Fulminant ulcerative colitis associated with both masseter muscle myositis and immunoglobulin M nephropathy.
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Adolescent↗
Biomedical subjects
H Niimi
Publications and source records attributed to H Niimi.
The vertical displacement sign: a technique for differentiating between left and right ribs on the lateral chest radiograph.
AIM: To evaluate a new approach to the differentiation of the right and left ribs, the vertical displacement sign, and to compare its efficacy with the big rib sign. MATERIALS AND METHODS: One hundred and nine lateral chest radiographs that clearly showed both the gastric air bubble sign and the cardiac silhouette sign were retrospectively reviewed by two radiologists. Each study was evaluated by consensus. Each radiograph was assessed for suitability of reading with each technique. Suitable radiographs were then reviewed using both the big rib sign and vertical displacement sign independently. RESULTS: Applicability of the vertical displacement sign [107 of 109 (98%)] was greater than that of the big rib sign [95 of 109 (87%)] (P = 0.0017). The accuracy of the vertical displacement sign [105 of 107 (98%)] was higher than that of the big rib sign [74 of 95 (78%)] (P < 0.001). CONCLUSION: The vertical displacement sign seems to be a reliable technique for the differentiation of right and left ribs on the lateral chest radiograph and can be used as a complementary technique when the big rib sign is not applicable.
Adult↗
Molecular defects in achondroplasia and the effects of growth hormone treatment.
Achondroplasia is a common skeletal dysplasia with severe growth retardation. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR3) were identified in patients with achondroplasia. In the present study, 70 of 75 Japanese patients with achondroplasia were found to have a G1138A mutation in FGFR3, and two patients had a G1138C mutation. Growth hormone therapy was given to 145 patients with achondroplasia. Significant dose-dependent effects on skeletal growth were obtained, with no long-term adverse effects.
Achondroplasia↗
The clinical usefulness of liquid human growth hormone (hGH) (Norditropin SimpleXx in the treatment of GH deficiency.
Human growth hormone (hGH) is an essential therapeutic drug for the treatment of GH deficiency. The development of recombinant GH using a pen injection system has enabled easy and safe treatment of GH-deficient patients; however, the process of dissolving hGH in the powder form is complicated and dangerous. In this study, we investigated the usefulness of a newly developed liquid form of hGH (Norditropin((R)) SimpleXx(TM)) in the treatment of 51 patients with GH deficiency. Fifteen previously untreated patients with GH deficiency were treated with liquid hGH (group A), and 36 patients who had previously used hGH in the powder form were changed to the liquid form (group B). Both groups were treated with liquid hGH 0.5 IU/kg per week for 6 months. The growth rate of patients in group A increased from 4.0 +/- 2.4 cm/year to 9.2 +/- 2.9 cm/year. The patients in group B continued to grow at the same rate as before using the liquid hGH therapy. Questionnaires to the patients in group B demonstrated that 85% preferred the convenience of using the new liquid form of hGH. Our results indicate that liquid hGH has similar efficacy to that of powder hGH, but its improved convenience may have a beneficial effect on patient compliance.
Body Height↗
Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease.
The molecular mechanism involved in pulmonary vascular disease (PVD) associated with congenital heart disease (CHD) remains uncertain. Evidence suggesting that angiotensin converting enzyme plays an important role in pulmonary vascular pathology led us to hypothesize that mast cell chymase, another angiotensin I converting enzyme, also had the potential to contribute to the development of PVD in CHD. Twenty-three patients 3 mo to 45 yr of age with atrial or ventricular or both septal defects with increased pulmonary arterial blood flow and pressure, with pulmonary vascular resistance ranging from 1.3 to 8.1 units/m(2), were studied. Mast cells and mast cell chymase were immunohistochemically identified in the lung biopsy tissues obtained during corrective surgery. There was a significant difference in numbers of total mast cells between patients (n = 23) and control subjects (n = 10) with normal pulmonary circulation (p < 0.01). Moreover, chymase-containing mast cells in the lung tissues of patients with CHD showed striking differences from those of control subjects. In the patients, 72% of lung mast cells contained chymase, compared with only 15% in control subjects (p < 0.0001). Chymase-containing mast cells predominantly appeared in the media and adventitia of vessel walls. Importantly, angiotensin II was immunohistochemically detected in perivascular lesions where chymase was present, but not in the lesions where chymase was sparsely seen. Furthermore, the number of chymase-containing mast cells was correlated with pulmonary vascular resistance (r = 0.64). These findings suggest a possible role of mast cell chymase in the development of early-stage PVD in patients with CHD.
Adult↗
No enzyme activity of 25-hydroxyvitamin D3 1alpha-hydroxylase gene product in pseudovitamin D deficiency rickets, including that with mild clinical manifestation.
Pseudovitamin D deficiency rickets (PDDR) is an autosomal recessive disorder caused by defect in the activation of vitamin D. We recently isolated 25-hydroxyvitamin D3 1alpha-hydroxylase gene and identified four homozygous inactivating missense mutations in this gene by analysis of four typical cases of PDDR. This disease shows some phenotypic variation, and it has been suspected that patients with mild phenotypes have mutations that do not totally abolish the enzyme activity. To investigate the molecular defects associated with the phenotypic variation, we analyzed six additional unrelated PDDR patients: one with mild and five with typical clinical manifestation. By sequence analysis, all six patients were proven to have mutations in both alleles. The mutations varied, and we identified four novel missense mutations, a nonsense mutation, and a splicing mutation for the first time. The patient with mild clinical symptoms was compound heterozygous for T321R and a splicing mutation. The splice site mutation caused intron retention. Enzyme activity of the T321R mutant was analyzed by overexpressing the mutant 1alpha-hydroxylase in Escherichia coli cells to detect the subtle residual enzyme activity. No residual enzyme activity was detected in T321R mutant or in the other mutants. These results indicate that all of the patients, including those of mild phenotype, are caused by 1alpha-hydroxylase gene mutations that totally abolish the enzyme activity.
25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
Outcome of a baby born from a mother with acquired juvenile hypothyroidism having undetectable thyroid hormone concentrations.
We report a baby born from a mother with strongly positive thyroid stimulation blocking antibody (TSBAB) and nearly undetectable T4 level. This case is a unique model of nearly complete absence of thyroid hormones during fetal and early neonatal life in humans. The infant girl was born by cesarean section, because of fetal bradycardia, after 41 weeks gestation and received mechanical ventilation for 3 days. The TSH level was more than 120 microU/mL in the neonatal thyroid screening. At age 17 days, the results of a thyroid function study showed undetectable free T3 and free T4 concentrations, TSH 550 microU/mL, and TSH receptor antibody (TRAB) 87%. Thyroxine at a dose of 30 microg/day was started at age 17 days. The patient required thyroxine treatment until age 8 months. The brain magnetic resonance image at age 2 months revealed reduced brain size. Her auditory brain stem response was absent at age 2 months. The audiogram at age 4 yr revealed sensorineural deafness of 70 dB. When she was 6 yr of age, motor development remained the same as that at age 4 months. Her height was 106 cm (- 1.5 SD). The results of thyroid function study of the mother 23 days after delivery showed undetectable free T3 and free T4, TRAB 84%, and TSBAB 83%. In conclusion, the outcome of severe thyroid hormone deficiency in utero and early in human neonatal life was normal physical growth, fetal distress resulting in cesarean section, difficulty in the onset of breathing, permanent deficit in auditory function, brain atrophy, and severely impaired neuromotor development despite the start of an adequate dose of thyroxine replacement during the neonatal period.
Adult↗
[A case of hypertensive encephalopathy secondary to nephrotic syndrome].
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.
Adolescent↗
Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets.
BACKGROUND: Pseudovitamin D-deficiency rickets is characterized by the early onset of rickets with hypocalcemia and is thought to be caused by a deficit in renal 25-hydroxyvitamin D3 1alpha-hydroxylase, the key enzyme for the synthesis of 1alpha,25-dihydroxyvitamin D3. METHODS: We cloned human 25-hydroxyvitamin D3 1alpha-hydroxylase complementary DNA (cDNA) using a mouse 1alpha-hydroxylase cDNA fragment as a probe. Its genomic structure was determined, and its chromosomal location was mapped by fluorescence in situ hybridization. We then identified mutations in the 1alpha-hydroxylase gene in four unrelated patients with pseudovitamin D-deficiency rickets by DNA-sequence analysis. Both the normal and the mutant 1alpha-hydroxylase proteins were expressed in COS-1 cells and were assayed for 1alpha-hydroxylase activity. RESULTS: The gene for 25-hydroxyvitamin D3 1alpha-hydroxylase was mapped to chromosome 12q13.3, which had previously been reported to be the locus for pseudovitamin D-deficiency rickets by linkage analysis. Four different homozygous missense mutations were detected in this gene in the four patients with pseudovitamin D-deficiency rickets. The unaffected parents and one sibling tested were heterozygous for the mutations. Functional analysis of the mutant 1alpha-hydroxylase protein revealed that all four mutations abolished 1alpha-hydroxylase activity. CONCLUSIONS: Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene are a cause of pseudovitamin D-deficiency rickets.
25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
Changes in urinary 6beta-hydroxycortisol/cortisol ratio after birth in human neonates.
OBJECTIVE: Urinary 6beta-hydroxycortisol/cortisol (6beta-OHF/C) ratio was measured in human neonates to assess the CYP3A enzyme activity. METHODS: Urinary 6beta-OHF/C ratio was determined on the day of birth in 94 neonates including those born prematurely. In addition, changes in the ratios after birth were also determined in 81 neonates. RESULTS: On the day of birth, a significant positive correlation was found between urinary 6beta-OHF/C ratios and gestational age (r = 0.476) and birth weight (r = 0.283). There was no gender difference in the urinary 6beta-OHF/C ratios in human neonates. Furthermore, delivery modes such as cesarean section and vaginal delivery did not appear to affect the urinary 6beta-OHF/C ratio. The mean ratio of urinary 6beta-OHF/C observed in 39 mature neonates (more than 37 weeks of gestational age) was higher than that observed in adults (16.5 vs 9.9). Within 5 days after birth, the ratio rapidly decreased to less than that in adults. In contrast, the mean ratio of urinary 6beta-OHF/C observed in 42 premature neonates (under 37 weeks of gestational age) was significantly lower than that observed in mature neonates (5.3 vs 16.5) and was virtually unchanged during the 14-days after birth. Therefore, no significant difference was observed in the mean ratio of urinary 6beta-OHF/C between mature and premature neonates at 5 days after birth. CONCLUSION: From these results, it was concluded that on the day of birth, mature neonates might possess a higher activity of CYP3A enzyme compared with premature neonates, and that the CYP3A enzyme activity in mature neonates might be promptly changed at an early stage after birth.
Aryl Hydrocarbon Hydroxylases↗
Expression analysis of two mutant human ornithine transcarbamylases in COS-7 cells.
Ornithine transcarbamylase (OTC) is located in the mitochondrial matrix of the liver and small intestine and catalyzes the second step of the urea cycle. OTC deficiency (OTCD) is an X-linked inborn error of metabolism and causes hyperammonemia. We reported in 1992 the A152V and G195R mutations in patients with OTCD. These mutant OTC cDNAs were prepared by site-directed mutagenesis using the polymerase chain reaction (PCR). The wild-type and mutant cDNAs were transiently expressed in COS-7 cells. The wild-type cDNA gave an OTC activity of 1180 +/- 47 nmol/min per mg protein. The OTC activities of the A152V and the G195R mutants were 3.7% and 2.5% of that of wild-type, respectively. Immunoblot analysis showed that the quantities of OTC proteins in the A152V and G195R mutants were 29% and 12% of that of wild-type, respectively. In pulse-labeling and pulse-chase experiments, the precursor form of OTC was synthesized and processed to the mature form. The A152V mutant OTC was processed to the mature form as rapidly as the wild-type precursor. However, the processed, mature form of the mutant OTC was rapidly degraded, presumably in the mitochondrial matrix. These results indicate that OTCD with the A152V mutation is due both to rapid degradation of the processed, mature form, and to a lower specific activity of the remaining protein.
Animals↗
Adolescent case of Alexander disease: MR imaging and MR spectroscopy.
A 17-year-old male was diagnosed as having Alexander disease from the clinical manifestations (psychomotor deterioration and megalencephaly), neuroradiologic findings (frontal dominant leukodystrophy), and elevation of alpha B-crystallin and heat shock protein 27 in the cerebrospinal fluid. He exhibited increased attenuation on computed tomography and T1 and T2 shortening on magnetic resonance imaging in the bilateral basal ganglia and thalamus. Some paramagnetic substances might be deposited in the basal ganglia and thalamus in the late stage of Alexander disease, at least 8 years after onset.
Adolescent↗
Evaluation of magnetic resonance angiography with selective maximum intensity projection in patients with childhood moyamoya disease.
To determine whether magnetic resonance angiography with selective maximum intensity projection can facilitate the detection of cerebral moyamoya vessels in patients with childhood moyamoya disease, six patients with moyamoya disease (6 to 9 years old) and ten controls (4 to 16 years old) were evaluated by means of high resolution magnetic resonance angiography (matrix 512x384) with/without selective maximum intensity projection, and conventional angiography. In the patients with moyamoya disease, moderate or marked moyamoya vessels were detected but underestimated in 2/12 hemispheres on magnetic resonance angiography without selective maximum intensity projection. On magnetic resonance angiography with selective maximum intensity projection, moyamoya vessels were correctly assessed in 11/12 hemispheres (92%). In the controls, bilateral mild moyamoya vessels were detected in eight of 20 hemispheres (four of ten patients, under 7 years old), which were compatible with normal lenticulostriate arteries. Magnetic resonance angiography with selective maximum intensity projection is an accurate modality for assessing moyamoya vessels in moyamoya disease.
Adolescent↗
Serum thrombopoietin levels in Kawasaki disease.
Kawasaki disease (KD) is an acute febrile vasculitic syndrome with thrombocytosis occurring in childhood. Transient thrombocytosis of KD is sometimes the cause of complications such as coronary aneurysmal thrombosis and myocardial infarction. We have analysed blood TPO levels in KD and found that 26/31 acute-phase KD patients had detectable blood TPO levels (mean 173 pg/ml; range 89-294 pg/ml), which decreased immediately with the elevation of platelet counts in 5/12 patients studied. Elevated serum level of TPO may have an important role for this ill-defined disease.
Child↗
Binding and regulation of thrombopoietin to human megakaryocytes.
Thrombopoietin (TPO, c-Mpl ligand) is considered to play an important role in the regulation of megakaryocytopoiesis and platelet production by activating the cytokine receptor c-Mpl. We have examined the binding of 125I-TPO to the human megakaryocytic cell line, CMK, and to primary human megakaryocytes. Scatchard analysis of TPO binding to its cognate receptor in megakaryocytic cells suggested the existence of a single class of c-Mpl receptors. CMK cells exhibited 1223 receptors per cell with a dissociation constant (Kd) of Kd = 223 pM, whereas primary human megakaryocytes exhibited 12140 receptors per cell and a dissociation constant of Kd = 749 pM. The pretreatment of CMK cells and primary bone marrow megakaryocytes with TPO resulted in a decreased binding of TPO to the c-Mpl receptors. This down-regulation was observed within 3 h and was not inhibited by cycloheximide. Phorbol ester, an activator of protein kinase C, also inhibited TPO binding to the c-Mpl receptors by reducing the number of these receptors. The pretreatment of CMK cells with IL-3, IL-6 and DMSO, all of which induced the differentiation of CMK cells, did not affect the binding of TPO to the c-Mpl receptors. These results suggest an additional mechanism, where protein kinase C may help to regulate the binding of TPO to these cells.
Dimethyl Sulfoxide↗
Computed tomography measurements of overinflation in chronic obstructive pulmonary disease: evaluation of various radiographic signs.
Using computed tomography (CT), the authors determined significant signs of overinflation. Both the pulmonary function tests (PFT) and CT of 74 patients who underwent thoracic surgery for lung cancer (44 with normal lung function, 30 with chronic obstructive pulmonary disease) were reviewed. The following were correlated with forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC): tracheal index (transverse/anteroposterior diameter), sterno-aortic distance, thoracic cage ratios (anteroposterior/transverse diameters) at the tracheal carina (TC1) and 5 cm below (TC2); and depth of the azygoesophageal recess and the presence of intercostal lung bulging (ILB). Significant correlations were observed between FEV1/FVC and tracheal index (r = 0.578, p < 0.0001), TC1 (r = -0.523, p < 0.0001), TC2 (r = -0.533, p < 0.0001), and ILB (r = -0.462, p < 0.0001). Correlations were significant but weak between FEV1/FVC and sterno-aortic distance (r = -0.351, p = 0.0027) and depth of the azygoesophageal recess (r = -0.308, p = 0.0085). Reduced tracheal index and increased anteroposterior diameter of the thoracic cage correlated most significantly with a pulmonary function index of chronic airway obstruction.
Adult↗
Difference in height associated with a translation start site polymorphism in the vitamin D receptor gene.
The function of 1,25-dihydroxyvitamin D3 in bone development is to regulate the differentiation or proliferation of osteoblastic, osteoclastic, and chondrocytic lineage, affecting bone mineralization and linear bone growth. An A(T/C)G substitution exists in the first of the two putative translation initiation sites in exon 2 of the vitamin D receptor (VDR) gene. We studied the relationship between exon 2 polymorphism and height in 90 healthy Japanese female subjects aged 18-20 y, who had attained final height, in 159 healthy Japanese aged 13 y, and 24 children with constitutional short stature aged 6-10 y less than -1.5 SD in height, mostly with parents of normal height. Exon 2 polymorphism was analyzed by PCR-single strand conformation polymorphism, PCR-direct sequencing, and PCR-restriction fragment length polymorphism. The frequency of the exon 2 polymorphism was genotype CC (ACG/ACG), 0.37; genotype CT (ACG/ATG), 0.51; and genotype TT (ATG/ATG), 0.12 in 249 normal subjects. The mean height of female subjects aged 18-20 y with the genotype CT was 160.3 +/- 4.3 cm (mean +/- SD), whereas that with CC was 4.4 cm lower (p < 0.0001), and that with TT was 2.7 cm lower (p = 0.0302). At age 13 y, this trend was observed, and the mean height SD score of subjects with the genotype CT was taller than homozygotes (CC/CT; p = 0.0363 and CT/TT; p = 0.0208) in 159 subjects. Genotype CT in 24 children with constitutional short stature was less frequent than other genotypes (CC, 0.62; CT, 0.21; TT. 0.17) (chi 2 p value, 0.0171). In conclusion, the exon 2 polymorphism affecting the VDR mRNA and protein is one of the major determinants of adult height at least in female Japanese, which was noted at the age of 13 y examined in both sexes.
Adolescent↗
The formation of thyrotropin receptor (TSHR) antibodies in a Graves' animal model requires the N-terminal segment of the TSHR extracellular domain.
Immunization of AKR/N mice with murine fibroblasts, transfected with the TSH receptor (TSHR) and a murine major histocompatibility complex class II molecule having the same H-2k haplotype (but not either alone), induces immune thyroid disease with the humoral and histological features of human Graves', including the presence of two different TSHR antibodies (TSHRAbs): stimulating TSHRAbs, which cause hyperthyroidism; and TSH-binding-inhibiting immunoglobulins. The primary functional epitope for both types of antibodies in Graves' patients is on the N-terminal portion of the extracellular domain of the TSHR, residues 25 to 165; most require residues 90-165 to express TSHRAb activity, as evidenced in studies using chimeras of the TSHR and lutropin-choriogonadotropin receptor (LH-CGR). To evaluate the role of this region of the TSHR in the formation of Graves' TSHRAbs, we immunized AKR/N mice with fibroblasts transfected with three human TSHR chimeras with residues 9-165 (Mc1+2), 90-165 (Mc2), or 261-370 (Mc4) substituted by equivalent residues of the rat LH-CGR. Mice immunized with the Mc1+2 and Mc2 chimeras, with the N-terminal portion of the extracellular domain of the TSHR substituted by LH-CGR residues, did not develop TSHRAbs. Mice immunized with the Mc4 chimera, having a major portion of the C-terminal portion of the extracellular domain of the TSHR replaced by comparable LH-CGR residues, can develop TSHRAbs. The results suggest that the N-terminal segment of the TSHR extracellular domain is not only a critical functional epitope for Graves' TSHRAbs, but it is important also in their formation in a mouse model of Graves' disease.
Animals↗