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A prospective trial of adrenocorticostertoid (steroid) withdrawal after pediatric renal transplantation was begun in 1990. Ninety-four pediatric renal transplant recipients were enrolled in our multicenter study. Immunosuppressive therapy with cyclosporine (CyA), methylprednisolone (MPL), and mizoribine (MZ) was started after transplantation. MPL was reduced to administration on alternate days in 69 patients (73.4%) and was withdrawn in 27 patients (28.7%). Rejection episodes occurred in nine patients (33.3%) after withdrawal of MPL. It occurred within 3 months after withdrawal of MPL in two patients and more than 6 months in the others. Among them, two patients lost the grafts. Thirteen-year patient survival rate and graft survival rate were 94.6 and 83.1%, respectively. Forty-four of the 94 patients reached their final height. Mean final height was 155.0 cm in males and 146.3 cm in females and their height standard deviation score was -2.6 s.d., the same as that at the time of transplantation. Management of growth retardation before transplantation and further reduction in the steroid dose after transplantation will increase the final height of children with chronic renal failure.

急性糸球体腎炎は通常, 溶連菌を始めとする感染症の既往の後に浮腫, 高血圧, 血尿の三主徴を伴い発症することが知られている。血清補体価の測定が普及している現在, 診断は比較的容易である。腎生検も通常行われることは少ない。一方以前より尿所見を全く伴わない, あるいは一過性に非常に軽度の尿異常のみしか呈さない症例が報告されている。これらは腎外症候性腎炎と表現されることが多い。今回, 我々は11歳男児, 腹痛, 呼吸困難, 浮腫, 高血圧を伴い鑑別診断のために腎生検を行い腎外症候性腎炎と診断した1例を経験した。臨床経過および組織所見の詳細を示す。原因不明の浮腫, 高血圧を認めた場合, 他の疾患を鑑別するとともに尿所見を認めなくても腎炎を疑い血清補体を測定することが診断の糸口になると思われた。腎生検については必須ではないが, 鑑別診断にて必要であれば積極的に施行すべきである。

Familial hypocalciuric hypercalcemia (FHH) is characterized by lifelong asymptomatic hypercalcemia without PTH hypersecretion and is inherited as an autosomal dominant trait with near 100% penetrance. In contrast, neonatal severe hyperparathyroidism (NSHPT) is a life-threatening disorder characterized by marked hypercalcemia and PTH hypersecretion. FHH/NSHPT results from inactivating mutations of the human calcium-sensing receptor (Casr) gene on chromosome 3q13.3–24. Nearly 30 different mutations of the Casr gene associated with FHH/NSHPT have been reported previously. In this report, genetic analysis of 1 Japanese NSHPT family revealed 2 novel mutations at codon 185 (CGA→TGA/Arg→Ter) in exon 4 of the Casr gene and at codon 670 (GGG→GAG/Gly→Glu) in exon 7. The Arg185Ter change was shown to occur in the proband’s unaffected father and paternal grandmother as well as in the proband. The other mutation in exon 7 was shown in the proband’s unaffected mother of Philippine origin as well as in the proband. This...

間欠的cyclophosphamide大量静注療法が症状のコントロールに有用であったループス腎炎の1例を報告する。 5歳時にネフローゼ症候群 (以下ネ症) で発症した膜性ループス腎炎 (WHO分類のV型) で，初期には経口ステロイド剤 (以下ス剤) を中心に治療していた。怠薬を契機に再燃をみて，ス剤に対する反応が不良となり，副作用も顕著になってきたため，間欠的cyclophosphamide大量静注療法を試みた。その後ネ症は寛解し，ス剤の減量が可能となった。制吐剤を併用し，感染症併発時に休薬したが，脱毛以外は問題となるような副作用もみなかった。 本例はV型ループス腎炎であったが，間欠的cyclophosphamide大量静注療法は，ネ症の寛解導入，維持に有効で，ス剤の副作用の軽減が可能であった。

水痘ワクチンの長期にわたる免疫能維持効果についてはまだ十分検討されていない。今回，ネフローゼ症候群の小児における水痘ワクチンの長期免疫効果について検討した。1974年1月から1976年8月の水痘ワクチン治験期間中に，水痘生ワクチンを接種したネフローゼ症候群で，接種から17年～19年の時点で行ったアンケート調査に解答の得られた10例を対象とした。アンケート調査の際に，一部の症例に水痘皮内テストを実施し，水痘抗体価をFAMA法にて測定した。長期予後は全例良好で，腎機能低下例はなく，完全寛解または不完全寛解であった。ワクチン接種後に水痘患者と明らかな接触機会のあったものが5例7回あったが，対象例に水痘・帯状疱疹の発症はなかった。皮内テストと抗体価測定が7例で実施できたが，全例で陽性で，抗体価も維持されていた。今回の検討の結果，水痘の予防効果のみならず，長期間の免疫能保持が確認できた。

Aim: The purpose of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C/T polymorphism and the prevalence and course of focal segmental glomerulosclerosis (FSGS) in our pediatric population. Methods: Genotypes for MTHFR were determined in 15 primary FSGS patients (male/female, 6/9) and 238 control subjects (male/female, 110/128) by the polymerase chain reaction and restriction fragment length polymorphism method. Results: For the whole group, the genotype frequencies (CC/CT/TT) of MTHFR in FSGS and control subjects were almost comparable. The TT genotype was associated with early onset of the disease as compared with the CC genotype. Furthermore, all the patients with the TT genotype had steroid-resistant FSGS and developed into end-stage renal failure, while those carrying either CC or CT genotype did not. Conclusion: We speculate that the TT genotype may be associated with early development and progression of childhood FSGS. Confirmatory studies using larger and ethnically distinct populations are needed to reveal the role of homocysteine in FSGS with consideration of medical interventions.

Sixty-five kidney transplant recipients and their (22 living related and 43 cadaveric) donors were studied prospectively to determine the relationship between kidney transplantation and human herpesvirus-6 (HHV-6) infection. The virus isolation from peripheral blood and other tissues and sequential determination of neutralizing antibodies to HHV-6 were performed during 3 months following the transplantation. All of the donors and their recipients examined had neutralizing antibodies to HHV-6 at the time of renal transplantation and the virus was not isolated from them. HHV-6 was isolated from 3 renal tissues (2 living related and 1 cadaveric) obtained during transplant surgery, but not from their blood at that time. HHV-6 viremia occurred in 9 (14%) of the 65 recipients around 2 to 4 weeks after the transplantation. An additional 27 recipients showed a significant rise in the antibody titer. Thus, the infection with HHV-6 was confirmed in 36 (55%) of the 65. These results indicate that the virus is activated in many cases in the early posttransplant period and that HHV-6 establishes in vivo latency in the kidney tissue. There was no correlation between HHV-6 infection and acute rejection or the antirejection prophylaxis.

During an epidemic of influenza A infection in Japan, a 7-year-old boy was admitted to our hospital because of high fever, convulsions, coma, and liver dysfunction on the 2nd day of a cold-like illness. His serum CPK was markedly elevated, but there was no hyperammonaemia or hypoglycaemia. His CSF showed an increased protein level, but the cell count and glucose level were normal. CT and MRI of the brain showed symmetrical thalamic lesions, and he was diagnosed with acute necrotizing encephalopathy in childhood. He had a significant increased in antibodies to influenza A H1N1 in serum and CSF, but the CSF was negative for influenza virus using virus isolation and a polymerase chain reaction assay. Conclusion Antibody production without detectable levels of influenza virus in cerebrospinal fluid suggests that virus infection occurred, but the virus did not replicate in sufficient numbers in his central nervous system. The thalamic lesion, the hallmark of acute necrotizing encephalopathy in childhood, may be initiated by a local virus infection and develop with subsequent local changes such as breakdown of the blood-brain barrier and the extravasation of blood.

We isolated genomic DNA from 15 patients with branchio-oto-renal (BOR) syndrome or BOR-related conditions. Seven patients had BOR syndrome (two familial and five sporadic), and eight had deafness and renal malformations without branchial fistula (BOR-related conditions). We analyzed all exons and exon–intron boundaries of EYA1 and SIX1 using the polymerase chain reaction (PCR) direct sequencing, and characterized their mutations. In some patients, analysis of mRNA by reverse transcription (RT)-PCR was performed to examine whether the mutation affects the mRNA splicing. We identified five novel disease-causing heterozygous EYA1 mutations in five patients with BOR syndrome (two familial and three sporadic, 5/7=71%), but EYA1 and SIX1 mutations were not detected in the other two patients with BOR syndrome or any of the patients with BOR-related conditions. The detected EYA1 mutations were two nonsense mutations, two splicing acceptor-site mutations, and a point mutation (G>T) of the first base of exon 10. Analysis of mRNA by RT-PCR direct sequencing revealed that the latter point mutation led to the skipping of exon 10. In conclusion, (1) EYA1 mutations are a major cause of BOR syndrome in Japanese, (2) EYA1 and SIX1 mutations were not a major cause of BOR-related conditions, (3) we demonstrated for the first time that the point mutation (G>T) of the first base of the exon in EYA1 gene induced exon skipping.

Since the first report on the development of a live attenuated varicella vaccine in 1974, the vaccine has been studied extensively, with largely favorable results, in both healthy and leukemic children. It is now licensed in Japan, Korea, and some European countries, and is being considered for licensure in the United States. Although various clinical trials have established the safety, immunogenicity, and the efficacy of the vaccine, concern has been expressed that waning immunity in the vaccine recipients might allow the occurrence of more severe varicella later in life. We show data relevant to this concern on the approximately 20-year follow-up study of the vaccine recipients; this work further extends the experience of a long-term protective efficacy of the vaccine.

Renal transplantation is the optimal form of therapy for children and adolescents with end-stage renal disease. Usually histocompatibility differences exist between donor and recipient, so it is necessary to modify or suppress the immune response to enable the recipient to accept a graft. Calcineurin inhibitors (CNI), which include cyclosporin (CsA) and tacrolimus (FK506), give many benefits on the outcome after renal transplantation, but have some toxic effects, especially nephrotoxicity. Therefore, inhibitors of purine synthesis revived as newer generation of more specific inhibitors, mizoribine (MZ) and mycophenolate mofetil (MMF). The Japanese pediatric renal transplantation clinical study group attempted to reduce and then discontinue steroid administration in combination with another three immunosuppressive drugs, CsA, MZ and anti-lymphocyte globulin (ALG). This study showed good clinical results. Mizoribine is an effective immunosuppressive drug in human renal transplantation. However, it is not as popular as other inhibitors of purine synthesis, such as azathioprine (AZA) and MMF, because MZ has been used mainly in Japan and infrequently in other countries. However, MZ is a more useful immunosuppressive drug than AZA, when it is used in combination with CNI.

Backtround: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). Methods: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 ± (SD) 5.0 years. Results: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. Conclusion: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes.

Hypertension is a major problem of patients with chronic renal failure or renal transplant recipients. To clarify the characteristics of blood pressure, heart rate, and circadian rhythms of these patients we used an ambulatory blood pressure monitor (ABPM) for 24 h monitoring and analyzed the data by the cosinor method. In eight chronic renal failure patients without dialysis the midline estimating statistic of rhythm (MESOR) of diastolic blood pressure was higher than in controls, but the MESOR of systolic blood pressure was not. Of 11 patients on dialysis some had hypertension and some had hypotension. In 14 renal transplant recipients, especially those with chronic graft rejection, the MESOR of systolic and diastolic pressures were higher than controls, and the increase of blood pressure MESOR had a significant correlation with the elevation of serum creatinine levels. Circadian rhythms of blood pressure were frequently absent in the patients on dialysis, but circadian rhythms of heart rate were not. The use of an ABPM is a non-invasive method to monitor patients and allowed us to know changes of blood pressure and heart rate in the daytime as well as during the night. For the control of hypertension in chronic renal failure, monitoring with an ABPM seems to provide invaluable information.

Several diphenylmethylpiperazine derivatives are potential therapeutic agents for prevention of ischemic injuries in the heart and brain, because of their ability to block Ca 2+ currents and their antioxidant activity. In this study, the current lead compound. U-92032 ((7-((bis-4-fluorophenyl)methyl)-1-piperazinyl)-2-(2-hydroxyethylamino)-4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one), has been compared with flunarizine and nifedipine (well-known T- and L-type Ca 2+ channel antagonists, respectively) for thier effects on Ca 2+ channels in a mouse neuronal cell line, N1E-115 cells, and their ability to preserve the phenomenon of long-term potentiation and to improve neurological symptoms in gerbil ischemic models. U-92032, like flunarizine, blocked transient Ba 2+ currents ( I Ba ) through T-type Ca 2+ channels with no effect on nifedipine-sensitive non-inactivating currents. Transient I Ba was reduced by U-92032 at a constant rate, the magnitude of which depended on the drug concentration, probably because of a time-dependent accumulation of the lipophilic drug in the membrane phase. For instance, the drug at 6 μM reduced I Ba by 21% per min and abolished it is less than 5 min, about 3 times faster than flunarizine at the same concentration. Otherwise, U-92032 behaved like flunarizine, showing a use-dependent block without noticeable effects on the current-voltage relationship for transient I Ba . Oral administration of U-92032 (1 and 25 mg/kg) or flunarizine (25 mg/kg), but not nifedipine (50 mg/kg), to gerbils 1 h prior to bilateral carotid artery occlusion, preserved long-term potentiation in hippocampal CA1 neurons, which were largely abolished by ischemia without the drug treatment. Also, U-92032 and flunarizine (10 mg/kg) improved neurological symptoms in gerbils with unilateral carotid artery occlusion. Similar improvements by nifedipine were observed at a higher dose (30 mg/kg). It appears that U-92032 is a potent, selective T-type Ca 2+ channel antagonist, and possesses the ability to protect neurons from ischemic injuries at least as effectively as flunarizine. At present, we do not know the extent of contribution by the antioxidant activity of U-92032 to its neuroprotective actions, but are certain of its beneficial effects because of the involvement of the oxygen-induced toxicity in the cascade of neuronal ischemic injuries.

In the past several decades, microorganisms have provided us with many antibiotics useful as chemotherapeutic agents. Screening for new enzyme inhibitors from microorganisms has led us to new knowledge about secondary metabolites that are important as pharmacologically active drugs.

レノグラムの排泄障害パターンは実際に尿路障害を伴わない例もある。このパターンを示す例にレノグラム開始後15～25分の時点でfurosemide (Lasix) を静注すると, その鑑別上有用である。排泄障害のない例では静注後数分内にレノグラム曲線が正常曲線のレベルまで低下する。排泄障害があると, その程度に応じて不完全ないし無反応となる。経時的シンチフォトより得た腎内局所レノグラムの解析と正常曲線および無機能型曲線で反応をみないことから, この反応はfurosemideによる停滞したRIの洗い流しによると考えられる。また腎結石例の術後の観察から, 不完全反応型はfurosemideへの反応性の低下も関与していると考えられる。

Chemical modifications of 8,9-anhydroerythromycin A 6,9-hemiacetal (1), which showed gastrointestinal motor stimulating (GMS) activity 10 times more potent than that of erythromycin A (EM-A), were undertaken to search for derivatives having stronger GMS activity and no antimicrobial activity; details are described in this and a subsequent paper. Displacement of a methyl group of the dimethylamino group of 1 with an ethyl group and an isopropyl group provided de(N-methyl-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal (55) and de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (58), respectively. They showed significant GMS activity and no antibacterial activity. In particular, the GMS activity of 58 was increased to 248 times that of EM-A. EM-A and the derivatives obtained in this study mimic exogenous motilin in the dog. The name "motilide", meaning a motilin-like macrolide, is proposed for this new family of macrolide compounds.

Diazaquinomycin A (1), a new thymidylate (TMP) synthase inhibitor, is poorly soluble in various solvents and exhibits no antitumor activity, while a series of the analogues prepared from 1 are more soluble in water and chloroform than 1, and some of them exhibit antitumor activity in mice. Some analogues in which the lactam rings are replaced by pyridine rings did not inhibit TMP synthase. The diethoxy analogue 25 is a 10-fold more potent inhibitor of TMP synthase than 1. The diacetoxy analogue 23 exhibits significant antitumor activity (T/C: 175%) against Meth-A fibrosarcoma in mice.

The calculation formulae ralating the stress in bending of the laminated wood-beam were checked by tests and verified their appricability to the plywood.The anisotropic properties of strength of the plywood can be represented by the ratios of AE=E90/E0, BE=EB90/EB0 and NR=R90/R0 where E0, EB0 and R0 denote respectively the elastic moduli in edgewise tension or compression, the elastic moduli in bending and modulus of rupture in bending of plywood parallel to the face grain, and E90, EB90 and R90 denote those values of plywood perpendicular to the face grain. These values in the cases of 3-ply, 5-ply and 7-ply plywood of LAUAN which are constructed from single species and have symmetetrical construction to their core are evaluated by the computed results using the basic strength of veneer, and the anisotropic properties of them are discussed.

The first discussion of the buckling of plywood appears to have been made by Balabuch.1) March1) has also dealt with the problem both theoretically and experimentally. There have been many writers besides them who have contributed to finding methods in various ways for the buckling of plywood plates.In many cases, the strain energy method has to be used. One of the few cases where an exact and simple solution is known is that of a simply supported 0° or 90° plate under unidirectional compression (P2=0, S=0 in Fig. 1). In this case, equation (4) reduces to the known accurate result (5). On the other hand, Norris has pointed out that the stress pcr at which the buckling first occurs can be written as equation (7) and the buckling stress coefficient kc is given in equation (8), where r is chosen to make pcr the minimun.Previous experimental discussions have been limited to specific construction of plywood of equal veneer thickness.In this report, plates of Lauan Plywood of various construtions as shown in Table I have been tested, and the observed values of kc have been compared with the calculated values. The values of kc is plotted against a/b(E2/E1)1/4. Examples of these curves are shown in Fig. 3 (a)-(g).When a/b(E2/E1)1/4 is greater than 1, the value of kc is approximately independent of a/b, and kc(a/b→∞) which is defined as equation (10) which is arranged to (11) including Q(=EL/ET), A and D, where A and D depend on the construction of plywood. The effect of A and D on kc(a/b→∞) is shown in Table III, when Q is equal to 20.E1 is Young's modulus of plywood parallel to the direction of compression (Parallel to the side a in Fig. 1), E2 is Young's modulus of plywood perpendicular to direction of compression (Parallel to the side b), EL is the longitudinal Young's modulus of the solid wood composing the plywood, ET is the tangential Young's modulus, and A is determined in formula (c), D is determined in (g), where tn are shown in Fig. 4.

We report on a child in whom kidneys from an anencephalic neonate were transplanted. The transplanted kidneys were rejected after they had been functioning well for 2 months.