Classification of Diabetes Mellitus by Studies of C-Peptide Secretory Capacity

Residual pancreatic B-cell function was investigated in children with diabetes mellitus in whom classification of the type of disease was difficult at the first visit. Intravenous glucagon tests were performed at the first visit and subsequently, the C-peptide responses compared. Based on our data on a limited number of patients, we propose C-peptide concentrations of 3.0 to 3.5 ng/ml at the peak or at 6 min after injection of glucagon, as the critical level which distinguishes non-insulin dependent from insulin-dependent diabetes mellitus. However, the degree of obesity, clinical stage and other factors also need to be considered in the classification of diabetes mellitus.     

Effects of Several Denervation Procedures on Distribution of Calcitonin Gene-Related Peptide and Substance P Immunoreactive in Rat Stomach

The effect of chemical deafferentation, vagotomy(VGX), and gangliosympathectomy (GSX) on the density offibers containing calcitonin gene-related peptide (CGRP)and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation bycapsaicin abolished the density of CGRP-immunoreactive(IR) fibers, not Sub.P-IR fibers. Ten days after VGX,the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reductionof CGRP-IR and Sub.P-IR fibers was seen in submucosaland muscular layers. GSX significantly reduced thedensity of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosaland muscular layers. Pretreatment with6-hydroxydopamine, a neurotoxin for noradrenergicnerves, did not affect the density of CGRP-IR fibers inthe gastric wall. The density of Sub.P-IR fibers in thegastric wall was not affected by GSX. These studiesindicate that the CGRP-IR and Sub.P-IR fibers in themucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and musclelayers, that a major portion of the CGRP-IR fibers inthe mucosa is of both vagal and spinal origin, and thata major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, thepresent results support that CGRP-IR fibers, notSub.P-IR fibers, in the rat stomach arecapsaicin-sensitive.     

Histopathological observations on orbital fatty tissue in dysthyroid ophthalmopathy

Seventeen specimens of orbital fatty tissue taken from cases of dysthyroid ophthalmopathy at the time of operation were observed by light and electron microscopy, and also by immunohistochemical staining. The pathological changes observed were infiltration of the chronic inflammatory cells, deposit of fibrin, sclerosis of vascular wall, occlusion of the vascular lumen, and accumulation of hydrophilic mucopolysaccharide. Immunoglobulin G was detected in fat cells and lymphocytes, and some of the infiltrating lymphocytes were determined to be T cells, by immunohistochemistry. These findings suggested that the pathology of the dysthyroid ophthalmopathy was closely related to the chronic inflammation induced by the immune reaction. The exophthalmos was considered to occur due to edema secondary to chronic inflammation and accumulation of the mucopolysaccharides.     

GM-CSF-producing CCR2+CCR6+ Th17 cells are pathogenic in dextran sodium sulfate-induced colitis model in mice

Although excessive immune responses by Th17 cells, a helper T cell subset, are implicated in the pathogenesis of inflammatory bowel disease (IBD), the mechanism by which its localization in an inflamed colon is regulated remains unclear. Chemokines and their receptors are involved in the pathogenesis of IBD, however, the relative significance of each receptor on Th17 cells remains unknown. We generated C–C motif chemokine receptor 2 (CCR2) knockout (KO) and CCR6 KO mice in the syngeneic background using the CRISPR/Cas9 system and found that the phenotypes of experimental colitis worsened in both mutant mice. Surprisingly, the phenotype of colitis in CCR2/CCR6-double knockout (CCR2/6 DKO) mice was opposite to that of the single-deficient mice, with significantly milder experimental colitis (p < .05). The same was true for the symptoms in CCR6 KO mice, but not in wild type mice treated with a CCR2 inhibitor, propagermanium. Colonic CCR2⁺CCR6⁺ Th17 cells produced a potentially pathogenic cytokine GM-CSF whose levels in the gut were significantly reduced in CCR2/6 DKO mice (p < .05). These results suggest that GM-CSF-producing CCR2⁺CCR6⁺ Th17 cells are pathogenic and are attracted to the inflamed colon by either CCR2 or CCR6 gradient, which subsequently exacerbates experimental colitis in mice.     

Longitudinal changes in the well-being of Japanese caregivers: variations across kin relationships

This study examined how the psychological well-being of Japanese caregivers changed over time; it also examined the variation across kin relationships with care recipients. Three interviews over the course of 30 months were conducted with a representative sample of community-dwelling caregivers of frail elderly persons living in a Tokyo suburb. Latent growth modeling demonstrated that mean levels of both depression and emotional exhaustion worsened over time. Change in emotional exhaustion over time showed significant individual variability, whereas change in depression showed little individual variability. Although wife caregivers tended to experience the worst trajectory of emotional exhaustion, daughters-in-law also showed a similar negative trend. The difference in individuals' well-being trajectories by kinship may be explained partly by differences in care recipients' disabilities.     

Factors related to under-utilization of in-home services under the long-term insurance system

PURPOSES: This study was conducted to examine factors associated with under-utilization of in-home services covered by the long-term care insurance. Under-utilization was measured in terms of the discrepancy rate between benefits limits and service costs for individuals. Based on the behavioral model, possible predictors were chosen; the level of nursing care as the need factor, living arrangements and income as enabling factors, and family caregiving consciousness as a predisposing factor. Both direct and interaction effects of those factors were examined. METHODS: 1,500 people were randomly selected from all people certified as needing long-term care in one ward, Tokyo to be interviewed. People categorized as "requires assistance" or "requires nursing care level 1" were interviewed directly. With people categorized as "level 2" to "level 5", their primary caregivers were interviewed. Information about in-home service utilization was collected from the insurer. RESULTS: People who were categorized as requiring a lower level of nursing care, lived with others, had a low income, or had high family caregiving consciousness demonstrated significantly greater under-utilization rate as compared with others. An interaction between living arrangements and the level of nursing was observed in this regard. While people who lived alone exhibited low a level of under-utilization rate without regard of the level of nursing care, the rate changed by those who lived with other. CONCLUSIONS: Under the new system, informal support might have a significant impact on under-utilization of in-home services. The responsibility for paying 10% of total care costs might be related to under-utilization by people with low income, though reduction of individual co-payments has been introduced for individuals in difficult financial conditions.     

Qualitative and quantitative analyses of Müller's muscle in dysthyroid ophthalmopathy

A portion of the Müller's muscle of the superior eyelid was obtained from 3 men and 6 women with dysthyroid ophthalmopathy, aged from 19 to 58 years, at the time of surgery to treat excessive lid retraction. Disturbance of ocular motility was seen in 7 out of the 9 cases. Electron microscopy of the excised portion of Müller's muscle showed that the muscles were classifiable into three types, 1) cells with normal appearance, 2) dark cells and 3) clear cells: the percentages of these cells averaged 35.7% (30.9-42.1%), 39.4% (24.8-56.3%) and 24.9% (12.8-40.0%), respectively. A quantitative analysis of the cell shape revealed that the dark cells were more irregular and the clear cells more rounded than the normal cells. The dark cells had a high electron density with a dense distribution of actin-like filaments, and the clear cells showed a low electron density with irregular cytoplasmic distribution. It was thought that the dark cells represented contractile changes and the clear cells represented degenerative changes. The dark cells appeared to decrease and the clear cells appeared to increase, as the exophthalmos increased. In 2 cases with no ocular motility disturbance, the percentage of the dark cells was higher and that of the clear cells lower than in the other cases with ocular motility disturbance. It is suggested that the contraction of the Müller's muscle contributes to lid retraction in dysthyroid ophthalmopathy and the muscles undergo degenerative changes as the ophthalmopathy progresses.     

Long-lasting effect of systemically administrated caerulein on monoaminergic neuronal pathways in rat brain

The effect of systemically administrated cholecystokinin analog, caerulein, on monoaminergic neurons was examined in discrete regions of rat brain. A single injection of caerulein (400 micrograms/kg, i.p.) significantly elevated 5-hydroxyindoleacetic acid (5HIAA) levels in the prefrontal cortex lateral field, nucleus accumbens, tuberculum olfactorium and striatum after 2 hours, together with a significant increase in striatal serotonin (5HT). Moreover, the time-course study showed that the caerulein-induced increase in both 5HIAA and 5HT levels lasted even for 24 hours, and their levels tended to recover to the control values gradually. This time-dependent change was not found in the other monoamines and their metabolites. These results suggest a long-lasting action of caerulein on 5HT neurons in specific regions of rat brain.