Search

Human parvovirus B19 (HPV-B19) infection is known to frequently induce aplastic crisis in patients with hemolytic anemia, but rarely causes hematological disorders in healthy subjects. We report a 5-year-old boy who showed transient myelodysplasia associated with HPV-B19 infection. He was admitted with severe nasal bleeding, and laboratory data showed marked thrombocytopenia (1,000/microliter), anemia (Hb: 8.4 g/dl), and mild leukopenia (3,000/microliter). A bone marrow smear revealed myelodysplastic changes in three cell lineages, but no giant proerythroblasts or megakaryocytes. The pancytopenia and myelodysplastic changes were resolved spontaneously within a week without any medication other than transfusion of red blood cells and platelets. Serological examination revealed an elevation of IgG antibody against HPV-B19 on days 15 and 120 and its subsequent decrease thereafter, although HPV-B19-specific DNA was not detected in the serum at onset. The clinical course and laboratory data suggest an etiologic role of HPV-B19 infection in the occurrence of transient myelodysplasia.

In current transformation systems, a selectable marker gene is co-delivered with the gene of interest to identify and separate rare transgenic cells from non-transgenic cells. Since, during transformation, only a few plant cells accept the integration of foreign DNA, most of the cells remain non-transgenic. Usually, conditional dominant genes, which have no influence on the growth or morphology of plants, are used as selectable markers because they remain in the transgenic plants after transformation. The corresponding selective agents, which inhibit the growth of non-transgenic cells, are applied to the culture medium to identify transgenic plants. However, these selection systems have three potential pitfalls. (1) The negative effects of selective agents decrease the ability of transgenic cells to proliferate and differentiate into transgenic plants. (2) The presence of marker genes in transgenic plants precludes the use of the same marker gene for gene stacking through re-transformation. (3) The recent public concerns regarding the release of antibiotic-resistance genes limit their use for the commercialization of transgenic crops.

We assume that the Higgs bosons are composed of a preon ≪a≫ and an antipreon ≪aCP≫. It is then shown that the composite Higgs bosons can give the mass to gauge bosons, quarks and leptons in the framework of the standardSU(2)L×U(1) electroweak model.

A 9-year-old girl with acute lymphoblastic leukemia in second remission underwent cord blood transplantation (CBT) from an HLA-mismatched (2 loci by serotype, 3 loci by genotype) unrelated donor. The infused nucleated cell count was 1.95 x 10(7)/kg. FK506 and mini-MTX were used to prevent graft-versus-host disease (GVHD), but grade II acute GVHD developed on the skin (stage III). The GVHD subsided after administration of corticosteroid, but marked hyperglycemia developed, which required transient insulin therapy for its control. Minimal residual disease (MRD) was assessed using a clone-specific probe for the JH region. MRD was positive before CBT, but became negative one month after CBT. Now, at 14 months after CBT, the patient is in a disease-free state without detectable MRD. These observations suggest that CBT with two mismatched HLA loci can be performed safely, and that sequential analysis of MRD is useful for evaluation of the disease status after CBT.

We have treated 93 ruptured aneurysms with Guglielmi Detachable Coils (GDC) in acute period. Seventy-three patients (78%) were independent on discharge. Among the patient of Hunt and Hess Grade I, II and III, 59 patients (88%) were independent. Acute re-rupture occurred in two elderly patients with insufficient embolization and two patients experienced re-rupture in the follow up period. Symptomatic vasospasm was reported in 17.6% of patients. The permanent morbidity rate is 4.4% and one patient died (1.5%). Although the long-term results remain to be determined, embolization with GDC is a safe and promising treatment for acutely ruptured aneurysms.

Pica is one of eating disorders characterized by continuous or repeated ingestion of non-food materials or sometimes of a tremendous amount of specified food. Known risk factors for developing pica include iron deficiency anemia, malnutrition, mental disorders, pregnancy, psychiatric conflict, and social and ethnic habituation, although the mild pica tendency associated with mental disorders is excluded from the definition of pica according to the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) by American Psychiatric Association. Pica is regarded as the common disorder than expected but commonly missed, and therefore is important to suspect of this disorder for its diagnosis when people with known risk factors show unexplained signs and symptoms.

We reported a 35-year-old male patient with acute type adult T cell leukemia(ATL) and human T-lymphotropic virus type I associated myelopathy. He presented meningitis and polyradiculoneuropathy and improved with steroid treatment. He presented headache and sensory ataxia and these symptoms responded to steroid treatment. The usual clinical features of ATL were absent at onset. There existed ATL-like cells in the cerebrospinal fluid and HTLV-I proviral DNA in the blood. Therefore, we surmised that there was monoclonal hyperplasia of the infected cells. He presented ATL after 2 years remission. We pointed out that there was acute type of ATL in patients with meningitis and polyradiculoneuropathy, for which steroid treatment could be effective.

Most chromosomal abnormalities associated with breakage at 11q23 in acute leukaemia involve the MLL gene, and the presence of this breakage strongly predicts a poor clinical outcome. We assessed the possibility of differentiation-inducing therapy for acute leukaemias with chromosomal translocations involving 11q23. Among the cell lines with MLL translocations that we examined, KOCL48 and KOPN-1 cells were induced to differentiate into granulocytes by all-trans retinoic acid (ATRA) or into monocytes by 1alpha,25-dihydroxyvitamin D3 (VD3). These cells expressed p16 mRNA before treatment with 5-aza-2'-deoxycytidine (5-AZA), an inhibitor of DNA methylation. On the other hand, differentiation was not induced in SN-1, KOCL33, KOCL51 or KOCL44 cells by ATRA or VD3, and these cells did not express mRNA of this gene. However, these cells were effectively induced to differentiate by ATRA or VD3 in the presence of 5-AZA, and concomitantly exhibited p16 gene expression, suggesting an association between DNA demethylation and restoration of sensitivity to differentiation-inducing activity of ATRA or VD3 in leukaemia cells with MLL abnormalities. Based on these findings, combined treatment with ATRA or VD3 plus 5-AZA may be clinically useful in therapy for acute leukaemia with MLL abnormalities.

Anti-galactocerebroside (anti-GC) antibody has recently been recognized as a possible demyelinating agent. On the 9th day of Mycoplasma pneumoniae (Mp) pneumonia, an 8-year-old boy had a seizure lasting three hours followed by loss of consciousness for 30 hours. Anti-GC antibody titers and myelin basic protein in the CSF were 1:640 and 8.1 ng/dl, respectively. There were no neurological sequelae. It is suggested that the degree of elevation of anti-GC antibody titers in CSF may not correlate well with the severity and neurological prognosis in Mp encephalitis.

We assume that the electron (e−), neutrino (ve), and gauge bosons (W±,Z0) are composed of only two kinds of particles, an ultimate particleu∞ at an infinite sublayer quark level and a chargeless fermiont, such thate−=(u∞cpu∞cpl),Ve=(u∞u∞cpl,W+=(u∞u∞),W−=(u∞cpu∞cp andZ0=(u∞u∞cp. It is then shown thatCP is violated in weak interactions associated with these electron, neutrino, and gauge bosons.

We propose a composite model in which quarks and leptons are made up of three preons and gauge bosons of two preons. It is then shown thatCP is violated in only one generation of u and d quarks and also in pure leptonic interactions.

A 72-year-old woman who presented with a unilateral oculomotor nerve palsy was shown to have a very rare condition: multiple dural arteriovenous fistulae (DAVF) involving the cavernous and sphenoparietal sinuses. The sphenoparietal DAVF was cured completely by transarterial embolisation. Symptomatic relief was accomplished by this procedure. The cavernous sinus DAVF progressed to acquire cortical venous drainage, and was obliterated completely by transvenous embolisation.

The in-vivo anti-influenza-virus activity of Stachyflin derivatives (III and its phosphate ester, III-Phos), a new class of haemagglutinin fusion inhibitor, and the improvement of their absorption after oral or intranasal administration were studied in mice, rats, and ferrets. The absorption of III in PEG 4000 and III-Phos aqueous solution increased about three and four fold in AUC after oral administration to uninfected mice compared with that of 0.5% HPMC (hydroxypropyl-methylcellulose) suspension. Using a mouse influenza virus infection model, significant anti-influenza-virus activity was observed in infected mice treated orally with these compounds dissolved in PEG 4000 or distilled water, respectively, but not in mice treated with 0.5% HPMC. The in-vivo anti-influenza-virus activity in ferrets, a good model for influenza virus infection in man, was also studied. Although the concentration of III in plasma was above the IC50 against the influenza virus strain used for 6h after the oral administration of III in PEG 400 to uninfected ferrets, no in-vivo anti-influenza-virus activity was observed at the same dosage given 4 times daily for 3 days. The intranasal administration of III-Phos, which was expected to have a more notable in-vivo anti-influenza-virus activity, was examined. III-Phos, whose intranasal absorption had been improved by the modification of III with phosphate ester in rats, inhibited viral replication in the nasal cavity and suppressed influenza-virus-induced fever when administered intranasally to infected ferrets. This study demonstrates that intranasally administered compounds with anti-influenza-virus activity must permeate the nasal membranes to produce their anti-influenza-virus effect.

We studied clinical symptomatology and somatosensory evoked potentials(SEP) of 7 pure sensory stroke patients due to pontine lesions. Clinical symptoms were examined by modality(pinprick, touch, vibration and joint position sense), intensity and distribution of the sensory disturbance. SEP were recorded by the median nerve stimulation in the upper extremities, and the posterior tibial nerve stimulation in the lower extremities. Patients 1-4 were characterized by decreased contra-lesional fingers or fingers, toes joint position sense, normal pinprick and vibration sense. We think that these patients' lesions were localized in the lemniscus medialis. Patients 5-7 were characterized by decreased contra-lesional upper extremity or upper and lower extremity vibration sense, decreased pinprick sense and normal joint position sense. We think that these patients' lesions involved spinothalamic tract. There was no abnormal finding of SEP with upper extremity stimulation, but disappearance or very low amplitude of P38 with lower extremity stimulation in 4 of the 7 patients. We conclude that 1) the vibration sense may be conducted also through the spinothalamic tract, 2) SEP findings are abnormal only with lower extremity stimulation in pontine pure sensory infarction.

Serum lactate dehydrogenase (LDH) activity is known to become elevated following granulocyte colony-stimulating factor (G-CSF) therapy in some patients, but no extensive studies on this phenomenon have been performed. In 26 children with malignancies in complete remission who received recombinant human G-CSF intravenously after combined chemotherapy, we measured serum LDH and its isozymes (81 episodes) before chemotherapy (pre-Tx), during administration of G-CSF (mid-Tx), and after stopping G-CSF (post-Tx) and compared the obtained data using paired t test. Twelve episodes were excluded from analysis because of liver dysfunction (alanine aminotransferase45 IU/L). Serum LDH at mid-Tx (343.1+/-19.8 IU/L; mean +/- SE) was significantly higher than that at pre-Tx (186.9+/-6.7 IU/L) and post-Tx, but this difference was observed only when change in white blood cell counts (WBCs) (WBC at mid-Tx minus WBC at pre-Tx) was greater than or equal to 4000/microL (58 episodes). Percentages of LDH isozymes 3, 4, and 5 at mid-Tx (23.5+/-1.0, 11.7+/-0.8, and 8.3+/-0.7) were significantly increased compared with those at pre-Tx (19.5+/-0.7, 6.3+/-0.3, and 4.2+/-0.5) and post-Tx, resulting in a significant decrease in percentages of LDH isozymes 1 and 2 at mid-Tx. In episodes of change in WBCsor =4000/microL, change in LDH significantly correlated to changes in WBCs and granulocytes but not to change in lymphocytes or monocytes. These results suggest that serum LDH is significantly elevated during G-CSF administration in accordance with the increase in peripheral granulocytes, which accompanies change in the pattern of percentages of LDH isozymes.

One hundred and thirteen strains of Streptococcus pneumoniae (S. pneumoniae) were isolated from the clinical specimens of patients with respiratory tract infections between January and December 1998 in three hospitals in Hokusetsu area of Osaka. We investigated susceptibility of 113 strains of S. pneumoniae to benzylpenicillin (PCG) and other antimicrobial agents and their serotypes. 1) Of the 113 strains of S. pneumoniae isolated, 25.7% were susceptible (PSSP), 51.3% were intermediate (PISP) and 23% were resistant to benzylpenicillin (PRSP). 2) The MICs of cefaclor, cefditoren, cefpodoxime, cefdinir, erythromycin, clindamycin and minocycline were elevated, but the MIC values of cefditoren ranged fromor = 0.03 to 1.0 microgram/ml. The susceptibility of 113 strains to cefditoren was comparatively high. 3) The MIC values of imipenem, meropenem and vancomycin for 81 strains of PISP and PRSP ranged fromor = 0.015 to 1.0 microgram/ml, fromor = 0.015 to 2.0 micrograms/ml and from 0.13 to 0.5 microgram/ml, respectively. The susceptibility of these strains to three antimicrobial agents was superior to that to the other antimicrobial agents examined. 4) Of the 60 strains examined, 19, 6, and 23 serotypes were 30, 25 and 18.3%, respectively. The three serotypes were observed in PISP and PRSP with a high frequency. 5) Isolates of S. pneumoniae were 37.2% for children under 2 years of age and 30.9% for children from 2 to 6 years of age. Most of the strains isolated from these children were resistant.

We applied the tuberculosis examination radiographs to scoliosis screening in high schools. Prevalence, physique, physical strength and motor ability of the students with scoliosis were investigated.In this study, 3,299 the first year high school students (1,597 males and 1,702 females) in Wakayama Prefecture, who had taken chest X-ray photographs between 1993 and 1995, were examined and 106 cases (22 males and 84 females) were identified with scoliosis of more than 10 degrees Cobb angle. Each of the cases was assigned age- and sex-matched controls without scoliosis. These pairs were investigated as to the following items: body height, body weight, sitting height, chest girth, leg length, body mass index, vertical jump, side-to-side jump, back strength, grasping power, trunk extension, standing trunk flexibility, 50 m dash, long jump, handball throwing, and chinning.The body weight, chest girth, and body mass index was significantly lower in girls with scoliosis. As to physical strength and motor ability, only standing trunk flexibility was significantly lower in girls with scoliosis.Tuberculosis examination radiographs were useful for scoliosis screening in high schools. We found that girls with scoliosis were thinner. We think it is necessary for school teachers to pay more attention to their students' life style.

We encountered 4-year-old boy who developed paroxysmal cold hemoglobinuria (PCH) in the middle of August. He was admitted due to progressive jaundice and pallor following fever and nausea. Laboratory data revealed severe anemia, increased serum indirect bilirubin and LDH, and decreased serum haptoglobin. Direct/indirect Coombs tests were positive. These findings yielded a diagnosis of autoimmune hemolytic anemia. Serological test for syphilis was negative. The patient's symptoms and signs promptly subsided after treatment with prednisolone, which was started on the 2nd hospital day. The patient has been in a disease-free state for 16 months without any medication. After discharge, he was finally given a diagnosis of PCH because a Donath-Landsteiner test was positive. The antibody belonged to an IgM subclass and showed anti-I specificity. Considering that development of PCH is common in winter, this case was unique because it developed in August. We speculated that exposure to a cool air-conditioned atmosphere prior to hospitalization and the cooling mechanism of the body after admission were involved in the summer onset of PCH and its prolonged clinical course.

We describe a boy with Fanconi anemia (FA) who developed acute lymphoblastic leukemia (ALL) (FAB-LI) followed by acute myeloid leukemia (AML) (FAB-M5) at relapse. The patient was diagnosed with early pre-B-cell ALL without preceding aplastic anemia and was treated with ALL-oriented chemotherapy which included doxorubicin (a total dose of 140 mg/m(2) administered), which is a topoisomerase II inhibitor. Complete remission was obtained, but after 38 weeks AML developed. The karyotype of ALL cells at diagnosis showed 46,XY, and that of AML cells at relapse was 46,XY, t(11;16)(q23;p13). An MLL gene rearrangement and MLL-CBP chimeric mRNA were found in AML, but not in ALL. A diagnosis of FA was confirmed by an increased number of chromosomal breaks and rearrangements in peripheral blood lymphocytes cultured with mitogen in the presence of mitomycin C. We conclude that this FA patient developed ALL followed by a therapy-related t(11;16)-AML resulting in an MLL-CBP fusion. Further examination of such patients would shed light on leukemogenesis in FA patients. Genes Chromosomes Cancer 27:264-269, 2000.

The antitumor efficacy of a combination of Nedaplatin (NDP) with 5-fluorouracil (5-FU) was evaluated using human squamous carcinomas in vivo. Because NDP was developed as a second generation platinum complex, we also compared the antitumor activity of NDP with 5-FU with that of Cisplatin (CDDP) with 5-FU.5-FU was injected daily for five days and either NDP or CDDP was injected once via the tail vein of mice implanted with KB3-1, OCC-1-JCK, LJC-1-JCK and Ma44 human squamous carcinomas. In some experiments, continuous administration of 5-FU using an osmotic pump was utilized.The sequential administration of 5-FU prior to NDP or CDDP (FN or FC therapy) resulted in enhanced inhibition of tumor growth in comparison with NDP, CDDP or 5-FU monotherapy against KB3-1, OCC-1-JCK and LJC-1-JCK squamous carcinomas. The combination of FN treatment was synergistic and as effective as that of FC treatment. FN treatment with continuous infusion of 5-FU using an osmotic pump, also led to enhanced tumor growth inhibition and prolonged survival against Ma44 squamous carcinoma.The results demonstrated the antitumor efficacy NDP with 5-FU against four human squamous carcinoma xenografts and suggested the clinical effectiveness of FN treatment.

A 5-year-old male patient with asymptomatic optic neuritis and mumps postinfectious encephalitis or acute disseminated encephalomyelitis is reported. Magnetic resonance imaging (MRI) with a short inversion time inversion recovery sequence was valuable in detecting clinically silent lesions of the unilateral right optic nerve in addition to visual evoked potentials. Evidence of concurrent optic neuritis was useful for detecting more extensive neurological involvement, leading to the diagnosis of mumps postinfectious encephalitis. A systematic MRI study should be performed in children with mumps encephalitis, regardless of appreciable clinical deficits.

BACKGROUND AND PURPOSE: Pelizaeus-Merzbacher's disease (PMD) is caused by mutations in the proteolipid protein (PLP) gene. Recent studies have shown that an increased PLP dosage, resulting from total duplication of the PLP gene, invariably causes the classic form of PMD. The purpose of this study was to compare the MR findings of PMD attributable to PLP duplication with those of PMD arising from a missense mutation. METHODS: Seven patients with PMD, three with a PLP missense mutation in either exon 2 or 5 (patients 1–3), and four with PLP duplication (patient 4 having larger PLP duplication than patients 5–7) were clinically classified as having either the classic or connatal form of PMD. Cerebral MR images were obtained to analyze the presence of myelination and T1 and T2 shortening in the deep gray matter. Multiple MR studies were performed in six of the seven patients to analyze longitudinal changes. RESULTS: Four patients (patients 1–4) were classified as having connatal PMD, whereas the other three (patients 5–7) were classified as having classic PMD. Myelination in the cerebral corticospinal tract, optic radiation, and corpus callosum was observed in three cases of classic PMD with PLP duplication. In patient 4, myelination extended to the internal capsule, corona radiata, and centrum semiovale over a 3-year period. No myelination was observed in three PMD cases with a PLP point mutation. T2 shortening in the deep gray matter was recognized in all patients with PMD. CONCLUSION: The presence of myelination in the cerebral corticospinal tract with diffuse white matter hypomyelination on MR images could be a marker for PMD with PLP duplication. It is suggested that progression of myelination may be present in connatal PMD with large PLP duplication.

We examined the antiangiogenic and antitumor efficacy of a newly-developed matrix metalloproteinase (MMP) inhibitor, BPHA (N-biphenyl sulfonyl-phenylalanine hydroxiamic acid). BPHA potently inhibits MMP-2, 9 and 14 but not MMP-1, 3 or 7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMP tested. Daily oral administration of BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth and liver metastasis, whereas (-)BPHA did not. These results demonstrate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential without hematotoxic effect or loss of body weight.

Summary: MR imaging depicted vertically oriented folia instead of the normal horizontal folial pattern, hypoplastic cerebellar vermis, fusion of the inferior posterior cerebellum, and probable polymicrogyria in the superior cerebellar hemispheres in a child with hypotonia, nystagmus, ataxia, and psychomotor retardation. We propose that this newly discovered cerebellar malformation be added to the list of malformations associated with aplasia or hypoplasia of the cerebellar vermis, such as Dandy-Walker malformation, Joubert syndrome, tectocerebellar dysraphia, and rhombencephalosynapsis.

We reported a 15-year-old boy with hypertensive encephalopathy secondary to nephrotic syndrome (minimal change). Based on his clinical symptoms such as anasarca and oliguria, and laboratory data, he was diagnosed as having nephrotic syndrome, and treated with corticosteroid. On the 6th days of admission, he experienced multifocal seizures with hypertension. Cranial T2-weighted MR imaging revealed multiple small cortical and subcortical high intensity lesions in the parieto-occipital lobes, and bilateral round shaped lesions in the cerebellar white matter. He was successfully treated with antihypertensive and anticonvulsant drugs. One year later, a follow up MR imaging revealed almost complete resolution of the brain lesions. MR imaging is a useful modality to demonstrate the lesions characteristic of hypertensive encephalopathy, which are distributed in the areas of posterior circulation.

The antiangiogenic activity and antitumor efficacy of a newly developed matrix metalloproteinase (MMP) inhibitor were examined. N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA) potently inhibits MMP-2, -9, and -14, but not MMP-1, -3, or -7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMPs tested. Daily oral administration of 200 mg/kg BPHA, but not (-)BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth, and liver metastasis. The growth inhibition activity of BPHA was 48% and 45% in a B16-BL6 melanoma and F2 hemangio-endothelioma model, respectively. BPHA also showed 42% inhibition of the liver metastasis of C-1H human colon carcinoma cells. These results indicate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential.

D-2-Hydroxyglutaric aciduria has been observed in patients with extremely variable clinical symptoms, creating doubt about the existence of a disease entity related to the biochemical finding. An international survey of patients with D-2-hydroxyglutaric aciduria was initiated to solve this issue. The clinical history, neuroimaging, and biochemical findings of 17 patients were studied. Ten of the patients had a severe early-infantile-onset encephalopathy characterized by epilepsy, hypotonia, cerebral visual failure, and little development. Five of these patients had a cardiomyopathy. In neuroimaging, all patients had a mild ventriculomegaly, often enlarged frontal subarachnoid spaces and subdural effusions, and always signs of delayed cerebral maturation. In all patients who underwent neuroimaging before 6 months, subependymal cysts over the head or corpus of the caudate nucleus were noted. Seven patients had a much milder and variable clinical picture, most often characterized by mental retardation, hypotonia, and macrocephaly, but sometimes no related clinical problems. Neuroimaging findings in 3 patients variably showed delayed cerebral maturation, ventriculomegaly, or subependymal cysts. Biochemical findings included elevations of D-2-hydroxyglutaric acid in urine, plasma, and cerebrospinal fluid in both groups. Cerebrospinal fluid gamma-aminobutyric acid was elevated in almost all patients investigated. Urinary citric acid cycle intermediates were variably elevated. The conclusion of the study is that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with at least two phenotypes.

Augmented antitumor activity was demonstrated in combination chemotherapy of Nedaplatin (NDP) or Cisplatin (CDDP) with 5-fluorouracil (5-FU) against murine lung carcinoma and human squamous carcinoma from head and neck. Either NDP or CDDP (1/4 to 1 maximum tolerated dose; MTD) was injected once and 5-FU (1/16 MTD) was injected daily for five days via tail vein to tumor-implanted mice. The sequential administration of either NDP or CDDP prior to 5-FU (NF or CF therapy) showed severe body weight loss followed by the toxic death of tumor-bearing mice at the MTD of NDP or CDDP. In contrast, the reverse sequence of the treatment, that is, 5-FU prior to NDP or CDDP (FN or FC therapy), resulted in the synergistically enhanced inhibition of tumor growth and the prolonged survival in comparison with NDP, CDDP or 5-FU monotherapy. The antitumor activities of the combinations of CDDP with 5-FU was less than those of the combination of NDP with 5-FU. Especially, at the MTD of NDP in FN therapy, long-term tumor-free survival was frequently observed. Thus, FN therapy was thought to be the most efficient regimen in combination of NDP with 5-FU as a clinical therapy.

This paper describes a control method for a three-phase five-level diode-clamp pulse width modulation (PWM) converter considering DC-link capacitor voltage balancing problem. The proposed control circuit uses multiband hysteresis comparators (MHCs) to simplify the control of the main circuit. The DC-link capacitor voltage balancing problem is solved by changing the shape of the MHC. The proposed method can (1) overcome voltage imbalance at the DC-link capacitors; (2) achieve a unity power factor; (3) generate nearly sinusoidal input currents; and (4) regenerate electric power back to the power system. Simulation and experimental results demonstrate the validity of the proposed method.

D-2-Hydroxyglutaric aciduria has been observed in patients with extremely variable clinical symptoms, creating doubt about the existence of a disease entity related to the biochemical finding. An international survey of patients with D-2-hydroxyglutaric aciduria was initiated to solve this issue. The clinical history, neuroimaging, and biochemical findings of 17 patients were studied. Ten of the patients had a severe early-infantile-onset encephalopathy characterized by epilepsy, hypotonia, cerebral visual failure, and little development. Five of these patients had a cardiomyopathy. In neuroimaging, all patients had a mild ventriculomegaly, often enlarged frontal subarachnoid spaces and subdural effusions, and always signs of delayed cerebral maturation. In all patients who underwent neuroimaging before 6 months, subependymal cysts over the head or corpus of the caudate nucleus were noted. Seven patients had a much milder and variable clinical picture, most often characterized by mental retardation, hypotonia, and macrocephaly, but sometimes no related clinical problems. Neuroimaging findings in 3 patients variably showed delayed cerebral maturation, ventriculomegaly, or subependymal cysts. Biochemical findings included elevations of D-2-hydroxyglutaric acid in urine, plasma, and cerebrospinal fluid in both groups. Cerebrospinal fluid γ-aminobutyric acid was elevated in almost all patients investigated. Urinary citric acid cycle intermediates were variably elevated. The conclusion of the study is that D-2- hydroxyglutaric aciduria is a distinct neurometabolic disorder with at least two phenotypes.

The antitumor efficacy of the combination of Nedaplatin (NDP) with cyclophosphamide (CPM) was evaluated using murine and human carcinoma implanted mice. NDP was developed as a second generation platinum complex. Because of its superior antitumor activity and lower nephrotoxicity than Cisplatin (CDDP), we also compared the antitumor activity of NDP plus CPM with that of CDDP plus CPM.Various doses of NDP or CDDP (1/4 to 1 maximum tolerated dose; MTD) and CPM (58 or 78 mg/kg) were injected once via the tail vein into mice implanted with Lewis murine lung carcinoma or Ma44 human lung carcinoma.Simultaneous administration of NDP or CDDP with CPM resulted in synergistically enhanced inhibition of tumor growth and prolonged survival in comparison with therapy using only NDP, CDDP or CPM. The combination therapy of NDP with CPM showed a superior survival effect with frequent long-term tumor-free survivors in comparison to that of CDDP plus CPM without increased hematotoxicity. The augmented antitumor efficacy of the combination of NDP with CPM was also demonstrated against Ma44 human lung carcinoma.The results suggested the effectiveness of using a combination of NDP with CPM for clinical therapy.

The present study investigated the effects of the catecholamine-depleting drug reserpine on cellular Ca2+ storage and mobilization in rat submandibular acinar cells. Adult rats received seven daily injections of reserpine (0.5 mg/kg) and inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization were measured in isolated submandibular acinar cells. Ultrastructural analysis demonstrated a significant reduction in rough endoplasmic reticulum (ER) and a dramatic accumulation of secretory granules in the cells of treated animals. Reserpine reduced acetylcholine (ACh)-stimulated IP3 formation by 46% and the initial increase in cytosolic Ca2+ concentration ([Ca2+]i) in response to ACh or thapsigargin was reduced by 21 and 56%, respectively. While norepinephrine (NE) did not induce significant IP3 formation, the [Ca2+]i response to NE was increased 360% by reserpine treatment. Reserpine treatment also enhanced the sustained [Ca2+]i increase following these stimuli. After stimulation with ACh or NE, exposure to ionomycin caused a further elevation in [Ca2+]i which was significantly larger in the cells of treated animals. After exposure to agonist + ionomycin, addition of monensin induced a third increase in [Ca2+]i which was significantly larger in cells of reserpine-treated animals. While capacitative Ca2+ entry was not altered, NE-activated Ca2+ influx was abolished after reserpine treatment. Reserpine treatment therefore alters IP3-sensitive and insensitive Ca2+ stores, non-capacitative Ca2+ influx and active Ca2+ transport in submandibular acinar cells of rats.

We studied the location of the electric generator of photoparoxysmal discharges using a scalp-skull-brain dipole tracing (DT) method. By this method, the location of epileptic discharges on each scalp EEG was calculated as an equivalent current dipole (ECD) in 8 cases of epilepsy who had photoparoxysmal discharges. We divided these cases into groups A and B (4 cases each), comprising of patients with and without visually-induced seizures, respectively. The ECDs of the 3 cases in group A corresponded to the small area adjacent to the lateral geniculate nucleus on MRI superimposed. On the other hand, the ECDs of all cases in group B located at the corpus callosum. This study suggests the pathways of epileptic discharges from the epileptic focus are different between two groups. It is supposed that neural activity of the lateral geniculate nucleus might be responsible for the generator mechanism of photoparoxysmal discharges which evokes photosensitive epilepsy.

A joint national survey on cord blood transplantation (CBT) was conducted in Japan and 18 sibling CBTs were reported. Diseases of the patients were leukemia (ten), neuroblastoma (one), bone marrow failure (four) and inborn errors of metabolism (three). A volume of 50-141 ml of cord blood containing 27-197 x 10(7) nucleated cells was collected from sibling infants soon after delivery. HLA antigens were identical in 14 and one to three antigens mismatched in four. Engraftment of donor cord blood was achieved in 17 cases. Autologous hematopoiesis was recovered in one case. Days of engraftment were 13-29 days (median 19 days) for neutrophils (500/microliter), 18-67 days (median 30 days) for reticulocytes (2%) and 21-96 days (median 46 days) for platelets (50 x 10(3)/microliter). Acute GVHD was grade 0 in seven cases, grade I in five cases and grade II in one case in HLA-identical pairs, but became grade II in two cases and grade III in two cases in HLA-mismatched pairs. Chronic GVHD of limited type developed in two out of 17 evaluable cases, however both responded to immunosuppressive therapy. Altogether, 14 out of 18 patients are currently surviving 4-27 months following transplantation. Probabilities of overall survival and disease free survival were estimated to be 77.0 and 71.8% using Kaplan-Meier tests. These findings suggest the feasibility of cord blood transplantation from sibling donors and the possibility of unrelated cord blood transplantation. A cord blood banking system is necessary for the universal use of cord blood stem cells from unrelated donors.

The elevated exogenous-methionine dependency of tumors for growth has been observed in all major cancer cell types. We have previously cloned a methioninase (rMETase) from Pseudomonas putida to deplete methionine. Growth inhibition followed by apoptotic cell death was induced by treatment of tumor cells with rMETase in vitro. A single i.p. injection of 300 units of rMETase can lower the serum methionine level in the mice from 70 microM to less than 1 microM within 2 h and maintain this depleted level for 8 h. Repeated dosing of rMETase of tumor-bearing mice could be administered without acute immune-hypersensitivity. rMETase treatment demonstrated growth inhibitory activity against human tumors in nude mice, including those which were multiple drug-resistant. No body weight loss or hematotoxicity, except a slight anemia, was found throughout the therapy. The combined treatment of the Lewis lung carcinoma with a fixed rMETase dose and increasing doses of 5-fluorouracil (5-FU) resulted in a dose-dependent enhanced antitumor efficacy for survival as well as tumor growth inhibition. Thus, methionine depletion by rMETase potentiates the antitumor efficacy of 5-FU. The data presented in this report thus indicate that rMETase is active alone, is synergistic in combination with 5-FU, and has negligible toxicity suggesting a novel clinical approach for effective cancer therapy.

A 48-year-old woman was admitted to our hospital because of abnormal shadow on the chest X-ray. Chest contrast CT scan showed roundly mass in the posterior mediastinum which were combined with and without contrast elements, and chest MRI (T2 weighted) showed high signal intensity. These features suggested mediastinal cyst or extralobar sequestration. The operation was performed through left 6th intercostal thoracotomy. Two different lesions connected to the mediastinum were confirmed, a cystic tumor and small accessory lung. The former was diagnosed as bronchogenic cyst and the latter as extralobar pulmonary sequestration.

Augmented antitumor activity in combination chemotherapy of Nedaplatin (NDP) or Cisplatin (CDDP) with Etoposide (ETP) against murine and human lung cancer cells was demonstrated. NDP and CDDP were administered once and ETP daily for five days via tail vein. In the mice bearing Lewis lung carcinoma, a combination of NDP and ETP resulted in synergistically enhanced inhibition of tumor growth, and prolonged survival in comparison with either NDP or ETP alone. NDP showed a more potent combination effect with ETP than CDDP did. These effects were also demonstrated in human lung cancer cell lines. Although body weight loss was enhanced by the combination of NDP or CDDP with ETP, it was tolerable, and no significant difference between NDP plus ETP and CDDP plus ETP was observed. Thrombocytopenia was not enhanced in the combined treatment of NDP with ETP. These results suggest the usefulness of the combination of NDP with ETP as a clinical therapy for lung cancer.

We report a 1-year-old boy with infantile lymphoblastic leukemia in first complete remission who received a cord blood stem cell transplantation (CBSCT) from an HLA identical sibling. We collected 120 ml of cord blood when his brother was born, which contained 4.2 x 10(8) mononuclear cells (4.2 x 10(7)/kg) and 3.1 x 10(5) CFU-GM (3.1 x 10(4)/kg). One month prior to transplantation, he showed persistent fever and liver dysfunction, and was finally diagnosed as having primary cytomegalovirus (CMV) infection which was demonstrated by elevation of serum anti-CMV-IgM. The administration of ganciclovir dramatically improved the clinical symptoms and abnormal laboratory findings, and was continued up to 1 month after transplantation to suppress the CMV reactivation. The preconditioning regimen consisted of busulfan (16 mg/kg/4 days) and cyclophosphamide (120 mg/kg/2 days), and cyclosporin A (CyA) alone was used for graft-versus-host disease (GVHD) prophylaxis. Fever suspicious of grade I GVHD developed on day 19, but subsided by increasing the dose of CyA. The WBC and platelet counts reached greater than 1,000/microliter and 50 x 10(3)/microliter on days 12 and 42, respectively. It is now at 13 months since transplantation, and he remains in a disease free state.

Magnetization properties of Bi(Pb)2212 single crystals were found to be systematically improved by increasing Pb-doping and oxygen doping levels. At the liquid nitrogen temperature, the heavily Pb- doped and moderately carrier overdoped sample exhibited the highest J c and H irr , which were even higher than the Pb-ion irradiated Bi2212. The mechanism of the improved flux pinning properties in the present system was explained by the cooperative effects of lowered electromagnetic anisotropy and generation of temperature- and field-induced pinning centers. The heavily Pb-doped Bi2212/Ag composite tapes were successfully synthesized by melt-solidification method under a reduced atmosphere and their magnetic properties were much better compared to the conventional Bi2212/Ag tapes.

We described a family of dentatorubral-pallidoluysian atrophy (DRPLA). The mother presented with cerebellar ataxia at 35 years of age and thereafter her neurological symptoms became exacerbated. Her daughter had mental retardation during the preschool period and epilepsy at 10 years. Her son presented with epilepsy at 14 years. Their clinical phenotypes demonstrated maternal anticipation in this family. Genetical analysis of their DNA revealed CAG repeat expansion of the DRPLA gene, the number of which was 51 (mother), 65 (her daughter), and 53 (her son). MR imaging showed disappearance of T, shortening of the red nucleus in the mother and her daughter in contrast to the normal appearance in her son. MR imaging was effective in evaluating neuropathological changes in the DRPLA patients.

We describe a patient who presented with isolated retrograde amnesia of 2-year duration after recovery from viral encephalitis. The patient was a 29-year-old right-handed male dentist and was admitted to our hospital with a complaint of generalized convulsion. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. Neuroradiological examinations (X-ray CT, MRI and 123I-IMP SPECT) revealed no significant abnormality. Immunological method showed no specific increase of viral antibody titers. However, with a tentative diagnosis of viral encephalitis, administration of acyclovir was started. After 3 weeks he became comprehensive, and several kinds of neuropsychological tests were performed. His intelligence and immediate memory were normal, and his procedural memory of dentist was intact. On the other hand, he could not recall any information about events, both personal and public, occurred within 2 years before the onset of present illness. His autobiographical memory disorder was also demonstrated using a series of weekly comic. In isolated retrograde amnesia following viral encephalitis like this case, memory of relatively short time duration, acquired prior to the onset of present illness, tend to be disturbed.

The outcome of cerebrovascular disease in the elderly, defined as persons 70 years of age and over, and in the non-elderly, those under 70 years, was compared. Fifty-one consecutive elderly and 156 non-elderly patients were studied. The patients in each group were classified according to type of cerebrovascular event: intracerebral hemorrhage, cerebral infarction, or subarachnoid hemorrhage. Patients were evaluated by using the Glasgow Outcome Scale both at the time discharge and 6 months later. The elderly patients were more severely disabled at the time of discharge than the non-elderly patients. The number of patients evaluated as "good recovery" or "moderate disability" had increased at the 6-month follow-up examination in the non-elderly patients, whereas the condition of many of the elderly patients had declined. The death rate of the elderly at the time of discharge and 6 months later was 17.6% and 52.0%, respectively, as opposed to 13.5% and 18.8% in the non-elderly group. The outcome of cerebrovascular disease was much worse in the elderly patients than in the non-elderly patients. Patient age and status at discharge were important predictors of the clinical course.

PURPOSE: To analyze the properties and embolic effect of microfibrillar collagen (MFC), Gelfoam powder, and polyvinyl alcohol (PVA) materials that are used in embolization procedures in the head and neck. METHODS: The shape and surface of these embolic agents were examined with scanning electron microscopy and phase-contrast microscopy. The mean number of areas of T2-weighted high signal intensity was measured on MR images in a rat embolization model to estimate the embolic effect. RESULTS: By scanning electron microscopy and phase-contrast microscopy, MFC appears fibriform and has various sizes and an irregular surface. Gelfoam is of uniform size and has a smooth surface. PVA materials are granulated and have a rough surface. MFC is somewhat suspendable and its shape changes moderately after suspension. Gelfoam is very suspendable and its shape changes rapidly. PVA showed only mild swelling. The embolic effect of MFC was the lowest of the materials examined. Large PVA particles (250 to 500 microns) showed a lesser embolic effect than Gelfoam or small PVA particles (50 to 150 microns) or medium-sized PVA particles (150 to 250 microns). No significant differences were observed among the embolic effects of Gelfoam, small PVA particles (50 to 150 microns), and medium PVA particles (150 to 250 microns). CONCLUSIONS: MFC and large PVA particles (250 to 500 microns) should be used for embolization of vascular anatomy involving potentially dangerous anastomoses. Gelfoam, PVA particles of 150- to 250-micron diameter, and PVA particles of 50- to 150-micron diameter are adequate for embolization involving homogeneous and peripheral anatomy.

The purpose of this study was to assess the utilization of tuberculosis examination radiographs for scoliosis screening in high schools, for early diagnosis and early treatment of adolescent idiopathic scoliosis in the health management of students. We examined 2,068 first year high school students (1,058 males and 1,010 females) in Wakayama Prefecture, who had chest X-ray photographs taken between 1994 to 1996, and 24 cases (3 males and 21 females) were identified with scoliosis of more than 10 degrees Cobb angle. Fifteen of the cases received further examinations in the hospital, and were diagnosed with definite adolescent idiopathic scoliosis, while 6 cases who did not receive hospital examinations had their abnormality of the spine noted in past periodic health examinations. In the remaining 3 students scoliosis could not be confirmed. The correlation coefficient between the Cobb angle measured in the tuberculosis examination radiographs and in the total spinal radiographs taken by the hospital was 0.815 (p0.001). These results suggest that the tuberculosis examination radiographs may be useful for scoliosis screening in high schools.

In this paper, we report an independent catalyst heating system on the Pt-catalyst metal organic vapor phase epitaxy (MOVPE) for Indium nitride (InN) growth, and the dependence of the NH3 decomposition rate on the Pt catalyst temperature (RT to 1000 °C) using a quadrupole mass spectrometer (Q-MS). When the catalyst temperature is increased above the growth temperature of InN, the NH3 decomposition rate is enhanced. The grain size of InN becomes larger and the full width at half maximum (FWHM) of the X-ray rocking curve (XRC) was drastically decreased. The increase of N atoms results in the incorporation of nitrogen into the InN layer and thus improves the crystal quality of InN. However, active H increases sharply when the catalyst heater temperature is over about 850 °C. Therefore, a great improvement in the crystal quality of InN film is expected by optimizing the growth condition including a catalyst temperature not exceeding 850 °C.

Azithromycin (AZM) was studied for its clinical efficacy in pediatric infections. The study on AZM was carried out in 43 patients whose diagnoses were given as follows: pharyngitis in five cases, tonsillitis in one, bronchitis in four, pneumonia in four, Mycoplasma pneumonia in 14, scarlet fever in nine, impetigo in four, pyodermia in one and Campylobacter enteritis in one. The patients received AZM once daily at 1.6 approximately 20.0 mg/kg body weight for three to five days. Effectiveness of AZM was evaluated in 39 cases and the drug was rated "excellent" in 15, "good" in 19, "fair" in one, "poor" in four, resulting in an efficacy rate of 87.2%. Twenty bacterial isolates were identified as causative isolates in 19 patients: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Campylobacter jejuni and Mycoplasma pneumoniae. AZM eradicated 16 isolates but four persisted after therapy. One patient complained of loose stool, while two patients were found with decreases in white blood cell counts, and seven showed increases in eosinophils. However, no serious case of adverse event was reported.