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Biomedical subjects

P A Berger

Publications and source records attributed to P A Berger.

At least 19 recordsLinked to original sources

Polyhydroxyalkanoate accumulation in Burkholderia sp.: a molecular approach to elucidate the genes involved in the formation of two homopolymers consisting of short-chain-length 3-hydroxyalkanoic acids.

Burkholderia sp. accumulates polyhydrox-yalkanoates (PHAs) containing 3-hydroxybutyrate and 3-hydroxy-4-pentenoic acid when grown on mineral media under limited phosphate or nitrogen, and using sucrose or gluconate as a carbon and energy source. Solvent fractionation and NMR spectroscopic characterization of these polyesters revealed the simultaneous accumulation of two homopolyesters rather than a co-polyester with random sequence distribution of the monomers [Valentin HE, Berger PA, Gruys KJ, Rodrigues MFA, Steinbuchel A, Tran M, Asrar J (1999) Macromolecules 32: 7389-7395]. To understand the genetic requirements for such unusual polyester accumulation, we probed total genomic DNA from Burkholderia sp. by Southern hybridization experiments using phaC-specific probes. These experiments indicated the presence of more than one PHA synthase gene within the genome of Burkholderia sp. However, when total genomic DNA from Burkholderia sp. was used to complement a PHA-negative mutant of Ralstonia eutropha for PHA accumulation, only one PHA synthase gene was obtained resembling the R. eutropha type of PHA synthases, based on amino acid sequence similarity. In addition to the PHA synthase gene, based on high sequence homology, genes encoding a beta-ketothiolase and acetoacetyl-CoA reductase were identified in a gene cluster with the PHA synthase gene. The arrangement of the three genes is quite similar to the R. eutropha poly-beta-hydroxybutyrate biosynthesis operon.

Acyltransferases↗

Clinical impact of MR spectroscopy when MR imaging is indeterminate for pediatric brain tumors.

OBJECTIVE: We undertook this study to determine if single-voxel proton (hydrogen) MR spectroscopy could have clinical impact on the management of pediatric brain tumors when MR findings were indeterminate. SUBJECTS AND METHODS: Eleven children (mean age, 9 years) being examined for brain tumors underwent MR imaging that revealed indeterminate criteria of enhancement, mass effect, and prolonged T1 and T2 signal. MR spectroscopy was then used to distinguish radiation necrosis from tumor in one patient, differentiate residual tumor from scarring in two patients, document early treatment response in three patients, and discriminate benign from malignant masses in five patients. RESULTS: In 10 of the 11 patients, spectra were successfully acquired. Based on the chemical analysis of the indeterminate area shown on MR imaging, clinical impact was achieved in these 10 patients. Clinical impact included treatment modification in five patients, follow-up studies replacing further treatment in three patients, and tumor characterization in the remaining two patients. Confirmation was by histology in four patients and by follow-up MR imaging and MR spectroscopy for up to 30 months in the remaining six patients. CONCLUSION: When MR imaging is indeterminate in evaluating pediatric brain tumors, MR spectroscopy can provide objective neurochemical information, thereby altering treatment.

Adolescent↗

Retraction.

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Retraction Notice↗

Oscillatory potentials as a marker for dopaminergic disease.

In an effort to find electrophysiologic correlates of dopaminergic disease in man, we measured oscillatory potentials of the electroretinogram in normal and unmedicated schizophrenic subjects, and in rabbits given D1 agonist or antagonist drugs. We found highly reproducible oscillatory potentials in twelve male schizophrenics that were indistinguishable from those in nine male normal volunteers. We also found little electroretinographic difference among four rabbits given intramuscular injections of SKF 38393 (a D1 agonist) and four control animals injected with saline. However, four animals given SCH 23390 (a D1 antagonist) showed diminution of the b-wave and selective suppression of the second oscillatory potential. This effect was more prominent in oscillatory potentials generated by 5-Hz flicker than by a single flash. These rabbit data suggest that further efforts at finding clinical correlations may be worthwhile, possibly with trial of flicker oscillatory potentials, and they support the concept that different oscillatory potentials have different generators.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

A paramagnetic agent causing ochronotic arthropathy.

Magnetic resonance imaging (MRI) identified a paramagnetic substance in the hyaline cartilage of the hips and knees in a patient with ochronosis. Chemical studies characterized the paramagnetic agent as melanin. The free radicals contained in melanin were shown to initiate cytotoxicity. The loss of cartilage in ochronotic arthropathy now can be explained at the electron level using the superoxide theory of oxygen toxicity. Inappropriate metabolism of oxygen also may explain early cartilage degeneration in hemochromatosis, hemosiderosis, and Wilson's disease.

Cartilage, Articular↗

A comparison of the neurochemical and behavioral effects of clenbuterol and desipramine.

Because both long-term adrenoceptor agonist administration and antidepressant treatment in animals down-regulate CNS beta-adrenoceptors and attenuate brain adenylate cyclase activity, beta-adrenoceptor agonists may also possess antidepressant properties. We compared the effects of the centrally acting beta-adrenoceptor agonist clenbuterol (5, 10 and 35 mg/kg per day), and the combination of propranolol (5 mg/kg per day) and clenbuterol (10 mg/kg per day), with desipramine (15 mg/kg per day) on forced swim test performance and on cortical beta-adrenoceptors in rats following 7 days of drug administration. Desipramine (15 mg/kg per day), and clenbuterol (10 and 35 mg/kg per day, but not 5 mg/kg per day) both significantly reduced immobility in the forced swim test. Frontal cortex beta-adrenoceptors were significantly down-regulated after desipramine and all 3 doses of clenbuterol. The co-administration of propranolol (5 mg/kg per day) blocked both the reduction in immobility and down-regulation of cortical beta-receptors induced by clenbuterol (10 mg/kg per day). Propranolol (5 mg/kg per day) alone up-regulated frontal cortex beta-adrenoceptors, but had no significant effect on swimming performance. These data suggest that the physiological consequences of beta-adrenoceptor down-regulation are important in the mechanism of action of antidepressants. The results also suggest that clenbuterol may be useful in the treatment of depression.

Animals↗

Abnormal rapid eye movement latencies in schizophrenia.

Several previous studies have observed short rapid eye movement (REM) latencies in schizophrenic patients without major affective disorder. This study was designed to meet several of the criticisms of those previous studies. Using Research Diagnostic Criteria, we compared the sleep patterns of schizophrenic patients with those of normal controls and patients with major depressive disorder and schizoaffective disorder. All patients were medication free, and REM latency was explicitly defined using both strict and lenient criteria. Chronically ill paranoid or undifferentiated schizophrenics could not be distinguished from patients with major depressive disorder or schizoaffective disorder using any definition of REM latency. These results were not due to longer REM latency in the particular sample of patients with major depressive disorder. They had abnormally low REM latencies; however, the schizophrenic patients showed similar decrements. These data cast serious doubt on the specificity of short REM latency as a biological marker for major depressive disorder.

Adult↗

TRH stimulation test and depression.

A thyrotropin-releasing hormone (TRH) stimulation test was performed in 52 male inpatients with major depressive disorder. Twenty-nine percent of the 52 subjects had a delta thyroid-stimulating hormone (delta TSH) less than 5 microU/ml. The cerebrospinal fluid (CSF) amine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA), were measured in 29 subjects, and a dexamethasone suppression test (DST) was performed in 48 subjects. Of the three CSF amine metabolites, only MHPG correlated significantly with baseline TSH and none correlated with delta TSH. The baseline TSH correlated positively with the TSH response at 30 minutes. Neither baseline TSH nor delta TSH correlated with cortisol levels before or after dexamethasone. The correlation between CSF MHPG and serum TSH suggests a relationship between central norepinephrine and baseline TSH.

Adult↗