Dietary Variety and Decline in Lean Mass and Physical Performance in Community-Dwelling Older Japanese: A 4-year Follow-Up Study.

OBJECTIVES: To examine associations of dietary variety with changes in lean mass and physical performance during a 4-year period in an elderly Japanese population. DESIGN: Four-year prospective study. SETTING: The Hatoyama Cohort Study and Kusatsu Longitudinal Study, Japan. PARTICIPANTS: 935 community-dwelling Japanese aged 65 years or older. MEASUREMENTS: Dietary variety was assessed using a 10-item food frequency questionnaire. Body composition was determined by multifrequency bioelectrical impedance analysis, and physical performance (grip strength and usual gait speed) was measured in surveys at baseline and 4 years later. Longitudinal analysis included only participants who were originally in the upper three quartiles of lean body mass, appendicular lean mass, grip strength, and usual gait speed. The outcome measures were decline in lean body mass, appendicular lean mass, grip strength, and usual gait speed, defined as a decrease to the lowest baseline quartile level at the 4-year follow-up survey. Associations of dietary variety with the outcome measures were examined by logistic regression analysis adjusted for potential confounders. RESULTS: In the fully adjusted model, the odds ratios for decline in grip strength and usual gait speed were 0.43 (95% confidence interval, 0.19-0.99) and 0.43 (confidence interval, 0.19-0.99), respectively, for participants in the highest category of dietary variety score as compared with those in the lowest category. Dietary variety was not significantly associated with changes in lean body mass or appendicular lean mass. CONCLUSION: Among older adults, greater dietary variety may help maintain physical performance, such as grip strength and usual gait speed, but not lean mass.

Association of Dietary Variety with Body Composition and Physical Function in Community-dwelling Elderly Japanese.

OBJECTIVES: To examine the associations of dietary variety with body composition and physical function in community-dwelling elderly Japanese. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: A total of 1184 community-dwelling elderly adults aged 65 and over. MEASUREMENTS: Dietary variety was assessed with a food frequency questionnaire (maximum, 10 points) that encompassed the 10 main food components of Japanese meals (meat, fish/shellfish, eggs, milk, soybean products, green/yellow vegetables, potatoes, fruit, seaweed, and fats/oils). Body composition was determined by multifrequency bioelectrical impedance analysis. Physical function was assessed by measuring grip strength and usual walking speed. Multiple linear regression analysis was used to examine the associations of dietary variety with body composition and physical function. RESULTS: After adjusting for potential confounders, higher dietary variety scores were independently associated with higher lean mass (ß (SE): 0.176 (0.049), p<0.001) and appendicular lean mass (ß (SE): 0.114 (0.027), p<0.001) but not with body fat mass. Elders with a higher dietary variety score had greater grip strength and faster usual walking speed (ß (SE): 0.204 (0.071), p=0.004, and ß (SE): 0.008 (0.003), p=0.012, respectively). CONCLUSION: Greater dietary variety was significantly associated with greater lean mass and better physical function in Japanese elders. The causal relationship warrants investigation in a prospective study.

Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia-lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group.

Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (P<0.001). Furthermore, relapse with a new lesion only in the absence of the primary lesion was more frequent in allo-SCT (P=0.014). Lesions were more frequently observed in the central nervous systems of patients who relapsed with new lesions only (P=0.005). Thus, the clinical manifestation of relapsed ATL was slightly complex, especially in post-transplant patients. Our results emphasized the need to develop adoptive modalities for early and accurate diagnoses of relapsed ATL.

Long-lasting enhancement of CYP activity after discontinuation of repeated administration of phenobarbital in dogs.

We investigated how long in vivo hepatic cytochrome P450 (CYP) activity is enhanced even after discontinuation of repeated oral administration of phenobarbital (PB) in dogs using antipyrine clearance, which reflects hepatic CYP activity. A single antipyrine (5 mg/kg) was administered intravenously before and 34 days after the repeated oral administration of PB (5 mg/kg, bid) and 2, 4, 6, and 8 weeks after the discontinuation of PB in 5 dogs. Antipyrine clearance was increased by the repeated administration of PB, and remained increased 2 and 4, but not 6 and 8 weeks after the discontinuation of PB. The result suggests that hepatic CYP activity was enhanced by the repeated administration of PB, and this enhancement may last for at least 4 weeks even after its discontinuation.

Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs.

The purposes of the present study were to elucidate the pharmacokinetics of zonisamide, determine the presence of a drug interaction with phenobarbital, and evaluate how long any interaction lasted after discontinuation of phenobarbital in dogs. Five dogs received zonisamide (5 mg/kg, p.o. and i.v.) before and during repeated oral administration of phenobarbital (5 mg/kg, bid, for 30-35 days). Zonisamide (5 mg/kg, p.o.) was also administered 8, 10, and 12 weeks after discontinuation of phenobarbital. Blood was sampled until 24 h after each zonisamide administration and serum concentrations of zonisamide were determined. Repeated phenobarbital decreased the maximum serum concentration, area under the serum concentration vs. time curve, apparent elimination half-life, and bioavailability of zonisamide. Total clearance increased. Time to maximum serum concentration and volume distribution were not changed. The maximum serum concentration and area under the serum concentration vs. time curve of zonisamide continued to be low until 10 weeks after the discontinuation of phenobarbital. They were restored to the same serum concentration as before phenobarbital administration 12 weeks after the discontinuation of phenobarbital. These data suggested that repeated administration of a clinical dose of phenobarbital enhanced the clearance of zonisamide and the enhanced clearance lasted at least 10 weeks after the discontinuation of phenobarbital. Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide.

Small number of HTLV-1-positive cells frequently remains during complete remission after allogeneic hematopoietic stem cell transplantation that are heterogeneous in origin among cases with adult T-cell leukemia/lymphoma.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can provide long-term remission for patients with adult T-cell leukemia/lymphoma (ATLL) caused by human retrovirus, human T-lymphocyte virus (HTLV-1). To understand how HTLV-1-positive cells including ATLL cells were suppressed by allo-HSCT, we examined HTLV-1 provirus load and residual ATLL cells in peripheral blood of transplant recipients using PCR-based tests. We found that the copy number of HTLV-1 genome, called provirus, became very small in number after allo-HSCT; however, in most cases, provirus did not disappear even among long-term survivors. Tumor-specific PCR tests demonstrated that most of HTLV-1-positive cells that remained long after transplantation were not primary ATLL cells but donor-derived HTLV-1-positive cells. We also found a case having very low amount of residual disease in peripheral blood even long after transplantation. There was only one recipient in whom we failed to show the presence of HTLV-1 genome and antibody against HTLV-1 even with an extensive search, which strongly suggested the elimination of HTLV-1 after allo-HSCT. These results demonstrated that after allo-HSCT the small amount of residual HTLV-1-positive cells were heterogeneous in origin and that long-term disease control for ATLL could be obtained without the complete elimination of HTLV-1.

Dosimetria proposta para o tratamento por ultra-som: uma revisão de literatura / Dosimetry propost for the treated for ultrasound: a literature of the review

Um dos equipamentos termoterapêuticos utilizados para a produção do calor é o que utiliza princípios de ultra-som (US) produzindo calor profundo pela propagação das suas ondas mecânicas, que são essencialmente as mesmas das ondas sonoras, mas com uma frequência mais alta. O US é produzido por uma corrente alternada que flui por um cristal piezoelétrico, alojado em um transdutor. Os efeitos do US dependem de muitos fatores físicos e biológicos, tais como a iontensidade, o tempo de exposição, a estrutura espacial e temporal do campo ultra-sônico e o estado fisiológico do local a ser tratado. Este grande número de variáveis complica a compreensão exata do seu mecanismo de ação na interação com os tecidos biológicos. Os efeitos do US vem sendo investigados e descritos de maneira empírica através dos tempos e as opinio~es sobre as dosagens utilizadas para o tratamento diferem significativamente, existindo poucas evidências dos seus efeitos clínicos. Sendo assim, este trabalho tem como objetivo apontar, mediante uma revisão bibliográfica, se existem parâmetros físicos e biológicos para determinaçãoi das doses de US, quando utilizado para fins terapêuticos

Interfering mutations provide in vivo evidence that Escherichia coli SecE functions in multimeric states.

SecY, SecE and SecG form a heterotrimer, which functions as a protein translocation channel in Escherichia coli. The cytosolic loop of SecE contains a segment that is conserved among different organisms. Here we show that mutational alterations in this segment not only inactivate the SecE function but confer dominant interfering properties on the altered SecE molecule. Such effects were especially evident in mutant cells in which the requirement for SecE function was increased. Overproduction of SecE, but not of SecY, alleviated the dominant negative effects. These results suggest that the inactive SecE molecule sequesters wild-type SecE. It was also found that an amino acid substitution, D112P, in the C-terminal periplasmic region intragenically suppressed the dominant interference. These results are consistent with a notion that there is significant SecE-SecE interaction in vivo, in which the C-terminal region has an important role. The data hence suggest that dimeric SecE participates in the formation of the functional translocation channel.

Holding characteristics of planar objects suspended by near-field acoustic levitation

The authors have found the acoustic levitation phenomenon where planar objects of 10 kg weight can be levitated near a vibration surface. This phenomenon has been studied for non-contact transportation. A circular planar object can be suspended without contacting a circular vibration plate. We have studied the holding force which acts horizontally on the levitated objects. The horizontal position of the object is stabilized by this force. In this paper, we discuss the effect of the radius of a levitated object, levitation distance, displacement amplitude of the vibration plate and the vibration mode on the suspending force.

Length recognition at the N-terminal tail for the initiation of FtsH-mediated proteolysis.

FtsH-mediated proteolysis against membrane proteins is processive, and presumably involves dislocation of the substrate into the cytosol where the enzymatic domains of FtsH reside. To study how such a mode of proteolysis is initiated, we manipulated N-terminal cytosolic tails of three membrane proteins. YccA, a natural substrate of FtsH was found to require the N-terminal tail of 20 amino acid residues or longer to be degraded by FtsH in vivo. Three unrelated sequences of this segment conferred the FtsH sensitivity to YccA. An artificially constructed TM9-PhoA protein, derived from SecY, as well as the SecE protein, were sensitized to FtsH by addition of extra amino acid sequences to their N-terminal cytosolic tails. Thus, FtsH recognizes a cytosolic region of sufficient length (approximately 20 amino acids) to initiate the processive proteolysis against membrane proteins. Such a region is typically at the N-terminus and can be diverse in amino acid sequences.

The plasmid F OmpP protease, a homologue of OmpT, as a potential obstacle to E. coli-based protein production.

OmpT, an outer membrane-localized protease of Escherichia coli, cleaves a number of exogenous and endogenous proteins during their purification. SecY, an endogenous membrane protein, is a target of this artificial proteolysis in vitro. Here we report that SecY cleavage occurs even in cell extracts from ompT-disrupted cells, if they carry an F plasmid derivative. A gene, ompP, on the F plasmid was shown to be responsible for this proteolysis. These results indicate that the absence of an F-like plasmid should be checked when choosing a host strain for E. coli-based protein production.

Conservation of histone binding and transcriptional repressor functions in a Schizosaccharomyces pombe Tup1p homolog.

The Ssn6p-Tup1p corepressor complex is important to the regulation of several diverse genes in Saccharomyces cerevisiae and serves as a model for corepressor functions. To investigate the evolutionary conservation of these functions, sequences homologous to the S. cerevisiae TUP1 gene were cloned from Kluyveromyces lactis (TUP1) and Schizosaccharomyces pombe (tup11(+)). Interestingly, while the K. lactis TUP1 gene complemented an S. cerevisiae tup1 null mutation, the S. pombe tup11(+) gene did not, even when expressed under the control of the S. cerevisiae TUP1 promoter. However, an S. pombe Tup11p-LexA fusion protein repressed transcription of a corresponding reporter gene, indicating that this Tup1p homolog has intrinsic repressor activity. Moreover, a chimeric protein containing the amino-terminal Ssn6p-binding domain of S. cerevisiae Tup1p and 544 amino acids from the C-terminal region of S. pombe Tup11p complemented the S. cerevisiae tup1 mutation. The failure of native S. pombe Tup11p to complement loss of Tup1p functions in S. cerevisiae corresponds to an inability to bind to S. cerevisiae Ssn6p in vitro. Disruption of tup11(+) in combination with a disruption of tup12(+), another TUP1 homolog gene in S. pombe, causes a defect in glucose repression of fbp1(+), suggesting that S. pombe Tup1p homologs function as repressors in S. pombe. Furthermore, Tup11p binds specifically to histones H3 and H4 in vitro, indicating that both the repression and histone binding functions of Tup1p-related proteins are conserved across species.

Complete DNA sequence analysis for 16S ribosomal RNA gene of the leproma-derived, cultivable and nerve-invading mycobacterium HI-75.

The complete 1493 nucleotide sequence of the 16SrRNA gene of the leproma-derived and cultivable mycobacterium HI-75 strain was analyzed to elucidate the taxonomic characteristics by direct sequencing of the polymerase chain reaction (PCR) products. The results revealed that the sequence of mycobacterium HI-75 was mostly similar to that of Mycobacterium scrofulaceum with 5 bases differences in the sequenced 1493 bases (0.35%) of the 16SrRNA gene. M. leprae differed from the strain with 47 bases (3.3%). Sasaki and Hamit reported the nerve-invasive activity of the inoculated mycobacterium HI-75 in nude mice or the 131I-treated immunocompromised Swiss mice. The results indicate that mycobacterium HI-75 could be a mutant of M. scrofulaceum possessing the ability to invade the peripheral nerve in addition to developing leproma-like lesions.

Syd, a SecY-interacting protein, excludes SecA from the SecYE complex with an altered SecY24 subunit.

Syd is an Escherichia coli cytosolic protein that interacts with SecY. Overproduction of this protein causes a number of protein translocation-related phenotypes, including the strong toxicity against the secY24 mutant cells. Previously, this mutation was shown to impair the interaction between SecY and SecE, the two fundamental subunits of the membrane-embedded part of protein translocase. We have now studied in vitro the mechanisms of the Syd-directed inhibition of protein translocation. Pro-OmpA translocation into inverted membrane vesicles (IMVs) prepared from the secY24 mutant cells as well as the accompanied translocation ATPase activity of SecA were rapidly inhibited by purified Syd protein. In the course of protein translocation, high affinity binding of preprotein-bearing SecA to the translocase on the IMV is followed by ATP-driven insertion of the 30-kDa SecA segment into the membrane. Our experiments using 125I-labeled SecA and the secY24 mutant IMV showed that Syd abolished both the high affinity SecA binding and the SecA insertion. Syd was even able to release the inserted form of SecA that had been stabilized by a nonhydrolyzable ATP analog. Syd affected markedly the proteolytic digestion pattern of the IMV-integrated SecY24 protein, suggesting that Syd exerts its inhibitory effect by interacting directly with the SecY24 protein. In accordance with this notion, a SecY24 variant with a second site mutation (secY249) resisted the Syd action both in vivo and in vitro. Thus, Syd acts against the SecY24 form of translocase, in which SecY-SecE interaction has been compromised, to exclude the SecA motor protein from the SecYE channel complex.

Genetic analysis of an essential cytoplasmic domain of Escherichia coli SecY based on resistance to Syd, a SecY-interacting protein.

We previously described a dominant negative secY-d1 allele in Escherichia coli, whose product interferes with protein export, presumably by sequestering SecE, the stabilizing partner of SecY. Syd is the product of a multicopy suppressor of the secY-d1 phenotype, and its overproduction preferentially stabilizes the wild-type SecY protein. In contrast, overproduction of Syd is toxic to the secY24 mutant, which shows a partial defect in SecY-SecE interaction. We isolated Syd-resistant revertants from the secY24 mutant. Pseudo-reversions mapped to sites at or near the secY24 mutation site (Gly240-->Asp). The secY249 mutation (Ala249-->Val) intragenically suppressed Syd sensitivity, but not the temperature-sensitive Sec phenotype of the secY24 mutation. The SecY249 mutant protein shows a reduced capacity to be stabilized by Syd, suggesting that the mutation weakens the SecY-Syd interaction. The other two mutations changed residue 240 (the site of the secY24 alteration) to Asn (secY245) or Ala (secY241) and restored the ability of the cell to export protein. Although the secY245 mutant retained some sensitivity to Syd overproduction, the secY241 mutant was completely Syd-resistant. Furthermore, the secY241 mutation seemed to represent a "hyper reversion" with respect to the SecY-SecE interaction. Protein export in this mutant was no longer sensitive to SecY-d1. When the secY-d1 mutation was combined intragenically with secY241, the resulting double mutant gene (secY-d1-241) showed an increased ability to interfere with protein export. On the basis of our model for SecY-d1, these results suggest that the secY241 alteration enhances SecY-SecE interaction. These results indicate that residue 240 of SecY is crucial for the interaction between the cytosolic domains of SecY and SecE required for the establishment of the translocase complex.

[A case of ovarian cyst presenting as urinary retention].

A 54-year-old woman presented with repeated episodes of urinary retention during an approximately 7-month period of dysuria. Computerized tomography scan revealed a right ovarian cyst and a small uterine myoma. At operation, the ovarian cyst was deeply incarcerated into the pouch of Douglas displacing the bladder neck and the uterine cervix in the anterocephalad direction. Histological diagnosis of the resected cyst was benign mucinous cystadenoma. This is the 5th reported case of urinary retention caused by ovarian cyst in the Japanese literature.

[Hansen's disease and nephropathy as its sequence].

Nephropathy as the sequences of Hansen's disease before and after the introduction of chemotherapy was compared referring to the report by Hayashi in 1943 and the summary of the autopsy reports from 1978 to 1981 at National Hansen's disease hospital Zenseien. Unlike the high rates of tuberculosis as the cause of death before the introduction of chemotherapy (41.3%) those thereafter decreased to be negligible. On the other hand the comparison of the rates of nephropathy with the same way as that of tuberculosis was impossible since the description about nephropathy by Hayashi was not sufficient to characterize each nephropathy since he included arteriolitis, glomerulonephritis and interstitial nephritis together in the term of nephritis. Death rate due to nephritis among Hansen's disease patients according to Hayashi at that time was 21.2% which was twice as many comparing to that in the other cases. According to the report about the cases of Zenseien those reported to have glomerulonephritis was 37.3% though those were not necessarily listed as the cause of death. Also the nephropathy including fibrinoid angitis with occasional microaneurysmal dilatation of afferent arteries, glomerulitis, sclerosis and stricture of efferent arteries likewise ischemic acute tubular necrosis possibly as the result of these angiopathy seemed to be present. These vascular changes partially resemble to that of microscopic periarteritis nodosa but seems to be common in the smaller arteries. In conclusion, unlike the case of tuberculosis the rate of nephritis including glomerulitis, arteriolitis and interstitial nephritis as Hayashi used as his criteria does not seem to have decreased. Therefore, the critical analysis of the nephropathy especially of that relating to the arteriolitis should be done to obtain the knowledge to suppress its occurrence.

A genomic study on the cultivable and nerve invading Mycobacterium HI-75 after the recovery 3 months of the inoculation to nude mice.

The sequence of the polymerase chain reaction (PCR) product of 16S ribosomal RNA (16S rRNA) of the leproma-derived and cultivable Mycobacterium HI-75 (M. HI-75) which was obtained from the infected regions of inoculated mice, was examined and compared with that of the cultured bacteria by the direct sequencing techniques. The sequence was completely consistent with the cultured bacilli in the comparable 837 bases of 16S rRNA. The mycobacterium examined in this study was originally isolated as M. leprae (ML) by Skinsnes, et al. in 1975 from leproma of a lepromatous type Hansen's disease patient and therefore named as Mycobacterium leprae HI-75 by them, and was maintained from 1984 using either Ogawa's or Sauton's media in the beginning and Ogawa's medium enriched with glucronic acid and N-acetyl-D-glucosamine recently. Sasaki and Hamit reported the nerve invasion and the growth of the inoculated bacilli either to the nude mice or the I131 treated immunocompromised Swiss mice. We previously reported that cultured HI-75 was most similar to M. scrofulaceum by the direct sequencing of the gene of 16S rRNA. The 16S rRNA obtained from the mouse tissue in the present study indicated that M. HI-75 would be a variant of M. scrofulaceum possessing an ability to invade into peripheral nerve. The results suggest that the HI-75 strain claims a nature as a pathogen to develop a leproma-like lesion.