Immunogestosis: a new etiologic concept of "essential" EPH gestosis, with special consideration of the primigravid patient; preliminary report of a clinical study

Evidence for immunologic processes taking part in the pathogenesis of what until now has been called the "essential" form of EPH gestosis is cited. The name of immunogestosis (IG) is introduced. The data of this preliminary study suggest that regular "inoculation" of the female genital tract with allogeneic spermatozoal histocompatibility antigens reduces the incidence of IG. Information about preconceptional sexual habits and contraceptive measures was obtained from 83 selected primigravid patients. Twenty-eight women had mild to moderate IG (Group B);55 did not (Group A). Women in Group B had had less contact with spermatozoa of partners than did women in Group A. Oral contraceptive consumption was less in Group B than in Group A. Women in Group B were younger than women in Group A. All these differences were statistically significant. A new immunoetiologic hypothesis referring to IG, as well as the theoretic and clinical implications arising from it, are discussed. This hypothesis is based on the assumption that spermatozoal histocompatibility antigens can either induce immunologic tolerance or be responsible for the phenomenon of immunologic enhancement in the maternal immunosystem. As the fetus inherits paternal histocompatibility antigens, it is concluded that pre-existing tolerance (or enhancement) exerts an IG-preventive function in a subsequent pregnancy.     

Neural basis for the genesis and control of digitalis arrhythmias

The author discussed the increase in the frequency of traumatic paralyses of the ocular muscles, and reported 6 cases of inferior oblique muscle paresis caused by local blunt or sharp traumas (haematoma, contusion, rupture, incarceration) and one case of traumatic Brownian pseudo-paralysis. The localisation of the injuries in 3 cases was on the inferior temporal part and in the other 3 cases on the superior part of the bulbar conjunctiva. Atypical horizontal deviation and characteristic vertical deviation, torsion and torticollis were observed in the majority of cases. One patient recovered spontaneously. 3 patients became asymptomatic after correction by prisms and one after recession of contralateral superior rectus muscle. The symptoms remained unchanged in the case of a "blow out" fracture (in spite of operation) and a Brown's syndrome (without treatment).     

Selective isolation of reversible cold sensitive variants from Chinese hamster ovary cell cultures

The fine structure and cellular associations of the large pigment cells (LPC's) of the compound eye of the house fly were studied with high voltage and conventional electron microscopy. Depending on the sector of the compound eye, the facets are either rectangular or hexagonal. The underside of each facet has indentations exactly aligned with those on top into which inserts an angulated sleeve of LPC's. Under the rectangular lens facet 6 or 8 small compact (in cross section) LPC's join four elongate LPC's. Clusters of compact cells alternate in this ring with elongate ones. Compact cells compress together and become quadrangular (in cross section) several microns below their insertion into the lens and form "building block" corners while elongate cells form "side rails" for the rectangular type of distal pseudocone enclosure. Beneath hexagonal facets all LPC's are rather elongate with out corner cells. In both facet types LPC's enclose the pseudocone for a longitudinal distance of 4 mum and then are displaced as bordering cells by a sleeve of two corneal pigment cells (CPC's), each of which encloses half of the proximal pseudocone. For the following 6 mum of longitudinal distance these concentric sleeves of CPC's and LPC's form a double layer around the pseudocone. At about 10 mum below lens base the two sleeves separate; LPC's become attenuated and extend cable-like to the basement membrane and CPC's enclose the proximal pseudocone, Semper cells and distal retinula. The junction between lens and LPC's has critical structural value in that (1) this is the sole anchorage to the lens by the lengthy remainder of the ommatidium, and (2) LPC's enclose the semiliquid pseudocone in the most distal portion of the pseudocone. In addition to vertical support, the LPC's send out numerous lateral processes that make structural contact among themselves, with the corneal pigment cells and the photoreceptor cells. The structural features of this array are discussed relative to possible physiological roles.     

Factors affecting length of herdlife in purebred and crossbred dairy cattle

The proportional hazards model with censoring was used to assess the effects of breeding value, disease, calving, size, and udder and lactation traits on length of herdlife of 3881 heifers in five herds. Data were recorded over 10 yr from three lines: a Holstein line, an Ayrshire-based line, and a crossbred line. Influences on survival were assessed from data collected at birth, 34, 50, and 82 wk, first freshening, and at 112 and 308 d postpartum. Median estimated herdlife (age at 50% culling) was 3.9 yr for animals alive at first freshening and increased to 4.3 yr for those that completed a first lactation (308 d postpartum). Herds differed greatly in the pattern of culling after freshening. Crossbred females had 21 wk longer median estimated herdlife than the mean of the purelines at 308 d postpartum. Individual milk yield was positively associated with longevity and had the greatest impact on length of herdlife. Abortion and fertility measured as days to last insemination were negatively associated with length of herdlife. Large heifers tended to have increased longevity. High feed intake postpartum was associated with reduced length of herdlife. Objective measures of conformation, which included measurements of the udder, were not important in determining herdlife.     

Growth and feed efficiency of pureline and crossline dairy heifers

Data on 3957 heifers from the Holstein H line, Ayrshire-based A line, and C line (crossbreds between H and A lines) were used. Growth, feed consumption, and feed efficiency from 26 to 34 wk were examined. The full model included the fixed effects of herd, year of birth, season of birth, and additive, maternal, and heterotic genetic effects with 26-wk weight as a covariate. Heterotic and maternal effects were not significant. Adjusted for the 26-wk weight covariate, H line heifers gained 3 kg more than A line heifers with C line heifers intermediate. Adjusted for 26 and 34-wk weight covariates, H line heifers ate 2 kg less TDN than A line heifers and, hence, were more efficient. Correlations among traits were estimated using the residual variance-covariance matrix from the full model. Body weight at 34 wk was correlated with 26-wk weight (r = .88) but essentially independent of rate of gain (r = .02). It was correlated with feed consumed (r = .51) and negatively associated with gain/feed consumed (r = -.25). Gain was correlated (r = .84) with gain/feed consumed but mildly so (r = .28) with feed consumed. Feed consumption was negatively correlated (r = -.25) with gain/feed consumed when the 26-wk weight covariate was included but became much larger (r = -.95) when both 26 and 34 wk weight covariates were included. Although genetic differences in feed consumption and feed efficiency of growing heifers exist, these are small and closely associated with weights and weight gains.     

End-of-life decision-making in the hospital: current practice and future prospects

The contributions of the various ulnar-innervated muscles of the hand to the hypothenar compound muscle action potential (CMAP) were estimated by directly stimulating individual muscles and by analyzing CMAP shape changes resulting from manipulations that changed individual muscle lengths. The results show that the first peak of the negative phase of the hypothenar CMAP comes from the hypothenar muscles, but that the second peak is due to a large volume-conducted potential from the interosseous muscles. The interosseous contribution affects both the amplitude and the area of the CMAP, and makes these parameters sensitive to changes in the configuration of the fingers and the temperature gradient in the hand. To reduce the interosseous contribution, a "balanced reference" consisting of two reference electrodes, one over each tendon, is proposed.     

The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues

Antifilaggrin autoantibodies (AFA) are a population of IgG autoantibodies associated to rheumatoid arthritis (RA), which includes the so-called "antikeratin" Abs and antiperinuclear factor. AFA are the most specific serological markers of RA. We previously showed that they recognize human epidermal filaggrin and other profilaggrin-related proteins of various epithelial tissues. Here, we report further characterization of the protein Ags and epitopes targeted by AFA. All the Ags that exhibit numerous neutral/ acidic isoelectric variants were immunochemically demonstrated to be deiminated proteins. In vitro deimination of a recombinant human filaggrin by a peptidylarginine deiminase generated AFA epitopes on the protein. Moreover, two of three filaggrin-derived synthetic peptides with a citrulline in the central position were specifically and widely recognized by AFA affinity-purified from a series of RA sera. These results indicate that citrulline residues are constitutive of the AFA epitopes, but only in the context of specific amino acid sequences of filaggrin. In competition experiments, the two peptides abolished the AFA reactivity of RA sera, showing that they present major AFA epitopes. These data should help in the identification of a putative deiminated AFA-inducing or cross-reactive articular autoantigen and provide new insights into the pathogenesis of RA. They could also open the way toward specific immunosuppressive and/or preventive therapy of RA.     

Two-year prospective, randomized trial comparing an innovative twice-a-week progestin regimen with a continuous combined regimen as postmenopausal hormone therapy

OBJECTIVE: To determine the relationship between matrix metalloproteinases (MMPs), their inhibitors, and the turnover of matrix molecules in articular cartilage from patients with osteoarthritis (OA). METHODS: Synovial fluid samples were collected from the knees of 54 patients with OA. Radiographic evaluations and magnetic resonance imaging were performed on the knees of 34 OA patients to classify the stage of the disease. Biochemical analyses and immunoassays were used to measure the concentrations of MMP-1, MMP-3, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, the disaccharide of hyaluronic acid, the proteoglycan glycosaminoglycan disaccharides of chondroitin 4-sulfate (delta di-CS4) and chondroitin 6-sulfate (delta di-CS6), the 846 epitope on chondroitin sulfate of cartilage proteoglycan aggrecan (putative biosynthetic marker), the keratan sulfate (KS) epitope of aggrecan (putative degradation marker), and the C-propeptide of cartilage type II procollagen (CPII) (biosynthetic marker). RESULTS: The concentration of TIMP-1 was directly correlated with the levels of MMP-1 and MMP-3 (both were also correlated with each other), confirming earlier results. There was an inverse correlation between the delta di-CS6:delta di-CS4 ratio and the concentration of MMP-3. The level of delta di-CS6 was correlated with that of the KS epitope, and to a lesser degree, with that of the 846 epitope (the latter was also correlated with the level of delta di-CS4). The concentration of TIMP-1 correlated with that of the 846 epitope, whereas TIMP-2 levels correlated with those of CPII. There were significantly lower concentrations of delta di-CS6, delta di-CS4, the 846 epitope, and CPII in synovial fluid from patients with late-stage OA. CONCLUSION: These observations suggest a link between proteolysis and inhibitor concentrations in OA cartilage. Production of TIMPs appears to be individually linked to the synthesis of specific cartilage molecules. The reduction in the amount of cartilage-matrix structural components suggests that there is a measurable loss of cartilage in the late stages of the disease, as suggested previously. The resultant composition of the cartilage suggests that the loss may primarily involve "resident" molecules originally present in healthy cartilage.     

U73122 and U73343 inhibit receptor-mediated phospholipase D activation downstream of phospholipase C in CHO cells

We investigated the effects of nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside on basal and K+-evoked release of [3H]noradrenaline from superfused synaptosomes from the rat cerebral cortex. Both substances produced concentration-dependent increases in the release of the labeled transmitter under basal and depolarized conditions. The effects of the donors on basal release were Ca2+-independent but were not inhibited by the carrier-uptake blocker, desipramine; the effects were abolished by hemoglobin (an NO scavenger). Thirty-five minutes after stimulation with sodium nitroprusside, the synaptosomes were still responsive to KCl stimulation, indicating that the donor's effects were not caused by damage to the synaptosome membrane. The cGMP analogue, 8-bromo-cGMP, had no effect on basal release, and the enhanced release produced by sodium nitroprusside was not inhibited by the specific inhibitor of soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, indicating that NO's effects on basal release of the neurotransmitter are guanylate cyclase-independent. Both of the NO donors had more marked effects on release of [3H]noradrenaline during K+-stimulated depolarization. The NO-mediated increase in this case was partially antagonized by 10 microM LH-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, and 8-Br-cGMP was also capable of producing concentration-dependent increases in the K+-stimulated release of the transmitter. These findings indicate that the effects of the NO donors on [3H]noradrenaline release during depolarization are partially mediated by the activation of guanylate cyclase.