[Colorectal cancers].
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Colorectal Neoplasms↗
Biomedical subjects
Y Miyoshi
Publications and source records attributed to Y Miyoshi.
[Hepatocellular carcinoma].
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Carcinoma, Hepatocellular↗
Dose response to intraventricular glial cell line-derived neurotrophic factor administration in parkinsonian monkeys.
A double-blinded study was conducted to evaluate the dose response of hemiparkinsonian rhesus monkeys to intracerebroventricular (ICV) injections of recombinant methionine human glial cell line-derived neurotrophic factor (GDNF). Thirty rhesus monkeys with stable hemiparkinsonian features were divided into six treatment groups (vehicle, 10, 30, 100, 300 and 1000 microg GDNF; n = 5/group). Each animal received 4 ICV administrations spaced at four week intervals. In addition, the animals were followed for 4 mo after the last injection. Standardized video taped behavioral tests were used to rate parkinsonian features using a nonhuman primate rating scale and assess side effects from treatment. Significant behavioral improvements were measured in animals receiving 100 to 1000 microg GDNF. One month after the last GDNF administration, parkinsonian features in animals receiving 100 and 1000 microg GDNF began to return to baseline levels. However, 300 microg GDNF recipients continued to display behavioral improvements. Parkinsonian features significantly improved were: bradykinesia, rigidity, posture and balance. The most common side effect was a transient weight loss after GDNF administration. Only one other side effect was observed, one animal receiving 1000 microg GDNF displayed dyskinetic movements. The results provide additional information for evaluating the possible clinical application of GDNF for treating Parkinson's disease.
Animals↗
[Effects of milrinone in patients undergoing cardiac surgery].
We investigated effects of milrinone in twenty consecutive patients (6 adults, 1 child, and 3 early infants) during cardiac surgery requiring cardiopulmonary bypass (CPB). The operations were: CABG 5, CABG+mitral valve repair 2, MVR 2, redo-MVR 4, aortic surgery 3 (total arch replacement 2), VSD+pulmonary hypertension 2 (infants), Tetralogy of Fallot 1, and PDA aneurysm 1 (infant). Ten minutes after release of aortic cross-clamp, all patients received milrinone by loading dose (50 micrograms/kg, bolus), followed by a continuous infusion of 0.5 or 0.75 microgram/kg/min. All of patients weaned from CPB with milrinone and low-dose of dopamine. The 75% of patients did not require any other drugs except for milrinone during post operative ICU stay. At the same time, we evaluated the effect of milrinone on platelet number in the patients before and after CPB. Milrinone administration did not cause significant changes in platelet number after CPB. No adverse effects attributable to this drug were found. Milrinone appears to be effective and safe in patients undergoing cardiac surgery of all kinds.
Adult↗
Isolation, mapping and mutation analysis of a human cDNA homologous to the doc-1 gene of the Chinese hamster, a candidate tumor suppressor for oral cancer.
We have isolated a human cDNA encoding a 115-amino-acid polypeptide that revealed 97% identity to a candidate tumor suppressor gene for oral cancer in Mesocricetus auratus (deleted in oral cancer-1; doc-1). It also showed a high degree of homology to a gene induced by TNF-alpha in Mus musculus. To investigate its possible role in esophageal carcinogenesis, we examined genetic alterations and expression levels of the gene in 13 esophageal carcinoma cell lines and 10 primary esophageal carcinomas. No mutation nor reduction of expression was observed in any of the 23 cancer materials examined. These results imply that the human doc-1 homologue is unlikely to play a significant role in esophageal carcinogenesis, although its role in the TNF-alpha signaling pathway remains unclear. We mapped DOC1 to chromosome band 12q24.31 by fluorescence in situ hybridization.
Animals↗
[Congenital mid-ureteral stricture: report of a case].
A rare case of congenital mid-ureteral stricture is reported. A 17-year-old woman was admitted with sudden onset of right flank pain. Intravenous urography demonstrated bilateral small renal calculi, left hydronephrosis and a stricture of the left ureter at the level of the pelvic brim. The diagnosis was determined as congenital mid-ureteral stricture because the ureter tapered smoothly from 25 mm to 5 mm in diameter at the stenotic site. She was successfully treated by partial ureterectomy with end-to-end anastomosis. Histopathologically, no dysplasia of muscular layer was recognized.
Adolescent↗
[A case of refractory diarrhea treated with somatostatin analogue].
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Amyloidosis↗
Mutations of the transforming growth factor beta type II receptor gene and microsatellite instability in gastric cancer.
Forty-three sporadic gastric cancers were analyzed with regard to whether mutations of simple repeated sequences in the transforming growth factor beta type II receptor (TbetaR-II) gene are associated with microsatellite instability (MSI) and gastric carcinogenesis. In 12 of the 43 cancers (28%), MSI was observed at least at 1 of the 2 microsatellite loci. Frameshift mutations of the TbetaR-II gene, all of which were 1 base deletion of 10 adenine repeats, were detected in 3 of 6 cancers, with MSI at 2 loci. However, mutations were not detected in 6 cancers, with MSI only at 1 locus and 31 cancers without MSI. Moreover, microanalysis in these cases revealed that the mutant-type alleles of TbetaR-II were invariably common in different areas within the tumor, in contrast to the markedly variable alleles of microsatellite loci. Our results suggest that frameshift mutation of the TbetaR-II gene may be a critical event associated with MSI and may contribute to carcinogenesis of the stomach. One of the possible mechanisms of escape from growth control by TGFbeta during gastric carcinogenesis could involve frameshift mutations of the TbetaR-II gene caused by DNA replication errors.
Adenine↗
Histological analysis of microencapsulated dopamine-secreting cells in agarose/poly(styrene sulfonic acid) mixed gel xenotransplanted into the brain.
PC12 cells were encapsulated within agarose/poly-(styrene sulfonic acid) (agarose/PSSa) mixed gel and xenotransplanted into the brains of guinea pigs. The immunoprotection capability and biocompatibility of the agarose/PSSa microcapsules were evaluated. Tyrosine hydroxylase-positive PC12 cells within the microcapsules were observed in all guinea pigs at least 5 weeks after transplantation. PC12 cells had a relatively uniform small size and occasionally formed cell clusters; however, cell necrosis was not apparent. The host reaction to agarose/PSSa microcapsules was minimal. The degree of glial fibrillary acidic protein-positive astrocyte density around the microcapsules was similar to that around the injection tracks. Necrosis around the brain/microcapsule interface was not apparent as assessed by Nissl staining. Normal-appearing neurons were observed in close vicinity to the capsule. High-performance liquid chromatography with electrochemical detection showed basal and potassium-evoked release of dopamine from the PC12 cell-enclosed microcapsules in vitro. We conclude that encapsulation using agarose/PSSa mixed gel can not only isolate the enclosed cells from the host immune system but can also allow diffusional exchange of nutrients and neurotransmitters. Encapsulation using agarose/PSSa mixed gel may expand the range of donor tissues for neural transplantation.
Animals↗
Starvation-induced decrease in the maximal binding capacity for triiodothyronine of the thyroid hormone receptor is due to a decrease in the receptor protein.
Biological responses to thyroid hormones are mediated by the nuclear thyroid hormone receptor (TR). Alterations in the maximal triiodothyronine (T3)-binding capacity (Cmax) of TR measured using a ligand binding assay have been reported under some pathophysiological conditions. Northern blot analysis has indicated that TR mRNA concentrations do not necessarily correlate with Cmax levels. For example, although the decrease in Cmax in rat liver induced by prolonged fasting is well established, TR mRNA concentrations have been reported to be constant. In the present study, we examined starvation-induced changes in TR by Western blot with anti-TR(alpha 1 + beta)antiserum and by Scatchard plot analysis. Starvation of rats for 72 hours decreased Cmax in the liver to 72.5% of control levels. The 47- and 55-kd TR proteins detected in hepatic nuclear extract by Western blotting also decreased to 64% and 66% of control values, respectively. The starvation-induced changes in Cmax and TR protein levels paralleled the change in total hepatic nuclear protein concentration. These results suggest that the decrease in T3-binding activity of the TR is due to a reduction of the TR protein itself.
Animals↗
Mild resistance to thyroid hormone with a truncated thyroid hormone receptor beta.
Recent studies have revealed mutations in the thyroid hormone receptor beta (TR beta) gene as a cause of the most cases of the thyroid hormone resistance syndrome. We have identified a novel nonsense mutation in codon 449 in the 3' end of exon 10 in the TR beta gene in a 16-year-old male patient with generalized resistance to thyroid hormone who also had familial thyroxine binding globulin deficiency. Receptor protein generated from this gene is thought to be 13 amino acid deficient at carboxy-terminus. Resistance to thyroid hormone was mild at least when the patient was evaluated. The patient was eumetabolic in the presence of elevated plasma-free thyroid hormone levels, and both thyrotrope and peripheral tissues responded to triiodothyronine (T3) administration. This mildness of resistance is in contrast to severe resistance to thyroid hormone in two previously reported cases with truncated receptors in which 16 amino acids or 11 amino acids were deficient at C-terminus. Thus, truncation of C-terminus of thyroid hormone receptor beta does not uniformly produce sever resistance.
Adolescent↗
High-dose intravenous steroid pulse therapy in thyroid-associated ophthalmopathy.
To evaluate the efficacy of high-dose intravenous steroid pulse followed by oral steroids in the treatment of thyroid-associated ophthalmopathy, we performed clinical assessment and measurement of retroorbital muscle enlargement in 27 patients before and after the therapy, and followed them up longitudinally. The mean duration of follow up is (mean +/- SD) 29.8 +/- 23.8 months (range 4-92). Diplopia disappeared in 10 patients and ameliorated in 11 patients. The degree of proptosis decreased in 15 patients and the fall in visual acuity improved in a third of the patients. The total ophthalmopathy index (OI) decreased from 7.0 +/- 1.9 to 3.0 +/- 1.5. The extraocular muscle enlargement (EME), expressed as the maximal ratio of extraocular muscle thickness to the diameter of the optic nerve, decreased from 2.33 +/- 0.56 to 1.27 +/- 0.26. No major side effects were found in any patient. The improvement in the eye disease was found immediately after the pulse therapy, prior to the start of the following therapy by oral steroids and/or orbital irradiation. Both of OI and EME decreased with time after the therapy and did not get worse after withdrawing oral steroids. The efficacy of the therapy evaluated by degrees of improvement in OI and in EME was significantly greater in females than in males. Although there was a significant positive correlation between initial OI and EME values and initial TBII and TSAb activities, a significant correlation was seen only between the degrees of improvement in EME and changes in TBII activity due to the therapy. The duration of eye disease, thyroid status, treatment with anti-thyroid drug, smoking and experience of previous treatment did not affect the efficacy of the present therapy. We conclude that high-dose intravenous steroid pulse therapy is effective and safe for thyroid-associated ophthalmopathy.
Adult↗
Chromaffin cell survival and host dopaminergic fiber recovery in a patient with Parkinson's disease treated by cografts of adrenal medulla and pretransected peripheral nerve. Case report.
A 55-year-old woman with severe Parkinson's disease was treated by cografting adrenal medulla with pretransected peripheral nerve into the bilateral caudate nuclei. The patient showed modest improvement of her akinesia; this effect persisted for 1 year after transplantation, when she suddenly died from upper gastrointestinal bleeding unrelated to the grafting procedure. At autopsy, a large number of tyrosine hydroxylase-immunoreactive chromaffin cells were observed within the caudate graft sites and a dense network of host dopaminergic fibers was visualized. This autopsy finding is very important for the field of experimental and clinical chromaffin cell grafting because it is the first evidence that cografts using pretransected peripheral nerve might enhance the survival of chromaffin cells and the recovery of host dopaminergic fibers in humans suffering from Parkinson's disease.
Adrenal Medulla↗
[Encapsulated dopamine-secreting cells transplanted into the brain: a possible therapy for Parkinson's disease].
Encapsulation of neurosecretory cells within a semipermeable membrane may possibly isolate the enclosed cells from the host immune system and allow inward diffusion of nutrients and outward diffusion of neurotransmitters. Moreover, the encapsulation procedure may prevent the tumor formation of enclosed cells, when they are derived from tumor cells. In the present study, PC12 cells, a dopaminergic cell line derived from a rat pheochromocytoma, were enclosed within an agarose/poly (styrene sulfonic acid) (agarose/PSSa) mixture and transplanted into the brains of rats (allogeneic transplantation) or guinea pigs (xenogeneic transplantation). Tyrosine hydroxylase (TH) immunoreactive PC12 cells within the microcapsules were observed in all rats and guinea pigs at least up to five weeks after transplantation. PC12 cells were round in shape and of relatively uniform small size. Although PC12 cells occasionally formed cell clusters, the formation of a tumor was not observed. The host reaction to agarose/PSSa microcapsules was minimum. The degree of glial fibrillary acidic protein (GFAP) positive astrocyte density around the microcapsules was similar to that around injection tracks. There was no apparent immunological rejection around the capsules. High-performance liquid chromatography with electrochemical detection (HPLC-EC) showed basal and potassium-evoked release of dopamine from the PC12 cell-enclosed microcapsules in vitro. Although our data is preliminary, we believe that agarose/PSSa microcapsules are promising for producing semipermeable membranes that enable allo-and xenotransplantation of neurosecretory cells into the brain in the absence of systemic immunosuppression. This approach is expected to be applied in Parkinson's disease in the near future.
Adrenal Gland Neoplasms↗
[Rhabdomyolysis related-acute renal failure in a patient with hyperosmolar nonketotic diabetic coma (HNKC): demonstration of myoglobin casts after normalization of renal function].
We report a patient with rhabdomyolysis secondary to hyperosmolar nonketotic diabetic coma (HNKC), who progressed to acute renal failure. A 43-year-old male with diabetes mellitus for three years was admitted to our hospital because of loss of consciousness. The laboratory findings at admission were as follows: serum glucose 1792 mg/dl, serum Na 129 mEq/1, BUN 71 mg/d1, serum creatinine 3.3 mg/d1, CPK 715 IU/1, plasma osmolality 370 mOsm/1, and negative urine ketone bodies. A diagnosis of HNKC was made. On the 2nd day, he had oliguria and the serum creatinine increased despite adequate treatment of HNKC by the administration of intravenous fluid and insulin. On the 4th day, CPK reached 47,300 IU/1, and serum myoglobin was also increased, indicating rhabdomyolysis. His renal function improved gradually and was almost normalized on the 20th day. Renal biopsy on the 23rd day showed myoglobin at the distal renal tubules, which appeared to be involved in the pathogenesis of renal failure by rhabdomyolysis. However, we found little abnormality association with diabetic nephropathy in the renal tissue. Since HNKC is known to induce acute renal failure rarely without diabetic nephropathy, these findings suggested that the acute renal failure was caused mainly by the rhabdomyolysis. Acute renal failure induced by rhabdomyolysis in patients with HNKC is rare, but fatal. The present study showed that the measurement of serum CPK and urine myoglobin was helpful for early diagnosis. Only 12 cases have been reported to have developed renal failure due to rhabdomyolysis among patients with HNKC. To our knowledge, we demonstrated for the first time that myoglobin at the distal renal tubules after renal function was normalized.
Acute Kidney Injury↗
[RB gene expression in gastrointestinal tract].
pRB, the retinoblastoma tumor suppressor gene product, regulates the cell cycle at G1/S transition negatively. Many cell cycle regulators modulate pRB function through its phosphorylation status. G1 cyclins (cyclin D, E)/cyclin-dependent kinases (cdk2, 4) inactivates pRB through its phosphorylation, while p21 (WAF1) and p16 inhibit cdks. In several kinds of cancer, Rb gene alteration or functional inactivation of pRB has been reported. In esophageal cancer, loss of heterozygosity of Rb gene and cyclin D gene amplification were frequently detected. But in gastric and colorectal cancer, Rb gene loss or deletion has been shown to be rare. In this study we investigated the expression of pRB, G1 cyclins, cdks and cdk-inhibitors in adenoma-carcinoma sequence of colorectum. And we compared the phosphorylation status of pRB in colorectal normal mucosa and cancer tissue. In adenoma only cyclin D and E were overexpressed but not cdks. In cancer in adenoma pRB and cdk2 were overexpressed with high frequency, and cdk4 overexpression was detected in advanced cancer. p16 overexpression was detected in almost all cancers, but in contrast p21 overexpression was rare event. Comparative study showed that pRB-positive cancer cells also expressed both cdc2/cdk2 and cyclin E. Densitometric analysis revealed that in advanced cancer pRB was hyperphosphorylated compared with normal mucosa. These results indicate that overexpression of cyclin D/cdk4 and cyclin E/cdk2 would phosphorylate pRB, and insufficient expression of p21 may accelerate pRB inactivation.
Cell Cycle↗
[A case of CEA and CA19-9 producing recurrent transitional cell carcinoma in an Indiana pouch after total cystectomy].
A 73-year-old female with transitional cell carcinoma (TCC) of the bladder underwent total cystectomy and Indiana pouch replacement in April, 1992. Histological examination revealed grade 3 TCC. In February 1995, she complained of gross hematuria. Intravenous pyelography (IVP) revealed a right non-functional kidney and filling defect in the Indiana pouch. We suspected colon cancer in the Indiana pouch because the levels of serum carcino-embryonic antigen (CEA) and CA19-9 were elevated. Endoscopic biopsy of intrapouch tumor was done. Pathological examination revealed grade 2 TCC. In July 1995, right nephroureterectomy with resection of Indiana pouch was performed and the surgical specimen revealed renal pelvic and ureteral cancer, grade 2 TCC. The levels of serum CEA and CA19-9 returned to the normal range 21 days after the operation. CEA and CA19-9 histochemical stain of renal pelvic and ureteral cancer were positive. Also CEA-, CA19-9-positive cells were detected in the specimens of the bladder tumor from the total cystectomy performed in 1992. This rare case is discussed and the literature is reviewed.
Aged↗
Two consecutive nucleotide substitutions resulting in the T3 receptor beta gene resulting in an 11-amino acid truncation in a patient with generalized resistance to thyroid hormone.
We identified unusual mutations in the T3 receptor (TR) beta gene in a 6-year-old Japanese girl with generalized resistance to thyroid hormone. Two consecutive base substitutions, T to A and C to A at nucleotide positions 1637 and 1638, respectively, changed the 451st codon coding for Phe(TTC) to stop codon (TAA), resulting in an 11-amino acid carboxyl(C)-terminus truncation. The patient was a heterozygote. Western blotting using an anti-TR antibody demonstrated the truncated receptor protein. The patient showed severe mental retardation (IQ41), disturbance in speech development, and attention deficit hyperactivity disorder. Thyroid functional status by clinical evaluation was considered within the normal range in spite of high serum thyroid hormone levels (T4 725.9 nmol/l, T3 12.7 nmol/l, FT4 166.0 pmol/l). TSH increased from 0.6 to 24 mU/L after TRH (150 micrograms) injection. TSH secretion as well as 123I-uptake was suppressed only partially by T3 (75 micrograms/day for a week). Close examination of thyroid functions and TR beta gene analysis were not possible in the family, except for paternal grandmother and one of her two sisters who showed no abnormality. The patient's truncated TR beta showed very low T3 binding activity (Ka = 0.1 x 10-10 M), transcriptional activity, and a very strong dominant negative effect. When co-expressed with wild-type TR beta at the molar ratio 1:1 in CV-1 cells, the mutant receptor inhibited the wild-type TR beta transcriptional activity by 74% at 10 nM T3. Even 1 microM T3 could not normalize these impaired functions.
Amino Acid Sequence↗