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Biomedical subjects

H Niimi

Publications and source records attributed to H Niimi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor.

Activating mutations of the extracellular calcium (Ca2+e)-sensing receptor (CaR) gene, mostly in its extracellular domain, can cause both familial and sporadic hypoparathyroidism. We report a Japanese family with severe hypoparathyroidism with pretreatment serum calcium (Ca) levels of 4.9-5.9 mg/dL. The proband presented with a seizure at 6 days of age. Her older brother and mother, who had also experienced seizures and tetany, respectively, likewise had hypoparathyroidism. A heterozygous missense mutation substituting a cysteine for the phenylalanine normally present at codon 788 (F788C) was identified in the CaR's fifth transmembrane domain and was shown to cosegregate with the disease. The mutation was absent in DNA from 50 control subjects. Analysis of the functional properties of the mutant receptor was carried out in transiently transfected HEK293 cells loaded with fura-2 by assessing Ca2+e-evoked increases in the cytosolic calcium concentration (Ca2+i). There was a leftward shift in the concentration-response curve for the mutant receptor [EC50 (effective concentration of Ca2+e producing half of the maximal Ca2+i response, 2.7 +/- 0.1 vs. 4.1 +/- 0.1 mmol/L for the wild-type receptor]. HEK293 cells cotransfected with both the wild-type and mutant CaRs (to mimic the heterozygous state in affected family members) showed an EC50 (3.0 +/- 0.1 mmol/L) similar to that of the mutant CaR alone. Thus, we confirm that 1) a gain of function mutation in the fifth transmembrane domain of the CaR causes severe familial hypoparathyroidism by rendering the receptor more sensitive than normal to activation by Ca2+e; 2) some patients in the family do not experience seizures despite their severe hypocalcemia; and 3) this condition needs to be differentiated from other causes of hypoparathyroidism.

Blotting, Western↗
PubMed1998

Timing for discontinuation of treatment with a long-acting gonadotropin-releasing hormone analog in girls with central precocious puberty. TAP-144SR CPP Study Group.

The optimal timing for discontinuing treatment with a long-acting gonadotropin-releasing hormone (GnRH) analog (TAP-144SR) was investigated in patients with central precocious puberty (CPP). Thirty-five girls with CPP (21 with idiopathic disease and 14 with organic disease) were treated with the analog for 3 to 5 years. No significant differences were seen between the idiopathic and the organic CPP in the suppressive effect of bone maturation. Advancement of bone maturation was noticeably suppressed during the period between bone ages (BA) of 11.0 and 11.9. The height standard deviation score (Ht-SDS) for BA was consistently improved from 10 to 11.5 years of BA, and patients reached peak Ht-SDS at a BA of 11.5 years. The deltaHt-SDS (annual change in Ht-SDS) was noticeably decreased at BA over 12 years in spite of prolongation of the treatment. In the eight patients who have reached final height, the average Ht-SDS was -0.49 at end of the treatment (BA 11.7 years) and the final Ht-SDS was - 1.1 SD, respectively. Predicted adult height at the end of the treatment was significantly higher than the actual final height (P<0.01). The results suggest that a fall in Ht-SDS for BA which usually occurs at approximately 12 years of BA, is an indication for cessation of the treatment with TAP-144SR, and residual growth potential judged solely from BA may be decreased in girls with CPP after discontinuation of the treatment.

Age Determination by Skeleton↗
PubMed1998

Autosomal dominant familial hypoparathyroidism and sensorineural deafness without renal dysplasia.

OBJECTIVE: A family is described which has a unique combination of autosomal dominant hypoparathyroidism and sensorineural deafness without renal dysplasia. CASE REPORT: The proband was a male infant aged 1 month with episodes of seizures for 20 days. He was born at 35 weeks' gestation without asphyxia, weighing 2040 g. His initial calcium, phosphorus and percentage of tubular reabsorption of phosphorus were 6.8 mg/dl (normal range 8.5-10.5 mg/dl), 8.9 mg/dl (normal range 5.5-7.4 mg/dl) and 96.8% (normal range 85-95%) respectively. He had normal values for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D. No abnormalities were found by renal imaging and a routine renal function study. He showed a brisk plasma cAMP increase in response to human PTH-(1-34) infusion. He had normal karyotype 46, XY, without a microdeletion in chromosome 22q11.2 by an in situ hybridization method. Five family members were affected with hypoparathyroidism with sensorineural deafness with autosomal dominant transmission. The study of calcium-sensing receptor and preproPTH gene showed a normal DNA sequence. CONCLUSION: The combination of familial hypoparathyroidism with sensorineural deafness without renal dysplasia is novel and the cause may be distinct from previously reported familial hypoparathyroidism with sensorineural deafness and renal dysplasia.

Adult↗
PubMed1998

Establishment of a new human megakaryoblastic cell line, CMY, with chromosome 17p abnormalities.

A new megakaryoblastic cell line CMY was established from a Down's syndrome patient suffering from acute megakaryoblastic leukemia. The karyotypes of CMY showed deletion of chromosome 17 or the translocation of 17p, whereas the blasts of the patient did not reveal these abnormalities of chromosome 17 by conventional karyotype analysis. Blasts of the patient failed to respond to chemotherapy and complete remission could not be attained. The abnormalities of 17p became progressively predominant in the patient. These results suggest that the blasts of a minor clone which had the abnormalities of chromosome 17p might have existed in the patient from the beginning and CMY was established from the minor clone. Investigation of p53 gene by PCR-SSCP analysis revealed that blasts of the patient showed normal patterns, while CMY showed an abnormally migrating band in exon 5 alone. This result suggests that another novel oncogenic factor(s) besides p53 might be present on chromosome 17p and other tumor suppresser genes need to be studied.

Cell Differentiation↗
PubMed1998

[HRCT findings of pulmonary Mycobacterium avium complex: a comparison with tuberculosis].

Computed tomographic (CT) findings of 70 patients with Mycobacterium avium complex (MAC) disease were analyzed by two chest radiologists and compared with those of 37 patients with Mycobacterium tuberculosis infection. Common CT findings in patients with MAC, included bronchiectasis (97%), small nodules (89%), parenchymal distortion (60%), bronchial wall thickening (56%), consolidation (50%) and cavity formation (49%) and small nodules (86%), bronchiectasis (70%), consolidation (57%) and bronchial wall thickening (51%) in patients with Mycobacterium tuberculosis. Bronchiectasis and parenchymal distortion were significant in patients with MAC compared with Mycobacterium tuberculosis patients. Bronchiectasis involving the RUL, RML, lingula and LLL and small nodules involving the RML were often seen in patients with MAC. Both bronchiectasis and small nodules were commonly observed in multiple lobes in both types of patients. Cavities in MAC infection tended to be thin and smooth walled, and less commonly associated with consolidation. We conclude that CT findings of MAC infection were characterized by widely distributed bronchiectasis and small nodules and/or cavities with thin, smooth walls. These CT findings are one of the keys in differentiating MAC from Mycobacterium tuberculosis.

Adolescent↗
PubMed1998

[Allergen-induced cytokine messenger RNA expression of peripheral blood mononuclear cells in active and remission of food allergy].

Substantial part of patients who suffer from food allergy outgrow their allergic reaction. Moreover the mechanisms of this phenomenon are poorly understood. We studied cytokine mRNA expression in peripheral blood mononuclear cells (PBMC) from children with egg allergy, nine patients on active stage and eight were outgrown, and four healthy controls, by use of reverse transcription polymerase chain reaction. Following ovalbumin (OVA) stimulation in vitro, active patients demonstrated increasing IL-5 mRNA. In comparison, no increasing expression of IL-5 mRNA was observed in outgrown and healthy children. IL-4 and IFN-gamma mRNA expression has no tendency either to increase or to decrease in all three groups. There was no difference of proliferative responses for OVA among these groups suggesting that outgrown patients' PBMC did not fall into anergy or clonal deletion. These data suggested the change in balance of cytokine production of PBMC which were stimulated by allergen is a trigger for "outgrow" of food allergy.

Allergens↗
PubMed1998

[Responsibility of the lateral geniculate nucleus in photosensitive epilepsy: dipole tracing method].

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.

Adolescent↗
PubMed1997

Abnormal DNA synthesis activity induced by X-rays in nevoid basal cell carcinoma syndrome cells.

DNA synthesis activity was examined in fibroblasts and isolated nuclei derived from patients with nevoid basal cell carcinoma syndrome (NBCCS) upon exposure to X-ray and ultraviolet (UV). The DNA synthesis activity in NBCCS fibroblasts increased after X-ray irradiation, i.e., to twice that on mock-irradiation, while it decreased in healthy donor-derived fibroblasts. The DNA synthesis activity in isolated nuclei of X-ray irradiated NBCCS fibroblasts also increased, i.e., more than twice that on mock-irradiated. In the experiments using synchronized cells, DNA synthesis activity showed the most marked increase when the fibroblasts at S phase were irradiated with X-rays. In contrast, UV-irradiated NBCCS fibroblasts showed no such increase in DNA synthesis. These results revealed that DNA synthesis is abnormally induced in X-ray irradiated NBCCS cells and that this abnormality might be related with the tendency of tumorigenesis in NBCCS patients after exposure to X-ray.

Ataxia Telangiectasia↗
PubMed1997

Visualization of mitochondria with green fluorescent protein in cultured fibroblasts from patients with mitochondrial diseases.

cDNAs for green fluorescent protein (GFP) and for a GFP fusion protein containing the presequence of human ornithine transcarbamylase (pOTC-GFP) were transfected into cultured human fibroblasts. GFP cDNA gave diffuse fluorescence throughout the cytoplasm and the nucleus, whereas pOTC-GFP cDNA gave mitochondria-associated fluorescence. Fluorescent mitochondrial structures could be classified into five patterns: thread-like mitochondria, fine thread-like ones, rod-like ones, granular ones, and granular ones with weak cytosolic fluorescence. pOTC-GFP mutants resulted in a loss of mitochondrial fluorescence and an appearance of weak fluorescence throughout the cytoplasm. pOTC-GFP cDNA was transfected into fibroblasts from patients with various mitochondrial diseases. Higher ratios of fibroblasts with granular mitochondria and those with fine thread-like ones were observed in a patient with Reye's syndrome and a patient with Kearns-Sayre syndrome. Weak cytosolic fluorescence was sometimes observed in fibroblasts from these patients. This method will be useful to analyze mitochondrial structural alterations and disorders of mitochondrial protein import.

Animals↗
PubMed1997

Dichloroacetate treatment in Leigh syndrome caused by mitochondrial DNA mutation.

Sodium dichloroacetate (DCA) was administered to a 1-year-old female case of Leigh syndrome, who had a T > G point mutation at nt 8993 of mitochondrial DNA. Her biochemical and clinical symptoms improved gradually, but proton magnetic resonance spectroscopy revealed reduction of the N-acetylaspartate/creatine ratio, and magnetic resonance imaging showed progressive cerebral atrophy despite the DCA therapy. These results suggest that DCA therapy may not retard the progress of the primary disease in Leigh syndrome, but produced clinical improvement most likely by reducing toxic accumulation of lactate.

Aspartic Acid↗
PubMed1997

Longitudinal MR imaging and proton MR spectroscopy in herpes simplex encephalitis.

Longitudinal MR imaging and proton MR spectroscopy were performed in an 11 year-old female case of herpes simplex encephalitis with a complete recovery. On MR imaging, the white matter lesions, which could be seen in the subacute stage, but not in the acute or chronic stage, might represent edema due to postinfectious neuroallergic phenomena. Proton MR spectroscopy revealed marked reduction of the NAA/Cr ratio in the chronic stage, which increased gradually to within normal range in a year.

Atrophy↗
PubMed1997

The clinical features of Sjögren's syndrome in Japanese children.

Sjögren's syndrome (SS) is thought to be uncommon in children. An epidemiological study to describe the clinical features distinguishing SS in Japanese children was performed by sending questionnaires to hospitals. A total of 61 cases of SS were reported from 1290 hospitals. The diagnosis of SS was based on histopathological changes and/or sialographic changes in the salivary glands. Forty-two cases had primary SS and 19 were secondary SS with other autoimmune disorders. Fourteen cases (65%) of secondary SS were associated with systemic lupus erythematosus. In primary SS, the initial symptoms were systemic manifestations (fever, exanthema, arthralgia, etc) except for sicca symptoms. In laboratory studies, antinuclear antibodies, elevated serum IgG, rheumatoid factor, anti-Ro/SS-B antibodies were frequently observed.

Child↗
PubMed1997

Comparison of specificity between IgG, IgE and T cells to three casein components: implication for the role of circulating allergen-specific T cells in food allergy.

In order to investigate the role of food antigen-specific T cells circulating in the blood of patients with food allergy, we compared T cell response to three casein components (alpha s-, beta- and, kappa-casein) with specificities of IgG and IgE binding to the casein components in four milk-allergic patients (P1-4) with atopic dermatitis. In all patients the binding activities of IgG antibodies to alpha s-casein were most dominant, followed by those to beta- and to kappa-casein. The major component of casein bound by IgE antibodies was alpha s-casein in P1 and P3, kappa-casein in P2, and alpha s-casein as well as kappa-casein in P4; the order of casein components bound by IgE antibodies was different from that by IgG antibodies. Proliferative responses of peripheral blood mononuclear cells (PBMC) to casein components were so low that the dominance of casein recognition could not be clearly demonstrated. However, short-term T cell lines that specifically respond to casein were successfully established from PBMC of the four patients and the proliferative responses of the T cell lines to the three components of casein were in accord with the IgE antibody specificity to casein components but not with that of IgG antibody specificity. When taken together, these results indicate that casein-specific T cells circulating in the blood are involved in or reflect an allergic reaction against casein.

Caseins↗
PubMed1997

Hypoparathyroidism and pseudohypoparathyroidism.

Hypoparathyroidism is a clinical disorder characterized by hypocalcemia and hyperphosphatemia in the absence of renal failure and hypomagnesemia. The causes of hypoparathyroidism can be classified as two groups: (i) insufficient parathyroid hormone (PTH) secretion in relation to the serum calcium level (hypoparathyroidism); and (ii) impaired PTH action (pseudohypoparathyroidism). The main emphasis in this report is to distinguish subgroups based on the etiology and pathophysiology of the various aspects of the disease.

Diagnosis, Differential↗
PubMed1997

Nasopharyngeal colonization with Haemophilus influenzae type b among infants and children in Japan.

Healthy carriers of Haemophilus influenzae type b (Hib) play an important role in the spread of invasive Hib disease. The aim of the present study was to estimate Hib colonization among infants and children in Japan. Specimens from throat and nasopharyngeal cultures were obtained by thorough swabbing of both tonsils and the posterior pharynx. Specimens were inoculated on Hib antiserum agar. This was prepared with Levinthal base and Hib antiserum. Conventional methods were used concomitantly. Four of 474 infants from 1-48 months of age (0.84%) had Hib cultured from their nasopharynx. The carriage rate in 1-12 months old infants was 0.62% (2/322 cases), and that in 13-48 month old children was 1.32% (2/152 cases). Five of 167 (3.0%) 13-year-old children, and five of 154 (3.2%) 9-year-old children were asymptomatic carriers. Thirty-five of 104 household contacts of a patient with invasive Hib disease (33.6%) had Hib colonization. The carriage rate in healthy Japanese children may not be different from that in the USA prior to the availability of the conjugate Hib vaccine. The Hib carriage rate in household contacts of patients with invasive Hib disease was higher than in healthy children (P < 0.005). Our results suggest the possibility of an outbreak of invasive Hib disease in Japan.

Adolescent↗