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Biomedical subjects

T Sakaguchi

Publications and source records attributed to T Sakaguchi.

At least 235 records · Page 13Linked to original sources

Electrophysiological evidence for terminal sprouting of locus coeruleus neurons following repeated mild stress.

To see if repeated mild stress causes plastic changes in central noradrenergic terminal axons, the density of terminal axons arising in locus coeruleus (LC) neurons of rats was quantified by antidromic stimulation technique. After the termination of stress treatments (immersion in warm water for 10 min daily) for 1 or 2 weeks, electrophysiological experiments were performed under urethane anesthesia. The frequency of LC neurons activated antidromically from the cerebral cortex increased in rats stressed for 2 weeks but not for 1 week. Since the increased frequency of antidromic responses was not due to a change in terminal excitability, the change observed here is considered to be morphological (terminal sprouting) rather than a physiological consequence. The results suggest that LC neurons dynamically alter their terminal morphology in response to environmental stimuli.

Action Potentials↗

Pancreatic vagal functional distribution in the secretion of insulin evoked by portal infusion of D-glucose.

The vagus glucose signal pathway relevant to hepatic portal control of insulin secretion was examined in bilaterally adrenalectomized rats. The increase in the insulin concentration after portal glucose injection was completely blocked by vagotomy of the hepatic branch which is bifurcated from the ventral vagus trunk at the subdiaphragmatic level. At the cervical level, the reduction in the insulin concentration showed no laterality following vagotomy on either side. The insulin response was mainly suppressed by prior section of the branch of the ventral vagus trunk at the celiac level. These results suggest that the hepatic glucose signal evoking insulin release has a specific pathway from the liver to the pancreas, and that there is functional laterality in this pathway in the visceral cavity.

Adrenalectomy↗

Systemic lupus erythematosus of childhood onset: correlation between T cells expressing early and late activation antigens and disease activity.

Correlation between T cell phenotypes, especially activated T cells expressing early (EA1) and late (HLA-DR) activation antigens and clinical features were investigated in 22 patients with systemic lupus erythematosus (SLE) of childhood onset. Percentages of T cells expressing EA1 and HLA-DR in 22 patients with SLE were significantly higher than those in controls. Comparison of T cell phenotypes between patients with active and inactive SLE showed that eight patients with active disease had significantly increased percentages of HLA-DR positive T cells than 14 with inactive disease (P less than 0.01). Serial examinations showed that the percentages of HLA-DR positive T cells were decreased after therapy in seven with active non-renal or active non-renal and renal diseases but not in one with only active renal disease. A possible significance of T cells expressing EA1 and HLA-DR in the management of patients with SLE is discussed.

Adolescent↗

Effect of a high-fat diet on firing rate of sympathetic nerves innervating brown adipose tissue in anesthetized rats.

Three experiments have examined the effects of ad lib and forced intake of a high-fat diet on sympathetic firing rate to brown adipose tissue. Seven days after beginning of ad lib intake of either a low-fat or high-fat diet, sympathetic activity was not significantly different in either group nor was it significantly different from the values obtained in animals measured at the switch from the chow to a semisynthetic high- or low-fat diet. After 22 days on the semisynthetic diet, however, the sympathetic firing rate of animals eating the high-fat diet had decreased nearly 25% and was significantly lower than the animals maintained on the semisynthetic low-fat diet or animals studied at the transition from the chow to the low-fat diet. In a second experiment animals were tube-fed for 3, 6 or 9 weeks on a high- or low-fat diet. Sympathetic firing rate of the rats eating the low-fat diet was higher at all three times, but the difference decreased with longer feeding. To eliminate differences in food intake, animals were tube-fed a moderate- or high-fat liquid diet three times a day for six days. The 80 kcal/day intake produced a steady weight gain in both groups. Liver weight, retroperitoneal white adipose tissue weight, and interscapular brown adipose tissue weight were all significantly greater in the animals fed the high-fat diet. Sympathetic firing rate, however, was significantly lower in the animals fed the high-fat semisynthetic diet as compared to animals fed the moderate-fat diet. These data show the high-fat diets are associated with a reduction in sympathetic activity to brown adipose tissue.

Adipose Tissue, Brown↗

Newcastle disease virus evolution. I. Multiple lineages defined by sequence variability of the hemagglutinin-neuraminidase gene.

We compared the hemagglutinin-neuraminidase gene sequence among 13 strains of Newcastle disease virus (NDV) isolated over the last 50 years. Although overall homology was remarkably high, the sequence variability demonstrated the existence of at least three distinct lineages, which must have co-circulated for considerable periods. The sequence variability also appears to reflect some accumulation of mutations over time. Strictly correlating with the lineages, the translation products could be classified into three size classes. One class lacked the interchain disulfide bond, and another represented unusual precursor protein of biologically inactive form. The lineages correlated to some extent with virulence and place of isolation of the strains. However, antigenic variations, which were neither cumulative nor progressive, did not correlate with the lineages. These analyses showing multiple lineages were greatly facilitated by a precise calculation of synonymous substitutions, which had been largely free from selective pressures and had occurred frequently and evenly throughout the coding region.

Amino Acid Sequence↗

Newcastle disease virus evolution. II. Lack of gene recombination in generating virulent and avirulent strains.

Sequence analysis and comparison of the fusion glycoprotein genes of 11 Newcastle disease virus (NDV) isolates indicated a high degree of functional and structural constraint exerted on the change of the glycoprotein. However, synonymous nucleotide substitutions occurred frequently throughout the coding region. Facilitated by an analysis of synonymous difference (Ks) in pairwise strain comparison, we defined the branching orders of the strains and identified three distinct evolutionary lineages correlating with the virulence as expressed by mean death time (MDT) for chick embryo. The typically virulent strains with MDT of about 50 hr were associated with one lineage, while the typically nonvirulent strains with MDT of infinity were of another lineage. The third lineage consisted of both virulent and avirulent strains whose MDTs lay on a continuum from 50 to 120 hr. Synonymous substitutions were found to occur with almost the same rates in the adjacent hemagglutinin-neuraminidase and membrane protein genes as in the fusion protein gene, and the branching orders based upon the Ks for these genes were essentially identical to those derived from the fusion protein gene. Therefore, no gene exchange by recombination seems to have occurred to generate the strains of distinct lineages. Rather, the different strains appear to have evolved through various degrees of accumulation of point mutations. Besides these evolutionary features, the present study strongly supports the importance of the previously identified signals for gene expression and for the proteolytic activation of the gene product.

Animals↗

Endoproteolytic activation of Newcastle disease virus fusion proteins requires an intracellular acidic environment.

Effects of weak bases, chloroquine and ammonium chloride, on the intracellular cleavage of the fusion protein precursor (F0) were examined in BHK cells infected with a virulent strain of Newcastle disease virus (NDV). Most of F0 molecules synthesized during a 15-min pulse period were chased out because of cleavage into F1 and F2 within a 60-min chase period in the absence of the weak bases. In contrast, significant amounts of the precursor were found to remain uncleaved when chloroquine or ammonium chloride was present. The uncleaved fusion proteins were incorporated into progeny virions as efficiently as cleaved ones, and about the half of fusion proteins were present as F0 in the virion released by the cells treated with 0.3 mM chloroquine. Taken together with the finding that the trans cisternae of Golgi apparatus and forming secretory vesicles have an acidic pH (K. G. W. Anderson and R. K. Pathak, Cell, 40, 685-643, 1985), the present results suggest that an acidic environment in these compartments is required for intracellular proteolytic activation of NDV fusion proteins.

Ammonium Chloride↗

Improved bone mineral status in very low birthweight infants fed human milk mixed with preterm formula.

The bone mineral status of very low birthweight (VLBW) infants fed exclusively their own mother's milk (group I) was compared with that of VLBW infants fed mother's milk in the initial 4 weeks followed by a 1:1 mixture of mother's milk and preterm formula containing high phosphorus (P) and calcium (Ca) (group II). In both groups, most infants showed a biochemical picture characteristic of phosphorus deficiency syndrome by the fourth week. Thereafter, serum alkaline phosphatase activity (ALP) decreased and serum P increased in all group II infants. Conversely, serum ALP rose and hypophosphatemia persisted in most group I infants. Group II had a significantly higher serum P at weeks 8 and 12 and a significantly lower ALP at week 12 than group I. Furthermore, group II had a lower incidence of severe radiographic abnormalities than group I at week 12. We confirmed previous observations that VLBW infants fed exclusively human milk require P and Ca supplementation to prevent metabolic bone disease of prematurity.

Bone and Bones↗

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.

The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors.

Anti-Bacterial Agents↗

Changes in relationship between blood glucose level and plasma 1,5-anhydroglucitol level in KK mice.

We compared the relationship of the blood glucose level to the plasma 1,5-anhydroglucitol (1,5AG) level between KK mice with abnormal glucose metabolism and ICR mice as controls. Although the plasma 1,5AG level did not show any significant correlation with the blood glucose level in the controls, it tended to logarithmically decrease with the rise in the blood glucose level in KK mice. Thus it is possible that the plasma 1,5AG level is specifically related to the abnormal glucose metabolism in this model of diabetes mellitus and that its routine examination in diabetic patients may help delineate the metabolic derangement in the disease.

Animals↗

Changes in the electrical activity of locus coeruleus neurons in pregnant rats.

Under urethane anesthesia, unit activity of locus coeruleus (LC) neurons was recorded extracellularly in pregnant and non-pregnant rats. The spontaneous firing of LC neurons was found to be reduced in pregnant rats. In addition, biochemical studies indicated that noradrenaline contents in the cerebral cortex, one of the major projection sites of LC neurons, were significantly higher in pregnant than non-pregnant rats. These results suggest that the electrical activity of noradrenergic neurons in the LC is reduced during gestation.

Action Potentials↗

Hepatic portal injection of glucose elevates efferent sympathetic discharges of interscapular brown adipose tissue.

Efferent sympathetic discharges of interscapular brown adipose tissue were recorded after three different concentrations of glucose (138, 277, and 416 mM) and 154 mM NaCl were injected into the portal vein or into the right jugular vein. When injected into the portal vein there was a significant increase in the discharge in response to both concentrations of glucose (277 and 416 mM), whereas only 416 mM glucose solution could cause an increase in the discharge when injected into the right jugular vein. There was no appreciable change in the discharge following the NaCl injections into the portal and jugular veins, and the portal glucose responses in the discharge were abolished by transection of the hepatic branch of the vagus nerve. Since stimulated sympathetic activity has been shown to elevate thermogenesis of the adipose tissue, these findings suggest that vagal glucose signals derived from the portal vein may be involved in the regulation of heat production of this tissue.

Adipose Tissue, Brown↗