Longitudinal Study of the Decline in Renal Function in Healthy Subjects

Background

Chronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan.

Methods

Retrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method.

Results

In the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7ml/min/1.73m². In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42ml/min/1.73m²/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6ml/min/1.73m².

Conclusions

The present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.     

Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results

We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013–14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38°C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39–52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56–69), 77% (95% CI, 59–87), and 26% (95% CI, 14–36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B.     

Foraminifera and their associations of a possibly Rhaetian section of the Nayband Formation in central Iran,northeast of Esfahan

The following paper describes the foraminiferal fauna and associated faunal assemblages of the bedded and reef carbonates of the Upper Triassic (most probably Rhaetian) Nayband Formation, which are exposed in a section south of the small town of Bagher-Abad, northeast of Esfahan. Foraminifers are extremely rare in sponge- or coral-dominated bioconstructions and in the bedded carbonates of the Nayband Formation in central Iran. Some carbonate beds are composed of bioclastic wackstone/packstone. These are exposed in the solenoporacean horizon at the uppermost part of the section. Here, the aulotortid- and trocholinid-type foraminifers are relatively abundant. The following foraminiferal taxa with different abundances were found within the carbonates of the investigated section: Trocholina umbo Frentzen, T. turris Frentzen, T. gracilis Blau, Aulotortus tumidus (Kristan-Tollmann), Aulotortus tenuis (Kristan), Aulotortus friedli (Kristan-Tollmann), Coronipora etrusca (Pirini), Semiinvoluta clari Kristan, Turrispirillina? licia variabilis Blau, Galeanella? laticarinata Al-Shaibani, Carter and Zaninetti, Ophthalmidium sp., Agathammina sp., “Sigmoilina” schaeferae Zaninetti, Planiinvoluta carinata Leischner, Planiinvoluta sp., Nubecularia sp., Endothyra sp., Paeolituonella sp. and some sessile agglutinated and nodosariid types. All mentioned taxa are very rare, except the involutinid and trocholinid types. The following species are described as new: Trocholina blaui nov. sp., Spirilina? iranica nov. sp., and Coronipora serraforma nov. sp. Trocholina blaui is usually attached to solenoporacean thalli. Four foraminiferal associations, which are named after the occurrence of the abundant species, were distinguished as Aulotortus tumidus association, Aulotortus friedli association, Trocholina umbo association, and Trocholina blaui association. Aulotortid types and Trocholina umbo were found within the bioclastic wackstone/packstone carbonates. Trocholina blaui is abundant in solenoporacean framestones. The foraminiferal association of investigated carbonates contains a mixed fauna, known from Upper Triassic–Liassic in the Tethyan realm. Carbonates of the whole investigated section are dated—due to occurrence of the genus Aulotortus, with species A. tumidus (Kristan-Tollmann), A. tenuis (Kristan), and A. friedli (Kristan-Tollmann)—as Upper Triassic (most probably Rhaetian). The “typical” foraminifers occurring in the reef biotopes in the northwestern Tethys are either missing or extremely rare in the Iranian bioconstructions.     

Dasycladales from the Permian Jamal Formation of the Shotori Mountains,northeast Iran

Calcareous algae of the Permian Jamal Formation were studied in three sections of the Shotori Mountains, located in northeastern Iran. In this paper, four genera including Imperiella Elliott and Süssli, Nanjinoporella Mu and Elliott, Tabasoporella nov. gen., and Pseudotabasoporella nov. gen. are described from the Howz-e Dorah locality, which is exposed about 2 km northeast of the type section of Jamal Formation in Mount Jamal. Tabasoporella nov. gen. is characterized by metaspondyl arrangement of phloiophore and wine-glass-shaped laterals with a stalk grouped to tufts. The individual tufts are separated by a ring-like cavity appearing as triangular, oval, or trapezoid in longitudinally dissected section. The arrangement and shape of the laterals in Pseudotabasoporella nov. gen. is similar to Tabasoporella nov. gen., but there are no cavities between the tufts. All four genera are highly developed and limited to the Permian period. They disappear at the end of Permian and are not found in the Triassic sediments. Until today, two species of Imperiella are found in Iran and Afghanistan. I. iranica Elliott and Süssli was described only from the Ruteh Formation of Alborz Mountains in north Iran and I. afghanica was described from the Permian of Afghanistan. The Jamal Formation of the Shotori Mountains is the second locality where both species are discovered. Moreover, species I. crassiparietalis and I. gracilis are the two new species described here. The genus Nanjinoporella—with type species N. pagoda Mu and Elliott—was known from the Permian (Artinskian) Chishia Formation of Nanjing, China. We describe the new species Nanjinoporella iranica from the Permian Jamal Formation of the Shotori Mountains, northeast Iran.     

Protein disulfide isomerase-P5, down-regulated in the final stage of boar epididymal sperm maturation,catalyzes disulfide formation to inhibit protein function in oxidative refolding of reduced denatured lysozyme

In mammalian spermiogenesis, sperm mature during epididymal transit to get fertility. The pig sharing many physiological similarities with humans is considered a promising animal model in medicine. We examined the expression profiles of proteins from boar epididymal caput, corpus, and cauda sperm by two-dimensional gel electrophoresis and peptide mass fingerprinting. Our results indicated that protein disulfide isomerase-P5 (PDI-P5) human homolog was down-regulated from the epididymal corpus to cauda sperm, in contrast to the constant expression of protein disulfide isomerase A3 (PDIA3) human homolog. To examine the functions of PDIA3 and PDI-P5, we cloned and sequenced cDNAs of pig PDIA3 and PDI-P5 protein precursors. Each recombinant pig mature PDIA3 and PDI-P5 expressed in Escherichia coli showed thiol-dependent disulfide reductase activities in insulin turbidity assay. Although PDIA3 showed chaperone activity to promote oxidative refolding of reduced denatured lysozyme, PDI-P5 exhibited anti-chaperone activity to inhibit oxidative refolding of lysozyme at an equimolar ratio. SDS-PAGE and Western blotting analysis suggested that disulfide cross-linked and non-productively folded lysozyme was responsible for the anti-chaperone activity of PDI-P5. These results provide a molecular basis and insights into the physiological roles of PDIA3 and PDI-P5 in sperm maturation and fertilization.     

Establishment of Alternative Culture Method for Spermatogonial Stem Cells Using Knockout Serum Replacement

Since spermatogonial stem cells (SSCs) are capable of both self-renewal and differentiation to daughter cells for subsequent spermatogenesis, the development of an efficient in vitro culture system is essential for studies related to spermatogenesis. Although the currently available system is serum-free and contains only chemically-defined components, it highly relies upon bovine serum albumin (BSA), a component with batch-to-batch quality variations similar to those of fetal bovine serum. Thus, we searched for an alternative BSA-free culture system that preserved the properties of SSCs. In this study, we utilized Knockout Serum Replacement (KSR) in the SSC culture medium, as a substitute for BSA. The results demonstrated that KSR supported the continuous growth of SSCs in vitro and the SSC activity in vivo without BSA, in a feeder-cell combination with mouse embryonic fibroblasts. The addition of BSA to KSR further facilitated cell cycle progression, whereas a transplantation assay revealed that the addition of BSA did not affect the number of SSCs in vivo. The combination of KSR with BSA also allowed the elimination of GFRA1 and FGF2, and the reduction of the GDNF concentration from 20 ng/ml to 5 ng/ml, while maintaining the growth rate and the expression of SSC markers. Furthermore, KSR was also useful with SSCs from non-DBA/2 strains, such as C57BL/6 and ICR. These results suggested that KSR is an effective substitute for BSA for long-term in vitro cultures of SSCs. Therefore, this method is practical for various studies related to SSCs, including spermatogenesis and germ stem cell biology.     

Successful selection of an infection‐protective anti‐Staphylococcus aureus monoclonal antibody and its protective activity in murine infection models

Recent clinical trials to develop anti‐methicillin‐resistant Staphylococcus aureus (MRSA) therapeutic antibodies have met unsuccessful sequels. To develop more effective antibodies against MRSA infection, a panel of mAbs against S. aureus cell wall was generated and then screened for the most protective mAb in mouse infection models. Twenty‐two anti‐S. aureus IgG mAbs were obtained from mice that had been immunized with alkali‐processed, deacetylated cell walls of S. aureus. One of these mAbs, ZBIA5H, exhibited life‐saving effects in mouse models of sepsis caused by community‐acquired MRSA strain MW2 and vancomycin‐resistant S. aureus strain VRS1. It also had a curative effect in a MW2‐caused pneumonia model. Curiously, the target of ZBIA5H was considered to be a conformational epitope of either the 1,4‐β‐linkage between N‐acetylmuramic acid and N‐acetyl‐D‐glucosamine or the peptidoglycan per se. Reactivity of ZBIA5H to S. aureus whole cells or purified peptidoglycan was weaker than that of most of the other mAbs generated in this study. However, the latter mAbs did not have the protective activities against S. aureus that ZBIA5H did. These data indicate that the epitopes that trigger production of high‐yield and/or high‐affinity antibodies may not be the most suitable epitopes for developing anti‐infective antibodies. ZBIA5H or its humanized form may find a future clinical application, and its target epitope may be used for the production of vaccines against S. aureus infection.     

Membrane-bound lipoxygenase of rat cerebral microvessels

The microvessels isolated from rat cerebral cortex has arachidonate lipoxygenase activity, which was not due to possible contamination of the platelets. The major product was identified to be 12-hydroxyeicosatetraenoic acid. After homogenization and sonication of the microvessel preparations, the lipoxygenase activity was recovered both in the membrane- and the cytosol-fractions, whereas that in the platelets was recovered in the cytosol fraction. Membrane-bound lipoxygenase of the microvessels has apparent Km value of 3.8 microM for arachidonic acid, which was corresponded to 1/5 of that in the platelet enzyme. Microvessel lipoxygenase was inhibited by nordihydroguaiaretic acid but not by indomethacin.     

The inheritance of β-amylase null in storage roots of sweet potato,Ipomoea batatas (L.) Lam.

Summary Several sweet potato genotypes were found to lack completely or to have only traces of-amylase in their storage roots. Such genotypes do not increase in sweetness during cooking because, without a sufficient amount of-amylase, the normal hydrolysis of starch to maltose does not occur in the cooking process. In order to study the inheritance of this biochemical variant in the genotype, 41 families were generated. The following conclusions were drawn from analyzing these families. (1) This trait is controlled by one recessive allele (designated-amy) (2) It is inherited in a hexasomic or tetradisomic manner, but not disomically or tetrasomically. This conclusion supports previous cytological data that sweet potato is an autohexaploid or has two identical genomes plus one genome which is somewhat different. (3) The-amy allele appears to exist at a high frequency in cultivated germplasm. (4) Breeding sweet potato for low-amylase activity is relatively easy. New types of sweet potato without normal-amylase activity have great potential for processing and as a staple food.