Insulin secretion and carbohydrate metabolism in the dystrophic mouse.

Dystrophic mice were investigated with regard to their regulation of blood glucose and insulin secretion in vivo. The following were also measured: tissue glycogen levels, activity of the glycogenolytic hydrolase, acid amyloglucosidase, and in vitro glucose utilization by liver, muscle and adipose tissue. Basal levels of blood glucose and plasma insulin of dystrophic mice were essentially within the same range as in the clinically unaffected littermate controls. Dystrophic mice had a decreased tolerance to glucose and glibenclamide; the secretion of insulin in response to these secretagogues was moderately reduced. Insulin release following beta-adrenergic stimulation, however, was increased in the dystrophic mice. Glycogen levels and acid amyloglucosidase activity were increased in dystrophic muscles but were normal in liver. Acid amyloglucosidase activity in pancreatic islets was lower in the dystrophic mouse. Glucose utilization in vitro appeared normal in liver tissue from dystrophic mice; in dystrophic muscle there was a threefold increase in 14CO2-production with no concomitant increase in either glycogen or 14C-incorporation into glycogen. 14CO2 production and 14C-incorporation into lipid and glycogen were increased in dystrophic adipose tissue. We suggest that the decreased glucose tolerance, and the reduced insulin response to glucose in the dystrophic mouse are compensated by an increased glucose utilization in muscle and adipose tissue and an increased beta-adrenergic-mediated secretion of insulin.     

Disproportionately severe calcinosis cutis in an 88-year-old patient with CREST syndrome

An 88-year-old woman with CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) presented with hyperglycemia, intravascular depletion, and atrial fibrillation. The patient was found to have unusually severe calcinosis cutis in both legs extending from the knees to the ankles bilaterally, as well as Raynaud’s phenomenon, sclerodactyly, and telangiectasias. The patient was normocalcemic and normophosphatemic. Although subcutaneous calcification is often seen with CREST syndrome, this case is unusual in that the area of involvement was much larger than previously described. Furthermore, the amount of calcinosis was disproportionately severe and was the major cause of symptoms and disability compared with the other components of the syndrome. Received: 1 February 2001 Revision requested: 21 March 2001 Revision received: 3 April 2001 Accepted: 4 April 2001     

痒疹样营养不良型大疱性表皮松解症误诊1例

患者女,46岁。反复双下肢结节、水疱13年,加重伴泛发全身2年。先后在各地多家医院进行了4次组织病理检查,诊断为"痒疹、扁平苔藓"等。躯干背部、肘关节、双下肢胫前对称性分布紫红色丘疹、斑块,部分斑块上可见水疱,Nikolsky征阴性,局部见散在抓痕、结痂。皮肤病理示表皮下裂隙形成,直接免疫荧光结果IgG,IgA,IgM,C1q,C3a均阴性。确诊为痒疹样营养不良型大疱性表皮松解症。     

Cytoskeletal alterations differentiate presenilin-1 and sporadic Alzheimer’s disease

Most cases of Alzheimer’s disease (AD) are sporadic in nature, although rarer familial AD (FAD) cases have provided important insights into major pathological disease mechanisms. Mutations in the presenilin 1 gene (PS1) are responsible for the majority of FAD cases, causing an earlier age of onset and more rapid progression to end-stage disease than seen in sporadic AD. We have investigated the cytoskeletal alterations in neuritic AD pathology in a cohort of FAD cases in comparison to sporadic AD and pathologically aged cases. Tau-immunoreactive neurofibrillary tangle (NFT) loads were similar between PS1 FAD and sporadic AD cases. Similarly, plaque loads, both β-amyloid (Aβ) and thioflavine S, in PS1 FAD and sporadic AD cases were not significantly different; however, in pathologically aged cases, they were significantly lower than those in PS1 cases, but were not different from sporadic AD cases. The ‘cotton wool’ plaque characteristic of PS1 cases did not demonstrate a high density of dystrophic neurites compared to other Aβ plaque types, but did demonstrate a localised mass effect on the neuropil. Despite minimal differences in plaque and NFT loads, immunolabelling demonstrated clear phenotypic differences in the NFTs and dystrophic neurites in PS1 FAD cases. Presenilin-1 cases exhibited significantly (P < 0.05) more tau-positive NFTs that were immunolabelled by the antibody SMI312 (anti-phosphorylated NF protein and phosphorylated tau) than sporadic AD cases. Presenilin-1 cases also exhibited numerous ring-like NF-positive and elongated tau-labelled dystrophic neurites, whereas these dystrophic neurite types were only abundant at the very early (pathologically aged cases) or very late stages of sporadic AD progression, respectively. These differences in cytoskeletal pathology in PS1 cases suggest an accelerated rate of neuritic pathology development, potentially due to mutant PS1 influencing multiple pathogenic pathways.     

Muscle regeneration and mitochondrial calmitine increase in the dystrophic dy/dy mouse after intramuscular chlorpromazine injection

We studied the effect of chlorpromazine injection on the gastrocnemius muscles of C57BL/6J dy/dy dystrophic mice. Changes in mitochondrial calmitine concentrations and differences in microscopy studies, fibre typing and morphometry were compared in gastrocnemius muscles of dystrophic and control mice before and 2 and 21 days after injection. In both cases, calmitine reduction associated with muscle degeneration was observed 2 days after drug injection. Calmitine then increased, reaching a level at day 21 nearly identical to that of controls before injection. This increase was associated with muscle regeneration. These results clearly indicate that dystrophic mouse muscle can regenerate calmitine after drug-induced damage.     

Progressive supranuclear palsy: extensive neuropil threads in addition to neurofibrillary tangles

Summary Light microscopic immunohistochemical investigations were performed on neurofibrillary tangles (NFT) in four histologically confirmed cases of Alzheimer's disease (AD) and in five patients with a progressive supranuclear palsy (PSP). The antibody panel included antisera to the neuronal microtubule-associated protein, tau, and to isolated paired helical filaments (PHF), as well as mouse monoclonal antibodies (MAbs) to phosphorylated epitopes on high and medium molecular weight neurofilament subunits (RT97 and BF10, respectively). Paraffin sections were also impregnated with the Gallyas silver method, which specifically stains tangles and cortical neuropil threads in AD, but does not stain normal neurofilaments. All tangles in PSP and AD showed consistent immunostaining with antibodies to tau protein and isolated PHF, regardless of their localization. MAbs RT97 and BF10, however, did not stain or only weakly stained, subcortical tangles in PSP and AD, whereas most cortical NFT in AD were intensely immunostained. All tangles in PSP were as heavily impregnated with Gallyas as they were in AD. Furthermore there were extensive networks of Gallyaspositive, tau- and PHF-immunoreactive neurites in subcortical gray areas containing NFT, and bundles of positive axons in white matter tracts interconnecting subcortical nuclei of PSP. Our studies indicate a much more extensive disruption of fibrillar proteins in PSP subcortical neurons than previously reported. They furthermore indicate a very similar antigenic profile of NFT in PSP and AD, as far as subcortical neurons are concerned.