• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.10
• /
• pp.5047-5052
• /
• 2012

Introduction: Breast cancer is the most common malignancy of women in Kashmir. This study was conducted with the objective of assessing hormone receptor positivity and its correlation with age at diagnosis, tumor size, histological grade and lymph node metastasis. Materials and Methods: 132 newly diagnosed cases of invasive breast cancer diagnosed at the Department of Pathology, SKIMS, Srinagar, J&K, were included after excluding biopsies, in-situ lesions and recurrence cases. Results: Mean age of the patients was 48.2 years, 59.1% being ${\leq}50$ years of age. Mean duration of symptoms was 6.32 months. Most lesions (65.1%) were 2-5 cm and 16.7% were ${\geq}5.0$ cm in greatest dimension. The predominant (80.3%) morphology was IDC-NOS. The majority of the cases presented as grade II (52.1%) lesions and lymph node involvement was present in 65.2%. ER and PR were positive in 66.3% and 63.4% cases, respectively, increasing with rising age. High grade lesions and larger size tumors were more likely to be ER and PR negative. No correlation was found between ER/PR status and lymph node metastasis. Conclusions: ER and PR expression in breast cancers in the current study was found to be higher than studies done in India/Asia but lower than studies conducted in the West, even on Indian/Asian immigrants. Markedly lower receptor expression in Indian/Asian studies is likely due to preanalytic variables, thresholds for positivity, and interpretation criteria. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer are strongly advocated for standardization of receptor evaluation and for clinical management of breast cancer patients to provide best therapeutic options.

• Journal of Pharmacopuncture
• /
• v.19 no.2
• /
• pp.163-166
• /
• 2016

Objectives: Quercetin is a flavonoid and an important dietary constituent of fruits and vegetables. In recent years, several pharmacological activities of quercetin, such as its neuroprotective activity and, more specifically, its anti-convulsant effects in animal models of epilepsy, have been reported. This study evaluated the role of quercetin pretreatment on gene expression of ${\gamma}$-amino butyric acid type A ($GABA_A$) receptor beta subunits in kainic acid (KA)-induced seizures in mice. Methods: The animals were divided into four groups: one saline group, one group in which seizures were induced by using KA (10 mg/kg) without quercetin pretreatment and two groups pretreated with quercetin (50 and 100 mg/kg) prior to seizures being induced by using KA. Next, the messenger ribonucleic acid (mRNA) levels of the $GABA_A$ receptor ${\beta}$ subunits in the hippocampus of each animal were assessed at 2 hours and 7 days after KA administration. Quantitative real-time polymerase chain reaction (RT-PCR) assay was used to detect mRNA content in hippocampal tissues. Results: Pretreatments with quercetin at doses of 50 and 100 mg/kg prevented significant increases in the mRNA levels of the ${\beta}_1$ and the ${\beta}_3$ subunits of the $GABA_A$ receptor at 2 hours after KA injection. Pretreatment with quercetin (100 mg/kg) significantly inhibited ${\beta}_1$ and ${\beta}_3$ gene expression in the hippocampus at 7 days after KA injection. But, this inhibitory effect of quercetin at 50 mg/kg on the mRNA levels of the ${\beta}_3$ subunit of the $GABA_A$ receptor was not observed at 7 days after KA administration. Conclusion: These results suggest that quercetin (100 mg/kg) modulates the expression of the $GABA_A$ receptor ${\beta}_1$ and ${\beta}_3$ subunits in the KA model of epilepsy, most likely to prevent compensatory responses. This may be related to the narrow therapeutic dose range for the anticonvulsant activities of quercetin.

• Animal cells and systems
• /
• v.13 no.4
• /
• pp.371-379
• /
• 2009

The endocannabinoid system (ECS) plays a key role in the regulation of appetite, body weight and metabolism. We undertook the present study to further clarify the regulation of the cannabinoid CB1 receptor (CB1, CNR1) in human adipose tissue in obesity. CB1 receptor mRNA expression was ~1.6-fold (p<0.004) and 1.9-fold higher (P<0.05) in subcutaneous adipocytes from obese compared to non-obese subjects in microarray and quantitative real-time PCR studies, respectively. Higher CB1 receptor mRNA expression levels in both adipose tissue (~1.2 fold, P<0.05) and adipocytes (~2 fold, P<0.01) were observed in samples from visceral compared to subcutaneous depots collected from 22 obese individuals. Immunofluorescence confocal microscopy demonstrated the presence of CB1 receptor on adipocytes and also adipose tissue macrophages. These data indicate that adipocyte CB1 receptor is up-regulated in human obesity and visceral adipose tissue and also suggest a potential role for the ECS in modulating immune/inflammation as well as fat metabolism in adipose tissue.

• Journal of Animal Reproduction and Biotechnology
• /
• v.38 no.2
• /
• pp.77-83
• /
• 2023

Background: Serotonin receptors can be divided into seven different families with various subtypes. The serotonin 1A (5-HT1A) receptor is one of the most abundant subtypes in animal brains. The expression of 5-HT1A receptors in the brain has been reported in various animals but has not been studied in horses. The 5-HT1A receptor functions related to emotions and behaviors, thus it is important to understand the functional effects and distribution of 5-HT1A receptors in horses to better understand horse behavior and its associated mechanism. Methods: Brain samples from seven different regions, which were the frontal, central, and posterior cerebral cortices, cerebellar cortex and medulla, thalamus, and hypothalamus, were collected from six horses. Western blot analysis was performed to validate the cross-reactivity of rabbit anti-5-HT1A receptor antibody in horse samples. Immunofluorescence was performed to evaluate the localization of 5-HT1A receptors in the brains. Results: The protein bands of 5-HT1A receptor appeared at approximately 50 kDa in the frontal, central, and posterior cerebral cortices, cerebellar cortex, thalamus, and hypothalamus. In contrast, no band was observed in the cerebellar medulla. Immunofluorescence analysis showed that the cytoplasm of neurons in the cerebral cortices, thalamus, and hypothalamus were immunostained for 5-HT1A receptors. In the cerebellar cortex, 5-HT1A was localized in the cytoplasm of Purkinje cells. Conclusions: In conclusion, the study suggests that 5-HT and 5-HT1A receptor systems may play important roles in the central nervous system of horses, based on the widespread distribution of the receptors in the horse brain.

• Korean Journal of Veterinary Research
• /
• v.27 no.2
• /
• pp.201-206
• /
• 1987

This study was carried out to investigate the action of ATP, which has been known as the neurotransmitter of noncholinergic- and nonadrenergic-nerve, on the motility of immature pig uterine smooth muscle. The results were summarized as follows; 1. The contraction and the contractile responses caused by ATP were increased in a dose-dependent manner between the concentration of ATP $10^{-6}M$ and $10^{-3}M$. The maximal contractile effect was appeared at the concentration of ATP $10^{-3}M$ and it was 70.2% of 100mM K contraction. 2. The contractile responses induced by ATP ($10^{-4}M$) were not blocked by the pretreatment with cholinergic receptor blocker, atropine ($10^{-6}M$). 3. The contractile responses induced by ATP ($10^{-4}M$) were not blocked by pretreatment with ${\alpha}$-adrenergic receptor blocker, phentolamine ($10^{-6}M$) and ${\beta}$-adrenergic receptor blocker, propranolol ($10^{-6}M$). 4. The contractile response induced by ATP ($10^{-4}M$) was not blocked by the pretreatment with $H_1-receptor$ blocker, pyrilamine ($10^{-6}M$) and $H_2-receptor$ blocker, cimetidine ($10^{-6}M$).

• Journal of Microbiology
• /
• v.44 no.4
• /
• pp.447-452
• /
• 2006

The murine ecotropic retroviral receptor has been demonstrated to function as a mouse cationic amino acid transporter 1(mCAT1), and is comprised of multiple membranespanning domains. Feral mouse (Mus dunni) cells are not susceptible to infection by the ecotropic Moloney murine leukemia virus (MoMLV), although they can be infected by other ecotropic murine leukemia viruses, including Friend MLV and Rauscher MLV. The relative inability of MoMLV to replicate in M. dunni cells has been attributed to two amino acids $(V_{214}\;and\;G_{236})$ located within the third extracellular loop of the M. dunni CAT1 receptor (dCAT1). Via the exchange of the third extracellular loop of the mCAT1 cDNA encoding receptor from the permissive mouse and the corresponding portion of cDNA encoding for the nonpermissive M. dunni receptor, we have identified the most critical amino acid residue, which is a glycine located at position 236 within the third extracellular loop of dCAT1. We also attempted to determine the role of the third extracellular loop of the M. dunni CAT1 receptor with regard to the formation of the syncytium. The relationship between dCAT1 and virus-induced syncytia was suggested initially by our previous identification of two MLV isolates (S82F in Moloney and S84A in Friend MLV), both of which are uniquely cytopathic in M. dunni cells. In an attempt to determine the relationship existing between dCAT1 and the virally-induced syncytia, we infected 293-dCAT1 or chimeric dCAT1 cells with the S82F pseudotype virus. The S82F pseudotype virus did not induce the formation of syncytia, but did show increased susceptibility to 293 cells expressing dCATl. The results of our study indicate that S82F-induced syncytium formation may be the result of cell-cell fusion, but not virus-cell fusion.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.2
• /
• pp.117-125
• /
• 1997

The N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission is involved in synaptic plasticity, developmental processes, learning and memory and many neuropathological disorders including age-related diseases. In the present study, regulation of the NMDA receptor properties by various ligands was investigated using $[^3H]MK-801$ binding studies in the synaptic membranes of young and aged rat forebrains. The binding in the presence of glutamate and glycine increased dramatically with growth between 1 and 6 weeks old, and thereafter declined gradually with aging. Glutamate, glycine or spermine respectively increased the binding with growth. Glutamate maintained the binding during aging, while glycine or spermine significantly decreased the binding in the aged brain. The maximum stimulation by glycine varied depending on the ages of brains. Greater sensitivity to glycine was observed at 1 week and 3 months and the sensitivity was significantly reduced in the aged brain. In contrast, spermine showed similar stimulation patterns in young and aged rats. These results indicated that the functional properties of the NMDA receptor-ion channel complex in young and aged rat forebrains are differentially regulated by agonists, and the reduction of the receptor function with normal aging may be, in some degree, due to the reduction of the receptor sensitivity to glycine.

• YAKHAK HOEJI
• /
• v.44 no.6
• /
• pp.558-565
• /
• 2000

SK-1080 is one of the newly developed orally active nonpeptide angiotensinII $AT_1-receptor$ antagonist that selectively acts at $AT_1$ receptor with high affinity. The cardiac effect on ischemia/reperfusion injury of SK-1080 was compared with those of losartan, a prototype of this class, in isolated rat hearts. Isolated perfused rat heart was pretreated with drug for 10 min and then subjected to global ischemia for 30 min followed by reperfusion with- or without drug for 30 min. The possible additive effect of SK-1080 on the platelet aggregation and coagulation in human blood was also studied. We investigated whether SK-1080 effects the platelet aggregation induced by ADP, a platelet agonist partially dependent on $thromboxaneA_2$. The clotting times in the prothrombin time (PT) and activated partial thromboplastin time (APTT) were also examined in human plasma in vitro as coagulation screening test. SK-1080 improved reperfusion function (LVDP, left ventricular developed pressure; PRP, rate-pressure product) in a dose-dependent manner. SK-1080 reduced ADP-induced platelet aggregation compared with vehicle but less than losartan, and did not affect clotting times.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.5
• /
• pp.467-475
• /
• 1997

Although one of the major physiological functions of taurine(2-aminoethanesulfonic acid) is the inhibitory action on the central nervous system(CNS), the mechanism of taurine in controlling the neuronal excitation in the CNS has been in controversy. Electrically evoked pEPSP and spontaneous activity induced by the perfusion of low $Mg^{++}-ACSF$ were recorded in the CA1 pyramidal cell layer of the hippocampal slice. To test the inhibitory effect of taurine on spontaneous responses, taurine was treated for 2 min at various concentrations(1 mM-10 mM). Taurine reduced the spontaneous activity by 22.2% at 1 mM, and 100% at 2 mM in low $Mg^{++}-ACSF$. Evoked response was induced by electrical stimulation of Schaffer collateral-commissural fibers. Taurine reduced the evoked response by 11.68% at 3 mM, and 24.25% at 5 mM. Even 20 mM of taurine reduced the evoked response only by 24 % after 5 min treatment. That is, the inhibitory efficacy was much higher in spontaneous activity than in evoked response. The $GABA_A$ receptor antagonist, 100 uM bicuculline, blocked the inhibitory action of taurine, while $GABA_B$ receptor antagonist, 700 uM phaclofen, did not. Taurine blocked the spontaneous activity in the presence of CNQX, and did not block the electrically evoked responce in the presence of APV. The results suggest that taurine causes hyperpolarization in the cell by binding to $GABA_A$ receptor and preferentially attenuates NMDA receptor-mediated hyperexcitation, leaving synaptic transmission unmodified.

• Biomolecules & Therapeutics
• /
• v.4 no.1
• /
• pp.103-109
• /
• 1996

To investigate the effect of the third intracellular loop (i3 loop) peptide of human $\beta$$_2$-adrenergic receptor on receptor agonist binding, we expressed third intracellular loop region of human $\beta$$_2$-adrenergic receptor as glutathione S-transferase fusion protein in E. coli. DNA fragment of the receptor gene which encodes amino acid 221-274 of human $\beta$$_2$-adrenergic receptor was amplified by polymerase chain reaction and subcloned into the bacterial fusion protein expression vector pGEX-CS and expressed as a form of glutathione-S-transferase (GST) fusion protein in E. coli DH5$\alpha$. The receptor fusion protein was identified by SDS-PAGE and Western blot using monoclonal anti-GST antibody. The fusion protein expressed in this study was purified to an apparent homogeneity by glutathione Sepharose CL-4B affinity chromatography. The purified i3 loop fusion proteins at a concentration of 10 $\mu\textrm{g}$/ι caused right shift of the isoproterenol competition curve of [$^3$H]Dihydroalprenolol binding to hamster lung $\beta$$_2$-adrenergic receptor indicating lowered affinity of isoproterenol to $\beta$$_2$-adrenergic receptor possibly due to the uncoupling of receptor and G protein in the presence of the fusion protein. The uncoupling of receptor and G protein suggests that i3 loop region plays a critical role on $\beta$$_2$-adrenergic receptor G protein coupling.