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G Cai

Publications and source records attributed to G Cai.

At least 55 records · Page 3Linked to original sources
PubMed1999

Age-associated impairment in brain MAPK signal pathways and the effect of caloric restriction in Fischer 344 rats.

Mitogen-activated protein kinases (MAPKs) play important roles in cell proliferation, differentiation, and apoptosis. Important functional roles for MAPKs in postmitotic cells have recently been suggested. In the present study, we investigated the effect of aging on the brain ERK (extracellular signal-regulated kinase) and p38 MAPK signaling pathways of Fischer 344 rats. The results show that basal tyrosine-phosphorylated ERK1/ERK2 in cortex of 24-month-old rats was reduced by 36%-59%, compared to 6- and 12-month-old rats (p<.05, 24- vs. 12- or 6-month-old rats). Similarly, the phosphotransferase activities of ERK and p38 MAPK, measured by in vitro immunocomplex kinase assays using myelin basic protein (MBP) as substrate, were shown to be reduced approximately 50% and 59% respectively, in the cerebrocortex of 24-month-old rats (p<.01, 24- vs. 12- or 6-month-old rats). The reductions in basal ERK and p38 MAPK activities are not due to altered protein levels of these kinases as assessed by Western analysis. Immunohistochemically, no age-related differences in ERK expression and cellular distribution were observed However, cytosolic ERK tended to aggregate in brain neurons of aged rats. In contrast brain tyrosine-phosphorylated PLCgamma1 did not change with age. Activation of ERK in response to EGF or PMA was also reduced in cortical brain slices of 24-month-old rats. These results demonstrate an age-associated selective impairment in the MAPK signaling pathways. Moreover, lifelong caloric restriction completely prevented the age-related decrease in basal brain ERK activity and diminished the age-related reduction of p38 MAPK activity. Taken together, these data indicate that ERK and p38 MAPK signaling pathways are impaired in the aged brain and that lifelong caloric restriction modulates these defects in brain intracellular signaling pathways.

Aging↗
PubMed1999

Incidence of DIS/DSM-IV social phobia in adults.

OBJECTIVE: The aim of the study was to estimate the incidence of social phobia in the general population. METHOD: The Baltimore cohort of 3481 subjects, sampled during the 1981 Epidemiologic Catchment Area study, was traced. A total of 1920 subjects were re-interviewed from 1993 to 1996 using the Diagnostic Interview Schedule (DIS). A subsample of 349 subjects was interviewed by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry. RESULTS: The estimated incidence of DIS/DSM-IV social phobia is 4-5/1000/year. New cases were found in all age groups, with the highest rates in subjects with baseline depressive and panic disorders. Psychiatric evaluations showed broad diagnostic concordance with DIS diagnoses in incident cases. However, validity indices were highly dependent on diagnostic thresholds. None of the psychiatrist-ascertained social phobics had received treatment for the disorder, although the majority were considered likely to benefit from treatment. CONCLUSION: New cases of social phobia occur in adults of all age groups, and are often secondary to other psychiatric conditions.

Adult↗
PubMed1999

Inverse agonist properties of dopaminergic antagonists at the D(1A) dopamine receptor: uncoupling of the D(1A) dopamine receptor from G(s) protein.

The interaction of dopaminergic antagonists with the D(1A) dopamine receptor was assessed in PC2 cells that transiently express this receptor. The maximal binding and dissociation constants for the D(1A) dopamine receptor, using the ligand [(125)I]SCH23982 were 0.38 +/- 0.09 nM and 1 to 4 pmol/mg, respectively, when assessed 48 h after transfection with cDNA encoding the rat D(1A) receptor. Basal adenylyl cyclase activity increased 50 to 60% in membranes of transfected PC2 cells compared with control membranes. The dopaminergic antagonists clozapine, cis-flupenthixol, (+)-butaclamol, haloperidol, chlorpromazine, and fluphenazine inhibited constitutive adenylyl cyclase activity in membranes of cells expressing the D(1A) receptor. SCH23390, a selective D(1) dopamine receptor antagonist, and (-)-butaclamol did not alter basal cyclase activity, whereas dopamine increased enzyme activity in membranes expressing the D(1A) dopamine receptor. The coupling of D(1A) receptors with G(s) proteins was examined by immunoprecipitation of membrane G(salpha) followed by immunoblotting with a D(1A) dopamine receptor monoclonal antibody. Clozapine, cis-flupenthixol, (+)-butaclamol, haloperidol, and fluphenazine but not SCH23390 or (-)-butaclamol decreased D(1A) receptor-G(salpha) coupling by 70 to 80%, and SCH23390 was able to prevent the receptor-G(salpha) uncoupling induced by haloperidol or clozapine. These results indicate that some dopaminergic antagonists suppress basal signal transduction and behave as inverse agonists at the D(1A) dopamine receptor. This action of the dopamine receptor antagonists may contribute to their antidopaminergic properties that seem to underlie their clinical actions as antipsychotic drugs.

Adenylyl Cyclases↗
PubMed1998

Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B.

We describe a diastrophic dysplasia (DTDST) gene mutation in a Japanese male fetus with achondrogenesis type 1B and his relatives. Diagnosis in the fetus was based on roentgenographic data and pathological findings of bones and cartilage. Nucleotide sequencing of the DTDST gene demonstrated that the fetus was homozygous for both delVal340 and Thr689Ser and his parents and a healthy brother were heterozygous for the mutations. The former mutation was reported previously in patients with achondrogenesis type 1B, and the latter was detected in 5 alleles of 26 healthy Japanese individuals. These data suggest that delVal340 is associated with achondrogenesis type 1B in the Japanese, whereas a serine to threonine substitution is most likely polymorphic.

Anion Transport Proteins↗
PubMed1998

Clinical study of multi-drug resistance gene (MDR1) expression in primary ovarian cancer.

This study was designed to measure the multi-drug resistance gene (MDR1) mRNA content and analyze clinical relationship between MDR1 expression and drug resistance in primary ovarian cancer. Reverse transcription PCR (RT-PCR) was used to measure MDR1 mRNA content in biopsy sample of 31 primary ovarian cancers (experimental group) and 30 gynecological tumors (control group). The level of 95.2% (20/21) MDR1 expression was relatively low, and the detected rate of MDR1 expression was 67.7% (21/31) in experimental group, which was higher than that in control group (40.0%, P < 0.05). The differences of MDR1 expression between the effective group and no effect group after combined chemotherapy was significant (P < 0.05). No significant relationship was found between MDR1 expression and clinical stage or histological classification or grade of differentiation in experimental group. We are led to concluded that primary ovarian cancers have drug-resistance clones which might express MDR1 spontaneously and expression of MDR1 may be used as a prognostic and predictive indicator for clinical response of ovarian cancers to combined chemotherapy.

Adolescent↗
PubMed1998

Clinical implication of serum sIL-2R levels in ovarian cancer.

The levels of serum soluble interleukin-2 receptor (sIL-2R) of 36 patients with ovarian cancer, 34 with benign gynecological tumors and 31 blood donors were measured by ELISA. Compared to those of benign and normal controls, serum levels of sIL-2R in patients with ovarian cancer elevated significantly (P < 0.01). Serum sIL-2R levels were likely related to types, clinical stage or histological grading of ovarian cancer. We were led to conclude that serum sIL-2R level may reflect the status of the immune system and the disease severity in patients with ovarian cancer. Its value as a marker for monitoring treatment and prognosis needs further studies.

Adolescent↗
PubMed1998

Characterization of the phosphoinositide-linked dopamine receptor in a mouse hippocampal-neuroblastoma hybrid cell line.

Previous studies have established that dopamine (DA) can stimulate phosphoinositide (PI) metabolism in the CNS and in the periphery. The present study summarizes our attempt to find a cell line that expresses this dopaminergic system. We describe that the stable clonal HN33.11 cell line, established by fusion of mouse hippocampal cells with neuroblastoma cells (N18TG2) that originate from A/J mouse, natively expresses the D1 DA receptor system that couples to PI hydrolysis. In this cell line, 500 microM DA or SKF38393 produced 43 and 75% increases in inositol phosphate (IP) accumulations, respectively. In contrast, noradrenaline or 5-hydroxytryptamine did not affect IP accumulations. The formation of IP that was stimulated by DA or SKF38393 was selectively blocked by the D1 DA receptor antagonist SCH23390 with IC50 values of 13 and 16 microM. This response was not mediated by the D1A DA receptor and was cyclic AMP-independent, as HN33.11 cells did not express this receptor, and DA or SKF38393 was unable to stimulate the formation of cyclic AMP. In Ca2+-free/100 microM EGTA medium, basal IP level was reduced by 31.5%, but SKF38393-stimulated PI hydrolysis was not affected. SKF38393-stimulated IP accumulation was also not affected by pertussis toxin (PTX) treatment (200 ng/ml), suggesting that this dopaminergic response is mediated by PTX-insensitive G proteins. Co-immunoprecipitation studies indicated that in membranes of HN33.11 cells, D1-like binding sites are coupled to G alpha(q) protein. Blockade of SKF38393-induced PI hydrolysis with antiserum against phospholipase C (PLC) isozymes, performed in permeabilized cells, as well as co-immunoprecipitation studies implicate PLCbeta3 and PLCbeta4 in this dopaminergically mediated PI hydrolysis cascade. The results indicate that HN33.11 cells express a D1-like DA receptor that couples to PLCbeta3/4 via G alpha(q) protein. These cells may therefore be a useful model system for investigating this receptor system.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Incidence of obsessive-compulsive disorder in adults.

This study addressed the incidence of obsessive-compulsive disorder (OCD) in adults in the general population. The Baltimore cohort of 3481 subjects, originally sampled during the 1981 multisite Epidemiologic Catchment Area Study, was traced. From 1993 to 1996, 1920 people were reinterviewed using the Diagnostic Interview Schedule. The incidence of DSM-III-R obsessive-compulsive disorder in adults was estimated at .55 per 1000 person-years. There was a relatively high rate of new cases in elderly women. It appeared that there were two peaks of onset of OCD over the life span, both of which occur later in female subjects. Subjects with adult incidence OCD often presented for psychiatric treatment, though they did not specify obsessive-compulsive symptoms as the reason. The difference in diagnostic criteria between DSM-III and DSM-III-R substantially influenced the threshold for new case identification.

Adolescent↗
PubMed1998

Onset and recovery from panic disorder in the Baltimore Epidemiologic Catchment Area follow-up.

BACKGROUND: The objective is to estimate parameters of the natural history of panic disorder, including its prodrome, incidence, recovery and recurrence. METHOD: In 1981 the Baltimore Epidemiologic Catchment Area Study interviewed 3481 individuals probabilistically selected from the household population. During 1993-1996, 1920 of these individuals (73% of survivors) were interviewed again. Baseline and follow-up interviews included the National Institute of Mental Health Diagnostic Interview Schedule. During the follow-up, a subsample was assessed by psychiatrists using the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry (SCAN). RESULTS: There were 35 new cases of panic disorder in 24,475 person years of exposure, yielding an annual incidence of 1.43 per 1000 per year. Data from the SCAN assessments suggest the incidence estimate is conservative. Incidence is greater in females and declines with age. About one-third of the new cases arise without agoraphobia, but about half have anxiety of some sort present for many years prior to meeting criteria for diagnosis. People with agoraphobia have less intense onsets but slower recoveries than those without agoraphobia. CONCLUSIONS: Panic is heterogeneous in its pattern of onset and recovery. Some of the heterogeneity is associated with the presence of other anxiety over a long period of the life.

Adolescent↗
PubMed1998

Analysis of localization of mutated tissue-nonspecific alkaline phosphatase proteins associated with neonatal hypophosphatasia using green fluorescent protein chimeras.

Hypophosphatasia is associated with a defect of the tissue-nonspecific alkaline phosphatase (TNSALP) gene. The onset and clinical severity are usually correlated in hypophosphatasia; patients with perinatal hypophosphatasia die approximately at the time of birth. In contrast, we describe a male neonatal patient with hypophosphatasia who had no respiratory problems and survived. He was compound heterozygous for the conversion of Phe to Leu at codon 310 (F310L) and the deletion of a nucleotide T at 1735 (delT1735), causing the frame shift with the result of the addition of 80 amino acids at the C-terminal of the protein. Because the C-terminal portion of TNSALP is known to be important for TNSALP to bind to the plasma membrane, the localization of wild-type and mutated TNSALP proteins was analyzed using green fluorescent protein chimeras. The expression vectors containing the complementary DNA of fusion proteins consisting of signal peptide, green fluorescent protein, and wild-type or mutated TNSALP, caused by delT1735 or F310L mutation, were introduced transiently or stably in Saos-2 cells. The delT1735 mutant failed to localize at the cell surface membrane, whereas the wild-type and the F310L mutants were located in the plasma membrane and cytoplasm. The assay for enzymatic activity of TNSALP revealed that the delT1735 mutant lost the activity and that the F310L mutant exhibited an enzymatic activity level that was 72% of the normal level. The F310L mutation was also detected in another neonatal patient with relatively mild (nonlethal) hypophosphatasia (reported in J Clin Endocrinol Metab, 81:4458-4461, 1996), suggesting that residual ALP activity of the F310L mutant contributes to the less severe phenotype. The patient is unique, with respect to a discrepancy between onset and clinical severity in hypophosphatasia.

Alkaline Phosphatase↗
PubMed1998

[Ceruloplasmin gene expression in silicotic rat lung].

In order to investigate the existence of extrahepatic ceruloplasmin (Cp) gene expression during silicotic process, molecular hybridization technique including dot blotting, in situ hybridization and Northern blotting was used. Twenty one days after silica dust intratracheal injection, Cp mRNA was detectable in lung, which was nearly double the content of that in the control (saline injection). In situ hybridization and Northern blotting revealed that the alveolar macrophages in silicosis could express Cp mRNA. It is concluded that lung is a prominent site for Cp gene expression during silicosis and Cp may play a previously unknown role in pulmonary injury or repair.

Animals↗
PubMed1998

Expression of type-I collagen and matrix metalloproteinase-9 mRNA in bone of castrated adult female rats: effects of estrogen.

OBJECTIVES: To elucidate the molecular changes of bone collagen during the development of postmenopausal osteoporosis and to investigate the molecular effects of estrogen replacement. METHODS: An adult ovariotomy rat model was used. Type-I collagen and matrix metalloproteinase-9 (MMP-9) expressions in bone tissues of rats treated by sham surgery (SH), bilateral ovariotomy (OVX) and OVX with estradiol (OVX-E2) were analysed at mRNA level by using dot blot technique. The distribution of mRNA of these two genes in bone tissues was studied by in situ hybridization. RESULTS: The expression levels of both type-I collagen and MMP-9 in bone tissues of OVX rats were higher than those of SH group, while treated with estradiol, the expression of both genes declined to some degree. In situ hybridization showed that type-I collagen mRNA located in osteoblasts, whereas MMP-9 was mainly expressed in osteoclasts, some lining cells on bone surface, and some mononuclear cells in bone marrow. CONCLUSIONS: The reduction of high bone turnover in osteoporotic bone tissues induced by estrogen replacement may result from alterations in gene expression related to bone formation and bone resorption. These alterations are consistent with the changes observed previously by histomorphometry and biochemical markers of bone metabolism on OVX animals and postmenopausal osteoporosis.

Animals↗
PubMed1998

[Acetabular dysplasia:an experimental study].

OBJECTIVE: To demonstrate whether acetabular dysplasia represents a primary feature of congenital dislocation of the hip or secondary defect. METHOD: The capsule of twelve puppies aged five to nine weeks was incised and the ligamentum teres was completely severed under anaesthesia. A part of gluteal medium muscle was implanted in the acetabulum and the head of the femur was dislocated from acetabulum. Roentagenogram was made three weeks after dislocation in all animals. RESULT: As early as three weeks after dislocation, acetabular dysplasia was clearly noted in all animals. There was more acetabular obliquity and increase of acetabular index. CONCLUSION: The acetabular dysplasia is the result but not the cause of congenital dislocation of the hip. This result provides probably support for the concept of developmental dislocation of the hip.

Acetabulum↗
PubMed1998

Age-related decline in beta adrenergic and adenosine A1 receptor function in the heart are attenuated by dietary restriction.

Previously published reports from this laboratory have shown that the antiadrenergic effect of adenosine A1 agonists declines with age in the rat heart [ J Mol Cell Cardiol 29:593-602] and that this decline may be caused by a decrease in coupling between adenosine A1 receptors (AdoA1R) and guanine nucleotide-binding proteins [ Circ Res 81:1065-1071]. Dietary restriction (DR; 60% calories of ad libitum) has been shown to attenuate age-related changes in cellular signal transduction pathways. Therefore, the present study investigated whether DR altered the age-related changes in AdoA1R-mediated function in senescent rat hearts. Ventricular membranes were isolated from the hearts of ad libitum (AL) fed and DR male F344 rats that were 6, 12 and 24 months of age. In AL rats, there was an age-related decline in isoproterenol (ISO)-stimulated adenylyl cyclase when compared with the 6-month-old rats. The decline in ISO-stimulated cyclase was attenuated in DR animals. In AL rats, inhibition of ISO-stimulated adenylyl cyclase by the AdoA1R agonist, N6-p-sulfophenyladenosine (SPA) decreased with age. In DR rats, the age-related decline in inhibition was attenuated. Previous results from this laboratory indicated that in AL fed rats, there was an age-related decrease in the percentage of high-affinity binding sites for SPA, from 55% at 6 months to 23% at 24 months. Diet restriction attenuated this age-related shift in high-affinity binding sites so that the percentage of high-affinity sites at 24 months was 42%. Our results suggest that DR maintains AdoA1R function by preventing a loss of high-affinity AdoA1R sites.

Adenylyl Cyclases↗
PubMed1998

[Hypophosphatasia].

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Alkaline Phosphatase↗
PubMed1997

Isolation from fetal bovine serum of a fragment b of complement factor B-like protein improving a long-term survival of human endothelial cells.

It is known that serum is a most important factor supporting cell survival and growth. Particularly, the deprivation of serum would result in the death of human endothelial cell. Our previous paper reported an endothelial cell-viability maintaining factor (EC-VMFa) purified from fetal bovine serum and identified as an apolipoprotein. In the present further study, it is demonstrated that another potent serum factor (refer as EC-VMFb) is also possessed of the endothelial cell-viability maintaining activity, improving a long-term survival of human endothelial cells in serum-free medium. EC-VMFb has a molecular weight of 66,000 (reduced and nonreduced), pI of 4.5 and has been identified as fragment b of complement factor B (Bb)-like protein by amino-terminal amino acid sequence.

Amino Acid Sequence↗