Dietary factors and progression of diabetic nephropathy

The role of dietary factors in patients with type 1 (insulin-dependent) diabetes is reviewed by examining three different aspects: the effect of an acute protein load, the effect of dietary protein restriction on the progression of nephropathy and the metabolic effects of low-protein diets. After an acute protein load some impairment of the renal functional reserve may be observed only in patients with type 1 diabetes and overt nephropathy. However, the renal functional reserve is not able to give useful indications of the extent of renal damage and the prognosis of the disease. Both short-term and long-term dietary protein restriction are followed by a significant decrease in glomerular filtration rate (GFR) and albuminuria in type 1 diabetics with incipient nephropathy. In patients with overt nephropathy the long-term administration of a low-protein diet is followed by significant reductions in the rate of decline of GFR and in urinary protein excretion only when started at GFR values higher than 45 ml/min. The rate of functional deterioration when dietary treatment is prescribed seems critical in modulating the effects of a low-protein diet. In addition, low-protein diets may exert important metabolic and clinical effects beyond their supposed effect on progression. Clearly, an adequate dietary regimen is only part of the medical treatment in patients with diabetic nephropathy.     

Deposition of amyloid β protein in non-Alzheimer dementias: evidence for a neuronal origin of parenchymal deposits of β protein in neurodegenerative disease

Summary In two elderly patients with frontal lobe dementia and in two others with progressive aphasia an inverse relationship between the severity of protein deposition and the principal pathology of these disorders was noted. Deposition of protein occurred only in areas of cortex where functional (viable) neurones were still present and was absent where neuronal decimation had taken place. Such findings suggest that the presence of functional neurones is necessary for protein deposition to occur and, therefore, that neurones may be the source of the amyloid protein that is deposited within brain parenchyma not only in these disorders but also in other conditions, particularly Alzheimer's disease.Supported by a grant from the North Western Regional Health Authority (DJ) and a B.Sc Intercalated Studentship from the MRC (PWS)     

Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Summary This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti- protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.     

Immunoelectron microscopic study of tubulin and microtubule-associated proteins after transient cerebral ischemia in gerbils

Summary Differential vulnerability of microtubule components to cerebral ischemia has been reported previously. We investigated the disintegration of microtubules using immunoelectron microscopy for -tubulin and microtubule-associated protein 1A and 2 (MAP1A and 2). Mongolian gerbils were subjected to bilateral carotid occlusion for 10 to 30 min and reperfusion for up to 72h following ischemia for 10 min. After ischemia for 10 min, some dendrites in the stratum moleculare of the subiculum-CA1 region lost immunoreaction products for -tubulin and MAPs. Loss of the reaction products spread to the medial CA1 region during progressive ischemia for 30 min. In some dendrites, electron-dense precipitates for MAPs were dispersed in the dendritic cytoplasm with little reaction product on microtubules and without alteration of the reaction for -tubulin. After recirculation, loss of electron-dense precipitates for -tubulin and MAPs, as well as disintegration of microtubules, propagated further to the medial CA1 region and to the proximal dendrites. The present study demonstrated prompt disintegration of microtubules with rapid disappearance of the reaction for MAPs which seemed to be caused by detachment of MAPs from the microtubule cores.     

The coexistence of Alzheimer's disease and Creutzfeldt-Jakob disease in a patient with dementia of long duration

Summary We report here a 75-year-old-male with a slowly progressive dementia of 5-year duration along with a rapid exacerbation of symptoms in the terminal 3 months. Neuropathological examinations revealed findings consistent with conspicuous Alzheimer's disease and mild Creutzfeldt-Jakob disease (CJD). The plaque amyloid was exclusively composed of -protein. The immunohistochemistry of prion protein using hydrolytic autoclaving pretreatment showed diffuse gray matter stainings in the sections of both the cerebral and cerebellar cortices. This method was thus considered useful in confirming the diagnosis of CJD for this case.     

Substance P-immunoreactive sensory axons in the rat respiratory tract: a quantitative study of their distribution and role in neurogenic inflammation.

Substance P is one of the peptides released from sensory nerves that mediate "neurogenic inflammation." Although substance P-immunoreactive (SP-IR) axons are known to be present within the mucosa of the respiratory tract, the relative extent of the innervation of various components of the mucosa is not known. Therefore, we determined the distribution and number of SP-IR axons in the rat trachea and bronchi, by using immunohistochemistry on tissue whole mounts. Specifically, we sought to learn whether these axons directly innervate the postcapillary venules involved in neurogenic plasma extravasation, the arterioles involved in neurogenic vasodilatation, and the airway smooth muscle involved in bronchoconstriction in pathogen-free, adult male F344 rats. We found that 90% of the SP-IR axons were single axons, usually having varicosities. Eighty-five percent of these were in the epithelium, 6% innervated arterioles, and the remainder elsewhere in the lamina propria. Only 10% of the mediator-sensitive postcapillary venules (i.e., venules labeled with Monastral blue pigment after challenge with capsaicin or substance P) were within 10 microns of SP-IR axons. SP-IR axons were more than 10 times as frequent in the smooth muscle of the distal bronchi as in the trachea. Capsaicin pretreatment (168 mg/kg over 7 days) reduced the number of SP-IR axons in the trachea by 96%, which is consistent with their being sensory. Unilateral vagotomy reduced the number of SP-IR axons bilaterally in the trachea and ipsilaterally in the main stem bronchus. Using an antibody to Protein Gene Product 9.5 as a nonspecific marker for all nerves in the trachea, we determined that SP-IR axons constituted 90% of the axons in the epithelium, 32% of the axons on arterioles, and only 4% of the axons in the smooth muscle. We conclude that most SP-IR nerves in the trachea are sensory axons and most of these axons end in the epithelium. SP-IR axons innervate mucosal arterioles, but few innervate postcapillary venules. Therefore, the mechanism by which sensory axons evoke plasma extravasation from these venules is likely to involve the diffusion of the peptide or a secondary mediator from the epithelium or from the arterioles upstream.     

Establishment of a human glioma cell line bearing a homogeneously staining chromosomal region and releasing α- and β-type transforming growth factors

Summary A human glioma cell line (YKG1), which was positively identified for glial fibrillary acidic (GFA) and S-100 proteins, was established from a surgical specimen of a patient with glioblastoma. Chromosome analysis of the cells revealed a homogeneously staining region (HSR) on a marker chromosome. The assay for transforming growth factors (TGFs) in the conditioned medium of the cell line revealed that it contained high levels of - and -type TGFs, which might regulate the growth of glioblastoma and influence on the peritumoral tissues.     

Experimental transplantation gliomas in the adult cat brain

Summary In adult cats experimental brain tumours were produced by stereotactical xenotransplantation of the rat glioma clone F 98 into the internal capsule of the left hemisphere. Two to four weeks after transplantation tumours and peritumoural oedema were investigated by magnetic resonance imaging (MRI), electrophysiological recording and analysis of tissue content of water, electrolytes and extravasated serum proteins.Spherical tumours with a diameter of about 10 mm developed at the injection site and were surrounded by massive white matter oedema. Water content in peritumoural white matter increased from 2.63 ± 0.17 to 3.65 ± 0.19 ml/g d.w. (means ± SD), sodium from 187±11 to 351±55 eq/g d.w. and calcium from 7.4±1.1 to 13.3 ± 1.3 ± 1.3 eq/g d.w. Potassium and magnesium did not change. Oedema development was associated with the extravasation of 18.0 ± 16.8mg/g d.w. albumin and 15.8 ± 12.2 mg/g d.w. immunoglobulin. The calculated electrolyte content of oedema fluid approximated that of plasma but the serum protein content was about 40% lower. The ratio of low (albumin) to high (immunoglobulin) molecular weight proteins was the same in blood and oedema fluid. It is, therefore, concluded that peritumoural oedema consist of two components,a whole plasma extravasate and a protein-free ultra-filtrate.Peritumoural oedema could be clearly detected by MRI but differentiation between tumour and oedema was only possible after contrast enhancement with gadolinium-DTPA. The ratios of the intensities of the MR signal correlated linearly with the water content within white matter. MRI, in consequence, allows quantification of oedema provided a reference area with normal water content is present.     

土荆皮甲酸的抗生育作用和毒性

土荆皮甲酸(Pseudolaric acid A),是从金钱松(Pseudolarix kamepferi)的根皮中分离得到的一个新型的二萜类化合物,将其混悬于1%羧甲基纤维素中,经口服给药,对大鼠、仑鼠及狗均可产生明显的抗早孕作用,其抗早孕的有效剂量各为7.5mg/kg,60mg/kg,0.5mg/kg qd×3d,土荆皮甲酸经皮下及阴道给药也能产生明显的抗早孕作用,其对大鼠口服的ED_(50),LD_(50)及95%可信限是14.5(11.7～17.7)mg/kg和219.8(193～250)mg/kg,得治疗指数10.2。狗的亚急性毒性试验表明,土荆皮甲酸对狗的中毒作用主要为呕吐、腹泻、便血等消化道的症状,显微镜下可见胃肠道粘膜及粘膜下组织广泛的出血点,其它器官未见到明显的病理变化。     

Successful pregnancy in advanced renal failure without dialysis

We describe a successful pregnancy in a 22-year-old patient with advanced renal failure, who gave birth to a living boy in the 35th week of pregnancy. At the time of spontaneous delivery the mother had a serum creatinine of 851 mol/l. No dialysis treatment had been instituted during this successful pregnancy.