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Biomedical subjects

T Momoi

Publications and source records attributed to T Momoi.

At least 73 records · Page 4Linked to original sources

Unfavorable effects of growth hormone therapy on the final height of boys with short stature not caused by growth hormone deficiency.

A group of 18 boys with non-growth hormone (GH)-deficient short stature without GH therapy (group A) and another group of 9 boys with non-GH-deficient short stature with GH therapy in doses of 0.5 IU (0.17 mg)/kg per week administered 5 to 6 times weekly (group B) were observed until they reached their final height. The mean duration of GH therapy was 4.2 years (range 3.2 to 5.0 years). These two groups were matched with respect to their standard deviation score (SDS) for bone age at the start of observation. Mean +/- SD of the final height for group A and group B was 162.0 +/- 5.4 cm and 154.2 +/- 4.2 cm, respectively. During the prepubertal period, height SDS for bone age of these two groups was not affected by GH therapy. During the pubertal period, however, height SDS for bone age remained constant for group A but decreased gradually for group B. Our observation indicates that for boys with non-GH-deficient short stature GH therapy does not improve height SDS for bone age during the prepubertal period, and in fact reduces it during the pubertal period, possibly resulting in a shorter final height than might have been attained naturally.

Age Determination by Skeleton↗

Amyloid beta 2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis.

We have recently demonstrated by immunohistochemistry that amyloid beta 2-microglobulin (beta 2m) is modified with advanced glycation end products (AGEs) in dialysis-related amyloidosis (DRA). To further investigate the role of the Maillard reaction in the pathogenesis of DRA, we produced a monoclonal antibody to imidazolone, a novel AGE, and a reaction product of arginine and 3-deoxyglucosone (3-DG) which was accumulated in uremic serum. Then we determined the localization of imidazolone in the amyloid tissues by immunohistochemistry using the antibody. The connective tissues in carpal tunnel and ligamentum flavum were obtained from six patients with carpal tunnel syndrome and two patients with destructive spondyloarthropathy. Imidazolone was localized to all the beta 2m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, beta 2m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of beta 2m with 3-DG produced imidazolone-modified beta 2m. In conclusion, amyloid tissue beta2m is modified with imidazolone in patients with DRA. 3-DG accumulating in uremic serum may be involved in the modification of beta 2m with imidazolone.

Aged↗

DAX-1 gene mutations and deletions in Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism.

Abnormality of the DAX-1 gene accounts for many instances of congenital adrenal hypoplasia. In the present study, we performed molecular genetic analysis of DAX-1 in 4 unrelated Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. A double-point mutation for V126M and W171X was identified in 1 family and a complex de novo insertion-deletion mutation was identified in a second. The DAX-1 gene was entirely deleted in a 3rd patient as well as in a 4th with the additional feature of glycerol kinase deficiency.

Adolescent↗

A case of Robinow syndrome accompanied by partial growth hormone insufficiency treated with growth hormone.

We report on a 10-year-old Japanese girl with Robinow syndrome accompanied by partial growth hormone (GH) insufficiency. We started GH replacement therapy at the chronological age of 6.5 years. In this case, improvement in the growth velocity was remarkable, but bone maturation accelerated even more. In order to avoid further acceleration of bone maturation, we started to treat our patient at the chronological age of 9.8 years with GH combined with gonadal suppression therapy using a luteinizing hormone releasing hormone analogue. However, no improvement in height SDS for bone age was attained. Our observations suggest that the indication of GH therapy for patients with Robinow syndrome needs careful consideration.

Body Height↗

Spatial expression of Sonic hedgehog in the lung epithelium during branching morphogenesis.

Sonic hedgehog (Shh), a homologue of Drosophila hedgehog, was specifically expressed in lung epithelium during branching morphogenesis, but was not uniformly expressed in lung epithelium. Shh was intensely expressed in the distal tips of the bronchial tubes during branching morphogenesis, and Shh was localized on the apical side of the epithelium. On the other hand, Bmp-4, one of the target genes of Shh, was also specifically expressed in the epithelium at the branching point. These results suggest that Shh and Bmp-4 are involved in the branching morphogenesis of lung epithelium.

Animals↗

Enhancement of CPP32-like activity in the TNF-treated U937 cells by the proteasome inhibitors.

CPP32, which is most closely related to CED-3 in the apoptotic protease in C. elegance, is activated during apoptosis induced by anti-Fas and TNF. Since processing of CPP32 is important for the activation, we examined the effects of protease inhibitors on CPP32-like activity in the TNF-treated U937 cells. Unexpectedly, proteasome inhibitors (at 5 microM) such as Z-LLnV, Z-LLL, and lactacystin enhanced CPP32-like activity, Ac-DEVD-MCA degrading activity, in the TNF-treated U937 cells in 3 hr, but E64d, cysteine protease inhibitor, did not. These proteasome inhibitors alone did not enhance CPP32-like activity in the untreated U937 cells under the condition used. The proteasome seems to protect the cells from apoptosis by degrading CPP32-like protease or its processing enzyme.

Caspase 3↗

Modification of beta 2m with advanced glycation end products as observed in dialysis-related amyloidosis by 3-DG accumulating in uremic serum.

beta 2microglobulin (beta 2m) isolated from the amyloid deposits in patients with dialysis-related amyloidosis (DRA) has been demonstrated to be modified with advanced glycation end products (AGEs). We demonstrated that AGE was localized to amyloid deposits in patients with DRA by immunohistochemistry using a monoclonal anti-AGE antibody. To clarify the mechanism of AGE modification of beta 2m-amyloid, we studied the effects of 3-deoxyglucosone (3-DG), a potent protein crosslinking the intermediate of the Maillard reaction, on the AGE modification of beta 2m, and quantified the serum levels of 3-DG in patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), and undialyzed patients. The serum levels of 3-DG were markedly increased in the dialyzed and undialyzed uremic patients. Although the serum level of 3-DG decreased after HD with a mean reduction rate of 67%, it was still significantly higher than in normal serum. Incubation of beta 2m with 3-DG at 37 degrees C emitted fluorescence characteristic for AGE, and caused AGE modification and dimer formation of beta 2m as demonstrated by Western blotting using the same monoclonal anti-AGE antibody used for immunohistochemical demonstration of AGE in DRA. The AGE-modified dimer of beta 2m could be extracted from the amyloid tissue of a patient with DRA. 3-DG showed more intense and faster reactivity with beta 2m to form AGE and dimer as compared with glucose, and aminoguanidine suppressed the AGE and dimer formation of beta 2m by 3-DG. In conclusion, 3-DG accumulating in uremic serum may be involved in the AGE modification of beta 2m-amyloid.

Amyloidosis↗

Identification of an interleukin-1 beta converting enzyme-like activity that increases upon treatment of P19 cells with retinoic acid as the proteasome.

We examined changes in proteinase activities in P19 embryonal carcinoma cells during retinoic acid-induced differentiation. The interleukin-1 beta converting enzyme (ICE)-like Ac-YVAD-MCA hydrolytic activity was increased about 6-fold by treatment with retinoic acid. This activity was inhibited by N-ethylmaleimide and Ac-YVAD-H but not by E-64, EDTA, PMSF, or amastatin. The ICE-like activity in P19 cells eluted as a single peak just after the void volume on gel filtration. No ICE-like activity was observed at a molecular mass of 30-50 kDa. Enzymatic purification, Western blot analysis, and an immunoabsorption study demonstrated that the ICE-like activity in P19 cells is caused by the proteasome, and is stimulated during retinoic acid-induced differentiation. The proteasome purified from mouse liver also cleaved Ac-YVAD-MCA. These results strongly suggest that the proteasome is a major ICE-like proteinase in P19 cells and may be involved in the neural differentiation and the apoptotic pathway.

Animals↗

Nephropathy and growth hormone deficiency in a patient with mitochondrial tRNA(Leu(UUR)) mutation.

A mitochondrial A 3243 G mutation in the tRNA(Leu(UUR)) gene was first described as a common cause of MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome). This same mutation is also the cause of a totally different disorder, a subtype of diabetes mellitus which is inherited maternally and often associated with sensorineural hearing loss. In this paper, we report on a Japanese boy with A 3243 G who developed a previously undescribed combination of symptoms, nephropathy and growth hormone deficiency. The patient first presented with short stature and moderate mental retardation. Growth hormone (GH) provocation tests showed deficient growth hormone secretion. During the course of follow up, he presented with progressive nephropathy followed by the development of diabetes mellitus. The results of laboratory tests and renal biopsy were against incidental association of known types of nephropathy. On PCR-RFLP analysis, the percentage of mutated mtDNA was higher in the renal biopsy specimen than 12 peripheral blood leucocytes. Our case suggests that mitochondrial diseases should be taken into account when there is nephropathy of unknown cause. In addition, the presence of growth hormone deficiency may account for part of the mechanism leading to short stature commonly seen in these patients.

Blotting, Southern↗

Amino acid sequence of a modified beta 2-microglobulin in renal failure patient urine and long-term dialysis patient blood.

We isolated and analyzed beta 2-microglobulin (BM) in urine of two renal failure patients and in ultrafiltrate from long-term dialysis patients. In both groups of patients, we found the native BM with pI 5.7 and some modified BM with pI 5.3. The amino acid sequence of the modified BM was determined and compared with that of the native BM; the N-terminal isoleucine residue was missing and the second glutamine residue was cyclized into pyroglutamic acid in the modified BM.

Amino Acid Sequence↗

Regulation of alternative splicing in the amyloid precursor protein (APP) mRNA during neuronal and glial differentiation of P19 embryonal carcinoma cells.

Cell-specific alteration in the splicing of exons 7, 8 and 15 of the amyloid precursor protein gene was investigated in differenting P19 EC cells into neuronal and glial cells. Exons 7 and 8 were skipped in the neuronal state and exon 15 was skipped in the glial state. Expression of U2AF, one of the essential factor for splicing in mammalian cells, was down-regulated during cellular differentiation. The skipping of exon 15 was suppressed in the glial cells transfected with U2AF. Thus, a reduction in U2AF is believed to play a crucial role in glial-specific splicing of the APP gene.

Alternative Splicing↗

Hepatocyte growth factor specifically expressed in microglia activated Ras in the neurons, similar to the action of neurotrophic factors.

Hepatocyte growth factor (HGF) mRNA and its receptor (c-Met) mRNA were detected in the fetal and adult rat brain. Expression of c-Met mRNA was increased after birth. HGF mRNA was preferentially expressed in the microglia of the rat brain, while c-Met mRNA was expressed in neurons as well as astrocytes and microglia. Most of the neurons were c-Met positive, and HGF stimulated tyrosine phosphorylation of c-Met (140-kDa) in the neurons. HGF as well as bFGF also activated Ras in the neurons. These results suggest that HGF plays a biological role as one of the neurotrophic factors in the brain.

Animals↗

Activin induces the expression of the Xenopus homologue of sonic hedgehog during mesoderm formation in Xenopus explants.

The Xenopus homologue of sonic hedgehog (Xhh) was detected in Xenopus embryos at stages 13 and 31 by RT-PCR, but it was not expressed in explants isolated from the animal hemisphere of Xenopus embryos at stage 8-9. Treatment of the animal cap with activin (1-100 ng/ml) induced the expression of Xhh. However, it was not induced by 100 ng/ml basic fibroblast growth factor (bFGF). Whole mount in situ hybridization confirmed the expression of Xhh in the animal cap treated with activin. The expression of Xhh induced by activin was not inhibited in the presence of cycloheximide, suggesting that Xhh is an early response gene induced by activin.

Activins↗

c-jun inhibited the alternative splicing of neuron-specific amyloid precursor protein, but stimulated the non-neuron type one in P19 EC cells.

Three alternative splicing products of amyloid precursor protein (APP), APP770, 751 and 695, were detected in mouse embryonal carcinoma (EC) P19 cells by reverse transcriptase RNA polymerase chain reaction (RT-PCR). Alternative splicing of APP pre-mRNA in P19EC cells was remarkably changed by c-jun transformation. The relative ratio of APP770 encoding exons 7 and 8, non-neuron type, was increased by c-jun transformation, while that of APP 695 not encoding exons 7 and 8, neuron-specific one, was decreased. These results suggested that skipping of exons 7 and 8 was specifically blocked in c-jun transformed cells. APP 695, which increases in P19 EC cells under the culture conditions that induce the neuronal differentiation, did not increase in C2C5 cells under the same conditions, suggesting that c-jun transformed cells were not in the neuronal cell lineage and lost the ability to differentiate into neurons.

Alternative Splicing↗

Type 3 GM1 gangliosidosis: clinical and neuroradiological findings in an 11-year-old girl.

An 11-year-old Japanese girl was diagnosed as having type 3 GM1 gangliosidosis by clinical symptoms and enzyme assay. She was the youngest among the patients with type 3 GM1 gangliosidosis whose clinical and neuroradiological findings have been documented. Clumsiness since early infancy and dystonia since early childhood which progressed slowly without mental deterioration and dysmorphism led us to the diagnosis of type 3 GM1 gangliosidosis. Genotype determination showed point mutation in exon 2 of the beta-galactosidase gene, which is common among the patients reported in Japan. T2-weighted MRI demonstrated bilateral symmetrical hypointensity in the putamen and globus pallidus. Single photon emission computed tomography using 99mTc-HMPAO showed bilateral hyperperfusion in the basal ganglia which decreased gradually during 1 year of observation. Twenty-two patients with type 3 GM1 gangliosidosis reported in the literature whose onset was at under 15 years of age were reviewed.

Child↗

Elevation of serum creatine phosphokinase during growth hormone treatment in patients with multiple pituitary hormone deficiency.

Serum creatinine phosphokinase (s-CPK) increased to more than 500 U/l in 5 out of 21 patients with growth hormone (GH) deficiency during the 2 years of treatment with biosynthetic GH. In three of these five patients, s-CPK had elevated gradually after the start of GH treatment and remained high in one patient except in the period when GH injection was interrupted, and gradually decreased in the other two patients during treatment. These three patients had complete GH deficiency associated with multiple pituitary hormone deficiency due to pituitary stalk transection. One of the remaining two patients had Noonan syndrome and his s-CPK levels before therapy were relatively high. The fifth patient was a baseball athlete and the elevation of s-CPK seemed to be attributable to the strenuous exercise. Conclusion. s-CPK increases significantly in a certain group of patients with GH deficiency during GH replacement therapy. Measurement of s-CPK is to be included in the follow up laboratory tests at least in the 1st treatment year to evaluate the potential hazardous effects of GH on muscle.

Adolescent↗