SEARCH · PubMed Health

Results for “Restrictive”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,279 records · Page 71Linked to original sources

PubMed1987

[Phenotypic characteristics of a new modification-restriction system in E. coli].

It has been demonstrated phenotypically that there exists a new modificational-and-restrictional system as synthesized by the recombinant Escherichia coli tF strain. A series of passages of the T3 and T7 phages and their mutants in E. coli tF has made it possible to ascertain a specific modification of the phage DNA, with was shown to be induced by the host strain. The high level of adsorption of these phages on the cell surface of E. coli tF has ruled out the possibility of existing of a 'nonclassical' modification and restriction of DNA. In view of the further characterizing of this modificational-and-restrictional system of E. coli tF it has been comparatively studied with the already known modificational-and-restrictional systems isolated from various Escherichia coli strains. Results have shown that no identity exists between the tested systems and the one in E. coli tF. It is stated that the new modificational-and-restrictional system of E. coli tF belongs to none of the three known types of restrictional endonucleases.

Adsorption↗

PubMed1987

Measurement of O6-alkylguanine-DNA alkyltransferase activity in human cells and tumor tissues by restriction endonuclease inhibition.

A sensitive assay for O6-alkylguanine-DNA alkyltransferase activity in cell or tumor extracts has been devised. The theoretical basis of the new assay lies in the observation that certain restriction enzymes will not cleave DNA containing methylated bases. Thus, if a synthetic oligodeoxynucleotide with a restriction sequence containing O6-methylguanine were incubated with the restriction enzyme, this synthetic oligodeoxynucleotide should remain intact. However, if the guanine-O6 methyl group were first removed by O6-alkylguanine-DNA alkyltransferase present in certain cell or tissue extracts the synthetic oligodeoxynucleotide would be cleaved by the restriction enzyme. The parental oligodeoxynucleotide and its restriction products are separated from each other and analyzed on denaturing polyacrylamide gels. The extent of cleavage by the restriction enzyme is a direct assay of the content of O6-alkylguanine-DNA alkyltransferase in the cell/tumor extracts. The assay has been tested against cell culture and xenograft tumor systems and has performed in a predictive manner, correctly predicting five Mer- and three Mer+ phenotypes. Furthermore, the assay is quantitative and the number of molecules of the O6-alkylguanine-DNA alkyltransferase per cell estimated using this assay agrees with those that have been published.

Base Sequence↗

PubMed1987

[Weakening of type I restriction in E. coli: the effect of 2-aminopurine and 5-bromouracil].

2-aminopurine (2-AP) and 5-bromouracil, strong mutagens of base analog type, were found to induce efficiently the alleviation of I type restriction in Escherichia coli. 2-AP induced restriction alleviation occurs in recA, lexA and mut- mutants, but no additional relief of restriction is registered in dam-bacteria in the presence of sublethal 2-AP concentrations. 2-AP specifically alleviates I type restriction in Escherichia coli (EcoA, EcoB, EcoD, and EcoK) and does not affect restriction systems of II (EcoRI) and III (EcoP1) types. We suggest that 2-AP-induced mismatches and other replication errors may be signals inducing restriction alleviation in Escherichia coli.

2-Aminopurine↗

PubMed1988

Interstrain restriction fragment length polymorphism of c-fos and c-src oncogene loci in spontaneously hypertensive and normotensive rats.

Interstrain restriction fragment length polymorphism was detected after Southern blot hybridization of spontaneously hypertensive (SHR) and control (WKY) rat DNA digested by Bam HI restrictase with a v-fos probe. The SHR genome was characterized by an additional minor band of 4.0 kb. Other restriction fragment length polymorphism was revealed in the c-src locus by Eco RI, Hind III and Pst I restrictases. The major characteristic bands were 1.6 kb (SHR) and 2.4 kb (WKY) after Eco RI restriction; 3.4 kb (SHR) and 4.1 kb (WKY) after Hind III restriction and 4.0 kb (SHR) and 4.6 kb (WKY) after Pst I restriction. This restriction fragment length polymorphism can be used as Mendelian traits in linkage studies on the distribution of blood pressure and other quantitative physiological traits in (SHR x WKY)F2 hybrids.

Animals↗

PubMed1986

Restriction fragment-length polymorphisms of class II gene sequences in mice expressing minor structural variants of I-Ak and I-Ap.

Serologic and structural analyses of the I-A molecules expressed among a large collection of wild mouse-derived H-2 haplotypes has led to the definition of "families" of I-A alleles which encode antigenically similar molecules that are identical in more than 90% of their tryptic peptides. Two of these families, denoted the I-Ak and I-Ap families, consist of 10 I-A alleles which encode I-A molecules whose structures are closely related to either I-Ap or I-Ak. The evolutionary relationships of the I-A alleles in these families were assessed by a molecular analysis of their genomic structures. The A alpha and A beta alleles within these I-A families were compared by analysis of restriction fragment-length polymorphisms (RFLP) detected at high stringency by Southern blot hybridization with DNA probes specific for either A alpha or A beta. The polymorphic restriction enzyme sites detected in this survey were distributed over more than 7 kb of genomic DNA surrounding each gene. Because both A alpha and A beta are encoded by about 700 bp of exon DNA, the majority of the restriction enzyme sites assayed by this RFLP analysis reflect polymorphisms in noncoding regions. The DNA sequence homologies of these alleles were estimated from the RFLP results with seven restriction endonucleases by calculating the fraction homologous value as defined previously. The results indicate that evolutionarily dissimilar I-A alleles can encode I-A molecules with very similar structures. The five I-A alleles in the I-Ak family could be divided into two discrete groups, denoted K1 and K2, on the basis of their restriction fragment (RF) genotypes. The RF genotypes of alleles within each group shared more than 80% of the restriction fragments for both A and A beta. In contrast, the RF genotypes of alleles in group K1 differed extensively from those in group K2, indicating that alleles in these separate groups may not be evolutionarily closely related. These observations suggest that gene conversion or intragenic recombinational events may have been involved in the evolution of groups K1 and K2 in the I-Ak family. The RF genotypes of alleles in the I-Ap family demonstrated a close evolutionary relationship among all but two of the alleles. These two alleles encoded I-A molecules whose structures were the least related to I-Ap of any of the alleles in the I-Ap family.(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗

PubMed1987

[Various characteristics of the anti-restriction mechanism in bacteriophage T5].

Bacteriophage T5 is not confined by the restriction systems of the second type EcoRII and EcoRV. Bacteriophage T5 DNA is not modified by EcoRII and EcoRV methylases in vivo. The sites of recognition for restriction endonuclease EcoRV are mapped at 24.4; 57.6; 68.5; 70.2% of T5 DNA, while the sites at 5.1; 7.6% are recognized by EcoRII, the sites at 5.75; 6.0 and 6.5% are recognized by HpaI in FST. A high activity of restriction endonucleases EcoRI and EcoRV is demonstrated in crude extracts of E. coli B834 (RI) and E. coli B834 (RV) cells infected by bacteriophage T5. The simultaneous infection of E. coli B834 (RI) or E. coli B834 (RV) cells by the amber mutants of bacteriophage T5 and the suppressing phage lambda NM761 does not result in the protection of lambda DNA by the T5 anti-restriction mechanism. The presented data support the hypothesis that the anti-restriction mechanism of bacteriophage T5 is based on prevention of T5 DNA contacts with restriction enzymes by a specific phage protein.

DNA Restriction Enzymes↗

PubMed1988

Restriction of tumor growth in mice by sodium-deficient diet.

Generalized malnutrition results in inhibition of tumorigenesis and tumor growth in experimental animal models. Neither the specific nutrient deficiency nor the mechanism has been definitely elucidated. We have shown previously that dietary sodium deprivation in rapidly growing rats retards protoplasmic growth. This effect was correlated to the extracellular fluid (ECF) volume expansion which is dependent on sodium accumulation. Since solid tumors are composed of a large quantity of ECF (which includes plasma volume) it was postulated that preventing the accumulation of new ECF by means of sodium restriction would influence tumor growth. The present study was designed to determine the effects of salt restriction on tumor growth and to relate these effects to ECF volume. Approximately 10(6) viable B16 melanoma cells were injected into C57BL/6 x DBA/2 F1 and C57 mice. A salt restricted diet (sodium less than 3 microeq/g) was provided ad libitum. The drinking solution was distilled water for the experimental group and 0.45% saline solution for the controls. There was a significant decrease in tumor growth rates during sodium restriction. The total body ECF volume increased when dietary sodium was supplied but did not change during salt restriction. Therefore, the only source for the ECF in the tumor mass was from nontumorous tissue. We conclude that during dietary sodium restriction solid tumor growth is retarded and can proceed only to the extent that ECF is released from cachectic body tissues.

Animals↗

PubMed1984

The organization and complete nucleotide sequence of the PstI restriction-modification system.

We have determined the nucleotide sequence of a 4.0-kilobase DNA fragment containing the genes of the PstI restriction-modification system. Two large open reading frames were identified within the sequence and were ascribed to the restriction enzyme and methylase by the analysis of a series of deletion mutants. The two genes are encoded on opposite DNA strands, and hence must be transcribed from separate promoters rather than as a polycistronic message. The sequence of the first 10 amino acids of the restriction endonuclease was determined by sequential Edman degradation of the purified protein, permitting the alignment of the polypeptide with the DNA sequence. The NH2 terminus of the modification enzyme was established by sequential Edman degradation of the protein synthesized in bacterial minicells with different radiolabeled amino acids. The initiation codons of the two genes are separated by 130 base pairs. The deduced amino acid sequences indicate that the restriction endonuclease contains 326 amino acids with a calculated Mr = 37,370; the modification enzyme is composed of 507 amino acids with a calculated Mr = 56,830. There is no significant homology between the two proteins at the level of the primary structure. Antibody raised against the purified restriction endonuclease did not immunoprecipitate the modification enzyme. The transcription initiation sites were mapped using mung bean nuclease. Both of the transcripts begin with adenosine. The initiation sites are separated by only 70 base pairs. This close proximity suggests that the promoters for the two divergent genes overlap. DNase I protection experiments show that Escherichia coli RNA polymerase has a higher affinity for the methylase promoter than for the restriction enzyme promoter.

Amino Acid Sequence↗

PubMed1995

Restriction endonuclease fingerprinting (REF): a sensitive method for screening mutations in long, contiguous segments of DNA.

Restriction endonuclease fingerprinting (REF) is a modification of single-strand confirmation polymorphism (SSCP) that was developed to detect the presence of essentially all mutations in a 1-kb segment. To test REF, a 1-kb segment of the human factor IX gene was amplified with PCR and digested with each of five groups of restriction endonucleases. The endonucleases in each group were chosen so that the average size of the fragments was about 150 bp. After separate digestions, the products were mixed, 5' end-labeled with T4 polynucleotide kinase, denatured and electrophoresed under nondenaturing conditions. Each lane screened 1 kb and typically contained 68 segments (6.8 fragments per average digestion x 5 digestions x 2 strands). REF was performed with 5.6% polyacrylamide and 7.5% GeneAmp at temperatures of either 23 degrees or 8 degrees C. Point mutations resulted in the gain or loss of a restriction site in 21% of 24 test mutations (informative restriction component). In cases in which the restriction component was not informative, mutations were detected if any of the five mutation-containing restriction fragments (producing 10 single-stranded segments) displayed abnormal mobility (SSCP component). The average efficiency per single-stranded segment of the SSCP component for the 24 point mutations ranged from 49% for polyacrylamide at 23 degrees C to 68% with GeneAmp at 8 degrees C. REF detected 96% of the mutations with polyacrylamide at 23 degrees C and 100% with GeneAmp at 23 degrees or 8 degrees C. GeneAmp at 23 degrees and 8 degrees C also detected 100% of a subsequent blinded sample that contained normal controls and 27 different point mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

Induction of DNA double-strand breaks by restriction enzymes in X-ray-sensitive mutant Chinese hamster ovary cells measured by pulsed-field gel electrophoresis.

This investigation was designed to determine whether the cytotoxic effects of different restriction endonucleases are related to the number and type of DNA double-strand breaks (DSBs) they produce. Chinese hamster ovary (CHO) K1 and xrs-5 cells, a radiosensitive mutant of CHO K1, were exposed to restriction endonucleases HaeIII, HinfI, PvuII and BamHI by electroporation. These enzymes represent both blunt and sticky end cutters with differing recognition sequence lengths. The number of DSBs was measured by pulsed-field gel electrophoresis (PFGE). Two forms of PFGE were employed: asymmetric field-inversion gel electrophoresis (AFIGE) for measuring the kinetics of DNA breaks by enzyme digestion and clamped homogeneous gel electrophoresis (CHEF) for examining the size distributions of damaged DNA. The amount of DNA damage induced by exposure to all four restriction enzymes was significantly greater in xrs-5 compared to CHO K1 cells, consistent with the reported DSB repair deficiency in these cells. Since restriction endonucleases produce DSBs alone as opposed to the various types of DNA damage induced by X rays, these results confirm that the repair defect in this mutant involves the rejoining of DSBs. Although the cutting frequency was directly related to the length of the recognition sequence for four restriction enzymes, there was no simple correlation between the cytotoxic effect and the amount of DNA damage produced by each enzyme in either cell line. This finding suggests that the type or nature of the cutting sequence itself may play a role in restriction enzyme-induced cell killing.

Animals↗

PubMed1994

Dde I restriction fragment length polymorphism of the alpha 2-adrenoceptor gene does not correlate with blood pressure in the F2 generation obtained from crossing stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats.

OBJECTIVE: A pathogenetic role of altered alpha 2-adrenoceptors in essential hypertension has been suggested, based on studies in humans and animals. To examine the role of the alpha 2-adrenoceptor in genetically hypertensive rats, we compared the alpha 2-adrenoceptor genes of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats by restriction fragment length polymorphism analysis using human alpha 2-adrenoceptor probes (alpha 2-C10) and Dde I restriction endonuclease, and conducted a genetic cosegregation study. METHOD: Five female WKY rats were bred with five male SHRSP. Eight pairs of F1 rats were mated in brother-sister pairs to yield an F2 population of 84 rats. Systolic blood pressure was determined by tail-cuff sphygmomanometry. Direct arterial blood pressure was taken under ether anaesthesia just before the rats were killed. Southern blots were performed using alpha 2C10 as a probe and the DNA from the F2 generation. RESULTS: A restriction fragment length polymorphism of the SHRSP allele of a 1.6-kb fragment and a WKY rat allele of a 0.9-kb fragment with a common band of 1.3 kb in SHRSP and WKY rats was found, as reported previously. The distribution of the genotype based on restriction fragment length polymorphism conformed to a 1:2:1 ratio in F2 rats, as expected for a Mendelian trait. There was no significant difference in the blood pressure of F2 rats with respect to alpha 2-adrenoceptor genotype. CONCLUSION: This study demonstrated that the alpha 2-adrenoceptor gene restriction fragment length polymorphism distribution is a Mendelian trait in the F2 rats of crossed SHRSP and WKY rats, but failed to show genetic cosegregation of this restriction fragment length polymorphism with blood pressure in this generation.

Alleles↗

PubMedDate not supplied

[A comparative restriction analysis of the DNA of strains of the malarial parasite sensitive and resistant to chloroquine].

A comparative restriction analysis was made for DNA in malaria parasites, strain H sensitive to chloroquinone, strain LNK-65 with spontaneously occurred resistance to the agent, and breeding strain LNK-65 ChlR highly resistant to it. DNA hydrolysis with EcoR1, HindIII, and BamH1 endonucleases revealed permanent differences in the DNA restriction pattern of malaria parasites. There were additional restriction bands as part of DNA restricts in the strain LNK-65 Chl bred from LNK-65 for high resistance to chloroquine on EcoR1-, HindIII-, and BamH1-hydrolysis. Great differences in the DNA restriction pattern in the strains H and LNK-65 are likely to be due to their belonging to various strains, such as P.berghei and P.yoelii, respectively. Comparison of the DNA restriction pattern of the host (murine leukocytes) and the malaria parasite suggests the plasmodium DNA is adequately removed from the host DNA.

Animals↗

PubMed1993

[Idiopathic restrictive cardiomyopathy].

PURPOSE: To characterize the idiopathic restrictive cardiomyopathy (RCM) through clinical manifestations and complementary tests and to analyze the surgical benefit on the correction of tricuspid regurgitation. METHODS: Five patients with RCM idiopathic were retrospectively studied, 4 female and 1 male, with ages ranging from 30 to 59 (mean 40) years. The patients presented heart failure due to restrictive syndrome and were submitted to chest X-ray, EKG, echocardiogram, right ventricular endomyocardial biopsy, hemodynamic study and surgery. RESULTS: X-ray showed heart enlargement in all patients, but only one had pulmonary venous capillary congestion. EKG presented atrial fibrillation, complex QRS with low voltage on frontal axis, abnormal ventricular repolarization, right bundle branch block, inactive area and right ventricular hypertrophy. Complete atrioventricular block was observed in one patient. The echocardiogram study showed biatrial enlargement in all patients, and left ventricular dilatation in one patient with left ventricular dysfunction. Mild tricuspid regurgitation were observed in one patient and moderate in four. Two patients had mild mitral regurgitation. Diastolic dysfunction were observed at Doppler-cardiography in all patients. Right ventricular endomyocardial biopsy showed interstitial fibrosis, myocytes hypertrophy and myofibrils disarray. The hemodynamic study disclosed right ventricular hypertension in all patients. Three patients had hypotension in left ventricle and aorta. The left ventricular end diastolic pressure and pulmonary capillary pressure (pulmonary wedge pressure) were elevated in all patients. Dilated left ventricle with mild hypokinesia and right ventricular inferior hypokinesia and diastolic restriction were observed in one patient. One patient had similar pattern without diastolic restriction. Mild tricuspid regurgitation was observed in one patient, moderate in three and severe in one. Mild mitral regurgitation were observed in two patients. The restrictive pattern (deep and plateau) was present in three patients. Surgery were performed in all patients, and confirmed the mild tricuspid regurgitation in one and the moderate in four. De Vega plastia were performed in four patients. CONCLUSION: Among the complementary methods, echocardiogram and hemodynamic study were those of higher contribution to the diagnosis of idiopathic RCM. The disease has a poor evolution, even with clinical or surgical treatment. Heart transplantation may would be the best procedure on patients with symptomatic idiopathic restrictive cardiomyopathy.

Adult↗

PubMed1993

Automated fluorescence-based restriction fragment analysis.

We describe a procedure for the automated analysis of DNA restriction fragments in an agarose gel matrix. The procedure is based upon simultaneously digesting DNA with restriction enzymes and ligating a fluorochrome-labeled linker to the cut ends. The fluorochrome-labeled restriction fragments are loaded on a horizontal agarose gel scanning system (Applied Biosystems Model 362 GENE SCANNER Fluorescent Fragment Analyzer) for electrophoresis and data analysis. Mobility parameters for DNA fragment migration and detection sensitivity for the instrument are described. In addition, we demonstrate some unique applications, including electrophoresis and fragment size conversion of up to 72 cosmid restriction digests in 4 h, applicability of the system for subsequent DNA transfers and hybridizations, utility for establishing overlapping restriction maps of cosmids, and discrimination of restriction digest specific fragment ends following a double-digest protocol.

Base Sequence↗

PubMed1996

Restriction by EcoKI is enhanced by co-operative interactions between target sequences and is dependent on DEAD box motifs.

One subunit of both type I and type III restriction and modification enzymes contains motifs characteristic of DEAD box proteins, which implies that these enzymes may be DNA helicases. This subunit is essential for restriction, but not modification. The current model for restriction by both types of enzyme postulates that DNA cutting is stimulated when two enzyme complexes bound to neighbouring target sequences meet as the consequence of ATP-dependent DNA translocation. For type I enzymes, this model is supported by in vitro experiments, but the predicted co-operative interactions between targets have not been detected by assays that monitor restriction in vivo. The experiments reported here clearly establish the required synergistic effect but, in contrast to earlier experiments, they use Escherichia coli K-12 strains deficient in the restriction alleviation function associated with the Rac prophage. In bacteria with elevated levels of EcoKI the co-operative interactions are obscured, consistent with co-operation between free enzyme and that bound at target sites. We have made changes in three of the motifs characteristic of DEAD box proteins, including motif III, which in RecG is implicated in the migration of Holliday junctions. Conservative changes in each of the three motifs impair restriction.

Amino Acid Sequence↗

PubMed1996

[Myocardiopathies (XI). Restrictive myocardiopathy: concept, classification, and clinical approach].

Currently, cardiomyopathies are defined as "heart muscle diseases of unknown etiology". Restrictive cardiomyopathy is the rarest type of this disease, and the only one with no uniformly accepted diagnostic criteria. Its importance lies primarily in properly distinguishing it from constrictive pericarditis because of the direct consequences of mistakenly treating a case of constrictive pericarditis as if it were inoperable. Restrictive cardiomyopathy must be considered within the broader spectrum of diastolic dysfunction. Diagnostic criteria used show a general consensus for the diagnosis of restrictive cardiomyopathy in patients with clinical signs of heart failure in the presence of a nondilated, nonhypertrophic left ventricle with preserved contractility but abnormal diastolic function. Characteristically, right and left ventricular filling pressures are elevated and a dip and plateau diastolic pressure pattern appears. Restrictive cardiomyopathy may be either idiopathic and thus be a true cardiomyopathy in the strict sense of the term or secondary to an infiltrative disease of the myocardium. In this article we review the clinical and hemodynamic features of this disease and the different imaging techniques used in patients to help differentiate restrictive cardiomyopathy from constrictive pericarditis. Finally we study some types of restrictive cardiomyopathies.

Cardiac Catheterization↗

PubMed1997

Effects of age and long-term caloric restriction on the aqueous collecting channel in the mouse eye.

PURPOSE: The mouse aqueous collecting channel, part of the mouse aqueous outflow pathway, was measured using a computer-assisted image analysis system. We used ad libitum-fed and calorie-restricted mice to investigate the effects of age and long-term caloric restriction on the lumen size of the channel. RESULTS: The ad libitum-fed mice showed a significant age-related reduction in the lumen area. In the ad libitum-fed group, the lumen area of the channel decreased by 30% at 30-35 months of age (p < 0.01), and the anteroposterior width declined by 21% (p < 0.001) as compared with mice 3-5 months of age. The calorie-restricted mice did not display any reduction with age in the lumen area or the anteroposterior width of the channel. When compared with the age-matched calorie-restricted mice, the lumen area of the channel of the ad libitum-fed mice measured less by 34%, and anteroposterior width less by 21% at 30-35 months of age (p < 0.01). CONCLUSIONS: These results indicate that an age-related morphological alteration in the mouse aqueous collecting channel occurred and that it is delayed by long-term caloric restriction. This suggests a possible role of life-long caloric restriction in reducing glaucomatous damages and perhaps delaying glaucoma development.

Aging↗

PubMed1998

Changes in plasma lipids and lipoproteins in humans during a 2-year period of dietary restriction in Biosphere 2.

BACKGROUND: A cohort study was performed of 8 people sealed inside Biosphere 2 to evaluate the effects of dietary restriction in humans on lipid and lipoprotein levels and the relationship of these levels to energy, fat, and protein content of the diet, and body weight, weight change, and energy expenditure. METHODS: Eight healthy people aged 27 to 67 years, 4 women and 4 men, were sealed inside Biosphere 2 from September 26, 1991, to September 26, 1993, the longest sustained period in an "isolated confined environment" on record. They were studied throughout confinement and for more than 2 years after their exit and return to an ad libitum diet. Food available was severely restricted during most of the 2-year period inside Biosphere 2. High work output was maintained and food quality remained high, resulting in prolonged restriction of energy intake without malnutrition. RESULTS: Fasting plasma cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol levels; HDL subfraction distribution; dietary energy, fat, and protein content intake; and height, weight, weight change, and energy expenditure were measured. Total plasma cholesterol and triglyceride levels decreased 30% and 45%, respectively. The HDL and low-density lipoprotein levels also decreased and, in some participants, levels of HDL2 subfractions were increased. Multivariate analysis showed that the major cause of these changes was energy restriction. CONCLUSIONS: Energy restriction was the major factor leading to low lipid and lipoprotein levels. Energy restriction with adequate nutrition of young and middle-aged people may substantially reduce risk for atherosclerosis and consequent coronary artery and cerebrovascular disease.

Adult↗