Expression of amyloid beta-protein precursor mRNAs in cultured skin fibroblasts taken from patients with dementia of the Alzheimer type.
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Aged↗
Biomedical subjects
A Okada
Publications and source records attributed to A Okada.
Analysis of amyloid precursor protein mRNAs in skin fibroblasts in Down's syndrome.
We examined amyloid precursor protein (APP) mRNAs expression in skin fibroblasts from Down's syndrome (DS) patients of different ages to determine the time of occurrence of abnormal splicing. The ratio of APP770 + 751 mRNA to APP695 mRNA (APP770 + 751/695) was significantly increased in the young DS group and adult DS group compared with the age-matched control groups (p < 0.01, p < 0.05), but no significant increase was observed in the aged DS group compared with the age-matched control group. These findings suggest that metabolic abnormalities of the APP gene occur at a very early stage of DS, at a mean age of about 5 years. Therefore, metabolic abnormalities of the APP gene are considered to appear at a very young age also Alzheimer's disease (AD). In this study, we confirmed that examination of the APP gene in skin fibroblasts might be useful for early diagnosis of AD.
Adult↗
Clinical course and CSF amyloid beta protein precursor having the site of application of the protease inhibitor (APPI) levels in patients with dementia of the Alzheimer type.
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Aged↗
Involvement of beta-adrenergic receptor kinase-1 in homologous desensitization of histamine H2 receptors in human gastric carcinoma cell line MKN-45.
The poorly differentiated human gastric carcinoma cell line MKN-45 possesses histamine H2 receptors which are homologously desensitized by histamine. In order to clone the cDNA of a receptor kinase specific for H2 receptors, we performed RT-PCR at a low annealing temperature using oligo-DNA primers bearing the conserved sequences of the kinase domain of the G protein-coupled receptor kinase (GRK) family. However, we were able to isolate only cDNAs for beta-adrenergic receptor kinase 1 (beta ARK1) and GRK6. Interestingly, treatment of MKN-45 cells with beta ARK1 antisense phosphorothioate oligo-DNA (PON) resulted in significant loss of desensitization of H2 receptors by histamine, whereas GRK6 antisense PON had no effect. Thus, beta ARK1 appears to be involved in the homologous desensitization of H2 receptors in MKN-45 cells.
Blotting, Northern↗
On-off study of manganese administration to adult patients undergoing home parenteral nutrition: new indices of in vivo manganese level.
BACKGROUND: Recently, there have been reports that magnetic resonance imaging (MRI) reveals high-intensity T1-weighted images (HI) in the basal ganglia (especially in the globus pallidus) of patients receiving total parenteral nutrition (TPN). This finding is presumably due to excess administration of manganese. We investigated the reversibility and reproducibility of these changes by means of an on-off manganese administration study. We also investigated the temporal relationships between the intensity of T1-weighted images (MRI intensity) and the whole-blood and plasma manganese concentrations to evaluate the potential for the MRI intensity to serve as an index of the in vivo manganese level. METHODS: Eleven adult patients undergoing home parenteral nutrition received TPN solutions containing manganese (0 or 20 micromol/d) according to an on-off design. The whole-blood and plasma manganese concentrations were determined at the same time the brain MRI was performed. RESULTS: Both the whole-blood manganese concentration and the MRI intensity in the globus pallidus changed in response to the administration and withdrawal of manganese. It took at least 5 months for HI to disappear when manganese was withdrawn, and this change was reversible and reproducible. The whole-blood manganese concentration showed strong correlations with both the MRI intensity and the T1 value (r = 0.7693, -0.7011). The MRI intensity and the T1 value showed a strong correlation (r = -0.9051). CONCLUSIONS: The whole-blood manganese concentration, the MRI intensity in the globus pallidus and the T1 value, an objective index of the MRI intensity, may be useful indices of the manganese level in the body.
Adult↗
Urinary excretion of 3-methylhistidine in patients receiving parenteral nutrition.
In an attempt to investigate the kinetics of the muscle protein during parenteral nutrition (PN) and surgical stress, the urinary output of 3-methylhistidine (3-Mehis) was measured in patients receiving PN, then the validity of urinary 3-Mehis excretion as an index for the patient's status of protein nutrition was examined. The amounts of 3-Mehis excreted in 24 hr urine in the 19 healthy males and 10 healthy females were 74.8 +/- 17.1 mg/day and 46.3 +/- 12.4 mg/day, respectively. The changes of daily urinary 3-Mehis output in 6 cases receiving PN for more than 4 weeks were also examined. The average urinary 3-Mehis excretion increased gradually during the course of PN, and by the third week was nearly twice as high as the level before PN. In a further study the influence of surgery upon the urinary excretion of 3-Mehis was examined in 9 patients. Finally, a comparison was made of the nutritional status before and 4 wks after PN in the 6 patients without surgical stress. Urinary 3-Mehis was found to be a good index of both the status of protein nutrition and the fluctuation of muscle protein catabolism.
Adolescent↗
Vitamin A and E requirements during total parenteral nutrition.
Studies were undertaken to determine rational dosages of vitamin A and E during long-term total parenteral nutrition (TPN). Four kinds of vitamin prescriptions containing different amounts of vitamin A and E were prepared from commercially available products and/or hospital pharmacy products. Patients were divided into four groups according to the vitamin prescription used. Plasma vitamin levels of different patient groups were determined by a modified fluorimetric method and were compared with those of a normal subject group. The stability of vitamin A and E in TPN solution after admixing was determining by measuring the remaining vitamin contents by high pressure liquid chromatography. From the results, it was concluded that 1) about 50% of vitamin A was decomposed by sunlight (about 2000 lux) 3 hr after admixing and an orange-colored vinyl cover could protect its photodecomposition; 2) vitamin E was stable at any condition tested; 3) 2500 IU of vitamin A and 15 IU of vitamin E could meet the daily requirements; 4) the plasma levels of vitamin A and E were correlative (p less than 0.01); and 5) concomitant administration of vitamin E was essential to keep the poorer level of vitamin A in plasma.
Drug Stability↗
Acute gastric mucosal lesions--a new experimental model and effect of parenteral nutrition.
Experiments were performed on 94 male Sprague-Dawley rats to explore the influence of starvation and parenteral nutrition on the development of acute gastric mucosal changes under stress. Comparative assessments were made of lesions in the gastric mucosa of rats on 1- or 6-day repeated exposure to the stress consisting of restraint with immersion in water. Marked hemorrhagic lesions over the extensive area of the glandular stomach and pronounced ulcerative changes in the nonglandular stomach were observed in 6-day stress group as compared to 1-day stress group where only a few hemorrhagic lesions were observed. Thus, this model has proven to provide an excellent experimental model suitable to the purpose of the present investigation. Parenteral nutrition significantly suppressed the development of mucosal damage either in the nonglandular or glandular stomach of rats under 6-day stress. Furthermore, it has been demonstrated that lesions caused in the glandular stomach increase in severity via exposure to stress and starvation while those evoked in the nonglandular stomach rise in incidence even in the presence of starvation alone.
Animals↗
Clinical studies on zinc metabolism during total parenteral nutrition as related to zinc deficiency.
In 99 adult patients receiving controlled total parenteral nutrition (TPN), a study was made on the time course of concentrations of zinc in plasma, erythrocyte and urine in relation to the development of zinc deficiency. Zinc deficiency developed in 11 cases receiving TPN solutions not containing zinc. The plasma zinc level was significantly lower at the time of onset of zinc deficiency than in normal subjects, before the procedure of TPN, or at the time of symptomatic relief achieved by administration of zinc. The erythrocyte zinc level was slightly but not significantly lower at time of onset of zinc deficiency than in normal subjects, before TPN or at time of symptomatic relief. The urinary zinc level at time of onset of zinc deficiency was significantly lower than that in normal subjects or at the time of symptomatic relief but not significantly lower than that before TPN. A comparison between patients developing and those not developing zinc deficiency within 4 wk of the outset of TPN showed that only the plasma zinc level was significantly lower in the former than the latter group. The urinary zinc level also tended to be lower, although not significantly, in the former than the latter group but varied widely. No difference was present between the groups as to the erythrocyte zinc level. Zinc deficiency developed in none of those patients who had a plasma zinc level of 50 micrograms/dl or more but in five of 10 (50%) patients with less than 50 micrograms/dl and in all three with less than 30 micrograms/dl of zinc in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of alternate and simultaneous administrations of calcium and phosphorus on calcium metabolism in children receiving total parenteral nutrition.
The effects of alternate and simultaneous administrations of calcium (Ca) and phosphorus (P) on Ca metabolism in children receiving total parenteral nutrition (TPN) were examined. Eight children, aged 2 to 36 months, were studied. The following three solutions were administered: solution 1 contains Ca (533 mg/liter); solution 2 contains P (413 mg/liter); and solution 3 contains Ca (267 mg/liter) and P (207 mg/liter). Solutions 1 and 2 were administered alternately for 24-hr periods. (Results) I. During administration of solution 1, significant hypophosphatemia (4.39 +/- 0.26 mg/dl) and hypercalcemia (9.96 +/- 0.15 mg/dl) were observed and, conversely, during administration of solution 2, significant hypocalcemia (8.36 +/- 0.18 mg/dl) and hyperphosphatemia (6.16 +/- 0.27 mg/dl) were observed. During administration of solution 3, the serum levels of both minerals were maintained within the normal ranges (Ca 9.46 +/- 0.12 mg/dl, P 5.65 +/- 0.21 mg/dl). II. The urinary excretion of cyclic AMP was significantly lower during administration of solution 1 (6.67 +/- 0.45 nmol/mg creatinine (Cr] as compared with solution 3 (7.50 +/- 0.61 nmol/mg of Cr). On the other hand, the excretion was significantly higher during administration of solution 2 (11.55 +/- 1.58 nmol/mg of Cr) as compared with solution 3, indicating the existence of secondary hyperparathyroidism. III. The Ca and P retention rates were significantly higher with solution 3 (Ca 79.0 +/- 5.5%, P 73.2 +/- 7.2% of the intake) than with solutions 1 and 2 alternately (Ca 62.7 +/- 4.5%, P 49.2 +/- 9.3%). (Conclusions) Simultaneous administrations of Ca and P are preferable to their alternate administrations for Ca metabolism in children receiving TPN.
Bone and Bones↗
Urinary excretion of 3-methylhistidine as an index of protein nutrition in total parenteral nutrition.
In 39 healthy adult volunteers and nine patients receiving total parenteral nutrition (TPN), determinations were made of the urinary excretion of 3-methylhistidine (3-Mehis) to estimate the degree to which the urinary output of 3-Mehis reflects the status of protein nutrition. In 19 males and 10 females of the former group, measurements were made of the amount of 3-Mehis and of creatinine (Cr) in 24-hr urine samples. The urinary output of 3-Mehis was also measured in two subgroups of five healthy adult male subjects who were fed one of the two different diets prescribed: meat (M) and meat-free (F) diet. Furthermore, in one of these subgroups which was fed on F diet, the urinary output of 3-Mehis was measured both while the subject was kept at bed rest and while the subject was allowed to live a normal life. From these measurements the standard value was determined for the urine 3-Mehis level and the 3-Mehis/Cr ratio in 24-hr urine in healthy adult human subjects of both sexes. In nine patients maintained on TPN these indices of nutritional status were measured before and at 4 weeks of TPN. The time course of the indices was also investigated. The results obtained suggest that both the urinary output of 3-Mehis and the 3-Mehis/Cr ratio can provide a sensitive index of the status of protein nutrition.
Adult↗
Branched-chain amino acids metabolic support in surgical patients: a randomized, controlled trial in patients with subtotal or total gastrectomy in 16 Japanese institutions.
A prospective, randomized, controlled trial of nutritional effects of branched-chain-enriched amino acid (BCAA) solution was undertaken in 173 surgical patients with gastric cancer. Eighty-six and 87 patients underwent subtotal and total gastrectomy, respectively. The effects were evaluated in total parenteral nutrition (TPN) in an isocaloric/isonitrogenous setting where the major difference between the group was the amount of BCAA received. Each 80 patients in the control and the BCAA groups completed the trial. The group receiving BCAA-enriched amino acid solution demonstrated a statistically significant improvement on days 2 and 3 in nitrogen balance in patients with total gastrectomy. Three-methyl-histidine excretion gradually decreased after day 1, and the values on day 7 were significantly lower than those on day 1 in the BCAA group in both those receiving subtotal and total gastrectomy. There were no significant differences of serum albumin and rapid turnover proteins between the control and BCAA groups in both those receiving subtotal and total gastrectomy. Plasma BCAA level and BCAA to aromatic amino acid (AAA) ratio were significantly higher, and AAA level was significantly lower in the BCAA group than in the control group. There were no serious complications encountered during the observation period in both groups. These results indicated that a BCAA-enriched amino acid solution can improve metabolism and maintains good nitrogen retention without increasing side effects as compared with a conventional amino acid solution for nutritional support of patients who have received subtotal or total gastrectomy.
Adolescent↗
Clinical studies on a newly devised amino acid solution for neonates.
In 97 neonates receiving total parenteral nutrition in the postoperative period, clinical assessment was made for a newly devised amino acid solution (PF-I-III) from the standpoint of plasma amino acid profile and nutritional effect. These amino acid solutions prepared are characterized by the high concentration of branched-chain amino acids up to 40%, increased arginine and decreased glycine, phenylalanine and methionine as compared with commercially available solutions. In the PF group, each amino acid was kept within the range of standard value. Correlation between plasma amino acid profiles and the dose of each amino acid administered was obtained, from which minimum, standard, and maximum doses for each amino acid was determined. Based on these values, we proposed new formula for neonates which elicits no abnormal plasma amino acid pattern even when amino acids are administered at the dosage level of 1.5-2.5 g/kg/day.
Amino Acids↗
Hyperbilirubinemia in neonates associated with total parenteral nutrition.
To identify the factors responsible for total parenteral nutrition (TPN) associated jaundice in the neonate, 77 newborns who had been started on TPN during the past 12 years had their charts reviewed. Forty-four (57%) of these infants developed jaundice during the 1st month of life. The incidence of jaundice was significantly higher in the presence of those diseases which were associated with impaired intestinal passage such as congenital duodenal atresia, jejunal atresia, etc, and those with an abnormal rotation of the gut such as diaphragmatic hernia, gastroschisis, etc. Thirty-two (42%) of these 77 infants had accompanying infectious signs, and 28 (88%) of those 32 infants with infectious signs developed jaundice. This incidence was significantly higher than that (36%) among those who had no infectious signs. Of the possible etiologic factors other than infection, neither the length of intrauterine life nor birth weight showed significant correlation with the incidence of jaundice. The incidence of jaundice tended to be higher in infants started on TPN at a younger age. There was no significant correlation between the incidence of jaundice and the duration of TPN or fasting period. Infants receiving 110 cal/kg/day or more during TPN developed jaundice significantly more frequently than those receiving fewer calories. No definite correlation was obtained between the incidence of jaundice and the amount of amino acids administered.
Humans↗
A newborn rabbit model for total parenteral nutrition: effects of nutritional components on cholestasis.
A newborn rabbit model for total parenteral nutrition (TPN) was developed to examine the effects of nutritional components on cholestasis. Thirty-five newborn Japanese white rabbits were divided into five groups. Rabbits in group I received glucose-based TPN solution, Group II received lipid-based solution, group III received larger amounts of amino acids than group I, and group IV received larger amounts of nonprotein calories than groups I and II. Rabbits in group V were given mother's milk freely. After the duration of TPN for 7 days, blood samples and liver were obtained when rabbits were killed. In group IV, the serum level of T-Bil (1.44 +/- 0.68 mg/dliter) was significantly higher than those in other groups (group I: 0.28 +/- 0.04 mg/dl; group II: 0.49 +/- 0.12 mg/dl; group III: 0.21 +/- 0.04 mg/dl; group V: 0.28 +/- 0.07 mg/dl), and serum level of GOT (44.2 +/- 25.2 units) and total bile acid (20.6 +/- 8.9 nmol/ml) were significantly higher than those in groups I, II, and III (group I: 16.8 +/- 7.8 units and 6.7 +/- 3.3 nmol/ml, group II: 21.5 +/- 7.9 units and 12.5 +/- 6.4 nmol/ml, group III: 14.3 +/- 4.2 units and 8.4 +/- 5.0 nmol/ml, respectively). Furthermore, there was histological cholestasis characterized by bile plugs in bile ducts, and bile pigments in Kupffer cells and hepatocytes, whereas there were no, or scarce findings of cholestasis in the other groups. These results indicate that an excessive administration of nonprotein calories in TPN contributes to the occurrence of cholestasis. In addition this animal model may be useful in investigating the etiology of cholestasis.
Animals↗
Copper deficiency during total parenteral nutrition: clinical analysis of three cases.
Three adult cases in which copper deficiency developed during long-term total parenteral nutrition (TPN) without copper supplementation have been described, together with a brief review of the literature. All three patients were suffering from malabsorption when TPN was instituted, and overt symptoms of copper deficiency developed an average of 5.8 months after the start of TPN. Clinically, leukopenia with neutropenia and low plasma levels of copper and ceruloplasmin were seen in all cases. The dosage of copper administration in these cases was 0.3 to 7.2 mg of copper/day, or 5.3 to 133 micrograms of copper/kg/day, with total doses of 7 to 176 mg of copper.
Adolescent↗
Platelet glutathione peroxidase activity in long-term total parenteral nutrition with and without selenium supplementation.
Selenium (Se) is not routinely included in total parenteral nutrition (TPN) solution; thus, patients receiving long-term TPN may be at risk of Se deficiency, which may cause fatal cardiomyopathy. Platelet glutathione peroxidase (GSH-Px) activity, as well as Se levels and GSH-Px activity in plasma and erythrocytes during prolonged TPN, was measured in six patients with chronic gastrointestinal disease. During the time course of TPN, Se administration was discontinued for 12 weeks, and then resupplemented for another 12 weeks. Before the study period, all Se indices had been maintained within the normal range. After discontinuation of Se supplementation, a significant decrease in platelet GSH-Px activity was observed after 1 week (from 64 +/- 7 [mean +/- SD] to 39 +/- 5 U/g of protein). After resupplementation, it increased after 1 week (from 44 +/- 9 to 65 +/- 10 U/g of protein). Plasma Se indices significantly changed within 3 weeks after withdrawal and reintroduction of Se (Se: from 136 +/- 28 to 75 +/- 14 and from 61 +/- 22 to 125 +/- 33 micrograms/L; GSH-Px: from 236 +/- 50 to 140 +/- 36 and from 128 +/- 32 to 220 +/- 64 U/L). Erythrocyte Se indices showed no significant changes during the study period. The results demonstrate that platelet GSH-Px activity is the most sensitive index of Se status in TPN patients.
Adult↗
Spontaneous partial fracture of the catheter of a totally implantable subcutaneous infusion port.
A totally implantable subcutaneous infusion port was inserted via the left subclavian vein with peel-away sheath in a 45-year-old male patient receiving home parenteral nutrition. Sixteen months after implantation, the patient noted pain in his left clavicular region during home infusion. This was found to be due to the leakage of infusion fluid resulting from partial fracture of the catheter at the level where the catheter passed between the clavicle and first rib. Because the fracture was partial, the catheter did not embolize to the heart or large vessels. Although subcutaneous infusion ports afford patients greater freedom and the ability to lead a more active life than do external catheters, it is emphasized that there may be the risk of spontaneous catheter fracture in patients using subcutaneous infusion ports.
Catheters, Indwelling↗