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Biomedical subjects

N Wada

Publications and source records attributed to N Wada.

At least 127 records · Page 7Linked to original sources

Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis.

Branched chain amino acids (BCAAs) and glutamine are both recommended in catabolic states. The object of this study was to compare the efficacies of alanylglutamine (Ala-Gln)-enriched and BCAA-enriched total parenteral nutrition (TPN) on the protein kinetics in peritonitis. Rats were divided into Ala-Gln and BCAA groups after intraperitoneal implantation of an osmotic pump, delivering a continuous infusion of Escherichia coli. Glutamine composed 30.0% (w/v) of the total amino acids in the Ala-Gln group, and BCAA composed 30.5% (w/v) of the total amino acids in the BCAA group. The two solutions were isocaloric and isonitrogenous. Whole body protein turnover and organ fractional protein synthetic rates (FSR) were measured on days 3 and 5. Serum amino acid levels and mucosal morphology were determined. Ala-Gln group had higher rates of whole body protein turnover, and hepatic FSR on both days. Serum glutamine levels correlated with hepatic and muscle FSR. Ala-Gln TPN group had greater mucosal thickness, numbers of mitoses per crypt, and FSR in distal intestine. Ala-Gln-enriched TPN may be a useful nutritional treatment modality in sepsis.

Amino Acids↗

Characteristics of juvenile dermatomyositis in Japan.

Questionnaires were sent to 1290 hospitals in Japan asking for data on patients with juvenile dermatomyositis (JDM) diagnosed between June 1984 and May 1994. Of the 204 patients identified by these questionnaires, 102 met the criteria for JDM. JDM is categorized into three subtypes: Banker-type JDM, Brunsting-type and fulminant-type; patients with the latter exhibit markedly elevated serum levels of creatinine phosphokinase (> 10,000 U/mL) and appear to be at risk of renal failure. Cutaneous manifestations were present in 98% of patients and preceded the appearance of other symptoms. This tendency is one of the reasons for the difficulty in some cases in diagnosing the onset of JDM. Better criteria for early treatment of JDM are needed. The results of the present study suggest that itching and calcinosis are factors that indicate a poor prognosis in patients with JDM. Muscle enzyme levels do not always reflect disease activity, suggesting that methods other than measurement of muscle enzymes, such as measurement of the levels of neoprerin and von Willebrand factor antigen, as well as magnetic resonance imaging should be used to be evaluate disease severity. Patients with Brunsting-type JDM who exhibit dysphagia and antinuclear antibody positivity and patients with Banker-type JDM should be treated aggressively. Pulse therapy should be selected as the initial therapy in patients with fulminant-type JDM.

Child↗

A monoclonal antibody affects chromophore apoprotein interactions of phytochrome A.

A monoclonal antibody designated Mep-1 was raised against phytochrome A from pea (Pisum sativum L.). The binding of this antibody (class IgG1) to partially degraded phytochrome (114 kDa) caused a considerable increase in the far-red peak at the red-light-induced stationary state. The effect reached a plateau value when the antibody and phytochrome were present in approximately equimolar amounts. The dark transformation of the far-red-light-absorbing form to the red-light-absorbing form of the 114 kDa phytochrome was inhibited by the addition of the antibody. However, binding of the antibody to the undegraded 121 kDa phytochrome had no effects on the spectrum of the red-light-induced steady state. The site at which the antibody bound to phytochrome was determined to be between amino acid residues 256 and 383 of pea phytochrome A. This is the first report of a monoclonal antibody that enhances the far-red absorption of phytochrome in the red-light-induced photostationary state.

Animals↗

A monoclonal antibody against very late activation antigen-4 inhibits eosinophil accumulation and late asthmatic response in a guinea pig model of asthma.

Preferential eosinophil accumulation is a characteristic of airway inflammation in asthma. Although little is known about its mechanism, recent in vitro observations suggest that the very late activation antigen-4 (VLA-4, CD49d/CD29) and vascular cell adhesion molecule-1 (VCAM-1) adhesion pathway may be involved in specific eosinophil migration. To test this hypothesis, we studied the effect of an anti-VLA-4 monoclonal antibody (mAb) on the airway eosinophilia in a guinea pig model of asthma. Guinea pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed a striking airway eosinophilia and late asthmatic response (LAR). In contrast, when guinea pigs were pretreated intravenously at 2 h before antigen challenge with a rat antimouse VLA-4 mAb, PS2/3, cross-reacting with guinea pig eosinophils and lymphocytes, eosinophil, basophil and lymphocyte infiltration in the tracheal wall was significantly inhibited as well as LAR in a dose-dependent manner. These results suggest that VLA-4 plays a critical role in antigen-induced airway eosinophilia and LAR.

Animals↗

Intra-amniotic interleukin-1 alpha treatment alters postnatal adaptation in premature lambs.

We measured the physiological and biochemical responses of preterm lambs to intra-amniotic injection of interleukin-1 alpha (IL-1 alpha). Singleton lamb fetuses at 126 days of gestation were randomized to receive 125 micrograms IL-1 alpha or vehicle control via ultrasound-guided intra-amniotic injection. Each lamb was delivered 48 h later by caesarian section and ventilated for 120 min. Relative to controls, IL-1 alpha-treated lambs had higher dynamic compliance, ventilatory efficiency indices, and saturated phosphatidylcholine levels (all p < 0.05). Umbilical cord plasma cortisol and catecholamine levels, white blood cells and differentials, cardiac output, regional blood flow, and kidney function did not differ between the groups. However, at 120 min after delivery, the cortisol levels for IL-1 alpha-treated animal were higher than for controls. Single intra-amniotic IL-1 alpha treatment increases surfactant pool size and improves dynamic compliance in the absence of an inflammatory response or differences in other indicators of fetal or newborn organ function.

Adaptation, Physiological↗

A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred.

Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasians. To our knowledge, no such documentation on Asians exists. Six of 8 members of a 3-generation Japanese family were found by us to carry the FDH phenotype. Serum total T4 levels ranged from 1763.2-2741.3 nmol/L (normal range, 65.6-164.7), serum total T3 levels ranged from 2.73-5.62 nmol/L (normal range, 1.47-2.95), and rT3 levels ranged from 1.08-2.52 nmol/L (normal range, 0.22-0.60). In the proband, the majority of [125I]T4 in serum T4-binding proteins was distributed in albumin fractions, and the isolated albumin had an increased affinity for T4. A guanine to cytosine transition in the second nucleotide of codon 218, resulting in replacement of normal arginine with proline, was detected in 1 of 2 alleles in all 5 subjects of the family with FDH. In all FDH-affected Caucasian subjects from 10 unrelated families with a moderate increase in serum T4, the guanine to adenine transition was demonstrated at the same position of the albumin gene as noted in our patients, but histidine, the replacement amino acid, differed from proline noted in our FDH Japanese subjects. It would thus appear that FDH has ethnic variations.

Adult↗

Distribution of motoneurons innervating tail muscles in the pigeon.

The distribution of motoneurons innervating the tail muscles, M. levator caudae, M. depressor caudae, M. pubocaudalis externus, M. pubocaudalis internus, M. lateralis caudae and M. flexor cruris, in the adult pigeon was examined by retrograde transport of horseradish peroxides. Labeled motoneurons innervating tail muscles were distributed in the longitudinal column of the spinal cord below the sacral spinal segment 5. The average diameter of cell bodies ranged from 23.7 to 62.5 microns. Each motoneuron pool was localized in a characteristic position in the ventral horn.

Animals↗

Rhythmical discharges recorded from cervical and trunk muscle nerves produced by stimulation of mesencephalic locomotor region (MLR) in the decerebrated cat.

This experiment investigated the effects of mesencephalic locomotor region (MLR) stimulation on cervical and trunk motoneurons in decerebrated cats. The experiments were performed on 28 adult cats (2.1-3.9 kg) of either sex. Stimulation of MLR produced the rhythmical discharge of muscle nerves of the splenius (SP), the longissimus lumborum (LL) and the obliquus externus abdominis (OEA). There was a close relationship between rhythmical discharge of SP, LL or OEA muscle nerve and hindlimb muscle nerve. This fact suggests that rhythmical discharges of cervical and trunk muscle nerves relate to locomotion.

Animals↗

Discharge of cutaneous afferent fibers innervating tail during passive tail movements in cats.

The discharge of cutaneous afferents innervating the tail were recorded from 145 single afferent fibers in 11 spinalized cats (conduction velocity: 32-58 m/s) during sinusoidal tail movements. Cutaneous afferent fibers were roughly classified into two groups, slowly-adapting (SA) and rapidly-adapting fibers (RA). The discharge patterns of afferent fibers during passive tail movements depended on the receptive field on tail skin. The results of the present experiments show that peripheral inputs from cutaneous afferent fibers sent various information regarding tail movement and position to central nervous systems.

Animals↗

[Uncoupling of cerebellar blood flow and metabolism in paraneoplastic cerebellar degeneration: report of a case].

We report a 65-year-old woman with paraneoplastic cerebellar degeneration (PCD) who showed reduced cerebellar metabolism with preserved blood flow. She was admitted to Gunma University Hospital because of progressive gait and speech disturbances. Neurologic examination revealed nystagmus, dysphagia, explosive speech, reduced muscle tone in limbs, and marked truncal and limb ataxia, and mild hypesthesia in hands and feet. Cranial MRI demonstrated slight cerebellar atrophy. Laboratory findings disclosed high levels of serum CA19-9 and other tumor markers, and positive anti-Yo antibody, indicating that she had PCD. A specimen obtained from an axillary lymph node revealed metastasis of poorly differentiated adenocarcinoma, although systemic and vigorous checkup failed to find its origin. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured using positron emission tomography (PET) 15 months after the onset. CMRO2 was clearly decreased in the cerebellum, while CBF was almost normal. Moreover, PET with 2 18F-fluoro-2-deoxy-D-glucose (FDG) revealed that glucose metabolism was also reduced in the cerebellum. Single photon emission tomography using 99mTc-ethyl cysteinate dimer (ECD) showed a normal blood flow pattern in the whole brain. These results indicated that uncoupling of circulation and metabolism in the cerebellum of this patient. There are several reports showing uncoupling of cerebral perfusion and metabolism in ischemic disorders, encephalitis, mitochondrial diseases, brain tumors, epilepsy and Gaucher disease, although its pathophysiology is not elucidated. Because anti-Yo antibody evidently gives a suppressive influence on the cerebellar neurons, understanding the way the autoantibody acts may give a clue to the mechanism of reduced cerebellar metabolism with preserved perfusion in PCD.

Adenocarcinoma↗

Morphological changes in the masseter muscle and its motoneurons during postnatal development.

BACKGROUND: It has been suggested that the morphological properties of the masseter muscle are changed by the masticatory activity pattern. In the rat, the activity pattern of the muscle alters from sucking to biting around 3 weeks after birth. The working hypothesis in this study is that the unique alteration in masticatory activity has an important influence on the development of the masseter muscle and its motoneurons. METHODS: We examined the morphological changes in the muscle fibers of the superficial masseter muscle and its motoneurons from 2 days to 280 days after birth in the rat. The change in masseter muscle activity sucking and biting was confirmed by electromyography. To label motoneurons innervating the muscle, horseradish peroxidase was injected into the muscle. The muscle and lower brain stem were sliced and processed histochemically to measure the diameters of muscle fibers and its motoneurons in the trigeminal motor nucleus. In addition, composition of myosin heavy chain (MHC) isoforms of the muscles were analyzed using gradient sodium dodecyl sulphate-polyacrylamide gel electrophoresis. RESULTS: There was a rapid growth in both types of muscle fibers (fast-twitch oxidative glycolytic muscle fibers and fast-twitch glycolytic fibers) for 42 days after birth, and then a gradual growth lasting until 280 days after birth. Particularly, rapid growth of the muscle fibers was seen between 21 days and 42 days after birth. A large amount of neonatal type MHC disappeared between 21 days and 42 days after birth. In the motoneuron, there was a rapid growth of motoneurons by 42 days after birth but no significant growth was seen thereafter. CONCLUSIONS: These results suggest that the alteration of mastication activity from sucking to biting has a significant influence on morphological development of both types of muscle fibers, but not on that of motoneurons innervating the masseter muscle.

Animals↗

Changes in serum levels of metalloproteinases and their inhibitors by treatment of chronic hepatitis C with interferon.

We treated 18 patients with chronic hepatitis C by recombinant interferon-alpha (6 MIU for 24 weeks). In seven patients, serum aminotransferase levels declined to normal (responders). To evaluate the effect of interferon on matrix metalloproteinases (MMPs) and their inhibitors, namely tissue inhibitors of metalloproteinases (TIMPs), the serum levels of these enzymes were determined by enzyme immunoassay (EIA) using a specific monoclonal antibody. In responders, there was a tendency, but not a significant one, towards either an increase in serum MMP 1 levels or a decrease in serum TIMP 1 levels. In contrast, in nonresponders, both a significant decrease in MMP 1 and MMP 3 and a significant increase in TIMP 1 were observed. The number of cases of either increase in serum MMP levels or decreased in serum TIMP levels was significantly larger in responders than in nonresponders. Furthermore, the ratio of MMP 1 to TIMP 1 significantly increased in responders, suggesting that the balance between matrix formation and degradation in hepatic fibrosis tended to move toward degradation. These data indicate that interferon may exert a beneficial effect on hepatic fibrosis in parallel with improvement of aminotransferase activity.

Adult↗

Pancreatic exocrine function during acute exacerbation in WBN/Kob rats with spontaneous chronic pancreatitis.

CONCLUSION: Pancreatic exocrine hypofunction is markedly deteriorated during acute exacerbation in a rat model with chronic pancreatitis. BACKGROUND: Little is known about pancreatic exocrine function during acute exacerbation in patients with chronic pancreatitis. We investigated changes in pancreatic exocrine function after inducing acute pancreatitis in an animal model of spontaneous chronic pancreatitis. METHODS: WBN/Kob rats with chronic pancreatitis sequentially underwent pancreatic exocrine function test 1-6 d after surgical preparation with external pancreatic fistula. We induced acute pancreatitis in another WBN/Kob rats by i.v. administration of cerulein at a rate of 10 micrograms/kg/h for 4 h 4 d after surgical preparation. Pancreatic exocrine function test was undertaken in a conscious state 1 d before and after cerulein administration. RESULTS: In WBN/Kob rats not given cerulein, pancreatic exocrine function remained almost constant at 3-6 d after surgery. Marked hyperamylasemia developed immediately after cerulein administration. After its administration, the pancreas microscopically showed prominent interstitial edema and intracellular vacuolization of acinar cells in addition to the finding of pre-existing chronic pancreatitis. Basal and cholecystokinin-stimulated flow rate, bicarbonate output, and protein output, which were substantially impaired 1 d before cerulein administration, were further reduced 1 d after its administration.

Acute Disease↗

Preoperative change of thyroid stimulating hormone receptor antibody level: possible marker for predicting recurrent hyperthyroidism in patients with Graves' disease after subtotal thyroidectomy.

To make the surgical treatment for Graves' disease more ideal, it is important to elucidate factors related to postoperative thyroid dysfunction in addition to thyroid remnant. Because TSH receptor antibody (TRAb) is thought to be one of the essential causes of Graves' disease, we investigated whether preoperative changes in serum TRAb levels are related to postoperative recurrent hyperthyroidism. Between 1987 and 1992 a total of 1520 patients with Graves' disease were treated by subtotal thyroidectomy. Of these patients 335 visited Ito Hospital with no history of drug treatment of their disease and were treated surgically after several courses of antithyroid drug (ATD) therapy. There were 68 males and 267 females with a mean age of 25.8 years. The mean follow-up period was 48 months (range 12-84 months). Factors analyzed by univariate and multivariate analysis were as follows: age, sex, duration of ATD treatment, weight of resected thyroid, weight of thyroid remnant, preoperative titer of MCHA, TRAb at the time of initial examination (TRAb1), TRAb at the time of surgery (TRAb2), and DeltaTRAb, the difference between TRAb1 and TRAb2 (DeltaTRAb = TRAb1 - TRAb2). The chi-square test was used for univariate analysis and a logistic model for multivariate analysis. Of this group, 119 patients were euthyroid (35.5%), 50 were hyperthyroid (14.9%), and 166 were hypothyroid (49.3%). Significant factors related to recurrent hyperthyroidism were weight of thyroid remnant and DeltaTRAb in both univariate and multivariate analyses. DeltaTRAb is a possible new marker for predicting postoperative recurrent hyperthyroidism. If the preoperative TRAb level is not improved by ATDs in patients with Graves' disease, the thyroid remnant should be made smaller.

Adolescent↗

Stable expression and secretion of the B-cell epitope of rodent malaria from Mycobacterium bovis BCG and induction of long-lasting humoral response in mouse.

The live bacterial vaccine Mycobacterium bovis BCG (BCG) is a vehicle worth noticing for various protective antigens. The gene encoding the B-cell epitope of the oligopeptide repeating in the circumsporozoite protein (C.S. protein) of the rodent malaria parasite, Plasmodium yoelii, was inserted into the plasmid vector under the control of an expression cassette carrying the promoter and signal sequence of the a antigen derived from Mycobacterium kansasii (k-a). The B-cell epitope was successfully expressed and secreted from BCG as a fusion protein with k-a. This recombinant BCG was administered subcutaneously into BALB/c mice and the antibody production was measured by the enzyme-linked immunosorbent assay (ELISA). Long lasting humoral response was found in one of seven mice.

Animals↗

Therapeutic efficacy of pamidronate in combination with chemotherapy to bone metastasis of breast cancer in a rat model.

Bone metastasis is clinically often recognized in breast cancer patients, and in the progression of bone destruction due to bone metastasis, osteoclastic bone resorption is an important step. Therefore, drugs such as bisphosphonates-which have anti-osteoclastic activity-are expected to inhibit the progression of bone metastasis. However, bisphosphonates demonstrate no cytotoxic effects for cancer cells. In the present study we have evaluated the therapeutic efficacy of pamidronate (3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid) combined with mitomycin C (MMC) on bone metastasis of breast cancer using an animal model. The model for bone metastasis was developed by injecting c-SST-2 (spontaneously developed rat mammary adenocarcinoma in a SHR rat) cells into the thoracic aorta of 45-46 day-old female SHR rats. Three weeks after the tumour cell injection, these 48 animals were divided into four groups: control, n = 16; pamidronate, n = 12; MMC, n = 10; pamidronate with MMC, n = 10). In order to evaluate therapeutic effects on bone metastasis in each animal, the whole spine was harvested for histological examination. The bone metabolic markers used were: pyridinoline/creatinine (Pyd/Cr), deoxypyridinoline/creatinine (Dpd/Cr), bone alkaline phosphatase (BAP), and osteocalcin-measured 1 week after therapy. Histological scores of bone destruction in the treatment groups were lower than those of the control, and there were no differences among treatment groups. Although the values of Pyd/Cr and Dpd/Cr in the treatment groups, including pamidronate, were significantly lower than those in the control (P < 0.05), the other markers did not differ. It was suggested that pamidronate inhibited the progression of bone resorption, mainly by osteoclast activation due to bone metastasis, and Pyd/Cr and Dpd/Cr could be useful in part as a marker which reflects therapeutic effect. However, no additional effects were observed when it was combined with MMC.

Animals↗

Long-lasting immune response induced by recombinant bacillus Calmette-Guérin (BCG) secretion system.

The recombinant bacillus Calmette-Guérin (rBCG) secretion system utilizing an extracellular alpha antigen of Mycobacterium kansasii (alpha-K) was characterized biochemically and immunologically. The human immunodeficiency virus type 1 (HIV-1) p17gag B cell epitope fused to alpha-K was secreted in extremely large amounts. At least three mice out of seven inoculated with rBCG generated high titres of antibody to the epitope. The long-lasting antibody production persisted more than 14 months.

Amino Acid Sequence↗