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Biomedical subjects

S M Resnick

Publications and source records attributed to S M Resnick.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance.

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.

Aged↗
PubMed1998

Enzyme specificity of 2-nitrotoluene 2,3-dioxygenase from Pseudomonas sp. strain JS42 is determined by the C-terminal region of the alpha subunit of the oxygenase component.

Biotransformations with recombinant Escherichia coli expressing the genes encoding 2-nitrotoluene 2,3-dioxygenase (2NTDO) from Pseudomonas sp. strain JS42 demonstrated that 2NTDO catalyzes the dihydroxylation and/or monohydroxylation of a wide range of aromatic compounds. Extremely high nucleotide and deduced amino acid sequence identity exists between the components from 2NTDO and the corresponding components from 2,4-dinitrotoluene dioxygenase (2,4-DNTDO) from Burkholderia sp. strain DNT (formerly Pseudomonas sp. strain DNT). However, comparisons of the substrates oxidized by these dioxygenases show that they differ in substrate specificity, regiospecificity, and the enantiomeric composition of their oxidation products. Hybrid dioxygenases were constructed with the genes encoding 2NTDO and 2,4-DNTDO. Biotransformation experiments with these hybrid dioxygenases showed that the C-terminal region of the large subunit of the oxygenase component (ISP alpha) was responsible for the enzyme specificity differences observed between 2NTDO and 2,4-DNTDO. The small subunit of the terminal oxygenase component (ISP beta) was shown to play no role in determining the specificities of these dioxygenases.

Amino Acid Sequence↗
PubMed1997

Early androgen effects on aggression in children and adults with congenital adrenal hyperplasia.

Males are more likely than females to show aggressive behavior across species, ages, and situations, and these differences may be partly influenced by early hormones. We studied aggression in three samples of subjects with congenital adrenal hyperplasia (CAH), who were exposed to high levels of androgen in the prenatal and early postnatal periods. Controls were siblings and first cousins similar in age. In Sample 1, adolescents and adults completed the Multidimensional Personality Questionnaire (MPQ), which includes an Aggression scale. In Sample 2, adolescents and adults completed the MPQ and a paper-and-pencil version of Reinisch's Aggression Inventory. In Sample 3, parents rated the aggression of children aged 3-12, using a modification of Reinisch's Inventory. In all three samples, control males had higher aggression scores than control females. Further, as predicted, females with CAH had higher aggression than control females, but the difference was significant only in adolescents and adults. These results suggest that early androgens contribute to variability in human aggression.

Adolescent↗
PubMed1997

Stereospecific oxidation of (R)- and (S)-1-indanol by naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4.

A recombinant Escherichia coli strain which expresses naphthalene dioxygenase (NDO) from Pseudomonas sp. strain NCIB 9816-4 oxidized (S)-1-indanol to trans-(1S,3S)-indan-1,3-diol (95.5%) and (R)-3-hydroxy-1-indanone (4.5%). The same cells oxidized (R)-1-indanol to cis-1,3-indandiol (71%), (R)-3-hydroxy-1-indanone (18.2%), and cis-1,2,3-indantriol (10.8%). Purified NDO oxidized (S)-1-indenol to both syn- and anti-2,3-dihydroxy-1-indanol.

Dioxygenases↗
PubMed1997

Estrogen replacement therapy and longitudinal decline in visual memory. A possible protective effect?

Estrogen replacement therapy (ERT) is increasingly recommended for postmenopausal women due to its beneficial effects on physical health in older women. Recent studies have suggested that ERT may have a protective effect on cognitive function and may reduce the risk of Alzheimer's disease. In the present study we test the hypothesis that ERT may have a protective effect on memory in nondemented women. Data on hormonal status and memory were examined in 288 postmenopausal women in the Baltimore Longitudinal Study of Aging. One hundred sixteen women who reported that they were receiving ERT during a cognitive assessment were compared with 172 women who had never received ERT. Women who were receiving ERT had fewer errors on the Benton Visual Retention Test (BVRT), a measure of short-term visual memory, visual perception, and constructional skills. Furthermore, ERT appeared to protect against age changes in BVRT performance in a subgroup of 18 women for whom BVRT data were available before and during treatment with ERT. These findings suggest that ERT may protect against memory decline in nondemented postmenopausal women and offer further support for a beneficial role of estrogen on cognitive function in aging women.

Aged↗
PubMed1996

Regio- and stereospecific oxidation of fluorene, dibenzofuran, and dibenzothiophene by naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4.

The regio- and stereospecific oxidation of fluorene, dibenzofuran, and dibenzothiophene was examined with mutant and recombinant strains expressing naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4. The initial oxidation products were isolated and identified by gas chromatography-mass spectrometry and nuclear magnetic resonance spectrometry. Salicylate-induced cells of Pseudomonas sp. strain 9816/11 and isopropyl-beta-D-thiogalactopyranoside-induced cells of Escherichia coli JM109(DE3)(pDTG141) oxidized fluorene to (+)-(3S,4R)-cis-3,4-dihydroxy-3,4-dihydrofluorene (80 to 90% relative yield; > 95% enantiomeric excess [ee]) and 9-fluorenol (< 10% yield). The same cells oxidized dibenzofuran to (1R,2S)-cis-1,2-dihydroxy-1, 2-dihydrodibenzofuran (60 to 70% yield; > 95% ee) and (3S,4R)-cis-3, 4-dihydroxy-3,4-dihydrodibenzofuran (30 to 40% yield; > 95% ee). Induced cells of both strains, as well as the purified dioxygenase, also oxidized dibenzothiophene to (+)-(1R,2S)-cis-1,2-dihydroxy-1, 2-dihydrodibenzothiophene (84 to 87% yield; > 95% ee) and dibenzothiophene sulfoxide (< 15% yield). The major reaction catalyzed by naphthalene dioxygenase with each substrate was stereospecific dihydroxylation in which the cis-dihydrodiols were of identical regiochemistry and of R configuration at the benzylic center adjacent to the bridgehead carbon atom. The regiospecific oxidation of dibenzofuran differed from that of the other substrates in that a significant amount of the minor cis-3,4-dihydrodiol regioisomer was formed. The results indicate that although the absolute stereochemistry of the cis-diene diols was the same, the nature of the bridging atom or heteroatom influenced the regiospecificity of the reactions catalyzed by naphthalene dioxygenase.

Benzofurans↗
PubMed1996

Initial reactions in the oxidation of 1,2-dihydronaphthalene by Sphingomonas yanoikuyae strains.

The substrate oxidation profiles of Sphingomonas yanoikuyae B1 biphenyl-2,3-dioxygenase and cis-biphenyl dihydrodiol dehydrogenase activities were examined with 1,2-dihydronaphthalene and various cis-diols as substrates. m-Xylene-induced cells of strain B1 oxidized 1,2-dihydronaphthalene to (-)-(1R,2S)-cis-1,2-dihydroxy-1,2-3,4-tetrahydronaphthalene as the major product (73% relative yield). Small amounts of (+)-(R)-2-hydroxy-1,2-dihydronaphthalene (15%), naphthalene (6%), and alpha-tetralone (6%) were also formed. Strain B8/36, which lacks an active cis-biphenyl dihydrodiol dehydrogenase, formed (+)-(1R,2S)-cis-1,2-dihydroxy-1,2-dihydronaphthalene (51%), in addition to (-)-(1R,2S)-cis-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene (44%) and (+)-(R)-2-hydroxy-1,2-dihydronaphthalene (5%). The cis-biphenyl dihydrodiol dehydrogenase of strain B1 oxidized both enantiomers of cis-1,2-dihydroxy-1,2-dihydronaphthalene, but only the (+)-(1S,2R)-enantiomers of cis-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene and cis-1,2-dihydroxy-3-phenylcyclohexa-3,5-diene. The results show that biphenyl dioxygenase expressed by S. yanoikuyae catalyzes dioxygenation, monooxygenation, and desaturation reactions with 1,2-dihydronaphthalene as the substrate, and cis-biphenyl dihydrodiol dehydrogenase catalyzes the enantioselective dehydrogenation of (+)-(1S,2R)-cis-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene and (+)-(1S,2R)-cis-1,2-dihydroxy-3-phenylcyclohexa-3,5-diene.

Naphthalenes↗
PubMed1996

Oxidation of 6,7-dihydro-5H-benzocycloheptene by bacterial strains expressing naphthalene dioxygenase, biphenyl dioxygenase, and toluene dioxygenase yields homochiral monol or cis-diol enantiomers as major products.

Bacterial strains expressing naphthalene, biphenyl, and toluene dioxygenase were examined for their abilities to oxidize 6,7-dihydro-5H-benzocycloheptene (benzocyclohept-1-ene). The major oxidation products were isolated, and their absolute configurations were determined by chiral 1H nuclear magnetic resonance analysis of diastereomeric boronate esters, chiral stationary-phase high-pressure liquid chromatography, and stereo-chemical correlation. Pseudomonas sp. strain 9816/11 and Sphingomonas yanoikuyae (formerly identified as a Beijerinckia sp.) B8/36 expressing naphthalene and biphenyl dioxygenases, respectively, oxidized benzocyclohept-1-ene to a major product identified as (-)-(1R,2S)-cis-dihydroxybenzocycloheptane (> 98% enantiomeric excess [ee], 50 and 90% yield, respectively). In contrast, Pseudomonas putida F39/D expressing toluene dioxygenase oxidized benzocyclohept-1-ene to (+)-(5R)-hydroxybenzocyclohept-1-ene (> 98% ee, 90% yield) as the major metabolite and to the "opposite" diol, (+)-(1S,2R)-cis-dihydroxybenzocycloheptane (> 98% ee, 10% yield). The results indicate that, for benzocyclohept-1-ene, the major reaction catalyzed by naphthalene and biphenyl dioxygenases is dioxygenation whereas toluene dioxygenase catalyzes mainly R-stereospecific benzylic monooxygenation. Although the type of reaction catalyzed by each organism was not predictable, the absolute configuration of the diol and monol products formed by naphthalene and toluene dioxygenases are consistent with the stereochemistry of the products formed by these enzymes from other benzocycloalkene substrates.

Bacteria↗
PubMed1996

Regio- and stereospecific oxidation of 9,10-dihydroanthracene and 9,10-dihydrophenanthrene by naphthalene dioxygenase: structure and absolute stereochemistry of metabolites.

The oxidation of 9,10-dihydroanthracene and 9,10-dihydrophenanthrene was examined with mutant and recombinant strains expressing naphthalene dioxygenase from Pseudomonas putida (NCIB 9816.4. Salicylate-induced cells of P. putida strain 9816/11 and isopropylthiogalactopyranoside-induced cells of Escherichia coli JM109(DE3)(pDTG141) oxidized 9,10-dihydroanthracene to (+)-cis-1R,2S)-1,2-dihydroxy-1,2,9,10-tetrahydroanthracene (> 95% relative yield; > 95% enantiomeric excess) as the major product. 9-Hydroxy-9,10-dihydroanthracene (< 5% relative yield) was a minor product formed by both organisms. The same cells oxidized 9,10-dihydrophenanthrene to (+)-cis-(3S,4R)-3,4-dihydroxy-3,4,9,10-tetrahydrophenanthrene (70% relative yield; > 95% enantiomeric excess) and (+)-(S)-9-hydroxy-9,10-dihydrophenanthrene (30% relative yield). The major reaction catalyzed by naphthalene dioxygenase with 9,10-dihydroanthracene and 9,10-dihydrophenanthrene was stereospecific dihydroxylation in which both of the previously undescribed cis-diene diols were of R configuration at the benzylic center adjacent to the bridgehead carbon atom. The results suggest that for benzocylic substrates, the location of benzylic carbons influences the type of reaction(s) catalyzed by naphthalene dioxygenase.

Anthracenes↗
PubMed1995

Sex differences in regional cerebral glucose metabolism during a resting state.

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.

Adult↗
PubMed1995

Resting cerebral glucose metabolism in first-episode and previously treated patients with schizophrenia relates to clinical features.

BACKGROUND: Functional neuroimaging can elucidate brain dysfunction in schizophrenia. The frontal, temporolimbic, and diencephalic regions have been implicated. There is a lack of prospective samples of first-episode and previously treated patients followed up longitudinally. METHODS: Patients and controls (42 per group) were studied. Positron emission tomography with flurodeoxyglucose, cross-registered with magnetic resonance imaging, measured metabolism. Scales assessed clinical features, premorbid adjustment, and outcome. RESULTS: There were no differences between groups in whole-brain metabolism or regional ratios or in anterior-posterior gradients, but left midtemporal metabolism was relatively higher in patients. This was pronounced in the negative and Schneiderian and absent in the paranoid subtypes. Higher metabolism and lower relative left hemispheric values were associated with better premorbid adjustment and outcome. A higher subcortical-cortical gradient was noted in first-episode patients. CONCLUSIONS: There are no resting metabolic abnormalities in any brain region, but abnormal gradients are evident. These vary in subtypes, and laterality is associated with functioning. The results support the hypothesis of temporolimbic disturbance in schizophrenia that is all ready present at the onset of illness.

Adult↗
PubMed1995

Age-associated changes in specific errors on the Benton Visual Retention Test.

While total errors on the Benton Visual Retention Test (BVRT) are known to increase in normal aging, there is little information on changes for specific error types. We examined the differential increase in seven specific error categories for 2,000 participants in the Baltimore Longitudinal Study of Aging. Cross-sectional analyses indicated that all errors increased with age, but differences between age groups in error profiles suggested relatively greater age effects for distortions, omissions, and rotations. There were also significant gender differences in error profiles, reflecting increased rotation and omission errors in females. Longitudinal analyses of age changes for a subset of 673 participants with three BVRT assessments were consistent with the cross-sectional data and indicated intra-individual increases with age in distortions, omissions, and rotations. While women made more omission errors, men showed steeper increases in omission errors with age. These findings suggest that cerebral aging impacts all categories of BVRT errors but has differential effects on particular error types.

Adult↗
PubMed1995

Magnetic resonance imaging reveals no ventriculomegaly in polydrug abusers.

Previous studies of cerebral structure in substance abusers yielded controversial results, largely due to issues of subject selection and/or limitations of experimental techniques. The purpose of the present study was to assess whether the ventricle-to-brain ratio (VBR), determined volumetrically by magnetic resonance imaging (MRI), differed in polysubstance abusers (n = 10), as compared with age-matched controls (n = 10). Subjects were male volunteers 21-39 years of age. The values of VBR in the polydrug abuse group were not larger than those in control group, nor was there any tendency toward relative ventriculomegaly in the substance abusers. Therefore, the present findings provide no evidence that polysubstance abuse produces abnormalities of gross brain structure in relatively young and physically healthy men.

Adult↗
PubMed1995

Desaturation, dioxygenation, and monooxygenation reactions catalyzed by naphthalene dioxygenase from Pseudomonas sp. strain 9816-4.

The stereospecific oxidation of indan and indene was examined with mutant and recombinant strains expressing naphthalene dioxygenase of Pseudomonas sp. strain 9816-4. Pseudomonas sp. strain 9816/11 and Escherichia coli JM109(DE3)[pDTG141] oxidized indan to (+)-(1S)-indanol, (+)-cis-(1R,2S)-indandiol, (+)-(1S)-indenol, and 1-indanone. The same strains oxidized indene to (+)-cis-(1R,2S)-indandiol and (+)-(1S)-indenol. Purified naphthalene dioxygenase oxidized indan to the same four products formed by strains 9816/11 and JM109(DE3)[pDTG141]. In addition, indene was identified as an intermediate in indan oxidation. The major products formed from indene by purified naphthalene dioxygenase were (+)-(1S)-indenol and (+)-(1R,2S)-indandiol. The results show that naphthalene dioxygenase catalyzes the enantiospecific monooxygenation of indan to (+)-(1S)-indanol and the desaturation of indan to indene, which then serves as a substrate for the formation of (+)-(1R,2S)-indandiol and (+)-(1S)-indenol. The relationship of the desaturase, monooxygenase, and dioxygenase activities of naphthalene dioxygenase is discussed with reference to reactions catalyzed by toluene dioxygenase, plant desaturases, cytochrome P-450, methane monooxygenase, and other bacterial monooxygenases.

Benzofurans↗
PubMed1995

Desaturation and oxygenation of 1,2-dihydronaphthalene by toluene and naphthalene dioxygenase.

Bacterial strains expressing toluene and naphthalene dioxygenase were used to examine the sequence of reactions involved in the oxidation of 1,2-dihydronaphthalene. Toluene dioxygenase of Pseudomonas putida F39/D oxidizes 1,2-dihydronaphthalene to (+)-cis-(1S,2R)-dihydroxy-1,2,3,4-tetrahydronaphthalene, (+)-(1R)-hydroxy-1,2-dihydronaphthalene, and (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. In contrast, naphthalene dioxygenase of Pseudomonas sp. strain NCIB 9816/11 oxidizes 1,2-dihydronaphthalene to the opposite enantiomer, (-)-cis-(1R,2S)-dihydroxy-1,2,3,4-tetrahydronaphthalene and the identical (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. Recombinant Escherichia coli strains expressing the structural genes for toluene and naphthalene dioxygenases confirmed the involvement of these enzymes in the reactions catalyzed by strains F39/D and NCIB 9816/11. 1-Hydroxy-1,2-dihydronaphthalene was not formed by strains expressing naphthalene dioxygenase. These results coupled with time course studies and deuterium labelling experiments indicate that, in addition to direct dioxygenation of the olefin, both enzymes have the ability to desaturate (dehydrogenate) 1,2-dihydronaphthalene to naphthalene, which serves as a substrate for cis dihydroxylation.

Dioxygenases↗
PubMed1995

Changes in immediate visual memory predict cognitive impairment.

Six-year changes in immediate visual memory performance assessed by the Benton Visual Retention (BVR) test predicted Alzheimer's disease (AD) prior to its onset. Subjects of this study were 371 community-dwelling adult participants in the Baltimore Longitudinal Study of Aging, seven of whom received probable or definite AD diagnoses using DSM-III-R and NINCDS-ADRDA criteria. Subjects with diagnoses of AD had larger changes in immediate memory performance over the 6-year interval prior to the estimated onset of their disease than subjects without AD. Six-year longitudinal change as well as level in immediate visual memory performance also predicted subsequent cognitive performance 6-15 and 16-22 years later, even after adjusting for the influences of age, general ability, and initial immediate memory. These results provide evidence that change and level in immediate visual memory performance has long-term prognostic significance over as many as 16-22 years. These results further suggest that change in recent memory performance, an important component in AD diagnoses, may be an important precursor of the development of the disease.

Journal Article↗