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Biomedical subjects

D Shore

Publications and source records attributed to D Shore.

At least 91 records · Page 5Linked to original sources
PubMed1988

Attenuation of ultrasound in homogenates of bovine skeletal muscle and other tissues.

The attenuation of ultrasound in homogenates of bovine skeletal muscle and suspensions of myofibrils was measured over the frequency range 1.5-7 MHz, and found to be proportional to protein concentration in both. In the homogenates it varied with frequency and temperature in a similar way to the attenuation in post rigor muscle tissue; myofibrils showed a higher frequency dependence. The attenuation in homogenates of bovine muscle, liver and kidney and in suspensions of myofibrils was measured over the pH range 3.5-13, and each showed a peak at about pH 11.5. This was thought to be due to a proton transfer process between NH3+ groups on the tissue proteins and OH- ions in the suspending fluid. A substantial peak at about pH 5 in the muscle and myofibril suspensions was not observed in homogenates of liver and kidney and was thought to be due to components of muscle that are absent from the other tissues. Myofibrils suspended in percoll solution of density 1.05 g cm-3, chosen to match approximately the density of the myofibrils, showed a slightly lower attenuation over the pH range 5-7, but a pH dependence similar to that of the myofibrils suspended in saline. The difference in the attenuations may be interpreted as the viscous component of the attenuation due to relative motion between the myofibril and its surrounding saline. The peak at pH 5 did not, however, appear to be due to the viscous loss mechanism peaking due to maximum shrinkage (and therefore maximum density) of the myofibril near this pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Violent crime arrests and paranoid schizophrenia: the White House case studies.

We have previously reported on typically paranoid schizophrenic patients who attempted to see the President or other prominent American political figures based on hallucinations or delusional beliefs. By obtaining arrest records on these White House Cases (WHCs), we were able to determine which individuals had murder or assault arrests before and/or after their WHC hospitalizations. During the 9-12 years following discharge, 31 of the 217 male WHCs (for whom adequate clinical records were available) had murder or assault arrests. Demographic characteristics such as prior violent crime arrest and male gender proved to be much better predictors of future violence than clinical symptom, history, or behavior items. Hospital incidents requiring seclusion and a history of weapons possession were both associated with later violence in WHCs with prior violent crime arrests, while certain clinical symptoms (e.g., persecutory delusions and command hallucinations) may be linked to future violence in WHCs without prior violent crime arrests. These data need replication in other patient samples.

Chronic Disease↗
PubMed1987

Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements.

A DNA binding protein (RAP1, previously called SBF-E) has been shown to bind to putative regulatory sites at both yeast mating-type silencers, yet is not the product of genetically identified regulators of the silent loci. Here, we report the purification of RAP1 by DNA affinity chromatography, and the isolation of its gene from a lambda gt11 genomic library using antibodies raised against the protein. Disruption of the chromosomal copy of this gene is lethal. We show that RAP1 protein also binds in vitro to the upstream activation site (UAS) of MAT alpha and ribosomal protein genes. In addition, we show that two different UAS-associated RAP1 binding sites can substitute in vivo for a silencer binding site. Our results suggest that RAP1 may be a transcriptional regulator that can play a role in either repression or activation of transcription, depending upon the context of its binding site.

Amino Acid Sequence↗
PubMed1987

Transcriptional regulation in the yeast life cycle.

The transition from haploid to diploid in homothallic yeast involves a defined sequence of events which are regulated at the level of transcription. Transcription factors encoded by SWI genes activate the HO endonuclease gene at a precise stage in the cell cycle of mother cells. The HO endonuclease initiates a transposition event which activates genes of the opposite mating type by causing them to move away from a silencer element. The activated mating type genes then regulate genes involved in cell signaling such as the mating type-specific pheromones and their receptors. Since HO is only activated in one of the sister cells after division (the mother), adjacent cells of opposite mating type are generated which respond to each others' secreted pheromones by inducing genes involved in conjugation. This leads to the formation of a diploid in which many of the genes involved in mating and mating-type switching become repressed due to the heterozygosity of the mating-type locus. This article summarizes what is known about these transcriptional controls and discusses possible parallels in higher eukaryotes.

Crosses, Genetic↗
PubMed1986

Attenuation of ultrasound in post rigor bovine skeletal muscle.

A pulse transmission method for measuring the attenuation of 1-7 MHz ultrasound in bovine skeletal muscle is described. Measurements of the attenuation coefficient at -20, 0, 20 and 40 degrees C conformed to the relation alpha = Afn, where A and n are temperature-dependent coefficients and f is the frequency. alpha/f varied slowly with frequency, and at 4 MHz and 20 degrees C mean values were 1.3 dB cm-1 MHz-1 along the fibres and 0.55 dB cm-1 MHz-1 across the fibres. These data are lower than most previous measurements of skeletal muscle, but comparable with recent measurements of canine heart muscle.

Animals↗
PubMed1986

Incentives and disincentives for schizophrenia research careers.

A meeting was convened to discuss schizophrenia research career incentives and disincentives. A diverse group of scientists from different fields and in different career stages discussed the causes of and potential solutions to schizophrenia research manpower problems. The scientific and clinical, individual and institutional factors involved were identified and numerous disincentives to careers in schizophrenia research were noted. A number of possible incentives were also suggested and debated. There was general agreement on the following issues: attracting and maintaining a larger group of young investigators is crucial; multidisciplinary studies combining clinical and basic science approaches should be strongly encouraged; and mechanisms for increasing funding and stimulating interest in schizophrenia research careers should be studied by the National Institute of Mental Health. Specific recommendations are now being assessed to determine how best to respond to the schizophrenia research manpower needs that were identified at the meeting.

Congresses as Topic↗
PubMed1986

Effects of alpha-naphthoflavone on levels of sister chromatid exchanges in lymphocytes from active and passive cigarette smokers: dose-response relationships.

The frequency of sister chromatid exchanges (SCE) were determined in lymphocytes of nonsmokers, passive smokers, and active smokers in the presence and absence of alpha-naphthoflavone (ANF). Higher levels of SCEs were detected for all smoking groups after in vitro addition of ANF when compared with an assay without ANF. There was a highly statistically significant difference between heavy smokers and nonsmokers (9.25 versus 7.43 SCE/cell) for the assay without ANF and for the ANF assay (14.2 versus 8.8). When considering the numerical difference in SCEs between the assays with and without ANF (delta SCE), higher values were noted for moderate smokers (2.7) and heavy smokers (4.9) compared to nonsmokers (1.4). Significant dose-response relationships were found between the frequency of SCEs and factors related to smoking, such as duration and frequency of cigarette use, tar, nicotine, carbon monoxide content of brand, and urinary measures of nicotine metabolites (cotinine and thiocyanate). No elevation of SCEs in passive smokers was found when compared to nonsmokers using either assay. The mechanism for SCE enhancement by ANF is unclear, but may be related to metabolic activation of the ANF by the cytochrome P-450 system in lymphocytes. The dosimetry relationships between cigarette smoke exposure and SCE frequency indicate that culture of human lymphocytes via ANF may provide a sensitive tool to detect exposure to cigarette smoke.

Adolescent↗
PubMed1985

White House Cases: psychiatric patients and the Secret Service.

Delusional visitors to the White House or other government offices (often seeking a personal audience with the President) are interviewed by the Secret Service and then sent to Saint Elizabeths Hospital if they are considered mentally ill and potentially dangerous to themselves or others. A review of the demographic characteristics and diagnoses of 328 of these "White House Cases" treated at the hospital between 1970 and mid-1974 showed that these patients were most commonly unmarried, white, and male, and most had a diagnosis of paranoid schizophrenia. Although 22% of this group have threatened some prominent political figure, to date none of this study's patients has attempted to assassinate any such government official.

Adult↗
PubMed1984

Characterization of two genes required for the position-effect control of yeast mating-type genes.

The mating type of haploid yeast (a or alpha) is determined by information present at the MAT locus. Identical copies of a and alpha information are present at distal loci (HMR and HML), but transcription of these copies is repressed by the action, in trans, of four unlinked genes called SIR (silent information regulator). Repression by SIR also requires, in cis, DNA sequences called E which are found to the left of HML and HMR (but not MAT) and are greater than 1 kb from the mating-type gene promoters. SIR control can act on other promoters when they are brought near the E sequence, and thus the SIR gene products act in some general manner to repress transcription. We have determined the DNA sequence of two fragments which complement mutations in the SIR2 and SIR3 genes and show that these contain the structural genes by mapping the cloned sequences onto the yeast chromosome. The SIR2 and SIR3 coding sequences were identified by constructing gene disruptions and using these mutations to replace the normal chromosomal copies. Such null mutants of both SIR2 and SIR3 are defective in the position-effect control of the silent loci but have no other detectable phenotype. We have mapped the 5' and 3' ends of the SIR2 and SIR3 mRNAs and show that their level is unaffected by mutations in any of the four known SIR complementation groups.

Amino Acid Sequence↗
PubMed1984

Hair and serum copper, zinc, calcium, and magnesium concentrations in Alzheimer-type dementia.

Several research groups have reported alterations in mineral concentrations in patients with Alzheimer's disease (AD). A study of serum copper, zinc, magnesium, calcium, and albumin concentrations in outpatients with Alzheimer's disease (in the early-to-middle stages) and in these patients' healthy spouses is reported. Hair concentrations of copper, zinc, magnesium, calcium, and manganese were also measured in these AD patients and controls. No differences in serum of hair concentrations were found, and determinations of these hair and serum mineral concentrations do not appear to be of use in the diagnosis of AD. Significant positive correlations were found between age and hair manganese (Mn) in the control spouses, and a similar (but statistically nonsignificant) trend in the AD patients.

Aged↗
PubMed1983

Energetics of DNA twisting. I. Relation between twist and cyclization probability.

The twisting potential of DNA has been determined directly by a method that measures the cyclization probability or j-factor of EcoRI restriction fragments as a function of DNA twist. The cyclization probability is proportional to Kc, the equilibrium constant for cyclization of the restriction fragment via its cohesive ends (Shore et al., 1981). Here we vary the twist of the DNA by making small internal additions to or deletions from a 242 bp EcoRI restriction fragment. A series of 12 DNA molecules has been studied, which range in length from 237 to 254 bp. The cyclization probability is measured from the rates of covalent closure by phage T4 DNA ligase of two systems: (1) a linear restriction fragment in equilibrium with its cyclized form and (2) half molecules (cut by a blunt-end endonuclease) in equilibrium with joined half molecules. The striking result is that, in this DNA size range, the j-factor depends strongly on the fractional twist: the difference between the total helical twist and the nearest integer. Thus j depends in an oscillatory manner on DNA length between 237 and 254 bp with a period of about 10 bp. These data give the free energy of DNA twisting as a function of twist. The curve of j versus DNA length can be fitted to a harmonic twisting potential with a torsional constant of C = 2.4 X 10(-19) erg cm. This value is in reasonable agreement with different estimates of C made by Barkley & Zimm (1979: C = 1.8 X 10(-19) to 4.1 X 10(-19) erg cm) and is somewhat larger than the value obtained resulting from the kinetics of DNA twisting measured by fluorescence depolarization of ethidium intercalated into DNA (C = 1.4 X 10(-19) erg cm; Millar et al., 1982; Thomas et al., 1980) or from spin label studies (Hurley et al., 1982). Our experiments provide a direct measurement of the torsional free energy and they show that the DNA twisting potential is symmetric. Our experiments also indicate that the DNA helix is continuous, or nearly so, in a nicked circle; presumably this happens because the DNA stacking interaction maintains the double helix in register across a single-strand nick. As a consequence, the twist of a singly nicked DNA circle is integral for small (approximately equal to 250 bp) planar DNA circles and there is a change in twist upon cyclization.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoradiography↗
PubMed1983

Energetics of DNA twisting. II. Topoisomer analysis.

A gel electrophoresis method has been developed for resolving small (approximately equal to 250 bp DNA topoisomers. In this size range only one major topoisomer band is observed, except for ligase closure conditions in which the probabilities are nearly equal for circularization by untwisting and overtwisting the corresponding linear DNA. The two probabilities are nearly equal when delta Tw is close to 0.5, if the mean helical twist of the linear DNA is n + delta Tw, where n is an integer and delta Tw is the fractional twist. We determine delta Tw of the linear DNA in standard conditions (20 degrees C, no ethidium) by titration experiments in which delta Tw is varied at the time of ligase closure, either by changing temperature or ethidium concentration. The endpoint (delta Tw = 0.5) is found when the two topoisomers formed by untwisting and overtwisting are present at equal concentrations. This analysis assumes that the net writhe is zero and the DNA helix is isotropically bendable. The results confirm the analysis of cyclization probabilities given in the preceding paper: delta Tw = 0 at the two maxima in the curve of j-factor versus DNA length and delta Tw = 0.5 at the minimum. Consequently, we can determine the DNA lengths at which Tw takes on integral values and use them to measure precisely the average helix repeat. From the difference between the delta Tw values of DNAs with 237 and 247 bp, we obtain an approximate value for the helix repeat of h = 10.4 +/- 0.1 bp/turn, in good agreement with earlier values found by the band-shift and nuclease-cutting methods. The twist is integral at 250.8 +/- 0.4 bp and from h = 10.4 +/- 0.1 we find n = 24; then 250.8/24 gives h = 10.45 +/- 0.02 bp/turn. The mean linking number (Lk) changes in a stepwise manner as delta Tw is varied for 250 bp DNAs. This result is expected when the free energy of twisting half a turn becomes large compared to thermal fluctuations. In these experiments, it is possible to obtain the mean Tw value from the mean Lk value only when delta Tw = 0.5, and consequently the mean Lk value is not simply related to DNA length for 250 bp DNAs except when delta Tw = 0.5.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoradiography↗
PubMed1983

Reproducible replacement of elongated or ruptured mitral valve chordae.

Anatomical rules that make it possible to accurately replace mitral anterior cusp chordae tendineae with tanned xenograft pericardium are defined. Anterior and posterior cusp chordae were replaced with xenograft and autologous pericardium in 11 patients who had ruptured or elongated chordae. The xenograft occasionally became calcified; however, because it did not become elongated or shortened, competence was maintained for up to 3 years. Insufficiency was corrected, and the correction maintained for up to 4 months. Degenerative disease proved easier to treat than rheumatic disease. Two-dimensional echocardiography was a valuable aid in both preoperative planning and postoperative evaluation.

Adult↗
PubMed1983

Aluminum and Alzheimer's disease.

There are many medical conditions that increase brain Al concentrations without producing the dementia or neuronal degeneration (with "paired-helical filaments" [PHFs]) typical of Alzheimer's disease (AD). Aluminum accumulations have been found in the nuclei of PHF-containing neurons in the brains of AD patients and elderly normal controls. We have, however, found no elevations of Al concentrations in the serum, cerebrospinal fluid, or hair in AD patients. These findings suggest that Al alone is not a "cause" of AD. Aluminum may be just a "marker" of PHF-bearing neurons, or AD patients may be "vulnerable" to Al neurotoxicity on the basis of some other neuronal dysfunction allowing Al to enter neuronal nuclei. It is too soon to tell whether any of the variety of experimental anti-Al approaches currently being evaluated have any effect on the rate of progression of AD symptoms.

Aluminum↗
PubMed1983

CSF copper concentrations in chronic schizophrenia.

The authors used a sensitive flameless atomic absorption spectrophotometric procedure to measure CSF copper concentrations in normal controls, former heroin addicts, and unmedicated and medicated chronic schizophrenic patients and found no significant differences in CSF copper levels between these groups. Schizophrenic women had significantly lower CSF copper levels than schizophrenic men, but no significant differences were found between control men and control women. There were no differences in CSF copper levels between patient subgroups with respect to diagnostic subtype (acute versus chronic, paranoid versus chronic undifferentiated), length of hospitalization, race, medication status, platelet monoamine oxidase values, or CAT scan abnormalities.

Adult↗