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J Wada

Publications and source records attributed to J Wada.

At least 91 records · Page 5Linked to original sources
PubMed1995

Cloning of mouse c-ros renal cDNA, its role in development and relationship to extracellular matrix glycoproteins.

Renal organogenesis ensues following reciprocal interactions between the uninduced metanephric mesenchyme and the ureteric bud. Conceivably, the presence of ligands or growth factors on a given cell type, and expression of receptors, including receptor proto-oncogenes, on the other cell type of different lineage would facilitate such epithelial-mesenchymal interactions. During these interactions, other macromolecules, such as extracellular matrix (ECM) proteins, present at the epithelial-mesenchymal surface, also play a role in the kidney morphogenesis. In this study the proto-oncogene, c-ros, was cloned and sequenced; its role in the metanephric development was examined, and correlated with the changes in the expression of ECM proteins. The mouse c-ros renal cDNA, belonging to phosphotyrosine kinase (PTK) receptor family, had a translation product of 2340 amino acids. The extracellular domain had 32 N-linked glycosylation sites and 30 cysteine residues. The transmembrane segment had a hydrophobicity approaching approximately 3.5. Multiple phosphorylation sites, typical of a PTK catalytic unit, were present in the cytoplasmic domain. The 3' noncoding region did not contain any A(U)nA mRNA instability motifs. The c-ros mRNA was highly expressed on the ureteric bud branches and their tips and on the developing glomeruli. Competitive RT-PCR analyses revealed the c-ros expression was the highest at 13th day of gestation, and it declined to very low levels during the neonatal period. Exposure of metanephric kidneys to c-ros antisense-oligonucleotide, derived from the PTK domain, caused dysmorphogenesis of the kidney and loss of c-ros expression on the ureteric bud branches. Concomitant with the reduced c-ros gene expression, a decreased expression of ECM glycoproteins, in particular the proteoglycans, was observed. These findings suggest that the c-ros plays a role in the metanephric development, and its effects may be modulated by the ECM macromolecules present at the epithelial-mesenchymal interface.

Amino Acid Sequence↗
PubMed1995

Stimulated Ca2+ entry activates Cl- currents after releasing Ca2+ from the intracellular store in submandibular gland cells of the rat.

In order to examine whether Ca2+ entry is directly involved in controlling exocrine secretion, the Ca(2+)-activated Cl- currents were recorded in single and clusters of rat submandibular gland cells using the whole-cell patch-clamp method. Extracellularly applied acetylcholine (ACh, 10 nM) as well as intracellularly applied GTP gamma S and InsP3 caused repetitive transients of the Cl- currents activated by intracellular Ca2+. These responses occurred also in the absence of external Ca2+, but disappeared after several minutes. Readmission of Ca2+ to the extracellular solution restored the repetitive current transients, while introduction of Sr2+ failed to restore the current signals in spite of the presence of Sr2+ entry detected by microfluorimetry. On the other hand, direct application of Sr2+ to the cell inside caused activation of the Cl- currents although less effectively than Ca2+. When Ca2+ was introduced to the extracellular solution during an interruption of ACh stimulation after the ACh-induced depletion of intracellular Ca2+ store, the Cl- current was not elicited. However, a subsequent challenge with ACh at the same concentration in the absence of extracellular Ca2+ caused repetitive transient Cl- currents. The results suggest that in this cell type the stimulated Ca2+ entry does not by itself activate the Cl- currents but activates them indirectly by triggering Ca2+ release from the intracellular Ca2+ store which may take up Ca2+ soon after the Ca2+ entry.

Acetylcholine↗
PubMed1995

[Activation of complement during hemodialysis].

In hemodialysis using 3 types of dialysis membrane materials [regenerated cellulose (RC), cellulose triacetate (CTA), and polysulfone (PS)], activation of the complement, reduction of white blood cells, and variation of vitronectin (VN) were observed. RC membrane caused a significant reduction of white blood cells and elevations of Bb and soluble membrane attack complex (S-MAC), indicating a strong activation of the alternative complement pathway. Especially, the increase of S-MAC persisted for a long time during hemodialysis. Because reduction of VN was transient, it was assumed that the S-MAC escaping removal by VN receptors might have persisted in the circulation. These findings suggested that S-MAC would become useful as an index for evaluating biocompatibility of various artificial organs including dialysis membranes.

Aged↗
PubMed1995

[A case of systemic lupus erythematosus associated with severe fibrinoid necrosis located mainly in the glomerular afferent arteriole].

We report here, a patient of systemic lupus erythematosus (SLE) with severe fibrinoid necrosis in the afferent arteriole of the glomerulus, in whom antiphospholipid antibody might have contributed to the pathogenesis. A 24-year-old female who was suffering from severe anemia with fragmented red blood cells, acute renal failure and thrombocytopenia, was admitted to our hospital. Further examinations revealed findings compatible with active lupus nephritis. Moreover, she was found to be positive for antiphospholipid antibody, and anticardiolipin antibody, as well as for lupus anticoagulant and syphilis test. Intensive treatment by methylprednisolone pulse therapy, hemodialysis, and double filtration plasmapheresis were performed. However, 13 days after admission she died suddenly because of intracranial hemorrhage. Pathological investigation of renal tissue revealed severe fibrinoid necrosis of the arterioles mainly in the glomerular afferent arteriole associated with diffuse proliferative lupus nephritis. In this case, hemolytic uremic syndrome (HUS) was associated with SLE. Antiphospholipid antibody was considered to be not only an accelerator in the arterial lesions of HUS, but also an initiator of HUS itself.

Adult↗
PubMed1994

Immunoreactivity of the JK-132 monoclonal antibody directed against basement membrane collagen in normal and diabetic glomeruli.

The possible involvement of basement membrane-associated collagen (recognized by the monoclonal antibody JK-132) in the evolution of diabetic nephropathy was studied in kidney specimens from seven patients with noninsulin-dependent diabetes mellitus, and its distribution was compared with those of antibodies against alpha 1 to alpha 4 chains of type IV collagen. JK-132, a monoclonal antibody against basement membrane-associated collagen, reacted immunohistochemically exclusively with the mesangial matrix of the glomerular capillary. In contrast, antibodies to the alpha 1 and alpha 2 chains (IV) reacted strongly with mesangial matrix, and less strongly with the glomerular basement membrane (GBM). Antibodies to the alpha 3 and alpha 4 chains (IV) reacted mainly with GBM. In diabetes, JK-132 reacted most extensively with the expanded mesangial matrix, its staining intensity increasing with progression of the diabetic glomerulosclerosis. Antibodies to the alpha 1 and alpha 2 chains (IV) reacted prominently with the expanded mesangial matrix but less strongly with the GBM. Antibodies to the alpha 3 and alpha 4 chains reacted intensely with the thickened GBM. These results suggest that basement membrane-associated collagen differs from alpha 1 to alpha 4 chains of type IV collagen and that basement membrane-associated collagen is a good marker of mesangial expansion in diabetic nephropathy.

Aged↗
PubMed1994

Callosal morphology and performance on intelligence tests.

Variation in the size of the human corpus callosum was examined in relation to variation in measured IQ. The midsagittal surface area of the corpus callosum, obtained by magnetic resonance imaging, was measured in 47 patients with epilepsy. Intellectual ability was positively related to a larger posterior callosal area. We suggest that the relationship between the posterior callosal region and measured intelligence is "non-functional" in itself, but rather, may reflect other anatomical-cognitive associations. That is, differences in splenial size may reflect differences in the number of cortical neurons and interconnections between areas of the brain that are important for processing the kind of information measured on intelligence tests. Our conclusions, however, must be tempered by a number of factors; in particular, the nature of our subjects and the relatively small sample size.

Adolescent↗
PubMed1994

Localization of fibril/microfibril and basement membrane collagens in diabetic glomerulosclerosis in type 2 diabetes.

Collagen is one of the major components of the extracellular matrices of the kidney. Basement membrane collagen, type IV collagen, is the major component in normal glomeruli. Fibril and interstitial collagen such as type III collagen, type V collagen, and type VI collagen are minor components of glomerular extracellular matrices and are localized mainly in the interstitium. Diabetic glomerulosclerosis is characterized by the expansion of the glomerular mesangial matrix as well as by thickening of the glomerular basement membrane. In order to clarify the roles of these various types of collagen in the development of diabetic glomerulosclerosis, immunohistochemical studies were performed in kidney specimens from patients with Type 2 diabetes. Early glomerulosclerosis is characterized by expansion of mesangial matrix with basement membrane collagen. However, in later stages glomerulosclerosis is characterized by an increase in the minor collagen components, such as type V and type VI collagen or collagens not normally present, such as type III collagen. Mesangial cells are known to synthesize all these types of collagen. In diabetes, phenotypic change in mesangial cells might produce excess amounts of fibril and interstitial collagen such as type III, type V, and type VI collagen, thus, leading to glomerulosclerosis.

Aged↗
PubMed1994

Trophic effect of insulin-like growth factor-I on metanephric development: relationship to proteoglycans.

Many hormones/factors influence the total body growth and development during embryonic life, and very few studies have been carried out to ascertain their effects on the individual organ system. In this study, the effect of exogenous insulin-like growth factor-I (IGF-I) on embryonic kidneys was investigated, and correlated with phenotypic and gene expression and synthesis of extracellular matrix (ECM) proteoglycans (PGs). Antisense experiments were carried out to elucidate the role of endogenous (IGF-I in metanephric development. Mouse metanephroi, harvested at 13th day of gestation, were exposed to IGF-I (100 ng/ml) in an organ culture for 7 days. An enlargement of the metanephroi with accentuation of its lobules, and increase in the nephron population and [3H]thymidine incorporation was observed. Immunofluorescence studies and Southern blot analysis of polymerase chain reaction products indicated augmented expression of the ECM PGs. A heavy concentration of [35S]sulfate-associated radioactivity over the tips of ureteric bud branches and ECM components of maturing glomeruli was seen. Maximal effect of radioincorporation was observed on day-4 of the culture, the period when the concentration of endogenous IGF-I is the highest. PGs synthesized had elevated proportions of chondroitin sulfate vs heparan sulfate and of free chains, and reduced charge-density characteristics. Immunoprecipitation studies of [35S]methionine-labeled glycoproteins revealed an increased synthesis of core-peptide of the PGs. IGF-I antisense oligonucleotide caused retardation in the growth of the kidneys along with the decrease in de novo synthesis of PGs. These findings indicate that IGF-I, a polypeptide essential to the renal growth and development, has a trophic effect on the embryonic kidney during the postinductive period of metanephric development, and the observed response has a temporal relationship with the increased synthesis of the PGs.

Animals↗
PubMed1994

[Effect of heparin and low-molecular-weight heparin on proliferative glomerulonephritis].

Effect of heparin and low-molecular-weight heparin (LMWH) were evaluated on 15 patients with proliferative glomerulonephritis with various degrees of sclerosing legion. Five cases were subcutaneously administered with 7000 to 11000 units of heparin for 4 weeks. Ten cases were administered with 60 unit/kg of LMWH by drip infusion for 4 weeks. Eleven cases were treated with prednisolone and all cases were treated with anti-platelet agent as well. Urinary protein excretion reduced from 3.0 +/- 1.8 to 1.8 +/- 0.6 g/day in the heparin-treated group and from 2.4 +/- 1.9 to 1.8 +/- 1.4 g/day in the LMWH-treated group, respectively. There were no remarkable changes in the renal functions of both groups. In one case, both heparin and LMWH brought about reduction of proteinuria. Therefore, LMWH reduced urinary protein excretion by the same mechanism as heparin. The LMWH has an advantage over heparin in that the former has less risk of causing bleeding. We conclude that heparin and LMWH reduce proteinuria in some patients with proliferative glomerulonephritis. The LMWH is beneficial in the treatment of proliferative glomerulonephritis with a sclerosing lesion.

Adolescent↗
PubMed1993

Cloning of cDNA for the alpha subunit of mouse insulin-like growth factor I receptor and the role of the receptor in metanephric development.

Various growth factors influence mammalian development by binding to specific cell surface receptors. These interactions are followed by a series of intracellular transductional events leading to a wide variety of biological effects. To establish the role of insulin-like growth factor I receptor (IGF-IR) in renal development, cDNA for the alpha subunit of the mouse IGF-IR was isolated, characterized, and used in expression studies and antisense experiments in a metanephric organ culture system. A 989-bp insert, encoding the signal peptide and 299 amino acids, isolated from a newborn mouse kidney cDNA library had 99% and 91% homology with the nucleotide sequences encoding the rat and the human IGF-IR, respectively. An approximately 11-kb message was readily detected by Northern blot analysis of RNA from the developing kidney at day 13 of gestation, and it declined during the subsequent embryonal and neonatal periods. In situ hybridization revealed high levels of message over the ureteric bud and its branches. A lower level of message was seen in the neonatal kidney, confined mainly to the tubules. Antisense oligodeoxynucleotide-treated metanephric kidneys were reduced in size and had a decreased population of nephrons with marked disorganization of ureteric bud branches. Immunofluorescence studies indicated an arrest of IGF-IR translation after antisense exposure. Immunoprecipitation studies showed a marked decrease in the biosynthesis of various extracellular matrix proteins that serve as regulators of morphogenesis. These studies suggest that the nucleotide sequence encoding the alpha subunit of mouse IGF-IR is highly conserved and that the receptor might play an essential role in the organogenesis of the kidney.

Aging↗
PubMed1993

Distribution and relevance of insulin-like growth factor-I receptor in metanephric development.

During embryogenesis, various ligand-receptor interactions take place to modulate the development and growth of various mammalian organs. During these interactions, a critical concentration of a given receptor is needed to elicit a ligand-induced biologic response at a defined gestational stage of the fetus. In this study, the distribution and the relevance of insulin-like growth factor-I receptor (IGF-IR) in metanephric development was investigated. Kidneys were harvested from mouse embryos at days 13 to 19 of fetal gestation, and maintained in a metanephric culture system. Immunofluorescence studies, using anti-IGF-IR, revealed a high expression of IGF-IR at day 13, which declined during the later stages of gestation through neonatal life. To study the relevance of IGF-IR expression in metanephric development, antisense-oligodeoxynucleotide (ODN) experiments were carried out. Antisense-ODN 43 mer probes were synthesized utilizing rat IGF-IR cDNA selected nucleotide sequences which are highly conserved in other mammalian species. Southern blot analyses of various restriction fragments of the rat and mice genomic DNA yielded similar bands when hybridized with the antisense-ODN or rat IGF-IR cDNA, suggesting a high degree of homology in the region of the gene selected for the synthesis of antisense-ODN. Also, the antisense-ODN hybridized with the appropriate murine fetal kidney mRNA species, as ascertained by S1 nuclease protection assay. Inclusion of antisense-ODN in the culture medium resulted in an inhibition of the growth of the kidney, reduction in the population of the nephrons and disorganization of the ureteric bud branches.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Wisconsin Card Sorting Performance: effects of age of onset of damage and laterality of dysfunction.

Wisconsin Card Sorting Performance was examined in patients with complex partial seizures of left (n = 35) or right (n = 42) temporal-lobe origin. Our findings suggest that poor performance, in the form of perseveration, occurs in the context of nonfrontal dysfunction and depends not only on the laterality of the epileptogenic disturbance but also on the age of onset of the damage. The ability to shift set is most impaired by left temporal-lobe dysfunction, but only when the damage occurs very early in life. Left temporal-lobe dysfunction after one year of age leaves sorting behavior relatively intact. Perseveration may also occur in the context of right temporal-lobe dysfunction, regardless of the age of onset of the damage, although the deficit tends to be less marked. Finally, the occurrence of the deficit does not depend upon the status of the cerebral speech pattern or general intellectual level.

Adult↗
PubMed1993

[Follow-up study of the elderly users of a geriatric intermediate care facility after discharge].

Geriatric intermediate care facilities (GICF) were started by subsidies from the Ministry of Health and Welfare in 1987 to promote the return of elderly from hospitals to their homes or nursing homes and to give support to the cared elderly and their families. This paper describes about the function of a GICF established in a rural community in Oita, Kyushu. One hundred seventy four elderly users (66 males, 108 females: mean age; 81 years old) who were discharged from the GIFC between July 1990 and June 1991 were studied. The main results were as follows: 1. The reason for admission to the GIFC of 174 elderly users were cerebrovascular disease in 50 cases, bone and/or joint diseases in 63, senile dementia in 25 and other diseases in 36.2. Eighty three persons (48%) needed continuous care. 3. The activities of daily living of approximately 37% of those who needed continuous care improved to some degree. 4. Ninety six users were discharged and went home, 43 were readmitted to a hospital, 32 were admitted to a nursing home, and 3 died at the GIFC. 5. The situation as of September 1991 was 70 persons (40%) at home, 12 persons in hospital, 33 persons in the GICF, 35 persons in nursing homes and 24 deaths. 6. Fifty two persons (37%) used the GICF more than twice. These findings suggested that the GICF enabled care for weak elderly persons at home.

Aged↗
PubMed1993

Natural course of osteoarthritis of the knee treated with or without intraarticular corticosteroid injections.

The natural course of primary osteoarthritis of the knee with or without treatment by intraarticular corticosteroid injections was investigated in 446 patients presenting from 1970 to 1973. Sixty-one of these patients were able to be followed up in 1982 and were divided into two groups. One group included 53 patients (82 knees) without corticosteroid injections. The other group had eight patients (14 knees) who received intraarticular steroids (mean number of injections: 25; range:4-78). The standing femorotibial angle at followup in the male patients receiving injections (p < 0.05) was four degrees of greater varus angulation. Radiographic degeneration was more advanced in 11 of the 24 steroid-treated knees (78.6%), and in 43 of the 82 knees without steroid injections (52.4%) (p < 0.01).

Adrenal Cortex Hormones↗