

Xenopus LIM motif-containing protein kinase, Xlimk1, is expressed in the developing head structure of the embryo.

The LIM double zinc finger motif locates in several developmentally functioning and cytoskeletal proteins, and is considered to act as a specific motif for protein-protein interactions. LIM kinase (LIMK) is a novel protein kinase containing two LIM motifs at the N-terminal, the function of which has yet to be clearly defined. In this study, we cloned a cDNA encoding Xenopus counterpart of human LIMK1 gene by RT-PCR mediated cloning, and designated in Xlimk1. Xlimk1 is highly homologous to mammalian LIMK1 in each structural domain, particularly in LIM and protein kinase domains. In Northern blot analysis, two distinct Xlimk1 transcripts of 9.0 Kb and 3.7 Kb were present in early cleavage stages of the embryo. Both mRNA species were subsequently decreased at the gastrula stages. The 9.0 Kb of Xlimk1 mRNA again appeared in late neurula stage, then the expression level gradually increased in later stages of the embryo. Whole-mount in situ hybridization analysis showed the localization of Xlimk1 transcripts in the animal half of the blastula embryo. In post-neurula stages, specific signals for Xlimk1 were predominant in the anterior (head) region of the embryo, including developing brain, hyoid and branchial arches, and anlagen of sensory organs. These results indicate that Xlimk1 may play an important role in neural development and formation of anterior (head) structures in the Xenopus embryo.

Amino Acid Sequence

Effect of albendazole on recurrent and residual alveolar echinococcosis of the liver after surgery.

Patients with alveolar echinococcosis of the liver (AEL) can be cured by complete excision of the lesions; however, it is not always completely resectable in advanced cases. Recently, benzimidazole-type drugs have been reported to be effective in nonresectable AEL. One hundred fifty-two patients with AEL have been surgically treated in our institution since 1937. Our clinical trial with albendazole, one of the benzimidazole carbamates, has included 26 cases of AE since September 1988, each of whom had undergone an operation. Complete resection was performed in only six cases. Evaluation of response to the treatment was possible in 20 cases. A favorable response to albendazole, such as decreases in the size of the lesions, changes in cyst morphology, and amelioration in clinical symptoms or signs, was achieved in 11 (55%) cases. These favorable responses were also seen in cases of noncurative resection and palliative operation. The cumulative survival rate of the patients was 87%, 15 years after the operation. A complete response was achieved in one case; the residual lesion in the liver completely disappeared on the computed tomography image 3.5 years after noncurative surgery. Palliative or mass reduction surgery combined with albendazole therapy may be a strategy for advanced disease, especially when complete resection might result in significant morbidity or mortality.

Adult