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Biomedical subjects

K Yan

Publications and source records attributed to K Yan.

At least 37 records · Page 2Linked to original sources

The G-protein betagamma complex.

The vast majority of signalling pathways in mammalian cells are mediated by heterotrimeric (alpha betagamma) G proteins. Reviewed here is regulation of signal transduction by the betagamma complex at different protein interfaces: subunit-subunit, receptor-G protein and G protein-effector. The role of diverse beta and gamma subunit types in achieving specificity in signalling and potentially unidentified functions for these subunits also are discussed.

Amino Acid Sequence↗

The increase of memory T cell subsets in children with idiopathic nephrotic syndrome.

Two-color and three-color flow cytometry was carried out to determine whether the memory T cells (CD45RO+ T cells) play a major role in lymphocyte dysfunction of 26 children with idiopathic nephrotic syndrome (INS). The INS patients were divided into three groups: (1) 10 patients who were not receiving glucocorticoid hormone (GCH) and were suffering from acute nephrotic state were referred to as N1; (2) 8 patients who were in remission maintained by GCH therapy alone were referred to as N2; (3) 8 patients who were free of GCH therapy for at least 4 months were referred to as N3. Group N1 demonstrated a significant increase in the percentage of CD45RO+CD4+ T cells and CD45RO+CD8+ T cells (p < 0.05) compared with 11 controls, and these subsets were noted to have a tendency to decrease to control levels in groups N2 and N3. Furthermore, interleukin-2 receptor-alpha expressed subsets in CD45RO+CD4+ T cells (CD45RO+CD4+CD25+ T cells) were also increased only in group N1 (p < 0.02). A similar tendency of absolute counts was observed in these subsets. These results suggest that activated memory T cells reflect lymphocyte dysfunction at initial onset or relapse in INS children.

Antibodies, Monoclonal↗

[Evaluation of body surface ultrasonography in the diagnosis of diseases of abdominal segment esophagus and early-stage carcinoma].

OBJECTIVE: To investigate the possibility of detecting esophageal carcinoma and other lesions by body surface ultrasound (BSUS). METHODS: BSUS examinations of the abdominal segment of the esophagus in 797 subjects were undertaken. Wall thickness more than or equal to 6 mm, wall echo abnormality, and lumen morphologic changes were referred as the criteria of the disease. RESULTS: A visualization rate of 92% (n = 729) was obtained. 716 subjects without any esophageal diseases had a wall thickness of 4 mm or less; Of other 13, one patient had a wall thickness of 5 mm, 11 had 6 mm or more, and one had luminal cystic dilatation without wall thickening. In the 13 cases, the final pathological examination showed 5 cases of esophageal carcinoma (intramucosal, mucosal muscle, submucosal, proper musculature, and serosal patterns, respectively), 2 of metastatic lesion, one of leimyoma, 2 of edematous benign ulcer, one of diverticulum with polyp, and 2 of normal result. CONCLUSION: BSUS can not only detect the early-stage carcinoma, but also further demonstrate wall echo and pathologic changes inside and outside the wall. In the visualization of the submucosal tumor, it is advantage ous to barium examination and endoscopy. With its high sensitivity, simplicity, and non-intervention, BSUS can become a better screening method in everyday practice and in the area with high incidence of esophageal carcinoma.

Adult↗

Precursor B cells for autoantibody production in genomically Fas-intact autoimmune disease are not subject to Fas-mediated immune elimination.

The Fas/Fas ligand (FasL) system participates in regulation of the immune system through the apoptotic process. However, the extent to which abnormalities in this system are involved in the loss of self-tolerance and development of autoimmune disease not associated with Fas/FasL mutations remains unknown. The present study addresses this issue in Fas/FasL-intact, systemic lupus erythematosus (SLE)-prone (NZB x NZW) (NZB/W) F1 mice. While splenic B cells from 2-month-old mice before overt SLE expressed Fas poorly, in vitro stimulation with an agonistic anti-CD40 mAb up-regulated their Fas expression, thus revealing the existence of two populations: one was Fashigh and highly susceptible to anti-Fas mAb-induced apoptosis, and the other was Faslow and apoptosis-resistant. The Faslow cells were included in the CD5(+) B cell subpopulation and contained most of the cells that produced IgM anti-DNA antibodies. The isotype of anti-DNA antibodies switches from IgM to IgG in NZB/W F1 mice at ages beginning at about 6 months. These IgG anti-DNA antibodies were produced almost exclusively by a subpopulation of splenic B cells that spontaneously expressed low levels of Fas in vivo and were apoptosis-resistant. The findings indicate that precursor B cells for autoantibody production and presumably autoantibody-secreting cells in these mice are relatively resistant to Fas-mediated apoptosis, a finding supporting the concept that abnormalities of Fas-mediated apoptotic process are involved in the development of autoreactive B cells in Fas/FasL-intact autoimmune disease.

Animals↗

Anterior decompression of foraminal stenosis below a lumbosacral transitional vertebra. A case report.

STUDY DESIGN: A case of unilateral far-out foraminal entrapment of the L5 spinal nerve below a transitional vertebra is presented with a review of the literature. OBJECTIVES: To describe management of a rare far-out foraminal stenosis below a transitional vertebra and to evaluate the surgical procedure and results. SUMMARY OF BACKGROUND DATA: Far-out foraminal stenosis with radiculopathy caused by bony spur formation secondary to anomalous articulation between the transverse process and the sacral ala is rarely reported. Decompression at this point traditionally has been performed through a posterior approach, similar to that performed for the far-out syndrome. There are no previous reports describing anterior decompression through an extraperitoneal approach. METHODS: The diagnosis was confirmed by computed tomography, magnetic resonance imaging, and selective radiculography. Anterior decompression was performed by resecting the bony spur using a wide muscle-splitting extraperitoneal approach. RESULTS: Anterior decompression was performed with minimal intervention to the spine and the trunk muscles. Good relief of low back pain and sciatica was obtained. CONCLUSIONS: Selective radiculography was the method of examination with the optimal diagnostic value for far-out foraminal stenosis. An anterior approach to the decompression of far-out foraminal stenosis below a lumbosacral transitional vertebra is a relatively simple and effective method.

Adult↗

Structural determinants for interaction with three different effectors on the G protein beta subunit.

In the yeast two-hybrid system, a 100-residue fragment (beta1A) from the N terminus of the beta1 subunit interacts with domains specific to adenylyl cyclase 2 (AC2), the muscarinic atrial potassium channel (GIRK1), and phospholipase C-beta2 (PLC-beta2). Based on the crystal structure of the G protein, beta1A is composed of an N-terminal alpha helix, a loop, and five beta strands in which the C-terminal four beta strands form a beta sheet, the first of seven sheets that make up the propeller structure of the beta subunit. A mutant of beta1A (L4P, L7P, and L14P), in which the alpha helix was potentially destroyed, interacted poorly with the G protein gamma subunit but effectively with domains of AC2, GIRK1, and PLC-beta2. In contrast, another mutant of beta1A (S72A, D76A, and W82A), in which a network of hydrogen bonds was disrupted, interacted poorly with GIRK1 and PLC-beta2 domains, but effectively with the gamma subunit and the AC2 domain. These results suggest that the proper folding of the first five beta strands in the G protein beta subunit is a requirement for appropriately positioning residues that interact with GIRK1 and PLC-beta2. Furthermore, since mutations that potentially disrupted the folding of these beta strands did not affect interaction with AC2, the structural determinants on the G protein beta subunit for interaction with various effectors may be different.

Adenylyl Cyclases↗

Plasma levels of nicotine and safety of smokers wearing transdermal delivery systems during multiple simultaneous intake of nicotine and during exercise.

Although transdermal nicotine patches have been studied extensively under recommended conditions, the present studies were designed to assess the nicotine plasma levels and the safety of transdermal nicotine patches in smokers undergoing situations suspected to result in increased nicotine plasma levels. The first study examined the effects of increasing nicotine intake through sequential administration of a nicotine patch (day 2), a patch followed by consumption of nicotine gum (day 3), and a patch followed by gum consumption and cigarette smoking (day 4). In this study, nicotine plasma levels increased transiently after the addition of each nicotine source. Mean areas under the concentration-time curves from 0 to 24 hours (AUC0-24) for nicotine were 453 +/- 120 ng.hr/mL (day 2), 489 +/- 143 ng.hr/mL (day 3), and 485 +/- 143 ng.hr/mL (day 4). The second study evaluated the effects of physical exercise on the kinetics and the safety of two different types of nicotine transdermal devices: Nicoderm and Habitrol. The mean delivered dose of nicotine was higher with Nicoderm compared with Habitrol, and the two products were not considered to be bioequivalent. During a 20-minute exercise period, nicotine plasma levels increased by 13 +/- 9% for Nicoderm and 30 +/- 20% for Habitrol. This increase in nicotine plasma levels was probably related to the exercise-induced increase in peripheral circulation at the patch site. Results from both studies indicate a clinically nonsignificant increase in blood pressure and heart rate after the administration of nicotine. After exercise, subjects taking Habitrol tended to have a higher incidence of adverse events compared with baseline values. Safety profiles remained acceptable in both studies despite the increases in nicotine plasma levels. It was concluded that both superimposed nicotine sources and physical exertion result in short-lived plasma nicotine elevations and temporarily increase nicotine pharmacodynamic parameters without increased risk to the volunteers.

Administration, Cutaneous↗

A case of central cord syndrome caused by intubation: a case report.

Following intubation for respiratory distress, a 42 year-old female patient sustained a hyperextension injury which produced a central cord syndrome. This paper illustrates an unusual mechanism whereby a central cord syndrome was caused by pure hyperextension without high velocity force.

AIDS-Related Opportunistic Infections↗

A domain on the G protein beta subunit interacts with both adenylyl cyclase 2 and the muscarinic atrial potassium channel.

The G protein betagamma complex modulates the function of a variety of effectors in biological signaling. However, the individual roles of the beta and gamma subunits in this interaction are unknown. Unlike in the case of the alpha subunit, domains on the betagamma complex that contact effectors have not yet been identified. We show here using the yeast two-hybrid system that the beta subunit and not the gamma subunit interacts with domains specific to adenylyl cyclase type 2 (AC2) and the muscarinic receptor-gated atrial inwardly rectifying potassium channel, GIRK1. Different beta subunit types interact with these effector domains with different efficacies. Furthermore, an N-terminal fragment of 100 residues interacts with both these effector domains as effectively as the whole beta subunit. This domain includes the region where the beta subunit contacts with the alpha subunit in the crystal structure and may therefore explain the ability of the alpha subunit to shut off the activity of the betagamma complex.

Adenylyl Cyclases↗

Differential ability to form the G protein betagamma complex among members of the beta and gamma subunit families.

We have determined the relative abilities of several members of the G protein beta and gamma subunit families to associate with each other using the yeast two-hybrid system. We show first that the mammalian beta1 and gamma3 fusion proteins form a complex in yeast and that formation of the complex activates the reporter gene for beta-galactosidase. Second, the magnitude of reporter activity stimulated by various combinations of beta and gamma subunit types varies widely. Third, the reporter activity evoked by a particular combination of beta and gamma subunit types is not correlated with the expression levels of these subunit types in the yeast cells. Finally, the reporter activity shows a direct relationship with the amount of hybrid betagamma complex formed in the cell as determined by immunoprecipitation. These results suggest that different beta and gamma subunit types interact with each other with widely varying abilities, and this in combination with the level of expression of a subunit type in a mammalian cell determines which G protein will be active in that cell. The strong preference of all gamma subunit types for the beta1 subunit type explains the preponderence of this subunit type in most G proteins.

Animals↗

Synaptic membrane G proteins are complexed with tubulin in situ.

The G proteins G S and Gi1 appear to be capable of binding to tubulin specifically, and it has been suggested that such binding results in G protein activation via direct transfer of GTP. This study was undertaken to demonstrate that consequences of G protein activation by tubulin, i.e., stimulation or inhibition of adenyl cyclase, were dependent on the G proteins expressed as well as unique aspects of the membrane or cytoskeleton in a given cell type. Membranes from rat C6 glioma cells, which express G s alpha but not G i alpha 1, responded to the addition of tubulin with a stable activation of adenyl cyclase. Conversely, membranes from rat cerebral cortex, which contain both G s and G i 1, responded to exogenous tubulin with a stable inhibition of adenyl cyclase. Unlike C6 membranes, cerebral cortex membranes are richly endowed with tubulin, and antitubulin antibodies immunoprecipitated complexes of tubulin and G i 1 and G s from detergent extracts of these membranes. Nearly 90% of the G s alpha from Triton X-114 extracts coimmunoprecipitated with tubulin, suggesting that these proteins exist as a complex in the synaptic membrane. Such complexes may provide the framework for a G protein-cytoskeleton link that participates in the modulation of cellular signal transduction.

Adenylyl Cyclase Inhibitors↗

Isolation of a beta-tubulin gene from Fusarium moniliforme that confers cold-sensitive benomyl resistance.

A beta-tubulin gene from a UV-irradiated benomyl-resistant mutant of Fusarium moniliforme was isolated, cloned, and sequenced. The gene encodes a 446-amino-acid polypeptide with homology to other fungal beta-tubulins. RNA blot analysis showed expression of the gene during vegetative growth and conidial germination but no expression during conidiation. A point mutation, which likely confers benomyl resistance, has been identified in the cloned gene; this mutation results in a single amino acid substitution of asparagine for tyrosine at position 50. Expression of benomyl resistance in the mutant was also cold sensitive. Sexual crosses betweeen the mutant and a wild-type strain indicated cosegregation of benomyl resistance and cold sensitivity.

Amino Acid Sequence↗

Regulation of the C3 production by gamma interferon from peripheral blood T cells in patients with membranoproliferative glomerulonephritis and poststreptococcal acute glomerulonephritis.

This study assessed the regulatory role of peripheral blood T cells in the C3 production in patients with poststreptococcal glomerulonephritis and branoproliferative glomerulonephritis. Peripheral blood T cells from patients at various stages of disease were cultured and the supernatants tested for gamma interferon (IFN-gamma) content and the capacity to stimulate C3 production by HuH-7 cells. Supernatants from patients with membranoproliferative glomerulonephritis and from convalescent patients with poststreptococcal glomerulonephritis significantly stimulated the C3 production; the degree of stimulation correlated with the IFN-gamma content of the supernatants. Similar results were obtained using recombinant IFN-gamma. In both cases, the effect was blocked by the addition of anti-IFN-gamma monoclonal antibody to the cultures. Interleukin 2 and interleukin 6 levels in supernatants from T cell cultures of patients and controls were essentially the same. In summary, IFN-gamma plays a regulatory role in C3 production by human hepatoma cell lines.

Acute Disease↗

Transformation of Pleurotus sapidus protoplasts by electroporation.

The total DNA of Pleurotus ostreatus was successfully transferred into the protoplasts of monokaryotic mycelia of Pleurotus sapidus by electroporation. The transformants were selected by their clamp connection of dikaryocyte, and the transformation frequency and transformation rate were 8.2 x 10(-5) and 3.6%, respectively. Analyzing the esterase isozyme, it was found that the transformants showed some isozyme bands of P. ostreatus and P. sapidus, and new non-parental bands. This proved that the recombination occurred between the DNAs of P. sapidus and P. ostreatus. The fruit bodies of the transformants showed morphological changes.

Electroporation↗

Hypercalciuria and nephrocalcinosis in patients with idiopathic low-molecular-weight proteinuria in Japan: is the disease identical to Dent's disease in United Kingdom?

Idiopathic low-molecular-weight (LMW) proteinuria is a newly described renal disease in Japan and Italy. We report on 7 patients who manifested bilateral or unilateral nephrocalcinosis, as demonstrated by abdominal computed tomography scans. Renal histology revealed calcinosis of renal tubules in 2 patients. Computed tomography is a reliable method for the detection of nephrocalcinosis in this disorder. Hypercalciuria was also seen in 6 patients. A calcium-loading test performed in 2 patients suggested that hypercalciuria was of renal origin. Although the true pathogenesis is still not known, hypercalciuria and nephrocalcinosis appear to be a common complication in patients with idiopathic LMW proteinuria. These complications and clinical features suggest that idiopathic LMW proteinuria in Japan is likely to be identical to Dent's disease in the United Kingdom.

Adolescent↗

Differential ultrasonic diagnoses of pulmonary benign and malignant space-occupied lesions of the peripheral type.

87 patients with pulmonary space-occupied lesions of the peripheral type which were either adhesive or close to pleura were examined using ultrasonography. Of them, 64 cases of lung cancers and 23 of benign lesions were then confirmed by histopathology. Five sonographic features, including configuration, echogenicity patterns, bronchial air phase in foci, margin, and pleural involvement, were significantly different between malignant and benign diseases (P < 0.01). The differential ultrasonography used in this series showed a sensitivity of 61% (14/23), a specificity of 95% (61/64), and an accuracy of 86% (75/87). The results of the study demonstrate that the ultrasonography is helpful in differentiating malignant and benign peripheral lung lesions near the plerua.

Adenocarcinoma↗

Transcutaneous ultrasound of the cervical esophagus in patients with esophageal carcinoma.

Transcutaneous ultrasound of the cervical esophagus was performed in 46 patients with esophageal carcinoma and in 35 controls. The former had 24 upper segmental lesions and 22 lower segmental lesions. The level of the sternoclavicular joint was used to divide the esophagus into the upper segmental (USE) and lower segmental esophagus (LSE). The anterior esophageal wall thickness and luminal dimensions were measured before and immediately after phonation. The mean wall thickness in the controls was 1.8 mm before phonation and 2.1 mm after phonation, with a significant difference (t test, P < 0.05). The mean wall thickness in the USE carcinoma group was 4.3 mm and 4.4 mm before and after phonation respectively. There was a significant difference between the controls and USE carcinoma groups (t test, P < 0.05). The cross sectional area, which was calculated as the product of anterio-posterior and lateral diameters, averaged 28 mm2 before phonation in the controls and increased to 44 mm2 after phonation (t test, P < 0.05). The mean cross sectional area in the USE carcinoma group was significantly smaller before phonation than that in the controls (t test, P < 0.05) and showed little change after phonation. No significant difference was found between LSE carcinoma and control groups. Transcutaneous ultrasound appears to be a promising non-invasive method of investigation for cervical esophageal carcinoma.

Adult↗