Biomedical subjects

B A Johnson

Publications and source records attributed to B A Johnson.

At least 73 records · Page 4Linked to original sources

PubMed1999

Upstream elements bestow T-cell and haemopoietic progenitor-specific activity on the granzyme B promoter.

Cytotoxic T cells and early haemopoietic progenitors share the expression of a number of specific genes. Of these, granzyme B has attracted particular interest because of its role in inducing apoptosis during cytotoxic T cell-mediated target cell killing, and its potential role in the mobilisation and homeostasis of haemopoietic stem cells. Studies of granzyme B regulation should therefore yield valuable information concerning the molecular control of these processes, and also identify elements capable of directing gene expression to two cell types of relevance to gene therapy. Here we show that proximal regulatory elements already known to direct promoter activity in T cells are similarly active in haemopoietic progenitors. However, this activity is not strictly specific, since the promoter regions also direct low levels of reporter gene expression in fibroblasts. More importantly, we also report the presence of two previously unidentified clusters of DNaseI hypersensitive sites upstream from the murine granzyme B gene, and show that these regions impart both increased transcriptional activity and the appropriate cell type specificity on the granzyme B promoter. These upstream regulatory regions are therefore likely to play a key role in the coordination of granzyme B expression in vivo.

Animals↗

PubMed1999

Flexible sigmoidoscopy: screening for colorectal cancer.

Flexible sigmoidoscopy is an important screening procedure because of its ability to detect early changes in the distal colon. The 60-cm flexible sigmoidoscope provides excellent visualization with minimal discomfort to patients. Successful sigmoidoscopy requires adequate patient preparation, proper equipment and an experienced examiner who can recognize both normal and abnormal findings. Complications arising from sigmoidoscopy are rare, but patients may experience some cramping, gas or watery stools. Screening and primary preventive measures, including regular exercise and increased dietary fiber intake, can lower the morbidity and mortality associated with colorectal cancer.

Colorectal Neoplasms↗

PubMed1999

The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory.

BACKGROUND: Fatigue is a major disease and treatment burden for cancer patients. Several scales have been created to measure fatigue, but many are long and difficult for very ill patients to complete, or they are not easy to translate for non-English speaking patients. The Brief Fatigue Inventory was developed for the rapid assessment of fatigue severity for use in both clinical screening and clinical trials. METHODS: The study enrolled 305 consecutive, consenting adult inpatients and outpatients with cancer who could understand and complete the self-report measures used in the study. The same instruments also were administered to 290 community-dwelling adults to obtain a comparison sample. Research staff completed a form that indicated the primary site and stage of the cancer, rated the Eastern Cooperative Oncology Group performance status of the patient, described the characteristics of the pain, and described the current pain treatment being provided to the patients. RESULTS: The BFI was shown to be an internally stable (reliable) measure that tapped a single dimension, best interpreted as severity of fatigue. It correlated highly with similar fatigue measures. Greater than 98% of patients were able to complete it. A range of scores defining severe fatigue was identified. CONCLUSIONS: The BFI is a reliable instrument that allows for the rapid assessment of fatigue level in cancer patients and identifies those patients with severe fatigue.

Case-Control Studies↗

PubMed1999

Flexible sigmoidoscopy: screening for colorectal cancer.

Colorectal Neoplasms↗

PubMed1999

Relationships of plasma tryptophan availability to course of illness and clinical features of alcoholism: a preliminary study.

RATIONALE: Serotonergic (5-HT) mechanisms may be involved in impulse control (including antisocial behavior) across psychiatric syndromes. Age of onset may differentiate alcoholics on psychopathological characteristics associated with impulse control, especially mood disturbance, hostility, and a broad range of antisocial behaviors. Thus, there may be a predictable relationship between markers of 5-HT function and age of onset-related characteristics. OBJECTIVE: We tested the hypothesis that there would be a predictable relationship between the ratio of plasma tryptophan to large neutral amino acids (i.e. TRYP/LNAA ratio), a marker of 5-HT function, age of onset and related psychopathological characteristics associated with impulse control. METHODS: Fifty-eight male and female DSM-IV diagnosed alcoholics attending an outpatient treatment center completing a comprehensive psychopathological assessment, and from whom blood samples were obtained. RESULTS: Plasma TRYP/LNAA ratio was positively correlated with symptoms of dysphoria, and negatively associated with harm avoidance on Cloninger's Temperament and Character Inventory. Low tryptophan availability was associated with antisocial-type personality characteristics. Interestingly, the few (nine) subjects who had both early onset alcoholism and antisocial personality disorder had a higher plasma tryptophan but similar TRYP/LNAA ratio to the others. CONCLUSIONS: These data suggest that a low plasma TRYP/LNAA ratio is associated with susceptibility to anxiety, antisocial-type personality characteristics, and an early age of onset for alcoholism. In contrast, a high plasma TRYP/LNAA ratio is associated with a later onset of alcoholism and dysphoria.

Age of Onset↗

PubMed1999

Isradipine, a dihydropyridine-class calcium channel antagonist, attenuates some of d-methamphetamine's positive subjective effects: a preliminary study.

RATIONALE: Dopamine (DA) pathways in the midbrain mediate d-methamphetamine's rewarding effects associated with its abuse liability. Isradipine, a dihydropyridine-class calcium channel antagonist, reduces the rewarding effects of psychostimulants such as cocaine and d-amphetamine, presumably by antagonizing these central DA pathways. This is the first experiment to test the hypothesis that the rewarding effects of d-methamphetamine, like other psychostimulants, can be reduced by isradipine. OBJECTIVE: We studied the effects of high dose isradipine (0.21 mg/kg orally), on the positive subjective effects associated with the abuse liability of low and high dose d-methamphetamine (0.21 mg/kg and 0.42 mg/kg orally, respectively). METHODS: Using a double-blind, double-dummy, placebo-controlled, Latin-Square, cross-over design, 18 healthy male and female volunteers received each of the following six treatments separated by a rest period of 2-7 days: a) placebo+placebo; b) low-dose d-methamphetamine+placebo); c) high-dose d-methamphetamine+placebo; d) high dose isradipine+placebo); e) low-dose d-methamphetamine+high dose isradipine, and f) high-dose d-methamphetamine+high dose isradipine. RESULTS: d-Methamphetamine produced orderly increases in positive subjective measures of both stimulation and mood. Pre-treatment with isradipine significantly reduced some of these positive subjective effects and craving for d-methamphetamine. CONCLUSION: Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d-methamphetamine dependence.

Adrenergic Agents↗

PubMed1999

Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on d-methamphetamine-induced reduction in hunger.

1. The authors studied the effects of isradipine, a dihydropyridine-class calcium channel antagonist, on d-methamphetamine-induced changes in somatic and psychological perceptions of hunger state using a placebo-controlled, double-blind, Latin Square, cross-over design in 18 healthy volunteers. 2. D-methamphetamine significantly decreased these subjective ratings of hunger, presumably by increasing monoaminergic turnover. 3. Effects on hunger are hypothesized to be mediated by norepinephrine primarily, while dopamine plays only a modest role. Isradipine alone, an inhibitor of dopamine release, had no significant effect on the hunger measures. Additionally, isradipine pretreatment did not significantly alter d-methamphetamine's anorexic effects. 4. Isradipine may, therefore, not significantly modify the control of hunger in humans.

Adolescent↗

PubMed1999

Biphasic stimulation of prostacyclin by endogenous nitric oxide (NO) in endothelial cells transfected with inducible NO synthase.

Nitric oxide (NO) regulates prostaglandin H synthase (PGHS) activity in various cell types, but reports conflict in regard to its stimulatory versus inhibitory role. Murine lung endothelial cells infected with a retroviral vector expressing the human inducible NO synthase gene were used to prevent ambiguous effects of NO from either exogenous chemical donors or cytokine-stimulated cells. Low concentrations of endogenous NO led to a dose-dependent increase in 6-keto PGF1alpha production (p < 0.05), whereas the highest production of NO resulted in lower 6-keto PGF1alpha production. These data demonstrate a complex regulation of PGHS activity by NO that needs to be considered when proposing a physiological or pathophysiological role for NO.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Ethnic differences in the neuroleptic treatment of schizophrenia.

Ethnic differences in psychopharmacological treatment have received much attention in the last two decades. Most of the research efforts conducted so far in the field of ethnopsychopharmacology have focused on comparative responses to neuroleptics and lithium between white and Asian-American patients, and on comparative responses to tricyclic antidepressants among white, African-American and Hispanic patients. In this article we focus on the response to neuroleptic treatment among white, African-American and Hispanic patients suffering from schizophrenia. Our findings suggest that Hispanic patients need lower doses of neuroleptics than white or African-American patients to attain a similar response in the treatment of schizophrenia. Additionally, our study suggests that, if weight is taken to consideration, African-American patients need the same dose of neuroleptics as do white patients in order to attain a similar response in the treatment of schizophrenia. Further studies are suggested to confirm our findings.

Acute Disease↗

PubMed1999

4-chloro-m-cresol triggers malignant hyperthermia in susceptible swine at doses greatly exceeding those found in drug preparations.

BACKGROUND: Chlorocresols are used as preservatives in numerous commercial drugs that have been shown to induce myoplasmic Ca2+ release; the most potent isoform is 4-chloro-m-cresol. The aims of this study were to (1) examine the in vivo effects of 4-chloro-m-cresol on swine susceptible to malignant hyperthermia and (2) contrast in vivo versus in vitro dose-response curves. METHODS: Susceptible swine (weight: 38.5 kg+/-3.55 kg) were anesthetized and monitored for variations in physiological responses, including end-tidal CO2, heart rate, blood pressure, blood chemistry, and temperatures. In the first animals studied, 4-chloro-m-cresol, at equivalent cumulative doses of 0.14, 0.28, 0.57, 1.14, 2.27, 4.54, and 9.08 mg/kg (n = 3; 12.5, 25, 50, 100, 200, 400, and 800 micromol) were administered, and in a second group, larger doses were used: 1.14, 3.41, 7.95, 17.04 (n = 4), and/or 35.22 (n = 1) mg/kg (100, 300, 700, 1,500, and/or 3,100 micromol). For comparison, in vitro rectus abdominis muscle preparations obtained from normal and susceptible swine were exposed to 4-chloro-m-cresol, at cumulative concentrations of 6.25, 12.5, 25, 50, 100, 200, 400, 800, and 1,600 micromol; standard caffeine and halothane contracture testing was also performed. RESULTS: Episodes of malignant hyperthermia were not triggered in response to administration of low doses of 4-chloro-m-cresol, but transient cardiovascular reactions (e.g., tachycardia, arrhythmias, and hypotension) were observed. Subsequently, episodes in these animals were triggered when halothane (0.87; 1 MAC) and succinylcholine (2 mg/kg) were given. Animals administered the higher doses of 4-chloro-m-cresol all had fulminant episodes of malignant hyperthermia that were fatal, when equivalent cumulative concentrations were greater than 1,500 micromol. The levels of 4-chloro-m-cresol in the plasma rapidly decreased: e.g., 5 min postadministration of the 1,500-micromol dose, the mean plasma level was only 52+/-18 micromol (n = 4). Hemolysis was detected following 4-chloro-m-cresol administration at concentrations > 200 micromol. In vitro, muscle from susceptible animals elicited contractures > 200 mg at 50-micromol bath concentrations of 4-chloro-m-cresol (n = 29), whereas normal muscle did not elicit such contractures until bath concentrations were > 800 micromol (n = 10). CONCLUSIONS: 4-chloro-m-cresol is a trigger of malignant hyperthermia in susceptible swine, but only when serum concentrations are far above those likely to be encountered in humans. A relatively low concentration of 4-chloro-m-cresol, 50 micromol, is sufficient to activate sarcoplasmic [Ca+2] release in vitro (e.g., contractures); this same bolus dose administered in vivo (0.57 mg/kg) has minimal effects due to the rapid decrease in its plasma levels.

Animals↗

PubMed1999

Epidurography and therapeutic epidural injections: technical considerations and experience with 5334 cases.

BACKGROUND AND PURPOSE: Even in experienced hands, blind epidural steroid injections result in inaccurate needle placement in up to 30% of cases. The use of fluoroscopy and radiologic contrast material provides confirmation of accurate needle placement within the epidural space. We describe our technique and experience with contrast epidurography and therapeutic epidural steroid injections, and review the frequency of systemic and neurologic complications. METHODS: Epidural steroid injections were performed in 5489 consecutive outpatients over a period of 5 1/2 years by three procedural neuroradiologists. In 155 cases (2.8%), the injections were done without contrast material owing to either confirmed or suspected allergy. The remaining 5334 injections were performed after epidurography through the same needle. Patients and referring clinicians were instructed to contact us first regarding complications or any problem potentially related to the injection. In addition, the referring clinicians' offices were instructed to contact us regarding any conceivable procedure-related complications. RESULTS: Only 10 patients in the entire series required either oral (n = 5) or intravenous (n = 5) sedation. Four complications (0.07%) required either transport to an emergency room (n = 2) or hospitalization (n = 2). None of the complications required surgical intervention, and all were self-limited with regard to symptoms and imaging manifestations. Fluoroscopic needle placement and epidurography provided visual confirmation of accurate needle placement, distribution of the injectate, and depiction of epidural space disease. CONCLUSION: Epidurography in conjunction with epidural steroid injections provides for safe and accurate therapeutic injection and is associated with an exceedingly low frequency of untoward sequelae. It can be performed safely on an outpatient basis and does not require sedation or special monitoring.

Adolescent↗

PubMed1999

Lesser metatarsal stress fractures.

Stress fractures continue to be a fact of military life. With appropriate attention to training issues, shoe gear, and physical training activities, however, their effect can be minimized.

Fractures, Stress↗

PubMed1999

Medications to treat alcoholism.

Advances in neurobiology support the development of medications to treat alcoholism by modifying the activity of specific chemical messengers (i.e., neurotransmitters) in the brain. Among the most promising new medications is acamprosate, which appears to decrease the intensity of craving after a person has stopped drinking. Naltrexone (ReVia) has been shown to decrease alcohol consumption, although its practical effectiveness may be compromised by poor patient compliance and other factors. Ondansetron shows promise for decreasing drinking and increasing abstinence rates among early onset alcoholics, who respond poorly to psychosocial treatment alone. Researchers are investigating whether the use of specific medications in combination can further enhance their effectiveness. Additional research is needed to determine how medications interact with different psychosocial factors and treatments.

Acamprosate↗

PubMed1998

Spatial coding of odorant features in the glomerular layer of the rat olfactory bulb.

In order to determine whether molecular features of odorants are represented spatially in the glomerular layer of the olfactory bulb, we used metabolic mapping of [14C] 2-deoxyglucose uptake in rats exposed to equal vapor concentrations of odorants differing systematically in chemical structure. The odorants were ethyl acetate, ethyl butyrate, isoamyl acetate, and isoamyl butyrate. Statistical analysis of anatomically standardized arrays of uptake revealed that each ester produced a characteristic spatial pattern of activity in the glomerular layer. The patterns were similar in different rats exposed to the same odorant, and their complexity increased with increasing odorant carbon number. This finding suggests that the presence of more potentially recognized molecular features is associated with a greater number of activated receptors. Individual regions of the glomerular layer responded specifically to isoamyl esters, and other regions preferred ethyl esters. Regions of similar specificity occurred in lateral and medial aspects of the bulb, the medial representation being more caudal and ventral than the lateral one. This pattern correlates with projections of olfactory sensory neurons expressing the same putative olfactory receptor gene. The patterns overlapped greatly in the posterolateral and posteromedial glomerular layer, a finding one should predict, given the large overlap in chemical structure across the aliphatic esters. Thus, molecular features appear to be encoded spatially in the glomerular layer, and the identity of the odorant may be determined by a subsequent decoding of the combination of molecular features represented in the glomerular layer.

Acetates↗

PubMed1998

Stability of diagnosis in bipolar disorder.

The study goals were: a) to determine factors associated with diagnostic change from bipolar disorder (BPD) to other disorders and vice versa and b) to focus on subjects with diagnostic changes specifically between BPD and schizophrenia. A total of 936 subjects with at least four hospitalizations within 7 years were identified from the hospital database to study the first goal. A subset of 443 subjects with initial and final diagnoses of bipolar disorder and/or schizophrenia was used for the second goal. Sixty-eight (28.9%) of 235 subjects with an initial diagnosis of BPD changed to another diagnosis, whereas 113 (16.1%) of 701 subjects with a non BPD diagnosis had a diagnostic change to BPD at a later episode. Only 8 of 43 subjects entering the study period with a diagnosis of schizoaffective disorder still had that diagnosis at the end of the period. Results suggest that diagnostic flux between BPD and other disorders, especially schizophrenia, is relatively frequent. Gender, ethnicity, and substance abuse/dependence have prominent roles in these diagnostic changes. Severity and variability of the course of illness and progression of concurrent substance use disorder are crucial to understanding diagnostic flow in BPD.

Adult↗

PubMed1998

The familial aggregation of adolescent suicide attempts.

The objective of this study was to determine whether the familial aggregation of suicidal behaviour is explained by the familial aggregation of personality disorder and aggression. The relatives of 62 clinically referred adolescent suicide attempters were compared with 70 never-suicidal psychiatric controls. The first-degree relatives of the suicide attempters had a higher rate of suicide attempts/completion than those of the psychiatric controls. This rate remained significantly higher after controlling for Axis I and II differences in the probands and the relatives, but familial personality disorder was significantly associated with suicidal risk in probands. Among the adolescent attempters, high scores on a measure of assaultiveness were associated with significantly higher familial rates of suicide attempts/completion. Our results support the hypothesis that suicidal behaviour may be transmitted as a trait independent of Axis I and II psychopathology but that, in addition, personality disorder has a role in the transmission of suicidal behaviour. An interrelationship between proband assaultiveness and the familial aggregation of suicidality was noted.

Adolescent↗

PubMed1998

Inhibiting geranylgeranylation blocks growth and promotes apoptosis in pulmonary vascular smooth muscle cells.

The activity of small GTP-binding proteins is regulated by a critical step in posttranslational processing, namely, the addition of isoprenoid lipids farnesyl and geranylgeranyl, mediated by the enzymes farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I), respectively. We have developed compounds that inhibit these enzymes specifically and in this study sought to determine their effects on smooth muscle cells (SMC) from the pulmonary microvasculature. We found that the GGTase I inhibitor GGTI-298 suppressed protein geranylgeranylation and blocked serum-dependent growth as measured by thymidine uptake and cell counts. In the absence of serum, however, GGTI-298 induced apoptosis in these cells as measured by both DNA staining and flow cytometry. The FTase inhibitor FTI-277 selectively inhibited protein farnesylation but had a minor effect on growth and no effect on apoptosis. To further investigate the role of geranylgeranylated proteins in apoptosis, we added the cholesterol synthesis inhibitor lovastatin, which inhibits the biosynthesis of farnesyl and geranylgeranyl pyrophosphates. This also induced apoptosis, but when geranylgeraniol was added to replenish cellular pools of geranylgeranyl pyrophosphate, apoptosis was reduced to baseline. In contrast, farnesol achieved only partial rescue of the cells. These results imply that geranylgeranylated proteins are required for growth and protect SMC against apoptosis. GGTase I inhibitors may be useful in preventing hyperplastic remodeling and may have the potential to induce the apoptotic regression of established vascular lesions.

Alkyl and Aryl Transferases↗

PubMed1998

How to save distressed IDS-physician marriages: a case study.

A hospital-driven IDS that encounters serious problems resulting from ownership of a physician practice should address those problems by focusing on three core areas: vision and leadership, effectiveness of operations, and physician compensation arrangements. If changes in these areas do not lead to improvements, the IDS may need to consider organizational restructuring. In one case study, a hospital-driven IDS faced the problem of owning a poorly performing MSO with a captive physician group. The IDS's governing board determined that the organization lacked effective communication with the physicians and that realization of the organization's vision would require greater physician involvement in organizational decision making. The organization is expected to undergo some corporate reorganization in which physicians will acquire an equity interest in the enterprise.

Delivery of Health Care, Integrated↗