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Focal glomerulosclerosis in the remnant kidney model--an inflammatory disease mediated by cytokines 总被引:7,自引:0,他引:7
BACKGROUND: The mechanism of progression of established renal disease
remains unclear. While a low protein diet slows this progression, the role
of cytokines in this process has been little investigated. METHODS: We
investigated cytokine expression by Northern blot and immunohistochemistry
in two groups of 5/6 nephrectomized rats (5/6 Nx) fed a normal (24%) or low
(6%) protein diet and compared them with sham operated controls. RESULTS:
The rats on 6% protein diet had significantly less focal glomerulosclerosis
(FGS) (17.4 +/- 4.4 vs 27.4 +/- 8.8%, P < 0.05) and global sclerosis
(GGS) after 7 weeks (0.4 +/- 0.8 vs 3.5 +/- 2.1% of glomeruli P < 0.05).
Both experimental groups showed three times control levels of MCP-I
expression after 2 weeks. However in the 5/6 Nx 6% protein group the
expression decreased at 4 weeks (1.5 times controls) and reached control
levels after 7 weeks. In contrast, the 5/6 Nx 24% protein group exhibited a
further marked increase after 4 weeks (5.6 times controls) and was still
two-fold higher after 7 weeks. TGF-beta expression was modestly but
consistently increased at all time points (120-160% of controls), with no
difference between the two study groups. Neither IL-1 beta or TNF-alpha was
detectable at any time. Immunohistochemistry demonstrated TGF-beta
intracellularly in distal tubular cells in both experimental and control
animals, while MCP-1 protein was found in the area of FGS and in the apical
pole of distal tubular cells in both experimental groups. Glomerular and
interstitial ED1 positive cells were significantly increased after four
weeks in the 5/6 Nx 24% protein group (P < 0.05). CONCLUSIONS: A
'mechanical' injury to the kidney clearly results in an inflammatory
response associated with the upregulation of MCP-1. A low protein diet
modulates the expression of MCP-1 and improves the morphological sequelae
seen after renal ablation.
相似文献
14.
D M Moran A W Wheeler D C Henderson N Whittall 《International archives of allergy and applied immunology》1986,81(4):357-362
Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen extracts, previously found to be capable of suppressing immature IgE antibody responses in mice, were shown to be highly effective at inhibiting the capacity of immune splenocytes to produce a secondary response in sub-lethally irradiated recipient animals. Anamnestic IgE responses in mice primed without adjuvant were also suppressed, but the effects were modest and of short duration. The predictive value of murine models for selecting clinically appropriate specific IgE suppressive agents and treatment schedules that might be successfully employed for clinical use are discussed. 相似文献
15.
N. J. Carty B. Moran C. D. Johnson 《Annals of the Royal College of Surgeons of England》1994,76(4):276-280
This article examines whether there is any clinical value in anorectal physiology measurements. The function of the human rectum is poorly understood and the factors which affect function of the anal sphincters are complex. Several laboratories have reported results of anorectal physiology measurements, but there is extensive variation between normal values in different laboratories. It is argued that anorectal physiology measurements fail to meet the criteria of a useful clinical test: 1. It is not widely available to clinicians; 2. It is not possible to establish a reproducible normal range; 3. Abnormal measurements do not correlate with disease entities or explain symptoms; 4. The results are often unhelpful in diagnosis and management; 5. Clinical outcome after intervention does not correlate with alteration in the measurements obtained. On the other hand it can be argued that anorectal physiology measurements do provide information that assists in the management of conditions such as constipation, anismus, Hirschsprung''s disease, faecal incontinence and tenesmus. Management based on biofeedback modification of physiological responses requires these techniques as part of the biofeedback system. There is evidence that this may be appropriate in anismus and solitary rectal ulcer syndrome. However, the assessment of these difficult conditions and the interpretation of the results are probably at present best confined to specialist units. 相似文献
16.
Percutaneous endoscopic gastrostomy in 41 patients: indications and clinical outcome. 总被引:2,自引:2,他引:0
Percutaneous endoscopic gastrostomy, under local anaesthetic, was successfully used in 40 out of 41 patients referred for nutritional support. The indications were neurological disorders of swallowing in 32 patients, head and neck cancer in four patients and supplemental feeding in a miscellaneous group of five patients. The main complications of this procedure were one failed insertion and one peritubal infection. At prospective follow-up, the tube continued to function in 16 patients (seven at home) a mean of 184 days post-insertion (range 6-610 days). In 11 patients resumption of swallowing at a mean of 122 (20-390) days allowed tube removal. Thirteen patients died from their disease, a mean of 96 (12-320) days post-insertion. Patient tolerance and patient and carer satisfaction have been excellent and early results suggest that recovery of speech and swallowing in acute neurological disorders may be enhanced. Percutaneous endoscopic gastrostomy should be performed in all patients referred for a gastrostomy and should be considered in all patients requiring long-term tube feeding. 相似文献
17.
Increased incidence of gap junctional coupling between spinal motoneurones following transient blockade of NMDA receptors in neonatal rats 总被引:3,自引:0,他引:3
George Z. Mentis Eugenia Díaz Linda B. Moran Roberto Navarrete 《The Journal of physiology》2002,544(3):757-764
Neonatal rat motoneurones are electrically coupled via gap junctions and the incidence of this coupling declines during postnatal development. The mechanisms involved in this developmental regulation of gap junctional communication are largely unknown. Here we have studied the role of NMDA receptor-mediated glutamatergic synaptic activity in the regulation of motoneurone coupling. Gap junctional coupling was demonstrated by the presence of graded, short latency depolarising potentials following ventral root stimulation, and by the transfer of the low molecular weight tracer Neurobiotin to neighbouring motoneurones. Sites of close apposition between the somata and/or dendrites of the dye-coupled motoneurones were identified as potential sites of gap junctional coupling. Early postnatal blockade of the NMDA subtype of glutamate receptors using the non-competitive antagonist dizocilpine maleate (MK801) arrested the developmental decrease in electrotonic and dye coupling during the first postnatal week. These results suggest that the postnatal increase in glutamatergic synaptic activity associated with the onset of locomotion promote the loss of gap junctional connections between developing motoneurones. 相似文献
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H Gerbaldo G Thaker P G Tittel J Layne-Gedge M Moran L Demisch 《Neuropsychobiology》1992,25(2):99-101
Electroretinographic (ERG) measurements were performed in 9 schizophrenic patients and in 13 control subjects. The measurements of schizophrenic patients as a group did not differ from those of normals. However, 6 schizophrenic patients who had a past history of sun gazing showed a decrease in retinal responsiveness under conditions of light adaptation. These results suggest that a subgroup of schizophrenic patients, who show deviant light-related behavior, have abnormal ERG. We postulate that an abnormality in retinal dopaminergic neurons, which are known to reduce light responsiveness of horizontal and ganglion cells, is the underlying pathophysiology of this clinical finding. 相似文献