Abstract  The most common haemodynamic abnormality in human essential hypertension is an increase in systemic vascular resistance. Morphologic substrate for increased flow resistance is a narrowing of the lumen of arteriolar resistance vessels. During the course of essential hypertension, this is associated with an increase in wall (mainly media) thickness due to hypertrophy and hyperplasia of vascular smooth muscle cells. In contrast to concepts interpreting media thickening strictly as structural adaptation to increased perfusion pressure, various lines of evidence also point to pressure independent factors. In this context, extracellular factors such as "growth factors" as well as alterations in the activity of intracellular messenger systems must be considered. Recent studies suggest that substances generally known to act as vasoconstrictors such as angiotensin II, noradrenaline and arginine-vasopressin may also stimulate vascular smooth muscle cell growth and proliferation. Intracellular messenger systems with possible significance in the response to trophins and/or mitogens of vascular smooth muscle cells are phospholipase C, protein kinase C and the Na+/H+-antiport. These systems have been demonstrated to be altered in hypertension supporting the concept that one endogenous factor in human essential hypertension with pathophysiological significance, at least in a subgroup of patients, may be an enhanced reactivity of vascular smooth muscle cells to trophic and mitogenic stimuli. In this context, intracellular messenger systems such as phospholipase C, protein kinase C and/or the Na+/H+-antiport may play an important pathophysiological role.

Abstract  The specificity and heterogeneity of the immune response of BALB/c mice immunized with prostaglandin E2 (PGE2) coupled to thyroglobulin was studied. All the animals (n = 50) responded to PGB2, a transformation product of PGE2. However, following repeated injections most of the animals (n = 30) were also able to respond to PGE2. Cellular hybridizations were performed and five anti-PGE2 monoclonal antibodies were isolated and analysed. They are mainly directed against the ring and the omega-chain of PGE2 but their specificity toward the alpha-chain is more limited. The association constants are greater than to 1 X 10(9) M-1. The monoclonal antibody 8E.57.71 (Ka = 1.3 X 10(10) M-1) is particularly convenient for sensitive radioimmunoassays (detection limit 25pg/ml, when iodinated tracer is used). Anti-PGE2 monoclonal antibodies were found to neutralize the specific binding of [3H]PGE2 to rat brain hypothalamic receptors and to inhibit the PGE2 induction of rat fundus muscular contraction.

Abstract  The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances (PFASs) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS. These made up half of the lower bound (LB) exposure to those PFASs with available occurrence data, the remaining contribution being primarily from PFASs with short half‐lives. Equal potencies were assumed for the four PFASs included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL10 of 17.5 ng/mL for the sum of the four PFASs in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake (TWI) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI, which is of concern.

Abstract  Changes in the process of wound healing and in the dental pulp were examined following anterior and posterior mandibular subapical osteotomies in pig-tailed macaque monkeys. Results of microangiographic and histologic investigations indicated that degenerative pulpal changes may occur following mobilization and repositioning of small dentoalveolar segments. The potential significance of such degenerative pulpal changes and the need for routine dental radiographic checkups following anterior and posterior mandibular dentoalveolar surgery are discussed.

Abstract  Related annual variations in United States suicide rates between 1972 and 1978 to annual variations in church attendance of representative subpopulations of the United States. Variations in the suicide rates of white males, black males, white females, and black females were significantly, inversely correlated with variations in the attendance of the respective subpopulations. No significant differences were found between the correlations for white and black females and for white and black males nor between those for black females and males and for white females and males. The general hypothesis that religiosity deters suicide was supported.

Abstract  A method for the screening of human sera for tetanus antibodies has been developed and evaluated. The toxin binding inhibition test (ToBI-test) is based on inhibition of the binding of tetanus toxin to an antitoxin-coated immunoassay microtitre plate by tetanus antibodies. Serum samples from 191 healthy adults with different vaccination histories have been titrated for tetanus antibodies by the toxin neutralization (TN) test in mice, by toxoid-ELISA and by the ToBI-test. In every respect, the ToBI-test proved to be the best in vitro alternative to the TN-test in mice. Comparisons showed a higher degree of correlation between the ToBI-test and the TN-test than between the toxoid-ELISA and the TN-test. Furthermore, no overestimation of antibody content was seen in titrating low titre sera by the ToBI-test. In contrast, several false positive results were seen when using the toxoid-ELISA. It is concluded that the ToBI-test is a reliable and precise alternative to the TN-test and can be performed under simple laboratory conditions in a short time.

Abstract  In amphibians, Chlamydia psittaci infections are known since 1982 as a fatal disease. Only documented in two amphibian species, the pathogen seems to be widespread in these coldblooded vertebrates. The detection of intracytoplasmatic inclusion bodies and following examinations (electronmicroscopy) were necessary for the postmortal diagnosis. In 26 amphibians (3 species) a specific immunological testkit (immunofluerescence test) have been used. In 18 cases a positive result was found. This is the first report about using an IFT for the detection of Chlamydia psittaci in amphibians. Two new host species for this pathogen were found, one bufonid anuran (Bufo maculatum) and the new Pachytriton sp.

Abstract  The complete nucleotide sequence has been determined for three newly cloned evolutionary variants from two different independently generated evolutionary series (1100 and 2100 series) of simian virus 40 (SV40). These naturally arising variants, designated ev-1110, ev-2102, and ev-2114, were isolated after five high multiplicity serial passages. The structure of the variants consists of a monomeric unit tandemly repeated four times (ev-2102 and ev-2114) or six times (ev-1110) in the variant genome; the variants have four or six copies, respectively, of the viral origin signal for DNA replication. The DNA content in the three variants is vastly different in that the genome of variant ev-2114 contains only rearranged viral sequences, while variant ev-2102 contains a substitution with monkey DNA sequences consisting of a nearly complete dimeric unit of Alu family sequences as well as less repetitive sequences and variant ev-1110 contains monkey DNA sequences derived solely from repetitive alpha-component DNA. Recombination events, cellular sequences, and structural features of these and other naturally arising SV40 variants are compared.

Abstract  To determine the participation of immune complexes during adenovirus infection, we evaluated serum and necropsy specimens of patients with confirmed adenovirus infection of the lower respiratory tract. In lung and kidney from seven dead patients, immunofluorescence revealed the presence of hexon, immunoglobulins and complement. These patients had clinical manifestations of kidney dysfunction. In dead patients (3/3 in whom serum was available) neither anti-adenovirus antibodies nor adenovirus-specific immune complexes could be found in the final stage of the infection. However, two of these patients had anti-adenovirus antibodies and immune complexes in samples obtained early in the infection. Most patients (16/19) who survived the infection had circulating anti-adenovirus antibodies. Half also had immune complexes specific for adenovirus in some moment of the illness. This suggests that immune complexes arise during respiratory infection by adenovirus, probably contributing to its clinical picture.

Abstract  Prevention and early detection of skin cancers are crucial to reducing morbidity and mortality. Armed with the above information and with some experience, the primary care physician can understand risk factors and recognize common benign and malignant skin tumors. This allows the primary care physician to play a key role in teaching patients about skin cancer prevention and in screening patients for skin cancers.