Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy

We measured serum alkaline phosphatase isoenzymes and osteocalcin levels in 40 healthy women at 4-week intervals throughout uncomplicated pregnancies and 6 weeks after delivery in 17 women. Serum bone alkaline phosphatase was significantly higher in the third trimester than in early pregnancy (P less than 0.001), and this elevation was still apparent at the end of the puerperium, suggesting increased bone turnover. Serum osteocalcin was not detected (less than 0.2 micrograms/L) after the first trimester in the majority of women, and it reappeared within 48 h after delivery. The disappearance of osteocalcin after the first trimester and its rapid reappearance after delivery suggest placental clearance of this peptide. We conclude that serum osteocalcin measurements cannot be used as a marker of bone metabolism during pregnancy.     

An immunochemical comparison of human myelin basic protein and its modified, citrullinated form, C8.

An immunochemical analysis was conducted to compare the C1 isomer of human myelin basic protein (MBP) with the newly described and less cationic, citrullinated isomer of MBP referred to as C8. Ten polyclonal antisera directed at multiple epitopes or restricted regions of MBP were used in radioimmunoassays to examine MBP-C1 and MBP-C8. Antisera reactive with MBP peptide 1-14 clearly distinguished MBP-C1 from MBP-C8. Antisera to human MBP peptides 10-19 and 90-170, but not to MBP peptide 69-89, showed modest differences between MBP-C1 and MBP-C8. The MBP-C8s from multiple sclerosis (MS) and non-MS brain reacted essentially the same. With murine monoclonal antibodies and enzyme-linked immunosorbent assay (ELISA), differences between MBP-C8 and other isomers were shown for anti-MBP 10-19 but not for anti-MBP 1-9 or anti-MBP 80-89. These findings imply differences in sequence or conformation in the structure of MBP-C7 compared to MBP-C1, most notably near the amino terminus.     

Measurement of immunoreactive myelin basic protein peptide (45-89) in cerebrospinal fluid

To measure myelin basic protein (MBP)-like material in cerebrospinal fluid, we compared two radioimmunoassays, both using the same antiserum to MBP but one using peptide (45-89) as the radioligand and standard (peptide assay), and the other using purified MBP as the radioligand and standard (MBP assay), with respect to their diagnostic sensitivity. Cerebrospinal fluid specimens from 185 patients with definite multiple sclerosis (MS) (n = 27), possible MS (n = 63), probable MS (n = 24), and other neurological disease (n = 71) were analyzed using both assays. The diagnostic sensitivity of the peptide assay was significantly better than that of the MBP assay in those with definite MS (sensitivity 59% and 30%, respectively); there was no significant difference in specificity. The peptide assay also showed better correlation with disease activity than the MBP assay: 14 patients classified as having active MS showed significantly higher sensitivity (78.6% versus 38%, p less than 0.04) when compared to patients with inactive disease. The MBP assay showed no significant difference between these two groups. Besides the increase in sensitivity, the actual molar concentrations of immunoreactive MBP detected using this peptide assay were considerably higher than those found using the MBP assay. These results show that the use of MBP antisera capable of recognizing epitopes present in the carboxyl half of MBP peptide (45-89) results in more sensitive detection of immunoreactive MBP when used with MBP peptide (45-89) as radiolabeled ligand in the assay.     

Pulsed dye laser (577 nm) treatment of portwine stains: ultrastructural evidence of neovascularization and mast cell degranulation in healed lesions

Portwine stains were examined before, immediately after, and 1 yr after successful clearance by a pulsed dye laser (577 nm) using ultrastructural techniques. Dilated vascular channels and mast cell hypoplasia characterized lesional skin before treatment. Immediately after treatment, widespread selective vessel necrosis, similar to changes previously described, was observed. One year after laser irradiation, the abnormally ectatic portwine stain vessels had been replaced by small venules and arterioles, similar in number and diameter to blood vessels in normal skin; the only difference noted was that these new vessels were surrounded by easily identifiable mast cells. Many of these mast cells exhibited evidence of activation and degranulation. We conclude that mast cells may play an important role in the neovascularization of portwine stains treated by 577-nm dye laser irradiation.     

Asbestos bodies in lung tissue following exposure to crocidolite

A series of 206 necropsies in Western Australia (WA) have had routine counts made of asbestos bodies in samples of lung tissue using conventional light microscopy. Thirty-two cases had worked in the asbestos industry at Wittenoom, WA and (log) counts of asbestos bodies in their lung tissue correlated well with estimates of their (log) cumulative airborne exposure to crocidolite fibers (r = 0.60). There was no association between the number of asbestos bodies and time since exposure to asbestos ceased. In subjects without known exposure to asbestos, there was a weak but nonsignificant increase in number of asbestos bodies with increasing age, with 26% of cases having no asbestos bodies present. It is concluded that the relatively simple technique of light microscopy for counting of asbestos bodies in lung tissue provides a reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. This could be extremely useful in follow-up studies of cohorts that lack reliable measures of airborne exposure to crocidolite asbestos.     

The effect of noradrenaline on the end-plate potential in twitch fibres of the frog

1. The action of noradrenaline in increasing the amplitude of the end-plate potential (e.p.p.) has been studied in magnesium-blocked frog skeletal muscle.2. Noradrenaline (10(-5)M) increased the e.p.p. by about 20% without causing any comparable change in the amplitude of the miniature end-plate potentials (m.e.p.p.s). It was concluded that noradrenaline acts by potentiating the release of acetylcholine by the nerve impulse, rather than by increasing the sensitivity of the end-plate.3. In support of this, it was found that the increase in e.p.p. amplitude was associated with a reduction in the variability of successive e.p.p.s, as is to be expected if the quantal content of the e.p.p. became larger. Further, noradrenaline was without effect on the response to iontophoretically-applied acetylcholine, although it potentiated depolarizations elicited by acetylcholine applied for much longer periods in the bathing fluid.4. Noradrenaline increased the frequency of occurrence of m.e.p.p.s, and unusually large m.e.p.p.s. were occasionally observed.     

Interaction of Angiotensin with Disseminated Intravascular Coagulation: A Possible Mechanism in the Genesis of Acute Renal Failure

Because of the importance of the renin-angiotensin system in renal homeostatic mechanisms, the effect of angiotensin administration upon disseminated intravascular coagulation has been studied in rabbits. An infusion of angiotensin II (0.1 μg/kg/min for 2 hours) produced neither histologic abnormalities in the kidneys nor an elevation of creatinine. After an infusion of thrombin (2.0 units/kg/min for 2 hours) only 3 of 10 rabbits, when sacrified 24 hours later, showed histologic lesions comprised of occasional fibrin thrombi and foci of tubular necrosis. Creatinine levels did not rise. In contrast, the combination of angiotensin and thrombin resulted in renal lesions in 12 of 14 animals. Four had frank cortical necrosis, while combinations of tubular necrosis, glomerular thrombosis and segmental glomerular infarction occurred in the others, together with elevated creatinine levels. Blockade of α-adrenoreceptors with phenoxybenzamine in 12 animals did not prevent either these histologic changes or creatinine elevation, showing that the effect of angiotensin was independent of α-adrenoreceptor stimulation. The synergistic interaction between angiotensin and disseminated intravascular coagulation was not explained by differences in the consumption of plasma fibrinogen but apparently was due to localization of fibrin thrombi within glomerular capillaries by the vasomotor actions of angiotensin, as has previously been shown to occur with α-adrenoreceptor simulation. Such a mechanism might contribute to renal glomerular deposition of fibrin in acute ischemic renal failure.