Lymphocyte and immature dendritic cell infiltrates in differentiated, poorly differentiated, and undifferentiated thyroid carcinoma.

OBJECTIVE: Numerous studies indicate that papillary thyroid carcinomas (PTC) with lymphocytic infiltrates are associated with a less extensive disease at diagnosis and improved disease-free survival. The infiltration of lymphocytes and immature CD1a+ dendritic cells (DC) was characterized in papillary, poorly differentiated (PDC), and undifferentiated (UC) carcinomas to evaluate their association with immunological infiltrates. DESIGN: A series of 527 consecutive cases of thyroid carcinoma treated by total thyroidectomy were investigated by histopathological and immunohistochemical methods. The inflammatory infiltrate was quantified and typed in intratumoral and peritumoral tissues as well as in the controlateral lobe. MAIN OUTCOME: The intratumoral infiltrate was strongly reduced or absent in PDC and UC. Intense infiltrates were detected in the PTC tall cell variant. In all histotypes, the extent of the intratumoral and peritumoral infiltrates was comparable. Immature DC were detected in PTCs and markedly reduced in PDC and UC. CD1a+ DCs were detected in a small percentage of PDC and UC. CONCLUSIONS: Though a relationship between the extent of lymphocyte/DC infiltrates and the prognosis of PTCs could not be demonstrated, tumors with poor prognosis (PDCs, UCs) were characterized by markedly reduced lymphocyte/DC infiltrates. The study appears to confirm the protective role of DC and infiltrating lymphocytes against thyroid tumors.     

Transfer pathways between the ovaries and the uterus in the cebus monkeys (Cebus apella)

The aim of this work was to study, in the Cebus apella monkey, the developmental changes in the microanatomy of the utero-ovarian ligament (UOL) and whether their vascular and neural elements might be involved in the transfer of signals between the ovaries and uterus. Sections including uterus, UOL, and ovary obtained from two foetuses, two prepubertal, and four cycling monkeys, two of them treated with a neuron-axonal tracer, diamidino yellow (DY) into the corpus luteum (CL) and the remaining two into the endometrium, were analyzed for the expression of neurofilament protein (NFP) and tracer distribution. Eight regularly cycling females were used to investigate the transfer to the CL of pulses of prostaglandin F(2alpha) (PGF(2alpha)) (n=4) or its vehicle (n=4) given intra-uterus. A convoluted artery, in conjunction with various vein channels, passed over the UOL allowing for a direct communication between uterus and ovaries. The artery acquired prominence during adulthood, in a manner well suited with the ovarian status. Immunohistochemical analysis revealed that NFP expression by the oocyte and by the endometrial epithelial cells was a highly conserved feature during development, whereas the appearance of NFP fibers in the ovaries, UOL, and uterus was a late event in the ontogenesis, likely regulated by the hormonal environment. Neurons, as an obvious source for these NFP fibers, were not recognized at any developmental stage, although some neuron-like cells were observed within the CL. The pattern displayed by the tracer DY, further suggested a reciprocal axonal transport among endometrial cells and follicular and luteal cells of both ovaries and between the ovaries themselves. The functionality of the utero-ovarian connection was assessed after injecting PGF(2alpha) intra-uterus. A short exposition to PGF(2alpha) pulses was required for lowering ovarian and peripheral progesterone concentrations causing luteolysis, indicating that transport mechanism operating between uterus and ovary must be very efficient. The results suggest that the vessels and axons contained in the UOL of the Capuchin monkeys might be two combined key pathways underlying the reciprocal transfer of signals controlling utero-ovarian homeostasis.     

Evidence for functional endothelial cell damage in early diabetic retinopathy

Summary Two aspects of endothelial cell function were examined in two matched groups of male insulin-dependent diabetics, six with background retinopathy and seven without retinopathy. Leakage of fluorescein from the retinal capillaries was estimated by vitreous fluorophotometry. In addition, factors VIII/von Willebrand (vWF) and VIII-related antigen (VIII-RAG), which are synthesized by the endothelial cells, were measured, together with VIII-antihaemophilic factor (VIII-AHF). The patients without retinopathy had normal leakage of fluorescein in the macula (mean ± SEM: 1.10±0.10 g × 10^-8/ml) and the posterior vitreous (0.45±0.11 g × 10^-8/ml), and normal circulating levels of vWF (123% of a normal reference plasma ± 18%), VIII-RAG (137±14%) and VIII-AHF (112±18%). In contrast, the patients with background retinopathy showed higher leakage of fluorescein in the macula (6.34±1.74 g ×10^-8/ml; p<0.01), and the posterior vitreous (3.09±0.94 g ×10^-8/ml; p<0.02), as well as increased levels of vWF (177±16%; p<0.05). There was a trend towards increased VIII-RAG (195±24%; p<0.1), but not VIII-AHF (126 ±13%). Alterations of endothelial cell function thus accompany the development of retinopathy. It cannot be said from the present study whether these alterations also precede the appearance of retinopathy.     

Carcinogenic activity in mice of diftalone,an anti-inflammatory agent

Summary The anti-inflammatory agent diftalone was administered in the diet to male and female BALB/c mice at 300-, 600-, and 1200-ppm dose levels for 80 weeks, starting at 8 weeks of age. The animals were kept under observation until 126–128 weeks of age, when the experiment was terminated. Diftalone treatment at the highest dose was hepatotoxic and induced hepatocellular tumors in females, angiomas of the liver in males, and angiosarcomas of the liver in male and female mice. The 300- and 600-ppm dose levels were not carcinogenic. The compound was not mutagenic for Salmonella typhimurium.     

Effects of spinal section and of positive-feedback excitatory reflex on sympathetic and heart rate variability

The sympathetic outflow appears to be capable of displaying a rhythmicity synchronous with cardiovascular Mayer's waves even after spinal section. To test the hypothesis that spinal sympathetic low frequency (LF) oscillation can be enhanced during sympathetic excitation, we recorded cardiac sympathetic nerve activity (SNA), R-R interval, arterial pressure, and ventilation in 9 unanesthetized decerebrate-vagotomized cats before and after C1 spinal section. LF and high frequency (HF) components were detected in the variability of SNA, R-R interval, and systolic arterial pressure both before and after spinal section. In this latter condition, a significant coherence between LF(SNA) and LF(R-R) was present in 5 animals, whereas HF(SNA) and HF(R-R) were correlated in 4 animals. During an excitatory sympathetic spinal reflex elicited by aortic constriction, the efferent sympathetic firing was markedly enhanced (from 7+/-2 to 33+/-7 spikes/s); concomitantly, the powers of both LF(SNA) and HF(SNA) were also increased. Coherence between LF(SNA) and LF(R-R) became significant in all cases, whereas HF(SNA) and HF(R-R) became correlated in 6 animals. In 3 animals, the reflex sympathetic excitation was no longer elicitable after interrupting a vast contingent of sympathetic afferents by means of thoracic dorsal root section. We report for the first time that LF and HF oscillations are detectable in SNA, R-R interval, and systolic arterial pressure variabilities of decerebrate-vagotomized spinal cats and that an excitatory spinal reflex is capable of increasing the power of both SNA spectral components.     

Stress hormones,sleep deprivation and cognition in older adults

Cognition can be deteriorated in older persons because of several potential mechanisms including the hormonal changes occurring with age. Stress events cause modification in hormonal balance with acute and chronic changes such as increase in cortisol and thyroid hormones, and simultaneous alterations in dehydroepiandrosterone sulphate, testosterone and insulin like growth factor-1 levels. The ability to cope with stress and regain previous healthy status, also called resiliency, is particularly impaired in older persons Thus, stressful conditions and hormonal dysregulation might concur to the onset of cognitive impairment in this population.