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Biomedical subjects

A Okada

Publications and source records attributed to A Okada.

At least 235 records · Page 13Linked to original sources

[Pancreatico-biliary maljunction and congenital dilatation of bile duct].

Congenital dilatation of bile duct (CDBD) or choledochal cyst has been demonstrated to be associated with pancreatico-biliary maljunction (PBM), and its various clinical signs and symptoms have been shown to be closely related with the presence of PBM. In almost all of the patients who were less than one year of age, the disease was of the cystic type and patients presented with either a palpable mass or jaunce as the main symptom. In patients with more than one year of age, the disease was of either the cystic or cylindrical type. A history of episodes of abdominal pain accompanied by elevated levels of serum amylase was present in most patients with both types of diseases. Histologic sections from the patients showed glandular formation with chronic inflammation, a result of refluxed activated pancreatic juice (possibly phospholipase A2): in contrast, histologic sections from the remaining patients of all ages showed only thickening of the fibrous layer. Thus, such variable morphologic features and clinical signs and symptoms in CDBD are highly dependent on two factors-the age at oset and the reflux of pancreatic juice into the bile duct through the common channel.

Adolescent↗

Biallelic inactivation of the APC gene in hepatoblastoma.

Familial adenomatous polyposis (FAP) is an inherited disorder caused by germline mutation of the adenomatous polyposis coli (APC) gene. Increased risk of hepatoblastoma (HBL) in FAP kindreds has been reported. To determine whether inactivation of the APC gene plays a role in development of HBL, 13 sporadic infantile hepatic tumors were analyzed for genetic alterations in the APC gene. A PCR-mediated RNase protection analysis was performed to detect subtle genetic alterations in the mutation cluster region and in exons 3 and 4 of the APC gene. The results showed that a G to T transversion at the splice acceptor site of the intron 3-exon 4 junction had occurred in one HBL. Sequence analysis of normal tissue of the patient proved the mutation to be germinal. Southern blot analysis at the APC locus revealed that the tumor had lost the opposite allele and was isodisomic at this locus. RNA analysis indicated that the tumor contained only the small APC transcript, from which exon 4 was entirely absent. Since abnormal splicing causes termination due to frameshift, it was hypothesized that only the truncated APC protein was expressed in this tumor. These findings suggest that inactivation of the APC gene is closely related to tumorigenesis of HBLs in FAP patients.

Alleles↗

The cDNA cloning and expression of the gene encoding rat gelatinase B.

During a study aimed at defining the role of tissue remodeling genes implicated in wound healing, we isolated cDNA clones encoding gelatinase B (GelB) from a cDNA library derived from healing rat skin wound. The predicted rat GelB comprising 708 amino acids shows 75% and 82% identity with the human and mouse GelB, respectively. By Northern blot analysis, two GelB transcripts of 2.4 and 3.0 kb were observed in rat tissues, and shown to arise through the differential use of polyadenylation signals. Recombinant rat pro-GelB produced in transfected COS-1 cells exhibited a molecular weight of 92 kDa, as shown by gelatin zymography. Autocatalytic processing to active lower-molecular-weight forms was induced by 4-aminophenylmercuric acetate, and this process was inhibited in the presence of EDTA.

Amino Acid Sequence↗

Unfavorable DNA ploidy and Ha-ras p21 findings in neuroblastomas detected through mass screening.

BACKGROUND: Urinary mass screening has been available for 6-month-old infants throughout Japan since 1985. It is still controversial as to whether the program contributes to the detection of unfavorable neuroblastomas destined to present clinically when a patient reaches an older age. DNA diploidy and tetraploidy, low expression of Ha-ras p21, and an amplified N-myc gene status relate to an unfavorable prognosis. The authors examined these biologic indicators in neuroblastomas detected by urinary mass screening. PATIENTS AND METHODS: Seventy-eight neuroblastomas detected by mass screening were studied for DNA ploidy using DNA flow cytometry, Ha-ras p21 expression using immunostaining, and N-myc gene copy number using slot-blot or Southern blot hybridization methods. RESULTS: Of 73 tumors with analyzable DNA flow cytometric results, 18 (24.7%) had diploidy (n = 7) or tetraploidy (n = 11). Twenty-eight (40.0%) of 70 tumors examined showed low-to-absent expression of Ha-ras p21. DNA diploid and tetraploid status correlated significantly with the low-to-absent expression of Ha-ras p21 (P = 0.00021). Fourteen (20.0%) of the 70 patients had both of these two unfavorable prognostic markers. N-myc amplification was not detected in 41 of 41 tumors studied. All 78 patients were alive 8-92 months after completion of treatment. CONCLUSIONS: At least 20.0% of neuroblastomas detected by mass screening have unfavorable biologic prognostic markers. These patients may benefit from early detection and immediate treatment. However, the biologic features associated with a poor prognosis are not predictive of poor outcome in individual patients, and, therefore, should not be used to justify more intensive therapies.

Aneuploidy↗

Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas.

From breast cancer cDNA libraries, we have cloned cDNAs that proved to correspond to the membrane-type matrix metalloproteinase (MT-MMP) recently identified in human placenta and proposed to be an activator of progelatinase A [Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E. & Seiki, M. (1994) Nature (London) 370, 61-65]. Using one of these cDNAs as a probe, we have detected MT-MMP gene expression in all 83 human carcinoma specimens examined by RNA in situ hybridization and have found MT-MMP transcripts in fibroblastic cells of tumor stroma but not in cancer cells. Comparison with other MMP genes expressed in fibroblastic cells of human carcinomas indicated that the expression pattern of the MT-MMP gene was more closely related to that of the gelatinase A gene than to those of the stromelysin 3 or interstitial collagenase genes. These observations are consistent with the hypothesis that MT-MMP and gelatinase A are cooperating during tumor progression and strengthen the concept that proteolytic activities originating from the stromal component of human carcinomas have a critical role in tumor progression.

Adenocarcinoma↗

Pancreatitis associated with choledochal cyst and other anomalies in childhood.

Fifty-one children with anatomical anomalies of the pancreatic duct developed pancreatitis associated with either congenital dilatation of the bile duct (choledochal cyst; n = 48) or other rare causes (n = 3). Among those with choledochal cyst, 41 underwent primary surgical resection of the dilated bile duct, while five of the remaining seven patients receiving cystenterostomy underwent secondary resection of the cyst.

Adolescent↗

Developmental changes in the distribution of the endoplasmic reticulum and inositol 1,4,5-trisphosphate receptors and the spatial pattern of Ca2+ release during maturation of hamster oocytes.

During maturation of hamster oocytes, the distribution of the endoplasmic reticulum (ER) and inositol 1,4,5-trisphosphate receptors (InsP3Rs) was found to change dramatically, as observed using confocal microscopy with DiI and electron microscopy for the ER and immunohistochemistry for InsP3Rs. In immature oocytes at the germinal vesicle (GV) stage, ER and InsP3Rs were located predominantly in several large masses near the surface and also in the perinuclear region near the surface. In contrast, fine ER networks and low-density InsP3Rs were present in the inner cytoplasm. The ER appeared to be formed as vesicles from annulate lamellae (AL) in the subcortical area. Rises in Ca2+ concentration occurred in the cytoplasm and the GV when immature oocytes were inseminated, but clear Ca2+ waves did not occur. Ca2+ rises began preferentially from the perinuclear region in response to low doses of serotonin or to uniform stimulation of InsP3Rs with photocleavage of caged InsP3. Serum also induced inhomogeneous Ca2+ release, shown by nonpropagating Ca2+ rises at multiple surface sites. Between the GV stage and prometaphase I the number and size of the surface ER masses increased, and the AL disappeared. This quantitative ER maturation was followed by a second step, spatial maturation. After prometaphase I, surface ER masses gradually dispersed to a number of much smaller ER clusters near the surface and, together with the perinuclear mass, were incorporated into thicker ER networks, resulting in a reticular pattern of the ER with small patches of InsP3Rs throughout the mature egg. The ER shifted to the peripheral surface with apposition to cortical granules. These developmental changes in ER Ca2+ stores may account, at least partly, for the acquisition of the ability of an egg to undergo normal fertilization.

Animals↗

Rapid turnover proteins as a prognostic indicator in cancer patients.

We investigated the relation between the plasma levels of various proteins, especially rapid turnover proteins (RTPs), and the prognosis in advanced cancer patients receiving total parenteral nutrition (TPN). In the patients with benign disease (n = 40), RTPs increased abruptly following TPN, but in patients with malignant disease, they rose slowly. Patients with malignant disease were divided into two different groups according to the outcome; group A, surviving 3 months or more after TPN and group B, who died within 3 months after TPN initiation. Whereas the RTP levels were elevated significantly in group A, they did not show any noticeable increase in group B. There was a close correlation between the plasma protein levels at 2 weeks and the survival time after TPN initiation. Thus, using the estimated critical values of RTPs with prognostic significance, the correct prognosis rate in 37 newly treated cases was: transferrin 75.7%, prealbumin: 91.9%, retinol-binding protein: 86.5%. These results clearly indicate that the TPN-induced changes in RTPs, notably in the PA value, can be a good prognostic indicator of survival in advanced cancer patients.

Adult↗

Report on the first annual survey of home parenteral nutrition in Japan.

An annual survey of the current national status of home parenteral nutrition (HPN) in Japan was begun in 1991, with a total of 231 registered patients from 142 institutions providing adequate data for evaluation and analysis. HPN was given for an average of 683 +/- 764 days to 93 patients with malignant diseases and 138 with benign disease, including 53 with inflammatory bowel disease and 79 with short bowel syndrome, 107 (46.3%) of whom were successfully rehabilitated. By the end of 1990, 61% of the patients investigated were still on HPN, 7% had already completed HPN, and 26% had died, the deceased accounting for 54% of the patients with malignant diseases and 7% of those with benign diseases. A total of 321 catheters had been used by all 231 patients, the most common being the subcutaneously implanted type, accounting for 33% of all catheters. By the end of 1990, 32% of these 321 catheters were still in place, 18% had been removed on the termination of HPN and 44% had been removed due to complications of total parenteral nutrition, including 20% for catheter fever. Rehospitalization was required in 62% of the patients, the cause being HPN-related in 21% of the total patients. Metabolic complications were experienced by 60% of the patients, but none of these were severe although 6% required hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunohistochemical analysis of proliferating cell nuclear antigen expression in human neuroblastoma.

Proliferative cell nuclear antigen (PCNA) is a cell-cycle-related nuclear protein that is maximally elevated in late G1 and S phase of proliferating cells. In this study, PCNA was identified immunohistochemically using paraffin section in 67 human neuroblastomas. Percentage of the PCNA-positive nuclei (PCNA index: PCI) ranged from 0% to 75%. There were significant relations between the PCNA expression and mitotic karyorrhexis index (MKI), histological classification, cell concentration, tumor weight, clinical stage, local invasion, lymph node metastasis, liver metastasis, or DNA ploidy. PCI was significantly low in patients who received aggressive chemotherapy before surgery. Patients with PCI higher than 30% showed a worse survival rate compared with those with PCI lower than 10% (P < .01). High PCI significantly related with poor survival, so that PCI may be an independent prognostic factor in neuroblastoma. Although further studies are required, PCNA immunostaining may be useful for assessing proliferating activity and for providing prognostic information in human neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Early postoperative change of plasma levels of amino acids in neonates with perforative peritonitis and its prognostic significance.

As a possible prognostic index, plasma levels of amino acids were serially measured for 1 week in 22 neonates with perforative peritonitis including gastric rupture and necrotizing enterocolitis and 28 neonatal surgical patients without infection as a control, who were subjected to total parenteral nutrition with hypertonic glucose and amino acids formulated for neonates. Plasma levels of branched chain amino acids significantly increased on the first day after operation in peritonitis group, whereas plasma levels of phenylalanine and histidine increased on the third postoperative day and tyrosine increased seventh postoperative day. In the peritonitis group, 5 neonates died within 2 weeks after operation (early death group) because of cardiopulmonary failure and 5 neonates died with hyperbilirubinemia from 1 month to 6 months after operation (late death group). The early death group showed increased levels of total amino acids compared with those in the late death group and survivors. The late death group also showed higher levels of total amino acids than survivors. Plasma levels of tyrosine increased in the early and late death groups compared with survivors. These results indicated that serial measurements of plasma amino acids early after operation showed the existence of liver dysfunction in addition to the derangement of amino acid metabolism in the liver and muscle caused by septic insult, which predicted the prognosis of perforative peritonitis in neonates.

Amino Acids↗

Bronchial reconstruction for bronchopulmonary foregut malformation: a case report.

In this case of bronchopulmonary foregut malformation (BPFM), the bronchus of the anomalous pulmonary tissue was reconstructed and tracheoplasty for associated congenital tracheal stenosis was performed at 5 days of age. After reconstruction the right lung was ventilated, which was followed by improved blood gas data. However, the persistent fatal circulation developed, and the patient died of respiratory insufficiency on postoperative day 5. The autopsy showed that both lungs were hypoplastic. This is the first case of bronchial reconstruction of BPFM.

Bronchi↗

Cu, Zn superoxide dismutase in patients with dementia of the Alzheimer type.

Cu, Zn superoxide dismutase (SOD) levels in the serum, cerebrospinal fluid (CSF) and skin fibroblasts of patients with dementia of the Alzheimer type (DAT) were estimated using enzyme immunoassay. The SOD mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the age-matched control groups of neurological patients without dementia, the AD group consisting of patients with DAT at ages under 65 years of age as well as the SDAT group of patients with DAT at ages over 65 years of age showed no significant changes in serum or CSF SOD levels. However, the skin fibroblast SOD- and SOD mRNA levels, which were correlate each other, were significantly higher in the AD group (p < 0.05), while lower in the SDAT group (p < 0.05). These results suggest that the determination of the SOD level of skin fibroblast may be useful for diagnosis of DAT and that the abnormality of SOD may play an important role in developing DAT.

Alzheimer Disease↗

Electrically induced blink reflex and clinical blinking ability in patients with amyotrophic lateral sclerosis.

A study of the electrically induced blink reflex was performed on 17 patients with amyotrophic lateral sclerosis (ALS), graded according to the voluntary and reflexive blinking ability. In the early stage, delay of bilateral R2 latencies, decrease of bilateral R2 amplitudes and disappearance of the contralateral R2 component occurred. Then, the ipsilateral R2 component vanished when the voluntary blinking was incomplete. In cases with the remaining R2 component, the recovery curves of R2 amplitude revealed the weakened influence of the central nervous system to the interneurons that constructed the R2 component. In highly impaired patients who had lost the reflexive blinking ability, the R1 component had disappeared. Electrically induced blink reflex is useful in assessing the degree of disability in the upper facial muscles.

Adult↗

Investigation of phagocyte-inducible factor in tumor-implanted mice.

The number of spleen Mac-1-positive cells was markedly increased in methylcholanthrene-induced Meth-A fibrosarcoma (Meth-A)-implanted mice. When the sera of Meth-A-implanted mice were added to normal bone marrow cells, granulocyte and macrophage colony stimulating factor (GM-CSF)-dependent growth of bone marrow cells was significantly enhanced. Analysis of the Meth-A-implanted mice sera showed that the levels of serum transferrin were markedly elevated. When the sera of Meth-A-implanted mice were pretreated with anti-mouse transferrin antibody, the enhancement of GM-CSF-dependent cell growth was almost abolished. Cell growth was also stimulated by the addition of transferrin which also caused an increase in the number of Mac-1-positive cells. Analysis of the effect of transferrin on bone marrow cells showed that the response of the cells to GM-CSF was significantly increased by preincubation with transferrin.

Animals↗

Multifocal fibrosclerosis with intracranial pachymeningitis.

A 29-year-old woman with a 4-year history of multifocal fibrosclerosis showed unique neurologic complications. Episcleritis, orbital pseudotumor, and eosinophilic phlegmon preceded intracranial inflammatory pachymeningitis. The pachymeningitis was associated with disturbance of the visual field, incomplete Gerstmann's syndrome, and pseudotumor cerebri. T2-weighted magnetic resonance images revealed a high signal intensity lesion in the left temporal and occipital lobes, and gadolinium-enhanced T1-weighted images revealed the enhancement of the thickened left tentorial leaf. The laboratory data suggested that the etiology might be autoimmunological. The disease and MRI abnormalities improved following administration of corticosteroids.

Adult↗

[A case of critical illness polyneuropathy in association with peritonitis after sigmoid colon perforation].

We presented a case of critical illness polyneuropathy after bacterial peritonitis. A 62-year-old male was received an emergency colectomy because of perforation of the sigmoid colon five days after the endoscopic polypectomy. He developed sepsis from peritonitis after operation in spite of the antibiotics therapy. On 15-th hospital days he developed muscle weakness and numbness of all limbs. He needed an artificial ventilator due to respiratory failure. Hematological and blood chemical findings showed a leukocytosis and metabolic acidosis with renal dysfunction because of sepsis. Serum anti-Campylobacter antibody was negative. Serial CSF examinations failed to show any abnormalities including albuminocytologic dissociation. Electrophysiological studies revealed a primary axonal degeneration, mainly in the motor, but also in the sensory nerve. Compound muscle and sensory action potentials were not elicited or markedly reduced without conduction velocity prolongation. Microscopic findings of the left sural nerve biopsy showed a primary axonal degeneration without evidence of inflammation. His prognosis was poor and three months later, he still required ventilatory assistance. Because of these clinical findings this patient was thought to have a critical illness polyneuropathy after excluding various etiologies of polyneuropathies. This case suggests that sepsis may be one of a cause of primary axonal polyneuropathy. The certain mechanism of this disease is still unknown. However cytokine, tumor necrotic factor(TNF) and/or Platelet activating factor(PAF) that secreted during sepsis may have an important role for the primary axonal degeneration.

Critical Illness↗