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Biomedical subjects

T Aihara

Publications and source records attributed to T Aihara.

At least 37 records · Page 2Linked to original sources

Does the iliolumbar ligament prevent anterior displacement of the fifth lumbar vertebra with defects of the pars?

We studied 23 patients with spondylolysis of the fifth lumbar vertebra (L5) and 20 with spondylolytic spondylolisthesis at this level. All were more than 40 years of age. The transverse processes at L5 were significantly wider in the former group than in the latter. We also dissected 56 cadavers to study the morphological relationship between the transverse process of L5 and the iliolumbar ligament, and found that the wider transverse process is associated with increased width of the posterior band of the iliolumbar ligament. If a patient with pars defects has wide transverse processes at L5, the lumbosacral junction may be stabilised by wide posterior bands of the iliolumbar ligament and the fifth lumbar vertebra by the ligament, preventing anterior displacement.

Adult↗

Expression of cell cycle regulator genes in KB, a human squamous cell carcinoma cell line, after irradiation.

DNA damage induced by irradiation causes overexpression of the p53 gene, and subsequently the upregulation of p53 downstream genes involved in cell cycle modification. Irradiated malignant cells which possess wild-type p53 have been known to undergo G1 arrest due to p21/Cip1/Waf1 upregulation. Other p53 downstream genes related to the modification of the cell cycle such as gadd45 may cause G2 arrest. Many of the genes which regulate the cell cycle progression have been identified, including the G1 phase specific ink4 family of cyclin-dependent kinase inhibitors (CDK-I), another group of CDK-Is, which affect the cyclin-CDK complexes ubiquitously, and S/G2 accelerator genes. The sequential changes in these cell cycle regulator genes after irradiation has not been clarified. We analyzed the appearance of the apoptotic fraction and cell cycle perturbation after irradiation using KB, a human squamous cell carcinoma line derived from oral floor, and examined the alteration of gene expression for cell cycle regulator genes. The KB cells proceeded to undergo apoptosis in a time and dose dependent manner after irradiation and showed G2 arrest accompanied by upregulation of p53, ubiquitous CDK-Is, and S and G2 accelerator genes.

Apoptosis↗

Identification and characterization of genes associated with human hepatocellular carcinogenesis.

Eight cDNAs encoding galectin 4 (Gal-4), UGT2B4 (UDP-glucuronosyltransferase), ribosomal phosphoprotein P0 (rpP0), dek, insulin-like growth factor binding protein (IGFBP) 1, vitronectin, retinoic acid-induced gene E (RIG-E), and CYP3A4 (cytochrome P450 nifedipine oxidase) were identified as differentially expressed genes between human hepatocellular carcinoma (HCC) and matched nontumorous liver tissues. Higher levels of UGT2B4, rpP0, dek, vitronectin, Gal-4, and IGFBP-1 mRNAs combined with a lower level of RIG-E mRNA were observed in at least four of five primary HCCs compared to matched nontumorous liver tissues. Furthermore, a pathological study suggested that the levels of UGT2B4, rpP0, dek, and vitronectin increased and the level of RIG-E decreased with the histological grading. On the other hand, the expression of CYP3A4 mRNA and CYP3A7 (P-450 Fla) mRNA, a transcript found in the fetus and highly homologous to CYP3A4, was higher in all nontumorous liver and some of the carcinoma tissues from five HCC patients, whereas it was significantly lower in normal liver tissues from two non-HCC patients. The examination using HCC cell lines HuH-7 and HepG2 under different growth conditions suggested that the expression of dek mRNA was growth-associated. In contrast, the expression of Gal-4, UGT2B4, IGFBP-1, and RIG-E mRNAs was regulated in a cell density-dependent manner: the levels of Gal-4, UGT2B4, and IGFBP-1 were undetectably low, whereas the level of RIG-E was high in rapidly proliferating, subconfluent HCC cells in 10% serum; however, the expression levels were reversed in dense, overcrowded cultures. In addition, IGFBP-1 and Gal-4 mRNAs were also induced by reducing the serum concentration to 0.1%. We also demonstrated that sodium butyrate, an inducer of differentiation, up-regulated and down-regulated RIG-E and dek mRNAs, respectively, in a dose-dependent manner in HuH-7 cells, supporting, in part, our pathological observation. In summary, therefore, high expression of Gal-4, UGT2B4, rpP0, dek, IGFBP-1, and vitronectin, together with low expression of RIG-E, was correlated with the malignant potential of HCC. CYP3A4 and CYP3A7 could be induced in HCC-bearing livers. These transcripts are differentially regulated depending on cell-cell contact, serum growth factors, growth and differentiation status, and/or other mechanisms in premalignant and malignant liver cells.

Antigens, Surface↗

Mammaglobin B as a novel marker for detection of breast cancer micrometastases in axillary lymph nodes by reverse transcription-polymerase chain reaction.

A novel reverse transcription-polymerase chain reaction (RT-PCR) assay using mammaglobin B gene was developed for detection of breast cancer micrometastases in axillary lymph nodes. Fourteen primary breast cancers and 56 axillary lymph nodes from six patients with primary breast cancer and 15 control lymph nodes from non-cancer bearing patients were subjected to this assay. The transcript of mammaglobin B gene was detected in none of the control lymph nodes, but in all of the 14 primary breast cancers. Eleven out of the 56 lymph nodes from the patients, which were shown to be positive by histological examination, were also proven positive by this assay. On the other hand, fourteen of the 45 (31%) histologically negative lymph nodes were also shown to express mammaglobin B mRNA, which suggested the presence of micrometastases in these lymph nodes. RT-PCR using mammaglobin B gene could therefore be a useful tool for detection of micrometastases of breast cancer.

Axilla↗

Successful transcutaneous arterial embolization of a giant hemangioma associated with high-output cardiac failure and Kasabach-Merritt syndrome in a neonate: a case report.

We describe the case of a patient with a neonatal giant cutaneous hemangioma with high-output cardiac failure and Kasabach-Merritt syndrome and successfully treated with transcutaneous arterial embolization aimed at controlling severe congestive heart failure and consumption coagulopathy. A patient was admitted to the neonatal care unit on the first day of age because of a large hemangioma on his right lateral chest wall and respiratory distress, associated with cardiac failure resulting from arteriovenous shunting. On the second day of age the platelet count decreased to 5.7 x 10(4)/microliter and fibrinogen level was 85 mg/dl. The values of prothrombin time and activated partial thromboplastin time were prolonged. Intravenous predonisone therapy was started immediately, but bleeding tendency was getting worse and the evidence of congestive heart failure persisted. On the third day the patient then underwent embolization of feeding arteries with microcoils. The cardiac failure and thrombocytopenic coagulopathy had improved significantly without complications. We conclude that transcutaneous arterial embolization is an effective and safe treatment in this neonate and should be considered for the treatment of control high-output cardiac failure and coagulopathy in infants with hemangioma and Kasabach-Merritt syndrome.

Cardiac Output, High↗

[Urine C-peptide excretion in hypocaloric states and factors affecting its excretion].

Recent evidence suggests that hyperinsulinemia may contribute to the development of various risk factors of atherosclerosis. To examine the effects of energy intake on insulin secretion, 24-h urine C-peptide was measured in twelve women with rheumatoid arthritis who were not taking any medicine and stayed in Koda hospital for a diet therapy which lasted 55 days. They were basically placed on a 1200 kcal/day vegan diet combined with three 3-5-day fasting periods (200 kcal/day). Urine C-peptide excretion markedly decreased from 31-40 to 8-14 micrograms/day during the fasting periods. Among the anthropometric variables examined, the average level of urine C-peptide excretions measured in the fasting periods showed a significant correlation with the percentage and the amount of body fat. However, such correlation was not observed while the calorie intake was 1200 kcal. No clinical laboratory parameter showed a significant correlation with urinary C-peptide excretion. These results suggest that the major determinant of urine C-peptide excretion is food intake and that hyperinsulinemia could be easily improved by restricting energy intake.

Arthritis, Rheumatoid↗

[The efficacy and limitation of hepatic arterial infusion chemotherapy for colorectal liver metastases].

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.

Administration, Oral↗

Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3.

We screened 75 primary hepatocellular carcinomas for somatic mutations in the entire coding region of the beta-catenin gene. We detected somatic mutations in 14 tumors; 12 were considered to cause amino acid substitutions and 2 were interstitial deletions of 51 or 195 nucleotides of genomic DNA, corresponding to exon 3. Among the 12 point mutations, 6 occurred at potential serine/threonine phosphorylation residues of codons 33, 41, or 45. The remaining six tumors contained a mutation at codon 32 (aspartic acid) or 34 (glycine), flanking to the serine residue at codon 33. By Western blot analysis, we confirmed accumulation of beta-catenin in five tumors for which frozen tissues were available; the five included tumors in which amino acid alterations had occurred at codons 32, 34, or 45, and one with a 17-amino acid deletion. Our results suggested that accumulation of beta-catenin due to amino acid substitutions at potential serine/threonine phosphorylation residues or at their neighboring codons or interstitial deletions involving exon 3 could contribute to hepatocellular carcinogenesis.

Carcinoma, Hepatocellular↗

Previously undescribed spondyloepiphyseal dysplasia associated with craniosynostosis, cataracts, cleft palate, and mental retardation: report of four sibs.

We report on four Japanese sibs (three brothers and one sister) with a previously unreported syndrome of spondyloepiphyseal dysplasia, craniosynostosis, cataracts, cleft palate, and mental retardation. Most clinical manifestations were evident neonatally, but skeletal changes and cataracts became substantial in early childhood. Radiological anomalies comprised coronal synostosis, mild epiphyseal dysplasia, particularly in the distal tibiae, strikingly delayed patellar ossification, mild metaphyseal splaying, hypoplastic ilia with iliac flare, and platyspondyly with ovoid-shaped or posteriorly humped vertebral bodies. The nonconsanguineous parents were mildly mentally retarded, and sibs of both gender were equally affected; thus, inheritance was likely autosomal recessive.

Abnormalities, Multiple↗

Allelic imbalance of insulin-like growth factor II gene expression in cancerous and precancerous lesions of the liver.

Allelic imbalance of the insulin-like growth factor II (IGF II) gene expression is often seen in hepatocellular carcinoma (HCC). To investigate the role of allelic imbalance in hepatocarcinogenesis, we have studied allelic expression status of the IGF II gene in dysplastic nodules, which are precancerous lesions of HCC, as well as in HCCs of different histological grade, and the influence of the allelic imbalance on IGF II gene expression has also been examined. Allelic imbalance was observed in 3 of 7 dysplastic nodules, in 7 of 9 well-differentiated HCCs, and in 8 of 9 moderately differentiated HCCs. IGF II gene expression level, which was studied by a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR), was significantly higher (3.6-fold) in the dysplastic nodules than the control livers, but a significant increase in the IGF II gene expression was not observed in well- and moderately differentiated HCCs as compared with the control livers. These results demonstrate that the allelic imbalance of the IGF II gene expression is seen in the early stage (precancerous lesions) of hepatocarcinogenesis. Association of the allelic imbalance with an increased expression of the IGF II gene in the precancerous lesions might suggest a possible involvement of an IGF II autocrine loop in the pathogenesis of these lesions.

Alleles↗

A distinct subtype of "metatropic dysplasia variant" characterised by advanced carpal skeletal age and subluxation of the radial heads.

BACKGROUND: "Metatropic dysplasia variants" are a group of bone dysplasias whose skeletal abnormalities are similar to, but milder than, those of classical metatropic dysplasia. The genetic and phenotypic heterogeneity has not been thoroughly elucidated. OBJECTIVE: The objective was to designate a distinct subtype of these metatropic dysplasia variants. MATERIALS AND METHODS: The subjects were four Japanese patients, two sporadic cases and two siblings, who all had identical skeletal changes. The radiological features in these patients were compared with those of previously reported metatropic dysplasia variants. RESULTS: Moderate platyspondyly with pear-shaped and/or anterior-tongued vertebral bodies, halberd pelvis, and dumbbell deformity of the tubular bones were regarded as hallmarks of metatropic dysplasia variants. The peculiar skeletal change in our patients was advanced carpal skeletal age in childhood, unlike most patients reported as metatropic dysplasia variants who manifest delayed carpal ossification. Another hallmark was congenital dislocation of the radial heads. A description of a patient with similar skeletal changes was found in the literature. CONCLUSION: These patients are considered to represent a distinct subgroup of metatropic dysplasia variants. It remains unknown whether the present siblings represent an autosomal recessive trait or an autosomal dominant trait with germinal mosaicism related to increased paternal age.

Abnormalities, Multiple↗

Cloning and mapping of SMARCA5 encoding hSNF2H, a novel human homologue of Drosophila ISWI.

We have isolated a novel cDNA encoding a peptide with 86% sequence homology to hSNF2L protein, a previously isolated human homologue of Drosophila ISWI. This gene, designated SMARCA5, contained an open reading frame of 3,156 nucleotides encoding a 1,052 amino-acid peptide (hSNF2H). As this product also revealed a significant (73%) identity in amino acid sequence to ISWI, a key component of chromatin-remodeling factors in Drosophila, hSNF2H may be another human homologue of this protein and, as such, could be involved in chromatin remodeling in humans. An ATPase domain characteristic of the SWI2/SNF2 family of proteins was highly conserved in ISWI, hSNF2L, and hSNF2H. Northern-blot analysis demonstrated ubiquitous expression of 5.1-kb and 4.1-kb transcripts of the hSNF2H gene. This gene was mapped by FISH to chromosome bands 4q31.1-->q31.2.

Adenosine Triphosphatases↗

Spontaneous regression of localized neuroblastoma detected by mass screening.

PURPOSE: To clarify whether and when neuroblastomas identified through screening do regress, and to ascertain how to treat them appropriately, we observed screened patients who had localized tumors, without any therapeutic intervention. PATIENTS AND METHODS: The criteria for the observation program were as follows: disease stage I or II; tumor less than 5 cm in diameter; no invasion to the intraspinal canal or growth to the great vessels; urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) less than 50 microg/mg creatinine; and informed consent. Of 25 patients identified through screening for 6-month-old infants in Saitama Prefecture, Japan between April 1994 and March 1996, 11 patients who met the criteria and one other patient with stage III tumor were enrolled onto the program. They were examined by abdominal ultrasonography (US) and their urinary VMA and HVA levels were assessed approximately once per month. The observation periods ranged from 4 to 27 months. RESULTS: The 11 tumors decreased in size, although one of these 11 tumors initially enlarged until the patient was 12 months of age and decreased in size thereafter. One other tumor slightly increased in size. Urinary VMA levels decreased in all patients. None of the tumors had completely disappeared by the last observation day. CONCLUSION: Our results suggest that regression of screened neuroblastoma is not a rare phenomenon. At present, it seems reasonable to adopt a wait-and-see strategy, with careful observation, for selected stage I or II tumors identified in infants screened at 6 months of age.

Homovanillic Acid↗

Fracture-dislocation of the fifth lumbar vertebra. A new classification.

We have studied fracture-dislocation of the fifth lumbar vertebra in seven patients and reviewed 50 previously reported cases. Based on this information, we have classified the injury into five types: type 1, unilateral lumbosacral facet-dislocation with or without facet fracture; type 2, bilateral lumbosacral facet-dislocation with or without facet fracture; type 3, unilateral lumbosacral facet-dislocation and contralateral lumbosacral facet fracture; type 4, dislocation of the body of L5 with bilateral fracture of the pars interarticularis; and type 5, dislocation of the body of L5 with fracture of the body and/or pedicle, with or without injury of the lamina and/or facet. Conservative treatment of fracture-dislocation of L5 is generally not effective because the lesion is fundamentally unstable. Planning of the operation should be made on the basis of the various types of injury.

Adolescent↗

[cDNA cloning of human testicular follicle-stimulating hormone receptor and analysis of its in vitro function].

A cDNA was cloned from human testis cDNA library by the use of rat FSH receptor cDNA as a probe. Transformation of 293 cells with the cloned cDNA led to expression of specific human FSH binding sites with high affinity (Kd: 1.5 x 10(-9) M), ligand dose-dependent production of cAMP and promotion of phosphatidyl inositol turnover, indicating that the cloned cDNA must encode a human FSH receptor. Northern blot analysis using human ovarian tissues revealed a high expression of mRNA at the stage of early follicular phase, but not luteal phase. Cross-linking of ligand with the expressed human FSH receptor showed that the molecular mass of the receptor should be 76 kDa, consistent with the estimated size of deduced amino acid sequence from the cloned cDNA. A polymorphism was found at 680th amino acid Ser or Asn, in the C-terminal region of the receptor although the influence of this difference upon the receptor function was not determined obviously in this study yet. The incidence of the polymorphism in the C-terminal region was not significantly correlated to the reproductive failures in 70 female cases of endometriosis, hyperprolactinemia, amenorrhea, PCOD or POF. However, elucidation of the structure and function in human FSH receptor using the cDNA will be applicable to diagnosis of some clinical cases associated with abnormal FSH receptor gene in the future.

Amino Acid Sequence↗

Detection of pancreatic and gastric cancer cells in peripheral and portal blood by amplification of keratin 19 mRNA with reverse transcriptase-polymerase chain reaction.

Reverse transcriptase-polymerase chain reaction (RT-PCR) targeted at keratin 19 mRNA was applied to detect circulating cancer cells in the peripheral and portal blood of pancreatic and gastric cancer patients. Keratin 19 mRNA expression was studied by RT-PCR in cancer tissues (12 pancreatic and 15 gastric cancers) and in peripheral and/or portal blood samples from patients with pancreatic cancer (stage I, n = 5; stage II, n = 1; stage III, n = 15; stage IV, n = 19), gastric cancer (stage la,b, n = 28; stage II, n = 9; stage IIIa,b, n = 5; stage IVa,b, n = 7) and benign pancreatic diseases (n = 7). Peripheral blood samples from 50 healthy volunteers served as controls. RT-PCR was conducted in duplicate in each sample, and only samples showing keratin 19 transcript in both determinations were considered as being positive. All the pancreatic and gastric cancers, but none of the control blood samples, were found to be positive. Dilution study using pancreatic cancer cells serially mixed against peripheral blood showed that detection sensitivity was more than one cancer cell in 10(6) peripheral blood mononuclear cells. In pancreatic cancer patients, RT-PCR analysis of the portal blood samples gave positive results in one stage III and one stage IV patient, and that of peripheral blood samples gave positive results in 2 stage IV patients. No positive results were obtained in any of the blood samples from gastric cancer patients. Our results indicate that incidence of circulating cancer cells is unexpectedly very low even in advanced pancreatic and gastric cancer patients.

Humans↗