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Biomedical subjects

G Yu

Publications and source records attributed to G Yu.

At least 199 records · Page 11Linked to original sources
PubMed1996

Steroid receptor transcriptional synergy is potentiated by disruption of the DNA-binding domain dimer interface.

The dimer interface within the DNA-binding domain (DBD) of the steroid receptors stabilizes receptor binding to a palindromic DNA site termed a hormone response element (HRE) and is essential for receptor transcriptional activity when a single HRE drives transcription of a target gene. However, most steroid-responsive genes are driven by multiple HREs, and synergy between HREs is an important determinant of receptor activity. We have examined the effects of mutations within the DBD dimer interface on synergistic transcriptional activation by the mineralocorticoid and glucocorticoid receptors. As expected, mutations in either the mineralocorticoid receptor or glucocorticoid receptor that destabilized the DBD dimer interface disrupted receptor binding and activity at a single HRE. However, in striking contrast, these same mutations markedly increased receptor synergistic activity on a reporter gene containing multiple HREs and modestly increased DNA binding. Reestablishing intersubunit contacts by compensatory mutation or by coexpression of complementary mutants returned activity to near-wild type levels. These observations strongly suggest that the DBD dimer interface restrains steroid receptor transcriptional synergy and may play an unexpected role in the regulation of receptor activity.

Amino Acid Sequence↗
PubMed1996

[The lateral abdominal island flap--the lateral intercostal neurovascular island flap].

This work studied the lateral abdominal island flap, its clinical value, transposition range and the practicability of a modified operative method. Five lateral abdominal island flaps were used in 5 patients. Four of them were for axillary radiation ulcers after radical mastectomy. One was for a sacral defect after resection of a recurrent fibrosarcoma. All the flaps obtained satisfactory results. Clinical applications revealed that the blood supply of the lateral abdominal skin was mainly from the lateral cutaneous branches of the 9th, 10th and 11th intercostal arteries, among which there were numerous anastomoses. The lateral abdominal island flap can be pedicled with any of these lateral cutaneous branches. The long pedicle of the flap provides a wide range of trnasposition from the axilla to the sacrum. As the pedicle of the flap contains the lateral cutaneous branch of the intercostal nerve, the flap can bring sensation function to the recipient area. The modified operative method of the lateral abdominal island flap is introduced.

Adult↗
PubMed1996

[Clinical evaluation of Doppler ultrasonic angiography].

The diagnosis of carotid surgery is based on angiography. 1607 Doppler cases of extracranial carotid Doppler ultrasonic angiography were examined. Among them, 1527 had remote cerebral stroke and 285 had carotid endarterectomy. The results indicated that the group of carotid endarterectomy conformed to Doppler ultresonic angiograph of preoperation and were consistent with 10 positive and 10 negative cases of random sampling. The method has advantages of easy operation, time-saving, low expenses, no complication and reliable diagnosis to use Doppler ultrasonic angiograph in carotid surgery. It was worth spreading in non-invasive arterial morphology and hemodynamics.

Adult↗
PubMed1996

[Traumatic facial nerve injury in rabbits: a quantitative pathologic study].

Six kinds of facial nerve injury in 136 facial nerves of 68 rabbits were studied by quantitative pathology. The ratio of intrafascicular axon crossing and the ratio of intrafascicular area can reflect the extent of the lesions for non-cut injury (exposure, compression, stretch and crush) effectively. However, the ratio of mesial to distal intrafascicular area should be combined for the evaluation of cut injury (division and anastomosis). The mean optical density (F1), axon area (F13), and homogeneous degree (F49) can reflect quantitatively the form and extent of the single axon lesion and its content. The morphologic parameter (F10) can reflect the change of axon morphology. The results of quantitative pathologic study support the histopathologic study, and provide additional knowledge about the progress of serial axon lesions.

Animals↗
PubMed1996

[The sialographic characteristics of Warthin tumor in the parotid gland].

The sialograms of 80 cases with Warthin tumor in parotid gland were analysed. The sialographic characteristics were found as follows: irregular arrangement, dilation and narrow of branch ducts which surrounded the tumor, sausagelike change of main ducts just like that seen in obstructive parotitis, and spot-like dilation of the terminal ducts. The comparative study on roentgen-pathology showed that the spot-like dilation of the terminal ducts was related to the dilation of interlobular duct of the gland surrounding the tumor. The roentgen differential diagnosis of Warthin tumor from the aggressive benign tumor and Sjögren syndrome is discussed.

Adenolymphoma↗
PubMed1996

[The relationship of function and pathology of submandibular gland with sialolithiasis].

Submandibular glands with sialolithiasis are analysed histopathologically. The formation of the calculi of the submandibular glands may be related to the sialoadentitis and to the changes of saliva composition. Mineralization of the organic matrix may be one of the cause of calculus formation. By comparison of the glandular function with the pathology of the gland, it shows that the reduction of glandular function is associated with the severity of grandular inflammation. When function index is normal, grandular inflammation is in the Stage I or II, while it decreases or zero, grandular inflammation is in the Stage III or IV. Glandular function index may predict the severity of grandular inflammation.

Adult↗
PubMed1996

[Functional evaluation of the mitochondria from Warthin tumor].

The mitochondria were isolated from 8 surgical specimens of Warthin tumor of the parotid and the activity of the respiration was evaluated. The average respiratory control rate (RCR) of the mitochondria of the tumors (1.12 +/- 0.50) was lower than that of the normal mitochondria (2.10 +/- 0.75). The preliminary experiment showed a loosely coupled state of oxidative phosphorylation. It indicates that the hyperplasia of the mitochondria in the Warthin tumor results from the metabolic disturbance of the tumor and it is a compensation in the cellular level.

Adenolymphoma↗
PubMed1996

[The application of regional excision of parotid gland in the treatment of Warthin tumors].

The regional excision of parotid gland (resection of the tumor with its surrounding glands) was applied in 54 cases with Warthin tumor. Its role was evaluated by follow-up study, iodine-starch test (Minor test), radionuclide scintigraphy, and comparison with superficial parotidectomy. The results showed that regional excision had the following advantages: shortening the time of operation, decreasing the injury of facial nerve, avoiding the facial deformity and Frey syndrome, and reserving the function of parotid glands. The theoretical basis, indications, and some considerable questions during the operation were discussed.

Adenolymphoma↗
PubMed1995

Alterations of alpha1-adrenoceptor subtypes in the hearts of thyroxine-treated rats.

Alterations in the cardiac alpha1-adrenoceptor and its subtypes in thyroxine-treated rats were studied by means of radioligand binding assays, measurement of contractile response and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that in thyroxine-treated rats the cardiac alpha1-adrenoceptor density (Bmax) was reduced from 51.6 +/- 6.0 fmol/mg in control to 40.9 +/- 3.7 fmol/mg (P<0.01); and the percentage of high affinity sites for 5-methyl-urapidil decreased from 23.3 +/- 2.0% in control to 10.8 +/- 2.0% in thyroxine-treated rats (P<0.05). The data indicated that the high-affinity sites for 5-methyl-urapidil (alpha1A-adrenoceptor) were reduced (from 12.0 to 4.4 fmol/mg), but the low-affinity sites for 5-methyl-urapidil (alpha1B- plus alpha1D-adrenoceptor) were not changed (from 39.6 to 36.5 fmol/mg). RT-PCR showed that steady-state levels of mRNA for alpha1A- and alpha1B-adrenoceptors were decreased, while that for alpha1D-adrenoceptor was raised in thyroxine-treated rats. In the isolated electrically driven left atria the phenylephrine-induced maximal contractions were reduced from 258 +/- 17 mg in control to 188 +/- 24 mg in thyroxine-treated rats (P<0.05). The pA2 values of 5-methyl-urapidil were reduced from 8.89 +/- 0.36 in control to the hyperthyroidism of 7.87 +/- 0.43 in thyroxine-treated rats (P<0.05). Chlorethylclonidine preincubation shifted concentration-response curves for phenylephrine to the right and reduced the maximal response to a lesser extent in thyroxine-treated rats than in control rats. Thus we concluded that the total number of cardiac alpha1-adrenoceptors is reduced in thyroxine-treated rats. The change is subtype selective, with alpha1A- and alpha1B-adrenoceptors being reduced in number and alpha1D-adrenoceptor being increased.

Animals↗
PubMed1995

Differential expression of CAP and CAP2 in adult rat tissues.

We previously reported the identification of the human CAP and CAP2 genes which encode proteins related to the yeast adenylyl cyclase (CYR)-associated CAP protein. The rat CAP homolog, MCH1, has also been previously cloned. We have cloned a cDNA encoding the rat homolog of CAP2. Rat CAP/MCH1 and CAP2 are 63% identical to each other. Using the reverse transcription-polymerase chain reaction (RT-PCR) method, we have examined CAP/MCH1 and CAP2 mRNA levels in various adult rat tissues. Our results show a dramatic difference in the pattern of expression of these two genes. Consistent with previous reports, we detected CAP/MCH1 mRNA in all tissues examined; however, levels vary substantially between tissues. In particular, we found that CAP/MCH1 mRNA are present at relatively high levels in spleen, testes and lung, at moderate levels in brain, kidney, liver and small intestine, and at significantly lower levels in heart, skeletal muscle and skin. We have also investigated the levels of CAP/MCH1 in rat tissues by immunoblotting with a polyclonal antibody raised against a human CAP::GST fusion protein. In general, we find that the CAP/MCH1 mRNA levels reflect the amount of CAP/MCH1 found in different tissues. In contrast, CAP2 transcripts were present at relatively high levels in testes, at moderate levels in brain, heart and skeletal muscle, at lower levels in lung, skin, kidney and small intestine, and were undetectable in liver or spleen. The differences between the sequences and expression patterns of CAP/MCH1 and CAP2 are significant and suggest that these proteins have distinct functional roles.

Adaptor Proteins, Signal Transducing↗
PubMed1995

The essential transcription factor, Mcm1, is a downstream target of Sln1, a yeast "two-component" regulator.

In a search for mutants exhibiting altered activity of the yeast transcription factor, Mcm1, we have identified the SLN1 gene, whose product is highly related to bacterial two-component sensor-regulator proteins. sln1 alleles identified in our screen increased Mcm1p-mediated transcriptional activation, while deletion of the SLN1 locus severely reduced Mcm1p activity. Our data establish that Mcm1p is a downstream target of the Sln1 signaling pathway. Yeast Sln1p was recently shown to be involved in osmoregulation and to depend on the Hog1 MAP kinase (Maeda, T., Wurgler-Murphy, S., and Saito, H. (1994) Nature 369, 242-245). We show that SLN1-mediated regulation of Mcm1p activity is independent of the Hog1 MAP kinase, and suggest that the role of SLN1 is not restricted to osmoregulation.

DNA-Binding Proteins↗
PubMed1995

Radicicol, a protein tyrosine kinase inhibitor, suppresses the expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide and in experimental glomerulonephritis.

Two isoforms of cyclooxygenase (COX) have been identified in eukaryotic cells: a constitutively expressed COX-1 and mitogen-inducible COX-2, which is selectively expressed in response to various inflammatory stimuli. Thus, COX-2 instead of COX-1 is implicated to produce prostanoids mediating inflammatory responses. Major efforts have been focused on identifying nonsteroidal anti-inflammatory drugs (NSAIDS) which can selectively inhibit the enzyme activity of COX-2. Such NSAIDS would be more desirable anti-inflammatory agents in comparison to NSAIDS which inhibit both COX-1 and COX-2. Other than glucocorticoids, pharmacological agents which can selectively suppress the expression of COX-2 without affecting that of COX-1 have not been identified. We report here that radicicol, a fungal antibiotic, is a potent protein tyrosine kinase inhibitor, and that it inhibits the expression of COX-2 without affecting COX-1 expression in lipopolysaccharide (LPS)-stimulated macrophages with the IC50 value of 27 nM. Radicicol inhibited tyrosine phosphorylation of p53/56lyn, a Src family tyrosine kinase and one of the major tyrosine-phosphorylated proteins in LPS-stimulated macrophages. Radicicol also inhibited COX-2 expression in vivo in glomeruli of rats with experimental glomerulonephritis induced by the anti-glomerular basement membrane antibodies, in which COX-2 expression is known to be enhanced. The enzyme activity of COX-1 or COX-2 was not affected by radicicol in macrophages. Radiciciol also suppressed the COX-2 expression induced by IL-1 beta in rat smooth muscle cells. Other protein tyrosine kinase inhibitors suppressed the LPS-induced COX-2 expression in macrophages but at much higher concentrations than needed for radicicol. Radicicol did not inhibit the COX-2 expression induced by phorbol 12-myristate 13-acetate in macrophages. These results suggest that the activation of tyrosine-specific protein kinases is the proximal obligatory step in the LPS-induced signal transduction pathway leading to the induction of COX-2 expression in macrophages. The magnitude of the inhibition of COX-2 protein synthesis by radicicol was much greater than that of the steady state levels of COX-2 mRNA. These results suggest that radicicol inhibits COX-2 expression mainly at post-transcriptional steps.

Animals↗
PubMed1995

Regulation of HIV-1 gag protein subcellular targeting by protein kinase C.

The human immunodeficiency virus type 1 internal structural protein precursor, p55, and its corresponding matrix proteolytic fragment, p17, are phosphorylated at Ser111 by protein kinase C. COS-7 cells transfected with plasmids encoding either the wild-type or Ser111-->Ala mutated human immunodeficiency virus type 1 gag gene matrix domain proteins were treated with phorbol 12-myristate 13-acetate (PMA), and the phosphorylation of the expressed p17 proteins was examined by radioimmunoprecipitation, SDS-polyacrylamide gel electrophoresis, and autoradiography. PMA treatment of transfected cells resulted in a 4-5-fold increase in wild-type p17 (but not mutated p17) phosphorylation; however, mutated p17 exhibited a low basal level of phosphorylation that was not affected by PMA, suggesting that additional sites were phosphorylated. PMA treatment of cells expressing wild-type p17 produced a dramatic shift in the localization of p17 from the cytosol to the membrane fraction within 8-15 min, followed by a slow quantitative dissociation of p17 back into the cytosol by 90 min. The cytosol-to-membrane translocation was dependent on N-myristoylated p17 since cells expressing p17 with a Gly2-->Ala mutation did not localize to the membrane. PMA also failed to induce the translocation of fully N-myristoylated Ser111-->Ala p17, suggesting that p17 phosphorylation at Ser111 was responsible for membrane association. This conclusion was confirmed by the finding of phosphorylated wild-type p17 in the membrane fraction only after PMA treatment. These results suggest that a "myristoyl-protein switch" regulates the reversible membrane targeting of p17 by protein kinase C-mediated phosphorylation. This signal may provide a mechanism for the cellular regulation of virus development through modulation of gag protein-related developmental steps such as capsid targeting, assembly, encapsidation, budding, and maturation.

Animals↗
PubMed1995

The structured clinical instruction module: a novel strategy for improving the instruction of clinical skills.

We have previously shown that both medical students and residents demonstrate numerous important deficits when evaluating patients with abdominal complaints. To address these deficits, we implemented a pilot instructional program derived from the Objective Structured Clinical Examination. Fifty third-year medical students were presented with a 1-hr Structured Clinical Instruction Module (SCIM) of five stations, each station addressing a different aspect of the surgical evaluation of the abdomen. Simulated patients were present at two of the stations. Faculty from appropriate disciplines were present at the stations to provide standardized instruction according to predetermined curricular objectives. The medical students evaluated the SCIM for its specific characteristics, and they evaluated each of the five stations for its efficacy in increasing their clinical skills. All the specific aspects of the SCIM were given a rating significantly higher than neutral (P < 0.0001). Students agreed most strongly that the faculty were well prepared for the SCIM and that the faculty were enthusiastic. All of the SCIM stations were given a rating significantly higher than average (P < 0.0001). When compared to a conventional workshop, the SCIM scored significantly higher on all three common evaluation items. The SCIM was very well received by medical students as a format for clinical instruction. This unique modification of the Objective Structured Clinical Examination has potential for teaching important clinical skills that are not consistently mastered within current surgical curricula.

Adult↗
PubMed1995

Interaction between gallopamil and cardiac ryanodine receptors.

1. In a sarcoplasmic reticulum fraction obtained from rat hearts, the analysis of equilibrium [3H]-ryanodine binding showed high and low affinity sites (KD = 1.3 nM and 2.8 microM, Bmax = 2.2 pmol mg-1 and 27.8 pmol mg-1). The dissociation rate constant increased at 1 microM vs 4 nM [3H]-ryanodine concentration, and micromolar ryanodine slowed the dissociation of nanomolar ryanodine. 2. The binding of 4 nM [3H]-ryanodine was not affected by gallopamil, while the binding of 100 nM to 18 microM [3H]-ryanodine was partly displaced. Data analysis suggested that gallopamil inhibited low affinity [3H]-ryanodine binding, with IC50 in the micromolar range. 3. Gallopamil decreased the dissociation rate constant of 1 microM [3H]-ryanodine. While gallopamil alone did not affect the dissociation of 4 nM [3H]-ryanodine, gallopamil and micromolar ryanodine slowed it to a greater extent than micromolar ryanodine alone. 4. Our results are consistent with the hypothesis that the ryanodine receptor is a negatively cooperative oligomer, which undergoes a sequential alteration after ryanodine binding. Gallopamil has complex actions: it inhibits ryanodine binding to its low affinity site(s), and probably modulates the cooperativity of ryanodine binding and/or the transition to a receptor state characterized by slow ryanodine dissociation. These molecular actions could account for the previously reported effect of gallopamil on the sarcoplasmic reticulum calcium release channel.

Animals↗
PubMed1995

Intraoperative diagnostic techniques for stereotactic brain biopsy: cytology versus frozen-section histopathology.

Stereotactic brain biopsy has gained widespread acceptance as a primary diagnostic tool for the evaluation of intracranial lesions. Intraoperative evaluation of such specimens has included the use of both cytological and frozen section histologic techniques. The current study seeks to compare the diagnostic utility of frozen section histopathology and cytology in the intraoperative evaluation of stereotactic brain biopsies in HIV-seropositive patients. Seventy-five HIV-seropositive patients undergoing stereotactic brain biopsy for the evaluation of intracranial lesions were evaluated; intracranial diseases were predominantly infectious or hematologic malignancies. Comparison of frozen section and cytology as a means of intraoperative evaluation showed cytology to have a greater sensitivity (86 vs. 78%), positive (95 vs. 90%) and negative (50 vs. 39%) predictive values and a greater overall diagnostic efficiency (84 vs. 75%) than frozen section. Thus, cytology is a highly effective tool equaling and in some cases surpassing frozen section in terms of sensitivity, predictive value, and overall accuracy. Cytologic examination may often be used as the sole means of intraoperative diagnosis, obviating the need for the freezing and sectioning of fresh tissue and potentially reducing specimen turn around time as well. In other cases, cytology can be used in conjunction with other methodologies for arriving at both intraoperative and final diagnoses in these often difficult cases.

Biopsy↗
PubMed1995

Postischemic changes in cardiac sarcoplasmic reticulum Ca2+ channels. A possible mechanism of ischemic preconditioning.

We investigated the modifications of cardiac ryanodine receptors/sarcoplasmic reticulum Ca2+ release channels occurring in ischemic preconditioning. In an isolated rat heart model, the injury produced by 30 minutes of global ischemia was reduced by preexposure to three 3-minute periods of global ischemia (preconditioning ischemia). The protection was still present 120 minutes after preconditioning ischemia but disappeared after 240 minutes. Three 1-minute periods of global ischemia did not provide any protection. In the crude homogenate obtained from ventricular myocardium, the density of [3H]ryanodine binding sites averaged 372 +/- 18 fmol/mg of protein in the control condition, decreased 5 minutes after preconditioning ischemia (290 +/- 15 fmol/mg, P < .01), was still significantly reduced after 120 minutes (298 +/- 17 fmol/mg, P < .05), and recovered after 240 minutes (341 +/- 21 fmol/mg). Three 1-minute periods of ischemia did not produce any change in ryanodine binding. The Kd for ryanodine (1.5 +/- 0.3 nmol/L) was unchanged in all cases. In parallel experiments, the crude homogenate or a microsomal fraction was passively loaded with 45Ca, and Ca(2+)-induced Ca2+ release was studied by the quick filtration technique. In both preparations, the rate constant of Ca(2+)-induced Ca2+ release decreased 5 and 120 minutes after preconditioning ischemia (homogenate values: 19.7 +/- 1.4 and 18.9 +/- 0.9 s-1 vs a control value of 25.4 +/- 1.7 s-1, P < .05 in both cases) and recovered after 240 minutes (23.0 +/- 1.9 s-1). The Ca2+ dependence of Ca(2+)-induced Ca2+ release was not affected by preconditioning ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗