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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 55 records · Page 3Linked to original sources

Initial pathological events in renal dysplasia with urinary tract obstruction in utero.

Multicystic dysplastic kidneys (MCDK) and obstructive renal dysplasia (ORD) are two different phenotypes of dysplasia commonly associated with urinary tract obstruction. However, the mechanisms whereby obstruction in the developing kidney leads to each dysplasia are unknown. In the present study, 16 fetal MCDKs and 3 fetal ORDs (18-35 weeks of gestation) were analyzed with light microscopy, point-counting morphometry, immunohistochemistry with a podocyte marker, and scanning electron microscopy. Additionally, reconstructions of dysplastic nephrons were done via serial section analysis. Early stages of MCDK and ORD similarly revealed numerous cyst formations, predominantly in the subcapsular nephrogenic zone. Occasionally, glomerular tuft remnants with mature podocyte phenotypes were observed in cysts, suggesting the acquisition of filtration. Three dimensionally, basic nephron structures were installed in the cystic nephrons, namely the macula densa with a primary loop structure. Cysts developed in the once-induced nephrons due to fluid retention in both MCDK and ORD. In utero urinary tract obstruction may cause urine retention in functioning nephrons and lead to glomerular cysts in the nephrogenic zone. These findings were common to MCDK and ORD, albeit at different sites of obstruction. Expansion of glomerular cysts with tubular dilatation (cysts) disturbs the subsequent nephrogenesis and may contribute to the misdevelopment of fetal kidneys.

Cysts↗

Spatial and temporal expression patterns of the cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2 during mouse development.

The cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2 are thought to regulate progression of the cell cycle. We have previously shown that the phenotypes of p27-/- mice are substantially different from those of p57-/- mice, suggesting that spatial and temporal expression patterns of p27Kip1 and p57Kip2 might be distinct. In this study, the roles of p27Kip1 and p57Kip2 in development were examined by characterizing their expression patterns during mouse embryogenesis by immunohistochemical analysis. Whereas certain organs and tissues (brain, lens, ganglion, lung, heart, liver, skin and kidney) expressed both proteins, others expressed only p27Kip1 (thymus, spleen, retina, testis and ovary) or only p57Kip2 (gut, palate, pancreas, cartilage and skeletal muscle). In addition, some organs expressed both p27Kip1 and p57Kip2 but showed mutually exclusive patterns of distribution among tissues. Thus, in the adrenal gland, p57Kip2 was expressed in the cortex but not in the medulla, whereas p27Kip1 was expressed in the medulla but not in the cortex. Whereas the expression of p57Kip2 in most tissues was restricted to embryogenesis, expression of p27Kip1 in many tissues was maintained in adult animals. Double-label immunofluorescence staining with either anti-p27Kip1 or anti-p57Kip2 and anti-BrdU revealed that the expression of p27Kip1 and p57Kip2 was inversely correlated with cell proliferation, suggesting that p27Kip1 and p57Kip2 are expressed exclusively in postmitotic cells. These complex spatial and temporal patterns of expression are consistent with the phenotypes of mice deficient in p27Kip1 or p57Kip2, and they suggest that these proteins might play important roles in tissue development.

Adrenal Cortex↗

Intracameral and Lenticular Penetration of Locally Applied Deuterium-Labeled Vitamin E in Rats.

Purpose: To confirm the intraocular dynamics of 1% deuterium (D) labeled alpha-tocopheral acetate (VEA) solution.Methods: The concentrations of D(3)-VEA and D(3)-alpha-tocopherol (VE) derived from D(3)-VEA in the aqueous humor and lens were measured after instilling 1% D(3)-VEA continuously into the cul-de-sac of rat eyes for one and three weeks. D(3)-VEA and D(3)-VE concentrations were determined by gas chromatograph/mass spectrometry.Results: D(3)-VEA and D(3)-VE concentrations in the aqueous humor after one and three weeks of continuous administration were 93.1 and 498.9, and 9.4 and 21.5 ng/mL, respectively. The concentrations in the lens were 15.0 and 6.1, and 9.8 and 4.8 ng/g, respectively.Conclusion: The penetration of VEA into the aqueous humor and lens by eyedrop application was confirmed.

Journal Article↗

Glomerular crescents in renal amyloidosis: an epiphenomenon or distinct pathology?

There have been several reports of cases of renal amyloidosis with glomerular crescents. However, it is not clear whether the association is fortuitous or pathogenic related. The present study analyzed 105 cases of renal amyloidosis (61 autopsy cases and 44 biopsy cases) and found glomerular crescents in 14 (13.3%) cases. Among the 14 cases with crescents, a female predominance was noted (male: female, 3: 11) and rheumatoid arthritis was the most common primary disease of amyloidosis. Immunohistochemical analysis demonstrated amyloid protein of AA type in 12 cases. According to the histologic classification, there were 11 cases of mesangial nodular type, which was almost exclusively accompanied by AA amyloid deposition. Of note, the incidence of crescents neither correlated with the extent of amyloid deposition nor the presence of nephrotic syndrome. By contrast, localization of amyloid deposition was closely related to crescent formation. Moreover, electron microscopic observation displayed rupture of the glomerular basement membrane at the site of amyloid deposition. Our results indicated that glomerular crescents were more frequently associated with renal amyloidosis than previously appreciated. Rupture of the fragile glomerular basement membrane by amyloid deposition, as revealed by immunostaining and electron microscopy, may be the mechanism of crescent formation. We suggest that glomerular crescents are a distinct pathology associated with renal amyloidosis, not fortuitous conditions.

Adult↗

Three autopsied cases of cystic fibrosis in Japan.

The incidence of cystic fibrosis (CF) is very rare in Japanese, while it is frequent in Caucasians. Here we report on three Japanese cases of CF. One of the patients had consanguineous parents. All three patients initially developed meconium ileus, and hepatobiliary and pancreatic changes became more severe as age increased. The DeltaF508 mutation, the most frequent mutation associated with CF in Caucasians, was not found in these patients. To evaluate the relationship between the severity of hepatic lesions and a history of meconium ileus, we examined hepatic lesions in the present three cases, and we reviewed 22 Japanese autopsied cases of CF in the literature. No correlation was found between the incidence of biliary cirrhosis and a history of meconium ileus, because the cases with meconium ileus showed a high mortality during the neonatal period, before biliary cirrhosis developed. The high incidence of meconium ileus in Japanese CF patients may relate to a clinically severe phenotype and reflect a different genetic background between Caucasians and Japanese.

Adolescent↗

Quantitation of human herpesvirus 6 DNA in infant with exanthem subitum by microplate PCR-hybridization assay.

BACKGROUND: Quantitative analysis of human herpesvirus 6 (HHV-6) genome is important for monitoring active virus infection. The purpose of our study is to evaluate the reliability of a hybridization-based microtiter plate assay (polymerase chain reaction enzyme-linked immunosorbent assay (PCR ELISA)) for quantifying the virus genome. METHODS: Semiquantitative analysis of the virus genome was carried out in 31 (18 male and 13 female) infants with primary HHV-6 infection. If the HHV-6 virus could be isolated from the peripheral blood mononuclear cells (PBMC), the infants were defined as being infected with HHV-6. The PCR ELISA method was used to determine the virus load. A titration of the virus was also carried out in the samples obtained during the acute phase of exanthem subitum. RESULTS: Specificity of the method was demonstrated by a lack of amplification of human herpesvirus 7 and cytomegalovirus DNA. The upper and lower detection limits of the method were 58 and 5800 copies of the virus genome, respectively. The quantity of HHV-6 DNA in the PBMC during the acute phase (879 +/- 975 copies/10(4) PBMC) was significantly higher than during the convalescent phase (54 +/- 76 copies/10(4) PBMC). Furthermore, the virus load in acute phase plasma (53 +/- 75 copies/microL) was also significantly higher than in the convalescent phase samples (2 +/- 9 copies/microL). Virus load in both PBMC and plasma gradually increased after the onset of exanthem subitum until about day 3 to 4 of the illness, but then decreased quickly. However, there was no significant association between virus load and the numbers of infected cells. CONCLUSION: Virus load in both PBMC and plasma gradually increased after the onset of exanthem subitum until about day 3 and day 4 of the illness, respectively, then it decreased quickly. These results indicate that our PCR ELISA system is reliable for monitoring active HHV-6 infection in vivo.

DNA, Viral↗

Increased QT dispersion does not reflect the increased regional variation of cardiac sympathetic nervous activity in hypertrophic cardiomyopathy.

BACKGROUND: QT dispersion (QTD) reflects regional variation of ventricular repolarization. However, the relationship between QTD and the regional variation of cardiac sympathetic nerve activity in hypertrophic cardiomyopathy (HCM) is not yet elucidated. METHODS: Cardiac sympathetic nerve activity was evaluated in 25 patients with HCM by iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy. With planar MIBG imaging, heart and mediastinum ratios (H/M) at early (20 minutes) and delayed (3 hours) acquisition and the washout rate (WR) were calculated. Polar maps of left ventricular myocardium were divided into 20 segments. The SD of early uptake (EU-SD), delayed uptake (DU-SD), and WR (WR-SD) in 20 segments as indices of regional variation were calculated. QT intervals were corrected by use of the Bazett formula. RESULTS: Maximum QTc correlated positively with H/M early, WR, and left ventricular wall thickness (LVWT). Minimum QTc correlated positively with WR and LVWT. Corrected QTD (QTDc) correlated negatively with EU-SD, DU-SD, and WR-SD and positively with the interventricular septal thickness/posterior wall thickness ratio. Stepwise regression analysis revealed that the most powerful determinants for maximum QTc, minimum QTc, and QTDc were WR, LVWT, and EU-SD, respectively. CONCLUSIONS: QTD correlated negatively rather than positively with the regional variability index of cardiac sympathetic nerve activity. These results suggest that increased QTD in patients with HCM may not reflect increased heterogeneity of cardiac sympathetic nerve activity.

Arrhythmias, Cardiac↗

Surgically-induced astigmatism following single-site phacotrabeculectomy, phacotrabeculotomy and advanced non-penetrating phacotrabeculectomy.

We study surgically-induced astigmatism following three kinds of glaucoma surgeries combined with cataract surgery with 6 months of follow-up. The mean surgically-induced astigmatism at 6 months postoperatively was 1.92 +/- 1.87 diopters in phacotrabeculectomy (n = 45), 0.72 +/- 0.40 diopters in advanced non-penetrating phacotrabeculectomy (n = 40) and 0.76 +/- 0.47 diopters in phacotrabeculotomy (n = 49), which appeared to be stabilized by 3 months. Each group revealed a tendency of "with the wound" induced astigmatism. Phacotrabeculectomy could induce greater surgically-induced astigmatism than advanced non-penetrating phacotrabeculectomy and phacotrabeculotomy.

Astigmatism↗

Trabeculotomy combined with phacoemulsification and implantation of intraocular lens for primary open-angle glaucoma.

Retrospective study examined the surgical effects of lowering intraocular pressure of trabeculotomy combined with phacoemulsification and implantation of an intraocular lens. Included in the retrospective study were 96 eyes of 64 patients with primary open-angle glaucoma. Preoperative mean IOP was 25.6 mmHg. At final examination, the IOP was well-controlled at 21 mmHg or lower without medications in 32 of 96 eyes. In another 62 eyes, the IOP was well-controlled with antiglaucoma medications. The postoperative IOPs were in the high teens after surgery. The life table analysis using Kaplan-Meier methods showed that the success probability after phacoemulsification and implantation of intraocular lens, combined with trabeculotomy (PIT)-I and PIT-II, were 93.9% and 82.6% at 4 years, respectively. Postoperative visual acuity improved by more than two lines in 79 of the 96 eyes. In no case was the visual acuity decreased by more than two lines. Deterioration of the visual field was found in 4 eyes. There were no complications such as shallow anterior chamber, choroidal detachment, malignant glaucoma, hypotonic maculopathy, and endophthalmitis. This triple procedure should be performed in the early stages of glaucoma. Trabeculotomy is thought to relieve the resistance to aqueous outflow by mechanical cleavage of the trabecular meshwork and the inner layer of Schlemm's canal. This technique leads to aqueous outflow the from the opening of the internal trabecular meshwork to the collector channel. For this reason trabeculotomy was developed by a number of surgeons. Recently, however, trabeculotomy has not been selected for those patients with advanced stages of primary open-angle glaucoma because of the disadvantages such as transient intraocular pressure (IOP) elevation several days after surgery and somewhat higher levels (18 mmHg) of postoperative intraocular pressure (Fig. 1). To avoid the IOP spike (transient IOP elevation) after trabeculotomy, we reported previously that the new technique of trabeculotomy combined with outer sclerectomy was a useful surgical option. The results of our previous study indicated that the postoprative intraocular pressure levels after combined trabeculotomy and outer sclerectomy were significantly lower than that of trabeculotomy alone. On the other hand, trabeculotomy with mitomycin C is currently the standard filtration procedure for glaucoma. This technique, however causes severe postoperative complication such as hypotonic maculopathy, bleb leakage and late bleb infection. The major advantages of trabeculotomy preclude these severe complications resulting from creating progressive filtration of aqueous humor from the anterior chamber to the subconjunctival space. The recent advance of small-incision phacoemulsification procedure prompted phacoemulsification and implantation of intraocular lens and trabeculotomy. The theoretical advantages of smaller scleral, conjunctival incision, reduced stimuli to wound healing, and inflammation, could improve long-term IOP control in patients with glaucoma. Therefore several reports have been published on the surgical outcomes of combined trabeculotomy and modern phacoemulsification. These reports suggested that the combined trabeculotomy and a small-incision with intraocular lens implantation is effective in controlling IOP in patients with glaucoma.

Aged↗

Trabeculectomy combined with phacoemulsification and intraocular lens implantation.

It has recently become popular to use mitomycin C (MMC) with trabeculectomy. MMC helps to maintain effective filtration and long-term intraocular pressure (IOP) control, while the use of laser suture lysis has improved the safety of this procedure. We evaluated the outcome of trabeculectomy alone and of trabeculectomy plus phacoemulsification (PEA) and intraocular lens (IOL) implantation, each supplemented with MMC. The mean preoperative IOP for the trabeculectomy alone group was 22.4 +/- 3.2 mmHg(bleb+), 25.3 +/- 2.6 mmHg(bleb-), and that of the combined surgery group was 22.4 +/- 2.8 mmHg(bleb+), 21.0 +/- 3.5 mmHg(bleb-). Mean postoperative IOP for the two groups were 13.3 +/- 2.7 mmHg(bleb+), 17.1 +/- 4.4 mmHg(bleb-) and 11.9 +/- 2.7 mmHg(bleb+), 16.4 +/- 3.4 mmHg(bleb-), respectively. After 4.5 years, the success probability for postoperative IOP control was 38%(bleb+), 3%(bleb-) in the trabeculectomy alone group and 53%(bleb+), 10%(bleb-) in the combined surgery group (<or=12 mmHg) and 65%(bleb+), 3%(bleb-) and 75%(bleb+), 10%(bleb-) (<or=14 mmHg)(Kaplan-Meier survival rate). With early complications, the frequency of shallow anterior chamber and choroidal detachment were significantly fewer in the combined surgery group. The combined surgery of PEA, IOL implantation and trabeculectomy is an effective procedure that offers visual rehabilitation, fewer early complications and good IOP control in patients with advanced, medically uncontrolled glaucoma and cataract.

Cataract↗

Advanced nonpenetrating trabeculectomy (advanced NPT) and combined surgery of advanced NPT and phacoemulsification and intraocular lens implantation.

We have devised a new glaucoma surgery combining deep sclerectomy with nonpenetrating trabeculectomy (NPT); we call this surgery advanced NPT. We evaluated intraocular pressure (IOP) control, postoperative complication and visual acuity after combined advanced NPT and phacoemulsification and intraocular lens implantation (combined surgery), and advanced NPT alone. The mean preoperative IOP for the trabeculectomy only group was 22.4 +/- 6.3 mmHg(bleb+), 23.0 +/- 4.9 mmHg(bleb-), and that of the combined surgery group was 18.1 +/- 4.5 mmHg(bleb+), 18.5 +/- 2.6 mmHg(bleb-). Mean postoperative IOP for the two groups were 13.0 +/- 2.3 mmHg(bleb+), 15.0 +/- 1.5 mmHg(bleb-) and 12.9 +/- 2.7 mmHg(bleb+), 13.3 +/- 2.4 mmHg(bleb-), respectively. After 15 months, the success probability for postoperative IOP control were 63%(bleb+), 23%(bleb-) in the advanced NPT only group (<or=12 mmHg), and 60% in the advanced NPT only group, 70% in the combined surgery group (<or=14 mmHg) (Kaplan-Meier survival rate). In early complication, there were significantly fewer cases of shallow anterior chamber, hypertension, hypotension and anterior chamber inflamation in both groups than that of trabeculectomy. Nd:YAG goniopuncture was performed for purposes of better IOP control; preferred performance being within a month after surgery. Regarding visual acuity after either advanced NPT alone or combined surgery, an earlier recovery can be expected than with trabeculectomy. Advanced NPT and combined procedure is a reliable technique for glaucoma and cataract surgery.

Aged↗

Translation and rotation of the mandible during habitual mouth opening movement in children with anterior reverse bite in the primary dentition.

Translation and rotation of the mandible during habitual mouth opening movements were studied in 13 children with skeletal-based anterior reverse bite (reverse bite group) and in 13 children with normal occlusion (normal occlusion group) whose dental stage was the primary dentition. Movements were recorded by an opto-electronic movement-analyzing system that could measure mandibular movements with six degrees of freedom. Inferior translation of the mandible was analyzed at the left primary central incisor, both of the primary canines, and both of the primary second molars. Anterior translation of the mandible was analyzed at both of the condyles. Rotation of the mandible was measured in the sagittal plane. The results showed that the associations between the translation and rotation of the mandible during habitual mouth opening in the reverse bite group differed from those in the normal occlusion group. The reverse bite group had greater anterior translation of both of the condylar points than did the normal occlusion group. No significant differences were found in the inferior translation or rotation of the mandible between the two groups.

Analysis of Variance↗

A growing family of dual specificity phosphatases with low molecular masses.

Five putative dual specificity protein phosphatases (DSPs), designated LMW-DSP1, -DSP4, -DSP6, -DSP10, and -DSP11, were cloned with a combination of RT-PCR and cDNA library screening strategies. Sequencing analysis revealed that all lacked the cdc25 homology domain that is conserved in most known DSPs/MAP kinase phosphatases (MKPs). LMW-DSP1 exhibited the highest similarity to plant DSPs. LMW-DSP4 exhibited the highest similarity to human YVH1 and rat GKAP, but its C-terminal region was much shorter than that of the human and rat clones. LMW-DSP6 was found to be identical to recently cloned TMDP, and LMW-DSP11 seemed to be a mouse ortholog of human VHR. LMW-DSP10 was found to have a DSP catalytic-like domain, but the critical cysteine residue for catalytic activity was missing. Recombinant LMW-DSP1, -DSP6, and -DSP11 exhibited obvious and strong activity against an artificial low molecular substrate, para-nitrophenyl phosphate (pNPP). Recombinant LMW-DSP4 exhibited slight but significant activity, whereas no activity was detected for LMW-DSP10. The phosphatase activity of the recombinant LMW-DSPs was inhibited by orthovanadate but not sodium fluoride. However, none of the DSPs could dephosphorylate MAP kinases such as ERK1, p38, and SAPK/JNK in transiently transfected COS7 cells under the conditions used. Northern blot analysis revealed that LMW-DSP1, -DSP6, -DSP10, and -DSP11 were specifically expressed in testis, while LMW-DSP4 was broadly expressed. The testis-specific expression and apparent absence of dephosphorylation action on MAP kinases suggest that LMW-DSP1, -DSP6, -DSP10, and -DSP11 play specific roles in testis. Taken together, it is conceivable that a distinct class of low molecular mass DSPs is present and plays a role in dephosphorylating unknown molecules other than MAP kinases.

Amino Acid Sequence↗

Aggregation and chemical reaction in hen lysozyme caused by heating at pH 6 are depressed by osmolytes, sucrose and trehalose.

We examined the effects of osmolytes, sucrose and trehalose, on the deterioration of hen lysozyme as a model protein. Sucrose and trehalose depressed the aggregation of lysozyme molecules caused by heating at 100 degrees C at pH 6. Since lysozyme was fully denatured under these conditions, the effects of sucrose and trehalose on the denatured state of lysozyme were investigated using reduced S-alkylated lysozyme, a model of denatured hen lysozyme. From analyses of circular dichroism spectra and fluorescence spectra, sucrose and trehalose were found to induce alpha-helical conformations and some tertiary structures around tryptophan residues in the reduced S-alkylated lysozyme. Moreover, these compounds also depressed chemical reactions such as deamidation and racemization, which often cause the deterioration of proteins, on the reduced S-alkylated lysozyme. Therefore, the data suggest that sucrose and trehalose have a propensity to depress such deterioration as the aggregation of protein molecules or chemical reactions in proteins by inducing some tertiary structures (including alpha-helical structures) in the polypeptide chain.

Alkylation↗

Surgical treatment for pancreatic metastasis from soft-tissue sarcoma: report of two cases.

We present two cases in which a soft-tissue sarcoma metastasized to the pancreas, but both patients survived as a result of repetitive surgical treatment during a 6- to 10-year period. The first case was a 29-year-old man who had a history of removal of mesenchymal chondrosarcoma in the left thigh in 1986 and who underwent distal pancreatectomy and the enucleation of a tumor in the head of the pancreas because of the development of three metastatic lesions in 1989. Afterward, although metastases were found in other organs, they were resected each time (for a total of five times) and the patient has survived over 10 years. The second case was a 40-year-old woman who had a history of the removal of synovial sarcoma in the right thigh and had 6 surgical resections of local or pulmonary recurrent tumors. She underwent pylorus-preserving pancreaticoduodenectomy in 1993 because of the development of a solitary metastatic lesion in the pancreas and survived more than 6 years after the pancreatectomy. Our report suggests, in selected cases, that long-term survival from pancreatic metastasis of soft-tissue sarcoma is expected as a result of curative resection. However, because pancreatic metastasis has a potential to recur in other organs, it is necessary to take aggressive surgical procedures repeatedly for the treatment of recurrences to improve prognosis after pancreatectomy.

Adult↗

Distribution and diversity of symbiotic thermophiles, Symbiobacterium thermophilum and related bacteria, in natural environments.

Symbiobacterium thermophilum is a tryptophanase-positive thermophile which shows normal growth only in coculture with its supporting bacteria. Analysis of the 16S rRNA gene (rDNA) indicated that the bacterium belongs to a novel phylogenetic branch at the outermost position of the gram-positive bacterial group without clustering to any other known genus. Here we describe the distribution and diversity of S. thermophilum and related bacteria in the environment. Thermostable tryptophanase activity and amplification of the specific 16S rDNA fragment were effectively employed to detect the presence of Symbiobacterium. Enrichment with kanamycin raised detection sensitivity. Mixed cultures of thermophiles containing Symbiobacterium species were frequently obtained from compost, soil, animal feces, and contents in the intestinal tracts, as well as feeds. Phylogenetic analysis and denaturing gradient gel electrophoresis of the specific 16S rDNA amplicons revealed a diversity of this group of bacteria in the environment.

Animals↗