JPH203, a newly developed anti-cancer drug, shows a preincubation inhibitory effect on L-type amino acid transporter 1 function.

JPH203 is a novel anti-cancer drug targeting L-type amino acid transporter 1 (LAT1), which plays a primary role in the uptake of essential amino acids in tumor cells. Although a co-incubation inhibitory effect of JPH203 has been shown in a conventional uptake assay, its preincubation inhibitory effects have remained undetermined. Therefore, we aimed to characterize the preincubation inhibitory effects of JPH203 on LAT1 function using leucine uptake assays in LAT1-positive human colon cancer HT-29 cells.

Sodium-coupled monocarboxylate transporter 1 interacts with the RING finger- and PDZ domain-containing protein PDZRN3.

Sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8) mediates monocarboxylate transport in the proximal tubule of the kidney. We have identified PDZK1 and PDZ domain-containing RING finger 3 (PDZRN3) as potent binding partners of SMCT1, which has a PDZ motif (Thr-Arg-Leu), by yeast two-hybrid screening and revealed that PDZK1 enhances the transport activity of SMCT1. In this study, we aimed to characterize the interaction between SMCT1 and PDZRN3 as well as to examine how PDZRN3 regulates SMCT1 function.

Identification of the multivalent PDZ protein PDZK1 as a binding partner of sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8) and SMCT2 (SLC5A12).

Sodium-coupled monocarboxylate transporters SMCT1 (SLC5A8) and SMCT2 (SLC5A12) mediate the high- and low-affinity transport of lactate in the kidney, but their regulatory mechanism is still unknown. Since these two transporters have the PDZ-motif at their C-terminus, the function of SMCTs may be modulated by a protein-protein interaction. To investigate the binding partner(s) of SMCTs in the kidney, we performed yeast two-hybrid (Y2H) screenings of a human kidney cDNA library with the C-terminus of SMCT1 (SMCT1-CT) and SMCT2 (SMCT2-CT) as bait.

Uncommon Human Telomerase Reverse Transcriptase Promoter Mutations Are Associated With Poor Survival in Ovarian Clear Cell Carcinoma.

Objectives: The present study assessed whether human telomerase reverse transcriptase (TERT) promoter mutations mediate the increased mortality risk observed in patients with ovarian clear cell carcinoma (CCC) and characterized the pathologic features of TERT promoter mutation-associated ovarian CCC.

Methods: The TERT promoter region in genomic DNA extracted from paraffin-embedded ovarian CCC specimens (n = 93) was bidirectionally sequenced.

Results: A total of 24 TERT promoter mutations were identified among the analyzed CCC cases, of which 11 were known "hotspot" mutations whose frequency was increased in CCC cases with compared to without coexistent adenofibroma (P < .

Influence of self-phase modulation effect on waveform degradation and spectral broadening in optical BPSK-SSB fiber transmission.

Self-phase modulation (SPM) effect is analyzed in a dispersion-compensated transmission using optical BPSK single sideband (SSB) modulation. The effect was evaluated numerically using both waveform degradation and spectral degradation, clarifying that waveform degradation is induced dominantly by peak power of the quadrature component of a Hilbert-transformed signal. Eye-opening degradation of BPSK-SSB is induced by lower fiber input power than the conventional double sideband (DSB) case because the SSB-homodyne system is sensitive to phase error resulting from SPM.

Effect of diet on the cardiovascular system in healthy beagles.

In management of canine cardiac disorders, cardiac drugs are commonly administered with food, although the cardiovascular effects of feeding and frequency of feeding are unknown. This study investigated the cardiovascular effect of feeding and frequency of feeding using a telemetry monitoring system in unanesthetized and unrestrained dogs. Systolic and diastolic blood pressure, heart rate and double product were steeply elevated during the five minutes immediately before feeding.

Influence of preemptive analgesia with meloxicam before resection of the unilateral mammary gland on postoperative cardiovascular parameters in dogs.

Preemptive analgesia is recommended in small animal medicine. However, many studies have evaluated the response to analgesic treatment by behavioral observation. Therefore, the influence of preemptive analgesia with meloxicam on postoperative cardiovascular and renal parameters remains to be clarified.

Influence of optical filters on pulse circulation in fiber rings with a frequency shifter and EDFA.

Optical fiber ring circuits constructed with frequency shifters and EDFAs are applicable to pulsed lightwave frequency sweepers, wavelength converters, and optical packet buffers. The salient criterion for those applications is how many times the optical pulse can circle the ring. Optical band-pass filters in the ring can serve an important role for pulse circulation because the filter determines the gain bandwidth at every circulation under the condition of signal wavelength shift.

Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel.

Functional and biochemical data have suggested a role for the cytochrome P450 arachidonate monooxygenases in the pathophysiology of hypertension, a leading cause of cardiovascular, cerebral, and renal morbidity and mortality. We show here that disruption of the murine cytochrome P450, family 4, subfamily a, polypeptide 10 (Cyp4a10) gene causes a type of hypertension that is, like most human hypertension, dietary salt sensitive. Cyp4a10-/- mice fed low-salt diets were normotensive but became hypertensive when fed normal or high-salt diets.

Hepatocellular toxicosis associated with the alternate administration of carprofen and meloxicam in a siberian husky.

A 4-year-old female Siberian Husky was diagnosed with pyogranulomatous steatitis at the site of a recurrence of left anal sac rupture (day 1). Carprofen and orbifloxacin were given for 13 days without improvement. A single dose of meloxicam was administered prior to surgical resection of the anal sac, and based on elevated liver enzyme activity, liver supportive therapy was initiated.

Thermal tuning of mechanically induced long-period fiber grating.

We have developed a wideband tunable optical filter that uses a long-period fiber grating (LPFG) in which both resonance wavelength and its signal attenuation can be adjusted. We create the grating mechanically by pressing a spring coil to an optical fiber. We achieve continuous fine tuning of wavelength and attenuation by varying the temperature of the LPFG.

Breeding season in female cats acclimated under a natural photoperiod and interval until puberty.

The breeding season was investigated in 174 female cats that were acclimated under a natural photoperiod, and determined the interval between birth and initial estrus (puberty) was determined in 125 cats. Although the breeding season differed noticeably among individual animals, the mean was 180.4 +/- 3.

Acquired mitral stenosis in a cat with hypertrophic cardiomyopathy.

A seven-year-old castrated male domestic shorthair cat was diagnosed with hypertrophic cardiomyopathy (HCM) and suspected mitral stenosis (MS) based on electrocardiography, thoracic radiographs and echocardiographic findings. Post-mortem examination of the heart revealed morphological features consistent with HCM. In addition, there was marked fibrous deposition on the surfaces of the chordae tendineae extending to both mitral valve leaflets, which caused total chordal fusion into pillars of fibrous tissue and fusion of the commissures.

Ebstein's anomaly in a beagle dog.

An intact male beagle dog aged 1 year was referred because of shortness of breath, exercise intolerance and cardiac murmur. Based on the results from electrocardiography, thoracic radiography and echocardiography, the dog was diagnosed as Ebstein's anomaly. Although the orally administered digoxin, vasodilators and diuretics partially improved congestive signs, the dog became to be refractory and died 20 months after the diagnosis.

Androgen-mediated induction of the kidney arachidonate hydroxylases is associated with the development of hypertension.

Hypertension is a leading cause of cardiovascular, cerebral, and renal disease morbidity and mortality, and epidemiological evidence suggests a role for sex-dependent mechanisms in the pathophysiology of hypertension. We show here that treatment of rats with 5alpha-dihydrotestosterone increases the activity of the kidney arachidonate omega/omega-1 hydroxylase and the biosynthesis of 20-HETE (165 and 177% of control untreated male and female rats, respectively) and raises the systolic blood pressures of male and females rats by 46 and 57 mmHg, respectively. These androgen effects are associated with an upregulation in the kidney levels of CYP 4A8 mRNA and a decrease in CYP 4A1 transcripts.

Lone atrial fibrillation in a dog.

An intact male Pointer aged 9 year was found to have atrial fibrillation (AF). Thoracic radiography and echocardiography as well as routine blood work revealed no cardiac disease. Thus, the dog was diagnosed as lone AF.

Hypertrophic cardiomyopathy in a mixed breed cat family.

A spayed female mixed cat (case 1) and its female offspring, the result of a pairing between case 1 and its male sibling, were diagnosed with hypertrophic cardiomyopathy (HCM). A pedigree survey revealed that the prevalence of HCM was at least 12.5% in the family, which was considered to be significantly higher than that in a hospital-based population (approximately 1.

Hyperzincemia with systemic inflammation: a heritable disorder of calprotectin metabolism with rheumatic manifestations?

A boy had infantile-onset systemic inflammation, growth failure, hepatosplenomegaly, anemia, leukocytopenia, progressive muscular dystrophy, and hypercalprotectinemia, resulting in marked hyperzincemia. His mother had a history of chronic arthritis since childhood and also showed hypercalprotectinemia/hyperzincemia. We postulate an inherent defect in calprotectin metabolism.