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Biomedical subjects

Q Yang

Publications and source records attributed to Q Yang.

At least 163 records · Page 9Linked to original sources

Women with a reduced ovarian complement may have an increased risk for a child with Down syndrome.

Advanced maternal age is the only well-established risk factor for trisomy 21 Down syndrome (DS), but the basis of the maternal-age effect is not known. In a population-based, case-control study of DS, women who reported surgical removal of all or part of an ovary or congenital absence of one ovary were significantly more likely to have delivered a child with DS than were women who did not report a reduced ovarian complement (odds ratio 9.61; 95% confidence interval 1.18-446.3). Because others have observed that women who have had an ovary removed exhibit elevated levels of FSH and similar hallmarks of advanced maternal age, our finding suggests that the physiological status of the ovary is key to the maternal-age effect. In addition, it suggests that women with a reduced ovarian complement should be offered prenatal diagnosis.

Adolescent↗

Thymidine phosphorylase expression in tumor stroma of uterine cervical carcinomas: histological features and microvessel density.

Immunohistochemical staining was performed on 91 cases of uterine neoplasm in order to determine if expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (TP) correlates with tumor microvessel density (MVD) and histological parameters of uterine carcinomas in tumor cells and in tumor stroma. The sample group consisted of 72 primary invasive squamous cell carcinomas of the cervix (ISC) and 19 cervical intraepithelial neoplasms (CIN) of the uterus. In ISC of the cervix, TP expression in tumor stroma showed a significant correlation with a non-keratinizing histological subtype (P < 0.001) and with an infiltrating invasive pattern (P < 0.001). However, in tumor cells the TP expression showed a higher correlation with a keratinizing histological subtypes (P = 0.009). MVD was significantly higher (P = 0.002) in tumors showing high TP expression in stroma than in tumors with low expression. These findings suggest that the TP expression in stromal cells, rather than in tumor cells, may play a role in promoting microvessel growth in cervical squamous cell carcinoma, and angiogenesis may also have an association with tumor cell invasion.

Carcinoma, Squamous Cell↗

The winged-helix/forkhead protein myocyte nuclear factor beta (MNF-beta) forms a co-repressor complex with mammalian sin3B.

Winged-helix/forkhead proteins regulate developmental events in both invertebrate and vertebrate organisms, but biochemical functions that establish a mechanism of action have been defined for only a few members of this extensive gene family. Here we demonstrate that MNF (myocyte nuclear factor)-beta, a winged-helix protein expressed selectively and transiently in myogenic precursor cells of the heart and skeletal muscles, collaborates with proteins of the mammalian Sin3 (mSin3) family to repress transcription. Mutated forms of MNF-beta that fail to bind mSin3 are defective in transcriptional repression and in negative growth regulation, an overexpression phenotype revealed in oncogenic transformation assays. These data extend the known repertoire of transcription factors with which mSin3 proteins can function as co-repressors to include members of the winged-helix gene family. Transcriptional repression by MNF-beta-mSin3 complexes may contribute to the co-ordination of cellular proliferation and terminal differentiation of myogenic precursor cells.

Adenovirus E1A Proteins↗

Effect of maturation on nerve excitability in an experimental model of threshold electrotonus.

Threshold electrotonus (TE) is a new tool for investigating axonal function noninvasively in vivo. To increase its potential clinical value, we developed a rat model of TE, and examined the effects of maturation and pharmacological intervention. We recorded TE in 92 male rats (body weight 90-650 g) by stimulating the motor nerve in the tail, and applying 100-ms conditioning currents. Motor conduction velocities increased up to a body weight of 330 g, and remained constant thereafter. TE in mature rats was similar to that in humans, and two parameters were analyzed: TEd(10-20) or the mean threshold reduction 10-20 ms after the onset of the depolarizing conditioning current at 40% of threshold intensity; and TEh(10-20) or the corresponding threshold decrease on hyperpolarization. Like latency, the absolute value of TEh(10-20) decreased up to 330 g, and then stabilized thereafter, probably reflecting the progressive increase in the axonal diameter and relative reduction in internodal impedance. In contrast, TEd(10-20) gradually decreased up to 330 g, and then jumped to a higher level, which was maintained for animals of >400 g. 4-Aminopyridine, a blocker of fast potassium channels, selectively increased TEd(10-20) only in the immature or young (<330 g) rats. This suggests that, in the mature animals, fast potassium channels become sequestrated from the nodal membrane and not activated in response to nodal depolarization. These findings indicate that mature rats (>400 g) may provide a useful experimental model for interpreting abnormal TE responses in humans, and provide evidence for nonlinear maturation of potassium channel function in myelinated axons.

4-Aminopyridine↗

The effect of transient balloon occlusion of the mitral valve on left atrial appendage blood flow velocity and spontaneous echo contrast.

BACKGROUND: Spontaneous echo contrast (SEC) is a phenomenon that is commonly seen in areas of blood stasis. It is a slowly moving, cloud-like swirling pattern of "smoke" or increased echogenicity recorded on echocardiography. SEC is commonly seen in the left atrium of patients with mitral stenosis or atrial fibrillation. The presence of SEC has been shown to be a marker of increased thromboembolic risk. HYPOTHESIS: By using transesophageal echocardiography during percutaneous balloon mitral valvotomy (PBMV), the study investigated the relationship between SEC and varying left atrial appendage (LAA) blood flow velocity in the human heart. METHODS: Thirty-five patients with rheumatic mitral stenosis underwent percutaneous balloon mitral valvotomy with intraoperative transesophageal echocardiography monitoring. We alternatively measured LAA velocities and observed the left atrium for various grades of SEC (0 = none to 4 = severe) before and after each balloon inflation. RESULTS: Left atrial appendage maximal ejection velocity was reduced from 35 +/- 14 to 6 +/- 2 mm/s at peak balloon inflation and increased to 40 +/- 16 mm/s after balloon deflation. In comparison with the values before balloon inflation and after balloon deflation, LAA velocities were significantly lower (p < 0.001). New or increased SEC grade was observed during 54 of 61 (88%) inflations and unchanged in 7 (12%) inflations at peak balloon inflation. Spontaneous echo contrast became lower in grade after 55 balloon deflations (90%), completely disappeared after 18 deflations (30%), and remained unchanged after 6 deflations (10%). The mean time to achieve maximal SEC grade (2.5 +/- 1.2 s) coincided with the mean time to trough LAA velocities (2.3 +/- 1.1 s) after balloon inflation. Upon deflation, the mean time to lowest SEC grade (2.9 +/- 1.8 s) coincided with mean time to achieve maximal LAA velocities (2.7 +/- 1.6 s). CONCLUSION: During balloon inflation, the severity of SEC was enhanced with corresponding reduction in LAA flow velocity. Upon balloon deflation, SEC lightens or disappears with increase in LAA flow velocity.

Adolescent↗

Open-loop and closed-loop optokinetic nystagmus (OKN) in myasthenia gravis and nonmyasthenic subjects.

Optokinetic nystagmus (OKN) eye movements of myasthenia gravis (MG) and nonmyasthenic ocular palsies, and normal subjects were examined under closed-loop and open-loop conditions. The open-loop OKN condition was achieved by adding the signal of eye-movement velocity of OKN to the computer-generated signal controlling the stimulus grating moving. The OKN was recorded by means of electromagnetic search scleral coil technique. In MG patients, the open-loop gains of OKN increased significantly after the intramuscular injection of an acetylcholinesterase inhibitor, neostigmine, while the closed-loop OKN gains were not significantly changed. Both the closed-loop and open-loop OKN gains of normal subjects and nonmyasthenic patients were not increased for the administration of neostigmine. The experimental results indicated that the open-loop OKN gain could be sensitive to reflect the changes of the function of neuromuscular junction in MG patients.

Adolescent↗

Thymidine phosphorylase expression correlates with tumor differentiation and Bcl-2 in invasive breast cancer.

BACKGROUND: Angiogenesis plays an important role in the growth and metastasis of solid tumors. Several angiogenic factors have been identified, and thymidine phosphorylase (TP) is thought to be one such factor. To date, little information is available on the relationship between TP and other clinicopathological variables. METHODS: Formalin-fixed, paraffin-embedded materials from 116 primary breast carcinomas were used. The expression of TP, estrogen receptor, Bcl-2, Bax, p53, c-erbB-2 and MIB-1 was examined by immunohistochemical methods. RESULTS: Nuclear and/or cytoplasmic TP expression was observed in the neoplastic cells, and accentuation of TP was often present at the infiltrating tumor edge and intraductal spread region. Tumor cell TP expression was significantly inversely correlated with histological grade (p< 0.05) and positively correlated with Bcl-2 expression, but no association with other tumor variables was found. CONCLUSIONS: TP is associated with Bcl-2 expression and tumor differentiation in breast cancer. TP may be a new prognostic parameter for breast cancer.

Breast Neoplasms↗

Differential complementation of a Neurospora crassa Galpha(i) mutation using mammalian Galpha protein genes.

Heterotrimeric (alphabetagamma) G proteins interact with sensory receptors to transduce signals to downstream effectors in eukaryotes. We previously reported that GNA-1 from Neurospora crassa is a microbial member of the Galphai family found in higher organisms. Deletion of gna-1 leads to female sterility, slower growth rates on normal and hyperosmotic solid medium, and increased resistance to heat and oxidative stress. In this study we compare mammalian genes for proteins of the Galphai sub-family (Galphai, Galphao, Galphat and Galphaz), and Galphas (which is not a member of the Galphai family) with the N. crassa gna-1 gene with respect to their ability to complement deltagna-1 phenotypes. Northern analysis detected full-length transcripts of all these genes, except that for Galphai, in N. crassa transformants. Measurements of pertussis toxin-catalyzed ADP-ribosylation and Western analysis showed that the GNA-1, Galphaz, Galphao and Galphas proteins were present in the respective transformed strains. Strains in which the mammalian Galpha protein could be detected were subjected to phenotypic testing. During the vegetative cycle, none of the mammalian Galpha genes complemented the thermotolerance phenotype of deltagna-1. However, the three expressed mammalian Galpha genes achieved at least partial complementation of the defects in vegetative apical extension rate. cAMP levels did not correlate with restoration of vegetative growth rate by the mammalian genes. During the sexual cycle, Galphao was the only mammalian Galpha gene that rescued the defect in female fertility characteristic of deltagna-1 strains. Alignment of GNA-1, Galphaz, Galphao and Galphas protein sequences revealed correlations between the observed complementation pattern and the degree of identity to GNA-1 in various functional motifs. The finding that Galphac gave the best restoration of vegetative growth but could not restore normal female fertility implies that GNA-1 regulates different pathways that are important for vegetative and sexual growth in N. crassa.

Amino Acid Sequence↗

R127W-HNF-4alpha is a loss of function mutation but not a rare polymorphism and causes Type II diabetes in a Japanese family with MODY1.

AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause the type 1 form of maturity-onset diabetes of the young (MODY1). The R127W mutation is a missense mutation located in the T-box region of HNF-4alpha that was first identified in a Japanese family with MODY. We have examined the functional properties of this mutation in order to clarify the molecular basis of MODY1. METHODS: The intracellular localisation, DNA binding ability, transactivation activity and functional synergism with the coactivator CREB-binding protein (CBP) of R127W-HNF-4alpha were investigated. RESULTS: The nuclear import and functional synergy with CBP of R127W-HNF-4alpha were normal. The DNA binding ability of the mutant was decreased as was its transcriptional activation of the HNF-1alpha and L-type pyruvate kinase (PKL) genes. CONCLUSION/INTERPRETATION: The R127W mutation seems to be a loss-of-function mutation.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

Identification of missense mutations in the hepatocyte nuclear factor-3beta gene in Japanese subjects with late-onset Type II diabetes mellitus.

AIMS/HYPOTHESIS: Hepatocyte nuclear factor (HNF)-3beta, a transcription factor expressed in pancreatic beta cells, is an upstream regulator of HNF-1alpha/MODY3, HNF-4alpha/MODY1 and IPF1/MODY5 genes. Our previous screening of MODY subjects showed that mutations in the HNF-3beta gene are not a common cause of this form of diabetes in the Japanese. We tested the hypothesis that mutations in the HNF-3beta gene cause late-onset Type II (non-insulin-dependent) diabetes mellitus in this population. METHODS: Genotyping of the polymorphic TCC repeat in the HNF-3beta gene was done in 112 Japanese subjects with Type II diabetes (age at diagnosis > 35 and family history of Type II diabetes among their second-degree relatives) and 96 Japanese control subjects. Furthermore, we screened 57 Type II diabetic patients for mutations of the HNF-3beta gene. Transactivation activity of variant HNF-3beta was investigated by transfection assay. RESULTS: The distribution of alleles of the TCC repeat was similar between diabetic and control groups. Mutation screening identified two missense mutations, A86T and G114E. Neither mutation was observed in 225 control subjects. The transactivation activity of G114E-HNF-3beta was similar to that of wild typeHNF-3beta. In contrast, the activity of A86T-HNF-3beta was statistically significantly reduced to 83-86 % of that of wild type. CONCLUSIONS/INTERPRETATION: The A86T mutation in the HNF-3beta gene might be involved in the development of late-onset Type II diabetes in a small group of Japanese people.

Adult↗

Morphological Purkinje cell changes in spinocerebellar ataxia type 6.

Spinocerebellar ataxia type 6 (SCA6) was recently identified as a form of autosomal dominant spinocerebellar ataxia associated with a small CAG repeat expansion of the gene encoding an alpha 1 A-voltage-dependent calcium channel gene subunit on chromosome 19p13. In this study 50-microm-thick sections of cerebellar tissue from one patient with SCA6 were subjected to free-floating immunohistochemical staining with calbindin-D and parvalbumin antibodies. Severe loss of Purkinje cells was found, particularly in the vermis, and various morphological changes in Purkinje cells and their dendritic arborizations were demonstrated. Many of the remaining Purkinje cells were found to have heterotopic, irregularly shaped nuclei, an unclear cytoplasmic membrane outline, and somatic sprouts. Increased numbers of spine-like protrusions from swelling dendritic arborizations were found in the molecular layer. The axonal arrangement was disordered, and many torpedos were found in the granular layer and white matters. These morphological changes are completely different from those observed in paraneoplastic cerebellar degeneration (PCD) and multiple system atrophy (MSA) and are considered to be related to the genetic abnormality that causes abnormal development of Purkinje cells.

Aged↗

Perforated peptic ulcer: is there a difference between Eastern Europe and Germany? Copernicus Study Group and Acute Abdominal Pain Study Group.

BACKGROUND AND AIMS: Ulcer surgery and the epidemiology of peptic ulcer perforation have changed considerably in recent decades. PATIENTS/METHODS: Within two prospective studies, 170 perforated peptic ulcer patients from 12 Eastern European centres and 37 patients from 11 German centres were analysed. RESULTS: The median age of patients was 43 years in the Copernicus study and 49 years in the MEDWIS study (P=n.s.), being higher for MEDWIS female patients (73 vs 53 years, respectively; P<0.05). Female patients made up 17% (29/170) of the Copernicus study and 35% (40/170) of the MEDWIS study (P<0.05). Twenty-three per cent (40/170) of patients in the Copernicus study and 54% (20/37) in the MEDWIS study had gastric ulcer perforation (P<0.001). The proportion of definitive operations was higher in Eastern Europe (41.1%; 67/163) than it was in Germany (16.1%; 5/31) (P<0.01). German patients experienced more general complications than Eastern European patients (35 vs 12%, respectively; P<0.01) and a higher mortality [13% (5/37) vs 2% (4/170), respectively; P<0.01]. Delayed admission > or =12 h and age > or =60 years remained predictors for complications in multivariate logistic regression analysis. CONCLUSION: The proportion of both women and gastric ulcers was higher among German patients, while Eastern European patients underwent more definitive operations. German patients experienced more general complications and a higher mortality. Complications were related to high age and delayed admission.

Acute Disease↗

Acute appendicitis in late adulthood: incidence, presentation, and outcome. Results of a prospective multicenter acute abdominal pain study and a review of the literature.

BACKGROUND: Acute appendicitis is the second most common cause of surgical abdominal disease in late adulthood. It is a serious condition: major errors in management are made frequently and the condition is associated with significant morbidity and mortality. Data collected within a multicenter prospective trial and a literature review were used to analyze diagnostic and therapeutic difficulties in detail. METHODS: In a multicenter intervention study (MEDWIS A 70) data from 2,280 patients with acute abdominal pain were collected prospectively. Patients with histologically proven acute appendicitis, aged 50 years and older (n=102), were compared with younger patients (n=417) to determine differences in presentation, clinical course, and outcome. The basis for the literature review was a Medline search for appendicitis in late adulthood and in the elderly, covering the years 1980-1998. In addition, studies on clinical presentation of acute appendicitis in all age groups were also reviewed and appropriate data were extracted. RESULTS: Patients aged 50 years and older with acute abdominal pain had a significantly higher incidence of surgery. Fourteen percent had acute appendicitis (27% in younger patients), with an increased complication rate (20% vs. 8%) and mortality (3% vs. 0.2%). Significantly more signs and symptoms suggestive of acute abdominal disease and peritonitis were recorded among older patients, reflecting the higher perforation rate (35% vs. 13%). Clinical presentation of appendicitis in younger patients was far more ambiguous. There were no significant differences in outcome between older and younger patients as regards perforations. Perforations are directly associated with treatment delay. Overall delay is a result of late presentation of older patients to hospital and postadmission delay. CONCLUSIONS: Appendicitis in late adulthood is characterized by a delay in treatment, high perforation rates, and unfavorable outcome parameters, all mutually correlating. Older patients with acute abdominal pain are high-risk patients, unlike their younger counterparts. They have to be clinically evaluated by experienced surgeons within a narrow time margin. The problem of late presentation and/or referral should be addressed, perhaps by education of primary care physicians and the public.

Abdomen, Acute↗

In-frame deletions of BRCA1 may define critical functional domains.

The identification of genomic rearrangements involving more than 0.5 kb of the BRCA1 gene has confirmed a more complex mutation spectrum than was initially appreciated. Genomic rearrangements in BRCA1 represent 15% of all mutations in a group of French and American breast and ovarian cancer families and 36% of all mutations in a group of Dutch families. The rearrangements described to date range in size from 510 bp to 23.8 kb, are found throughout the gene, and are most frequently attributable to homologous recombination. We describe the identification of rearrangements in two breast and ovarian cancer families that involve 3.4 and 11.5 kb of the BRCA1 gene and span multiple exons but maintain the reading frame. Both gene rearrangements appear to result from Alu-mediated homologous recombination and have been detected by using a combination of protein truncation analysis and Southern blot analysis. These rearrangements result in the loss of amino acids that lie at the carboxy-terminus of the protein and that have previously been shown to have functional significance. Because these rearrangements result in the deletion of exons but maintain the reading frame, they may provide insights into specific regions and amino acids that have functional significance for the BRCA1 protein.

Alu Elements↗

Macroscopic assessment of the appendix at diagnostic laparoscopy is reliable.

BACKGROUND: Healthy-looking appendixes are often removed at laparoscopy for suspected appendicitis. This practice may have adverse secondary effects. METHODS: We reviewed the literature for the years 1978 to 1998 to analyze the negative appendectomy rates, complication rates, the accuracy of laparoscopic appendix assessment, and the incidence of false negative diagnosis of appendicitis at surgical and gynecological laparoscopy. RESULTS: The respective negative appendectomy rates were 22% and 15% in studies that compared laparoscopic with open appendectomy. The appendix was left in situ in 37% of 4,281 surgical diagnostic laparoscopies. There were instances of missed appendicitis among the 3,367 gynecological diagnostic laparoscopies performed on women for lower abdominal pain, and there were 188 appendectomies in this group. Studies comparing the macroscopic appearance of the appendix at operation with microscopic findings from the excised specimen had a false negative error rate of 3%. CONCLUSIONS: Contrary to general opinion, there is no substantial evidence to support the assumption that the macroscopic diagnosis of appendicitis is unreliable. High rates of conflicting diagnoses of excision specimens suggest that endoappendicitis has little clinical significance. At present, negative appendectomy rates are considerably higher for laparoscopic appendectomy than for the open approach. The role of diagnostic laparoscopy in suspected appendicitis should be reconsidered. It may be useful in particular subgroups of patients, but it is no substitute for good clinical judgment. Furthermore, it is not always necessary to perform an incidental appendectomy.

Appendectomy↗

Potato micro-tuber inducing hydroxylasiodiplodins from Lasiodiplodia theobromae.

Three hydroxylasiodiplodins were isolated from the mycelium extracts of Lasiodiplodia theobromae IFO 31059; and their structures were identified as (3R),(4S)-4-hydroxylasiodiplodin, (3R),(6R)-6-hydroxy-de-O-methyllasiodiplodin and (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin. All showed potato micro-tuber inducing activity.

Heterocyclic Compounds, 2-Ring↗

In vitro and in vivo characterization of biodegradable enoxacin microspheres.

The in vitro release and plasma concentration profiles of sustained release enoxacin microspheres intended for the treatment of bone and systemic infections due to sensitive strains of bacteria were investigated. Microspheres of enoxacin were prepared by using poly(glycolic acid-co-DL-lactic acid) (PLGA) by the emulsion solvent evaporation technique and characterized by in vitro release in an incubator, and in vivo release in the rat subcutaneous model. The microspheres were spherical in nature, and particle size range had a significant influence on the in vitro release. The enoxacin plasma concentration 2 h after the administration of treatments was two-fold higher in animals who received the free drug compared with those who received microspheres of size range 125-250 microm. The plasma of animals who received the free drug was depleted of enoxacin by the end of the first day. However, the plasma concentration of enoxacin in the animals who received microspheres was sustained above 0.5 microg/ml for about 8 days. The results show that biodegradable microspheres of enoxacin can be prepared which release the antibiotic in vivo for days following a subcutaneous administration. This should provide a means for the sustained treatment of infections due to sensitive strains of bacteria.

Animals↗