From April 1986 to Dec 1988, fifty one patients with carcinoma of lung were treated by radiation therapy in Department of Therapeutic Radiology, Yeungnam University Hospital Of the 51 patients, $31(61\%)$ were squamous cell ca, $8(15.7\%)$ were small cell ca, and remained $4(7.9\%)$ were other cell types. Total radiation dose was average $64Gy (60\~75 Gy)$ for group A and 45Gy $(40\~59Gy)$ for group B. The mass regression and the response of airway obstruction to radiation therapy was established on the basis of follow up chest X-ray. The mass regression above $50\%$ of total volume was noted in 23 patients $(74.2\%)$ among 31 patients and the difference between two groups was not seen. In squamous cell ca, however, the mass regression rate (above $50\%$ of total volume) was $83.3\%$ (10/12) in group A compared to $50\%$ (3/6) in group B(p<0.05). The alleviation of airway obstruction was noted as follows. In group A, CR $42.9\%$, PR $35.7\%$, no response $21.4\%$ and in group B, CR $55.6\%,\;PR\;33.3\%$, no response $11.1\%$. But, in squamous cell ca, responsiveness is higher than group B. The study indicates that the importance of higher radiation dose in the management of primary tumor mass and airway obstruction caused by lung cancer especially squamous cell ca. So, meticulous treatment planning and multimodality combination therapy without increasing si.do elect or complication is recommended in management of inoperable bronchogenic carcinoma.
The modulation of leukocyte cell surface adhesion molecules may influence the development of cellular events that determine the course of the inflammatory process. Direct interaction between activated T cells and monocytes resulted in a large production of $IL-1{\beta}$ by monocytes. In this reactions, adhesion molecules play an important part, yet the role of them in Tmonocytes interaction remain unclear. This study was undertaken in an effort to elucidate, 1) the influence of 1.25(OH)$_2D_3-induced$ differentiation on the monocyte responsiveness to direct contact with T lymphocytes, and 2) the role of adhesion molecules on the T-monocyte direct interaction. Initially, I observed that direct contact of monocyte cell line THP-1 with stimulated fixed T cell line HuT78 markedly induces IL-1${\beta}$ production by THP-1. $IL-1{\beta}$ production was higher when THP-1 had been previously exposed to 1.25(OH)$_2D_3$ as compared to control, with ${\alpha}$- 1.25(OH)$_2D_3$ dose-dependent and exposure time-dependent manner. It was shown that 1.25(OH)$_2D_3$ also increased the expression of ${\beta}_2$ integrin adhesion receptor Mac-1(CD11b/CD18) dose- and timedependently, but did not increase the expression of human leukocyte antigen- D(HLA-D) and intercellular adhesion molecule-1(ICAM-1). The $IL-1{\beta}$ producing activity of THP-1 cells correlated well with the ability to induce the Mac-1 expression on THP-1 surface. Monoclonal antibody raised against relevant cell surface glycoproteins on THP-1 were tested for their ability to block the response of THP-1 to T cells. Antibody to Mac-1 only partially blocked $IL-1{\beta}$ production by THP-1, whereas antibodies to ICAM-1 and HLA-D did not. These data indicate that regulation of Mac-1 expression on THP-1 cells can alter the responsiveness of these cells to contact by activated T cells, however other unknown structures on the THP-1 cells may be involved in this process also.
Endocrine disruptors (EDs) are exogenous chemicals which interfere several aspects of natural hormone properties. EDs with estrogenic activity have been recently reported to cause animal reproductive problems. This study was performed to investigate the effects of bisphenol A (BPA) on the mouse spermatogenesis in vivo. Male ICR mice were orally injected on a daily basis with low dose of BPA 20 mg/kg, high dose of BPA 200 mg/kg, or corn oil (vehicle control) for 7 days, and litter size and weights of body, testis, and cauda epididymis were measured. The level of serum testosterone and the expression of TGF- $\beta$$_1$ mRNA were also analyzed using RIA and RT-PCR, respectively. Also, morphological differences of testes after treatments were examined. Sperm concentration and level of serum testosterone showed a decreasing tendency detected as untreated >corn oil >low >high dose BPA treated mice, although there were no significant statistical differences. Interestingly, in mice treated with a high dose of BPA, partial disappearance of spermatozoa in seminiferous tubular lumen and the expression of TGF-$\beta$$_1$ mRNA were observed. Spermatogenesis was disrupted through TGF-$\beta$ system in the seminiferous tubules, resulting in no development of germ cells. Similarly, the litter size treated with a high dose of BPA was significantly different from that of untreated control group. In conclusion, these results that a high dose of BPA (200 mg/kg) acts as an endocrine disruptor during apermatogenesis in male mice md that there are BPA-specific lesions in the adult male reproductive tract might represent a permanently altered responsiveness to testosterone by BPA in the affected target tissue.
Seung-Hyun Rhee;Young-Seok Kweon;Dong-Ok Won;Seong-Whan Lee;Kwang-Suk Seo
Journal of Dental Anesthesia and Pain Medicine
/
v.24
no.1
/
pp.19-35
/
2024
Background: This study investigated a safe and effective bolus dose and lockout time for patient-controlled sedation (PCS) with dexmedetomidine for dental treatments. The depth of sedation, vital signs, and patient satisfaction were investigated to demonstrate safety. Methods: Thirty patients requiring dental scaling were enrolled and randomly divided into three groups based on bolus doses and lockout times: group 1 (low dose group, bolus dose 0.05 ㎍/kg, 1-minute lockout time), group 2 (middle dose group, 0.1 ㎍/kg, 1-minute), and group 3 (high dose group, 0.2 ㎍/kg, 3-minute) (n = 10 each). ECG, pulse, oxygen saturation, blood pressure, end-tidal CO2, respiratory rate, and bispectral index scores (BIS) were measured and recorded. The study was conducted in two stages: the first involved sedation without dental treatment and the second included sedation with dental scaling. Patients were instructed to press the drug demand button every 10 s, and the process of falling asleep and waking up was repeated 1-5 times. In the second stage, during dental scaling, patients were instructed to press the drug demand button. Loss of responsiveness (LOR) was defined as failure to respond to auditory stimuli six times, determining sleep onset. Patient and dentist satisfaction were assessed before and after experimentation. Results: Thirty patients (22 males) participated in the study. Scaling was performed in 29 patients after excluding one who experienced dizziness during the first stage. The average number of drug administrations until first LOR was significantly lower in group 3 (2.8 times) than groups 1 and 2 (8.0 and 6.5 times, respectively). The time taken to reach the LOR showed no difference between groups. During the second stage, the average time required to reach the LOR during scaling was 583.4 seconds. The effect site concentrations (Ce) was significantly lower in group 1 than groups 2 and 3. In the participant survey on PCS, 8/10 in group 3 reported partial memory loss, whereas 17/20 in groups 1 and 2 recalled the procedure fully or partially. Conclusion: PCS with dexmedetomidine can provide a rapid onset of sedation, safe vital sign management, and minimal side effects, thus facilitating smooth dental sedation.
The most common form of genetic nephrogenic diabetes insipidus(NDI), a rare inherited disorder, is congenital and is transmitted in an X-linked recessive mode. It is refractory to the antidiuretic effect of normal to moderately increased levels of plasma arginine vasopressin(AVP) but, in some cases, may respond to high levels of the hormone or its analogue, deamino-D-arginine vasopressin(DDAVP). X-linked congenital NDI has now been linked to over 128 different mutations in diverse coding regions of the AVP receptor 2(AVPR2) gene. The functional effects of these mutations vary from complete loss of responsiveness to a simple shift to the right in the dose response curve. We report a case of congenital partial NDI, with transversion of A to G at codon 280 of the AVPR2 gene, resulting in a subsequent change of amino acid from tyrosine to cysteine, and that has been effective with hydrochlorothiazide and high dose of DDAVP.
Kwak Ho Kyung;Blumberg Jeffrey B.;Chen Chung Yen;Milbury Paul E.
Nutritional Sciences
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v.9
no.1
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pp.48-54
/
2006
Methods have been developed to evaluate the total antioxidant capacity of foods and plasma but limitations are associated with their ability to determine precisely the contribution of lipophilic antioxidants in a lipid milieu as well as interactions among them Thus, we modified the Oxygen Radical Absorbance Capacity (ORAC) assay to determine the peroxyradical scavenging ability of both hydrophilic and lipophilic compartments in plasma The hydrophilic ORAC assay was performed in a phosphate buffer system utilizing 2,2'-azobis (2-amidinopropane) dihydrochloride as a peroxyradical generator and fluorescein as the target The lipophilic ORAC assay was carried out in a dimethylsulfoxide :butyronitrile (DMSO/BN, 9:1 v/v) system using 2,2'-azobis (2,4-dimethyl valeronitrile) as a peroxyradical generator and BODIPY C11 581/591 as the target Analyses were conducted in bovine serum supplemented with water - and lipid - soluble antioxidants and in human plasma. Albumin (0.5$\sim$5 g/dL) and uric acid (0.1$\sim$0.5 $\mu$mol/L) increased hydrophilic ORAC values in a dose-dependent fashion ($R^{2}$=0.97 and 0.98, respectively) but had no impact on lipophilic ORAC values. $\alpha$-Tocopherol (15$\sim$200 $\mu$mol/L) increased lipophilic ORAC values in a dose-dependent fashion ($R^{2}$=0.94); neither $\alpha$-tocopherol nor $\beta$-carotene had an impact on hydrophilic ORAC values. However, addition of $\beta$-carotene at physiological concentration (0.23$\sim$1.86 $\mu$mol/L), either alone or in combination with other carotenoids, had no significant impact on lipophilic ORAC values. Thus, while assays of 'total antioxidant capacity' in biological matrices would be a useful research and clinical tool, existing methods are limited by the lack of complete responsiveness to the full range of dietary antioxidants.
Ikeda, Youko;Wolf-Johnston, Amanda;Roppolo, James R.;Buffington, Charles A.T.;Birder, Lori
International Neurourology Journal
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v.22
no.4
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pp.246-251
/
2018
Purpose: To determine whether responses to serotonin are altered in bladder strips from cats diagnosed with a naturally occurring form of bladder pain syndrome/interstitial cystitis termed feline interstitial cystitis (FIC). Methods: Full thickness bladder strips were isolated from aged matched healthy control cats and cats with clinically verified FIC. Bladder strips were mounted in an organ bath and connected to a tension transducer to record contractile activity. A serotonin dose response ($0.01-10{\mu}M$) was determined for each strip with the mucosa intact or denuded. Results: Bladder strips from control and FIC cats contracted in response to serotonin in a dose-dependent manner. The normalized force of serotonin-evoked contractions was significantly greater in bladder strips from cats with FIC (n=7) than from control cats (n=4). Removal of the mucosa significantly decreased serotonin-mediated responses in both control and FIC bladder preparations. Furthermore, the contractions in response to serotonin were abolished by $1{\mu}M$ atropine in both control and FIC bladder strips. Conclusions: The effect of serotonin on contractile force, but not sensitivity, was potentiated in bladder strips from cats with FIC, and was dependent upon the presence of the mucosa in control and FIC groups. As atropine inhibited these effects of serotonin, we hypothesize that, serotonin enhances acetylcholine release from the mucosa of FIC cat bladder strips, which could account for the increased force generated. In summary, FIC augments the responsiveness of bladder to serotonin, which may contribute to the symptoms associated with this chronic condition.
In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.
BACKGROUND/OBJECTIVES: This study investigated whether Padina arborescens extract (PAE) protects INS-1 pancreatic ${\beta}$ cells against glucotoxicity-induced apoptosis. MATERIALS/METHODS: Assays, including cell viability, lipid peroxidation, generation of intracellular ROS, NO production, antioxidant enzyme activity and insulin secretion, were conducted. The expressions of Bax, Bcl-2, and caspase-3 proteins in INS-1 cells were evaluated by western blot analysis, and apoptosis/necrosis induced by high glucose was determined by analysis of FITC-Annexin V/PI staining. RESULTS: Treatment with high concentrations of glucose induced INS-1 cell death, but PAE at concentrations of 25, 50 or $100{\mu}g/ml$ significantly increased cell viability. The treatment with PAE dose dependently reduced the lipid peroxidation and increased the activities of antioxidant enzymes reduced by 30 mM glucose, while intracellular ROS levels increased under conditions of 30 mM glucose. PAE treatment improved the secretory responsiveness following stimulation with glucose. The results also demonstrated that glucotoxicity-induced apoptosis is associated with modulation of the Bax/Bcl-2 ratio. When INS-1 cells were stained with Annexin V/PI, we found that PAE reduced apoptosis by glucotoxicity. CONCLUSIONS: In conclusion, the present study indicates that PAE protects against high glucose-induced apoptosis in pancreatic ${\beta}$ cells by reducing oxidative stress.
Jang, Cheol-Ho;Lee, Gayeon;Park, Yong-Cheol;Kim, Kyoung Heon;Lee, Do Yup
Journal of Microbiology and Biotechnology
/
v.27
no.6
/
pp.1150-1156
/
2017
Understanding phosphorus metabolism in photosynthetic organisms is important as it is closely associated with enhanced crop productivity and pollution management for natural ecosystems (e.g., algal blooming). Accordingly, we exploited highly time-resolved metabolic responses to different levels of phosphate deprivation in Chlamydomonas reinhardtii, a photosynthetic model organism. We conducted non-targeted primary metabolite profiling using gas-chromatography time-of-flight mass spectrometric analysis. Primarily, we systematically identified main contributors to degree-wise responses corresponding to the levels of phosphate deprivation. Additionally, we systematically characterized the metabolite sets specific to different phosphate conditions and their interactions with culture time. Among them were various types of fatty acids that were most dynamically modulated by the phosphate availability and culture time in addition to phosphorylated compounds.
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