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Biomedical subjects

H Kawaguchi

Publications and source records attributed to H Kawaguchi.

At least 271 records · Page 15Linked to original sources

IGF-I as an early indicator of malnutrition in patients with end-stage renal disease.

The present study was performed to clarify the possibility of IGF-I as an early indicator of malnutrition in patients with end-stage renal disease. Thirty-two patients (19 males, 13 females; mean age 49.6 +/- 10.0 years) undergoing dialysis were enrolled in the study. Body weight, skinfold thickness, and midarm muscle circumferences (MAMCs) were measured for anthropometric nutritional indices. Blood samples were collected to measure the following endocrinological, biochemical and hematological indices: IGF-I, growth hormone, (GH), total protein, prealbumin, albumin, transferrin, hematocrit, and lymphocyte count. Nutritional indices were measured again 1 month later to calculate the percent difference among them. Moreover, 2 patients who showed a decrease in IGF-I and suffered from malnutritional complications, such as hypoproteinemia and emaciation, which could not be successfully treated by conventional therapies were selected in order to confirm the nutritional role of IGF-I mediated by recombinant human GH (r-hGH). The serum IGF-I concentration distribution ranged from 22 to 225 ng/ml. In 15 patients (10 males, 5 females), it fell from 22 to 82 ng/ml below the normal range. Partial correlation coefficient analysis demonstrated that baseline IGF-I and the percent difference of each the body weight, MAMC, prealbumin and albumin were highly significantly correlated (r = 0.431, 0.641, 0.624 and 0.348, respectively; p = 0.014, 0.001, 0.001 and 0.028, respectively). The percent difference of IGF-I did not correlate significantly with that of any other nutritional index during the 1-month observation without administration of r-hGH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Probucol reduces renal injury in the ExHC rat.

To investigate the potential roles of oxidized lipoproteins and glomerular macrophages in the pathogenesis of lipid-induced glomerular injury, we examined the effects of administration of probucol on the development of renal injury in ExHC rats. ExHC rats are derived from the Sprague-Dawley strain and are highly susceptible to dietary hypercholesterolemic stimuli. We reported previously that ExHC rats fed a cholesterol-supplemented diet (HCD) develop proteinuria and characteristic glomerular lesions. These lesions include marked accumulation of numerous lipid-filled foam cells, which have a surface marker that identifies them as macrophages, within mesangial regions, as well as segmental clusters of foam cells that are associated with capsular adhesions, the destruction of glomerular tufts and glomerular sclerosis. ExHC rats were maintained on an HCD or on an HCD supplemented with 5% (wt/wt) probucol for 8 weeks. Probucol reduced the extent of renal injury, as evidenced by proteinuria and segmental glomerular lesions, in ExHC rats fed an HCD, in the absence of any significant reduction in plasma cholesterol levels. Both low-density lipoprotein and beta-very-low density lipoprotein isolated from the plasma of probucol-treated rats were found to be resistant to oxidative modification by cupric ions. Both the size and the number of foam cells within glomeruli in the probucol-treated rats were significantly reduced as compared to those of foam cells in the untreated rats. Probucol might reduce renal injury in ExHC rats by limiting the oxidative modification of lipoproteins and, subsequently, by restricting the foam cell transformation of macrophages within glomeruli and by inhibiting the recruitment of macrophages into glomeruli. The results of the present study may be interpreted to indicate that local glomerular oxidative modification of lipoproteins might occur in vivo, and both oxidized lipoproteins and glomerular macrophages may play important roles in the pathogenesis of lipid-induced glomerular injury.

Animals↗

Hereditary nephrotic syndrome with progression to renal failure in a mouse model (ICGN strain): clinical study.

The clinical course of murine hereditary nephrotic syndrome (ICGN strain) was determined by examining 201 animals under different conditions. In the early stage, significant hypoproteinemia and hypoalbuminemia developed (p < 0.001) in parallel with a progressive rise in urinary protein concentration (p < 0.001). In the middle stage, the concentrations of total cholesterol, triglyceride, and beta-lipoprotein markedly increased (p < 0.01, p < 0.001, and p < 0.001, respectively), suggesting that type IIb hyperlipoproteinemia developed as in human nephrotic patients. Systemic edema appeared in 8 of 24 animals. In the terminal stage, both BUN and creatinine values greatly increased (p < 0.001), indicating rapid deterioration of renal function. The present study suggests that ICGN mice could be a useful model to study the pathophysiology of human nephrotic syndrome and its progression to renal failure.

Animals↗

Preparation of DNA-carrying affinity latex and purification of transcription factors with the latex.

We have developed DNA-carrying latex particles for the separation and purification of transcription factors. These particles consist of styrene (St), glycidyl methacrylate (GMA) and divinylbenzene (DVB). It was confirmed that the ethanolamine-treated surface of these particles suffered no nonspecific adsorption of proteins. To the latex particles sequence-specific DNA oligomers were immobilized via covalent coupling. A transcription factor, E4TF3, was efficiently purified to homogeneity using the latext particles. In contrast, the purification using DNA-carrying Sepharose gel yielded poor results. Compared to DNA-carrying Sepharose gel, the latex particles exhibited several times higher efficiency in the purification of E4TF3 from the crude nuclear extract.

Adsorption↗

Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin-diabetic rats.

The effect of local application of recombinant human basic fibroblast growth factor (rhbFGF) on fracture repair was examined using normal rats and streptozotocin-diabetic rats with impaired repairing ability. Immediately after fracturing the fibula, rhbFGF was applied by a single injection to the fracture site. Application of rhbFGF increased the volume and mineral content of callus in a dose-dependent manner in both normal and diabetic rats, and callus formation of diabetic rats was stimulated to levels similar to those in nontreated normal rats. The marked effect of rhbFGF on fracture repair was associated with an improvement in the mechanical properties of the healing fibula in both normal and diabetic rats. Immunohistochemical staining showed that endogenous bFGF was widely distributed in normal rats 1 and 3 weeks after fracture, especially in the soft callus and periosteum, whereas much less bFGF was detected in diabetic rats. Insulin treatment of diabetic rats restored the immunostaining for bFGF. These results demonstrate that bFGF is expressed during the early stage of fracture repair, and that the impaired fracture-repairing ability in diabetic rats is associated with reduced expression of bFGF at the fracture site. A single application of bFGF immediately after fracture not only facilitates the repair process in normal rats, but also recovers the impaired repairing ability in diabetic rats. These results suggest that local application of bFGF may facilitate bone union in patients with impaired as well as normal repairing ability.

Animals↗

Anabolic effects of 3,3',5-triiodothyronine and triiodothyroacetic acid in cultured neonatal mouse parietal bones.

We previously reported that both T3 and triiodothyroacetic acid (Triac) stimulate bone resorption in organ culture, with Triac somewhat more potent than T3. In this study we compared the effects of T3 and Triac on DNA and protein synthesis in cultured neonatal mouse calvariae. After 24 h of preculture, with 72 h of treatment, but not 24 or 48 h, these hormones stimulated [3H]thymidine incorporation. After 72 h of preculture, stimulation was observed with only 24 h of treatment. These effects were significant at 10(-10) M and maximal at 10(-9) M for both T3 and Triac (treated/control ratios, 2.2 and 2.0, respectively). In contrast to their effects on bone resorption, T3 was more potent than Triac in stimulating [3H]thymidine incorporation. Insulin-like growth factor-binding protein-3 did not decrease the stimulation of DNA synthesis by T3 or Triac. The medium insulin-like growth factor-I concentration was less than 10(-10) M and was not regulated by these hormones. T3 and Triac stimulated [3H]proline incorporation into both collagen and noncollagen protein to a similar extent (approximately 30% at 10(-8) M). Indomethacin did not alter the effects of T3 and Triac on DNA or collagen synthesis. Aphidicolin, which blocked DNA synthesis completely, partially decreased the effects of thyroid hormones on collagen synthesis. The effect of aphidicolin on bone formation was less than that observed previously on bone resorption. We speculate that the effects of thyroid hormones on bone formation as well as bone resorption may be partially dependent on their mitogenic effects. As Triac is more potent in stimulating resorption and less potent in stimulating formation, Triac may be more catabolic than T3.

Animals↗

Regulation of the two prostaglandin G/H synthases by parathyroid hormone, interleukin-1, cortisol, and prostaglandin E2 in cultured neonatal mouse calvariae.

A second prostaglandin G/H synthase (PGHS-2), encoded by a gene separate from that for the original PGHS (PGHS-1), has recently been identified. We have shown that PGHS-2 is expressed in cultured mouse calvariae and have compared regulation of PGHS-2 and PGHS-1 messenger RNA (mRNA) levels. PGHS-2 mRNA was not detectable in freshly isolated bones, but was induced during culture and further stimulated by interleukin-1 (IL-1) and PTH. Both factors also increased PGHS-2 protein levels. Changes in medium prostaglandin E2 (PGE2) production correlated with increases in PGHS-2 mRNA levels. However, with IL-1, PGE2 production was increased more than PGHS-2 mRNA levels (treated/control ratio, 3.4 and 1.5, respectively), whereas with PTH there was a closer correspondence (2.0 and 2.1). Cortisol reduced PTH-stimulated PGE2 production (treated/control ratio decreased from 3.1 to 0.2) more than PGHS-2 mRNA levels (2.8 to 0.8). In the presence of exogenous arachidonic acid, changes in PGHS-2 mRNA levels with IL-1, PTH, and cortisol correlated closely with changes in PGE2 production. PGE2 itself increased PGHS-2 mRNA, and nonsteroidal antiinflammatory drugs decreased PGHS-2 mRNA levels by 80%. In contrast, PGHS-1 mRNA was expressed constitutively and was not affected by IL-1, PTH, or cortisol when measured by competitive reverse transcriptase-polymerase chain reaction. We conclude that regulation of PGE2 production is predominantly through PGHS-2, rather than PGHS-1; that IL-1 and cortisol may also regulate arachidonic acid release; and that PGE2 may amplify its own production through stimulation of PGHS-2.

Animals↗

Expression of antral gastrin and somatostatin mRNA in Helicobacter pylori-infected subjects.

OBJECTIVES: We investigated the gene expression of antral gastrin and somatostatin in Helicobacter pylori-infected subjects. Twelve asymptomatic men with normal endoscopic findings participated in this study, four of whom were infected with H. pylori. METHODS: Biopsy specimens of the gastric mucosa were obtained after subjects had fasted overnight. Serum gastrin levels, antral gastrin and somatostatin content, and antral G- and D-cell densities also were measured. RESULTS: Fasting serum gastrin levels were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. There were no differences between groups in antral gastrin content, G-cell density, or gastrin mRNA levels. Antral somatostatin content, D-cell density, somatostatin mRNA levels, and the somatostatin mRNA:D-cell density ratio were significantly decreased in H. pylori-positive subjects. CONCLUSIONS: Our results suggest that in addition to reduced antral D-cell density, a suppression of somatostatin synthesis in D-cells may have contributed to the decrease in antral somatostatin in H. pylori-infected subjects.

Adult↗

[A case of generalized disseminated atypical mycobacteriosis caused by M. avium complex with a giant gravitation abscess].

A case of generalized disseminated atypical mycobacteriosis caused by M. avium complex (MAC) was reported. The case was a female of 52 years of age. She was admitted to our hospital due to high fever and polyarthralgia. Her chest X-ray and CT scan revealed infiltrative shadows in the right S2b and S4 segments, and multiple accumulation shadows were seen on osteoscintigraphy. Pus aspirated from a lesion of the right fifth rib were acid-fast bacilli positive by smear (Gaffky v). The administration of four drugs, INH, RFP, EB and SM, was introduced, then corticosteroid was added, and the case became afebrile. Later, acid-fast bacilli were also isolated from bronchial washing and aspirated specimen from bone marrow, and all of them were identified as MAC. Based on these findings, the case was diagnosed as generalized disseminated mycobacteriosis. After several months remission, tenderness over the fifth lumbar vertebra deteriorated, and MRI scan on lumbar vertebrae showed high-intensity area both on T1-weighted and T2-weighted images. MAC was isolated from the pus of the fifth lumbar vertebra. Lumbar lesions deteriorated gradually, and a giant gravitation abscess which involved right ilium was revealed by CT scan of the pelvis. In spite of vigorous treatment including chemotherapy, aspiration of pus and drainage, general condition of the case deteriorated, and the case finally died of renal insufficiency.

Abscess↗

[Recent advances in immunological diagnosis for tuberculosis].

Recent advances in immunological diagnosis for tuberculosis including tuberculin Mantoux test and serodiagnosis were reviewed. New tuberculins (T1327, T1456) were reported to be more specific than the conventional one (RT23). Tuberculins from atypical mycobacteria (PPD-B, PPD-Y, PPD-F) were reported as a useful tool for the diagnosis of atypical mycobacteriosis. Optical density index method is a most appropriate method for a clinical use among several methods for the expression of antigen titer in serodiagnosis using ELISA. The duration of disease is important for understanding the results. IgM antibody rises in the early stage of the disease and comes down in 10 weeks after onset, while IgG antibody rises lately. Anti-cord factor antibody is a highly specific antibody for tuberculosis and may be a potent candidate for a clinical diagnostic tool. Anti-PPD-B antibody was elevated in atypical mycobacteriosis and pulmonary tuberculosis also. The ratio of anti-PPD-B antibody to anti-PPDs antibody was elevated in atypical mycobacteriosis while it was lowered in pulmonary tuberculosis. It may be helpful for suggesting the causative organism when the sputum smear is positive. The opposite results have been reported on the serodiagnosis in HIV infection. The usefulness of serodiagnosis for tuberculosis in HIV infected patients remained controversial.

Antibodies, Bacterial↗

Plasmin and thrombin inhibitors in essentially untreated patients with coronary artery spasm.

We examined activities or levels of plasmin and thrombin inhibitors in essentially untreated patients with angiographically documented coronary artery spasm. The patients received the ergonovine malate provocation test and were classified into two groups: (a) those with significant coronary artery spasm that produced reduction of the internal luminal diameter of 50% or greater with chest pain and change of electrocardiography (n = 18), and (b) those without coronary artery spasm (n = 17). There was no significant differences in alpha 1-antitrypsin and alpha 2-macroglobulin levels, and C1-inactivator activity between the control and patients with coronary artery spasm. On the other hand, the lower antithrombin III and alpha 2-plasmin inhibitor activities were noted in patients with coronary artery spasm than the control. Thrombin/antithrombin III complex and alpha 2-plasmin inhibitor/plasmin complex levels were significantly higher in coronary artery spasm patients. These results suggest that the coagulation and fibrinolytic systems may maintain their equilibrium in untreated patients with coronary artery spasm.

Antifibrinolytic Agents↗

Differential regulation of inducible and constitutive prostaglandin endoperoxide synthase in osteoblastic MC3T3-E1 cells.

Regulation of mRNA levels for the constitutive and inducible prostaglandin endoperoxide synthases, PGHS-1 and PGHS-2, was examined in murine osteoblastic MC3T3-E1 cells. Serum induction of PGHS-2 mRNA levels was rapid, transient, increased by cycloheximide, and inhibited 72% by cortisol. The cortisol inhibition was blocked by cycloheximide. Serum stimulation of PGHS-1 mRNA was slower, decreased by cycloheximide, and inhibited 28% by cortisol. Increased prostaglandin E2 (PGE2) production and induction of PGHS-2 immunoreactive protein paralleled changes in PGHS-2 mRNA. PGHS-2 mRNA was induced at 2 h in serum-free cells by transforming growth factor-beta (TGF-beta), phorbol 12-myristate 13-acetate, and, to a lesser extent, by forskolin. The combination of phorbol 12-myristate 13-acetate and forskolin was synergistic. TGF-beta induction was prolonged compared with serum, inhibited 67% by cortisol, and the inhibition was not blocked by cycloheximide. TGF-alpha had little effect on PGHS-2 mRNA at 2 h, but the combination of TGF-beta and TGF-alpha was synergistic for PGHS-1 and PGHS-2. PGE2 itself induced PGHS-2 mRNA, and inhibition of PGE2 production decreased the serum induction by 55%, suggesting an important role for autoamplification. The rapidity and amplitude of changes in PGHS-2 suggest that it may be involved in bone responses to acute stresses, such as mechanical strain, inflammation, and injury.

Animals↗

Increased calcium release from sarcoplasmic reticulum stimulated by inositol trisphosphate in spontaneously hypertensive rat heart cells.

It is known that inositol (1, 4, 5)-trisphosphate (IP3) stimulates Ca2+ release from sarcoplasmic reticulum (SR) in several tissues, but in cardiac myocytes this phenomenon has not been confirmed. The purpose of the present study was to confirm the effect of (1, 4, 5)-IP3 on Ca2+ release from SR in cardiac myocytes. The effect of IP3 on Ca2+ release from SR in hypertrophic cardiac cells was also determined. We examined the effects of IP3 on Ca2+ release from cardiac myocyte SR by the digital-image method in a single cell. We also determined the effect of IP3 on calcium release from isolated SR. SR was prepared from spontaneous hypertensive rat hearts and Wistar kyoto rat hearts. The SR was prelabeled with 45Ca2+, and then incubated with the indicated concentrations of IP3 for 1 min at 37 degrees C. In cardiac myocytes treated with saponin, Ca2+ release stimulated by 10 microM (1, 4, 5)-IP3 was detected by fura-2. In 45Ca2+ prelabeled SR, the maximal Ca2+ release was achieved at 10 microM IP3 incubated for 1 min. The release of Ca2+ was higher in SR of SHR than in the SR of WKY. IP3 stimulates Ca2-release from cardiac SR, and this release is greater in SHR than in WKY. However, it is uncertain whether this phenomenon plays a role in cardiac hypertrophy.

Animals↗

Percutaneous transhepatic cholecystostomy for acute acalculous cholecystitis.

The effectiveness and long-term results of percutaneous cholecystostomy for acute acalculous cholecystitis are evaluated. Fifteen patients with acute acalculous cholecystitis were treated prospectively by this procedure, using a pigtail catheter successfully placed under ultrasonographic and fluoroscopic guidance. Prompt relief of the signs and symptoms of cholecystitis was achieved in 14 patients. One required emergency cholecystectomy for uncontrolled bleeding after drainage. Another patient underwent prophylactic cholecystectomy before further chemotherapy for leukaemia. The remaining 13 patients required no further surgery. Morbidity and mortality rates were 13 per cent and nil respectively. Long-term follow-up showed no recurrence of cholecystitis after removal of the catheter. Percutaneous cholecystostomy is a safe, effective and usually definitive procedure for the treatment of acute acalculous cholecystitis.

Acute Disease↗

Effects of thiol protease inhibitors on fodrin degradation during hypoxia in cultured myocytes.

The effects of thiol protease inhibitors on fodrin (a cell membrane nonerythroid spectrum-like protein) degradation were studied during hypoxia in cultured myocytes. Cardiac myocytes, isolated from neonatal rat hearts, were incubated under hypoxic conditions for 6 h. Cell membrane proteins, including fodrin, prepared from hypoxic myocytes were examined with electroblots stained for fodrin by the peroxidase method. Cell death during hypoxia rose to 80% after 6 h. Intracellular protease activity was also elevated in hypoxia. This intracellular protease activity was markedly inhibited by the cysteine protease inhibitor E-64 and calpain inhibitor 1. Hypoxic cell death was also suppressed by E-64 and calpain inhibitor 1. A 125 kDa immunoreactive degradation product of fodrin was found in hypoxic conditions. Treatment with E-64 and calpain inhibitor 1 decreased both the appearance of this band and the degradation of fodrin. These observations indicate that intracellular thiol proteases, including calpains, are activated during hypoxia and that these are related to cell membrane protein degradation, especially of fodrin. The data also suggest that protease inhibitor E-64 treatment may be beneficial in protection against hypoxic myocyte injury.

Animals↗

Partial kidney transplantation: a successful kidney transplantation in a child with severe cardiac failure by surgical mass reduction of an adult donor kidney.

We report on a trial of partial kidney transplantation performed on a low body weight child with impaired cardiac function due to mitral valve stenosis and uremic cardiomyopathy. The weight of the donated kidney was successfully reduced by one-third using bench surgery in order to obtain sufficient graft perfusion and function. Our procedure is justified when a graft is too large to be adequately perfused in a recipient suffering from cardiac failure.

Adult↗