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Biomedical subjects

H Azuma

Publications and source records attributed to H Azuma.

At least 127 records · Page 7Linked to original sources
PubMed1996

Rotational acetabular osteotomy for severe dysplasia of the hip with a false acetabulum.

We have divided Severin group-V severely dysplastic hips with a false acetabulum into three subtypes, based on the height and shape of the socket. We performed rotational acetabular osteotomy (RAO) in 19 hips in 17 young adults with a type-1 'low' false acetabulum which had direct contact with the true acetabulum. This is a periacetabular osteotomy which gives acetabular coverage with articular cartilage and produces a nearly normal position of the head. Concomitant osteotomies of the proximal femur were carried out in 11 hips. We reviewed the patients clinically and radiologically at a mean of ten years (6 to 18) after operation. Of the 19 hips, 15 showed very good or good results. This operation is indicated in young adults with a dysplastic hip and a type-1 low false acetabulum. Subclassification of Severin group V is a convenient way of defining those patients who would benefit from the procedure.

Acetabulum↗
PubMed1996

A case report of an elderly patient with acromegaly.

We encountered a 91-year-old patient with acromegalic features. The serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) were increased to 23.3 ng/ml and to 268 ng/ml, respectively. Both thyrotropin-releasing hormone and luteinizing hormone-releasing hormone tests demonstrated a 2-3 fold increase in the serum GH level. Magnetic resonance imaging disclosed a pituitary mass in the enlarged sella. The patient was diagnosed as having acromegaly due to overproduction of GH from a pituitary tumor. She manifested cardiac hypertrophy with severe aortic stenosis and mild hypertension, but without diabetes mellitus. After the administration of octreotide subcutaneously at a dose of 25 to 50 micrograms daily for 20 days, the serum GH level increased transiently but decreased rapidly to approximately half the initial level, and suppression of the GH level persisted thereafter for over 2.5 months. This patient seems to be the oldest patient with acromegaly among those reported in Japan.

Acromegaly↗
PubMed1996

[Comparison of measuring an area with a planimeter and by rectangular dimensional methods].

We have developed a system that measures the volume of air cells in the temporal bone through computerized digital processing of high-resolution CT images. By using this method, the volume of pneumatization was measured, and the results were compared with the measured area of pneumatization obtained from two conventionally used simple ear X-ray methods (the planimeter and rectangular dimensional methods). A total of 57 ears, from 34 subjects, confirmed as normal by CT were examined. The average volume of pneumatization measured on CT images was 5.97 +/- 4.15ml, and the average areas of pneumatization measured by the planimeter and rectangular methods were 9.08 +/- 5.64 and 17.39 +/- 9.77 cm2, respectively. Graphically, when the volume of pneumatization was plotted on the Y axis and the planimeter-measured area of pneumatization on the X axis, a regression formula of Y = 0.651X + 0.054 was obtained, with a correlation coefficient of 0.89. With the volume of pneumatization plotted on the Y axis and the rectangular-dimensional-measured area of pneumatization on the X axis, the regression formula was Y = 0.375X - 0.559, with a correlation coefficient of 0.88. Both these correlation coefficients were considered high. Furthermore, 3D models of the air cells in the temporal bone were created and compared for patients with high and low correlations. In order to capture the morphological characteristics of these 3D models, they were examined from four different angles (lateral, upper lateral, anterior lateral and upper medial). The results showed that regardless of whether air-cell growth was present in the direction of the apex partise petrosae in patients with a low correlation coefficient, such growth played a major role in the degree of the correlatiton. Future studies will be required to clarify this point, though it can already be said that 3D models are indispensable for studying the air cells in the temporal bone. When we compared the volume and area of pneumatization in the temporal bone at different CT cross-sections, we found correlation coefficients in the vicinity of the canalis semicircularis lateralis of about 0.9 or higher. A statistical comparison of correlation coefficients for the CT, planimeter, and rectangular dimensional methods, made by using the CT cross-section with the highest coefficient, found a significant difference between the CT method and the other two methods (p < 0.05). In other words, the volume of pneumatization can be estimated more accurately with CT images than with simple ear X-rays.

Adolescent↗
PubMed1996

Augmenting kidney mass at transplantation abrogates chronic renal allograft injury in rats.

Conventional renal transplantation, which substitutes a single allograft for two native kidneys, imposes an imbalance between nephron supply and the metabolic and excretory demands of the recipient. This discrepancy, which stimulates hyperfunction and hypertrophy of viable allograft nephrons, may be intensified by nephron loss through ischemia-reperfusion injury or acute rejection episodes occurring soon after transplantation. In other settings where less than 50% of the total renal mass remains, progressive glomerular injury develops through mechanisms associated with compensatory nephron hyperfiltration and hypertrophy. To determine whether responses to nephron loss contribute to chronic injury in renal allografts, nephron supply was restored to near-normal levels by transplanting Lewis recipients with two Fisher 344 kidneys (group 2A) compared with the standard single allograft F344 --> LEW rat model of late renal allograft failure (group 1A). At 20 weeks, indices of injury were observed in 1A but not 2A rats. These indices included proteinuria (1A: 45 +/- 13; 2A: 4.0 +/- 0.29 mg/day) and glomerulosclerosis (1A: 23 +/- 4.9%, 2A: 0.7 +/- 0.3%) (p < .05). Double-allograft recipients maintained near normal renal structure and function, whereas 1A rats showed evidence of compensatory hyperfiltration (single-nephron glomerular filtration rate of 63 +/- 10 versus 44 +/- 2.0 nl/min in 2A rats) and hypertrophy (mean glomerular volume of 2.64 +/- 0.15 versus 1.52 +/- 0.05 microns3 x 10(6) in 2A rats) (p < .05). Thus, we conclude that a major component of late allograft injury is attributable to processes associated with inadequate transplanted renal mass, a finding that has major implications for kidney transplantation biology and policy.

Animals↗
PubMed1996

A novel missense mutation in two families with congenital plasminogen deficiency: identification of an Ala675 to Thr675 substitution.

We used a polymerase chain reaction (PCR) strategy and restriction fragment polymorphism analysis to evaluate all 19 exons of the plasminogen (PLG) gene in a Japanese patient with congenital PLG deficiency and her family members (family C). Sequence analysis following amplification of each exon and its flanking regions showed a single G to A transition in exon 17, resulting in the conversion of an Ala675 codon (GCT) to Thr675 codon (ACT). Since this mutation generates a new Mae III site, the Mae III digestion patterns of the PCR-amplified exon 17 fragments from each family member were analyzed. In all cases, the patterns correlated with the activities and antigen levels of plasma PLG in those members. The identical G to A transition in the same codon of exon 17 was detected by a Mae III digestion experiment in another proband and her family members with congenital PLG deficiency (family K). Furthermore, 20 normal individuals examined had no Mae III restriction site at this location. We conclude that a G to A transition in exon 17 is responsible for the congenital PLG deficiency inherited in these two Japanese families.

Adolescent↗
PubMed1996

Effects of mycophenolic acid mofetil on acute rejection of kidney allografts in rats.

Mycophenolic acid mofetil (MMF) is an agent which has recently gained a lot of attention. In clinical trials MMF has reduced the rate of acute rejection episodes in human recipients of kidney allografts by inhibiting inosin-monophosphat-dehydrogenasis (IMPDH), an enzyme involved in the purin metabolism and related to the expression of adhesion molecules. The aim of the present study was to analyze the effects of MMF upon the expression of adhesion molecules in transplanted kidney allografts. LBNF1 kidneys were orthotopically transplanted into Lewis rats and either treated with MMF (20 mg/kg/day) or vehicle. Rats were harvested 3, 5 and 7 days following transplantation. Immunohistology was performed with various monoclonal antibodies. In general, MMF resulted in a better preservation of graft structure by 7 days. Cellular infiltration and tubular atrophy were less pronounced. At day 3, macrophages were diminished in MMF-treated animals to a high extent, while the number of T-cells was almost identical as compared to controls. In addition, the number of cells positive for MHC class II and LFA-1 was reduced in the MMF-treated animals. In conclusion, MMF resulted in a markedly reduced leukocyte infiltrate, presumably based on a reduced expression of lymphocytic adhesion molecules and an interaction with macrophages.

Animals↗
PubMed1996

[Molecular biological approach for congenital abnormality of blood coagulation].

Proteins of blood coagulation are categorized into three major groups, coagulation proteins, regulatory proteins and fibrinolytic proteins, in terms of their physiologic functions. Congenital deficiencies or abnormalities of these proteins elicit bleeding or thrombotic disorders. In general, defects of coagulation proteins are associated with a predisposition to bleeding disorders. By contrast, both defects of regulatory and fibrinolytic proteins are associated with a predisposition to thrombosis. The marked advances in molecular biology in the 1980s has allowed us to detect gene defects in most patients with congenital bleeding or thrombotic disorders. The information has contributed to our understanding of the structure and function relationship of the blood coagulation proteins. We have reported patients with congenital deficiencies or abnormalities of blood coagulation proteins. Herein, we describe the general approach for elucidating gene defects in patients with congenital bleeding or thrombotic disorders and provide a case of a Japanese family with congenital plasminogen deficiency in whom the genetic abnormality was identified.

Adult↗
PubMed1996

Infections and reduced functioning kidney mass induce chronic rejection in rat kidney allografts.

The etiology of chronic rejection of kidney allografts is unknown, although hyperfiltration, acute rejection, viral infection and initial graft ischemia have been implicated. To test whether endothelial activation may be the link between these factors and chronic rejection, the endotoxin (lipopolysaccharide-LPS), a potent activator of endothelial cells, was evaluated in an established chronic rejection model. Bilaterally nephrectomized Lewis recipients of orthotopically transplanted Fisher 344 kidneys were treated briefly with low dose cyclosporine (1.5 mg/kg/day x 10). Recipients were given a non-lethal dose of LPS (2 mg) i.p. at 8 weeks and compared to allografted controls treated with vehicle. Urine protein was measured every 4 weeks. Rats in the treated group were sacrificed at 12 and 16 weeks, control animals at 12, 16 and 24 weeks (20/group) and examined histologically. In the chronically rejecting control allografts, progressive interstitial and glomerular sclerosis and vascular intimal proliferation had become apparent by 12 weeks. Infiltration of glomeruli, particularly by macrophages (M phi), and the coincident presence of cytokines were prominent, peaking at 16 weeks. LPS treatment accelerated and intensified these changes; proteinuria was more pronounced (16 weeks: 79 mg/24 h vs. 49 mg/24 h, p < 0.05). Numbers of infiltrating M phi peaked at 12 weeks in LPS treated hosts (69 c/FV vs. 27 c/FV in untreated controls, p < 0.01), accompanied by an increased upregulation of MHC class II and cytokine expression, particularly TNF alpha and PDGF around arteries and areas of infiltration. BY 16 weeks, 35 +/- 3% of glomeruli in LPS treated recipients had become sclerotic vs. 15 +/- 6% (p < 0.05) in controls, again associated with increased expression of cytokines (PDGF, TNF alpha, TGF beta), adhesion molecules (ICAM-1) and extracellular matrix proteins. Overall, the extent of chronic rejection of grafts in LPS treated rats at 16 weeks was similar to that developing in non-treated rats at 24 weeks. Activation of graft endothelium and/or host leucocytes increased the pace of graft infiltration and the expression of cytokines and other molecules. These events accelerate the process of chronic rejection.

Analysis of Variance↗
PubMed1996

[Early intervention for very-low-birth-weight infant].

In order to establish an early intervention (EI) system for very-low-birth-weight infants, we designed a randomized trial at multiple institutions in Japan. We also reviewed the concept and history of early intervention in USA. Eight medical institutions in different locations were selected for participation. Sixty-two EI group patients and 48 controls without neurological abnormalities (age 2 years) were selected for study. The developmental quotient (DQ) by the revised Kyoto-K method and 15 questionnaire items were monitored twice, at the age of 2 and after one year of EI (3 years). Improvements in behavioral problems, circadian rhythm, and speech were significantly greater in the EI group than in the control group. (P < 0.01). Data on all patients are being collected, and further evaluation and analysis of DQ are planned. The most effective EI method in each specific location and the financial support of its official institutions are required for the success of the EI program for very-low-birth-weight infants.

Early Intervention, Educational↗
PubMed1996

[Simultaneous measurement of the tension, elongation, and refractive power of the bovine lens zonule].

We developed a device to measure simultaneously the tension and elongation of the lens zonules, and the refractive power of the lens in 12 bovine eyes. Each sample, which consisted of the lens-zonuleciliary body was fixed to the device at the position of the ciliary process from four directions, and was stretched radially in a container filled with saline solution. The tension was measured by a force transducer, the elongation by a laser-displacement-meter, and the refractive power by a Campbell type refractometer. The refractive power of the lens in the relaxed condition was 24.6 +/- 3.4 D (n = 12, mean +/- standard deviation). When samples were stretched 1 mm from the relaxed condition, the increased change in tension was 2.8 +/- 1.5 g, and the decreased change in refractive power was 1.8 +/- 1.2 D.

Animals↗
PubMed1996

Management conditions during dialysis therapy influence the occurrence of complications after renal transplantation?

We investigated whether the management condition of patients during dialysis therapy has an influence on the occurrence of complications after renal transplantation. Thirty-one patients who underwent renal transplantation were investigated: thirteen received kidneys from living related donors and 18 received cadaveric transplants. The relations between weight gain ratio, cardiothoracic ratio (CTR) and blood pressure during dialysis and the rate of episodes of acute rejection or infection after renal transplantation were analyzed. The rate of acute rejection tended to be higher among patients whose CTR was less than 45% than in those whose CTR was 45% or more. There was no relation found between the rate of infection after transplantation and weight gain ratio. CTR, or blood pressure during dialysis therapy. These results suggest the possibility that the management condition of patients during dialysis therapy influences the rate of acute rejection after these patients undergo renal transplantation.

Adolescent↗
PubMed1995

Prevention of functional, structural, and molecular changes of chronic rejection of rat renal allografts by a specific macrophage inhibitor.

Chronic rejection is the primary cause of long-term allograft loss. Macrophages and their products have been shown to be critical in the development of this process in an established kidney allograft rat model. A new synthetic agent, Gamma lactone, is a specific inhibitor of macrophages and monocytes that inhibits the generation of these populations in vitro and their activities in the effector phase of host alloresponsiveness. We tested its effects on the development of chronic changes in the model. Untreated control allograft recipients developed increasing proteinuria after 12 weeks; progressive glomerulosclerosis, interstitial fibrosis, and arterial obliteration developed thereafter. Infiltrating ED1+ macrophages as noted by immunohistology increased dramatically between 12 and 16 weeks, localizing preferentially in glomeruli and perivascular areas. The presence of these cells was associated with dense expression of their products. Reverse transcription polymerase chain reaction confirmed and expanded the immunohistological findings, showing significant gene expression of macrophage-derived mediators. In contrast, recipients treated with G-Lac daily for 32 weeks never developed proteinuria; macrophage infiltration was dramatically reduced, and expression of their products was virtually absent. At 32 weeks, most glomeruli and arteries remained histologically normal. In another group in which treatment was stopped at 24 weeks, however, proteinuria began to develop by 32 weeks; macrophages infiltrated the organs and expression of their products became manifest. These results confirm the importance of macrophages and macrophage-derived factors in chronic rejection and suggest that a specific inhibitor of macrophage activation may be useful in the prevention of the process over the long term.

Animals↗
PubMed1995

Rapamycin inhibits transplant vasculopathy in long-surviving rat heart allografts.

We have examined the effects of rapamycin (RPM) on transplant vasculopathy in long-surviving F344 rat heart allografts transplanted heterotopically into Lewis recipients. RPM was administered intraperitoneally for the first 14 days in groups 1 and 2 (0.5 and 2 mg/kg/day), and daily throughout the follow-up period in groups 3 (0.5 mg/kg/day) and 4 (5 mg/kg for 14 days, followed by a maintenance dose of 2.5 mg/kg/day). Treatment with low dose cyclosporine (CsA; 1.5 mg/kg/day) in combination with RPM (0.5 mg/kg/day for 14 days) (group 5) and immunosuppression with CsA only (5 mg/kg for 14 days, followed by 1.5 mg/kg/day) (group 6) were also examined. F344 isograft recipients treated with RPM (0.5 mg/kg/day for 14 days) (group 7), those that were untreated (group 8), and hearts in naive F344 animals (group 9) served as controls. Grafts of group 1 were removed at 50, 75, 100, 150, and 200 days and infiltrating cell populations and surface molecules were compared with those of the other groups at 100 days. All allografts in treated hosts functioned > 100 days; in contrast, grafts in untreated recipients were rejected acutely by 8 +/- 1 days (MST +/- SD). The incidence of transplant vasculopathy in group 1 increased progressively (MST +/- SD = 10 +/- 2%, 59 +/- 7%, 85 +/- 15%, and 80 +/- 12% at 50, 100, 150, and 200 days, respectively), as manifested by myointimal proliferation with dense mononuclear infiltration (predominantly ED1+ macrophages). Numbers of MHC class II+ infiltrating cells were prominent, as was expression of adhesion molecules and cytokines. The incidence of graft disease and extent of cellular infiltration at 100 days was significantly lower in animals receiving increased maintenance doses of RPM (for groups 2, 3, and 4: 25 +/- 15%, 22 +/- 11%, and 10 +/- 3%, respectively; P < 0.005). CsA treatment either in combination with RPM or alone (groups 5 and 6) failed to improve transplant vasculopathy, but reduced mononuclear cell infiltration. Isografts (groups 7 and 8) and naive hearts (group 9) developed no structural abnormalities throughout the follow-up period, regardless of RPM treatment. We conclude that the extent of transplant vasculopathy can be reduced markedly in this rat cardiac transplant model with maintenance RPM. Addition of CsA modifies the morphological picture but does not improve myointimal proliferation.

Animals↗
PubMed1995

Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1.

Chronic rejection, the most important cause of long-term graft failure, is thought to result from both alloantigen-dependent and -independent factors. To examine these influences, cytokine dynamics were assessed by semiquantitative competitive reverse transcriptase-PCR and by immunohistology in an established rat model of chronic rejection lf renal allografts. Isograft controls develop morphologic and immunohistologic changes that are similar to renal allograft changes, although quantitatively less intense and at a delayed speed; these are thought to occur secondary to antigen-independent events. Sequential cytokine expression was determined throughout the process. During an early reversible allograft rejection episode, both T-cell associated [interleukin (IL) 2, IL-2 receptor, IL-4, and interferon gamma] and macrophage (IL-1 alpha, tumor necrosis factor alpha, and IL-6) products were up-regulated despite transient immunosuppression. RANTES (regulated upon activation, normal T-cell expressed and secreted) peaked at 2 weeks; intercellular adhesion molecule (ICAM-1) was maximally expressed at 6 weeks. Macrophage products such as monocyte chemoattractant protein (MCP-1) increased dramatically (to 10 times), presaging intense peak macrophage infiltration at 16 weeks. In contrast, in isografts, ICAM-1 peaked at 24 weeks. MCP-1 was maximally expressed at 52 weeks, commensurate with a progressive increase in infiltrating macrophages. Cytokine expression in the spleen of allograft and isograft recipients was insignificant. We conclude that chronic rejection of kidney allografts in rats is predominantly a local macrophage-dependent event with intense up-regulation of macrophage products such as MCP-1, IL-6, and inducible nitric oxide synthase. The cytokine expression in isografts emphasizes the contribution of antigen-independent events. The dynamics of RANTES expression between early and late phases of chronic rejection suggest a key role in mediating the events of the chronic process.

Animals↗
PubMed1995

A new mutation in exon 12 of the gp91-phox gene leading to cytochrome b-positive X-linked chronic granulomatous disease.

We have previously reported a patient with cytochrome b-positive X-linked chronic granulomatous disease. Although the O2- production of neutrophils from the patient was completely defective, we presented data suggesting that the patient's cytochrome b was present at a normal level and possibly had normal spectroscopic features. Thus, to look for a mutation in the cytochrome b heavy chain (gp91-phox) gene, DNA analysis of gp91-phox cDNA derived from this patient was performed. As a result, we found that five nucleotides (1521 through 1525) within exon 12 were deleted, and a new sequence of eight nucleotides was inserted. This mutation converted Gln507-Lys508-Thr509 into His-Ile-Trp-Ala. Mismatched polymerase chain reaction showed that the mother has both wild and mutated alleles, confirming that this case was transmitted in an X-linked fashion. This mutation is different from those previously reported by others. The translocation of p47-phox and p67-phox to the membrane fraction occurred, indicating the complete formation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. We conclude that this case suggests that the structure encoded on exon 12 of gp91-phox is important for electron transfer.

Adult↗
PubMed1995

Effects of RS61443 on functional and morphological changes in chronically rejecting rat kidney allografts.

No immunosuppression agent is as yet available that prevents the process of chronic allograft rejection, the most critical cause of late organ allograft loss. RS61443 (mycophenolate mofetil) inhibits de novo DNA synthesis as well as diminishes expression of cell surface molecules and antibody production. As these factors seem important in the pathophysiology of the chronic phenomenon, we investigated the effects of the agent in an established model of chronic rejection of kidney allografts in a F344-to-Lewis rat strain combination. All recipients were treated for the first 10 days after engraftment with low-dose cyclosporine (1.5 mg/kg/day) to reverse an initial acute rejection episode. Since functional and morphological changes do not become manifest in this model until after 12 wk, treatment with RS61443 (15 mg/kg/day, p.o.) was either initiated at the day of grafting (Gp 1) or 8 wks thereafter (Gp 2), and continued throughout the follow-up period. Non-RS61443-treated allografted rats receiving vehicle only (Gp 3) developed progressive proteinuria after 12 wk. Peak cellular infiltration (particularly macrophages in glomeruli and perivascular areas) at 16 wk was associated with densely expressed adhesion molecules (ICAM-1 on endothelium), cytokines and growth factors (TNF-alpha and TGF-beta in glomeruli and PDGF on arterial smooth muscle cells). Interstitial fibrosis, with tubular atrophy, glomerulosclerosis, and varying degrees of intimal proliferation and luminal obliteration of vessels, progressed thereafter. In vitro binding of MNC from naive animals to chronically rejecting allografted kidneys generally confirmed the immunohistological observations, peaking at 12 wk; this binding was significantly inhibited by mAbs against specific adhesion molecules (CD11a, CD18, and ICAM-1). Serum-allospecific IgG and IgM peaked at 1-2 wk after engraftment in the control recipients, decreasing thereafter. Although IgM declined to baseline after 12 wk, low levels of allospecific IgG persisted throughout the follow-up period. In contrast, recipient treatment with RS61443 (both Gp 1 and Gp 2) allowed the allografts to function normally throughout follow-up period. Proteinuria was virtually absent, and morphological and immunohistological manifestations of the chronic process were markedly diminished. In addition, treated recipients developed no significant side effects, including leukopenia, anemia, thrombopenia, nephrotoxicity, and hepatotoxicity. It appears that this agent can safely prevent the changes of chronic rejection of kidney allografts in this rat model.

Animals↗