Density-dependent effects of non-native brown trout Salmo trutta on the species-area relationship in stream fish assemblages.

The spatial scale and density-dependent effects of non-native brown trout Salmo trutta on species richness of fish assemblages were examined at 48 study sites in Mamachi Stream, a tributary of Chitose River, Hokkaido, Japan. The density of age ≥1 year S. trutta was high in the upstream side of the main stem of Mamachi Stream. Fish species richness increased with increasing area of study sites (habitat size), but the increasing magnitude of the species richness with area decreased with increasing age of ≥1 year S. trutta density. The relationships between age ≥1 year S. trutta, however, and presence-absence of each species seemed to be different among species. Species richness was also determined by location and physical environmental variables, i.e. it was high on the downstream side and in structurally complex environments.

The induction of antigen-specific CTL by in situ Ad-REIC gene therapy.

An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.

Pilot evaluation of Enterococcus faecium SF68 as adjunctive therapy for oclacitinib-responsive adult atopic dermatitis in dogs.

OBJECTIVE: To evaluate the adjunctive effect of supplementation with Enterococcus faecium SF68 (FortiFlora; Purina Pro Plan Veterinary Diets) on oclacitinib (Apoquel, Zoetis) dose reduction, while maintaining or reducing the Pruritus Visual Analog Score and Canine Atopic Dermatitis Extent and Severity Index values in client-owned adult dogs with environmental atopic dermatitis. MATERIALS AND METHODS: Enrolled dogs had exhibited control of atopic dermatitis on oclacitinib for at least 6 months before, and continuing throughout, the study. Dogs with non-seasonal pruritus were blindly randomised to receive either SF68 (1×108 colony forming units/g orally twice daily) or placebo for 12 weeks. After 8 weeks of supplementation, oclacitinib dose was decreased by approximately 25%, aiming to maintain and reduce the clinical disease scores. RESULTS: Supplementation with SF68 was associated with no difference in oclacitinib dose reduction versus placebo in 21 client-owned dogs with atopic dermatitis. Clinical disease scores were not different between groups at study completion. CLINICAL SIGNIFICANCE: Further larger-scale studies are warranted to investigate optimal strain(s), dosing and duration of probiotic supplementation as an adjunctive strategy in management of canine atopic dermatitis.

Health-related quality of life among renal-transplant recipients in Japan.

BACKGROUND: This study had four goals: (1) to evaluate an index of health-related quality of life (HQOL) among renal-transplant recipients in Japan, (2) to compare HQOL of renal-transplant recipients with that of the Japanese population as a whole, and (3,4) to study associations of HQOL with renal function and with the time since transplantation. METHODS: Questionnaires were distributed to 570 subjects. All were outpatients, were 16 years old or older, and were studied at least 1 year after they had received their latest renal transplant. HQOL was assessed with the Short Form 36-item health survey. Subjects' physicians provided data on renal function. Associations of HQOL with serum creatinine concentration and with the time since transplantation were evaluated by logistic regression. RESULTS: The response rate was 83%. Data from patients with diabetes and from those who had had at least two renal transplants were excluded; data from 395 recipients were analyzed. On the physical functioning, general health perception, vitality, and social functioning scales, the patients' scores were significantly lower than the Japanese national-norm scores. General health perception was particularly low. Serum creatinine concentrations were associated with general health perception, vitality, and social functioning. Longer times since transplantation were associated with better social functioning. CONCLUSIONS: Although social and physical functioning may improve after transplant surgery, a low self-rating of general health seemed to remain. The rarity of renal transplantation in Japan and other psychosocial factors may explain the low self-rating of general health in Japanese renal-transplant recipients.

Serotonin-induced 5-HT1A receptor desensitization in C6BU-1 glioma cells transfected with 5-HT1A receptor gene.

In this study, it has been clearly demonstrated that a selective 5-hydroxytryptamine (5-HT)1A agonist, 8-OH-2-(di-n-propylamino)-tetraline (8-OH-DPAT, 1 microM) significantly inhibited forskolin (10 microM)-stimulated cyclic AMP (cAMP) accumulation in the C6BU-1 cells transfected with 5-HT1A receptor gene. Further, this 8-OH-DPAT-induced inhibition of forskolin-stimulated activity was significantly attenuated after pre-exposure to 5-HT (10 microM) for 12 h. Spiperone (10 microM), a 5-HT1A and 5-HT2A antagonist, prevented 5-HT-induced desensitization of 5-HT1A receptor, but a selective 5-HT2A receptor antagonist, ketanserin, did not. In addition, pre-exposure to a selective 5-HT2A agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 10 microM), for 24 h did not alter the inhibitory effect of 8-OH-DPAT on forskolin-stimulated cAMP accumulation in these transfected cells, suggesting that prolonged exposure to 5-HT induced 5-HT1A receptor desensitization, mediated by 5-HT1A receptor but not 5-HT2A receptors.

Clinical profile and outcome of primary hyperparathyroidism accompanied by chronic renal failure.

We encountered 5 cases of primary hyperparathyroidism (PHPT) accompanied by chronic renal failure over the past 4 years. Neither hypocalcemia nor hyperphosphatemia was found in the past records. The parathyroid hormone (PTH) levels in these cases were extraordinarily higher than those in usual patients suffering from renal failure. The manifestation of PHPT-developed insidiously together with the decline of renal function. Serum 1,25(OH)2D3 levels were lower than normal range in all cases, and which in turn might accelerate the progression of PHPT in a similar way as the development of secondary hyperparathyroidism. Parathyroidectomy (PTX) was done successfully in 4 cases, and the pathology of the biggest gland was adenoma but hyperplasia was found in other glands simultaneously. These results revealed the polymorphism of parathyroid glands in case of complication with renal failure. Furthermore, the interruption of postoperative 1 alpha(OH)D3 treatment induced the relapse of hyperparathyroidism (HPT). The case which refused PTX was treated by oral pulse therapy with 1,25(OH)2D3. The calcium/intact PTH sigmoidal curve examined 3 years later revealed that the set point shifted to right and upward despite therapy. It suggested that functional parathyroid mass became larger and the sensitivity to calcium became less under continuous stimuli on parathyroid glands. According to these results, PHPT accompanying with renal failure is resistant to medical therapy, and surgical treatment is a possibility. In this occasion, total PTX with autograft transplantation is better than simple adenectomy because even the glands not responsible to clinical manifestation of PHPT can have some pathological abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Three new reduced anthracycline related compounds from pathogenic Nocardia brasiliensis.

Three new metabolites were isolated from a pathogenic bacterium, Nocardia brasiliensis IFM 0075 strain, a producer of a new anthracycline antibiotic (SO-075R1) and its mutant strain (IFM 0075-13-1). The structural studies showed that they are reduced anthracyline related compounds. Some biosynthetic routes of these metabolites were discussed.

Nephrotic syndrome with massive accumulation of type I and type III collagen in the glomeruli.

A 54-year-old woman with nephrotic syndrome underwent renal biopsy. By light microscopy, the glomerular capillary lumen was remarkably narrowed because of diffuse accumulation of Periodic acid Shiff (PAS) positive material along the glomerular capillary wall. By electron microscopy, collagenous fibers were observed in the mesangium and subendothelial area. The fibrous material reacted with antibodies against type I and III collagen but not with those against laminin or type IV collagen by an indirect immunofluorescence technique. This case seemed to be a case of collagenofibrotic glomerulonephropathy.

Indocyanine green angiographic findings of chorioretinal folds.

PURPOSE: To analyze indocyanine green (ICG) angiographic findings of chorioretinal folds. METHODS: Eight patients (9 eyes) in whom chorioretinal folds had been diagnosed were enrolled in this study. Color photography, fluorescein angiography (FA) and ICG angiography (IA) were performed. RESULTS: Indocyanine green angiography demonstrated choroidal venous congestion and a filling delay of the choroidal vessels in one case with an orbital tumor. In one posterior scleritis case, IA showed a filling delay of choroidal vessels in the early phase and multiple patchy hypofluorescent lesions scattered in the posterior pole during the late phase. Idiopathic cases showed choroidal venous dilatation. No abnormalities of the choroidal vasculature in the form of radial folds, were revealed in two cases of AMD. Linear hyperfluorescent areas suggestive of chorioretinal folds seen on IA were less numerous and wider than those observed on FA in some eyes. On the other hand, they were equally numerous and wider on IA than those on FA in other eyes. CONCLUSION: Indocyanine green angiography is useful for evaluating both pathological conditions of the choroidal vasculature and the width of chorioretinal folds at the level of the choroidal vasculature.

[Evaluation of secondary hyperparathyroidism in the patients undergoing hemodialysis--focused on parathyroid hormone assay system].

We evaluated the degree of secondary hyperparathyroidism (SHPT) in the patients undergoing long-term hemodialysis treatment. Most patients showed improvement of SHPT by administration of the active vitamin D3 analogue. However, some patients developed overt SHPT even under intensive treatment. Pulse therapy with large dose of vitamin D3 for those who suffered from overt SHPT was an effective treatment modality at the initial stage, however, hypercalcemia which developed in the majority of the patients at the later stage of this treatment became an obstacle for the continuation of this treatment. Therefore, early detection of the hypersecretion state of parathyroid hormone (PTH) as well as earlier initiation of intensive therapy are important factors in preventing overt SHPT. Establishment of a suitable assay system for early detection of SHPT is an important task and the high sensitivity-PTH assay system may be the most desirable. Though diabetic patients were not likely to develop overt SHPT, this system could detect even the mild chronological increase of serum PTH level in diabetic patients. On the other hand, relatively earlier initiation of vitamin D3 therapy to the predialysis patients from the conservative treatment stage caused aggravation of deterioration of renal function. Therefore, we should be prudent to initiate vitamin D3 therapy on predialysis patients suffering from renal failure. Strict management of the patients by vitamin D3 as well as calcium supplement therapy along with evaluation of the serum PTH level is still an important measure to avoid overt SHPT.

Pharmacokinetic study of recombinant human erythropoietin treatment in pre-dialysis end stage renal disease patients.

We treated pre-dialysis ESRD patients with recombinant human erythropoietin (rHuEPO) by either the subcutaneous (s.c.) or intravenous (i.v.) route, and investigated the pharmacokinetics of rHuEPO. Twenty patients were divided equally into two groups by the difference in route, and rHuEPO was administered once per week for 8 weeks. The dose was 3,000 and 6,000 IU in the s.c. group and 3,000, 6,000 and 9,000 IU in the i.v. group. Although anemia was corrected significantly in both groups, residual renal function was not affected significantly. Pharmacokinetic study revealed that none of the parameters changed between the initial and final treatments in any of the groups. Area under the curve (AUC) and maximum concentration (Cmax) was consistently smaller in the s.c. --than in the i.v.--treated group. Mean residence time (MRT) was 3 times longer in the s.c. group than in the i.v. group. Bioavailability of rHuEPO in the s.c. group was around 35%, and mean absorption time (MAT) was around 25 hours. Though the s.c. route has been reported to be more effective for correcting anemia with rHuEPO than the i.v. route when rHuEPO was administered either twice or three times per week, our study demonstrated that the effect of rHuEPO was almost equal between the s.c.-treated and i.v.-treated groups when rHuEPO was administered once per week. We assume that this equivalent degree of efficacy in the s.c. group in spite of low values of AUC and Cmax might be derived by the longer MRT. Thus, we consider that MRT is an important factor and the efficacy of rHuEPO should be investigated with evaluation of MRT when the administration route is different.

[Pharmacokinetics and clinical effect of recombinant human erythropoietin on the anemia of predialysis patients].

The marvelous effect of recombinant human erythropoietin (EPOCH) on the anemia of the patients suffering from chronic renal failure had been already reported even in the predialysis patients. However, the influence on residual renal function as well as pharmacokinetics of EPOCH in predialysis patients was not clarified yet. Therefore, we made a clinical study of EPOCH in 10 predialysis patients to investigate the clinical effect as well as pharmacokinetics. EPOCH was administered intravenously once a week with the dosage of 3,000-9,000 IU for 8 weeks. All patients showed prominent improvement of anemia. Though no patient show serious adverse effect, two patients showed controllable hypertension accompanying with the increase of hematocrit. Meanwhile, the speed of the deterioration of residual renal function obtained from the regression line by reciprocal of the serum creatinine was not aggravated by the correction of anemia. Pharmacokinetic study revealed that the halflife of EPOCH was extended compared to normal but the degree of extension was same as that of in dialyzed patients. The plasma concentration-time curves showed the pattern of monoexponential disappearance and the area under the curve (AUC 0 to 48 hr.) showed dose-response increase. However, both parameters mentioned above as well as systemic clearance rate did not show any change between those of on day 0 and on day 56. These results no long-term accumulation of EPOCH, though the level of intrinsic erythropoietin was decreased after EPOCH treatment. Thus, the beneficial effect of EPOCH on the correction of anemia was revealed even in the predialysis patients without affecting on residual renal function.