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Biomedical subjects

A Black

Publications and source records attributed to A Black.

At least 73 records · Page 4Linked to original sources
PubMed1995

The induction of cytotoxic T cells and tumor regression by soluble antigen formulation.

CTLs specific for tumor antigens play a major role in the immunity against cancer. We have shown that class I-restricted CTLs can be induced by injecting soluble antigens mixed in an antigen formulation (AF) that consists of squalane, Tween 80, and Pluronic L121 (S. Raychaudhuri et al., Proc. Natl. Acad. Sci. USA, 89: 8308-8312, 1992). In this study, using ovalbumin and the ovalbumin-expressing transfectoma (EG7) as a tumor model system, we examined the in vivo antitumor effect of antigen-AF mixture. Vaccination of mice with ovalbumin in AF 2 or 3 days after EG7 tumor challenge showed significant inhibition of tumor growth compared to mice vaccinated with ovalbumin in alum or in saline. Depletion of CD8+ cells at the time of immunization completely abrogated the AF-induced tumor protection, indicating that CD8+ T cells are the major effectors in tumor protection in vivo. Depletion of CD4+ cells led to a marginal loss of tumor protection, which may be the result of inhibition of ovalbumin-specific CTL response due to the lack of T-helper activity. Our results demonstrate that AF can be used in subunit vaccines to stimulate CTLs and tumor regression in vivo.

Animals↗
PubMed1995

Families created through ovum donation: a preliminary investigation of obstetrical outcome and psychosocial adjustment.

PURPOSE: This study attempted to obtain preliminary follow-up information regarding obstetrical outcomes and the psychosocial well-being of families created through the ovum donation. There is presently very little known about this population with respect to obstetrical care, health status of offspring, family and marital relationships of recipient couples, or how couples feel about having chosen ovum donation as a family-building option. RESULTS: Fifty-nine couples were initially surveyed and, ultimately, extensive information was obtained for 30 husbands, 31 wives, and 51 offspring. There was a very high percentage of cesarean section deliveries (81.6%), and although a few children experienced health problems at birth, they are all now in good health and developmental milestones are within normal limits. Information was also obtained about breast-feeding experiences, choice of donor (known [sister] or anonymous), reasons for choosing ovum donation over other parenting options, and the impact of this choice on marital and family relationships. Demographic data were also obtained. CONCLUSIONS: For many infertile couples, the long struggle to become parents culminated in a successful birth, and the experience of pregnancy seemed to meet a need to be both biological and psychosocial parents. In general, subjects were extremely cooperative with the investigation and they indicated a desire to learn as much as possible about the psychosocial status of families created through ovum donation. As the assisted reproductive technologies move rapidly into the 21st century, it now seems imperative that health and mental health professionals gain more knowledge about the impact of third party reproduction and the psychosocial adjustment and well-being of families created by this medical technology.

Adaptation, Psychological↗
PubMed1995

Preliminary report: double-blind, placebo-controlled study of fluoxetine in depressed alcoholics.

The selective serotonergic agonist fluoxetine has demonstrated efficacy in the treatment of depression and has possible efficacy in the treatment of nondepressed and depressed alcoholics. However, no double-blind, placebo-controlled trials with any selective serotonergic medication have been reported in patients who have both major depression and alcoholism. In this study, 21 patients with DSM-III-R diagnoses of both major depressive disorder and alcohol dependence were randomized to fluoxetine or placebo in a 12-week, double-blind, parallel group trial. The patients reported a high level of current episode (52.4%), prior episode (61.9%), and lifetime (76.2%) suicidal behavior. Total alcohol consumption during the 12-week treatment course was significantly lower in the fluoxetine group than the placebo group, after controlling for baseline differences in consumption. The fluoxetine group demonstrated a four-fold greater improvement in depressive symptoms, but this difference did not reach statistical significance in this small sample. These preliminary findings suggest that fluoxetine has potential for treating the excessive alcohol ingestion of depressed alcoholics and may have potential for treating the depressive symptoms of these patients as well.

Adolescent↗
PubMed1994

Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia. Trial Group Mainz/Marburg.

Although histamine release is recognised as a common event during anaesthesia and surgery, few clinicians judge the resultant cardiorespiratory disturbances serious enough to warrant prophylaxis with antihistamines. We have assessed the incidence and importance of histamine release in a randomised 2 x 2 factorial study. 240 patients representing a routine throughput of major general surgery were studied during a standardised induction of anaesthesia and preoperative loading of the circulation with either Ringer solution or Haemaccel-35, with or without antihistamine prophylaxis with dimetindene (H1) plus cimetidine (H2). Cardiorespiratory disturbances were graded as detectable, clinically relevant, or life-threatening from observers' records of the anaesthesia and the actions taken by the anaesthetists. Disturbances that were accompanied by significant rises in plasma histamine were further designated histamine-related, and those that were not were designated histamine-unrelated. Anaesthetists, observers, and designators were blinded to whether or not the patients had received antihistamines and to which solution was used for circulatory volume loading. Clinically relevant or life-threatening histamine-related disturbances occurred in 8% of the patients who after induction of anaesthesia received Ringer without antihistamines, in 26% of those who received Haemaccel without antihistamines, and in 2% or less of those who received antihistamines (p < or = 0.0001). There were 4 life-threatening histamine-related disturbances, all in patients who received Haemaccel without antihistamines (p < 0.01). Histamine-unrelated disturbances occurred in 16% overall, with no obvious effect of Haemaccel or antihistamines. The histamine-related disturbances under anaesthesia were remarkable for their severity (even with small rises in histamine concentrations), for the prevalence of bradycardia, and for the absence of skin signs. Their likelihood and severity were increased in patients with tumours. The results of the trial make a case for routine prophylaxis with antihistamines as part of anaesthetic management.

Adolescent↗
PubMed1994

Determination of 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl) dodecanamide, CI-976, in rat plasma by reversed-phase high-performance liquid chromatography.

A quantitative reversed-phase high-performance liquid chromatographic procedure was developed to facilitate the preclinical development of a new Acyl-CoA:cholesterol acyltransferase inhibitor, CI-976 (I). This procedure has a lower quantitation limit of 0.06 micrograms/ml and a quantitation range of 0.06 to 8.0 micrograms/ml of I in rat plasma. The method was applied to pharmacokinetic and toxicokinetic studies of I in rat. With minor modifications, it has also been employed for analysis of I in human, monkey, and rabbit plasma.

Anilides↗
PubMed1994

Initial and long-term results of percutaneous transluminal balloon angioplasty for chronic total occlusions: an analysis of 184 procedures.

BACKGROUND: Coronary angioplasty, although of proven use in partial occlusion, has not been shown to be of similar benefit in chronic total occlusion. AIMS: To assess the utility of coronary angioplasty in chronically totally occluded vessels in patients undergoing angioplasty and to determine the success of TIMI-I flow before angioplasty compared to those patients with TIMI-O flow. METHODS: A group of 178 consecutive patients (from 1984 to 1992), who underwent angioplasty of a chronic occlusion, were analysed. There were 136 males and 42 females with a mean age of 56.9 years. RESULTS: Initial technical success was achieved in 65%. Patients with TIMI-I flow before angioplasty had a higher chance of success (70%) compared to those with TIMI-O flow (53%), p < 0.04. During hospitalisation six patients suffered myocardial infarction (MI), two required surgery and one patient died. During a mean follow-up of 2.8 years the overall survival rate was 95% for the group as a whole. Freedom from coronary surgery was significantly greater in patients with successful angioplasty (93%) than those without (66%, p < 0.002). The above two populations also showed a significant difference in the incidence of angina (35% vs 56%, p < 0.0003). However, the incidence of MI (6% vs 5%, p > 0.5) and cardiac survival (98% vs 94%, p > 0.1) did not differ significantly in the two groups. Restenosis occurred in 63% of the 95 patients (82%) who returned for follow-up angiography. Eighteen of the 59 patients (28%) with restenosis had a reocclusion. CONCLUSION: The success rate for angioplasty of chronic total occlusions is acceptable. Long-term clinical benefit in patients with successful angioplasty is suggested by the high freedom from angina and the lesser need for coronary surgery. No major impact on either the incidence of MI or cardiac survival was noted when patients who had coronary surgery were included, although it must be emphasised that the sample size in this study was insufficient to detect a difference in these outcome variables.

Angioplasty, Balloon, Coronary↗
PubMed1994

Staff attachment and loss in a long term baby ward.

Little systematic attention has been given to the intense involvement of nursing and medical staff, and its emotional consequences for them, whilst caring for long stay very sick infants. This survey of 12 doctors and 14 nurses involved in such work confirmed the presence of consistent attachment behaviours, and examined the contributory elements such as direct contact and interaction in determining that attachment. Staff were found to relate to infants on an individualized basis, and clearly recognized temperamental differences. Differences in attachment patterns between nurses, consultants and registrars were evident, and appeared to again reflect specific opportunities for contact and interaction. Implications for hospital policy were raised.

Adult↗
PubMed1993

Divergent pharmacologic activities of PD 132301-2 and CL 277,082, urea inhibitors of acyl-CoA:cholesterol acyltransferase.

The in vitro potencies and hypocholesterolemic properties of CL 277,082 and PD 132301-2, two urea inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT) were compared. PD 132301-2 was several-fold more potent at inhibiting ACAT in microsomes from rat and rabbit tissues and in cultured cells (murine macrophages and the human HepG2 cell line). This disubstituted urea was also relatively specific for ACAT as other cholesterol esterifying enzymes (e.g., lecithin:cholesterol acyltransferase, pancreatic cholesterol ester hydrolase), as well as intestinal diglyceride synthesis (acyl-CoA:monoglyceride acyltransferase), were unaffected in vitro at relevant concentrations. In normal chow-fed rats, both compounds reduced plasma triglycerides at doses > 50 mg/kg, but only PD 132301-2 reduced plasma cholesterol. In rat and rabbit models of hypercholesterolemia the greater in vitro potency of PD 132301-2 translated into greater in vivo efficacy (i.e., ED50 values 2- to 3-fold higher for CL 277,082 in both acute and chronic rate models). Of particular note was the greater elevation of high-density lipoprotein-cholesterol and parenteral activity of PD 132301-2 compared to CL 277,082 in the chronic rat model. Inhibition of cholesterol absorption in rats was also greater with PD 132301-2. In guinea pigs, in which 77% of plasma cholesterol was transported in low-density lipoprotein, PD 132301-2 potently reduced plasma total cholesterol (lowest significant dose = 1 mg/kg) as well as plasma triglycerides. CL 277,082 only reduced cholesterol at doses > 100 mg/kg in this low-density lipoprotein model. In a canine model of hypercholesterolemia CL 277,082 was inactive at doses up to 50 mg/kg, but PD 132301-2 was active at 3 mg/kg. Moreover, efficacy in dogs with PD 132301-2 was positively correlated with plasma drug concentration, an observation not previously demonstrated for other hypolipidemic drugs. The combined data illustrate that pharmacologic activities can vary widely among ACAT inhibitors of the same general class. In addition, the unique observation of proportionality between efficacy and blood drug levels in nonrodent animal models may not only help to simplify early stages in drug development but also may help to predict or monitor a direct action of the drug on vascular disease.

Absorption↗
PubMed1993

Proliferation of mouse lung epithelial cells after inhalation exposure to 239PuO2.

The aim of this study was to investigate cell proliferation in mouse lungs up to 12 weeks after exposure to 239PuO2. CBA mice were exposed (nose-only) to 239PuO2 to give an initial alveolar deposit of 500 Bq. The main morphological change observed was hypertrophy of Type II cells. The labeling index (LI) of alveolar cells, which was monitored by immunocytochemical detection of DNA-incorporated 5-bromo-2'-deoxyuridine (BrdU), increased with time after exposure and was eight times that of controls by the end of the study. The LI of the bronchiolar cells was increased markedly after exposure but declined thereafter. The cell proliferation patterns of the alveolar and bronchiolar cells (mainly Type II and Clara cells, respectively) could be related to the distribution and clearance patterns of the deposited particles of 239PuO2 and to the effects of alpha-particle radiation on these cells. This study showed that significant cellular changes, particularly cell proliferation, occurred at early times after exposure of mouse lung to 239PuO2. However, the relevance of these results to the late carcinogenic effects of 239Pu could not be assessed because of the limited duration of this study.

Administration, Inhalation↗
PubMed1992

The biochemistry and pharmacology of PD 116124 (8-amino-2'-nordeoxyguanosine), an inhibitor of purine nucleoside phosphorylase (PNP).

PD 116124 (8-amino-2'-nordeoxyguanosine; 2,8-diamino-1,9-dihydro-9- ([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)-6H-purin-6-one) is a competitive, reversible inhibitor of human purine nucleoside phosphorylase with an apparent inhibition constant of 0.41 microM. In a cell line system using human MOLT-4 and CEM T lymphoblasts and human MGL-8 and NC-37 B lymphoblasts, PD 116124 failed to inhibit [3H]thymidine uptake at concentrations up to 500 microM. However, in the presence of 10 microM 2'-deoxyguanosine (dGuo), a noninhibitory dGuo concentration by itself, PD 116124 produced potent inhibition of growth of both T cell lines but not of either B cell line. Significant elevation of intracellular 2'-deoxyguanosine triphosphate was observed in both inhibited T cell lines but not in either B cell line. Greater and more sustained accumulation of 2'-deoxyguanosine triphosphate was observed in T lymphoblasts cultured with PD 116124 plus dGuo than with dGuo only. PD 116124 was only weakly inhibitory in human mixed lymphocyte cultures (IC50 approximately equal to 1420 microM), but in the presence of 10 microM dGuo, the IC50 for PD 116124 was reduced to 108.7 microM. Administration of PD 116124 p.o. to normal male Wistar rats caused dose-dependent elevation of plasma inosine up through 500 mg/kg. Maximal inosine elevation occurred at 30 min after dosing, and elevation was significant even 24 hr after dosing. Guanosine was also elevated, although not in a dose-dependent manner. Administration of PD 116124 i.v. produced marked and statistically significant elevation of both inosine and guanosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗