Effect of adrenergic-blocking or -stimulating agents on plasma growth hormone, immunoreactive insulin, and blood free fatty acid levels in man.

In order to determine whether an adrenergic mechanism is involved in the secretion of growth hormone and insulin, the effect of adrenergic-blocking or -stimulating agents on plasma human growth hormone (HGH), immunoreactive insulin, blood free fatty acids (FFA), and glucose levels was studied in normal human subjects. The intravenous infusion of propranolol, a beta adrenergic-blocking agent, caused a rise in plasma HGH, a transient decrease in blood FFA, and no significant change in plasma insulin. This increase in plasma HGH was inhibited either by the combined administration of isoproterenol, a beta adrenergic-stimulating agent, along with propranolol or by oral glucose loading immediately before the start of propranolol infusion. The concomitant administration of epinephrine and propranolol brought about a rise in plasma HGH comparable with that produced by propranolol alone, without any significant change in blood FFA. Alpha adrenergic blockade by the intravenous infusion of phenotolamine significantly suppressed plasma HGH responses to insulin-induced hypoglycemia and to arginine infusion, and enhanced plasma insulin response to arginine infusion. It also stimulated lipid mobilization significantly. The intravenous infusion of alpha adrenergic-stimulating agents, phenylephrine and methoxamine, caused an increase in plasma HGH, a slight decrease in blood FFA, and no significant change in plasma insulin. This increase in plasma HGH was significantly inhibited by the simultaneous administration of phentolamine along with methoxamine. On the contrary, a beta adrenergic stimulant, isoproterenol, raised plasma insulin and blood FFA, and abolished the plasma HGH response to propranolol. Another beta stimulator, isoxsuprine, raised blood FFA but not plasma insulin. It is concluded that either beta adrenergic blockade or alpha stimulation enhances HGH secretion and inhibits insulin secretion and fat mobilization, whereas either alpha blockade or beta stimulation stimulates insulin secretion and fat mobilization and inhibits HGH secretion.

Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection.

The most severe form of virus-induced inflammation at the ocular surface is epidemic keratoconjunctivitis (EKC), often caused by group D human adenoviruses (HAdVs). We investigated the dynamics and mechanisms of changes in natural killer (NK) cell types in the human ocular mucosal surface in situ over the course of infection. In the acute phase of infection, the mature CD56(dim)NK cells that comprise a major subpopulation in the normal human conjunctiva are replaced by CD56(bright)NK cells recruited to the ocular surface by chemokines produced by the infected epithelium, and NKG2A-expressing CD56(dim) and CD56(bright) NK cells become the major subpopulations in severe inflammation. These NK cells attracted to the mucosal surface are however incapable of mounting a strong antiviral response because of upregulation of the inhibitory ligand human leukocyte antigen-E (HLA-E) on infected epithelium. Furthermore, group D HAdVs downregulate ligands for activating NK cell receptors, thus rendering even the mature NKG2A(-)NK cells unresponsive, an immune-escape mechanism distinct from other adenoviruses. Our findings imply that the EKC-causing group D HAdVs utilize these multiple pathways to inhibit antiviral NK cell responses in the initial stages of the infection.

Diabetic osteopenia and circulating levels of vitamin D metabolites in type 2 (noninsulin-dependent) diabetes.

The degree of diabetic osteopenia and serum vitamin D metabolite levels were measured in 168 type 2 (noninsulin-dependent) diabetic patients. Based on six indices obtained by microdensitometry, we found the bone mass in 26.2% of diabetic patients to be clearly decreased and in 11.9% to be severely decreased. Our direct method of analysis of bone mass shows that diabetic osteopenia differs from typical osteoporosis in character. In addition, serum 24,25-dihydroxyvitamin D was significantly decreased (P less than 0.01), but 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were similar to those of controls.

Enhancement of photoelastic constant of optical thin film waveguide assisted by surface acoustic wave

In the present research, we proposed a method of controlling the photoelastic constant using surface acoustic waves, which had not previously been reported, and carried out experimental studies thereof. A Bragg diffraction was carried out to determine the photoelastic constants of Ta2O5. As a result, it is confirmed that the photoelastic constant of a Ta2O5 thin film undergoing a sputtering process, during which surface acoustic waves were excited on the substrate, was about 2.19-2.27 times larger than those of thin films on which surface acoustic waves were not excited.

Effect of adrenergic blocking agents on plasma gastrin and secretin levels in man.

The effect of adrenergic blocking agents on gastrin and secretin secretion before and after a bolus arginine injection (arginine pulse) was investigated in normal subjects. Repeated arginine pulses given at 30-minute intervals caused abrupt and almost identical rises of plasma gastrin with each pulse. On the other hand, plasma secretin levels were unchanged by repeated injections of arginine. The increase in plasma gastrin induced by arginine pulse was significantly suppressed by the infusion of beta-adrenergic blocking agent, propranolol, while the infusion of alpha-adrenergic blocking agent, phentolamine tended to enhance the arginine-induced gastrin secretion slightly but not significantly. Whereas, the infusion of neither phentolamine nor propranolol had significant influence on secretin secretion. These results suggest that alpha- and beta-adrenergic receptors play an important role in the regulation of arginine-induced gastrin secretion.

Nucleotide sequence analysis of the approximately 35-kb segment containing interferon-gamma-inducible mouse proteasome activator genes.

The proteasome activator PA28 is an interferon-gamma-inducible complex made up of two related subunits, named PA28 alpha and PA28 beta, with approximately 50% amino acid sequence identity. Accumulated evidence indicates that binding of this complex to the 20S proteasome enhances the generation of class I-binding peptides. Previously, we showed that the genes coding for PA28 alpha and PA28 beta, designated Psme1 and Psme2, respectively, are located approximately 6 kb apart with their 3' ends pointing toward each other on mouse Chromosome 14. In the present study, we sequenced the regions adjacent to Psme1 and Psme2. In a contiguous stretch of approximately 35 kb, we identified six genes arranged in the following order: Cg10671-like (a gene similar to Drosophila CG10671)-Psme1-Cgi112 (a ubiquitously expressed gene with no known function)-Psme2-Flj10111 (a gene coding for a protein with two RING finger domains)-Isgf3g (an interferon-gamma-inducible gene coding for an interferon-dependent, positive-acting transcription factor 3 gamma). Interestingly, the 3' untranslated region of Psme1 overlaps with that of Cgi112 by 7 bp. Database analysis indicates that the corresponding human genes also overlap by up to 7 bp in their 3' untranslated regions. The 5' end of the mouse, but not the human, gene coding for PA28 beta undergoes alternative splicing that is predicted to alter the N-terminal amino acid sequence. Comparison of the mouse sequence with a human draft sequence deposited in the NCBI database revealed that the overall organization of the region coding for the interferon-gamma-inducible proteasome activator is conserved between human and mouse.

Effect of glucocorticoids on gastrin secretion in man.

In order to investigate the effect of glucocorticoids on gastrin secretion, plasma gastrin levels were measured by radioimmunoassay in patients with Cushing's syndrome and those treated with glucocorticoids. Fasting plasma gastrin levels were significantly higher in these patients than in normal subjects, with exaggerated response to food. Conversely, short-term treatment or intravenous infusion of glucocorticoids had no significant influence on gastrin secretion in normal subjects. The possible mechanism by which glucocorticoids cause hypergastrinaemia are discussed.

The polymorphism linked to the human insulin gene: its lack of association with either IDDM or NIDDM in Japanese.

Polymorphism of 5' portion of the human insulin gene was examined in 188 unrelated Japanese subjects (49 normal, 71 with IDDM, and 68 with NIDDM) using restriction endonuclease analysis. Restriction fragments were classified according to the insertion size: Class 1 (600 base pairs), Class 2 (1300 base pairs), and Class 3 (2000 base pairs). We found a very high frequency of Class 1 alleles (96.8%) and a low frequency of both Class 2 (0.8%) and Class 3 alleles (2.4%) and that approximately 94% of the genotypes were Class 1/Class 1 homozygote. In addition, there was no correlation of allelic or genotypic frequency with NIDDM or IDDM. We conclude that length polymorphism of the human insulin gene cannot be a useful marker for diabetes in Japanese.