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Biomedical subjects

N Wada

Publications and source records attributed to N Wada.

At least 217 records · Page 12Linked to original sources
PubMed1990

Suppressor T-lymphocyte dysfunction in MCNS: role of the H2 histamine receptor-bearing suppressor T lymphocytes.

To evaluate the number and function of suppressor T cells in children with minimal change nephrotic syndrome (MCNS), we performed an inhibition test of rosette formation and measured leukocyte procoagulant activity. The number of histamine H2 receptor-bearing T lymphocytes (histamine H2 R+ lymphocytes) was markedly decreased at the onset of MCNS but gradually increased and was normalized following steroid therapy. The production of leukocyte procoagulant activity by normal T lymphocytes was abolished by incubation with patient's lymphocytes. However, pretreatment of the normal T lymphocytes with cimetidine markedly decreased the suppression. The results suggest an abnormality in the histamine H2 receptors on the patient's suppressor T lymphocytes.

Blood Coagulation Factors↗
PubMed1990

[Clinicopathological studies of 10 cases with focal segmental glomerulosclerosis].

The clinical picture, histopathological findings, therapy and prognosis of focal segmental glomerulosclerosis (FSGS) were investigated in a retrospective study involving 10 cases. The age of patient at the time of detection ranged from 3 to 19 years, 11 years on the average, being 9 years or above in 6 cases. There was noted a slight tendency toward predominance of males in this series. The disease was detected casually on the occasion of mass survey of urine at school in 6 cases (60%), while by clinical examination on visiting us with nephrotic syndrome in the other 4 (40%). Of the former 6 cases, 5 developed nephrotic syndrome while placed under medical surveillance. Nine of the 10 cases were treated mainly with corticosteroids, to which 5 (50%) were unresponsive and 4 (40%) responsive, with 1 (10%) of these 4 becoming unresponsive since a recurrence. Corticosteroids were not used in 1 case (10%). During follow-up period (which ranged from 1 to 10 years) 6 experienced an elevation of serum creatinine above 2.0 mg/dl, with 5 of them being unresponsive to corticosteroids and 3 begun on hemodialysis therapy. Histologically, cases in which the sum of the proportions of glomeruli affected with segmental sclerosis and with global sclerosis exceeded 30% and, in addition, there were severe tubulointerstitial lesions tended to have a poor prognosis, while those in which sclerosis involved less than 30% of glomeruli and no interstitial damage was discernible had a relatively favorable prognosis and were more frequently responsive to corticosteroids. These findings led us to conclude that FSGS has an ominous prognosis as reported previously and notably, the prognosis is much poorer for the non-steroid-responding type than for the responding type. The study also suggests that the degree of severity of histological changes is determinant of the prognosis of the disease.

Adolescent↗
PubMed1990

Portions of basement membrane with decreased negative charge in various glomerulonephritis.

The decrease in negative charge was evaluated in different portions of the basement membrane as well as the lamina rara externa (LRE) and lamina rara interna (LRI). The subjects were nine patients [2 patients with focal segmental glomerulosclerosis (FGS), 2 with membranoproliferative glomerulonephritis (MPGN), 3 with IgA nephropathy, and 2 with Henoch-Schoenlein purpura nephritis (HSPN)] and 2 patients with minor glomerular abnormalities and 1 with tubulo-interstitial nephritis (TIN) as controls. Polyethyleneimine (PEI) was used as a cationic probe. The basement membrane was divided into the peripheral portion (loop basement membrane 7 microns or more from the anchor portion), proximal portion (within 3 microns of the anchor portion), and the paramesangial portion in the paramesangial basement membrane. In each portion, PEI granules per 1 micron of the LRE and LRI were counted. Anionic sites were decreased in the patients with FGS and MPGN, but the damage pattern differed between the two diseases. In the patients with FGS, the decrease in anionic sites was most marked in the peripheral portion with an even greater decrease in the LRI. In the patients with MPGN, the decrease was uniform among the portions. On the other hand, no significant difference was observed in any portion between the patients with IgA nephropathy or HSPN and the controls. The portions with decreased negative charge varied among various glomerular diseases, suggesting different developmental mechanisms.

Adolescent↗
PubMed1989

Effect of nucleus raphe magnus stimulation on recurrent inhibition of the monosynaptic reflex in the cat.

Experiments were performed on 8 cats anesthetized with urethan-chloralose. The effects of nucleus raphe magnus (NRM) conditioning stimulation on recurrent inhibition of posterior biceps semitendinosus nerve (PBSt) monosynaptic reflex elicited by electric stimulation of a part of L7 ventral root were investigated in the cat. It was found that (1) the PBSt monosynaptic reflex was facilitated by NRM conditioning stimulation at 30, 50 and 80 ms conditioning-test stimulus intervals, but that (2) the inhibited monosynaptic reflex by recurrent inhibition was further inhibited by NRM conditioning stimulation at the same conditioning-test stimulus intervals, and that (3) the activity of Renshaw cells as recorded by glass microelectrode was enhanced by NRM conditioning stimulation. These facts indicated that recurrent inhibition pathways are enhanced by NRM conditioning stimulation.

Animals↗
PubMed1989

Long-lasting afterdischarge of alpha-motoneurons after muscle vibration or electrical stimulation of group I afferent fibers in the anemically decerebrated cat.

Experiments were performed on anemically decerebrated cats. Motoneuronal activity in the spinal cord was intracellularly or extracellulary recorded and muscle vibration or electrical stimulation of the peripheral nerve was applied for 1 s every 2 s. Such stimulation elicited monosynaptic responses and afterdischarge, a response which lasts after cessation of the stimuli. Stimulus frequencies from 50 to 200 Hz were effective in eliciting the afterdischarge, while frequencies higher or lower than this range of stimulation were ineffective. The interspike intervals of the motoneuron afterdischarge were almost constant and did not correspond to the stimulus frequency. The mean intervals obtained from the motoneurons examined ranged from 70 to 120 ms. Power spectrum analysis of the membrane potential ripples recorded immediately after stimulation revealed increased activity at 38 and 62 Hz components. Since the spike interval of the afterdischarge in this motoneuron was 80 ms, the interval was almost equal to 5- and 3-fold the cyclic time of the increased frequency components. This indicates that the interval of afterdischarge was determined by the specifically increased frequency components of the membrane potential ripples.

Animals↗
PubMed1989

[Prognostic factors in HIV seropositive children by materno-fetal transmission].

Ninety-four cases with HIV seropositive children who were found in the Hospital Necker Enfants Malades in France from April 1983 till September 1988 due to materno-fetal transmission were surveyed for immunological studies as well as the relationship between clinical symptoms and the prognosis. Lymphoadenopathy and/or hepatosplenomegaly were found in 98% of the total cases. Opportunistic infections, severe neurological problems and LIP were found in 28%, 16% and 15%, respectively. At the first laboratory examination, cases showing under 500/mm3 of OKT4 lymphocytes and with negative antigen-induced proliferative responses were observed in 24% and 44% of the cases, respectively. Negative serological profiles of antibodies to P18 and P25 HIV antigens appeared to show low values of OKT4 lymphocytes and abnormal responses to antigens. The survival cases with these findings were minimum. These data indicate that it is very much worth, while to estimate the degree of immunological deficiency and infectious complications.

CD4-Positive T-Lymphocytes↗
PubMed1989

Effects of eperisone-HCl on the stretch reflex in anesthetized cats.

The effect of eperisone-HCl on the spinal stretch reflex was investigated in cats anesthetized with urethane-chloralose. The reflex activity, elicited by muscle stretches, was recorded from the split ventral root and analyzed using a cross-correlation histogram between the motoneuronal spikes and muscle stretches. Eperisone-HCl was intravenously applied at a dose of 5 mg/kg. It was found that eperisone weakly inhibited the reflex activity of tonic motoneurons (approximately 30%), and that of the phasic ones was either moderately (approximately 70%) or completely (100%) inhibited by eperisone. The cross-correlation analysis suggested that the membrane potentials of both tonic and phasic motoneurons are equally lowered by eperisone or that monosynaptic transmission from primary afferents of muscle spindles to motoneurons is inhibited by eperisone.

Anesthesia↗
PubMed1989

Study of anionic sites on the mesangium in aminonucleoside nephrosis.

In recent years, various reports have appeared concerning anionic sites in glomerular lesions. However, no detailed results for anionic sites in the mesangium have been reported. The authors therefore prepared nephrotic rats by the administration of puromycin aminonucleoside (PA) and investigated the anionic sites in various mesangial regions, using polyethyleneimine (PEI) as a cationic probe. In the mesangium of the control group as well as the experimental groups, PEI particles were most numerous in the subendothelial regions, followed by the central region and paramesangial region, in that order. In the group treated with PA, the numbers of PEI particles in each mesangial region decreased as compared with those in the control group. Among the three mesangial regions considered, this decrease was most pronounced in the paramesangial region. In the group which received elastase, no significant decrease in numbers of PEI particles was observed in subgroups I and II, indicating maintenance of the anionic sites. The results obtained suggested that regional investigations of the mesangial matrix may be of considerable significance for elucidating the etiologic factors in glomerular sclerosis, and that negative charge impairment in the mesangial matrix plays an important role in the development of glomerular sclerotic lesions.

Animals↗
PubMed1988

A novel yeast secretion signal isolated from 28K killer precursor protein encoded on the linear DNA plasmid pGKL1.

Saccharomyces cerevisiae harboring linear dsDNA plasmids, pGKL1 and pGKL2, secretes a killer toxin consisting of 97, 31 and 28 kilodalton subunits (Nucleic Acids Res., 15, 1031-1046, 1987). We isolated the DNA encoding the N-terminal pre-sequence of the 28K precursor protein and constructed a new secretion vector in S. cerevisiae. Mouse alpha-amylase fused to the 28K signal sequence was secreted into the culture medium with a high efficiency similar to those fused to the mating factor alpha and 97K-31K killer signal sequences. This data clearly indicates that 28K presequence functions as a secretion signal. Glycosylated and nonglycosylated alpha-amylase molecules were detected in the culture medium. The secretion of alpha-amylase was blocked by sec18-1 mutation. The secreted alpha-amylase recovered from the medium was found to migrate faster in SDS-polyacrylamide gel than the precursor form of alpha-amylase synthesized in vitro. These lines of evidence suggest that mouse alpha-amylase fused to 28K killer signal sequence was processed, glycosylated and secreted through the normal secretion pathway of the yeast.

Amino Acid Sequence↗
PubMed1988

A murine monoclonal anti-metallothionein autoantibody recognizes a chemically synthesized amino-terminal heptapeptide common to various animal metallothioneins.

A murine hybridoma clone (MT 189-14-7) producing an IgM-class monoclonal antibody specific for metallothionein (MT) was produced with rat Zn-MT 2-keyhole limpet hemocyanin conjugate as an immunogen. The reactivity of the monoclonal antibody with MTs obtained from various animal species was determined by the competitive radioimmunoassay. The MT 189-14-7 antibody bound equally to various MTs 1 and 2 including mouse MTs 1 and 2. This indicates that the antibody is a murine autoantibody reactive with various animal MTs and recognizes a common structure of the various MTs. Subsequently, the location of the antigenic determinant recognized by the MT 189-14-7 antibody was determined by using various synthetic human MT 2 peptides. Among the synthetic peptides examined, both the amino-terminal beta-domain, Ac-(hMT 2 1-29)-OH, and an amino-terminal heptapeptide, Ac-(hMT 2 1-7)-OH, but not the carboxy-terminal alpha-domain peptides, H-(hMT 2 29-35)-OH and H-(hMT 2 30-61)-OH, showed inhibitory activities slightly higher than the native MTs in the competitive radioimmunoassay. These results demonstrate that the MT 189-14-7 autoantibody recognizes the epitope located within the amino-terminal heptapeptide common to various MTs.

Animals↗
PubMed1988

[Acute toxicity study of cefodizime sodium].

Acute toxicity of cefodizime sodium (THR-221) was examined in mice of both sexes, rats of both sexes (including 5-day-old young), and male dogs. The LD50 values of THR-221 (mg/kg) were as follows: (1) mice: intravenous, 7200 for males and 5000 for females; intraperitoneal, 10500 for males and 11000 for females; subcutaneous, 17500 for males and 16500 for females; and oral, 28000 for males and 29000 for females. (2) rats (adult): intravenous, 7000 for males and 8200 for females; intraperitoneal, 9500 for males and 8800 for females; subcutaneous, 17000 for males and 15500 for females; oral, more than 20000 for both sexes; and intramuscular, more than 3200 for both sexes. (3) 5-day-old rats: subcutaneous, 5278 for males and 5314 for females. (4) male dogs: intravenous, more than 5000. Major changes in general conditions observed in mice and rats were decreased spontaneous activity, lying prone, respiratory changes, staggering gait, clonic or clonic-tonic convulsions, and cyanosis, and in the animals dosed orally, diarrhea or salivation was also noted. The changes in 5-day-old rats were respiratory changes, agony, loss of reflex to an external stimulus, and congestion at the injection site, and those in dogs were vomiting, dryness of the nose, and soft or mucous stools. Autopsies on the mice and rats which died revealed hemorrhage on the brain surface. In addition, the following were seen: intraperitoneal retention of fluid and dark red spots on the abdominal wall (i.p.), subcutaneous retention of fluid or jellylike material and hemorrhage at the injection site (s.c.), and retention of fluid and dark red spots on the mucosa in the digestive tract (mice p.o.). In 5-day-old rats which died, the subcutaneous tissue at the injection site showed hemorrhage macroscopically and inflammatory changes microscopically. Hematological and blood chemical tests performed in dogs showed an increase in white blood cells and changes suggesting anemia, increases in GOT, LDH and ALP activities, and slight changes in urea nitrogen and inorganic phosphorus. In one animal given a low dose of 2500 mg/kg, an increase in GPT activity was also seen. However, these changes were all transient. Microscopic findings in dogs were slight inflammatory changes in the subcutaneous tissue around the injection site.

Administration, Oral↗
PubMed1988

[Six-month chronic subcutaneous toxicity study of cefodizime sodium in rats].

Six-month chronic subcutaneous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 3000, 1000, 300 and 100 mg/kg/day. The systemic change observed was slightly decreased spontaneous activity, which appeared only in a very few animals. At the injection site of the animals at 1000 and 3000 mg/kg/day, various cutaneous changes (subcutaneous retention of fluid, incrustation, loss of hair and perforation) were observed. The body weight gains of the males at 1000 and 3000 mg/kg/day were depressed from 1 month of administration onward, but the food consumption was not affected in any group. The water intakes at 1000 and 3000 mg/kg/day were increased. Hematological findings were signs of anemia, a slight decrease in red blood cell count or increases in platelet and/or reticulocyte counts in all THR-221 groups. At 3000 mg/kg/day, increases in white blood cell and neutrophil counts and a decrease in lymphocyte count were also observed. Plasma chemistry revealed decreases in total protein amount and, albumin (A) or globulin (G) amounts, and a decrease or increase in A/G ratio in all compound groups. Autopsy revealed dilation of the cecum and hematoma, dark red spots and yellowish brown spots in the subcutaneous tissue at the injection site in all THR-221 groups. Hypertrophy of the spleen was also noted at 300-3000 mg/kg/day. Changes in organ weights were a decrease in liver weight in all compound groups and an increase in spleen weight at 3000 mg/kg/day. Microscopically, the following were observed: brown granules or hyaline droplets in the epithelium of renal tubules; hemorrhage and inflammatory changes in the subcutaneous tissue at the injection site; and an increased number of lymphocytes or granulocytes in the spleen and bone marrow. Urinalysis and ocular and auditory tests showed no changes related to THR-221. From the present results, the toxicologically non-effective doses of THR-221 are considered to be 300 mg/kg/day for male rats and more than 1000 mg/kg/day for female rats.

Anemia↗
PubMed1987

A novel yeast secretion vector utilizing secretion signal of killer toxin encoded on the yeast linear DNA plasmid pGKL1.

The NH2-terminal signal region comprising of approximately 70% length of the prepro-sequence of the pGKL killer precursor protein was found to direct an efficient secretion of the mouse alpha-amylase into the culture medium of Saccharomyces cerevisiae. The alpha-amylase molecule secreted into the culture medium was identified by both immuno-blotting and assay of the enzyme activity. The amount of alpha-amylase secreted via the killer toxin signal was comparable to that directed by the leader sequence of mating factor alpha. The secretion of alpha-amylase using the killer toxin signal was blocked at 37C but not at 25C in sec18-1 host, indicating that alpha-amylase is exported through the normal secretion pathway of S. cerevisiae.

Amino Acid Sequence↗
PubMed1987

Expression and identification of immunity determinants on linear DNA killer plasmids pGKL1 and pGKL2 in Kluyveromyces lactis.

The linear dsDNA plasmids, pGKL1 (8.9 kb) and pGKL2 (13.4 kb) discovered in Kluyveromyces lactis, confer killer and immunity characteristics upon various yeast strains. We have devised an immunity assay and have been able to show the expression of an immunity phenotype in the K. lactis transformants harbouring conventional circular plasmids which contain DNA fragments of pGKL1. Using this expression system, the immunity determinant on pGKL1 was identified as ORF5. In addition, the presence of pGKL2 was proved to be essential for the expression of the immunity phenotype. This is the first demonstration of this new pGKL2 function, as distinct from its known functions for the replication and maintenance of pGKL1 in yeast cells.

DNA Restriction Enzymes↗