Aspiration biopsy of the kidney. 1951.
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Biopsy, Needle↗
Biomedical subjects
C Brun
Publications and source records attributed to C Brun.
[Mental deficiency preceded by transitory hypertonic cerebral motor disorder].
OBJECTIVE: To analyse clinical and outcome features of patients with mental retardation and transient hypertonia in early life which lead to the diagnosis of hypertonic cerebral palsy. MATERIAL AND METHODS: We study six patients that presented with the above features in our neuropediatric out patients clinic. Clinical data related with the hypertonic signs and its evolution were collected. All the patients were assessed to find their present cognitive and development state. RESULTS: Clinical and radiological signs of a possible prenatal neurological damage were found in all the patients. Structural anomalies were presented in neuroimaging in five cases. Agenesia or hypoplasia of corpus callosum was the most common finding. The pattern of progression of this cases were: 1. Improvement of hypertonia with almost normal tone by the age of two years. 2. Despite of the resolution of motor signs, persistence of different degrees of mental retardation. CONCLUSIONS: Our reported patients presented a peculiar pattern of progression within the wide variability of the cerebral palsy group.
Agenesis of Corpus Callosum↗
pDblet, a stable autonomously replicating shuttle vector for Schizosaccharomyces pombe.
We have constructed a new multipurpose stable shuttle vector for the fission yeast Schizosaccharomyces pombe (Sp). Plasmid pDblet was designed to provide convenient features for molecular work and to overcome the inconveniences of previously designed Sp vectors. It contains the Sp ura4 gene as selectable marker and a new highly efficient ARS (autonomously replicating sequence) element, allowing the vector to remain stable as a monomer in Sp. In addition, pDblet transforms Sp with high efficiency and has high mitotic stability and low copy number.
DNA Replication↗
SARs, ARSs, and A,T-rich regions evidenced by restriction mapping on an 835-kb DNA fragment from Drosophila.
In Drosophila, sequences anchoring the DNA molecule to the scaffold (SARs) and sequences able to replicate autonomously (ARSs) had been shown to comap on an 835-kb DNA fragment (Brun et al. (1990) Mol. Cell. Biol. 10, 5455-5463). To investigate the question of whether this comapping results from the coincidental recruitment of SARs and ARSs in A,T-rich regions, A,T-rich regions of the 835-kb DNA fragment have been identified by restriction analysis with enzymes recognizing motifs made exclusively of A and T. Within the limits of sensitivity of this approach, the obtained data favor the idea of a noncoincidental recruitment: obviously a SAR and an ARS subpopulation are preferentially localized in the A,T-rich regions, but not every A,T-rich region displays a SAR activity, or an ARS activity, or both, nor are all SARs or ARSs localized in the A,T-rich regions. In addition, the data support the idea that a statistical assessment of base composition using restriction analysis might be developed into a general useful approach to genome organization.
Adenine↗
Yeast and mammalian replication intermediates migrate similarly in two-dimensional gels.
In the budding yeast, Saccharomyces cerevisiae, DNA replication initiates at specific, discrete chromosomal locations. At each initiation site, a single small replication bubble is generated, which subsequently expands at Y-like replication forks. We wanted to know whether other eukaryotic organisms utilize similar initiation mechanisms. For this purpose, replication intermediates (RIs) from three different organisms (Schizosaccharomyces pombe, Chinese hamster and human) were mixed individually with RIs from S. cerevisiae and then subjected to two-dimensional (2D) gel electrophoresis under conditions known to resolve molecules having different structures. All of the RIs detected by the hybridization probes we used for each organism migrated nearly identically to specific RIs of similar size from S. cerevisiae, implying that the detected RIs from all the studied organisms have very similar structures and may therefore employ the same basic initiation mechanism.
Animals↗
Mapping of replication initiation sites in human ribosomal DNA by nascent-strand abundance analysis.
New techniques for mapping mammalian DNA replication origins are needed. We have modified the existing nascent-strand size analysis technique (L. Vassilev and E.M. Johnson, Nucleic Acids Res. 17:7693-7705, 1989) to provide an independent means of studying replication initiation sites. We call the new method nascent-strand abundance analysis. We confirmed the validity of this method with replicating simian virus 40 DNA as a model. We then applied nascent-strand abundance and nascent-strand size analyses to mapping of initiation sites in human (HeLa) ribosomal DNA (rDNA), a region previously examined exclusively by two-dimensional gel electrophoresis methods (R.D. Little, T.H.K. Platt, and C.L. Schildkraut, Mol. Cell. Biol. 13:6600-6613, 1993). Our results partly confirm those obtained by two-dimensional gel electrophoresis techniques. Both studies suggest that replication initiates at relatively high frequency a few kilobase pairs upstream of the transcribed region and that many additional low-frequency initiation sites are distributed through most of the remainder of the ribosomal DNA repeat unit.
Animals↗
Relationship between scaffold-attached regions, sequences replicating autonomously in yeast, and a chromosomal replication origin in the Drosophila rDNA.
The potential relationship between anchorage of Drosophila rDNA to a nuclear substructure and replication mechanisms was studied. First, two scaffold-attached regions (SARs) were identified, in the internally transcribed spacer and in the region spanning both the intergenic spacer (IGS) and the externally transcribed spacer (ETS), respectively. These SARs define two possible loops containing the sequence coding for the 18S rRNA and part of that coding for the 28S rRNA, respectively. They also bind yeast scaffolds. Then, the presence of sequences able to promote extrachromosomal replication in yeast (ARSs) was tested. The identified ARSs comap with SARs. The tight relationship between SARs and ARSs was further investigated in the IGS-ETS region which contains a chromosomal replication origin. The topological correlation observed between SARs, ARSs, and a chromosomal replication origin suggests the physical association of the replication origin to the nuclear substructure.
Animals↗
Identification and characterization of a complex chromosomal replication origin in Schizosaccharomyces pombe.
In the budding yeast, S. cerevisiae, two-dimensional (2D) gel electrophoresis techniques permit mapping of DNA replication origins to short stretches of DNA (+/- 300 bp). In contrast, in mammalian cells and Drosophila, 2D gel techniques do not permit precise origin localization; the results have been interpreted to suggest that replication initiates in broad zones (several kbp or more). However, alternative techniques (replication timing, nascent strand polarity analysis, nascent strand size analysis) suggest that mammalian origins can be mapped to short DNA stretches, just like S. cerevisiae origins. Because the fission yeast, Schizosaccharomyces pombe, resembles higher organisms in several ways to a greater extent than does S. cerevisiae, we thought that S. pombe replication origins might prove to resemble--and thus be helpful models for--animal cell origins. An attempt to test this possibility using 2D gel techniques resulted in identification of a replication origin near the ura4 gene on chromosome III of S. pombe. The 2D gel patterns produced by this S. pombe origin indeed resemble the patterns produced by animal cell origins and show that the S. pombe origin cannot be precisely located. The data suggest an initiation zone of 3-5 kbp. Some aspects of the 2D gel patterns detected at the S. pombe origin cannot be explained by the rationale of initiation in broad zones, suggesting that future biochemical and genetic studies of this complex origin are likely to provide information useful in helping to understand the apparent conflict between the 2D gel mapping techniques and other mapping techniques at animal cell origins.
Chromosomes, Fungal↗
Prognosis in glomerulonephritis. III. A longitudinal analysis of changes in serum creatinine and proteinuria during the course of disease: effect of immunosuppressive treatment. Report from Copenhagen Study Group of Renal Diseases.
A total of 395 consecutive patients with biopsy-proven glomerulonephritis were followed up for 14 years. At the time of entry to the study the patients were classified as having one of nine states of kidney disease according to serum creatinine levels and proteinuria. The transitions of the patients between the nine states were analysed. The influence of 14 independent variables including treatment with cytostatic drugs and prednisolone was estimated by the Cox proportional hazard model. Treatment with immunosuppressive drugs had an influence that emerged within the first month and continued for the next 2 months. Subsequent treatment with cytostatic drugs in combination with prednisolone delayed further improvement. Treatment with prednisolone or cytostatic drugs as single therapy for up to 6 months increased the risk of improvement of the disease, and had no significant effect on deterioration. The beneficial effect of the treatment persisted after withdrawal of the immunosuppressive drugs. The analysis revealed only a slight influence of the histological character of the glomerular changes. Post-streptococcal glomerulonephritis carried an increased tendency for improvement. Arterial hypertension affected the process in several states of kidney disease. Heavy proteinuria increased the risk of increasing serum creatinine levels.
Azathioprine↗
Studies of an 800-kilobase DNA stretch of the Drosophila X chromosome: comapping of a subclass of scaffold-attached regions with sequences able to replicate autonomously in Saccharomyces cerevisiae.
We have previously mapped scaffold-attached regions (SARs) on an 800-kilobase DNA walk from the Drosophila X chromosome. We have also previously shown that the strength of binding, i.e., the ability of SARs to bind to all nuclear scaffolds or only to a fraction of them varied from one SAR to another one. In the present study, 71 of the 85 subfragments that bind scaffolds and 38 fragments that do not bind scaffolds were tested for their ability to promote autonomous replicating sequence (ARS) activity in Saccharomyces cerevisiae. Sixteen SAR-containing fragments from the chromosome walk were also examined for association to yeast nuclear scaffolds in vitro. All identified ARSs (a total of 27) were present on SAR-containing fragments, except two, which were adjacent to SARs. There is thus a correlation between ARS and SAR activities, and this correlation defines a SAR subclass. Moreover, the presence of an ARS on a DNA fragment appeared to be highly correlated with the strength of binding. The binding activity was highly conserved from Drosophila melanogaster to yeast. These data suggest that Drosophila DNA sequences responsible for binding to components of the nuclear scaffold from either D. melanogaster or yeast may be involved in the process of heterologous extrachromosomal replication in yeasts.
Animals↗
Long-term effects of lithium on the kidney: functional-morphological correlations.
Correlations between quantitative kidney biopsy findings and clinical renal function in 46 unselected patients treated with lithium for an average of eight years were studied. A significant relationship between maximum renal concentrating capacity and degree of tubular atrophy was found. GFR correlated significantly with sclerotic glomeruli as well as atrophic tubules in patients on a multiple dosage schedule, whereas no relationship was seen in patients receiving lithium in a single daily dose. Thus, renal dysfunction may have a structural basis in a subgroup of lithium-treated patients on a multiple dosage schedule.
Adult↗
Cytostatic treatment of glomerular diseases. V. Treatment of glomerulonephritis with cyclophosphamide plus prednisone, azathioprine plus prednisone and cyclophosphamide as monotherapy. A comparative study. A report from a Copenhagen Study Group of Renal Diseases.
Thirty-two patients suffering from biopsy-proven glomerulonephritis with proteinuria greater than or equal to 1.2 g/24 hours and/or creatinine clearance less than 50% of normal value were treated for 6 weeks with prednisone plus cyclophosphamide (C+P), azathioprine (A+P) or cyclophosphamide as a monotherapy (C). The effect of the treatment was evaluated after 6 and 16 weeks. The results were entered consecutively in a sequential analysis. The three treatment regimes were compared mutually as well as with the results of 16 weeks' treatment with C and placebo, published previously. Six weeks' treatment with C+P or A+P was superior to C and at least as efficient as 16 weeks' C treatment. C treatment for 6 weeks was less efficient than 16 weeks' C treatment. The side-effects of the 6 weeks' A+P or C+P treatment were fewer and less serious than those reported from the long-term C treatment.
Adult↗
Early arteriolopathy following "high-dose" cyclosporine in kidney transplantation.
Thirty-seven consecutive kidney graft biopsies from 37 patients immunosuppressed with "high-dose" cyclosporine (CsA) were mixed with 37 random biopsies obtained from 37 patients given azathioprine and prednisone (Aza/P) and reexamined by light microscopy, without knowledge of the therapy, for occurrence of early arteriolopathy. All biopsies were taken within 35 days after transplantation. Arteriolopathy was demonstrated in 12 biopsies from 37 patients given CsA but in none of those from 37 patients on Aza/P. The specific alteration found in those 12 biopsies was glycogen storage in the muscular layer of the arterioles. The average donor was significantly older in those grafts in which arteriolopathy was shown than in those without arteriolopathy but also given CsA (p less than 0.001). All kidneys from donors more than 53 yr old had arteriolopathy. The occurrence of arteriolopathy was independent of the average CsA level from transplantation to biopsy, but the CsA level had never been below 380 ng/ml in those patients with arteriolopathy. The clinical course in grafts with arteriolopathy was characterized by poorer graft function as judged from the renograms, delayed onset of function and a high proportion of "never-functioning" grafts (50%). We concluded that patients receiving a cadaver graft from a donor older than 50 yr should not be treated with "high-dose" CsA. If the arteriolopathy is demonstrated in kidney graft biopsies within the first 5 weeks after transplantation in patients treated with CsA, one should consider a change or modification of the treatment strategy.
Age Factors↗
Lithium: long-term effects on the kidney--II. Structural changes.
Forty-six patients treated with lithium for an average of 8 yr participated in a follow-up study involving a kidney biopsy. The results were compared with renal biopsy specimens from an age-matched group of controls never treated with lithium. The average number of totally scelerotic glomeruli and atrophic tubuli was higher in lithium-treated patients. The histopathological changes showed significant correlations with lithium dosage schedule. Both the proportions of sclerotic glomeruli, atrophic tubuli and focally distributed interstitial fibrosis were higher in patients receiving their lithium two or three times a day than when lithium was given in a single daily dose.
Adult↗
Demonstration and classification of amyloidosis in needle biopsies of the kidneys, with special reference to amyloidosis of the AA-type.
To examine whether sequence-specific antibodies directed against serum amyloid A were useful in the demonstration and classification of amyloidosis, needle biopsy specimens from the kidneys of 152 cases with renal disorders were investigated using the avidin-biotin-peroxidase complex technique of immunohistochemistry. A distinct immunoreactivity of protein AA was seen in biopsies from all 42 individuals who were clinically classified as having the AA-type of amyloidosis. The stained areas coincided with deposits stained by Congo red. Four of these cases demonstrated immunoreactivity of both protein AA and light immunoglobulin chains and all biopsies except one showed immunoreactivity for the amyloid P-component. After treatment with potassium permanganate, the amyloid deposits in the biopsies of all 42 cases lost their affinity for Congo red. Ten patients with clinical and laboratory findings compatible with the AL-type of amyloidosis were also investigated. All their biopsies demonstrated Congophilic amyloid deposits but none of them showed any immunoreactivity of protein AA. Amyloid deposits of lambda light immunoglobulin chains-but not kappa-were demonstrated in biopsies from four patients. The amyloid P-component was found in biopsies from six individuals and positive Congo red staining after treatment with potassium permanganate was seen in biopsies from four of the cases. Biopsies of 100 patients suffering from non-amyloid renal disorders were also examined. None of them displayed any immunoreactive deposits of protein AA. The investigation shows that amyloid deposits of the AA-type can be identified in needle biopsies when sequence-specific antibodies against serum amyloid A are used in the avidin-biotin-peroxidase complex technique. Both the diagnostic sensitivity (42 of 42) and specificity (110 of 110) of the assay were optimal (1.0). The method was found to be superior to other investigated techniques and useful for classifying amyloidosis in formalin-fixed renal biopsies.
Amyloidosis↗
Lithium: long-term effects on the kidney. I. Renal function in retrospect.
46 patients treated with lithium for an average of 8 years participated in a functional-morphological follow-up study based on a 12-day hospitalization and involving a kidney biopsy. The functional part of the study showed that tubular function was markedly influenced, leading to increased urine volume (average 3 1/24 h) and a decreased renal concentration capacity in 85% of the patients. Glomerular function was generally not influenced, and only 10% of the patients had glomerular filtration rates below their age-corrected normal ranges. Both urine volume and glomerular filtration rates showed significant correlations with dosage schedule. Urine volume was lower and glomerular filtration rate higher on a one-dose schedule than when lithium was given in divided doses during the day. It is concluded that discontinuity in lithium treatment minimizes lithium effects on kidney function.
Adult↗
Prognosis in glomerulonephritis. II. Regression analyses of prognostic factors affecting the course of renal function and the mortality in 395 patients. Calculation of a prognostic model. Report from a Copenhagen study group of renal diseases.
The course of the renal function and mortality were analysed in 395 patients with biopsy-proven glomerulonephritis (GN), using Cox's proportional hazards model. Seventeen clinical, biochemical and histopathological parameters were analysed for prognostic information. The patients were grouped according to their serum creatinine levels. Increase in serum creatinine, decrease in serum creatinine, cure and death were used as endpoints for the analysis. Caplan Meyer curves were made for 7 transitions between different groups and the variables were reduced by a step-wise procedure to a final model. Thirteen of the variables considered offered significant prognostic information (p less than 0.05) for at least one of the transitions. Short duration of disease, young age, non-nephritic urinary sediment and preceding streptococcal infection were predictors of cure. Extracapillary, membranoproliferative and unclassifiable GN, old age and arterial hypertension predicted increase in serum creatinine in patients with low serum creatinine, while male sex, short duration of disease and pathological electrocardiogram favoured a further increase in patients with high serum creatinine. A later decrease in serum creatinine was signified by a preceding streptococcal infection, short duration of disease, absence of arterial hypertension and low urinary protein excretion. Death without uremia was predicted by high age, connective tissue disease and extracapillary GN. Using these parameters and the models, it is possible to make a prognostic forecast for the individual GN patient. Examples of such a forecast are described.
Adult↗
Prognosis in glomerulonephritis. A follow-up study of 395 consecutive, biopsy-verified cases. I. Classification, renal histology and outcome. Report from a Copenhagen study group of renal diseases.
Between 1967 and 1977, 395 consecutive cases of glomerulonephritis (GN) were collected by a Copenhagen study group. The diagnosis was established by histological and biochemical criteria. Light microscopy investigations of thin silver-stained sections were applied. In a follow-up in 1980 all cases were categorized by one of the following end points: death without uremia, uremia, recovery, or censored cases. The course is presented in figures showing the cumulated distribution of outcomes in relation to observation time. Each histological subgroup of GN had its own characteristic course with respect to initial rates of changes in the renal state, as well as to frequency of recovery, uremia and death. The prognosis was good in minimal changes GN and proliferative GN, bad in unclassified GN and worst in extracapillary GN. When part of a connective tissue disease, GN carried a poor prognosis. We conclude that histological classification of GN based on light microscopy offers a reliable means of predicting the long-term prognosis.
Adolescent↗