Ubiquitination of molluscum body and its implications for pathophysiology.
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Epidermis↗
Biomedical subjects
I Takai
Publications and source records attributed to I Takai.
Health-related quality of life among dialysis patients in Seattle and Aichi.
We used the 36-item Short-Form Health Survey to compare health-related quality of life (HRQOL) between 104 dialysis patients in Seattle, WA, and 2,178 patients in Aichi, JAPAN: Compared with Aichi patients, Seattle patients had lower scores on three scales related to physical HRQOL: Physical Functioning (PF; P = 0.03), Role-Physical (RP; P = 0.004), and Vitality (VT; P < 0.001). However, scores related to mental HRQOL were higher for Seattle patients compared with those of Aichi patients, which included scores for Role-Emotional (RE; P = 0.005) and Mental Health (MH; P < 0.001). Scores for Bodily Pain, General Health Perception, and Social Functioning did not differ significantly between the two groups. These differences persisted even after potential confounding factors were controlled for. However, after taking into account national norm data for the United States and Japan, differences in PF and VT disappeared, whereas differences in RP, RE, and MH persisted. These results suggest that the higher scores for PF and VT in Aichi patients were partly explained by the higher physical HRQOL of the Japanese general population. Although these data may not be representative of the total dialysis populations in the United States and Japan, they suggest potential differences in HRQOL between patients in the two countries. Additional research is needed to confirm these results and understand the factors associated with these differences. The findings suggest the need for further attention to the physical limitations of US dialysis patients and the mental health of Japanese dialysis patients.
Adult↗
Translation, cultural adaptation, and initial reliability and multitrait testing of the Kidney Disease Quality of Life instrument for use in Japan.
BACKGROUND: The Kidney Disease Quality of Life instrument (KDQOL) consists of 79 items: 36 asking about health-related quality of life (HRQOL) in general (the Medical Outcomes Study SF-36) and 43 asking about QOL as it is affected by kidney disease and by dialysis. AIM: Translation, cultural adaptation and initial reliability and multitrait testing of the KDQOL for use in Japan. METHODS: Translation and cultural adaptation began with two translations into Japanese, two backtranslations into English, and discussions among the translators, the project coordinators in Japan, and the developers of the original (US-English) version. Focus-group discussions and field testing were followed by analyses of test-retest reliability, internal consistency, and convergent and discriminant construct validity. RESULTS: All eight of the SF-36 scales met the criterion for internal consistency (Cronbach's alpha ranged from 0.73 to 0.92) and were reproducible (intraclass correlations between test and retest scores ranged from 0.60 to 0.82). Of the 10 kidney-disease-targeted scales, only two had alpha coefficients of less than 0.70: 'sleep' (0.61) and 'quality of social interaction' (0.35). One item on the 'quality of social interaction' scale had a very weak correlation with the remainder of that scale (r = 0.10). Eliminating that item from scoring increased the alpha coefficient of the scale from 0.35 to 0.64. All three items on the 'quality of social interaction' scale had very strong correlations with other scales. CONCLUSIONS: First, in Japanese patients receiving dialysis the SF-36 scales are internally consistent and their scores are reproducible. Second, with the possible exception of the 'quality of social interaction' scale, the Japanese version of the KDQOL, can provide psychometrically sound kidney-disease-targeted data on quality of life in such patients.
Adult↗
A new method for assaying adhesion of cancer cells to the greater omentum and its application for evaluating anti-adhesion activities of chemically synthesized oligosaccharides.
A new ex vivo method for assaying adhesion of cancer cells to the greater omentum has been developed using mouse greater omentum and [3H]labelled human gastric and mouse colorectal cancer cells. Since the adhesion rates were found to increase up to 18 h and labelled cells seemed to be stable during the period, the present method could be useful for investigating adhesion of cancer cells to the greater omentum, which must occur at the first step of the peritoneal dissemination. The adhesion of cancer cells to the greater omentum was inhibited by a series of chemically synthesized oligosaccharides and Gal beta1,3[3OMeGal beta1,4GlcNAc beta1,6]alphaBn was found to be the best inhibitor. The anti-tumor effect of this novel tetrasaccharide in vivo was shown in preliminary experiments using Balb/c mice and colon26 cells.
Animals↗
Health-related quality of life among renal-transplant recipients in Japan.
BACKGROUND: This study had four goals: (1) to evaluate an index of health-related quality of life (HQOL) among renal-transplant recipients in Japan, (2) to compare HQOL of renal-transplant recipients with that of the Japanese population as a whole, and (3,4) to study associations of HQOL with renal function and with the time since transplantation. METHODS: Questionnaires were distributed to 570 subjects. All were outpatients, were 16 years old or older, and were studied at least 1 year after they had received their latest renal transplant. HQOL was assessed with the Short Form 36-item health survey. Subjects' physicians provided data on renal function. Associations of HQOL with serum creatinine concentration and with the time since transplantation were evaluated by logistic regression. RESULTS: The response rate was 83%. Data from patients with diabetes and from those who had had at least two renal transplants were excluded; data from 395 recipients were analyzed. On the physical functioning, general health perception, vitality, and social functioning scales, the patients' scores were significantly lower than the Japanese national-norm scores. General health perception was particularly low. Serum creatinine concentrations were associated with general health perception, vitality, and social functioning. Longer times since transplantation were associated with better social functioning. CONCLUSIONS: Although social and physical functioning may improve after transplant surgery, a low self-rating of general health seemed to remain. The rarity of renal transplantation in Japan and other psychosocial factors may explain the low self-rating of general health in Japanese renal-transplant recipients.
Adolescent↗
Altered cellular responses by varying expression of a ribosomal protein gene: sequential coordination of enhancement and suppression of ribosomal protein S3a gene expression induces apoptosis.
A growing body of evidence indicates that individual ribosomal proteins and changes in their expression, participate in, and modulate, a variety of cellular activities. Our earlier studies have found that apoptosis could be induced by inhibiting expression of ribosomal protein S3a (RPS3a) in many tumor cells which constitutively express RPS3a at levels much higher than in normal cells. This study aimed to investigate cellular responses to enhancement of RPS3a expression, and whether apoptosis could be induced by sequential alterations in RPS3a expression involving enhancement from an initially low constitutive level, followed by suppression. Stably transfected NIH 3T3- derived cell lines were established in which exogenous RPS3a expression could be readily manipulated. Enhancement of RPS3a expression appeared to induce transformation as assessed by well-established criteria such as foci formation and anchorage-independent growth in vitro, and formation of tumors in nude mice. These properties were compared with those observed in ras-transformed NIH 3T3 cells. Apparent transformation occurred only when enhanced RPS3a-expressing cells were in close cell-cell contact. Suppression of enhanced RPS3a expression was observed to induce apoptosis as assessed by various morphological and biochemical characteristics including cell shrinkage, membrane blebbing, chromatin condensation, nuclear and cell fragmentation, phosphatidylserine externalization, and internucleosomal DNA fragmentation. This induction of apoptosis was not specific to apparently transformed cells, as cells at low confluence, which likewise expressed RPS3a at enhanced levels but exhibited no morphological transformation, underwent apoptosis when RPS3a expression was inhibited. These results support a role for RPS3a in the apoptotic process, but not as an oncoprotein per se.
3T3 Cells↗
A novel method for determination of alpha1,6fucosyltransferase activity using a reducing oligosaccharide from egg yolk as a specific acceptor.
A new method for determination of alpha1,6fucosyltransferase activity has been described. Recently, the disialyl-biantennary undecasaccharide was prepared in high yield from egg yolk [(1996), Carbohydr Lett 2: 137-42]. By treatment of this oligosaccharide with neuraminidase and beta-galactosidase, we readily obtained an asialo-agalacto-biantennary heptasaccharide (GlcNAcbeta 1,2Manalpha1,6[GlcNAcbeta1,2Manalpha1,3]Manbeta1 ,4GlcNAcbeta1,4GlcNAc). Using this asialo-agalacto-oligosaccharide as an acceptor, fucosyltransferases from human plasma and extracts of various human hepatoma cell lines were assayed in the presence of GDP-[3H]fucose. The reaction mixture was applied to a column of GlcNAc-binding, Psathyrella velutina lectin coupled gel. All the fucosylated acceptor were bound to the column which was eluted with 50 mM GlcNAc. Structural analyses revealed that only the innermost GlcNAc residue of the acceptor was fucosylated through an alpha1,6-linkage, and the oligosaccharide prepared could be used as a specific acceptor for alpha1,6fucosyltransferase. The present method was used to screen plasma alpha1,6fucosyltransferase in several patient groups, and significantly elevated activities were found in samples from patients with liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.
Acetylglucosamine↗
Effects of L-carnitine supplementation on muscular symptoms in hemodialyzed patients.
Various muscle symptoms are well recognized among patients on maintenance hemodialysis. Carnitine deficiency may be an important factor of dialysis-associated muscle symptoms, whereas high-dose L-carnitine supplementation may result in unphysiologically high plasma levels of carnitine and carnitine esters. We studied the effect of low-dose L-carnitine treatment (500 mg/d) on muscle symptoms, plasma carnitine fractions, and lipid profiles in 30 periodically dialyzed patients with muscular weakness, fatigue, or cramps/aches. After 12 weeks of L-carnitine treatment, about two-thirds of patients had at least some improvement in muscular symptoms, whereas carnitine fractions were normal or slightly above normal ranges, but lipid profiles showed no demonstrable changes. This study also showed the correlation between plasma-free carnitine deficiency and months on dialysis. These results suggest that prolonged low-dose L-carnitine treatment can improve dialysis-associated muscle symptoms by restoring carnitine tissue levels and washing out acyl moieties.
Administration, Oral↗
Peripheral deletion of gammadelta T cells in haemodialysis patients.
Many patients with end-stage renal disease have altered host defenses against infectious agents. We have demonstrated that T cells, which play an important role in the immunological response, may undergo apoptosis by the Fas system in uraemia. To elucidate whether gammadelta T cells, which function as a first defense against intracellular pathogens, are altered in number or characteristics in dialysis patients, surface expressions of TCR, LFA-1 and Fas antigen on peripheral T cells were examined by immunofluorescence analysis. We demonstrated that the proportions of peripheral gammadelta T cells are altered significantly in haemodialysis (HD) patients. Interestingly, there were marked differences in the levels of expression of LFA-1 and Fas antigen between the two types of T cells. Moreover, both the expression of LFA-1 and that of Fas antigen were enhanced significantly in HD patients compared with normal controls. These results suggest that circulating gammadelta T cells may be susceptible to activation-induced cell death in comparison with alphabeta T cells in uraemic environments.
Adult↗
Increased soluble CD4 and CD8 in chronic renal failure.
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CD4 Antigens↗
lpr T cells have lower ability to maintain bcl-2 expression ex vivo.
Autoimmune-prone lpr mice develop lymphoproliferative disorders, whereas their lymphocytes show accelerated apoptosis in culture. To elucidate whether the bcl-2 protein, a repressor of apoptosis, is critical to the discrepancy between in vivo and in vitro survival, we examined bcl-2 expression in T cells from +/+ and lpr mice during culture. The expression levels of bcl-2 in cultured T cells from lpr mice were significantly down-modulated compared to those from +/+ mice and freshly obtained T cells. Besides, the reduction of bcl-2 protein levels was inhibited in T cells cultured in the presence of T cell receptor (TCR) signalling. These results suggest that lpr T cells might be susceptible to apoptosis in vitro due to down-modulation of bcl-2 by withdrawal of TCR signalling.
Journal Article↗
New method to calculate creatinine generation rate using pre- and postdialysis creatinine concentrations.
The creatinine (Cr) generation rate reflects the muscle mass, a possible indicator of protein nutritional status. Thus, in this study, we developed equations for calculating the Cr generation rate. Depner and Daugirdas recently developed a method for determining the protein catabolic rate (PCR) from the pre- and postdialysis blood urea nitrogen concentrations. We modified their method to develop equations for calculating the total Cr generation rate from the measured predialysis Cr concentration and estimated postrebound concentration. The total Cr generation rate is defined as the sum of the intrinsic Cr generation rate and the extrinsic Cr generation rate (i.e., the generation rate of Cr derived from food). In the present study, the postrebound Cr concentration was estimated on the basis of postdialysis Cr concentration and the K/V for Cr. The intrinsic Cr generation rate was obtained by subtracting the extrinsic Cr generation rate, which was estimated on the basis of the PCR, from the total Cr generation rate calculated. The intrinsic Cr generation rate determined with this method was virtually the same as that obtained using the postrebound Cr concentration, the concentration immediately before the next hemodialysis (HD) session, and the PCR. The intrinsic Cr generation rate determined with the present method did not vary with changes in the HD prescription (i.e., with an increase in blood flow rate, a prolongation of the HD duration time, or a change in dialyzer membrane area). The present study also indicated that the intrinsic Cr generation rate decreased with age in both males and females.
Adult↗
Purification and characterization of perlecan fragment in urine of end-stage renal failure patients.
We found a new spot on the two-dimensional electrophoresis pattern of the urine protein from hemodialysis patients. In order to identify the protein forming this new spot, the protein was purified by five steps of chromatography. It was shown that the amino acid sequence of this new protein from the N-terminal to the 20th amino acid was identical with the sequence from the 4197th to 4216th amino acid of perlecan, which is the core protein of the proteoglycan localizing in the systemic capillary basement membranes. It was also found that the molecular weight (25,000 daltons) of this new protein was comparable to the calculated molecular weight of the molecular region of the perlecan from the 4197th amino acid to the C-terminal. Lastly, it was shown that the antibodies against this new protein reacted with the perlecan produced by human fibroblasts. All these findings indicated that the new protein is a perlecan fragment.
Amino Acid Sequence↗
Effective method for purification of lysozyme from human urine.
Lysozyme in the urine of a hemodialysis patient was purified in two steps: DEAE Sephadex chromatography followed by Sephacryl chromatography. The Sephacryl S-100 column chromatographed fraction showing lytic activity was proven to give one band on SDS-PAGE and to have a molecular mass of 14500, in agreement with that of lysozyme. The N-terminal amino acid sequence of this purified protein was identical to that of lysozyme. These results indicate that the protein purified was indeed lysozyme. The specific affinity of lysozyme for Sephacryl S-100 may explain the greater purity of the same protein isolated by this method.
Amino Acid Sequence↗
First evidence for accumulation of protein-bound and protein-free pyrraline in human uremic plasma by mass spectrometry.
Glucose-derived advanced glycation end products (AGEs) cross-link proteins and cause various biological tissue damage. One of them, pyrraline [epsilon-2-(formyl-5-hydroxymethyl-pyrrol-1-yl) -L-norleucine], has been demonstrated by utilizing antibody to accumulate in plasma and sclerosed matrix of diabetic individuals, suggesting responsibility for diabetic complications. To elucidate the involvement of pyrraline in uremia, we examined the pyrraline levels in patients with chronic renal failure by a mass spectrometric approach. Here we show that protein-free pyrraline as well as pyrraline with binding protein are significantly increased in non-diabetic uremic plasma compared to healthy subjects. Our results suggest that circulating pyrraline could be a substance contributing to complications in uremia.
Blood Proteins↗
Alternate repetition of short fore- and backfiltrations reduces convective albumin loss.
An effective therapeutic means to remove relatively large polypeptide uremic toxins seems to be a hemofiltration (HF) or hemodiafiltration (HDF) employing a larger-pore membrane, that is, a protein-permeable membrane. With either method, however, a significant amount of albumin will be lost into the ultrafiltrate or dialysate. Now, repetition of alternate short fore- and backfiltrations may prevent the development of the ultrafiltration-induced higher albumin concentration on the membrane surface (protein concentration polarization), where a single forefiltration time is shorter than the time needed for completion of protein concentration polarization. Since the albumin concentration on the protein-permeable membrane surface will be one of the determinants of albumin loss by convection, such HDF treatment may reduce protein loss into the dialysate. To examine this assumption, we alternately repeated short and rapid fore- and backfiltrations (push/pull HDF) through a protein-permeable membrane, each less than 1 second in duration and at each filtration volume of 15 ml, where a pyrogen-free dialysate was supplied. The present results indicated that the albumin amount lost by push/pull HDF was approximately one-third of that by conventional HDF. Nevertheless, the reduction rates of beta 2-microglobulin and myoglobin were significantly greater by push/pull HDF than by conventional HDF.
Blood Proteins↗
Relationship between susceptibility to apoptosis and Fas expression in peripheral blood T cells from uremic patients: a possible mechanism for lymphopenia in chronic renal failure.
Chronic renal failure (CRF) is often complicated by lymphopenia, which may be partly responsible for immune deficiency. We hypothesized that lymphopenia in CRF might result from apoptosis of T cells in vivo. To elucidate the involvement of Fas antigen which mediates apoptosis, we analyzed Fas expression on peripheral blood T cells in uremic non-dialyzed (non-HD) patients and hemodialysis (HD) patients. T cells from both uremic groups expressed Fas with higher intensity than control T cells. When two uremic groups were compared, Fas intensity on T cells was significantly higher in non-HD patients than in patients on HD. Moreover, uremic T cells were shown to undergo accelerated apoptosis when cultured in vitro, in correlation with Fas expression. Our results suggest that T cells in CRF may undergo apoptosis by the Fas system and that hemodialysis treatment has beneficial effects in the light of the inhibition of T cell apoptosis.
Apoptosis↗
Determination of Kt/V and protein catabolic rate using pre- and postdialysis blood urea nitrogen concentrations.
We developed a new urea kinetic method for simultaneous determination of the Kt/V and protein catabolic rate (PCR) only from blood urea nitrogen (BUN) concentrations before and after a single dialysis session. Using this method, the parameters were calculated within 1.5 s even when a hand-held computer with a low central processing capacity is used. The total amount of urea eliminated during three dialysis sessions in 1 week is assumed to be equal to urea volume (Gw) generated over a 1-week period (Tw): [formula: see text]. Here, G is the generation rate, K is the dialyzer urea clearance, T is the dialysis time and C1, C2 and C3 are BUN during the respective dialysis session. If this equation and the equation expressing the urea kinetics during a single dialysis session are solved together, we have a solution for Kt/V and G. The thus-obtained Kt/V and G are corrected using the change in body weight. The corrected Kt/V showed a good correspondence with the parameter calculated with the classical method, and the midweek PCR derived from G determined by the present method being equivalent to the PCR averaged for a 1-week period determined by the classical methods.
Blood Urea Nitrogen↗