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Biomedical subjects

F Gejyo

Publications and source records attributed to F Gejyo.

At least 37 records · Page 2Linked to original sources

The circadian blood pressure rhythm in non-diabetic hemodialysis patients.

This study investigates the circadian blood pressure variation of non-diabetic chronic hemodialysis (HD) patients on both HD and non-HD days as well as the factors affecting diurnal BP variation. Forty-nine HD patients aged 61.8 +/- 12.9 years who were on daytime HD for 97 +/- 68 months were studied. No significant difference was found in every daytime and nighttime BP between the first (HD) and the second (non-HD) day. However, the ratio nighttime/daytime BP was significantly higher on the second day. Each BP diurnal variability pattern was classified as either Dipper (D: the ratio nighttime/daytime mean BP 0.8-0.9), non-dipper (0.9 < ND < 1.0), or inverted dipper (ID > 1.0). More than 75% of the cases were classified as ND (26 cases) or ID (11 cases). The ultrafiltration rate in D was significantly less than that in ND and ID. The difference of plasma renin activity between pre- and post-HD (dRen) was significantly higher in ID than in D and ND. The amount of dialysis (Kt/V) was found to be significantly correlated with nighttime BP fall. Ultrafiltration, dRen and Kt/V were independent factors for the abnormal BP diurnal variability. In conclusion, the decreased nocturnal BP fall seen in non-diabetic HD patients is associated with increased extracellular fluid even in the patients without overt overhydration, whereas relatively insufficient amount of dialysis (low Kt/V) may be another possible cause. The increased dRen observed only in ID patients may reflect occult cardiovascular damage or functional disturbances in aortic and carotid baroreflexes caused by arterial structural changes.

Adult↗

Determination of optimal blood pressure for patients with IgA nephropathy based on renal histology.

To evaluate the optimal BP control for patients with IgA nephropathy (IgAN) based on the histologic severity of the nephropathy and the degree of renal dysfunction. We analyzed 332 consecutive renal biopsy specimens and clinical data from patients with IgAN. Patients were divided into three groups based on their BP at the time of biopsy: an optimal BP (SBP<120 mmHg and DBP<80 mmHg), a hypertensive BP (SBP > or = 140 mmHg and/or DBP > or = 90 mmHg), and an intermediate BP group. Each biopsy specimen was evaluated for mesangial proliferation, degree of sclerosis and/or hyalinosis of the arterioles and the interlobular artery using a semiquantitative method. Creatinine clearance and the percentage of sclerosed glomeruli were also determined. Both the degree of renal dysfunction and the histologic changes correlated significantly with BP, even in patients with a BP <140/90 mmHg. The patients with an optimal BP at the time of biopsy had significantly less histologic damage with respect to mesangial proliferation and vessel changes than those with an intermediate or hypertensive BP. In the patients with a hypertensive BP, the percentage of sclerotic glomeruli was significantly higher and the creatinine clearance was significantly lower. The optimal BP proposed by the WHO in 1999 prevents histologic evidence of renal damage for patients with IgAN.

Adult↗

Three-dimensional analysis of nephrogenesis in the neonatal rat kidney: light and scanning electron microscopic studies.

In order to clarify the process of renal development more precisely than previously, the present study observed the rat neonatal kidney by scanning electron microscopy (SEM) of KOH digested tissue as well as by light microscopy of plastic sections. In the subcapsular region, aggregation of the mesenchymal cells was closely associated with the upper side of the ureteric duct ampulla. These mesenchymal cells projected a number of fine irregular processes at the basal portion facing the ureteric duct. A spherical cluster transformed from the mesenchymal cell aggregation was found on the lower side of the terminal ampulla, and was differentiated into the renal vesicle. Some cells at the top of the renal vesicle formed a cone-shaped projection and invaded the ureteric duct ampulla, forming a connection with it. In the advanced stage, a shallow transverse cleft appeared on the outer lateral side of the renal vesicle, and a second cleft was formed on the opposite side close to the junction between the renal vesicle and the ampulla. As the two clefts deepened, the vesicle assumed the well-known S-shaped body. In the advanced S-shaped body, the lower limb became cup-shaped, while the segment between the middle and lower limbs of the "S" elongated to form a tubular structure (i.e., the prospective proximal tubule and Henle's loop). The upper limb of the "S" also increased its length to form a distal tubule. The middle limb of the "S", however, was attached firmly to the cup-shaped lower limb (i.e., the prospective renal corpuscle) and was considered to become the macula densa of the mature nephron. In the maturing renal corpuscle, irregularly shaped cells were observed as a sheet-like aggregation at its vascular pole and were continuous with the vascular smooth muscle cells. These findings will help toward a better understanding of the morphological complexities of nephrogenesis.

Animals↗

Association of gene polymorphism of polymeric immunoglobulin receptor and IgA nephropathy.

OBJECTIVE: In order to explore the possibility that genetic predisposition to dysfunction of mucosal immunity and the IgA processing pathway plays a role in the pathogenesis of mesangial IgA1 deposition in IgAN, we examined the possible association of the gene polymorphism of pIgR in the patients with and without IgAN. SUBJECTS AND METHODS: Genomic DNA of peripheral blood cells was isolated from 372 individuals including 172 histologically confirmed IgAN patients. Segments of the pIgR gene were PCR amplified and restriction fragment length polymorphism was determined as A1 and A2 with and without Pvu II site, respectively. RESULTS: The pIgR genotype distribution was significantly different between the patients with IgAN and those without IgAN. Allele frequency of A2 was higher in IgAN than in other renal diseases (A1 and A2; 0.516 and 0.484 in IgAN, 0.641 and 0.359 in others, chi2 = 9.84, P = 0.0017, Odds ratio = 1.71). Moreover, the subjects with A2A2 genotype were associated with a relatively low level of serum IgA only in the patients with IgAN but not in other renal diseases. The difference of allele frequencies was more remarkable in the patients with a serum IgA level of less than 300 mg/dl (A1 and A2; 0.439 and 0.561 in IgAN, 0.702 and 0.298 in others, chi2 = 12.44, P = 0.0004, Odds ratio = 3.01). CONCLUSION: This is the first demonstration of the pIgR gene polymorphisms in IgAN which are associated with its clinical phenotype. Gene polymorphisms of pIgR may be candidate genetic markers of susceptibility to IgAN.

Alanine↗

Extension of A beta2M amyloid fibrils with recombinant human beta2-microglobulin.

In order to elucidate the pathogenesis of A beta2M amyloidosis, we established an experimental system to study the mechanism of amyloid fibril formation or degradation in vitro. We compared the kinetics of A beta2M amyloid fibril (fA beta2M) extension with native beta2microglobulin (n-beta2M) purified from the urine of a patient suffering from renal insufficiency, with that with recombinant beta2M (r-beta2M) in vitro. n-Beta2M and r-beta2M were incubated with fA beta2M purified from synovial tissues excised from A beta2M amyloidosis patients. The fA beta2M extension reaction could be explained by a first-order kinetic model in both beta2Ms. The extension reaction was greatly dependent on the pH of the reaction mixture and maximum around pH 2.5-3.0 in both beta2Ms. The fA beta2M extended with both beta2Ms assumed the similar helical filament structure, although the fibrils extended with r-beta2M were slightly wider than those extended with n-beta2M and the former fibrils assumed a helical structure more clearly as compared to the latter. In order to obtain pure, unmodified fA beta2M, we next extended fA beta2M repeatedly by the algorithmic protocol with r-beta2M. As the generation of the extended fibrils proceeded, the initial rate of the extension reaction increased The ultrastructure of fibrils was completely preserved throughout the repeated extension steps. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting revealed that fA beta2M extended repeatedly with r-beta2M were composed solely of r-beta2M. The use of these r-beta2M and fA beta2M will be advantageous to assess the effects of several amyloid-associated molecules in the formation or degradation of fA beta2M in vitro.

Amyloid↗

[Beta 2-microglobulin and dialysis-related amyloidosis].

Dialysis-related amyloidosis is a common complication encountered in patients receiving chronic hemodialysis. beta 2-microglobulin(beta 2-m) constitutes the causative protein of amyloidosis, and its deposition in tissues has been proven to be a primary cause of the onset. However, many other risk factors are also associated including (1) prolonged duration of dialysis, (2) advanced age, (3) dialysate of low purity, and (4) the use of a dialysis membrane with poor biocompatibility. Recently we confirmed that apolipoprotein E is a risk factor for the onset of carpal tunnel syndrome associated with dialysis-related amyloidosis. Dialysis using high-flux membranes and the clinical application of a column that selectively adsorbs beta 2-m are currently being assessed interms of the ability to remove as much beta 2-m from the blood as possible. Drug therapy may also be useful at present in symptomatic treatment; a low dose of adrenocorticosteroids has recently been demonstrated as extremely effective for joint pain associated with beta 2-m amyloid deposits. The long-term use of drugs, however, carries a risk of side effects. As a therapeutic approach to dialysis-related amyloidosis, high-flux dialysis membranes permitting the elimination of beta 2-m with satisfactory biocompatibility have been developed and positive clinical effects have been observed both in the retrospective and prospective studies in the use of high-flux membranes together with a decrease in the serum beta 2-m level. However, there is no evidence yet of the long term reduction of amyloid deposits when the elimination of beta 2-m is maintained using a high-flux membrane.

Amyloid beta-Protein Precursor↗

[Lung involvement in rapidly progressive glomerulonephritis].

The purpose of this study is to evaluate pulmonary involvement in rapidly progressive glomerulonephritis (RPGN). Of 71 patients in whom RPGN was diagnosed, 32 (45.1%) had pulmonary involvement: 12, alveolar hemorrhage (AH) (16.9%); 10, interstitial pneumonia (IP) (14.1%); four, chronic bronchial lesions (5.6%); two, consolidation (2.8%), and four, old inflammatory lesions (5.6%). Investigation of which organ of the twelve AH patients, the kidney or the lung, was the first to be involved, showed that the lung preceded in one patient, the kidney was first in three, and the lung and kidney occurred at the same time in the other eight. Of the ten IP patients, the lung preceded in eight, the kidney was ahead in two, and lung and kidney were simultaneous in one. Three patients had a history of pneumoconiosis, and two had acute progressive IP. Seventeen (45.9%) of 37 patients who tested positive for antineutrophil cytoplasmic autoantibodies (MPO-ANCA) had lung involvement, and three (30.0%) of the ten patients who tested negative for MPO-ANCA, PR 3-ANCA and anti-GBM antibody also had lung involvement.

Aged↗

[Effect of Bakumondo-to on increased sensitivity of the cough reflex in a Sjögren syndrome patient with interstitial lung disease].

A 63-year-old woman had complained of a persistent dry cough. Comparison of chest roentgenograms obtained 3 months earlier and at hospital admission, revealed progressive infiltrative shadows in bilateral middle and lower lung fields and mild volume loss. Hematologic study showed polyclonal hyper-gamma-globulinemia, positive anti-nuclear antibodies, and positive antibodies to Ro (SS-A) antigens. Ophthalmologic study demonstrated keratoconjunctivitis sicca. Parotid sialography showed an apple tree sign. Histopathologic features of labial salivary gland biopsy revealed agglomeration of at least 50 mononuclear cells. Chest CT showed non-segmental dense opacity in outer zones of middle and lower lung fields. Lung function test revealed a restrictive pattern with low diffusion capacity. Blood gas analysis showed hypoxemia (PaO2: 74 Torr, PaCO2: 32 Torr). Bronchoalveolar lavage fluid disclosed increased lymphocytes, and histologic features of a transbronchial lung biopsy included thickening of alveolar walls, infiltration of lymphocytes in the interstitium, and foamy cells in alveolar spaces. Therefore, the patient was diagnosed with primary Sjögren syndrome with interstitial lung disease. Bakumondo-to (Mai men dong tang) was started for the troublesome dry cough. The cough was subjectively relieved, cough scores were decreased, QOL scores improved, and sensitivity of the cough reflex measured by inhalation of capsaicin improved, but the chest roentgenogram was unchanged. Steroid hormone therapy was added, and radiographic abnormalities improved subsequently. Bakumondo-to, a traditional Chinese blended medicine, has notable antitussive activity in bronchitic guinea-pigs and in patients with postinfectious cough. It was concluded that Bakunondo-to may provide effective antitussive activity in some cases of interstitial lung disease with increased sensitivity of the cough reflex.

Adrenergic beta-Agonists↗

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1999)].

From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.

Adolescent↗

[A case of systemic fat embolism in mixed connective tissue disease associated with interstitial pneumonia during steroid treatment].

A 67-year-old man with a four-year history of mixed connective tissue disease (MCTD) associated with interstitial pneumonia was admitted to our hospital with a complaint of dyspnea and moist cough. Because the interstitial pneumonia was exacerbated, he was given high-dose steroid treatment (pulse therapy and sequential oral treatment of PSL 50 mg/day). After treatment his general condition showed some improvement, but then he suddenly died of acute respiratory failure. Autopsy disclosed fat emboli in the lungs, kidneys, liver and myocardium. The fat embolism may have been a consequence of the steroid treatment. Fat embolism should be taken into account as one of the causes of the acute respiratory failure in collagen vascular disease patients receiving steroid treatment.

Acute Disease↗

[A case of pulmonary inflammatory pseudotumor with hypergammaglobulinemia, elevated ANA, and uveitis].

A 63-year-old man presented with a chronic myeloproliferative disorder complicated with left pneumonia. His pneumonia was cured with antibiotics, but a nodular lesion remained in his chest radiographs together with hypergammaglobulinemia, a high titer of anti-nuclear antigen, and uveitis with secondary glaucoma. Specimens obtained by transbronchial lung biopsy showed a mixed accumulation of plasma cells, lymphocytes, and histiocytes as well as a spindle cell proliferation diagnosed as pulmonary inflammatory pseudotumor. The specimen did not show any recombination indicative of a heavy or a light chain of immunoglobulin in Southern blotting analysis. Oral prednisolone treatment improved the pulmonary nodular lesion, the abnormal laboratory data, and the uveitis. These findings suggest that much of the gammaglobulin produced by plasma cells in the inflammatory pseudotumor caused a variety of clinical symptoms.

Administration, Oral↗

[Two cases of alveolar hemorrhage due to inhalation of detergent aerosol].

We report on two cases of alveolar hemorrhage after inhalation of detergent aerosol. Case 1: A 54-year-old woman was referred to our hospital with a complaint of hemoptysis. She used a spray type detergent for ventilation fan cleaning, and recognized hemoptysis later for eight hours. She had mild anemia and severe hypoxemia, and chest radiographs and CT films infiltrative shadows were recognized predominantly in the right middle, left lingual lower lobes. Case 2: A 22-year-old woman was admitted to our hospital complaining of bloody sputum and dyspnea. She had used a spray-type detergent for bathroom cleaning intermittently for one week. Between the beginning of this activity and the seventh day, cough and dyspnea developed. Chest radiographs and CT films disclosed diffuse infiltrative shadows in both lung fields. In both cases, the condition was diagnosed by bronchoalveolar lavage as alveolar hemorrhage. In case 2, a transbronchial lung biopsy specimen revealed alveolitis without vasculitis or capillaritis. Both the clinical symptoms and the CT images were improved by steroid administration. The steroid dosage was decreased gradually and stopped, but there was no relapse of the hemoptysis. Neither patient was positive for antinuclear antibodies or antibodies against the cytoplasm of granulocytes. Urinalysis showed no pathological findings. Since the hemoptysis appeared after inhalation of a detergent aerosol, it was possible that inhalation was the cause of the hemorrhage.

Adult↗

The three-dimensional structure of the neonatal mouse kidney as revealed by scanning electron microscopy after KOH treatment.

The shape and arrangement of the developing nephrons were studied three-dimensionally by scanning electron microscopy (SEM) of the neonatal mouse kidney. The specimens were treated with the KOH digestion method in order to remove extracellular connective tissue components, thus enabling the direct observation of the developing nephrons at various stages. At the subcapsular region of the renal cortex, the ureteric ducts were observed as branched tubules with terminal swellings or ampullae. Newly formed blood vessels were often associated with terminals of these ureteric ducts. The cup-shaped renal corpuscles had aggregations of mesangial cells with blood vessels in the groove. At the vascular pole of mature nephrons, extraglomerular mesangial cells were observed as a cellular sheet, which was continuous with the smooth muscle layer of afferent and efferent blood vessels. The present study also demonstrated the shape of the immature podocytes in relation to the endothelial morphology of glomerular capillaries.

Aging↗

Characterization and chromosomal mapping of a novel human gene, ANKHZN.

Ankhzn (ankyrin repeats hooked to a zinc finger motif) was originally isolated by means of the gene trap method, as a novel cytoplasmic protein on mouse embryonic stem cells. The Ankhzn protein is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes. In the present study, we have cloned human ANKHZN cDNA by PCR using candidate EST clones exhibiting a high homology to mouse Ankhzn cDNA. The human ANKHZN cDNA encoded a 1166aa protein exhibiting 84.9% identity to the mouse one. The size of the transcript was found to be about 7kb on a Northern blot analysis, and ANKHZN mRNA was found to be ubiquitously expressed in human tissues on RT-PCR analysis. Western blot analysis showed that a 130kDa protein was detected at various levels in human tissues and also present in both membrane and soluble fractions obtained on subcellular fractionation. Human ANKHZN is a single copy gene consisting of predicted 25 exons in the human genome, and has been mapped to human chromosome 17p13 by radiation hybrid panel and fluorescence in-situ hybridization.

Amino Acid Sequence↗

Continuous erythropoietin delivery by muscle-targeted gene transfer using in vivo electroporation.

It has been demonstrated that gene transfer by in vivo electroporation of mouse muscle increases the level of gene expression by more than 100-fold over simple plasmid DNA injection. We tested continuous rat erythropoietin (Epo) delivery by this method in normal rats, using plasmid DNA expressing rat Epo (pCAGGS-Epo) as the vector. A pair of electrodes was inserted into the thigh muscles of rat hind limbs and 100 microg of pCAGGS-Epo was injected between the electrodes. Eight 100-V, 50-msec electric pulses were delivered through the electrodes. Each rat was injected with a total of 400 microg of pCAGGS-Epo, which was delivered to the medial and lateral sides of each thigh. The presence of vector-derived Epo mRNA at the DNA injection site was confirmed by RT-PCR. The serum Epo levels peaked at 122.2 +/- 33.0 mU/ml on day 7 and gradually decreased to 35.9 +/- 18.2 mU/ml on day 32. The hematocrit levels increased continuously, from the preinjection level of 49.5 +/- 1.1 to 67.8 +/- 2.2% on day 32 (p < 0.001). In pCAGGS-Epo treated rats, endogenous Epo secretion was downregulated on day 32. In a control experiment, intramuscular injection of pCAGGS-Epo without subsequent electroporation did not significantly enhance the serum Epo levels. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful procedure for the continuous delivery of Epo.

Animals↗

Augmentation of Valpha14 NKT cell-mediated cytotoxicity by interleukin 4 in an autocrine mechanism resulting in the development of concanavalin A-induced hepatitis.

The administration of concanavalin A (Con A) induces a rapid severe injury of hepatocytes in mice. Although the Con A-induced hepatitis is considered to be an experimental model of human autoimmune hepatitis, the precise cellular and molecular mechanisms that induce hepatocyte injury remain unclear. Here, we demonstrate that Valpha14 NKT cells are required and sufficient for induction of this hepatitis. Moreover, interleukin (IL)-4 produced by Con A-activated Valpha14 NKT cells is found to play a crucial role in disease development by augmenting the cytotoxic activity of Valpha14 NKT cells in an autocrine fashion. Indeed, short-term treatment with IL-4 induces an increase in the expression of granzyme B and Fas ligand (L) in Valpha14 NKT cells. Moreover, Valpha14 NKT cells from either perforin knock-out mice or FasL-mutant gld/gld mice fail to induce hepatitis, and hence perforin-granzyme B and FasL appear to be effector molecules in Con A-induced Valpha14 NKT cell-mediated hepatocyte injury.

Adoptive Transfer↗