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2.
Nat Commun ; 13(1): 2159, 2022 04 20.
Article in English | MEDLINE | ID: mdl-35444239

ABSTRACT

Macular degeneration is a leading cause of blindness. Treatments to rescue vision are currently limited. Here, we study how loss of central vision affects lateral feedback to spared areas of the human retina. We identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in macular degeneration. This finding provides an insight into the negative effects of geographic atrophy on vision. Therefore, we develop a strategy to restore this feedback mechanism, through activation of laterally projecting cells. This results in improved vision in Cnga3-/- mice, which lack cone function, as well as a mouse model of geographic atrophy. Our work shows that a loss of lateral gain control contributes to the vision deficit in macular degeneration. Furthermore, in mouse models we show that lateral feedback can be harnessed to improve vision following retinal degeneration.


Subject(s)
Geographic Atrophy , Macular Degeneration , Retinal Degeneration , Animals , Geographic Atrophy/genetics , Geographic Atrophy/therapy , Macular Degeneration/genetics , Mice , Retinal Cone Photoreceptor Cells/physiology , Retinal Degeneration/complications , Retinal Degeneration/genetics , Retinal Degeneration/therapy , Vision, Ocular
3.
Benef Microbes ; 10(6): 641-651, 2019 Jul 10.
Article in English | MEDLINE | ID: mdl-31179713

ABSTRACT

Gut microbiome development affects infant health and postnatal physiology. The gut microbe assemblages of preterm infants have been reported to be different from that of healthy term infants. However, the patterns of ecosystem development and inter-individual differences remain poorly understood. We investigated hospitalised preterm infant gut microbiota development using 16S rRNA gene amplicons and the metabolic profiles of 268 stool samples obtained from 17 intensive care and 42 term infants to elucidate the dynamics and equilibria of the developing microbiota. Infant gut microbiota were predominated by Gram-positive cocci, Enterobacteriaceae or Bifidobacteriaceae, which showed sequential transitions to Bifidobacteriaceae-dominated microbiota. In neonatal intensive care unit preterm infants (NICU preterm infants), Staphylococcaceae abundance was higher immediately after birth than in healthy term infants, and Bifidobacteriaceae colonisation tended to be delayed. No specific NICU-cared infant enterotype-like cluster was observed, suggesting that the constrained environment only affected the pace of transition, but not infant gut microbiota equilibrium. Moreover, infants with Bifidobacteriaceae-dominated microbiota showed higher acetate concentrations and lower pH, which have been associated with host health. Our data provides an in-depth understanding of gut microbiota development in NICU preterm infants and complements earlier studies. Understanding the patterns and inter-individual differences of the preterm infant gut ecosystem is the first step towards controlling the risk of diseases in premature infants by targeting intestinal microbiota.


Subject(s)
Feces/microbiology , Gastrointestinal Microbiome , Gram-Positive Cocci/classification , Intensive Care Units , Acetates/analysis , Bifidobacterium/classification , Bifidobacterium/isolation & purification , Enterobacteriaceae/classification , Enterobacteriaceae/isolation & purification , Female , Gram-Positive Cocci/isolation & purification , Hospitalization , Humans , Hydrogen-Ion Concentration , Infant, Newborn , Infant, Premature , Male , Metabolome , RNA, Ribosomal, 16S/genetics , Staphylococcaceae/classification , Staphylococcaceae/isolation & purification
4.
Ann Oncol ; 29(4): 979-984, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29211833

ABSTRACT

Background: There is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC). Patients and methods: We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities. Results: Thirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%-59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%-87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3-12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient. Conclusion: This study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study. Clinical Trial Registration: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.


Subject(s)
Androgen Antagonists/therapeutic use , Leuprolide/therapeutic use , Neoplasm Metastasis , Receptors, Androgen/metabolism , Salivary Gland Neoplasms/drug therapy , Aged , Aged, 80 and over , Androgen Antagonists/administration & dosage , Anilides/administration & dosage , Anilides/therapeutic use , Disease-Free Survival , Female , Humans , Leuprolide/administration & dosage , Male , Middle Aged , Nitriles/administration & dosage , Nitriles/therapeutic use , Prospective Studies , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/pathology , Tosyl Compounds/administration & dosage , Tosyl Compounds/therapeutic use , Treatment Outcome
5.
Benef Microbes ; 8(5): 705-716, 2017 Oct 13.
Article in English | MEDLINE | ID: mdl-28884590

ABSTRACT

Gut microbiota affects the host's metabolism, and it is suggested that there are differences in gut microbiota composition between patients with type 2 diabetes and healthy individuals. Additionally, dysbiosis may increase the concentration of lipopolysaccharides (LPS), causing metabolic endotoxemia, which induces impaired glucose tolerance. Several studies have reported relationships between metabolic diseases and the gut microbiota; and prebiotics, such as oligosaccharides, are commonly consumed to regulate gut microbiotas in healthy individuals. Galacto-oligosaccharides (GOS) are a major prebiotic, which specifically increase Bifidobacteriaceae abundance. Recent studies have reported that Bifidobacteriaceae improved metabolic endotoxemia or impaired glucose tolerance. However, there are few studies reporting the effects of GOS on patients with type 2 diabetes. In the current study, we compared clinical parameters, faecal gut microbiota, their associated metabolic products and their components such as LPS, and LPS-binding protein (LBP) produced by the host, between patients with diabetes and healthy controls. We then assessed the effects of GOS on glycaemic control, and gut microbiotas and metabolites in patients with type 2 diabetes in a double-blind controlled manner. LBP levels were significantly higher in patients with diabetes than those of healthy subjects, which was consistent with previous reports. The abundance of Bifidobacteriaceae and the diversity of intestinal microbiota were significantly lower in patients with diabetes than in healthy subjects. Interestingly, Bifidobacteriaceae was markedly restored in patients with diabetes after consumption of GOS, whereas LBP and glucose tolerance did not improve during this short-term trial period. In the present study, we demonstrated that GOS can ameliorate dysbiosis in patients with diabetes, and continuous intake of GOS may be a promising method for managing type 2 diabetes.


Subject(s)
Bifidobacterium/isolation & purification , Diabetes Complications/therapy , Diabetes Mellitus, Type 2/complications , Dysbiosis/therapy , Oligosaccharides/administration & dosage , Prebiotics/administration & dosage , Actinobacteria , Adult , Aged , Asian People , Double-Blind Method , Feces/microbiology , Female , Glycemic Index , Humans , Male , Middle Aged , Treatment Outcome , Young Adult
6.
Benef Microbes ; 7(4): 453-61, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27120106

ABSTRACT

The objective of the study was to investigate whether an infant formula supplemented with galacto-oligosaccharides (GOS; OM55N) was able to stimulate the growth of indigenous bifidobacteria and to establish microbiota similar to that of breastfed infants. A randomised, double-blind, placebo-controlled trial was performed using 35 healthy term infants (31-54 days of age; 42±6 days) to determine whether infant formula with 0.3 g/dl GOS (OM55N) stimulated the growth of bifidobacteria in the infants' guts. At the trial onset and 2 weeks after, the infants' faecal samples were examined for microbiota composition (bacterial abundance and α-diversity) and faecal characteristics. Among the 35 infants, 5 were withdrawn and 8 were excluded from the final evaluation before breaking the blinding since the indigenous bifidobacteria were not detected at the trial onset. After 2 weeks, the abundance of Bifidobacteriaceae was significantly increased in the GOS feeding group compared to the control (+11.6±24.1% vs -3.9±13.0%; P=0.043). The Shannon index, which accounts for both abundance and evenness of the present species, was significantly decreased with GOS supplementation (-0.1±0.4 vs +0.4±0.4; P=0.014). Faecal characteristics such as pH and organic acids were similar in both groups, with no statistical differences. No adverse side effects related to the formula consumption were reported. Although the concentration of GOS was relatively low, the infant formula with GOS increased the abundance of bifidobacteria and resulted in a reduced α-diversity of the microbiota.


Subject(s)
Bifidobacterium/growth & development , Dietary Supplements , Infant Formula/chemistry , Microbiota , Oligosaccharides/pharmacology , Bifidobacterium/genetics , Double-Blind Method , Female , Galactose/administration & dosage , Galactose/pharmacology , Humans , Infant , Male , Microbiota/genetics , Oligosaccharides/administration & dosage , RNA, Bacterial , RNA, Ribosomal, 16S
7.
Neuroscience ; 284: 217-224, 2015 Jan 22.
Article in English | MEDLINE | ID: mdl-25286384

ABSTRACT

Orexins are bioactive peptides, which have been shown to play a pivotal role in vigilance state transitions: the loss of orexin-producing neurons (orexin neurons) leads to narcolepsy with cataplexy in the human. However, the effect of the need for sleep (i.e., sleep pressure) on orexin neurons remains largely unknown. Here, we found that immunostaining intensities of the α1 subunit of the GABAA receptor and neuroligin 2, which is involved in inhibitory synapse specialization, on orexin neurons of mouse brain were significantly increased by 6-h sleep deprivation. In contrast, we noted that immunostaining intensities of the α2, γ2, and ß2/3 subunits of the GABAA receptor and Huntingtin-associated protein 1, which is involved in GABAAR trafficking, were not changed by 6-h sleep deprivation. Using a slice patch recording, orexin neurons demonstrated increased sensitivity to a GABAA receptor agonist together with synaptic plasticity changes after sleep deprivation when compared with an ad lib sleep condition. In summary, the GABAergic input property of orexin neurons responds rapidly to sleep deprivation. This molecular response of orexin neurons may thus play a role in the changes that accompany the need for sleep following prolonged wakefulness, in particular the decreased probability of a transition to wakefulness once recovery sleep has begun.


Subject(s)
Brain/pathology , Gene Expression Regulation/physiology , Neurons/physiology , Orexins/metabolism , Receptors, GABA-A/metabolism , Sleep Deprivation/pathology , Animals , Cell Adhesion Molecules, Neuronal/metabolism , Dose-Response Relationship, Drug , GABA Agents/pharmacology , Gene Expression Regulation/drug effects , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , In Vitro Techniques , Inhibitory Postsynaptic Potentials/drug effects , Inhibitory Postsynaptic Potentials/genetics , Mice , Mice, Transgenic , Nerve Tissue Proteins/metabolism , Neurons/drug effects , Orexins/genetics , Patch-Clamp Techniques , Sleep Deprivation/physiopathology , Wakefulness/physiology
8.
Rev Sci Instrum ; 85(11): 11E804, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25430369

ABSTRACT

A 12 × 12 pixel detector has been developed and used in a laboratory experiment for lost fast-ion diagnostics. With gamma rays in the MeV range originating from nuclear reactions (9)Be(α, nγ)(12)C, (9)Be(d, nγ)(12)C, and (12)C(d, pγ)(13)C, a high purity germanium (HPGe) detector measured a fine-energy-resolved spectrum of gamma rays. The HPGe detector enables the survey of background-gamma rays and Doppler-shifted photo peak shapes. In the experiments, the pixel detector produces a gamma-ray image reconstructed from the energy spectrum obtained from total photon counts of irradiation passing through the detector's lead collimator. From gamma-ray image, diagnostics are able to produce an analysis of the fast ion loss onto the first wall in principle.

9.
Benef Microbes ; 3(2): 113-25, 2012 Jun 01.
Article in English | MEDLINE | ID: mdl-22683836

ABSTRACT

The faecal microbiota of 166 healthy Japanese newborns was analysed periodically from day 1 after birth until the age of 3 years by using the reverse transcription-quantitative PCR. Faecal pH and the organic acid concentration were also examined. Colonisation by both facultative anaerobes and strict anaerobes was confirmed in 95% of the meconium tested. Bifidobacterium-predominant microbiota was established subsequently in most of the infants by 3 months after birth. Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium catenulatum group and Bifidobacterium bifidum were the species mainly detected. Intergroup correlation analysis revealed that the bifidobacterial population levels, but not other strict anaerobe groups, were found to be negatively correlated with those of the Enterobacteriaceae from 7 days until 3 months after birth. Faecal pH was maintained at about 6 until 6 months after birth and reached 6.6 at 3 years after birth. The initial concentration of faecal organic acids (19 µM/g of faeces) just after birth increased until 3 years after birth to the level of 111 µM/g of faeces. Early start of feeding formula milk promoted colonisation by obligate anaerobes such as the Clostridium coccoides group, the Clostridium leptum subgroup, Prevotella, and Atopobium cluster during the 3 months after birth. Population levels of the bifidobacteria until 1 month after birth and those of the Bacteroides fragilis group until 6 months after birth were lower in infants delivered by Caesarean section than in those delivered normally. The results suggested that both earlier start of feeding of formula milk and the mode of infant delivery were found to be important in the development of intestinal microbiota in early infancy.


Subject(s)
Bacteria/classification , Bacteria/genetics , Biota , Feces/microbiology , Gastrointestinal Tract/physiology , Metagenome , Asian People , Carboxylic Acids/analysis , Child, Preschool , Feces/chemistry , Female , Humans , Hydrogen-Ion Concentration , Infant , Infant, Newborn , Japan , Male , Pregnancy
10.
J Laryngol Otol ; 125(12): 1315-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21888753

ABSTRACT

OBJECTIVE: Supracricoid partial laryngectomy is a reliable laryngeal preservation procedure for tumour stage 2 and selected stage 3 to 4 laryngeal cancers. Of 70 patients thus treated, two (3 per cent) had 'flaccid neoglottis', i.e. redundant mucosa at the inner arytenoid edge which intermittently obstructed the neoglottis. We discuss the mechanism and management of this complication. METHOD: The two cases are presented. A navigation system was used to assist surgery. Neoglottal spatial alteration (specifically cross-sectional area) was assessed pre- and post-operatively using three-dimensional computed tomography. Voice was also evaluated. RESULTS: Inspiratory stridor and delayed stomal closure were the main symptoms. Minimum neoglottal cross-sectional area was smaller in case one than in non-affected patients. Both patients had relatively rougher and breathier voices, but had adapted well to this. CONCLUSION: Flaccid neoglottis is mainly due to excessive anterior retraction of residual laryngeal mucosa and to excessive mucosal pliability with age. A navigation system was useful for confirmation, but the potential for incorrect image recognition should be kept in mind. Flaccid neoglottis was treatable, with improved laryngeal function.


Subject(s)
Carcinoma, Mucoepidermoid/surgery , Carcinoma, Squamous Cell/surgery , Laryngeal Mucosa/physiopathology , Laryngeal Neoplasms/surgery , Laryngectomy/adverse effects , Surgery, Computer-Assisted/methods , Aged , Carcinoma, Mucoepidermoid/physiopathology , Carcinoma, Squamous Cell/physiopathology , Cautery , Cricoid Cartilage , Glottis/diagnostic imaging , Glottis/physiopathology , Humans , Imaging, Three-Dimensional , Laryngeal Mucosa/diagnostic imaging , Laryngeal Mucosa/surgery , Laryngeal Neoplasms/physiopathology , Laryngectomy/methods , Laryngoscopy , Laryngostenosis/etiology , Laryngostenosis/surgery , Male , Radiography , Reoperation , Respiratory Sounds/etiology , Treatment Outcome , Voice Disorders/etiology
11.
J Oral Rehabil ; 34(9): 645-51, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17716263

ABSTRACT

The aim of this study was to elucidate the influence of change in sound tone of playing wind instruments on activity of jaw-closing muscles and the effect of sustained playing for a long time on fatigue of jaw-closing muscles. Electromyograms (EMG) of 19 brass instrument players and 14 woodwind instrument players were measured while playing instruments in tuning tone and high tone and under other conditions. Nine brass instrument players and nine woodwind instrument players played instruments for 90 min. Before and after the exercise, power spectral analyses of EMG from masseter muscles at 50% of maximum voluntary clenching level were performed and mean power frequency (MPF) were calculated. Root mean square (RMS) of EMG in masseter and temporal muscles while playing were slightly larger than those at rest but extremely small in comparison with those during maximum clenching. Root mean square in orbicularis oris and digastric muscles were relatively large when playing instruments. In the brass instrument group, RMS in high tone was significantly higher than that in tuning tone in all muscles examined. In the woodwind instrument group, RMS in high tone was not significantly higher than that in tuning tone in those muscles. Mean power frequency was not decreased after sustained playing in both instrument groups. These findings indicate that contractive load to jaw-closing muscles when playing a wind instrument in both medium and high tone is very small and playing an instrument for a long time does not obviously induce fatigue of jaw-closing muscles.


Subject(s)
Masseter Muscle/physiology , Music , Temporal Muscle/physiology , Adolescent , Adult , Electromyography/methods , Female , Humans , Male , Muscle Contraction/physiology , Muscle Fatigue , Signal Processing, Computer-Assisted
12.
Article in English | MEDLINE | ID: mdl-16329650

ABSTRACT

IL-1 receptor antagonist (IL-1Ra)-deficient mice spontaneously develop several inflammatory diseases, resembling rheumatoid arthritis, aortitis, and psoriasis in humans. As adoptive T cell transplantation could induce arthritis and aortitis in recipient mice, it was suggested that an autoimmune process is involved in the development of diseases. In contrast, as dermatitis developed in scid/scid-IL-IRa-deficient mice and could not be induced by T cell transfer, a T cell-independent mechanism was suggested. The expression of proinflammatory cytokines was augmented at the inflammatory sites. The development of arthritis and aortitis was significantly suppressed by the deficiency of TNFalpha or IL-17. The development of dermatitis was also inhibited by the deficiency of TNFalpha. These observations suggest that TNFalpha and IL-17 play a crucial role in the development of autoimmunity downstream of IL-1 signaling, and excess IL-1 signaling-induced TNFalpha also induces skin inflammation in a T cell-independent manner.


Subject(s)
Autoimmune Diseases/immunology , Interleukin-17/immunology , Interleukin-1/immunology , Mice, Knockout/immunology , Receptors, Interleukin-1/metabolism , Signal Transduction/physiology , Tumor Necrosis Factor-alpha/immunology , Animals , Aortitis/immunology , Aortitis/pathology , Arthritis, Experimental/immunology , Arthritis, Experimental/pathology , Dermatitis/immunology , Dermatitis/pathology , Humans , Mice , Receptors, Interleukin-1/genetics
13.
Exp Gerontol ; 37(8-9): 1121-6, 2002.
Article in English | MEDLINE | ID: mdl-12213562

ABSTRACT

We used a fluorescence differential display-PCR (FDD-PCR) technique to analyze the genes expressed in mouse brains collected at nine different developmental stages ranging from 3 days to 15 months after birth, and 5 age-dependently expressed genes were found. Age-dependent expression of each of these 5 genes was confirmed by quantitative real-time PCR analysis. Of the 5 genes, 4 (B1-B4) had high homology with the nucleotide sequences of cDNA clones of known mouse genes (myelin proteolipid protein, transferrin, embryo cDNA from the RIKEN full-length enriched library, and protein tyrosine phosphatase), and the rest (B5) with expressed sequence tags of an unknown gene. Sequencing analysis of the full-length cDNA constructed based on the B5 sequence demonstrated that the gene product of B5 was identical to G-substrate, a specific substrate for cGMP-dependent protein kinase. The expression patterns of known genes obtained in our study may provide a further opportunity to investigate the biological and physiological roles of the proteins they encode.


Subject(s)
Brain/metabolism , Gene Expression Profiling , Polymerase Chain Reaction/methods , Age Factors , Animals , DNA, Complementary/chemistry , Fluorescence , Mice , Mice, Inbred C57BL
14.
Int J Legal Med ; 116(3): 191-4, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12111327

ABSTRACT

From sequence database information we have newly identified three male-specific and polymorphic tetranucleotide STRs, DYS443 (GDB: 10807127), DYS444 (GDB: 10807128) and DYS445 (GDB: 10807129) on the Y chromosome. Analysis of 190 Japanese males revealed 6, 5 and 4 alleles in the DYS443, DYS444 and DYS445 systems, with calculated STR diversities of 0.68, 0.57 and 0.53, respectively. The cumulative haplotype diversity of the five Y-STRs DYS441, DYS442, DYS443, DYS444 and DYS445 was calculated to be 0.95 and therefore application of these STRs may yield very useful information for forensic individualization.


Subject(s)
Haplotypes , Polymorphism, Genetic , Tandem Repeat Sequences/genetics , Y Chromosome , Base Sequence , DNA/genetics , Forensic Medicine/methods , Humans , Japan , Male , Molecular Sequence Data
15.
Ann Neurol ; 50(4): 547-51, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11601509

ABSTRACT

The molecular basis of double cortex syndrome was investigated in 2 male patients. Magnetic resonance imaging of the patients' heads showed diffuse subcortical band heterotopia, as is seen in female patients. We found a heterozygous mutation for Asp50Lys or Arg39Stop in both patients. Microsatellite polymorphism analysis revealed that both patients had inherited a single X chromosome from their mothers. Restriction enzyme analysis using DNA extracted from the hair roots of each patient showed four different patterns in the combination of cells carrying wild and mutant alleles, which strongly suggest somatic mosaicism. We conclude that somatic mosaic mutations in the doublecortin gene in male patients can cause subcortical band heterotopia, and that molecular analysis using hair roots is a useful method for detecting somatic mosaicism.


Subject(s)
Cerebral Cortex/abnormalities , Microtubule-Associated Proteins , Mosaicism , Neuropeptides/genetics , X Chromosome , Child , Doublecortin Domain Proteins , Genetic Testing/methods , Hair Follicle , Humans , Infant , Male , Microsatellite Repeats , Polymorphism, Single Nucleotide
16.
Int J Legal Med ; 115(1): 54-6, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11599770

ABSTRACT

From sequence database information, we have identified two male-specific and polymorphic tetranucleotide STRs, DYS 441 (GDB:10013873) and DYS 442 (GDB: 10030304), on the Y chromosome. Analysis of 184 males allowed 7 and 5 alleles to be distinguished in the DYS 441 and DYS 442 systems, respectively, yielding 21 haplotypes. The gene diversities were 0.72 and 0.51, respectively and the haplotype diversity was 0.85.


Subject(s)
Forensic Medicine , Polymorphism, Genetic , Tandem Repeat Sequences/genetics , Y Chromosome , Base Sequence , DNA/genetics , DNA Fingerprinting , Databases, Nucleic Acid , Haplotypes , Humans , Male , Molecular Sequence Data , Polymerase Chain Reaction
17.
Brain Res ; 916(1-2): 1-10, 2001 Oct 19.
Article in English | MEDLINE | ID: mdl-11597585

ABSTRACT

Mammalian Per proteins are thought to be important in the mechanism of circadian rhythm. We identified a novel protein PIPS (Per1 interacting protein of the suprachiasmatic nucleus) with the yeast two-hybrid system using PAS domain of rat Per1 (rPer1) as a bait. PIPS is about a 180-kDa protein and expressed mainly in the brain, especially in the hypothalamus including the suprachiasmatic nuclei (SCN). PIPS interacts with mouse Per1 (mPer1) in vitro and in cultured cells transfected with both molecules. Furthermore, it was found that mPer1 translocated PIPS into the nuclei in the cultured cells. Thus, these findings suggest a possibility that PIPS is involved in the feedback loop or output mechanism of circadian rhythm through interacting with Per1 in the SCN.


Subject(s)
Biological Clocks/physiology , Circadian Rhythm/physiology , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Nuclear Proteins/metabolism , Suprachiasmatic Nucleus/metabolism , Amino Acid Sequence/genetics , Animals , Base Sequence/genetics , COS Cells , Cell Compartmentation/genetics , Cell Cycle Proteins , Cell Nucleus/metabolism , Cloning, Molecular , DNA, Complementary/chemistry , DNA, Complementary/isolation & purification , Feedback/physiology , Gene Library , Immunohistochemistry , Male , Molecular Sequence Data , Nerve Tissue Proteins/isolation & purification , Neurons/cytology , Period Circadian Proteins , Protein Structure, Tertiary/genetics , Rats , Rats, Wistar , Suprachiasmatic Nucleus/cytology , Translocation, Genetic/physiology , Two-Hybrid System Techniques
18.
J Nutr Sci Vitaminol (Tokyo) ; 47(2): 172-6, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11508710

ABSTRACT

The aim of this study was to determine the effect of a probiotic, i.e. fermented milk prepared with Lactobacillus casei strain Shirota, on indigenous Lactobacilli in the pig large intestine. This fermented milk was given as a probiotic to experimental pigs for 2 weeks. The fecal organic acid concentration increased with the fermented milk; acetate and propionate increased significantly (p<0.05). At the same time, lactate and butyrate tended to increase. The fecal pH was significantly reduced by the fermented milk (p<0.05). Although the number of bacteria of strain Shirota in the intestinal contents was much smaller than those of indigenous Lactobacilli, 10(4) vs 10(8) (cfu/g), the numbers of indigenous Lactobacilli and Bifidobacteria in the pig intestine appeared to increase with the fermented milk. In addition, the phenotypic diversity (phenotypic group numbers) of indigenous Lactobacilli increased from 3 to 8 with the fermented milk supplementation. Thus the fermented milk affected the indigenous Lactobacillus population and constitution.


Subject(s)
Intestine, Large/microbiology , Lacticaseibacillus casei/metabolism , Lactobacillus/growth & development , Milk/microbiology , Probiotics/administration & dosage , Animals , Colony Count, Microbial , Feces/chemistry , Feces/microbiology , Fermentation , Hydrogen-Ion Concentration , Swine
19.
Int J Urol ; 8(7): 366-73, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11442658

ABSTRACT

BACKGROUND: Prognostic factors for survival in transitional cell carcinoma of the upper urinary tract have been extensively evaluated, but detailed analyses of patterns of bladder recurrence after surgery have been rare. METHODS: The outcome and tumor recurrence of 93 patients with transitional cell carcinoma of the upper urinary tract surgically treated between 1975 and 1999 were reviewed, retrospectively. Disease-specific survival by pathologic stage and grade were analyzed by the Kaplan-Meier METHOD: Prognostic factors for survival and bladder recurrence were examined by univariate and multivariate analysis. RESULTS: The 5-year disease-specific survival rates of the patients with pTa, T1 and T2 were 92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9% and the median survival of the pT4 cases was only 7 months. Bladder recurrence was seen in 40 cases and recurrences occurred within 1 year in 32 of these patients. The stage and grade of metachronous bladder tumors usually resembled those of primary tumors, but invasive recurrences were seen in 19% of recurrent cases with primary pTa, pT1 tumors. The significant prognostic factor for survival was pathologic stage (pT3, pT4), but no significant variables were detected for bladder recurrence by multivariate analysis. CONCLUSIONS: The prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is necessary. Invasive bladder recurrence occurred in 19% of patients with superficial primary tumors. As no significant prognostic variables for bladder recurrence were identified, careful follow up for bladder recurrence is important even if the primary tumors are non-invasive.


Subject(s)
Carcinoma, Transitional Cell/mortality , Urinary Bladder Neoplasms/mortality , Administration, Intravesical , Adult , Aged , Aged, 80 and over , Antibiotics, Antineoplastic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , BCG Vaccine/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Cisplatin/pharmacology , Doxorubicin/analogs & derivatives , Doxorubicin/pharmacology , Female , Humans , Male , Methotrexate/pharmacology , Middle Aged , Neoplasm Recurrence, Local/mortality , Prognosis , Retrospective Studies , Survival Analysis , Urinary Bladder Neoplasms/drug therapy , Vinblastine/pharmacology
20.
Biochem Biophys Res Commun ; 283(2): 292-6, 2001 May 04.
Article in English | MEDLINE | ID: mdl-11327696

ABSTRACT

We have identified a mouse full-length cDNA and gene encoding a novel protein (M-LP), based on an expressed sequence tag (EST) sequence (GenBank Accession No. AI482564) obtained by differential display screening of age-dependently expressed genes in mouse kidney. The ML-P gene is composed of three exons, ranges over 5 kb on mouse chromosome 16B1-B2 and is expressed as two transcripts (1455 and 3058 bp), both of which include the same open-reading frame encoding 194 amino acids. M-LP is expressed mainly in kidney and spleen and shows age-dependent expression. M-LP has sequence homologies and membrane topologies very similar to the Mpv17 protein, a peroxisomal protein involved in the development of early-onset glomerulosclerosis. Search of the protein domain family database (ProDom) revealed that M-LP is a new member of the Mpv17 domain family (PD008400).


Subject(s)
Membrane Proteins/genetics , Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Chromosome Mapping , Cloning, Molecular , DNA Primers/genetics , DNA, Complementary/genetics , Exons , Gene Expression , Genome , In Situ Hybridization, Fluorescence , Introns , Kidney/metabolism , Membrane Proteins/chemistry , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Peroxisomes/genetics , Protein Structure, Tertiary , Proteins/chemistry , Sequence Homology, Amino Acid
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