Transcription factors: an overview

In this article, we report complementation of the genetic defect of isolated Gunn rat hepatocytes by a highly efficient method for lipofection. Transfections were performed 24 h after plating by using the cationic liposome DOTAP. On average, transfection efficiencies of 21% lacZ+ cells with Wag/Rij rat cells and 27% lacZ+ cells with Gunn rat cells could be obtained when the parenchymal cells were transfected in a hormone-defined, serum-free medium. LacZ expression vectors with the CMV promoter were more effective than constructs containing the RSV or the TK promoter. A linear relationship between the viability of hepatocytes after isolation and the percentage of lacZ+ cells was observed with both rat strains, with a maximum of 40% lacZ+ cells at a viability of 94%. The transfection efficiencies were significantly lower in the absence of growth factors, in dexamethasone-containing medium, or when serum was present during plating. Our data are consistent with the assumption that a mitotic event is required for efficient lipofection. Bilirubin conjugation activity could be detected in microsomes from Gunn rat hepatocytes after transfection with two different B-UDPGT expression constructs. Highest conjugation activity was achieved with a vector containing a terminal intron. With this construct on average 4% of the bilirubin conjugation activity of normal human liver microsomes could be achieved in total microsomes of transfected Gunn rat hepatocytes. The implications of our data for gene therapy of hepatic disease with nonviral vectors, in particular bilirubin conjugation deficiency (Crigler-Najjar disease) are discussed.     

Cross-sectional and longitudinal changes in total and high-density-lipoprotein cholesterol levels over a 20-year period in elderly men: the Honolulu Heart Program

PURPOSE: The purpose of this report is to describe levels of total cholesterol and high-density-lipoprotein cholesterol (HDL-C) in a group of elderly men and to compare these levels to those that were observed 20 years earlier. METHODS: From 1965-1968, the Honolulu Heart Program began following 8006 men of Japanese ancestry living on the island of Oahu, Hawaii, in a prospective study of coronary heart disease and stroke. This report presents data for 971 men who participated in a separate fasting study of lipids and lipoproteins that first occurred from 1970-1972 and in those who received repeat examinations 10 and 20 years later. Men were aged 71-93 years at the last examination. RESULTS: Over the 20-year period, total cholesterol declined by 1.6-1.8 mg/dL per year (P < 0.001), from average baseline values of 219-222 mg/dL. Levels of HDL-C rose 0.2-0.3 mg/dL per year (P < 0.001), from average baseline values of 44-46 mg/dL. After adjustment for baseline cholesterol levels, men with prevalent coronary heart disease at the end of the 20-year follow-up experienced significantly greater reductions in total cholesterol levels than men without disease (P < 0.001). Men who developed coronary heart disease within the first 10 years of follow-up had the greatest yearly decline in total cholesterol (1.9 mg/dL), followed by men who developed heart disease later (1.8 mg/dL) and men who remained disease free (1.5 mg/dL). Differences between men with recent and earlier disease were not statistically significant, although men without coronary disease experienced a significantly smaller decrease in total cholesterol than either of these groups (P < 0.05). CONCLUSIONS: Changes in total cholesterol and HDL-C levels with advancing age may be part of a natural aging process. Some changes, however, such as large reductions in total cholesterol, may signal occult disease or declines in overall health. Selective survival may contribute to these findings since improvements in lipid and lipoprotein levels that are beneficial in younger ages were common in this long-lived cohort of men.     

Left ventricular morphology in chronic renal failure by echocardiography

M-mode, two-dimensional, and Doppler echocardiography were performed in 38 chronic renal failure (CRD) patients on conservative management, 35 patients on hemodialysis, and 36 matched controls. The controls were matched for age, sex, and comorbidities. The incidence of hypertension, left ventricular (LV) end diastolic volume, LV end systolic volume, and LV mass index were significantly higher in patients on hemodialysis compared to the controls. The LV parameters in the predialysis patients were not significantly different from the controls, except the LV end systolic internal dimensions were significantly higher in the CRF patients. Multiple regression analysis underscored the strong association between increase in LV mass index (LVMI) and hypertension. The diabetic patients with renal failure had large LV internal diameter and end diastolic volume compared to non-diabetics. Systolic function was well preserved even in hypertensive and diabetic patients with uremia. The incidence of diastolic dysfunction and asymmetrical septal hypertrophy were not significantly different in the three groups of patients.     

Effects of cytosolic Ca2+ on the Ca2+ content of the sarcoplasmic reticulum in saponin-permeabilized rat ventricular trabeculae

After a brief presentation of the development of free walking interpreted as learning dynamical equilibrium, the problem of sensory integration in the process of walking development is discussed. A critical review of the role of vision in the development of posturo-locomotor task is presented, along with recent test results on the development of the vestibular system. A final section presents the development of head stabilization and coordination as a necessary means to assist sensory integration. It is suggested that if sensory information is necessary to enhance posturo-locomotor skills, a good mastery of walking is in turn necessary to increase the efficiency of sensory integration.     

Appendiceal inflammation in ulcerative colitis

The epoxyalkanoyl derivatives were designed and synthesized as ACE inhibitors. Coupling of unsaturated carboxylic acids with amino acids and following epoxidation with dimethyldioxirane gave the epoxyalkanoyls with high yield. The inhibitory activity of synthesized compounds on angiotensin converting enzyme was IC50 values of 0.06-5.5 microM.     

Human immunodeficiency virus seroprevalence in community-based primary care practices, 1990-1992. A report from the Ambulatory Sentinel Practice Network

OBJECTIVE: To estimate the seroprevalence of human immunodeficiency virus type 1 (HIV-1) infection in primary care practices. METHODS: Fifty-four practices in the United States participated in an anonymous, unlinked HIV seroprevalence study between January 1990 and December 1992. Residual blood samples drawn for routine clinical tests from patients 15 to 49 years of age were centrally tested for the HIV-1 antibody for 1 month of each quarter. Information about patient demographics, clinician-recognized risk factors, the known HIV status of the patient, and whether the blood was drawn for HIV testing was recorded with each specimen. RESULTS: Of 21,998 specimens collected, 99 (0.45%) were seropositive. Of these 99 seropositive persons, 31.3% (a seroprevalence of 0.15%) were not suspected by their clinicians of being infected with HIV. Seroprevalences in men (0.96%) exceeded those in women (0.22%), and rates in rural practices (0.18%) were lower than in urban practices (0.71%). Among patients with unsuspected HIV infection, however, the gender differences, especially in rural areas, were less pronounced. Risk factors for HIV infection were infrequently noted. There was an increase in the overall seroprevalence during the 1990 to 1992 study period (0.36% to 0.53%); however, this trend was not statistically significant. CONCLUSIONS: Within a 3-year period, clinicians in at least two of five primary care practices can expect to encounter patients infected with HIV, regardless of practice location. Also, nearly one third of the patients with HIV infection will not be suspected of having this condition by their clinician.     

Alterations in pallidal neuronal responses to peripheral sensory and striatal stimulation in symptomatic and recovered parkinsonian cats

The spontaneous activity, responses to peripheral sensory and ipsilateral caudate nucleus stimulation of globus pallidus (GP) and entopeduncular nucleus (ENTO) neurons were studied in cats while normal, symptomatic for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced parkinsonism, and when spontaneously recovered from gross parkinsonian motor deficits. Administration of MPTP resulted in parkinsonian motor symptoms that spontaneously recovered approximately 4-6 weeks after the MPTP administration. Post-mortem dopamine levels in recovered animals was approximately 95% below levels previously measured in normal animals. In symptomatic animals, the mean spontaneous firing rate for GP units was decreased by 50% and increased by 55% for ENTO units recorded. Spontaneous firing rates for GP and ENTO units in recovered cats were not significantly different from those observed in normal cats. In normal cats, 31.4% of GP and 29% of ENTO units tested responded to tactile stimulation of the face. Only 12.2% of GP and 13% of ENTO units responded to such stimulation in parkinsonian animals while the responses were generally less specific (larger receptive fields, more bilateral receptive fields, and more responses to multiple stimulation types) than normal. In recovered cats GP and ENTO responses resembled those observed in normal cats. There was no difference in the overall percentage of pallidal units responding to striatal stimulation across the 3 experimental conditions. There was, however, an increase in the percentage of units responding with complex response sequences (i.e. decrease in activity followed by an increase in activity) in symptomatic animals as compared to normal and recovered animals. The results suggest that loss of striatal dopamine in parkinsonian animals has profound effects on the sensory responsiveness of GP and ENTO neurons and that these effects coincide with the appearance of and recovery from parkinsonian motor deficits. These data further support the notion that sensory information processing by the basal ganglia may play an important role in influencing motor output.     

Immediate argon laser peripheral iridoplasty as treatment for acute attack of primary angle-closure glaucoma: a preliminary study

OBJECTIVE: This study aimed to examine the intraocular pressure (IOP)-lowering effects and safety of immediate argon laser peripheral iridoplasty (ALPI) as a first-line treatment for acute primary angle-closure glaucoma (PACG). DESIGN: A prospective cohort study. PARTICIPANTS: Ten consecutive patients with their first attack of PACG, with IOP of 40 mmHg or greater, were recruited into the study. INTERVENTION: On presentation, each patient received topical pilocarpine (4%) and timolol (0.5%) and immediate ALPI as primary treatment. The IOPs at 15, 30, and 60 minutes after ALPI were documented by applanation tonometry. When the corneal edema had settled, laser peripheral iridotomy was performed as a definitive treatment. MAIN OUTCOME MEASURES: The IOP, corneal edema, and complications from ALPI were measured. RESULTS: The mean IOP of this group of patients was reduced from 59.5+/-10.4 mmHg to 28.7+/-14.9 mmHg at 15 minutes, 21.7+/-13.1 mmHg at 30 minutes, and 16.0+/-9.4 mmHg at 60 minutes after ALPI. No complications from the laser procedure were encountered during the study period. In nine of the ten patients, the corneal edema cleared up 1 hour after ALPI. In the remaining patient, the cornea cleared up 2 hours after ALPI. CONCLUSION: From this preliminary study, immediate ALPI, without adjunctive systemic antiglaucoma treatment, appeared to be very effective in controlling the IOP and returning corneal clarity in acute PACG. Its safety also appeared reassuring and did not have the risks associated with conventional systemic therapies.