Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl

We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P < 0.0001) states. Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P < 0.0001, fed). Lipoprotein fractionation showed increased VLDL and IDL + LDL with an increased cholesterol/triglyceride ratio (0.114 vs 0.065, P = 0.02, in VLDL). The VLDL apo E/apo B ratio was decreased 3.4-fold (P = 0.05) and apo CII and apo CIII decreased in proportion to apo E. Triglyceride and apo B production rates were normal, but clearance rates of VLDL triglycerides and postlipolysis lipoprotein "remnants" were significantly slowed. Plasma apo B was significantly elevated. Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. In summary, apo CI overexpression is associated with decreased particulate uptake of apo B-containing lipoproteins, leading to increased levels of several potentially atherogenic species, including cholesterol-enriched VLDL, IDL, and LDL.     

Increased socioeconomic differences in mortality in eight Spanish provinces

In Spain, the study of socioeconomic differences in mortality has been limited by the fact that death certificates often do not include complete information on occupation. In this study, we chose those geographic areas with the highest quality information on occupation of the deceased in order to study socioeconomic differences in mortality from various causes of death. We used information from the death certificates of males who died between 30 and 64 years of age in eight Spanish provinces to compare mortality from the leading causes of death in professionals and managers (group I) and in manual laborers (group II) in 1980-82 and 1988-90. In each period the standardized mortality ratios (SMRs) were higher in group II, except for ischaemic heart disease during the first period, and cancer of the colon and rectum in both, although in the latter case the differences were not statistically significant. The ratio between the SMR from all causes in group II and group I was 1.27 in 1980-82, and 1.72 in 1988-90; for cancer of the colon and rectum the ratio went from 0.98 to 0.84, and for ischaemic heart disease, from 0.80 to 1.31. Except for cancer of the colon and rectum, which resulted in higher mortality in occupational group I, the excess mortality in occupational group II increased between the first and second period. The relation between socioeconomic level and mortality for ischaemic heart disease was reversed, a phenomenon similar to that which took place in the 1960s and 1970s in the developed countries.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tibial torsion?

A longitudinal study evaluating the degree of rotation of the bimalleolar axis of tibia and fibula at birth, 6 month, 12 months and 24 months revealed a gradual statistically significant external rotation from a mean of 4 degrees at birth to a mean of 11 degrees at 24 months. There was no correlation with the sex or race of the child or with the age at which the child began independent walking. It is concluded that this external rotation is a part of normal growth and development of the infants' lower extremities.     

Arterial radio-anatomy of the extrahepatic biliary system (author's transl)

The uni-arterial vascularisation of the lateral bilary duct makes it impossible to systematise the arteries which supply the common bile duct. Only the cystic artery is seen at coelio-mesenteric catheterization. The techniques essential for visualisation of the cystic artery are discussed, on the basis of one hundred coelio-mesenteric arteriograms: frequency of demonstration, origin, course, termination, calibre and length. The frequent finding of opacification of the wall of the gall bladder under normal conditions is stressed.     

Pyridoxal 5'-phosphate and the regulation of ornithine decarboxylase activity and stability

There are two forms of ornithine decarboxylase with respect to pyridoxal 5'-phosphate (pyridoxal-P) affinity in exponentially-growing Swiss 3T3 mouse fibroblasts: form I (Km approximately 10 muM) accounts for 30% of the total activity, and form II (Km approximately 0.4 muM) the remainder. Each form of the enzyme is in rapid equilibrium with ornithine and pyridoxal-P; neither form recognizes the Schiff base between ornithine and pyridoxal-P as a substrate. Total pyridoxal-P concentrations indicate that both forms may normally be at least partially active in vivo. Upon stimulation of 3T3 cells by pituitary growth factors, form I becomes undetectable within 4 h. As total activity increases over 10-fold during this time and continues to increase thereafter, a possible conversion of form I to form II could account for this increase only if the Km change reflects other changes in preexisting enzyme. The rates of cofactor dissociation are apparently the same for each form and neither rate changes with the growth state. Since rapid equilibrium kinetics apply, the forms apparently differ in their rate of cofactor association. The half-lives of the two forms in vivo are the same in unstimulated cells when measured concurrently. Also, the half-life of total activity decreases markedly upon stimulation as form II becomes dominant. These and other observations are not consistent with pyridoxal-P serving a major protective function for the enzyme in vivo.     

Complement activation in vivo in cancer patients receiving C. parvum immunotherapy

Serum complement levels were assayed in 26 patients with disseminated cancer, who received immunotherapy with infusion of C. parvum. Complement activation, indicated by the consumption of C3 or C4 or both, was found in 46% of the patients. Serum samples showed direct correlation between decreased C3 and conversion of C3 proactivator, whereas such conversion did not occur when C4 alone was decreased. It is concluded that the bypass (properdin) pathway was activated in patients in whom C3 consumption was detected, while the classical (C1) pathway was activated in the patients with C4 consumption unaccompanied by C3 decrease. Direct correlation was observed between delayed cutaneous hypersensitivity reactions to recall antigens and the incidence of C. parvum-associated complement activation.