[Transactivation: a fundamentally biological phenomenon implicated in carcinogenesis].
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Biomedical subjects
Publications and source records attributed to R Thomas.
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Bovine leukaemia virus (BLV) is the aetiological agent of a chronic lymphatic leukaemia/lymphoma in cows, sheep and goats. Infection without neoplastic transformation has also been demonstrated in pigs, rhesus monkeys, chimpanzees and rabbits and observed in capybaras and water buffaloes. Structurally and functionally, BLV is a relative of human T lymphotropic viruses 1 and 2 (HTLV-I and HTLV-II) since all three viruses show clear-cut sequence homologies. The pathology of the BLV-induced disease, most notably the absence of chronic viraemia, a long latency period and lack of preferred proviral integration sites in tumours, is similar to that of adult T-cell leukaemia/lymphoma induced by HTLV-I. The most striking feature of the three naturally transmitted leukaemia viruses is the X region located between the env gene and the long terminal repeat (LTR) sequence. The X region contains several overlapping long open reading frames, one of which, designated XBL-1, encodes a trans-activator function capable of increasing the level of gene expression directed by BLV-LTR and is most probably involved in genetic instability of BLV-infected cells of the B-cell lineage. The 'genetic instability' may put the cell into a state of fragility, ready to move along a number of stages towards full malignancy. Little is known about these events and their causes and we present some theoretical possibilities. BLV infection has a worldwide distribution. In temperate climates the virus spreads mostly through iatrogenic transfer of infected lymphocytes. In warm climates and in areas heavily populated by haematophagous insects, there are indications of insect-borne propagation of the virus.
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Thyroid disorders are often ubiquitous and insidious in their presentation. They have been implicated in a broad spectrum of reproductive disorders ranging from abnormal sexual development to menstrual irregularities and infertility. If pregnancy occurs in a patient with thyroid disease, the physician must ensure that therapeutic measures instituted to restore the health of the mother do not adversely affect the developing fetus. This review examines the role of thyroid disease in disorders confronting the obstetrician/gynecologist and provides a theoretical framework upon which to base practical management decisions.
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It has been postulated that pulsatile blood flow helps to preserve the myocardium after ischemia. However, its effect on postischemic myocardium during cardiopulmonary bypass has not been clearly defined. To determine if pulsatile reperfusion improves postischemic recovery of cardiac metabolism and performance, we subjected 20 dogs to 60 minutes of aortic cross-clamping followed by 45 minutes of pulsatile (P group; 10 dogs) or nonpulsatile (NP group; 10 dogs) reperfusion. Left ventricular function was measured at a controlled preload in both groups before induction of global ischemia and after termination of bypass. Segmental length (assessed by sonomicrometry) was used to determine dimensional changes. Ventricular pressures were measured with solid-state micromanometers. Percent recovery of left ventricular peak systolic pressure, its first derivative, and stroke work were 66%, 59%, and 38%, respectively in the NP group and 82%, 76%, and 65% in the P group. The postarrest decrease in segmental shortening was minimized in the P group; left ventricular function curves and the slope of the end-systolic pressure-length relationship also indicated better performance after pulsatile reperfusion than after nonpulsatile reperfusion. Myocardial lactate extraction was transiently improved during the early pulsatile reperfusion period. We conclude that pulsatile reperfusion provides better myocardial preservation than nonpulsatile perfusion after 60 minutes of induced global ischemia.
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Parkinson's disease is a neurodegenerative disorder characterized mainly by damage to the dopaminergic nigrostriatal system. Recently, the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce damage in the nigrostriatal system, accompanied by Parkinson-like symptoms in humans. We present here evidence that MPTP treatment in aged 21-month-old mice produced a marked reduction in the presence and intensity of fluorescence in noradrenergic neurons of the locus coeruleus and in dopaminergic neurons of the ventral tegmental area in addition to extensive damage to the substantia nigra. Aged mice treated with MPTP also showed physical signs of movement disability characterized by marked akinesia, rigidity of the hind limbs, and an initial resting tremor of the entire body. Such symptoms were less evident in young mice treated with MPTP. These remarkable initial behavioral effects of MPTP treatment in aged mice and evidence of reduced catecholamine fluorescence in the locus coeruleus and ventral tegmental area suggest that aged mice are more sensitive to, and more severely affected by MPTP treatment than young mice. We suggest that these MPTP-treated aged mice provide a useful animal model for studying both anatomical and functional characteristics of Parkinson's disease.
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The 5 alpha H-cardenolide, gomphoside, is one of a small group of naturally occurring cardiac glycosides in which the sugar residue is bilinked to the steroid ring system. This arrangement prevents the sugar moiety from rotating and this makes gomphoside and related compounds potentially useful for structure-activity relationship (SAR) studies. When gomphoside was tested for inotropic activity using guinea pig left atria, the compound was found to have very high potency comparable to the most active 5 beta H-cardenolides. Removal of the sugar moiety reduced inotropic activity almost 500-fold indicating that it was the presence of the sugar moiety that was mainly responsible for the drug's high potency. Modification of the steroid or sugar residue of gomphoside reduced activity in all cases. It would thus appear that gomphoside with its high potency and non-rotatable glycosidic linkage is an excellent tool for SAR studies.
Previous reports have suggested that patients with heart failure and coexistent ventricular tachyarrhythmias have a 1-year mortality of 40% to 60%. To assess whether an antiarrhythmic management program could reduce mortality, we studied 20 consecutive patients with ventricular fibrillation (12) or ventricular tachycardia (eight) and heart failure. Coronary disease was the most common underlying cardiac disorder (85%). Heart failure was managed with digoxin (16), diuretics (16), and vasodilators (seven). All patients received antiarrhythmic drug therapy guided by both noninvasive and invasive studies. This included single (10) or combination drug therapy (10). Beta blockers were used alone or in combination for arrhythmia control in 11 patients. One-year survival was 89%. We conclude that an effective program can be developed for patients with life-threatening ventricular tachyarrhythmias and heart failure. Combination antiarrhythmic drug therapy is often required. Despite impaired left ventricular function, beta-blocking drugs can be used, and may be important.
Survival following 3 hr of total circulatory arrest under profound hypothermic conditions was explored in 19 adult mongrel dogs. Thermoregulatory management included combined surface/perfusion hypothermia and azeotrope anesthesia in 95% O2/5% CO2. All animals were resuscitated and survived for at least 12 hr. During the last seven trials (Group II) the following principles were applied: uniform whole-body cooling where differences between rectal, esophageal, and pharyngeal temperatures averaged less than 1 degree C, induction of circulatory arrest at approximately 3 degrees C, constant lung inflation (10-12 cm H2O between 20 degrees C cooling and 20 degrees C rewarming, including the 3-hr arrest period) and ventilation assistance with positive end-expiratory pressure (4 cm H2O) after 20 degrees C rewarming, intraoperative maintenance of colloid osmotic pressure (COP) above 11 mm Hg, replacement of the cooling perfusate with a colloid-rich rewarming prime (COP = 15 mm Hg) and restoration of hemostasis with fresh whole blood transfusions. The application of these principles resulted in the long-term survival of five animals with four survivors displaying no clinically detectable neurological abnormalities. However, two animals developed optic impairment and one animal died from intusseption on the fourth postoperative day. Despite the improved results, it should also be noted that during pilot (Group I) studies (from which the aforementioned principles were derived) fatalities from complications attributed to systemic edema, central nervous system, or pulmonary or coagulation dysfunctions occurred in 9 out of 12 trials. We conclude that whole body protection following 3 hr of total circulatory arrest at a uniform temperature less than 5 degrees C can be successfully accomplished.
Description of the interactions between bovine herpesvirus type 1 (BHV-1) and cattle was performed by the method known as kinetic logic. This logical formalization uses variables with two possible values, 1 and 0, which tell whether an element is present or not at a significant level. To each variable is associated a function which tells if the element is being produced at a significant rate. The temporal relation between a variable and its associated function is given by specific time delays. The BHV-1 infection system is described by a set of five logical equations which tell in what conditions each function is on or off. The five functions are: V, development of viral multiplication; R, development of reactivation of the latent virus; A, development of an immune response; G, establishment of the viral genome; M, development of a memory of a first immune response. Several examples are detailed in a dynamic analysis, in connection with known experimental data.
An unusual and hitherto unreported presentation of a bull gore injury sustained during harvest festival celebrations is described. The patient was seen with the metal horn cover complete with decorative ribbons impacted in his orbit. The injury had caused a blowout fracture of the orbital floor, and at surgery the globe was retrieved from the maxillary antrum. The development of optic atrophy precluded useful vision in the injured eye.