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Biomedical subjects

R Brenner

Publications and source records attributed to R Brenner.

At least 19 recordsLinked to original sources
PubMed1992

Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta.

Extracellular matrix proteins synthesized by bone cells isolated from 16 patients with different forms of osteogenesis imperfecta (OI) were analyzed in vitro. Specific components of the extracellular matrix by OI and age-matched cultures were investigated by steady-state radiolabeling followed by quantitation of label into specific proteins and comparison of OI cultures to those of age-matched controls. The in vitro proliferation of OI bone cells was found to be lower than that of control cells. In seven patients, abnormalities of the alpha 1(I) and/or alpha 2(I) chains of type I collagen were detected by gel electrophoresis. In two of these patients, the mutations in the COLIA1 and COLIA2 genes have been previously identified. Although the amount of total protein synthesized by the cells in culture was the same for OI bone cells and age-matched control cells, OI bone cells showed a significantly reduced synthesis of not only collagen but also other bone matrix glycoproteins. The synthesis of osteonectin (SPARC/BM40) and three proteoglycans [a large chondroitin sulfate proteoglycan, biglycan (PGI), and decorin (PGII)] was found to be decreased in OI cells. The reduction was most pronounced at the developmental age at which these macromolecules reach maximal levels during normal development.

Adolescent↗
PubMed1992

Volume measurement of multiple sclerosis lesions with magnetic resonance images. A preliminary study.

The ability to visualise multiple sclerosis lesions in vivo with magnetic resonance imaging suggests an important role in monitoring the course of the disease. In order to help the long-term assessment of prospective treatments, a semi-automated technique for measuring lesion volume has been developed to provide a quantitative index of disease progression. Results are presented from a preliminary study with a single patient and compared to measurements taken from lesion outlines traced by a neuroradiologist, two neurologists and a technician. The semi-automated technique achieved a precision of 6% compared to a range of 12-33% for the manual tracing method. It also reduced the human interaction time from at least 60 min to 15 min.

Brain↗
PubMed1992

Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype.

The primary structures of human neuronal alpha 1, alpha 2, and beta subunits of a voltage-dependent Ca2+ channel were deduced by characterizing cDNAs. The alpha 1 subunit (alpha 1D) directs the recombinant expression of a dihydropyridine-sensitive L-type Ca2+ channel when coexpressed with the beta (beta 2) and the alpha 2 (alpha 2b) subunits in Xenopus oocytes. The recombinant channel is also reversibly blocked by 10-15 microM omega-conotoxin. Expression of the alpha 1D subunit alone, or coexpression with the alpha 2b subunit, did not elicit functional Ca2+ channel activity. Thus, the beta 2 subunit appears to serve an obligatory function, whereas the alpha 2b subunit appears to play an accessory role that potentiates expression of the channel. The primary transcripts encoding the alpha 1D, alpha 2, and beta subunits are differentially processed. At least two forms of neuronal alpha 1D were identified. Different forms of alpha 2 and beta transcripts were also identified in CNS, skeletal muscle, and aorta tissues.

Amino Acid Sequence↗
PubMed1992

Collagen type II in Langer-Saldino achondrogenesis: absence of major abnormalities in a less severe case.

Collagen extracted either from cartilage or synthesized in vitro was analyzed to identify possible molecular defects in the cartilaginous matrix of a male fetus suffering from a mild form of type II achondrogenesis (Langer-Saldino). The tissue architecture of the patient's cartilage was markedly altered and showed numerous fibrous vascular canals which were focally stained by antibodies against collagens I and III. Collagen II was present, although heterogenously distributed throughout the cartilaginous matrix. Upon electrophoretic separation, however, the patient's femoral head cartilage showed the presence of collagens II, IX and XI only, which was similar to an age-matched control. The hydroxyproline/hydroxylysine ratio of collagen II of the patient was not significantly different from that of the control. Likewise, the compositions of collagens synthesized by cultured chondrocytes as well as fibroblasts were similar in the patient and the control. The results provide strong evidence that, in the present mild case of Langer-Saldino achondrogenesis, collagen II is expressed and regularly hydroxylated at its lysyl residues. This may indicate that cartilage components other than collagen II may be responsible for the altered tissue organization observed. Along with previous observations, our data suggest that the degree of biochemical matrix alterations may be related to the severity of the clinical phenotype.

Achondroplasia↗
PubMed1991

Dysrhythmia associated with fluoxetine treatment in an elderly patient with cardiac disease.

Although fluoxetine has been shown to be both efficacious and well tolerated, few data are available on the use of this drug in patients with preexisting heart disease and in the elderly. The authors report a case of an elderly patient in whom atrial fibrillation and bradycardia developed shortly after she began treatment with fluoxetine. The dysrhythmias recurred on rechallenge with the drug. A review of the pertinent literature is presented and possible pathophysiologic mechanisms are discussed.

Age Factors↗
PubMed1990

Occult diastematomyelia in adults--report of two cases.

Two cases of diastematomyelia discovered in adults with minimal symptoms are described. In one case the presence of an associated thoracic neurenteric cyst supports the theory that a diastematomyelic spur represents a persistent neurenteric canal. The imaging findings are described and the incidence of diastematomyelia in adults is briefly discussed on the basis of cases previously reported in the literature.

Female↗
PubMed1989

Osteogenesis imperfecta in childhood: cardiac and renal manifestations.

We examined 58 children aged 1-16 years with various forms of osteogenesis imperfecta (OI). Congenital cardiac malformations were diagnosed in 4 children (valvular aortic stenosis, 2 with atrial septal defect II, Fallot Tetralogy). Two additional children developed holosystolic mitral valve prolapse and regurgitation. Children suffering from a severe clinical course (type III according to the Sillence classification) showed aortic root dilatation (28%) and increased septal (40%) and posterior left ventricular wall thickening (68%) on initial evaluation. All three parameters were significantly correlated to body surface area. Kidney stones and renal papillary calcifications were detected in 4 children. Cardiovascular abnormalities and nephrolithiasis may be important extraskeletal manifestations of childhood OI.

Adolescent↗
PubMed1989

A psychiatric study of 247 liver transplantation candidates.

This study prospectively evaluated 247 consecutive liver transplantation candidates for the presence of psychiatric disorders. While one-half did not meet DSM-III criteria for a psychiatric diagnosis, 18.6% had delirium, 19.8% had an adjustment disorder, 9% had alcohol abuse or dependence, 4.5% had major depression, and 2% had other drug abuse or dependence. Delirious subjects were significantly more likely to have a lower serum albumin, lower Mini-Mental State exam scores, higher Trailmaking Test scores (both A and B), and more dysrhythmia on electroencephalogram (EEG). In addition, while both delirious and nondelirious subjects were judged to have high levels of overall stress, those with delirium had significantly poorer adaptive functioning and lower occupational, family, and social scale ratings. Thus, while all liver transplant candidates are under substantial psychosocial stress and require psychosocial support, those identified as being delirious require particular attention because of their numerous cognitive, medical, and psychosocial problems.

Adolescent↗
PubMed1988

Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel.

Complementary DNAs were isolated and used to deduce the primary structures of the alpha 1 and alpha 2 subunits of the dihydropyridine-sensitive, voltage-dependent calcium channel from rabbit skeletal muscle. The alpha 1 subunit, which contains putative binding sites for calcium antagonists, is a hydrophobic protein with a sequence that is consistent with multiple transmembrane domains and shows structural and sequence homology with other voltage-dependent ion channels. In contrast, the alpha 2 subunit is a hydrophilic protein without homology to other known protein sequences. Nucleic acid hybridization studies suggest that the alpha 1 and alpha 2 subunit mRNAs are expressed differentially in a tissue-specific manner and that there is a family of genes encoding additional calcium channel subtypes.

Amino Acid Sequence↗
PubMed1987

Fate of viruses in artificial wetlands.

Little is known about the ability of wetlands to remove disease-causing viruses from municipal wastewater. In this study we examined the survival of several indicators of viral pollution (indigenous F-specific bacteriophages, seeded MS2 bacteriophage, and seeded human poliovirus type 1) applied in primary municipal wastewater to artificial wetland ecosystems. Only about 1% of the indigenous F-specific RNA bacteriophages survived flow through the vegetated wetland beds at a 5-cm-day-1 hydraulic application rate during the period from June through December 1985. The total number of indigenous F-specific bacteriophages (F-specific RNA and F-specific DNA phages) was also reduced by about 99% by wetland treatment, with the mean inflow concentration over the period of an entire year reduced from 3,129 to 33 PFU ml-1 in the outflow of a vegetated bed and to 174 PFU ml-1 in the outflow of an unvegetated bed. Such superior treatment by the vegetated bed demonstrates the significant role of higher aquatic plants in the removal process. Seeded MS2 bacteriophage and seeded poliovirus were removed more efficiently than were the indigenous bacteriophages, with less than 0.2% of MS2 and 0.1% of the poliovirus surviving flow at the same hydraulic application rate. The decay rate (k) of MS2 in a stagnant wetlands (k = 0.012 to 0.028 h-1) was lower than that for flowing systems (k = 0.44 to 0.052 h-1), reflecting the enhanced capacity for filtration or adsorption of viruses by the root-substrate complex (and associated biofilm).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophages↗
PubMed1986

Skeletal growth in fetal rats. Effects of glucose and amino acids.

The modified hyperglycemia-hyperinsulinism hypothesis, which characterizes intrauterine growth of diabetic pregnancy, was studied in fetal rats. From day 19 to day 21 postconception, pregnant rats were constantly infused with saline, amino acids, or glucose. In the fetus, serum somatomedin activity was determined, with the porcine bioassay and the incorporation of 3H-thymidine into rib cartilage and isolated chondrocytes in vivo in response to serum from normal maternal or fetal rats. In comparison with control fetuses, body weights were decreased in glucose-exposed fetuses (4.66 +/- 0.25 versus 3.75 +/- 0.99, N = 121; P less than 0.001), and increased (4.87 +/- 0.57, N = 105; P less than 0.05) in amino acid-exposed fetuses. Serum somatomedin activity (U/ml) was higher in glucose-treated (0.79 +/- 0.40, N = 11; P less than 0.05) and amino acid-treated animals (0.90 +/- 0.16, N = 10; P less than 0.001) than in controls (0.55 +/- 0.04, N = 13). In vivo labeling with thymidine resulted in a higher radioactivity of cartilage in small fetuses compared with large fetuses when the dams had been infused with saline (r = -0.531, N = 56; P less than 0.001) or amino acids (r = -0.292, N = 52; P less than 0.01). Opposite results were obtained in hyperglycemic animals (r = 0.542, N = 54; P less than 0.001). When isolated chondrocytes were incubated with serum from normal fetal rats, the incorporation of thymidine was about 10 times higher into cells from small fetuses than from large fetuses, irrespective of the infusion regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1985

Tricyclic antidepressant and metabolite levels in chronic renal failure.

Serial blood samples were drawn from 12 patients undergoing hemodialysis who were receiving tricyclic antidepressants (TCAs). Samples were drawn before, during, and after a dialysis session (two to 17 sessions per subject). Samples were analyzed by HPLC before and after hydrolysis with beta-glucuronidase/sulfatase to determine the conjugated and nonconjugated metabolites. Analysis of these data in comparison with those of controls with depression and normal renal function showed that: (1) at steady state, tertiary and secondary amine TCA levels did not differ; (2) levels of the hydroxylated metabolites had greater variability and were somewhat higher at steady state; (3) levels of the conjugated hydroxylated compounds were markedly elevated, reaching 500% to 1500% normal; (4) the time to reach a steady-state level appeared to be slightly increased; and (5) elimination t1/2 s of unconjugated and conjugated drug forms were longer in our patients with normal renal function than those reported in the literature. Levels of the tertiary, secondary, and hydroxylated metabolites were not changed by dialysis, whereas there were substantial decrements in glucuronidated metabolite levels. These findings demonstrate increased concentrations of conjugated drug forms and suggest an abnormal distribution or delayed elimination of unconjugated and conjugated metabolites. These observations may shed some light on the apparent hypersensitivity of these patients to TCA side effects, particularly because glucuronides may exert peripheral pharmacologic effects.

Adult↗
PubMed1984

Methylphenidate challenge as a predictor of relapse in schizophrenia.

Although neuroleptics are the major treatment for schizophrenia, there are no effective measures to determine the appropriate or necessary length of neuroleptic maintenance. To test the ability of a psychostimulant challenge to predict relapse following neuroleptic withdrawal, the authors administered methylphenidate and placebo infusions to 11 stable schizophrenic outpatients who had been on a neuroleptic maintenance regimen for at least 6 months. Patients withdrawn from neuroleptics were followed until relapse. All three patients with a positive response to methylphenidate challenge relapsed in 1 to 7 weeks; one of seven negative responders relapsed at week 21. Differences in relapse rates (p = .033) and survival time (p = .005) between negative and positive responders were significant.

Adult↗