Biomedical subjects

J A Coffman

Publications and source records attributed to J A Coffman.

At least 19 recordsLinked to original sources

PubMed1995

Genetic evidence for Gln3p-independent, nitrogen catabolite repression-sensitive gene expression in Saccharomyces cerevisiae.

The expression of many nitrogen catabolic genes decreases to low levels when readily used nitrogen sources (e.g., asparagine and glutamine) are provided in the growth medium; this physiological response is termed nitrogen catabolite repression (NCR). Transcriptional activation of these genes is mediated by the cis-acting element UASNTR and the trans-acting factor Gln3p. A second protein encoded by URE2 possesses the genetic characteristics of a negative regulator of nitrogen catabolic gene expression. A third locus, DAL80, encodes a repressor that binds to sequences required for Gln3p-dependent transcription and may compete with Gln3p for binding to them. These observations are consistent with an NCR regulatory pathway with the structure environmental signal-->Ure2p-->(Gln3p/Dal80p)-->UASNTR operation-->NCR-sensitive gene expression. If NCR-sensitive gene expression occurs exclusively by this pathway, as has been thought to be the case, then the NCR sensitivity of a gene's expression should be abolished by a ure2 delta mutation. This expectation was not realized experimentally; the responses of highly NCR-sensitive genes to ure2 delta mutations varied widely. This suggested that NCR was not mediated exclusively through Ure2p and Gln3p. We tested this idea by assaying GAP1, CAN1, DAL5, PUT1, UGA1, and GLN1 expression in single, double, and triple mutants lacking Gln3p, Dal80p, and/or Ure2p. All of these genes were expressed in the triple mutant, and this expression was NCR sensitive for four of the six genes. These results indicate that the NCR regulatory network consists of multiple branches, with the Ure2p-Gln3p-UASNTR pathway representing only one of them.

Asparagine↗

PubMed1992

Complexity of sea urchin embryo nuclear proteins that contain basic domains.

We describe a quantitative two-dimensional gel electrophoretic analysis of nuclear extract from 24-hr sea urchin embryos. The extract was fractionated by using a weak cation-exchange resin, and eight known DNA-binding proteins were shown to be entirely included in a salt eluate that releases proteins containing basic domains. This fraction and a lower-salt fraction containing the majority of the protein species were mapped two-dimensionally by using new algorithms that permit reproducible spot identification, storage of intensity and map-position data, and subtractive comparison of one pattern with respect to another. By reference to a previously characterized DNA-binding factor, spot intensity could be interpreted in terms of the number of molecules per embryo nucleus. A map was constructed displaying all nuclear proteins containing basic domains that are present within the concentration range per nucleus of a set of known DNA-binding factors of the sea urchin embryo. The map includes 265 spots that fulfill both of these criteria, probably representing about 100 different protein species.

Animals↗

PubMed1992

Expression of spatially regulated genes in the sea urchin embryo.

Spatially controlled genes expressed in the early sea urchin embryo have been characterized, and the patterns of expression in terms of the mechanisms by which this embryo accomplishes its initial set of founder cell specifications are the subject of current discussion. Sea urchin transcription factors that have been cloned are classified with respect to their target sites and the genes they regulate. Among the best known of the sea urchin cis-regulatory systems is that controlling expression of the Cyllla gene, which encodes an aboral ectoderm-specific cytoskeletal actin. The Cyllla regulatory domain includes approximately 20 sites of DNA-protein interaction, serviced by about ten different factors. Certain of these factors are known to negatively control spatial expression, while others positively regulate temporal activation and the level of Cyllla gene expression. Differential, lineage-specific gene expression is instituted in the sea urchin embryo by mid-late cleavage, prior to any cell migration or overt differentiation, and shortly following lineage segregation.

Animals↗

PubMed1992

Defining the dose range for esmolol used in electroconvulsive therapy hemodynamic attenuation.

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting, beta-adrenergic receptor blocking drug, to control the sinus tachycardia and increase in arterial blood pressure induced by electroconvulsive therapy (ECT). Each of 20 patients, ASA physical status I-III, participated in a double-blind, randomized Latin-Square study involving two matched-pair trials (placebo versus esmolol given as a 500-micrograms/kg bolus followed by either 300 micrograms.kg-1.min-1 [high dose], 200 micrograms.kg-1.min-1 [medium dose], or 100 micrograms.kg-1.min-1 [low dose] infusion of esmolol) during ECT. Each patient acted as his or her own control (total number of ECT procedures were 160). We administered a 1-min bolus of placebo (normal saline) or esmolol at the rate of 500 micrograms.kg-1.min-1 followed by either high-, medium-, or low-dose esmolol or placebo for an additional 3 min. We then induced anesthesia with methohexital (1 mg/kg) and succinylcholine (0.5 mg/kg) IV. Ninety seconds after the administration of succinylcholine, the electrical stimulus was applied to induce seizure. The infusion of placebo or esmolol was discontinued 3 min after the electrical stimulus. Significant decreases were found in mean heart rate from minute 3 until minute 7 and in the maximum heart rate. The mean of each patient's maximum heart rate after seizure changed from 147 +/- 18 bpm in placebo patients to 112 +/- 20 bpm in high-dose esmolol patients; to 121 +/- 23 bpm in medium-dose esmolol patients; and to 124 +/- 20 bpm in low-dose esmolol patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1992

Commitment along the dorsoventral axis of the sea urchin embryo is altered in response to NiCl2.

Few treatments are known that perturb the dorsoventral axis of the sea urchin embryo. We report here that the dorsoventral polarity of the sea urchin embryo can be disrupted by treatment of embryos with NiCl2. Lytechinus variegatus embryos treated with 0.5 mM NiCl2 from fertilization until the early gastrula stage appear morphologically normal until the midgastrula stage, when they fail to acquire the overt dorsoventral polarity characteristic of untreated siblings. The ectoderm of normal embryos possesses two ventrolateral thickenings just above the vegetal plate region. In nickel-treated embryos, these become expanded as a circumferential belt around the vegetal plate. The ectoderm just ventral to the animal pole normally invaginates to form a stomodeum, which then fuses with the tip of the archenteron to produce the mouth. In nickel-treated embryos, the stomodeal invagination is expanded to become a circumferential constriction, and it eventually pinches off as the tip of the archenteron fuses with it to produce a mouth. Primary mesenchyme cells form a ring in the lateral ectoderm, but as many as a dozen spicule rudiments can form in a radial pattern. Dorsoventral differentiation of ectodermal tissues is profoundly perturbed: nickel-treated embryos underexpress transcripts of the dorsal (aboral) gene LvS1, they overexpress the ventral (oral) ectodermal gene product, EctoV, and the ciliated band is shifted to the vegetal margin of the embryo. Although some dorsoventral abnormalities are observed, animal-vegetal differentiation of the archenteron and associated structures seems largely normal, based on the localization of region-specific gene products. Gross differentiation of primary mesenchyme cells seems unaffected, since nickel-treated embryos possess the normal number of these cells. Furthermore, when all primary mesenchyme cells are removed from nickel-treated embryos, some secondary mesenchyme cells undergo the process of "conversion" (Ettensohn, C. A. and McClay, D. R. (1988) Dev. Biol. 125, 396-409), migrating to sites where the larval skeleton would ordinarily form and subsequently producing spicule rudiments. However, the skeletal pattern formed by the converted cells is completely radialized. Our data suggest that a major effect of NiCl2 is to alter commitment of ectodermal cells along the dorsoventral axis. Among the consequences appears to be a disruption of pattern formation by mesenchyme cells.

Animals↗

PubMed1992

Automated sequential affinity chromatography of sea urchin embryo DNA binding proteins.

An automated method of running a tandem sequence of oligonucleotide affinity columns was used to purify factors that interact specifically with cis-regulatory sites of the CyIIIa cytoskeletal actin gene of the sea urchin embryo (Strongylocentrotus purpuratus). The method allows quantitative enrichment in a single chromatographic run of up to 12 different sequence-specific DNA binding proteins, each of which may then be readily purified to homogeneity by methods such as preparative gel electrophoresis. The affinity chromatography and identification of six different CyIIIa-regulatory factors is described, and the general utility of the method is discussed.

Actins↗

PubMed1991

Perinatal brain injury and cerebellar vermal lobules I-X in schizophrenia.

Several studies, including our own, have reported atrophy of the cerebellar vermis in some schizophrenic patients. A recent report by Courchesne et al (1988) of hypoplasia of a developmentally specific region of the cerebellar vermis in autism prompted us to hypothesize that the cerebellar "atrophy" in some schizophrenic patients may also have developmental origins. We measured the area of the vermal lobules in 30 male schizophrenics. Contrary to expectation, the patients as a group had consistently larger cerebellar structures than the controls. Patients with perinatal injury had smaller structures than the nonperinatally injured group, but these measures were still larger than in the control subjects. Patients without perinatal injury differed from controls, having larger lobules VI-VII (p less than 0.03). These preliminary findings tentatively suggest a role for developmental factors for cerebellar structures in schizophrenia. Further research is needed to clarify the cerebellar vermal changes observed in some schizophrenic patients.

Adult↗

PubMed1990

Cognitive impairment and cerebral structure by MRI in bipolar disorder.

The distinction between bipolar disorder and schizophrenia customarily follows examination of the clinical symptomatology and course of illness. The presence of cognitive impairment has been held to be uncommon in bipolar disorder and more likely in schizophrenia. This study explored neuropsychological function in 30 ambulatory outpatients with a DSM-III-R diagnosis of bipolar affective disorder (all of whom had been psychotic during manic episodes), comparing their performance with that of controls. These bipolar patients proved to have significant levels of diffusely represented cognitive impairment when compared with controls. Further, the degree of impairment was significantly correlated with reduction in midsagittal areas of brain structures measured on magnetic resonance imaging scans. The implications of these findings in relation to bipolar disorder are discussed.

Adult↗

PubMed1990

Leukoaraiosis in asymptomatic adult offspring of individuals with Alzheimer's disease.

The presence of white matter changes on magnetic resonance imaging (MRI), which has been referred to by Hachinski (1987) as leukoaraiosis, is frequently noted in elderly individuals in conditions ranging from health to frank dementia. This study involved the use of MRI to document cerebral structure if 41 healthy 50-60-year-old individuals, 28 of whom were offspring of Alzheimer's disease victims. On visual inspection of spin-echo images, 13 of the 28 offspring showed white matter lesions whereas all of the controls were free of leukoaraiosis. This statistically significant difference suggests that the presence of leukoaraiosis might be of importance in understanding changes in the white matter among populations at increased risk for Alzheimer's disease.

Alzheimer Disease↗

PubMed1990

A hyaline layer protein that becomes localized to the oral ectoderm and foregut of sea urchin embryos.

An antigen is described which is a marker for the oral ectoderm and foregut of the sea urchin embryo. In Lytechinus variegatus, the antigen is first detectable by immunofluorescence on the surface of fertilized eggs, and remains globally distributed through the early stages of gastrulation. Thereafter the antigen is localized to the oral ectoderm and foregut, coincident with the morphogenesis of these regions. The antigen is a large, detergent-insoluble, filamentous glycoprotein associated with the tips of the microvilli in the hyaline layer. This glycoprotein is present in two forms, a approximately 350-kDa form that is maternally synthesized and a much larger form which is synthesized at late gastrula stage as a 350-kDa precursor before becoming modified and assembled into the hyaline layer. The timing of synthesis of the zygotic form of the molecule correlates precisely with the localized expression of the antigen. The antigen copurifies with intact hyaline layers and cosediments with hyalin in the presence of calcium, suggesting that it is a structural component of the hyaline layer.

Animals↗

PubMed1990

Neuropsychological deficit in schizophrenic subtypes: paranoid, nonparanoid, and schizoaffective subgroups.

Schizophrenic patients were carefully diagnosed and screened for a history of neurological disorders. Diagnosis and subtyping was based on DSM-III-R criteria, using the Structured Clinical Interview for DSM-III-R, which was administered by trained interviewers and confirmed by a research psychiatrist. The schizophrenic patients were compared with an age-matched control group on an extensive battery of neuropsychological measures. The undifferentiated/disorganized schizophrenic patients were consistently the most impaired on a broad range of tasks. When the effect of symptom severity and drug level were statistically controlled (analysis of covariance), however, the magnitude and number of differences were substantially reduced. The perseverative error score from the Wisconsin Card Sort Test showed the greatest difference between the groups. However, the strongest and most consistent effects were observed in relation to symptom ratings. These data indicate the importance of controlling for medication and symptom severity, and suggest that current diagnostic classifications may not be the most useful factors for studies of the cognitive correlates of schizophrenia.

Adult↗

PubMed1990

Gender differences in schizophrenia on MRI brain scans.

There are many reports of clinical and biological gender differences in schizophrenia. Gender differences in structural brain abnormalities in schizophrenia have been reported on both computed tomographic (CT) and magnetic resonance imaging (MRI) scans. We present here a new MRI study of cerebral structures in schizophrenia. On the basis of previous findings, we hypothesized that schizophrenic males are more likely than females to show smaller brains and larger ventricles compared to their control counterparts. Our results indicated that the opposite was true: schizophrenic females, but not schizophrenic males, had smaller craniums and brains and larger lateral and third ventricles on MRI scans. The possible significance and implications of these data are discussed.

Adolescent↗

PubMed1990

Esmolol reduces autonomic hypersensitivity and length of seizures induced by electroconvulsive therapy.

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting beta 1-adrenergic receptor blocking drug, to control the sinus tachycardia and increase in arterial blood pressures induced by electroconvulsive therapy (ECT). Each of 20 patients, ASA physical status I-III, participated in a double-blind, randomized study, involving four match-pair trials (placebo versus esmolol) during ECT. Each patient acted as his or her own control (total number of ECT procedures, 160). We administered a 4-min infusion of either placebo or esmolol at the rate of 500 micrograms.kg-1.min-1. We then induced anesthesia with methohexital and succinylcholine. After administration of electrical stimulation for ECT, the rate of infusion decreased to 300 micrograms.kg-1.min-1 for three additional minutes and was then discontinued. Statistically significant reductions in mean heart rate from minute 2 until minute 15 and in maximum heart rate (the mean of each patient's maximum heart rate after seizure changed from 152 +/- 23 to 115 +/- 24 beats/min) occurred in patients given esmolol. During and immediately after infusion, arterial blood pressure also decreased. Finally, the length of seizures decreased, as manifested clinically from 48 +/- 18 to 39 +/- 14 s and on electroencephalogram from 86 +/- 41 to 67 +/- 28 s. We conclude that esmolol effectively controls the hyperdynamic response to ECT and reduces the length of seizures. The significance of the latter to the overall effectiveness of ECT is not known.

Adrenergic beta-Antagonists↗

PubMed1990

Third and lateral ventricular volumes in schizophrenia: support for progressive enlargement of both structures.

Third and lateral ventricular enlargement exists in a subgroup of schizophrenic patients. It is unclear, however, whether these abnormalities consistently coexist in the same patients or represent distinct pathologies. Whether these changes are static or progressive in nature is also unresolved. Third and lateral ventricular volumes (magnetic resonance imaging, total volumes calculated on complete coronal series) were examined in controls (n = 20) and schizophrenic patients (n = 20). Third ventricular, but not lateral ventricular, volume was increased in patients. Ventricular intercorrelations differed significantly between patients and controls. Ventricular measures were more highly correlated in patients than in controls. Age was also significantly more positively correlated with ventricular measures in patients. Results replicate the finding of third ventricular enlargement in some schizophrenic patients. The high correlation between lateral and third ventricular size in schizophrenic patients suggests a pathologic process affecting both structures. Enlargement of both third and lateral ventricles may be more specific to schizophrenic patients than enlargement of either structure alone. The data also indirectly support progression of ventricular enlargement.

Adult↗

PubMed1989

Perinatal complications and genetic loading in schizophrenia: preliminary findings.

History of perinatal complications (PCs) and first degree family history (FH) of psychiatric illness were examined in groups of schizophrenic/schizoaffective (n = 21) and bipolar (n = 10) patients. PCs were significantly more frequent in the schizophrenic and schizoaffective patients than in bipolar patients. An inverse relationship was found between PCs and FH status, with FH-positive patients having significantly fewer PCs than the FH-negative group. This relationship persisted when the bipolar patients were excluded. Findings emphasize the etiological importance of genetics and perinatal events in the psychoses, and support the validity of a familial/sporadic distinction.

Brain Damage, Chronic↗

PubMed1989

Event-related brain potentials in depressed patients treated with electroconvulsive therapy.

1. As impairment of attention has long been recognized as a clinical feature of depression, we undertook to evaluate in depressed subjects and controls a feature of the event-related brain potentials (ERP) the N100 wave which has been linked to attentional processes. 2. This study involved collection of EEG data in an "auditory oddball" ERP paradigm in 9 depressed subjects prior to and following a course of 6 electroconvulsive therapy (ECT) treatments, as well as 11 controls. Concurrent Hamilton depression rating scales provided a measure of symptomatic severity. 3. Pretreatment N100 amplitude was significantly lower in the depressed group while N100 latency was greater than among controls, with treatment differences from control values disappeared. Further a robust correlation (r = 0.85 p less than or equal to .0038) emerged between N100 amplitude (increased amplitude being lower) and severity of depression. 4. Those results provide evidence for a physiological attentional disturbance in depression and suggest that certain features of this disturbance relate directly to symptom severity.

Adult↗

PubMed1989

Structural brain-imaging findings in affective disorders: an overview.

In recent years, numerous reports of structural brain abnormalities found with computerized tomography (CT) scans in affective disorders (e.g., major depression, bipolar disorder) have been published. More currently, magnetic resonance imaging (MRI) studies have provided additional data on brain structure in affective disorders. In this article, the various CT and MRI findings in affective disorders are reviewed, and the clinical and research relevance of those neuroanatomical findings are presented and discussed.

Brain↗

PubMed1989

Cholinergic hypothesis of depression: a reappraisal.

Evidence for the cholinergic hypothesis of depression is reviewed, arguments directed against this hypothesis are set forth, and the strengths and weaknesses of these criticisms are discussed. The authors conclude that the cholinergic hypothesis is tenable but suggest new areas of study.

Acetylcholine↗