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It is not clear whether archived cytological specimens (ACSs) obtained with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with rapid onsite evaluation (ROSE) can be used for genomic profiling of tumors. We used ACSs to perform genomic analysis of specimens to identify oncogenic and druggable mutations.A panel of 60 significantly mutated genes specific to pancreatobiliary cancer was created and used for genomic analysis of 113 specimens of 44 formalin-fixed paraffin-embedded (FFPE) tissues and 69 ACSs obtained by EUS-FNA with ROSE were included. The quantity and quality of DNA extracted from FFPE tissues and ACSs were compared. We also compared DNA from spray and touch ACSs. Next, genomic profiles were compared. We also evaluated detection of target gene mutations in each specimen.The amount of DNA in FFPE tissues was greater than in ACSs (P = 0.014), but the quality of DNA was comparable (P = 0.378). There was no quantitative or qualitative difference between spray and touch ACSs (P = 0.154 and P = 0.734, respectively). Oncogenic mutations were shared at 82 % in FFPE tissues and ACSs and 82 % in spray and touch ACSs. The sensitivity of genomic analysis in ACSs was 97 % (67 of 69), which was comparable to that of cytology (62 of 69, 90 %; P = 0.165), and was significantly higher than that of histology (32/44, 73 %; P 0.001). Drug-matched mutations were identified in five of the 44 lesions (11 %).Genomic analysis of ACSs is useful in the prognosis of pancreatic cancer because detection of driver mutations is similar to detection in FFPE tissues.

This study was performed to investigate the effect of the inclusion rate of corn silage (CS) in ensiled total mixed ration (TMR) on dry matter intake (DMI), nutrient digestibility, and ruminal fermentation in Japanese Wagyu steers. Four ensiled TMRs, in which the crude protein (CP) and total digestible nutrients (TDN) levels were adjusted to be similar, were prepared with 0, 15, 30, and 45% CS, respectively. Four Japanese Wagyu steers during the fattening period were used in a feeding trial with the four dietary treatments of the ensiled TMRs in a 4 × 4 Latin square design. Increasing the inclusion rate of CS resulted in higher pH values and lower lactate production in the ensiled TMR, although all TMR silages showed good fermentative characteristics, such as low pH value and high lactate content. The DMI linearly increase when the inclusion rate of CS in the TMRs increased. There were differences in the apparent digestibilities of CP, non-fibrous carbohydrate, acid detergent fiber, and neutral detergent fiber. The TDN contents were greater in the ensiled TMRs with 15 and 30% CS. The feeding of TMRs with higher inclusion rates of CS gave rise to slower fermentation in the rumen. Corn silage should be utilizable as a TMR material, and its inclusion at approximately 30% in a TMR is a safe upper limit for Japanese Wagyu steers during the fattening period.

Background: The Tokyo Guidelines (TG; 2013) indicated that emergency cholecystectomy is an important early treatment option for acute cholecystitis; however, surgical intervention is not necessarily indicated in patients with advanced age. We evaluated percutaneous transhepatic gallbladder aspiration (PTGBA), percutaneous transhepatic gallbladder drainage (PTGBD), and the administration of antibiotics alone as treatment options for acute ­cholecystitis. Methods: From January 2010 to December 2017, 159 patients with acute cholecystitis were treated at our institution. The data from these patients were retrospectively analyzed. Results: Of these 159 cases, 109 underwent PTGBA, 28 underwent PTGBD, and 22 were administered antibiotics alone. None of the 159 patients needed urgent (early) cholecystectomy, and all patients were discharged without mortality. PTGBA was unsuccessful in only 6 of 109 patients; PTGBD was performed in these 6 cases. Long-term follow-up was conducted in all cases. Of the 159 patients, 146 had gallbladder stones initially, while 13 had none at the time of presentation. Of these 146 patients with gallbladder stones, 84 underwent elective cholecystectomy, while 62 did not. Of the 84 patients who underwent elective cholecystectomy, 2 developed choledocholithiasis; of the 62 patients who did not undergo elective cholecystectomy, 5 developed choledocholithiasis and 2 developed acute cholecystitis. The incidences of choledocholithiasis and acute cholecystitis did not significantly differ between the 2 groups (p = 0.06). Conclusions: Despite the recommendations in the TG (2013), emergency cholecystectomy was not needed in any of the present patients with acute cholecystitis. Acute cholecystitis can be successfully treated with ­PTGBA or PTGBD, which are simple procedures with good short- and long-term safety. These procedures are highly recommended for patients with acute cholecystitis, especially in the elderly population.

The objective of this study was to evaluate the effect of replacing corn with brown rice (BR) on dry matter intake (DMI), milk production, blood metabolites and energy balance (EB) in cows during the periparturient period. Twenty-four nonlactating multiparous Holstein cows in late gestation were studied from 3 week before the expected calving date through 6 week after parturition. The cows were divided into one of two dietary treatment groups based on parity and the expected calving date. The treatments were a diet containing steam-flaked corn and a diet containing steam-flaked BR. Prepartum DMI and body weight (BW) and postpartum DMI, BW, milk yield, milk protein and lactose yield were not affected by the dietary treatment. However, the milk fat content and fat yield were higher ( P = 0.02 and P = 0.01) for cows fed BR than for cows fed corn. Thus, cows fed BR-based total mixed ration (TMR) tended to have more negative EB in early lactation ( P = 0.06) compared with cows fed corn-based TMR. During the prepartum period, the plasma concentrations of glucose, insulin, β-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), aspartate transaminase (AST) and Ca were not affected by dietary treatments. On the other hand, the postpartum plasma glucose and insulin concentrations were decreased ( P P = 0.02) and the BHBA and AST concentrations were increased ( P P = 0.02) by replacing corn with BR with no dietary effect on postpartum plasma NEFA and Ca concentrations. These results show that feeding BR instead of corn does not affect DMI or milk yield, but increases milk fat production and leads to a more negative EB state in early lactation. Replacing corn with BR during the periparturient period has adverse effects on the metabolism and energy status in early lactating cows.

Background The clonality of primary tumors is well elucidated. In contrast, the relation to metastatic foci is not well understood. We examined genomic clonality of primary tumors and metastatic foci. Method We studied 144 foci (34 primaries, 104 lymph nodes, 6 organ mets) from 10 patients with gastrectomy (c-Stage 3). We also searched the expression of MMR proteins. Results In 10 primaries, mutations were found in all (range 3-12, mean 6). Of 104 lymph nodes, 64 lymph nodes carrying mutations identical to corresponding primaries in all. In addition, all the genomic profiles were replicated in corresponding lymph nodes and visceral mets. Among 3 cases with dMMR, all metastatic foci showed identical phenotypes. Conclusion Surprisingly, significantly mutated genes (SMGs) profiles in all lymph nodes and visceral mets were identical to the primaries. In addition, MMR/MSI status was also identical. These results indicated proper selection of chemo-, molecular-, and immune-oncology treatments could be effectively applied to the spreaded mets. Internoduler ""de novo"" heterogeneity was so scarce. Often claimed tumor heterogeneity could be due to inappropriate selection of drugs and due to their pressure.

The effects of the substitution of brown rice (Oryza sativa L.; BR) for corn (Zea mays L.) in ensiled total mixed ration (TMR) that had a high proportion of grain on feed intake, lactation performance, ruminal fermentation, digestion, and N utilization were evaluated. Nine multiparous Holstein cows (51 ± 9 d in milk) were used in a replicated 3 × 3 Latin square design with 3 dietary treatments: a diet containing 0, 20, or 40% steam-flaked BR and 40, 20, or 0% steam-flaked corn (dry matter basis). Cows were fed ad libitum an ensiled TMR consisting of 40.7% alfalfa silage, 11.8% grass silage, 7.1% soybean meal, and 40.0% steam-flaked grain (dry matter basis). The ensiled TMR was prepared by baling fresh TMR, and then sealed by a bale wrapper and stored outdoors at 5 to 30 °C for over 6 mo. Dry matter intake and milk yield were lower for cows fed 40% BR than for cows fed 40% corn. The ruminal pH and total volatile fatty acid concentrations were not affected by dietary treatment. The ruminal ammonia-N concentration decreased as the percentage of BR in the diets was elevated. The proportion of acetate decreased, and that of propionate and butyrate increased with the increasing levels of BR. Plasma urea-N concentrations was lower and glucose and insulin concentrations were higher for cows fed 40% BR than for cows fed 40% corn. The whole-tract apparent digestibility of dry matter, organic matter, and starch increased, and the digestibility of neutral detergent fiber and acid detergent fiber decreased with the increasing BR level in the diet, with no dietary effect on crude protein digestion. As a proportion of N intake, the urinary N excretion was lower and the retention of N was higher for cows fed 40% BR than for cows fed 40% corn, with no dietary effect observed on N secretion in milk and fecal N excretion. These results show that substituting BR for corn decreases urinary N losses and improves N utilization, but causes adverse effects on milk production when cows are fed high-grain diets at 40% of dietary dry matter.

The objective of this study was to evaluate the effect of substituting brown rice grain for corn grain in total mixed ration (TMR) silage containing food by-products on the milk production, whole-tract nutrient digestibility and nitrogen balance in dairy cows. Six multiparous Holstein cows were used in a crossover design with two dietary treatments: a diet containing 30.9% steam-flaked corn (corn TMR) or 30.9% steam-flaked brown rice (rice TMR) with wet soybean curd residue and wet soy sauce cake. Dietary treatment did not affect the dry matter intake, milk yield and compositions in dairy cows. The dry matter and starch digestibility were higher, and the neutral detergent fiber digestibility was lower for rice TMR than for corn TMR. The urinary nitrogen (N) excretion as a proportion of the N intake was lower for rice TMR than for corn TMR with no dietary effect on N secretion in milk and fecal N excretion. These results indicated that the replacement of corn with brown rice in TMR silage relatively reduced urinary N loss without adverse effects on feed intake and milk production, when food by-products such as soybean curd residue were included in the TMR silage as dietary crude protein sources.

Some anthocyanins have been reported to exhibit antioxidant activity and to enhance antioxidant enzyme activity. The aim of this study was to determine the fermentative quality of purple rice, which is abundant in anthocyanin, and its effects on digestibility, ruminal fermentation and oxidative status markers in sheep. The whole crop silages of purple and control rice were prepared in drum silos after the materials were chopped and lactic acid bacteria was inoculated. These were followed by a feeding trial using eight wethers in a 2 × 2 crossover design. Both the purple and control rice silages showed excellent fermentative qualities. Although the purple rice silage contained abundant anthocyanin, it had inadequate nutritional values in comparison to the control rice silage, including higher levels of fiber fractions, lower nutrient digestibility and lower production of ruminal volatile fatty acids. The feeding of the purple rice silages led to an elevation in plasma activity of superoxide dismutase, which is an important antioxidant enzyme. The results of this study suggest that purple rice may become a source of anthocyanin to improve oxidative status in ruminants. To achieve that, however, a new variety of purple rice with good nutritional value is needed for practical use as a ruminant feed.

Anthocyanins are pigments found widely in plants. They have been reported to possess antioxidant activity and an enhancing effect on superoxide dismutase (SOD) activity in monogastric animals. Thus, anthocyanins could also affect the status of the antioxidative defense system in ruminants. This study aimed to investigate the effect of the supplementation of purple pigment from anthocyanin-rich corn on blood antioxidant activities and oxidation resistance in sheep. Twelve sheep were used in a crossover design with two dietary treatments: a diet with purple corn pigment (pigment treatment) and one without (control). The pigment was added to the diets at an anthocyanin concentration of 0.5%. Blood and urine samples were collected to determine the markers of oxidative status. A portion of the plasma was used for an oxidation resistance test, in which plasma was incubated with an oxidizer at 37 °C for 0, 4 and 8 h, and then the degree of oxidation was measured. The pigment addition to the diet caused a significant increase in the SOD activity of the plasma, although the total antioxidant capacity and glutathione concentration in the plasma of both treatment groups were similar. In the oxidation resistance test, the oxidation in the plasma from the pigment treatment group was significantly suppressed compared to that in the control group at 4 and 8 h after the onset of the incubation. These findings indicate that the intake of purple pigment from anthocyanin-rich corn increases the SOD activity and the potential of the antioxidant activity of plasma in sheep.

Nine multiparous Holstein cows were used in a replicated 3 × 3 Latin square design to determine the effects of substituting corn grain with brown rice (BR) grain in total mixed ration (TMR) silage on milk yield, ruminal fermentation and nitrogen (N) balance. The TMR silages were made from the ensiling of TMR containing (dry matter basis) 50.1% forage in rice silage and corn silage combination, and 49.9% concentrate. The grain portion of the diets contained 31.2% steam-flaked corn, 31.2% steam-flaked BR or an equal mixture of corn and BR. Dietary treatments did not affect dry matter intake, milk yield and milk fat, protein and lactose yields. The ruminal pH and total volatile fatty acid concentrations were not affected by dietary treatment. The urinary N excretion decreased linearly (P < 0.01) in response to increased levels of BR, with no dietary effect on N intake, N secretion in milk and fecal N excretion. Our results indicate that steam-flaked BR is a suitable replacement for steam-flaked corn in dairy cow diets, and that it can be included in rations to a level of at least 31.2% of dry matter without adverse effects on milk production, when cows were fed rice silage and corn silage-based diets.

Immunolocalization of lingual antimicrobial peptide (LAP), a member of the β-defensin family, in the digestive tract of calves was investigated to determine its distribution in the digestive tract of Holstein-Friesian calves. Various regions of the digestive tract were collected from slaughtered calves, and fixed in 10% formalin in PBS. Paraffin sections were stained with anti-LAP antibody, followed by visualization of immunoreactions products utilizing the avidin-biotin complex method. Expression of LAP mRNA was analyzed with reverse transcription-PCR. Immunoreactive LAP was localized in the stratum corneum of the stratified squamous epithelium of the tongue, esophagus, rumen, reticulum and omasum but not in their basal layer and lamina propria. In the gastric glands of the abomasum, only chief cells showed LAP positive reaction at the apical side of their cytoplasm. Lamina propria and Peyer's patch of the ileum had some leukocyte-like cells immunopositive for LAP. Weak immunoreaction of LAP was also detected in the mucosal epithelium of the intestinal gland of the cecum, colon and rectum. All regions of digestive tract showed LAP mRNA expression with PCR. These results indicate differential localization of LAP in the mucosal epithelium of digestive tracts in calves. The LAP expressed in stratum corneum of stratified squamous epithelium and chief cells of abomasum specifically may play role in the innate immune function in these tissues.

Lingual antimicrobial peptide (LAP), a member of the beta-defensin family in cows, is involved in the innate immune system and plays a crucial role in killing a large variety of microorganisms. The aim of the present study was to demonstrate the immunolocalization of LAP in the mammary glands of cows. A LAP antibody was raised in a rabbit by immunity with a synthetic 11 amino acid sequence out of a 42-amino acid sequence of the mature form of LAP. The specificity of the LAP antibody was checked using a competitive immunoassay and Western blotting. Paraffin sections of the mammary gland were immunostained with LAP antibody. In the competitive immunoassay, an increase of synthetic LAP concentration suppressed the optical density. Western blotting analysis for LAP revealed the presence of the LAP peptide in mammary alveolar tissue. When the mammary gland was immunostained with LAP antibody, epithelial cells of both infected and non-infected alveoli were immunopositive. These results indicate that LAP is localized in the epithelium of non-infected as well as infected alveolus in the mammary gland in cows.

An experiment was conducted to examine feed intake, apparent digestibility, nitrogen balance, ruminal fermentation and blood components of wethers fed diets containing increasing levels of wet green tea grounds (WGTG). The experimental design was a 4 x 4 Latin square with four wethers in four 15-day periods. Wethers were allowed access to diets ad libitum, and allotted to one of four treatments in which WGTG replaced 0% (no WGTG added, CTG), 5% (low level, LBG), 10% (medium level, MTG), and 15% (high level, HTG) of total mixed ration (TMR) dry matter (DM) as wet brewers grains (WBG). All TMR silages were ensiled for 120 days and, irrespective of the WGTG addition, they were well preserved with a high lactic acid content, low pH and ammonia-N contents. There were no differences among treatments in feed intake, with the exception of ether extract intake (P = 0.032). Digestibilities for LTG and MTG treatments were not different from CTG. However, the organic matter, crude protein, acid detergent fiber and energy digestibilities for HTG treatment were lower than the CTG (P < 0.05). As the level of WGTG increased, nitrogen intake did not differ, but fecal nitrogen increased (P = 0.002), while urinary nitrogen decreased (P < 0.001). No differences among treatments were found in pH level and volatile fatty acids concentrations. However, the ruminal ammonia-N of the HTG silage was lower than for the CTG silage at all times (P < 0.05). Increasing concentrations of WGTG in the TMR silage decreased (P = 0.019) plasma urea nitrogen content. Therefore, the possible mixing proportion of WGTG for TMR silages can be 10% of the diet DM.

The effects of the lengths of growth of round bale whole-crop corn silage on its nutritive value, the methane production, chewing time, and ruminal fermentation were evaluated in three Holstein steers (599.3 ± 31.5 kg). Corn forages were harvested, baled and wrapped on the same day at 129 (D129), 118 (D118) and 107 (D107) days from planting. All steers were fed the three corn silages along with urea at maintenance energy requirements during three 14-day periods in a 3 × 3 Latin square design. A balance trial was conducted to investigate whole tract digestibility by the collection of total feces and urine over a 7-day test period. For 2 days of the test period, a head hood-type respiration chamber was used to measure methane production. Ruminal fluid was collected immediately before and 3 h after, the morning feeding on the last day of the test period. There was no spoilage in any of the silages (n = 9). The average fresh weight of the bales was 326.4 ± 10.7 kg. The DM content of the corn silage was highest in D118 and lowest in D129 (P

The aim of this research was to investigate the effect of peppermint feeding on dry matter intake, nutrient digestibility, ruminal fermentation and milk production in early lactating cows. Four Holstein cows were offered a diet with 5% dried peppermint and four Holstein cows remained on a diet without 5% of dried peppermint on a dry matter basis. The addition of peppermint to feed did not affect dry matter intake, although the eating time of feed was increased by mixing the feed with peppermint. There were no significant differences in the nutrient digestibilities between the two treatments. The ruminal ammonia and volatile fatty acids concentrations were similar in the two treatments, however, peppermint ingestion by cows led to a decrease in ruminal pH. The lowered pH value was within the stable pH condition range. No significant differences in the treatments were observed in milk production or milk composition except for the milk fat content. These results suggest that feeding peppermint to early lactating cows had little effect on their dry matter intake, nutrient digestibility, ruminal fermentation and milk production.

Seven Holstein cows (BW = 639.4 +/- 28.8 kg, age = 62.6 +/- 6.9 mo, parity = 3.1 +/- 0.4 yr) (mean +/- SE) were used to measure uterine blood flow using a transit time ultrasonic flow meter. Ultrasonic flow probes were implanted (d 218 +/- 4 of gestation) around both uterine arteries (n = 3) or the gravid uterine artery (n = 4) to measure variations in uterine blood flow through this vessel in response to postural change (standing and lying). Implantation of the ultrasonic blood flow probe was successful in all 7 cows. Uterine blood flow was measured for 22.9, 23.1, and 21.4 h/d on d 226, 248, and 269 of gestation, respectively. Cows exhibited normal durations of gestation (272.8 +/- 1.6 d), gave birth to normal healthy calves (birth weight = 41.5 +/- 3.0 kg), and did not retain their placenta. Uterine blood flow to the gravid horn during lying was greater than during standing on d 226 (standing vs. lying, 8.04 vs. 8.79 L/min, respectively), d 248 (9.87 vs. 11.06 L/min), and d 269 (8.15 vs. 9.74 L/min) of gestation. Cows spent nearly 50% of their time lying during our observations at all gestational ages. Greater blood supply to the gravid uterus was observed during lying than during standing in this study.

As a novel method for measuring bone resorption, an immunoassay system for human N-terminal osteocalcin (N-OC) was developed to determine if osteocalcin molecules are released from bone degraded by osteoclasts in vitro. The assay system employed a monoclonal antibody to the first 20 N-terminal residues of osteocalcin as the solid phase and polyclonal antibodies against these same residues as an enzyme conjugate. This assay system could detect the N-terminal portion of osteocalcin formed during the degradation of the human osteocalcin molecule by trypsin or cathepsin D. Osteoclasts were isolated from human alveolar bone and cultured on human bone slices; the osteocalcin content in the media from these cultures was measured by this N-OC assay method. The N-terminal fragment of osteocalcin was the major form of osteocalcin released during osteoclastic bone resorption along with small amounts of intact osteocalcin. Interleukin-1 (IL-1β) and interleukin-6 (IL-6), stimulators of osteoclastic bone resorption, increased the N-OC level by 1.5 fold compared with the level of N-OC in osteoclast cultures in the absence of stimulators. In contrast, treatment of the cultures with calcitonin or an inhibitor of cathepsin D (E-64), both of which inhibit osteoclastic bone resorption, decreased the amount of N-OC in the culture supernatants. These results suggest that the N-terminal fragment of osteocalcin is released during osteoclastic bone resorption and that its level may serve as an index of bone resorption in vitro.

Pulmonary surfactant protein A (SP-A) is known to be a major phospholipid-associated glycoprotein in pulmonary surfactant, which is specific to the lung. In this study, the SP-A concentrations in sera of patients with various lung diseases were determined using an enzyme-linked immunosorbent assay. Patients with idiopathic pulmonary fibrosis (IPF) and pulmonary alveolar proteinosis (PAP) exhibited prominently high concentrations of serum SP-A compared to those of other lung diseases and healthy volunteers, although there were significant increases in serum SP-A concentrations in patients with pulmonary tuberculosis, chronic pulmonary emphysema, diffuse panbronchiolitis and bacterial pneumonia compared to those of healthy volunteers. Successive measurement in 2 patients with IPF showed that serum SP-A levels reflect the disease activity of IPF. In patients with IPF, serum SP-A concentrations were significantly correlated with those of serum lactate dehydrogenase, whereas there were no significant correlations of serum SP-A concentrations with erythrocyte sedimentation rate, arterial oxygen saturation, vital capacity and carbon monoxide diffusing capacity. Determination of serum SP-A will contribute to diagnosing IPF and PAP, and may reflect the disease activity of IPF.

Anthocyanin in purple corn (Zea mays L.) has been reported to show several functional and biological attributes, displaying antioxidant, antiobesity and antidiabetic effects in monogastric animals. The objective of this study was to investigate the effect of feeding anthocyanin-rich corn (Zea mays L., Choko C922) silage on digestibility, milk production and plasma enzyme activities in lactating dairy cows. The cows were fed diets based on the control corn or the anthocyanin-rich corn silage (AR treatment) in a crossover design. The anthocyanin-rich corn silage-based diet had a lower starch content, nutrient digestibility and total digestible nutrients content when compared to the control diet. The milk yield, lactose and solids-not-fat contents in the AR-treatment cows were lower than in the control cows. The feeding of the anthocyanin-rich corn silage led to a reduction in aspartate aminotransferase (AST) activity and an increase in superoxide dismutase (SOD) activity in the plasma. These data suggest that the anthocyanin-rich corn has a lowering effect on AST activity with concomitant enhancement of SOD activity in lactating dairy cows. However, a new variety of anthocyanin-rich corn with good nutritional value is needed for practical use as a ruminant feed.

Two feeding trials were performed to evaluate the effect of soy sauce cake (SSC) on digestibility, ruminal fermentation and nitrogen (N) balance as well as methane production in Holstein steers. Six animals received a diet without or with the SSC at 10% (Experiment 1) and 20% (Experiment 2) in a 2 × 2 crossover design with a balance trial and respiratory exchange measurement. The SSC feeding showed a strongly inhibitory effect on methane production when its proportion was elevated up to 20%. The digestibility of nutrients with the 10% SSC treatment was similar to that of the control, whereas that for the 20% SSC treatment was significantly decreased in comparison with the control. The 20% SSC treatment also inhibited ruminal fermentation. A lower N partition to urine and a higher N partition to retention were observed in the animals receiving the 20% SSC treatment. These results suggested that SSC feeding at 20% suppressed methane production and changed the N balance; however, the feeding level of 20% caused deterioration in some productive aspects, such as nutrient digestibility and ruminal fermentation. In addition, a feeding level of SSC at 10% of the diet should be considered a reasonable level in cattle.

Heat stress (HS) induces adaptive responses that are responsible for alterations of carbohydrate and lipid metabolism. This study aimed to evaluate the effects of chronic heat treatment on the expression and secretion of leptin and adiponectin, important regulators of energy homeostasis, food intake and insulin action. C57BL/6 mice were subdivided into three groups (24 mice each). The first group was kept under control conditions (C: 22±2 °C). The second group was exposed to HS (35±1 °C). The third group was kept under control conditions and was food restricted (FR). The HS group had higher rectal temperature than the C and FR groups and lower food intake than the C group. Hspa1 (Hspa1a) gene expression in adipose tissue, muscle and liver was higher under HS than FR and C. Heat treatment resulted in decreased blood glucose and non-esterified fatty acids; increased leptin, adiponectin and insulin secretion; and greater glucose disposal. Leptin, adiponectin, leptin and adiponectin receptors, insulin receptor substrate-1 and glucose transporter mRNAs were up-regulated in HS mice. This study provides evidence that HS improves leptin and adiponectin signalling in adipose tissue, muscle and liver. Heat stress was responsible for improving insulin sensitivity and glucose uptake in peripheral tissues, probably mediated by adipokines. Changes in the adipokine levels and sensitivity to them may be considered as an adaptive response to heat.

Background. Resistance to chemotherapeutic agents is a major problem in non-small cell lung cancer (NSCLC) chemotherapy, and recent studies have indicated that glutathione S-transferase-π (GST-π) may play an important role in the resistance of cancer cells to alkylating agents that include platinum compound. Methods. GST-π in serum of 121 patients with NSCLC was measured by a sandwich enzyme-linked immunosorbent assay, and the serum concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, and neuron-specific enolase (NSE) were also examined. Serum levels of these tumor markers were also evaluated in relation to therapeutic response in 69 patients who received combination chemotherapy with platinum compound. Results. Fifty of 121 patients with NSCLC (41.3%) showed elevated serum GST-π levels above a cutoff value of 34.8 ng/ml (mean + two standard deviations in 30 healthy control subjects). The positive rate of GST-π in patients with NSCLC was higher than those of CEA (37.2%), SCC (15.7%), and NSE (14.9%). The mean pretreatment GST-π level was significantly lower in patients with a partial response to chemotherapy than in those with no response (26.9 ± 11.3 ng/ml versus 38.8 ± 16.7 ng/ml; P < 0.003). Among patients with elevated levels of pretreatment serum GST-π, only 13.8% (four of 29) responded to the combination chemotherapy, whereas partial response was observed in 40.0% of patients (16 of 40) with serum GST-π concentration below the cutoff level (P < 0.02). Neither CEA, SCC, nor NSE showed such a relationship. Conclusions. The serum GST-π level may have limited value as a tumor marker for NSCLC. Interestingly, pretreatment serum GST-π levels may be a useful parameter for predicting therapeutic response to combination chemotherapy regimens that include platinum compound. Cancer 1994; 73:1377–82.