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Biomedical subjects

H Niimi

Publications and source records attributed to H Niimi.

At least 109 records · Page 6Linked to original sources

[Clinical usefulness of pediatric population parameter of slow-releasing preparation of sodium valproate].

We predicted the serum level of a slow-releasing preparation of sodium valproate (VPA-SR) in 9 children with epilepsy by pediatric population parameter obtained previously or by two adult parameters. The accuracy of prediction was evaluated as an absolute error standing for the difference between the measured and the predicted serum concentration in each patient. The mean absolute error (MAE) based on the pediatric population parameter was 5.5 +/- 5.2%, although MAEs from two adult parameters were 13.8 +/- 9.9 and 15.1 +/- 9.2%, respectively. Statistical analysis revealed that the pediatric population parameter was significantly more accurate for the prediction to serum concentrations. In conclusion, the pediatric population parameter was greatly useful for pharmacokinetic analysis of VPA-SR by Bayesian method in children with epilepsy.

Adolescent↗

[Nasal smear cytology in bronchial asthma: correlation of appearance and numbers of nasal smear mast cells, eosinophils or basophils and serum IgE antibodies to house dust mite in patients with bronchial asthma].

Nasal smear cytology was studied in pediatric patients with bronchial asthma with special reference with IgE RAST to house dust mite, Dermatophagoides pteronyssinus (Dp). Results obtained were as follows: (1) Numbers of eosinophils on the nasal smear correlated well with Dp RAST score, (2) mast cells were detected before Dp RAST becoming positive and appearance of eosinophils, (3) basophils appeared after detection of eosinophils and only in patients with nasal smear eosinophils. These results suggest that mast cells are the early marker for allergic inflammation and basophils and eosinophils appear in association with overt sensitization with house dust mite in house dust mite-sensitized asthmatic patients.

Adolescent↗

MR evaluation of tuberous sclerosis: increased sensitivity with fluid-attenuated inversion recovery and relation to severity of seizures and mental retardation.

PURPOSE: To evaluate the utility and possible increased sensitivity of fluid-attenuated inversion recovery (FLAIR) images for the detection of tubers in patients with tuberous sclerosis, compared with standard T2-weighted images, and to evaluate whether the tubers are correlated with neurologic symptoms. METHOD: We examined the number, size, and location of tubers in five tuberous sclerosis patients using T2-weighted and FLAIR images. Their intelligence quotients, ages at the onset of the first seizure, seizure types, and epileptic severity also were studied retrospectively. RESULTS: The number of tubers observed ranged from 4 to 17 on T2-weighted images, and from 10 to 33 on FLAIR images. All the tubers, other than the myelination line on T2-weighted images, were remarkably demonstrated as high-intensity lesions on FLAIR images. No correlation was found between the neurologic outcome and the number, size, or location of tubers on FLAIR images. CONCLUSION: FLAIR images were very sensitive for the detection of tubers, especially small subcortical ones, the number, size, and location of which are not related to the neurologic symptoms.

Adolescent↗

Thrombocytopenia: a risk factor for acute myocardial infarction during the acute phase of Kawasaki disease.

BACKGROUND: We report on 10 patients with Kawasaki disease and thrombocytopenia who were found to have a high incidence of coronary artery aneurysm and acute myocardial infarction. The clinical features of these patients, the cause of their thrombocytopenia and the relationship between cardiovascular pathology and thrombocytopenia were analyzed. METHODS: The clinical features of 10 patients with Kawasaki disease found to have thrombocytopenia (group A: mean age 8.0 +/- 7.0 months) and those of 293 patients with Kawasaki disease (group B, controls: mean age 13 +/- 20 months) were analyzed. Coagulation studies and bone marrow aspiration were performed to ascertain the cause of the thrombocytopenia in nine out of 10 subjects in group A. RESULTS: The minimum platelet count was 4-12 x 10(4)/mm3 (average day of illness, 10.3) and platelet counts were elevated to the baseline value within 1-2 weeks of onset of the illness. Low fibrinogen concentrations, high levels of fibrin degradation products, and low erythrocyte sedimentation rates with high C-reactive protein levels were observed in seven patients. In two other patients, immature megakaryocytes with normal coagulation values were observed. The differences in the incidence of coronary artery aneurysm and acute myocardial infarction between groups A and B were highly significant (coronary artery aneurysm: 60% in group A, 8.9% in group B; acute myocardial infarction: 40% in group A, 0.3% in group B). CONCLUSIONS: In many patients with Kawasaki disease and thrombocytopenia, the thrombocytopenia appears to be a result of intravascular coagulation, and to be one of the risk factors for acute myocardial infarction.

Acute Disease↗

[Serum levels of intact molecular osteocalcin in children with growth hormone (GH) deficiency during GH therapy: an early predictor of GH therapy].

Recently we developed a sandwich enzyme immunoassay (EIA) specific for intact molecular osteocalcin (I-OC), produced only by osteoblast cell and partially released into blood circulation, to establish a specific biochemical marker of bone formation. In order to confirm whether serum I-OC levels constitute a specific marker for bone formation and to assess the relationship between serum I-OC levels and growth response to growth hormone (GH) therapy, we measured the serum I-OC in serial serum samples using this EIA from 61 children with GH deficiency who showed significant bone growth during GH therapy. The serum I-OC levels in children with GH deficiency before GH therapy were slightly lower than those in normal children (Kanzaki S. et al., J. Clin Endocrinol Metab. 1992;75:1104-9), and had a wide distribution overlapped with the normal range. These levels were apparently increased during GH treatment; that is, in contrast to the levels of 22.9 +/- 1.5 ng/ml (mean +/- SE) before GH treatment, the levels after 1 and 2 months of GH treatment were 29.1 +/- 1.6 ng/ml and 32.5 +/- 1.8 ng/ml, respectively. However, they decreased slightly at 3 months and then they gradually rose to 37.5 +/- 2.8 ng/ml after 12 months, I-OC ratios, represented by the I-OC level at each month of GH therapy in relation to pretreatment level, correlated well with the growth response (growth velocity, growth velocity SD score and delta growth velocity SD score) after 12 months of GH treatment. Correlation coefficients of the growth velocity versus I-OC ratio at 1 and 6 months of GH treatment were 0.677 (p < 0.001, N = 58) and 0.752 (p < 0.001, N = 55), respectively. However, both IGF-I and ALP ratios represented in the same way as the I-OC ratio, correlated poorly as compared with the I-OC ratio. These results demonstrate that the change of serum I-OC levels indicates a direct and sensitive reflection of bone formation, because serum I-OC levels significantly increased with the growth response to GH therapy. The measurement of serum I-OC levels after 1 month of GH treatment may be a useful tool in predicting improved growth velocity during long-term GH therapy.

Body Height↗

[Clinical study of 15 children with acute suppurative thyroiditis].

From 1969 to 1990, 15 children with acute suppurative thyroiditis (AST) were diagnosed in our hospital. Their clinical, laboratory and radiologic findings were reviewed. The characteristic features were as follows: 1) Males to female ratio was 1.5:1. 2) The ages at diagnosis ranged from 3 to 14 years, with a mean age of 6 years. 3) A painful, tender mass in the anterior neck was detected in all cases and fever was detected in 10 cases (67%). 4) The left lobe of the thyroid was affected in 11 cases (73%), whereas the right lobe was affected in the remaining 4 cases. No cases was bilateral. 5) Five cases (33%) were found to be recurrent. 6) Eight pathogenic organisms were identified on culture from 7 cases; among them 3 were due to anaerobic pathogen. 7) Leukocytosis was increased and acute-phase reactant tests were positive in most cases. 8) Thyroid function was found to be normal in all 9 cases examined. 9) Radiologic studies, which included radionuclide thyroid scan, ultrasonography, computed tomography and barium esophagogram, were very helpful for the diagnosis of AST. 10) A barium esophagogram was performed in 9 cases and a fistula originating from the pyriform sinus was found in 4 cases (44%). 11) Three cases (20%) had the complete removal of the fistula as a permanent cure. This report summarizes the clinical features of 15 children with acute suppurative thyroiditis diagnosed in our hospital during the past twenty years.

Acute Disease↗

Comparative studies of the same adenocarcinoma cells, macrophages, and mesothelial cells by light microscopy, scanning electron microscopy, and transmission electron microscopy.

The identification of cells in body cavities of cancer patients is sometimes difficult to make. In order to make a definite cytological diagnosis, we observed the same cells by using light microscopy (LM)-scanning electron microscopy (SEM)-transmission electron microscopy (TEM). In this study we first stained cells by the Papanicolaou method after fixation in 1% glutaraldehyde for LM, and then attempted to observe them successively by SEM-TEM after fixation in 1% paraformaldehyde and 1.25% OsO4. Our method and procedures in examining successively one and the same cells in body cavity fluids by using LM, SEM, and TEM ensured accurate discrimination among adenocarcinoma cells, mesothelial cells, and macrophages. The results of this study suggest that LM-SEM-TEM may be of diagnostic value in distinguishing among mesothelial cells, macrophages, and adenocarcinoma cells. This method also succeeded in disclosing differences between the ultrastructure of the cell surfaces, and those of the cytoplasm, and of the nuclei. It is desirable that LM-SEM-TEM observation can be introduced into various aspects in order to obtain an improvement in the diagnosis by cytologic examination, the judgment of therapeutical effects, drug selection, and prognostic presumption.

Adenocarcinoma↗

Guillain-Barré syndrome associated with IgM anti-GM1 antibody following Campylobacter jejuni enteritis.

We report a 4-year-old girl diagnosed as having Guillain-Barré syndrome after infection by Penner serotype 19 of Campylobacter jejuni. The patient had the HLA-B35 antigen. Neurological examination revealed distal-dominant weakness and intact sensation. Serial electrophysiological studies indicated that the predominant process was axonal degeneration involving motor nerves. An enzyme-linked immunosorbent assay revealed the presence of high titres of serum IgM antibodies to gangliosides GM1 and GM2. The IgM auto-antibody titres decreased concurrently with the clinical course of the illness and no switching from IgM to IgG secretion took place.

Antibodies, Anti-Idiotypic↗

Suppression of sex steroids by a gonadotrophin-releasing hormone agonist increases serum growth hormone-binding protein activity in girls with central idiopathic precocious puberty.

OBJECTIVE: The high-affinity growth hormone (GH)-binding protein corresponds to the extracellular domain of GH receptor. The direct role of sex steroids in pubertal bone growth may be an increased GH receptor-coupled GH action. We examine the GH-binding protein (GHBP) activity before and after the suppression of female sex steroids and the relation of GHBP to pubertal growth. PATIENTS: We studied six girls with central idiopathic sexual precocity without any prior gonadal suppression therapy. DESIGN: We measured GHBP activity before and 12, 24 and 48 weeks after the treatment with s.c. injection of a GnRH agonist (leuprolide acetate) every 4 weeks. MEASUREMENT: GHBP activity was measured by immunoprecipitation using anti-GH receptor monoclonal antibody. RESULTS: The treatment caused a decrease in the LH and FSH responses to GnRH test and plasma oestradiol, which resulted in decreased urinary GH excretion, plasma IGF-I levels, height velocity and bone age maturation. GHBP activity before the start of the treatment was normal (75 +/- 27% relative to adult pooled serum, mean +/- SD), and it was increased above adult level (122 +/- 29% at 48 weeks, P < 0.01) by the suppression of the pituitary-gonadal axis. There were significant negative correlations between GHBP and oestradiol (r = 0.452, n = 24, P < 0.05) and between GHBP and urine GH excretion (r = -0.462, n = 24, P < 0.05). CONCLUSIONS: The high-affinity GHBP is increased by the withdrawal of female sex steroid. The clinical significance of this finding may be interference with the binding of GH to its receptor resulting in a reduced IGF-I level and decreased height velocity. The mechanism warrants further study.

Body Height↗

Two cases of insulin-dependent diabetes mellitus under insulin treatment with slow height velocity: relationship of growth hormone-binding protein, metabolic control and growth.

Inadequate blood sugar control in children with insulin-dependent diabetes mellitus (IDDM) sometimes results in low insulin-like growth factor-I (IGF-I) and sluggish height growth. High affinity growth hormone-binding protein (GHBP), which is identical to the extracellular domain of growth hormone (GH) receptor, is present in the human sera. We have determined GHBP activity in two cases of poorly controlled IDDM with low height velocity in relation to metabolic control in order to determine the mechanism of resistance to GH in this condition, as indicated by low levels of GH-dependent growth factor IGF-I in the face of high serum GH levels. GHBP activity was within the normal range in two cases of IDDM with slow height velocity, low IGF-I and high hemoglobin-A1. In both cases, improved blood sugar control normalized IGF-I to result in accelerated height velocity without a major change in GHBP levels. These results may indicate either normal peripheral GH receptor or normal free portion of serum GH, and may suggest that the major defect in slow growth in poorly controlled diabetes is due to the post GH receptor.

Body Height↗

A comparative magnetic resonance imaging study of the corpus callosum in neurologically normal children and children with spastic diplegia.

To determine the extent of brain damage in children with spastic diplegia, we analyzed the true midsagittal magnetic resonance imaging findings for the corpus callosum in 43 children with spastic diplegia and in 69 neurologically normal children. In the normal children, the thicknesses of the genu, midbody, splenium and the entire corpus callosum were found to increase with age, while the ratios of the thickness of the splenium and of the midbody to the length were constant, regardless of age. Both ratios were significantly reduced in diplegic children and the ratio for the splenium was highly correlated with the extent of motor impairment. Assessment of the morphometric changes in the corpus callosum using magnetic resonance imaging may contribute to the determination of the extent of brain damage in diplegic children.

Adolescent↗

Attainment of normal height in severe juvenile hypothyroidism.

Prolonged juvenile hypothyroidism results in a permanent loss in height that is related to the duration of thyroxine deficiency before adequate thyroxine replacement treatment. A 13 year old girl with severe juvenile hypothyroidism was studied prospectively. She had an undetectable serum thyroxine concentration, a height SD score of -6.6 SD, and a bone age of 5.8 years. The enlarged pituitary gland involuted with thyroxine treatment to produce an empty sella. In addition to thyroxine the girl was treated with a gonadotrophin releasing hormone agonist to avoid the progression of puberty for 18 months and with growth hormone to achieve normal adult height.

Adolescent↗

Specificities of IgE, IgG and IgA antibodies to ovalbumin. Comparison of binding activities to denatured ovalbumin or ovalbumin fragments of IgE antibodies with those of IgG or IgA antibodies.

We studied the binding activities of IgE, IgG and IgA antibodies in patients with allergy to hen's egg white against two different ovalbumin (OVA) preparations, which were physically or chemically denatured OVA and enzyme-digested OVA fragments. The binding activities of IgE antibodies to these OVA preparations with those of IgG or IgA antibodies were compared. It was found that the binding activities of IgE antibodies to denatured OVA by treatment with dithiothreitol, urea or hydrochloric acid were similar to those of IgG or IgA antibodies. In contrast, the binding activities of IgE antibodies to heat-denatured OVA or by treatment with sodium hydroxide at pH 11.0 were different from those of IgG or IgA antibodies to these denatured OVA. Furthermore, we found that the binding activities of anti-OVA antibodies in sera from patients with allergy to hen's egg white against fragmented OVA were different between IgE antibodies and IgG or IgA antibodies. Thus, it can be concluded that IgE antibodies to OVA in sera from patients with allergy to egg white differ from IgG or IgA antibodies in respect to binding activities against different preparations of denatured or fragmented OVA, probably due to differences in fine specificities of these antibodies against OVA.

Allergens↗

Identification of the disease-related T cell epitope of ovalbumin and epitope-targeted T cell inactivation in egg allergy.

An ovalbumin (OVA)-specific T cell line (TCL) was established from a patient with hen egg allergy. The TCL was CD4+, expressed alpha beta T cell receptor, and recognized OVA presented by HLA-DR10. Based on the response of the TCL to synthetic OVA peptides, it was found that the TCL recognized OVA 323-339, which is a major T cell epitope presented by murine I-Ad. The TCL secreted high levels of IL-5, but undetectable amounts of IL-2, interferon-gamma, and IL-4 when stimulated with OVA or the OVA 323-339 peptide. Since IL-5 is an important growth and chemotactic factor for eosinophils, it is possible that these OVA 323-339-specific T cells can contribute to human egg allergy. To our knowledge, this is the first demonstration of food allergen-specific TCL establishment and identification of a T cell epitope possibly related to the allergic reaction to food antigens. An analog peptide of the OVA 323-339 which is known to strongly bind to I-Ad partially inhibited the response of the TCL to OVA 323-339 presented by HLA-DR10, raising the possibility of peptide-based immunotherapy of food allergy.

Amino Acid Sequence↗

Thyroglobulin-specific T cell line from a healthy individual does not produce proinflammatory cytokines on antigenic stimulation: an implication for possible fail-safe mechanism to avoid autoimmunity.

In order to investigate the regulation of autoimmune response to thyroglobulin (Tg), one of the thyroid autoantigens, we established a Tg-specific T cell line by stimulation of peripheral blood mononuclear cells from a healthy volunteer with Tg and characterized its cytokine production pattern. The Tg-specific T cell line, designated DH5D1, obtained from a limiting dilution culture bore alpha beta T cell receptor and was CD4 and CD45RO positive. Upon stimulation with Tg, DH5D1 secreted little or no titers of IL-2, TNF-alpha, and IFN-gamma, whereas activation with combination of phorbol myristate acetate and calcium ionophore produced measurable levels of these cytokines. These results indicate that the Tg-specific T cell line is not defective in its capacity to produce proinflammatory cytokines and suggest that the inability of cytokine production by autoreactive T cells of healthy individuals is one fail-safe mechanism for preventing aggression of harmful autoimmune response.

Antigens↗

[Chemical iodination of hormonogenic tyrosine residues of human thyroglobulin is critical for the production of anti-thyroglobulin autoantibody and for the induction of experimental autoimmune thyroiditis in mice].

There is evidence from animal models that the iodine content of thyroglobulin (Tg) may influence its antigenicity in thyroid autoimmunity. To elucidate the effect of iodination of hormonogenic sites of human Tg (hTg) on its autoantigenicity, a synthetic peptide (TB: hTg 2546-2571), containing two hormonogenic tyrosine residues of hTg, and a chemically-iodinated peptide (TB-I) were prepared. We immunized C3H/He (H-2k) mice, a high responder strain to Tg, and BALB/c (H-2d), a low responder strain, with TB or TB-I plus lipopolysaccharide. Lymph node cells from the two strains immunized with TB or TB-I proliferated in response to both TB and TB-I. Anti-Tg autoantibodies were detected in both strains when immunized with TB-I, while immunization with TB failed to produce anti-Tg antibodies. Furthermore, one of the C3H/He mice immunized with TB-I developed diffuse thyroiditis, but BALB/c mice did not. These findings indicate that the iodination of the hormonogenic tyrosine residues of hTg, in other words, the synthesis of mono- and di-iodotyrosine (MIT and DIT) residues, is necessary for the production of anti-Tg autoantibodies in high and low responder mice and for the induction of autoimmune thyroiditis in high responder mice.

Amino Acid Sequence↗

[Identification and immunopathogenicity of a common T cell epitope between human thyroglobulin and human thyroid peroxidase].

Human thyroglobulin (hTg) and human thyroid peroxidase (hTPO) share common B cell epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis. Furthermore, we have demonstrated a functional common T cell epitope between hTg and hTPO in mice. Four hTg peptides in which 5 amino acid residues were identical to those of hTPO, and one hTPO peptide were prepared. Among these peptides, Tg-P4 (residues 2730-2743) and TPO-P4 (residues 118-131) shared the common T cell epitope and both peptides were highly antigenic. In addition, when the spleen cells from mice immunized with mouse Tg (mTg) were restimulated in vitro by Tg-P4 or TPO-P4, as well as by mTg, these cells transferred thyroiditis to naive recipient mice. These findings indicate that this common T cell epitope is immunogenic and related to the development of murine experimental autoimmune thyroiditis. The common T cell epitope between hTg and hTPO may play a role in the pathogenesis of human autoimmune thyroid disease.

Amino Acid Sequence↗

[Clinical evaluation of a new carbapenem antibiotic, biapenem (L-627), in the pediatric field].

Biapenem (L-627) was evaluated for its safety and efficacy in 27 children with various bacterial infections. L-627 was effective in cases with osteomyelitis due to Staphylococcus aureus, pneumonia and purulent meningitis due to penicillin-resistant Streptococcus pneumoniae, and urinary tract infections due to Enterococcus faecalis, Escherichia coli, or Pseudomonas aeruginosa. However, L-627 failed to produce good responses in 2 of 7 cases of Haemophilus influenzae infections. Pharmacokinetic parameters of 30-minutes infusion of 12 mg/kg were as follows: Cmax 29-46 micrograms/ml, T 1/2 0.68-0.94 hr. Adverse reactions were minimal. These data suggest that L-627 is safe in children, and is valuable especially for treatment of infections in immunocompromised hosts and infections due to multiply resistant bacteria.

Adolescent↗