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Biomedical subjects

B R Brooks

Publications and source records attributed to B R Brooks.

At least 109 records · Page 6Linked to original sources

Thyrotropin-releasing hormone (TRH) degradation in NIH:N mouse cerebral cortex and spinal cord.

Thyrotropin-releasing hormone (TRH) metabolism in NIH:N mouse cerebral cortex and spinal cord was studied with high pressure liquid chromatography. Degradation of added TRH was significantly (P less than 0.001) slower in the spinal cord (2.19 +/- 0.46%/min) than in the cerebral cortex (7.54 +/- 0.31%/min). Bacitracin, a non-competitive inhibitor of TRH deamidase, inhibited TRH degradation by 61.3 +/- 3.7% in the spinal cord but only by 35.9 +/- 1.0% in the cerebral cortex (P less than 0.001). Catabolism of TRH in the mouse spinal cord proceeds at a slower rate and predominantly via the TRH deamidase pathway.

Amidohydrolases↗

Molecular dynamics simulations of native and substrate-bound lysozyme. A study of the average structures and atomic fluctuations.

Molecular dynamics simulations of hen egg-white lysozyme in the free and substrate-bound states are reported and the nature of the average structures and atomic fluctuations are analyzed. Crystallographic water molecules of structural importance, as determined by hydrogen-bonding, were included in the simulations. Comparisons are made between the dynamics and the X-ray results for the atomic positions, the main-chain and side-chain dihedral angles, and the hydrogen-bonding geometry. Improvements over earlier simulations in the potential energy function and methodology resulted in stable trajectories with the C alpha co-ordinates within 1.5 A of the starting X-ray structure. Structural features analyzed in the simulations agreed well with the X-ray results except for some surface residues. The Asx chi 2 dihedral distribution and the geometry of hydrogen bonding at reverse turns show differences; possible causes are discussed. The relation between the magnitudes and time-scales of the residue fluctuations and secondary structural features, such as helices beta-sheets and coiled loops, is examined. Significant differences in the residue mobilities between the simulations of the free and substrate-bound states were found in a region of the enzyme that is in direct contact with the substrate and in a region that is distant from the active-site cleft. The dynamic behavior of the structural water molecules is analyzed by examining the correlation between the fluctuations of the water oxygens and the lysozyme heavy-atoms to which they are hydrogen-bonded.

Animals↗

Structural brain correlates of emotional disorder in multiple sclerosis.

Eighty-seven patients with definite multiple sclerosis (MS) were examined neurologically and administered the Mini-mental State examination (MMS) to assess cognitive disability at the beginning and end of a one-year study. A CT scan was performed in 37. A group of 16 patients with stable spinal cord injuries (SCI) were studied in a similar manner. Of the MS patients, 47% had a mean General Health Questionnaire (GHQ) score in the abnormal range. This was a higher rate than in SCI patients (P = 0.004). Mean depression scores were similar in MS and SCI patients, but MS patients with brain involvement were more depressed than those with cord lesions only (P = 0.05). Depression score was unrelated to functional disability but was correlated with the degree of neurological impairment (P = 0.03). Euphoric patients were more likely to have brain involvement (P = 0.006), to have progressive MS (P less than 0.0001), and to have enlarged ventricles (P = 0.04) and were more impaired cognitively (P = 0.04) than noneuphoric patients. These results suggest that depression in MS patients is partly determined by the presence of brain involvement, but that it is also an emotional reaction to the disorder. Euphoria and cognitive disorder are reflections of brain involvement.

Adult↗

Patient teaching manuals improve retention of treatment information--a controlled clinical trial in multiple sclerosis.

Retention of information concerning steroid medication dosage, side effects, and course of action to follow when certain danger signs or side effects occur was tested prospectively in multiple sclerosis patients about to be treated with alternate-day steroid medication. Each patient received identical oral instruction from both a physician and a clinical nurse specialist, followed by a written pretest of the orally imparted information. Alternate patients then received a written instruction booklet to reinforce the information concerning steroid medications. After one month, a written posttest was given. Patients who received the written instructional booklet showed a significant increase in retained knowledge concerning steroids.

Adult↗

Demonstration of thyrotropin-releasing hormone immunoreactivity in neurons of the mouse spinal dorsal horn.

Thyrotropin-releasing hormone-like immunoreactivity was demonstrated in neurons within the superficial laminae (I, II, III) of the mouse spinal dorsal horn by light-microscopic peroxidase immunocytochemistry. The immunoreactivity was distributed in a narrow dorsoventral band that enclosed the substantia gelatinosa (lamina II), with a higher concentration along the lamina II/III border. At present, the functional significance of these neurons is unknown. Their existence within the substantia gelatinosa suggests a role in sensory information processing.

Animals↗

Transition from B to Z DNA: contribution of internal fluctuations to the configurational entropy difference.

The internal motions of the double-stranded DNA oligomer (dCdG)3 (dC, deoxycytidylate; dG, deoxyguanylate) in the B and Z forms have been calculated in the harmonic approximation. A complete vibrational analysis has been made, and the resulting normal mode frequencies have been used to evaluate the vibrational entropy of B and Z DNA. The greater flexibility of the B DNA hexamer leads to an entropic stabilization relative to the stiffer Z DNA hexamer of 22 calories per mole per kelvin at 300 K. The calculated value is of the same order as that (21 to 27 calories per mole per kelvin) obtained from nuclear magnetic resonance measurements on the methylated duplexes (m5dCdG)3 and (dCdGm5dCdGdCdG). This result demonstrates the importance of internal motions, which have been neglected in earlier studies of the transition from B to Z DNA, in the stability of different nucleic acid conformers.

DNA↗

Progressive multifocal leukoencephalopathy.

PML is a progressive opportunistic infection of the CNS caused by a commonly occurring virus that may become manifest in the context of reduced host resistance in persons of any age. The authors review the disease and its causes, including a discussion of treatment attempts and differential diagnoses.

Adolescent↗

Oligoclonal IgG bands in cerebrospinal fluid in various neurological diseases.

We studied the frequency of oligoclonal immunoglobulin G bands in the cerebrospinal fluid (CSF) of patients with various neurological diseases. We used a micromethod employing sodium dodecyl sulfate polyacrylamide gel electrophoresis that required only 50 microliters of unconcentrated CSF. Oligoclonal bands were detected in the CSF of 95% of the patients with multiple sclerosis, 90% with subacute sclerosing panencephalitis, and 100% with herpes simplex encephalitis, but less frequently in other central nervous system infections. No oligoclonal bands were detected in the CSF of patients with Parkinson, Huntington, Creutzfeldt-Jakob, or herniated disc diseases. Bands were detected in some patients with Alzheimer disease, cerebrovascular accident, idiopathic vertigo, idiopathic seizures, amyotrophic lateral sclerosis, polyneuropathy, and central nervous system glioma. Patients with other conditions infrequently had positive bands. The determination of oligoclonal bands is a useful aid in the diagnosis of multiple sclerosis, subacute sclerosing panencephalitis, and herpes simplex encephalitis. The presence of oligoclonal bands indicates an immunological response but is not diagnostic for a particular condition.

Central Nervous System Diseases↗

Disease activity and emotional state in multiple sclerosis.

The prevalence and nature of emotional disturbance in patients with multiple sclerosis (MS) was studied prospectively in 64 MS patients and 23 spinal cord-injured (SCI) control patients by administration of the 28-item subscale General Health Questionnaire (GHQ). MS patients in remission had a mean GHQ score of 4.4, and patients with acute exacerbation or progressive nonremitting MS had a mean score of 15.7, a significant difference (p less than 0.001). The prevalence of emotional disturbance was 90% in exacerbating or progressing patients, 39% in stable patients, and 12% in SCI control patients. The presence of emotional disturbance was not related to age, sex, or other demographic variables, to duration or severity of disease, or to the degree of disability. In the group of MS patients in remission, somatic complaints, anxiety, and social dysfunction were more prevalent than symptoms of depression.

Adult↗

Spinal cord metabolic changes in murine retrovirus-induced motor neuron disease.

Decreased cerebrospinal fluid concentrations of cyclic nucleotides in human motor neuron disease and decreased spinal cord concentrations of cyclic nucleotides in murine (Wobbler) motor neuron disease suggest that an abnormality in cyclic nucleotide metabolism may play a role in motor neuron degeneration. Retroviruses cause decreased cellular levels of cyclic nucleotides in infected cells. We induced a motor neuron degeneration with a neurotropic retrovirus, but not with a non-neurotropic retrovirus. In paralyzed mice, mean cAMP was decreased 21% in posterior horn segments and 34% in anterior horn segments compared to controls. The proportion of spinal cord phosphorylase a decreased 24% in paralyzed mice compared to controls. The content of cGMP decreased 48% in the cerebellum and 25% in both anterior and posterior horn segments of the spinal cords of paralyzed mice compared to controls. White matter content of these chemicals did not decrease in the posterior column of affected animals. Spinal cord content of ATP increased 20-22% in all three compartments, but the spinal cord content of phosphocreatine increased dramatically in white matter (46%), posterior horn gray matter (69%), and anterior horn gray matter (103%) compared to controls. Changes in high-energy phosphate intermediate and cyclic nucleotide metabolites occurred only in topographical regions showing neuronal and astrocyte pathological changes, but did not occur in the cerebral cortex.

Adenosine Triphosphate↗

Dynamics of DNA oligomers.

The techniques of molecular and harmonic dynamics are used to study the internal mobility of three double-stranded DNA hexamers. A 60 ps molecular dynamics simulation and a normal mode description of d(CpGpCpGpCpG)2 in the B conformation characterize the atomic fluctuations of this structure. A comparison between the two approaches validates the harmonic results at room temperature. Detailed examination of the normal modes indicates that only the low-frequency modes are needed to determine atomic fluctuations. A harmonic analysis is made of d(CpGpCpGpCpG)2 in the Z conformation and of d(TpApTpApTpA)2 in the B conformation using only the low-frequency modes. The atomic fluctuations of the three alternating pyrimidine-purine helices are compared and the dependence on conformation and sequence are discussed. The insights which theoretical calculations can provide for the interpretation of experimental results are explored.

Base Sequence↗

Cerebrospinal fluid myelin basic protein in hydrocephalus.

Immunoreactive myelin basic protein (MBP) levels were measured in cerebrospinal fluid (CSF) samples taken from 57 patients with active hydrocephalus (age range 3 weeks to 60 years). Of these patients, 28 (49%) had elevated MBP values (greater than 4.5 ng/ml). Elevated MBP levels were found in 44% of patients with congenital hydrocephalus, 75% of patients with posttraumatic hydrocephalus, 80% of patients with normal-pressure hydrocephalus, and 83% of patients with porencephaly. Also associated with abnormal MBP levels was the ventricular size as measured by computerized tomography scanning (chi 2: p less than 0.05): 36% of the patients with small ventricles (ventricle:brain ratio 0 to 0.4:1) had elevated MBP in the CSF, whereas 61% of those with moderate ventricles (0.41 to 0.6:1 ratio) and 100% of those with large ventricles (0.61 to 0.85:1 ratio) had abnormal values. Only 33% of those with maximal hydrocephalus (0.86 to 1.0:1 ratio) had elevated MBP levels, perhaps because of dilution effects. In three patients in whom CSF was obtained simultaneously by ventricular and lumbar punctures, the ventricular fluid had a consistently higher concentration of MBP, suggesting a cerebral origin. It is concluded that active hydrocephalus produces significant periventricular demyelination, probably as the result of mechanical stretching.

Adolescent↗