Search PubMed⌕ Search

Biomedical subjects

M Yao

Publications and source records attributed to M Yao.

At least 91 records · Page 5Linked to original sources

[Von Hippel-Lindau disease].

The von Hippel-Lindau (VHL) disease is a multitumor syndrome characterized by CNS hemangioblastoma, pheochromocytoma and renal cell carcinoma. The VHL disease gene is a putative tumor suppressor gene responsible for VHL disease. VHL disease without pheochromocytoma (pheo) and those with pheo are classified as type 1 or type 2, respectively. Germline missense mutations are clustered in 4 regions in the VHL gene. The VHL protein is now regarded as a one of the key protein for ubiquitination and further degradation of certain transcription factors such as hypoxia inducible factor (HIF). Since almost of germline mutations are detectable, presymptomatic diagnosis of the VHL disease with DNA analyses is important to improve the prognosis of VHL disease.

Follow-Up Studies↗

[Transurethral electrovaporization-ablation of superficial bladder carcinoma].

OBJECTIVE: To observe short-term curative effect of transurethral electrovaporization-ablation of superficial bladder carcinoma. METHODS: 82 cases of superficial bladder carcinoma were treated using transurethral electrovaporization-ablation. RESULTS: The mean operative time was 36 min. One patient was complicated with extraperitoneal bladder perforation. No patients experienced TUR syndrome and severe hemorrhage. During the follow up for 2-18 months, 3 patients had recurrence respectively at 7, 8 and 10 months after the operation. CONCLUSIONS: Cut-electrode had vaporization and ablation with smooth surface of the wound and speed. The advantage includes safety, few complication, evident efficacy, and short hospitalization.

Adult↗

[Measurement of T and DHT contents in normal and diseased human prostate tissues].

OBJECTIVE: To measure T and DHT contents in normal and diseased human prostate tissues. METHODS: Serum and prostatic T and DHT levels were measured in patients with normal, benign prostatic hyperplasia and prostate cancer. RESULTS: A decline was observed in serum T level, but no change in DHT concentration with aging. There were no significant differences in both blood T and DHT levels between the patients with BPH or PCA and normal controls. Serum T level remained constant. There were excessive accumulation of DHT in BPH, and cancerous prostate tissues were responsible for the pathogenesis of BPH and PCA. Finasteride treatment did not produce a reduction in prostatic DHT content. CONCLUSION: More than one form of 5a-reductases is responsible for the high level of DHT in the gland.

Adult↗

The effect of left ventricular diastolic dysfunction on the pathogenesis of angina decubitus.

OBJECTIVE: To investigate the effect of left ventricular diastolic dysfunction on the pathogenesis of angina decubitus (AD). METHODS: The study population consisted of three groups: 20 individuals without cardiovascular studied as group I. Group II included 20 patents with coronary artery disease and without AD. Thirty-one patients with AD and ejection fraction (EF) > 50% were studied as group III. Group II and III were matched for age, EF and extent of coronary artery disease. RESULTS: Left ventriculography (LVG) showed that left ventricular (LV) first 1/3 filling fraction (1/3FF) was significantly lower in group III than in group II and I (both P < 0.001), but LV late 1/3 FF was much higher in group III than in group II and I (P < 0.05, P < 0.01). Left ventricular end-diastolic pressure (LVEDP) was markedly increased before and after LVG in group II and III as compared with group I (both P < 0.05, both P < 0.001). The difference of LVEDP caused by left atrial contraction (left atrial contraction pressure difference, LACPD) before and after LVG was much higher in group III than in group I ( P < 0.01, P < 0.001). However, there we significant differences in LVEDP and in LACPD between before and after LVG only in group III (both P < 0.01). CONCLUSION: The patients with AD have LV diastolic dysfunction, which may be closely related to the pathogenesis of angina decubitus.

Adult↗

Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch.

Presenilin-1 (PS1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both Notch and beta-amyloid precursor protein (APP) within their trans- membrane domains. The activity that cleaves APP (called gamma-secretase) has properties of an aspartyl protease, and mutation of either of the two aspartate residues located in adjacent transmembrane domains of PS1 inhibits gamma-secretase processing of APP. We show here that these aspartates are required for Notch processing, since mutation of these residues prevents PS1 from inducing the gamma-secretase-like proteolysis of a Notch1 derivative. Thus PS1 might function in Notch cleavage as an aspartyl protease or di-aspartyl protease cofactor. However, the ER localization of PS1 is inconsistent with that hypothesis, since Notch cleavage occurs near the cell surface. Using pulse-chase and biotinylation assays, we provide evidence that PS1 binds Notch in the ER/Golgi and is then co-transported to the plasma membrane as a complex. PS1 aspartate mutants were indistinguishable from wild-type PS1 in their ability to bind Notch or traffic with it to the cell surface, and did not alter the secretion of Notch. Thus, PS1 appears to function specifically in Notch proteolysis near the plasma membrane as an aspartyl protease or cofactor.

3T3 Cells↗

Direct interaction of the beta-domain of VHL tumor suppressor protein with the regulatory domain of atypical PKC isotypes.

VHL tumor suppressor protein contains two domains, alpha and beta. The alpha-domain is involved in the formation of a large protein complex suggested to be involved in ubiquitin-mediated protein degradation. However, the role of the beta-domain, which may recognize the target proteins for protein degradation, remains unknown. Here we report that the beta-domain interacts directly with atypical PKC isotypes, PKCzeta and PKClambda. Further, the regulatory domain of aPKC is sufficient for this direct protein-protein interaction. Since aPKC isotypes have been implicated in the regulation of cell growth and apoptosis, these results suggest that aPKC isotypes are potential direct target of the VHL beta-domain.

Amino Acid Sequence↗

Evidence for a physical interaction between presenilin and Notch.

Genetic analyses in Caenorhabditis elegans demonstrate that sel-12 and hop-1, homologues of the Alzheimer's disease-associated presenilin genes, modify signaling through LIN-12 and GLP-1, homologues of the Notch cell surface receptor. To gain insight into the biochemical basis of this genetic interaction, we tested the possibility that presenilin-1 (PS1) physically associates with the Notch1 receptor in mammalian cells. Notch1 and PS1 coimmunoprecipitated from transiently transfected human embryonic kidney 293 cell lysates in a detergent-sensitive manner, consistent with a noncovalent physical association between the two proteins. The interaction predominantly occurred early in the secretory pathway prior to Notch cleavage in the Golgi, because PS1 immunoprecipitation preferentially recovered the full-length Notch1 precursor. When PS1 was immunoprecipitated from 293 cells that had been metabolically labeled with [35S]methionine and [35S]cysteine, Notch1 was the primary protein detected in PS1 immunoprecipitates, suggesting that this interaction is specific. Furthermore, endogenous Notch and presenilin coimmunoprecipitated from cultured Drosophila cells, indicating that physical interaction can occur at physiological expression levels. These results suggest that the genetic relationship between presenilins and the Notch signaling pathway derives from a direct physical association between these proteins in the secretory pathway.

Alzheimer Disease↗

A novel gene delivery system targeting cells expressing VEGF receptors.

Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-beta-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) and human malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with the relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.

Amino Acid Sequence↗

Extramedullary relapse after all-trans retinoic acid treatment in acute promyelocytic leukemia--the occurrence of retinoic acid syndrome is a risk factor.

All-trans retinoic acid (ATRA) is now a standard agent for remission induction of acute promyelocytic leukemia (APL). Recently, extramedullary relapse, which was a rare condition in APL patients after chemotherapy alone, was reported with an increased frequency after ATRA treatment. However, it is not yet clear whether ATRA truly increases the risk of extramedullary recurrence and what are the risk factors. In this study, three of 13 patients with recurrent APL after prior treatment of ATRA were found to have extramedullary involvement, compared with none in 11 recurrent patients previously treated with chemotherapy alone (estimated relative risk 2.100, 95% confidence interval 1.341-3.289). Furthermore, in the former group of patients, the development of retinoic acid (RA) syndrome during prior induction treatment was significantly associated with extramedullary involvement at relapse (three in five patients with RA syndrome vs none in eight without the syndrome, estimated relative risk 5.000, 95% confidence interval 1.448-17.271). In conclusion, ATRA may predispose APL patients to extramedullary involvement at relapse and the occurrence of RA syndrome is a risk factor for it. Further studies are needed to confirm these findings. It also remains to be clarified whether treatment modification is necessary in patients who develop RA syndrome during ATRA treatment.

Adolescent↗

Genetic control of uterine receptivity during implantation.

Implantation involves complex molecular interactions between implanting blastocysts and the hormonally primed uterus. Gene targeting allows the generation of mice lacking a specific gene or genes and has proved to be of considerable value when combined with classical physiology in understanding many biological questions, such as the process of implantation. In this article, we review genes that have been demonstrated by gene targeting in mice to be required in the uterus for implantation. In particular, we focus on a specific class of developmental control genes, the mammalian Hox genes, and their role in this process. Lastly, we attempt to synthesize current knowledge about the genetic control of implantation and to build a working genetic model for the implantation pathway.

Animals↗

Dietary variety within food groups: association with energy intake and body fatness in men and women.

BACKGROUND: Short-term experimental studies suggest that dietary variety may influence body fatness but no long-term human studies have been reported. OBJECTIVE: The purpose of this study was to determine whether dietary variety within food groups influences energy intake and body fatness. DESIGN: Seventy-one healthy men and women (aged 20-80 y), who provided accurate reports of dietary intake and completed a body-composition assessment, were studied. RESULTS: Dietary variety was positively associated with energy intake within each of 10 food groups (r = 0.27-0.56, P < 0.05). In multiple regression analysis with age and sex controlled for, dietary variety of sweets, snacks, condiments, entrées, and carbohydrates (as a group) was positively associated with body fatness (partial r = 0.38, P = 0.001) whereas variety from vegetables was negatively associated (partial r = -0.31, P = 0.01) (R2 = 0.46, P < 0.0001). In separate models, both a variety ratio (variety of vegetables/variety of sweets, snacks, condiments, entrées, and carbohydrates) and percentage dietary fat were significant predictors of body fatness (controlled for age and sex, partial r = -0.39 and 0.31, respectively, P < 0.01). However, dietary fat was no longer significantly associated with body fatness when the variety ratio and dietary fat were included in the same model. CONCLUSIONS: Our data, coupled with those of previous short-term studies, suggest that a high variety of sweets, snacks, condiments, entrées, and carbohydrates coupled with a low variety of vegetables promotes long-term increases in energy intake and body fatness. These findings may help explain the rising prevalence of obesity.

Adipose Tissue↗

Peripheral nerve regeneration in CNTF knockout mice.

OBJECTIVES: To determine the role of ciliary neurotrophic factor (CNTF) in the regeneration of the mouse sciatic nerve following injury by studying the CNTF knockout mouse in a blinded, randomized and controlled evaluation. STUDY DESIGN: Fifty-eight wild-type and 57 CNTF knockout mice were randomly assigned to one of four treatment groups: sham surgery (sciatic nerve exposure), sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair using 10-0 monofilament suture. Walking track analysis was performed before and after surgery at weekly intervals for 7 weeks, using a previously described formula. At the completion of walking track analysis, morphometric histological analysis of axon number and axon diameter in the distal sciatic nerves was performed. RESULTS: The wild-type and knockout mice that underwent only sham surgery had no change in their walking tracks during the study interval (P = .30 on postoperative day 49). The wild-type mice that underwent sciatic nerve crush showed complete functional recovery (P = .66 on postoperative day 28), but the CNTF knockout mice whose sciatic nerves were crushed did not fully recover (P = .05 on postoperative day 49). The CNTF knockout and wild-type mice showed similar levels of recovery after transection without repair (P = .78), and the rate of contracture formation was not significantly different (P = .40). The CNTF knockout and wild-type mice showed similar levels of recovery after epineurial repair (P>.31), however the rate of severe contractures was greater in the CNTF knockout mice (6 of 13) than in the wild-type mice (2 of 12) (P = .11). CONCLUSION: The absence of CNTF impairs the ability of mice to recover from a sciatic nerve crush injury. There is also a trend toward a greater rate of contracture formation after sciatic nerve transection and epineurial suture repair when CNTF is unavailable. These findings suggest that CNTF is important for recovery of neuronal function following crush and transection nerve injuries.

Animals↗

Genomic structure of the rat major AP endonuclease gene (Apex) with an adjacent putative O-sialoglycoprotease gene (Prsmg1/Gcpl1) and a processed Apex pseudogene (Apexp1).

Genomic sequencing and chromosomal assignment of the gene encoding rat APEX nuclease, a multifunctional DNA repair enzyme, were performed. An active Apex gene and a processed pseudogene were isolated from a rat genomic library. The active Apex gene consists of 5 exons and 4 introns spanning 2.1 kb. The putative promoter region of the Apex gene lacks the typical TATA box, but contains CAAT boxes and a CpG island having putative binding sites for several transcription factors, such as Sp1, AP-2, GATA-1 and ATF. A putative O-sialoglycoprotease (a homologue of Pasteurella haemolytica glycoprotease, gcp; abbreviated as Prsmg1/Gcpl1) gene consisting of 11 exons and 10 introns spanning 7.3 kb lies immediately adjacent to the Apex gene in a 5'-to-5' orientation. The Apex gene locus was mapped to rat chromosome 15p12 using in situ hybridization. The processed pseudogene (designated as rat Apexp1) has a nucleotide sequence 87.1% identical to that of the rat Apex cDNA, although several stop codons interrupting the coding sequences and multiple nucleotide deletions were observed. The Apexp1 is located in an inactive LINE sequence. Calculation of nucleotide substitution rates suggests that the immediate, active progenitor of Apexp1 arose 23 million years ago and that the non-functionalization occurred 15 million years ago.

Animals↗

Chromophobe renal cell carcinoma: an immunohistochemical study of 21 Japanese cases.

Chromophobe renal cell carcinoma (RCC) is a newly established category of RCC composed histologically of characteristic "chromophobe" tumor cells. Although ultrastructural and immunohistochemical studies showed that these tumor cells present several features similar to those found in the intercalated cells of the collecting duct, immunohistochemical studies using antibody panels on a large number of cases are limited. We performed an immunohistochemical study of 21 Japanese cases of chromophobe RCC, along with cases of clear RCC and renal oncocytoma, to find hallmarks useful for precise differential diagnosis of these tumors. Chromophobe RCC was positive for epithelial membrane antigen but negative for vimentin. Cytokeratins did not show constant immunoreactivity in the three types of renal tumors. Furthermore, all of the chromophobe RCCs and renal oncocytomas were positive for E-cadherin but not for N-cadherin, whereas all of the clear RCCs were negative for E-cadherin, and 58% were positive for N-cadherin. The Ki-67 labeling indices were significantly lower in cases classified as (pT1) or Grade 2 chromophobe RCC than in cases of clear RCC. Immunoreaction for E-cadherin was demonstrated to be useful for distinguishing chromophobe RCC from clear RCC, and a low Ki-67 labeling index might indicate a favorable prognosis, as reported in several previous studies.

Adenocarcinoma↗