Stress and dental caries in the rat

The stress of crowding and exposure to inescapable electric shock increased both the incidence and the severity of dental caries in rats housed in a conventional animal facility. Male Osborne-Mendel rats were inoculated intraorally with cariogenic bacteria, fed a high-sucrose diet, and housed in either a conventional or a sheltered facility. Rats in both housing conditions were subdivided into control and stress groups. At the end of the 56-day trial period, stressed rats from conventional housing had a significant increase in both incidence and severity of dental caries in comparison to their controls. In contrast, stressed rats from sheltered housing had a trend toward increased cariogenesis which reached significance in only one of five scores. These rats also failed to gain weight comparable to their controls, making it possible that stress-induced reduction in appetite partially offset stress-induced exacerbation in cariogenesis.This investigation was supported in part by the following Grants from the United States Public Health Service: CA 20093, HL 22727, and HL 07374.     

Small reduction of capsaicin-induced neurogenic inflammation in human forearm skin by the glucocorticoid prednicarbate

Capsaicin applied to human skin provokes a response known as neurogenic inflammation. Neuropeptides (substance P, CGRP), released from afferent C-fiber terminals and histamine, secondarily released from mast cells, are supposed to participate in this reaction. We investigated the contribution of arachidonic acid and metabolic products to neurogenic inflammation, using a potent topically applied glucocorticoid and the corresponding vehicle. Arachidonic acid is liberated from membrane phospholipids by phospholipase A₂, an enzyme that can be blocked by glucocorticoids. In 12 healthy volunteers, neurogenic inflammation was induced by capsaicin 1% on both upper forearms after 16 h of topical pretreatment with either prednicarbate or vehicle. Neurogenic inflammation was assessed by laser Doppler flowmetry and by planimetry of flare sizes. Prednicarbate significantly reduced the laser Doppler flow values inside the flare responses, as well as the flare sizes themselves. These results show that to some extent glucocorticoids reduce capsaicin-induced neurogenic inflammation.     

Pregnancy outcome after blastocyst transfer as compared to early cleavage stage embryo transfer

BACKGROUND: Retrospective cohort study to evaluate differences in outcome when embryo transfer was performed either on day 2-3 (cleavage stage, CS-group) or on day 4-5 (blastocyst stage, BS-group). METHODS: A total of 1259 consecutive cycles yielding 500 live born babies performed at a single centre in Bregenz, Austria, were included. Main outcome measures were implantation and (multiple) pregnancy rates and neonatal outcome including birth defects. RESULTS: Total Pregnancy rate was 44% vs 28% (P < 0.001) and the total 'take home baby rate' was 37% vs 22% in the BS-group and the CS-group, respectively. Rate of multiple gestations (34% vs 17%, P = 0.001) was significantly higher among the BS-group, resulting in a higher rate of preterm deliveries < 36 weeks (26% vs 17%, P = 0.045). Female factor causing infertility (40% vs 21%, P < 0.001) was significantly higher among the BS-group. For the CS-group, rate of singleton pregnancies (83% vs 66%, P = 0.001) and idiopathic cause of infertility (34% vs 22%, P = 0.012) were significantly higher. No statistically significant differences were found in sex, Caesarean section rate, Apgar score and umbilical artery pH-values, total mean birth weight, admission rate to intensive care unit, days of hospitalization and number of minor and major birth defects. CONCLUSIONS: Our data suggest that blastocyst transfer may lead to a higher pregnancy rate with an overall better take-home baby rate (THBR) at the cost of higher rates of multiples and preterm deliveries.     

Localization of dopamine-1 receptors along the microdissected rat nephron

Dopamine exerts numerous actions on the kidney but the precise location of its receptor subtypes along the nephron is unknown. Using a microassay we determined the specific binding of ¹²⁵I-Sch 23982, a specific and selective dopamine-1 (DA₁) receptor antagonist, to microdissected glomeruli and tubule segments. Binding of ¹²⁵I-Sch 23982 in the proximal convoluted tubule (PCT) was timeand concentration dependent, saturable and reversible. The linear Scatchard plot of saturation experiments suggested binding to a single site with an apparent K _d of 16.7 nM and B _max of 0.4 fmol·mm^–1 in the PCT, and 6.2 nM and 0.1 fmol·mm^–1 in the cortical collecting tubule (CCT). Mapping of DA₁ binding sites along the nephron revealed their presence in each of the segments examined, albeit in markedly different concentrations: the highest specific binding was measured in PCT followed by the pars recta. Binding was less in the distal nephron, and least in the medullary and cortical thick ascending limb. Modest binding was also detected in glomeruli. In cortical collecting tubules competition studies with unlabeled dopamine and probes for DA₁ (Sch 23390, fenoldopam), DA₂ (domperidone, S-sulpiride), serotonergic (serotonin, ketanserin, mianserin), and -(phentolamine) and -(propranolol) adrenergic receptors indicated a rank-order potency for displacement of ¹²⁵I-Sch 23982 binding, consistent with labeling of DA₁ receptors. Dopamine inhibited Na/K-ATPase both in PCT and CCT, an effect duplicated in the latter segment by the DA₁ agonist fenoldopam, and blocked by the DA₁ antagonist Sch 23390. These results demonstrate specific DA₁ binding sites in a nonhomogeneous pattern along the entire nephron, and suggest that dopamine may exert its effect on Na transport in distal as well as in proximal nephron segments.     

Feinstrukturell-morphometrische Befunde an der Kammerwand hypertrophierter menschlicher linker Ventrikel

Zusammenfassung An den KammerwÄnden menschlicher linker Ventrikel, die auf Grund einer Aortenstenose, einer Aorteninsuffizienz oder eines kombinierten Aortenvitium hypertrophiert waren, wurden licht- und elektronenmikroskopisch morphometrische Untersuchungen angestellt. Die Ergebnisse wurden mit denen, die an nicht belasteten menschlichen linken Ventrikeln gewonnen wurden, verglichen.Lichtmikroskopisch unterscheiden sich die Anteile der Volumendichten des Interstitium und der Herzmuskelzellen am gesamten Herzmuskelgewebe nicht statistisch signifikant. Es konnte morphometrisch eine Zellvergrö\erung festgestellt werden, die aus der signifikanten Verringerung der Volumendichte der Zellkerne (P<0,001) und der Anzahl der Zellkerne pro TestflÄche (P<0,0001) gegenüber den beiden Normalkollektiven resultiert. Elektronenmikroskopisch ist eine Zunahme der Volumendichten der Myofibrillen (P<0,0001) auf Kosten des restlichen Cytoplasmas (P<0,001) festzustellen, wÄhrend die Volumendichte der Mitochondrien im Vergleich mit den jungen und alten Patienten abnahm (P<0,0001). Die OberflÄchendichte der Mitochondrien verringerte sich gegenüber den beiden Vergleichskollektiven (P<0,001) ebenso wie die der Cristae mitochondriales (P<0,0001). Diese Ergebnisse finden ihr morphologisches Korrelat in Mitochondriendestruktionen. Eine vermehrte Myolyse hat bei den hypertrophierten Herzen, die alle gewichtsmÄ\ig über dem kritischen Herzgewicht lagen, noch nicht eingesetzt. Bei allen Patienten wurde der herzchirurgische Eingriff mit Erfolg durchgeführt.

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Ultrastructural morphometric analysis of hypertrophied human myocardial left ventricles

Summary Biopsies of hypertrophied human myocardial left ventricles were investigated morphometrically. The diagnoses of the patients were stenosis of the aortic valve, aortic insufficiency or a combination of both lesions. The results were compared with those from normally loaded human left ventricles.There are no differences on light microscopical level between the volume densities of interstitial tissue and of heart muscle cells in the three groups of patients. A significant diminution of the volume density of the nuclei (P<0.001) and the number of nuclei per test area (P<0.0001) when compared with normal groups suggests an increase in volume of the single heart muscle cell. The ultrastructural study shows marked increase in volume density of myofibrils (P<0.0001), with accompanying decrease in the volume densities of mitochondria (P<0.0001) and the remaining cytoplasm (P<0.001). A gross decrease in the surface area of mitochondria (P<0.001) and of cristae mitochondriales (P<0.0001) is found. The morphological equivalents of this result are numerous stages of mitochondrial destruction including cristolysis. All myocardial weights were beyond the critical heart weight.

Mit dankenswerter Unterstützung der Deutschen Forschungsgemeinschaft über den Sonderforschungsbereich SFB 104     

Identification of two homologous antigenic peptides derived from L1 HPV-16 and 18 proteins specific for the HLA-B*3901 allele

Summary.  In this work we present evidence that the homologous peptides IHSMNSTIL and IHSMNSSIL derived from L1 HPV-16 and 18 proteins respectively, and with high specificity for the allele HLA-B^*3901, according with an algorithm prediction program, induced T cell stimulation in patients with advanced cervical cancer positive for HPV-16 or 18 infection and for the HLA-B^*3901 allele. Interestingly, T lymphocytes derived from a patient with HPV-18 infection and stimulated with the peptide IHSMNSTIL were capable to kill a cervical cancer cell line named Rova, derived from the tumor of the same patient. In addition, the cytotoxic activity was strongly increased when this cell line was previously treated with hrIFN-γ. These results suggest that the CTL immune response to L1 HPV-16 and 18 protein derived epitopes is maintained in patients with advanced cervical cancer within specific alleles, and opens the possibility that homologous epitopes may be used in the generation of prophylactic vaccines for cervical tumors bearing different HPV-types. Received March 4, 2002; accepted May 20, 2002     

fMRI activation in the human frontal eye field is correlated with saccadic reaction time

Variation in response latency to identical sensory stimuli has been attributed to variation in neural activity mediating preparatory set. Here we report evidence for a relationship between saccadic reaction time (SRT) and set-related brain activity measured with event-related functional magnetic resonance imaging. We measured hemodynamic activation time-courses during a preparatory "gap" period, during which no visual stimulus was present and no saccades were made. The subjects merely anticipated appearance of the target. Saccade direction and latency were recorded during scanning, and trials were sorted according to SRT. Both the frontal (FEF) and supplementary eye fields showed pre-target preparatory activity, but only in the FEF was this activity correlated with SRT. Activation in the intraparietal sulcus did not show any preparatory activity. These data provide evidence that the human FEF plays a central role in saccade initiation; pre-target activity in this region predicts both the type of eye movement (whether the subject will look toward or away from the target) and when a future saccade will occur.     

Neuropathological Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD) and Other Human Spongiform Encephalopathies (Prion Diseases)

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD - sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immuno-reactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spon-giosis. This includes status spongiosus (“spongiform state”), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of “burnt-out” CJD), “spongy” changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.     

Effect of temporal and spatial temperature gradients on the ampullae of Lorenzini

Summary Afferent single fiber impulses were recorded from isolated ampullae of Lorenzini of dogfishes (Scyliorhinus canicula). The ampullae were placed between two thermodes, each of which could be circulated separately with water at 12°, 18° and 24° C, thus allowing cooling and warming with various combinations of spatial temperature gradients. At constant temperature, there was a static discharge in the ampullary fibers. Cooling elicited a dynamic overshoot in frequency, followed by adaptation to a new steady state, whereas warming led to a transient inhibition. Within the limits of error the direction and slope of the spatial temperature gradient had no influence whatsoever on the static and dynamic responses of the ampullae, the only effective parameters being the temperature at the site of the receptor and the rate of temperature change with time.About 13% of the single fibers responded with bursts of impulses, interrupted by silent intervals, and 10% showed an inversed dynamic response, i.e. dynamic overshoot on warming and transient inhibition on cooling. It is possible that these patterns of activity are anomalous responses.This work was supported by the Deutsche Forschungsgemeinschaft.