Screening for Malnutrition in Community Dwelling Older Japanese: Preliminary Development and Evaluation of the Japanese Nutritional Risk Screening Tool (NRST).

BACKGROUND: Early and effective screening for age-related malnutrition is an essential part of providing optimal nutritional care to older populations. OBJECTIVE: This study was performed to evaluate the adaptation of the original SCREEN II questionnaire (Seniors in the Community: Risk Evaluation for Eating and Nutrition, version II) for use in Japan by examining its measurement properties and ability to predict nutritional risk and sarcopenia in community-dwelling older Japanese people. The ultimate objective of this preliminary validation study is to develop a license granted full Japanese version of the SCREEN II. PARTICIPANTS: The measurement properties and predictive validity of the NRST were examined in this cross-sectional study of 1921 community-dwelling older Japanese people. MEASUREMENTS: Assessments included medical history, and anthropometric and serum albumin measurements. Questions on dietary habits that corresponded to the original SCREEN II were applied to Nutritional Risk Screening Tool (NRST) scoring system. Nutritional risk was assessed by the Geriatric Nutrition Risk Index (GNRI) and the short form of the Mini-Nutritional Assessment (MNA-SF). Sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People. RESULTS: The nutritional risk prevalences determined by the GNRI and MNA-SF were 5.6% and 34.7%, respectively. The prevalence of sarcopenia was 13.3%. Mean NRST scores were significantly lower in the nutritionally at-risk than in the well-nourished groups. Concurrent validity analysis showed significant correlations between NRST scores and both nutritional risk parameters (GNRI or MNA-SF) and sarcopenia. The areas under the receiver operating characteristic curves (AUC) of NRST for the prediction of nutritional risk were 0.635 and 0.584 as assessed by GNRI and MNA-SF, respectively. AUCs for the prediction of sarcopenia were 0.602 (NRST), 0.655 (age-integrated NRST), and 0.676 (age and BMI-integrated NRST). CONCLUSIONS: These results indicate that the NRST is a promising screening tool for the prediction of malnutrition and sarcopenia in community-dwelling older Japanese people. Further development of a full Japanese version of the SCREEN II is indicated.

Coexistence effect of UVA absorbers to increase their solubility and stability of supersaturation.

OBJECTIVE: Sunscreens containing UVA absorbers in high concentrations are expected to be developed, since recent studies have suggested the possibility of involvement of UVA ray in skin cancer and early skin aging. Solubility and stability of supersaturation of UVA absorbers in UVB absorber were determined in the absence and the presence of cosmetic oil. Coexistence effect of UVA absorbers was analyzed to dissolve them in high concentrations. METHODS: Two UVA absorbers, diethylamino hydroxybenzoyl hexyl benzoate (DHHB) and butyl methoxydibenzoylmethane (BMDM), a UVB absorber, 2-ethylhexyl methoxycinnamate (EHMC), and a cosmetic oil, 2-ethylhexyl ester of oligomer of hydroxystearic acid (EH-O-HSA), were used. Their solutions were prepared at 80°C and cooled to 5°C. The solid DHHB and/or BMDM were added to it, and the time evolution of concentrations of the UVA absorbers in the solution phase was monitored. RESULTS: At the saturation in the absence of EH-O-HSA at 5°C, weight ratio of DHHB and BMDM to EHMC was 0.39/1.00 and 0.22/1.00, respectively. Addition of EH-O-HSA slightly changed the solubility of DHHB and BMDM. When the weight ratio of EH-O-HSA to EHMC was 0.20/1.00, weight ratio of DHHB and BMDM to EHMC was 0.35/1.00 and 0.25/1.00, respectively at the saturation at 5°C. In the presence of EH-O-HSA, a strong coexistence effect of DHHB and BMDM was found on their solubility. A thermodynamically stable saturated solution at 5°C having the composition that DHHB: BMDM: EHMC: EH-O-HSA = 0.47: 0.46: 1.00: 0.20 was obtained by the simultaneous addition of solid DHHB and BMDM into the initial solution. CONCLUSION: The solution type composite having the highest concentrations of DHHB and BMDM prepared in this study exhibited critical wavelength at 368 nm that was just below the border for sunscreens being qualified as 'Broad Spectrum' protection under the new rule launched by US FDA.

Problems of in vitro SPF measurements brought about by viscous fingering generated during sunscreen applications.

Up to date, no worldwide standard in vitro method has been established for the determination of the sun protection factor (SPF), since there are many problems in terms of its repeatability and reliability. Here, we have studied the problems on the in vitro SPF measurements brought about by the phenomenon called viscous fingering. A spatially periodic stripe pattern is usually formed spontaneously when a viscous fluid is applied onto a solid substrate. For the in vitro SPF measurements, the recommended amount of sunscreen is applied onto a substrate, and the intensity of the transmitted UV light through the sunscreen layer is evaluated. Our theoretical analysis indicated that the nonuniformity of the thickness of the sunscreen layer varied the net UV absorbance. Pseudo-sunscreen composites having no phase separation structures were prepared and applied on a quartz plate for the measurements of the UV absorbance. Two types of applicators, a block applicator and a 4-sided applicator were used. The flat surface was always obtained when the 4-sided applicator was used, while the spatially periodic stripe pattern was always generated spontaneously when the block applicator was used. The net UV absorbance of the layer on which the stripe pattern was formed was found to be lower than that of the flat layer having the same average thickness. Theoretical simulations quantitatively reproduced the variation of the net UV absorbance led by the change of the geometry of the layer. The results of this study propose the definite necessity of strict regulations on the coating method of sunscreens for the establishment of the in vitro SPF test method.

Circulating tumor cells as a potential biomarker in selecting patients for pulmonary metastasectomy from colorectal cancer: report of a case.

Pulmonary metastasectomy is indicated for selected patients with metastatic colorectal cancer. A 43-year-old woman presented with solitary pulmonary metastasis from descending colon cancer and pulmonary metastasectomy was performed because of absence of any other active metastasis as well as normal serum carcinoembryonic antigen value. However, she died due to early development of nodal and bone metastases within 6 months after thoracotomy. The presence of circulating tumor cells (CTCs) in the peripheral blood (6 CTCs/7.5 ml) was the only factor to predict such a poor prognosis, suggesting that the CTC test is useful in selecting patients for pulmonary metastasectomy.

Helicobacter pylori dupA gene is not associated with clinical outcomes in the Japanese population.

The dupA gene of Helicobacter pylori was suggested to be a risk factor for duodenal ulcer but protective against gastric cancer. The present study aimed to re-examine the role of dupA in H. pylori-infected Japanese patients. We found that dupA status was not associated with any gastroduodenal disease, histological score of chronic gastritis or with the extent of interleukin-8 production from gastric cell lines. These results indicate that dupA is unlikely to be a virulence factor of H. pylori in the Japanese population.

Neutralizing antibody levels for protection against betanodavirus infection in sevenband grouper, Epinephelus septemfasciatus (Thunberg), immunized with an inactivated virus vaccine.

Abstract An inactivated betanodavirus, red-spotted grouper nervous necrosis virus (RGNNV), is a vaccine candidate for viral nervous necrosis (VNN). The present study was conducted to examine inoculation doses of the vaccine and neutralizing antibody titre levels to protect fish against VNN. Young sevenband grouper, Epinephelus septemfasciatus, averaging 25.4 g, were immunized at 25 degrees C water temperature by a single intraperitoneal injection of formalin-inactivated RGNNV. Fish immunized at vaccine doses of 10(8.5), 10(8.0), 10(7.5), 10(7.0) and 10(6.5) TCID(50) per fish produced antibodies at mean titres of 1:907, 1:511, 1:259, 1:197 and 1:96, respectively, at 20 days post-immunization (p.i.). Neutralizing antibodies were not detected in any control fish (titre <1:80). When fish were challenged with RGNNV (10(5.0) and 10(4.0) TCID(50)/fish) at 20 days p.i., cumulative mortalities of the fish groups immunized with 10(8.5), 10(8.0), 10(7.5) and 10(7.0) TCID(50) per fish were significantly lower than those of the control group, and the relative percent survival values were higher than 60% in fish groups immunized with 10(7.5) TCID(50) per fish or higher doses. However, no significant differences were found in mortality between the group immunized with 10(6.5) TCID(50) per fish and the control group. From these results, it was deduced that the minimum effective inoculation dose of the vaccine is 10(7.0) TCID(50) per fish and the minimum mean neutralizing antibody titre giving significant protection is approximately 1:200. This antibody titre level is a possible measure of vaccine efficacy against VNN in sevenband grouper, instead of a virus challenge test.

Multipotent progenitor cells isolated from adult human pancreatic tissue.

The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus.

FR226807: a potent and selective phosphodiesterase type 5 inhibitor.

We describe the pharmacological characteristics of a novel phosphodiesterase type 5 inhibitor FR226807, N-(3,4-dimethoxybenzyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]-5-nitrobenzamide. FR226807 inhibited phosphodiesterase type 5 isolated from human platelets with an IC(50) value of 1.1 nM. FR226807 also inhibited phosphodiesterase type 6 with an IC(50) of 20 nM; however, the IC(50) value for phosphodiesterase type 6 was 18-fold higher than that for phosphodiesterase type 5. The IC(50) values of FR226807 for other phosphodiesterases (phosphodiesterase type 1, phosphodiesterase type 2, phosphodiesterase type 3, and phosphodiesterase type 4) were 1000-fold higher than that for phosphodiesterase type 5. FR226807 increased the cyclic guanosine monophosphate (cGMP) content in corpus cavernosum isolated from rabbit, an effect associated with relaxation of the muscle. FR226807 enhanced the relaxation response induced by electrical field stimulation of corpus cavernosum isolated from the rabbit. In an anesthetized dog model for the evaluation of erectile function, intravenous administration of FR226807 prolonged the time to return to 75% of maximal intracavernosal pressure after cessation of electrical stimulation of the pelvic nerve. In summary, FR226807 is a potent and highly selective phosphodiesterase type 5 inhibitor with an augmentative effect on penile erection and will be useful for the treatment of erectile dysfunction.

Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli.

Inorganic polyphosphate (polyP), a polymer of hundreds of phosphate (Pi) residues, accumulates in Escherichia coli in response to stresses, including amino acid starvation. Here we show that the adenosine 5'-triphosphate-dependent protease Lon formed a complex with polyP and degraded most of the ribosomal proteins, including S2, L9, and L13. Purified S2 also bound to polyP and formed a complex with Lon in the presence of polyP. Thus, polyP may promote ribosomal protein degradation by the Lon protease, thereby supplying the amino acids needed to respond to starvation.

4-(Benzoylindolizinyl)butyric acids; novel nonsteroidal inhibitors of steroid 5alpha-reductase. III.

A novel series of indolizinebutyric acids with various benzoyl substituents was synthesized to develop nonsteroidal inhibitors of steroid 5alpha-reductase, and the structure-activity relationships in this series were studied. We previously reported the structure-activity relationships in a series of indolebutyric acids as well as the discovery of the novel nonsteroidal 5alpha-reductase inhibitor, FK143. We have now made other modifications to this compound to improve in vivo inhibitory activity. By altering the heterocyclic nucleus and changing the benzoyl substituent we have succeeded in identifying the strongly active compound, FK687, (S)-4-[1-[4-[[1-(4-isobutylphenyl)butyl]oxy]benzoyl]indolizin-3-yl]butyric acid, which displays strong in vitro inhibitory activity against the human enzyme and in vivo inhibitory activity against the castrated young rat model. This compound should be a useful agent for the treatment of benign prostatic hyperplasia.

Cloning and characterisation of tandem-repeat type galectin in rainbow trout (Oncorhynchus mykiss).

Fish beta-galactoside binding lectin (galectin) cDNA was cloned from the cDNA library of rainbow trout (Oncorhynchus mykiss) head kidney. The clone contained a single open reading frame encoding 341 amino acids (aa) (38 kDa protein), including the initiator methionine. Significant sequence homology to mammalian galectin-9 (40-55% identity) was observed. Its amino acid sequence showed two distinct N- and C-terminal domains (148 and 130 aa, respectively) connected by a peptide linker (63 aa). The galectin contains two consensus WG-E-R/K motifs thought to play an essential role in sugar-binding, indicating that this lectin is a member of the tandem-repeat type galectins which have not been identified in fish. The 1.6 kDa mRNA of the lectin was found by Northern blot analyses to be widely expressed in the spleen, head kidney, thymus, peritoneal exudate cells, ovary, gills and heart. Southern blot analyses with the probe for C-terminal of the lectin showed the existence of two hybridising genes. These results suggest that rainbow trout has at least one tandem-repeat type galectin as well as proto-type galectin.

Isolation and characterization of the Enterobacter cloacae cheR mutant defective in phosphate taxis.

A chemotaxis-defective mutant of Enterobacter cloacae IFO3320, designated EC1, was isolated after N-methyl-N'-nitro-N-nitrosoguanidine (NTG) mutagenesis. Computer-assisted capillary assays showed that EC1 failed to show chemotactic responses to peptone and inorganic phosphate (Pi). Cloning and sequence analysis showed that EC1 is a cheR mutant, suggesting that Pi taxis by E. cloacae is dependent on a methyl-accepting chemotaxis protein(s) (MCP). EC1 was further mutagenized with NTG to construct cheR pstS and cheR pstA double mutants. A recombinant plasmid pECT01.2, which contained the E. cloacae cheR gene, restored the ability of these double mutants to show chemotaxis toward peptone but not Pi. These results suggest that the phosphate-specific transport (Pst) system, together with a MCP(s), is required for detecting Pi in E. cloacae.

Evaluation of pancreatic secretion after administration of secretin: application of magnetic resonance imaging.

BACKGROUND: To evaluate pancreatic exocrine function, we measured the changes in T2 enhanced hydrograhic intensity on magnetic resonance (MR) images of the pancreas following an injection of secretin, which is representative of the changes in duodenal fluid volume. METHODS: The subjects were 10 patients with normal pancreatic function (N > 70% detected by using a pancreatic function diagnostant test) and 12 patients with hypo-function, including those with mild hypo-function (MH, 50-70%, six patients) and severe hypo-function (SH < 50%, six patients). RESULTS: In the N group, T2 enhanced intensity of the pancreas increased to a maximum value (more than 10% compared with baseline) within 5 min of stimulation, then gradually decreased. No significant difference in the response was observed between the head and body of the pancreas. Changes in the MH group were similar to those of the N group. In contrast, significantly lower changes in T2 enhanced intensity were observed in SH group, relative to both the N and MH group (P < 0.05). The amount of secretin-induced increase in duodenal fluid after 16 min was not significantly different among the three groups. Furthermore, an evaluation of the residual pancreatic tissue after a pancreatoduodenectomy was also feasible. CONCLUSIONS: Our results indicate that the MR-secretin test is useful for the evaluation of severe pancreatic exocrine dysfunction. The diagnostic test is simple, direct and non-invasive.

Chemotaxis of the nematode Caenorhabditis elegans toward cycloheximide and quinine hydrochloride.

We investigated the chemotaxis of the nematode Caenorhabditis elegans toward cycloheximide, denatonium benzoate, 6-n-propyl-2-thiouracil, and quinine hydrochloride. Interestingly, C. elegans was strongly attracted to cycloheximide, while avoiding quinine hydrochloride. This is the first report thus far to describe the chemotactic responses of C. elegans toward bitter tastants for humans.

Mutational analysis of the multicopy hao gene coding for hydroxylamine oxidoreductase in Nitrosomonas sp. strain ENI-11.

The ammonia-oxidizing bacterium Nitrosomonas sp. strain ENI-11 contains three copies of the hao gene (hao1, hao2, and hao3) coding for hydroxylamine oxidoreductase (HAO). Three single mutants (hao1::kan, hao2::kan, or hao3::kan) had 68 to 75% of the wild-type growth rate and 58 to 89% of the wild-type HAO activity when grown under the same conditions. A double mutant (hao1::kan and hao3::amp) also had 68% of the wild-type growth and 37% of the wild-type HAO activity.

Involvement of an extracellular protease in algicidal activity of the marine bacterium Pseudoalteromonas sp. strain A28.

The marine bacterium Pseudoalteromonas sp. strain A28 was able to kill the diatom Skeletonema costatum strain NIES-324. The culture supernatant of strain A28 showed potent algicidal activity when it was applied to a paper disk placed on a lawn of S. costatum NIES-324. The condensed supernatant, which was prepared by subjecting the A28 culture supernatant to ultrafiltration with a 10,000-M(w)-cutoff membrane, showed algicidal activity, suggesting that strain A28 produced extracellular substances capable of killing S. costatum cells. The condensed supernatant was then found to have protease and DNase activities. Two Pseudoalteromonas mutants lacking algicidal activity, designated NH1 and NH2, were selected after N-methyl-N'-nitrosoguanidine mutagenesis. The culture supernatants of NH1 and NH2 showed less than 15% of the protease activity detected with the parental strain, A28. The protease was purified to homogeneity from A28 culture supernatants by using ion-exchange chromatography followed by preparative gel electrophoresis. Paper-disk assays revealed that the purified protease had potent algicidal activity. The purified protease had a molecular mass for 50 kDa, and the N-terminal amino acid sequence was determined to be Ala-Thr-Pro-Asn-Asp-Pro. The optimum pH and temperature of the protease were found to be 8.8 and 30 degrees C, respectively, by using succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as a substrate. The protease activity was strongly inhibited by phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate, antipain, chymostatin, and leupeptin. No significant inhibition was detected with EDTA, EGTA, phenanthroline or tetraethylenepentamine. These results suggest that Pseudoalteromonas sp. strain A28 produced an extracellular serine protease which was responsible for the algicidal activity of this marine bacterium.

Interleukin-4 inhibits interleukin-11 production by rheumatoid synovial cells.

OBJECTIVE: To examine the effect of interleukin-4 (IL-4) on IL-11 production by rheumatoid synovial cells. METHODS: Freshly isolated rheumatoid synovial cells (FRS) were obtained by collagenase digestion of rheumatoid arthritis (RA) synovial tissue specimens taken at the time of operation. Rheumatoid synovial cells at four to eight passages were used as cultured rheumatoid synovial fibroblasts (RSF). IL-11 concentration was measured by ELISA. RESULTS: IL-4 inhibited the production of IL-11 by FRS in a dose-dependent manner. This inhibition was observed in FRS obtained from six patients, and the mean inhibition was 46.5%. The inhibitory effect of IL-4 on IL-11 production was cancelled by the addition of anti-IL-4 antibody. IL-4 also inhibited IL-11 production by IL-1alpha-stimulated cultured RSF. CONCLUSION: IL-4 inhibited IL-11 production by rheumatoid synovial cells. IL-4 has a protective effect on bone resorption. On the contrary, IL-11 participates in bone resorption via osteoclastogenesis. Therefore, IL-4 may exert its protective effect on bone resorption, at least in part, via inhibition of IL-11 production in rheumatoid joints.

Identification and characterization of two chemotactic transducers for inorganic phosphate in Pseudomonas aeruginosa.

Two chemotactic transducers for inorganic phosphate (P(i)), designated CtpH and CtpL, have been identified in Pseudomonas aeruginosa. The corresponding genes (ctpH and ctpL) were inactivated by inserting kanamycin and tetracycline resistance gene cassettes into the wild-type genes in the P. aeruginosa PAO1 genome. Computer-assisted capillary assays showed that the ctpH single mutant failed to exhibit P(i) taxis when the concentration of P(i) in the capillary was higher than 5 mM. Conversely, the ctpL single mutant could not respond to P(i) at the concentration of 0.01 mM. The ctpH ctpL double mutant was defective in P(i) taxis at any concentration ranging from 0.01 to 10 mM. To investigate regulation of P(i) taxis, the ctpH and ctpL genes were also disrupted individually in the P. aeruginosa phoU and phoB single mutants. The ctpH phoU and ctpH phoB double mutants were defective in P(i) taxis, regardless of whether the cells were starved for P(i). The ctpL phoU double mutant was constitutive for P(i) taxis, whereas the ctpL phoB double mutant was induced by P(i) limitation for P(i) taxis. The region upstream of ctpL, but not ctpH, contained a putative pho box sequence. Expression of ctpL::lacZ was induced by P(i) limitation in PAO1, while it was constitutive in the phoU mutant. In contrast, the phoB mutant showed only background levels of ctpL::lacZ expression. These results showed that ctpL is involved in the pho regulon genes in P. aeruginosa. The ctpH phoU mutant, which failed to exhibit P(i) taxis, was constitutive for ctpL::lacZ expression, suggesting that the P(i) detection by CtpL requires PhoU. Like PAO1, the phoB and phoU single mutants were constitutive for expression of ctpH::lacZ. Thus, the evidence that the ctpL phoU mutant, but not the ctpL phoB mutant and PAO1, was constitutive for P(i) taxis raised the possibility that PhoU exerts a negative control on P(i) detection by CtpH at the posttranscriptional level.