Regulation of protein synthesis in ventricular myocytes by vasopressin. The role of sarcoplasmic/endoplasmic reticulum Ca2+ stores

Protein synthesis in H9c2 ventricular myocytes was subject to rapid inhibition by agents that release Ca2+ from the sarcoplasmic/endoplasmic reticulum, including thapsigargin, ionomycin, caffeine, and arginine vasopressin. Inhibitions were attributable to the suppression of translational initiation and were coupled to the mobilization of cell-associated Ca2+ and the phosphorylation of eIF2alpha. Ionomycin and thapsigargin produced relatively stringent degrees of Ca2+ mobilization that produced an endoplasmic reticulum (ER) stress response. Translational recovery was associated with the induction of ER chaperones and resistance to translational inhibition by Ca2+-mobilizing agents. Vasopressin at physiologic concentrations mobilized 60% of cell-associated Ca2+ and decreased protein synthesis by 50% within 20-30 min. The inhibition of protein synthesis was exerted through an interaction at the V1 vascular receptor, was imposed at physiologic extracellular Ca2+ concentrations, and became refractory to hormonal washout within 10 min of treatment. Inhibition was found to attenuate after 30 min, with full recovery occurring in 2 h. Translational recovery did not involve an ER stress response but rather was derived from the partial repletion of intracellular Ca2+ stores. Longer exposures to vasopressin were invariably accompanied by increased rates of protein synthesis. Translational inhibition by vasopressin, but not by Ca2+-mobilizing drugs, was both preventable and reversible by treatment with phorbol ester, which reduced the extent of Ca2+ mobilization occurring in response to the hormone. Larger and more prolonged translational inhibitions occurred after down-regulation of protein kinase C. This report provides the first compelling evidence that hormonally induced mobilization of sarcoplasmic/endoplasmic reticulum Ca2+ stores is regulatory upon mRNA translation.     

Seroepidemiology of canine leptospirosis on the island of Barbados

Previous surveillance in Barbados documented the absence of infection with Leptospira serogroup Canicola in dogs. The aim of this study was to survey the current state of canine leptospirosis in Barbados, 10 years after the last survey. Sera from 78 unwanted dogs scheduled for euthanasia and 61 dogs suspected of having acute leptospirosis were tested by microscopic agglutination (MAT) and by an ELISA method adapted for canine IgM and IgG antibodies. The seroprevalence in unwanted dogs was 62% (48/78), at an MAT titre of > or = 100. The majority of animals had low titres, suggestive of previous infection. Serogroup Autumnalis was the most common reactor (45%), followed by serogroups Icterohaemorrhagiae and Australis (each 16%) and Pomona (13%). Serogroup Ballum was uncommon in this group. The seroprevalence determined by MAT in acutely-ill dogs was 75% (46/61). The most common predominant serogroup was Icterohaemorrhagiae (36%) followed by serogroup Australis (13%), while serogroups Autumnalis and Ballum were also of little significance. Paired specimens were available from eight acutely-ill dogs. One animal was seronegative while five dogs showed evidence of seroconversion. An IgM-ELISA titre of > or = 320 was used to confirm current infection in eight of these nine animals. Previous studies in Barbados showed a higher prevalence of serogroup Icterohaemorrhagiae than of Autumnalis, but the relative frequency of these two serogroups may be changing. The high seroprevalence in dogs is of public health concern because the close contact between dogs and man may provide the link between a reservoir in the environment and susceptible humans.     

Cervical tissue and plasma concentrations of alpha-carotene and beta-carotene in women are correlated

Results from epidemiologic studies suggest that a carotenoid-rich diet may reduce risk for cervical cancer, possibly by inhibiting the progression of cervical intraepithelial neoplasia, a preneoplastic lesion of the cervical tissue. Laboratory studies suggest that the mechanism may be linked to the metabolism of carotenoids to retinoic acid or retinoic acid-like compounds, which has been hypothesized to occur in the cervical tissue. The purpose of this study was to demonstrate the presence of provitamin A carotenoids in biopsied samples of this peripheral tissue in human subjects and to examine the relationship between baseline concentrations of these carotenoids in plasma and normal cervical tissue in subjects who were being evaluated for possible participation in a diet intervention trial. Subjects were 13 women aged 19-41 y. With the use of HPLC methodology, plasma concentrations of alpha-carotene, beta-carotene and beta-cryptoxanthin were determined with UV/visible light detection for plasma and electrochemical detection for cervical tissue. Relationships between plasma and cervical tissue were evaluated with Pearson correlation analysis. Adjusted for plasma cholesterol concentration, plasma alpha-carotene and beta-carotene were correlated with cervical tissue concentrations (r = 0.91, P < 0.001; r = 0.90, P < 0.001; respectively). Adjusted for plasma cholesterol concentration, plasma beta-cryptoxanthin tended to be correlated with cervical tissue concentrations (r = 0.62, P = 0.058). These findings suggest that plasma concentrations of alpha-carotene and beta-carotene are good predictors of cervical tissue concentrations of these compounds in human subjects and describe a first step toward demonstrating a biological link between provitamin A carotenoids and cervical cancer in vivo.     

The mouse mutation sarcosinemia (sar) maps to chromosome 2 in a region homologous to human 9q33-q34

The autosomal recessive mouse mutation sarcosinemia (sar), which was discovered segregating in the progeny of a male whose premeiotic germ cells had been treated with the mutagen ethylnitrosourea, is characterized by a deficiency in sarcosine dehydrogenase activity. Using an intersubspecific cross, we mapped the sar locus to mouse chromosome 2, approximately 15-18 cM from the centromere. The genetic localization of this locus in the mouse allows the identification of a candidate region in human (9q33-q34) where the homologous disease should map.     

Analysis of the role of MHC class II presentation in the stimulation of cytotoxic T lymphocytes by antigens targeted into the exogenous antigen-MHC class I presentation pathway

By conjugation of proteins to beads, Ags can be selectively targeted into the MHC class I pathway of phagocytes in vivo and can stimulate CTL responses. Because phagocytes also present particulate Ag on MHC class II molecules, we examined whether these Ags stimulated concomitant CD4 T cell immunity. Although the priming of CD4 T cells with soluble OVA required adjuvants, particulate Ag was stimulatory when injected in saline. We next examined whether CD4 T cell responses played a role in the generation of CTL to particulate Ag. At low concentrations of Ag, OVA primed CTLs in wild-type mice but not in MHC class II-deficient animals, indicating that MHC class II presentation of Ag was essential for CTL generation. These data both support a model where CD4 T cells collaborate with CTLs as part of a three-cell interaction and identify a phagocyte as the third cell in this reaction. Interestingly, injection of higher concentrations of the same Ag primed equivalent CTL responses in both wild-type and MHC class II-deficient mice. These results indicate that a key variable in determining whether CTL generation is helper cell dependent or independent is the dose of immunogen. This may explain in part why CTL responses to abundant Ags, such as viruses, tend to be helper independent, while responses to less abundant Ags, such as minor histocompatibility Ags, require T helper cells. In addition, these results also point to the potential of using particulate Ags to prime or boost responses in settings with CD4 immunodeficiency.     

Stereokinetic effect and its relation to the kinetic depth effect.

The stereokinetic effect (SKE) has been defined and studied by nested circular patterns rotating on a turntable. Circles must appear not to rotate as they revolve, which in turn results in their appearing to translate relative to one another. A powerful illusion of object depth results even though the individual circles do not undergo an appropriate foreshortening consistent with their apparent changes in slant. It is suggested and tested that the SKE is based on the changing positions between the nested contours despite the absence of any change within each contour, whereas the kinetic depth effect (KDE) entails both kinds of change. It follows that a turntable method of presentation is not necessary, and between-contour transformations can be stimulated by computer animation. Displays consisting of simple translations were shown to evoke robust depth impressions as were patterns consisting of contours of varying shapes. Comparisons of the depth, compellingness, and rigidity of matched SKE and KDE displays are reported. The SKE is taken to be paradigmatic for how the visual system perceives depth when observing small object rotations that occur in everyday situations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Palliation of recurrent endometriosis with radiotherapeutic ablation of ovarian remnants

OBJECTIVE: To review the use of radiotherapy for relieving the symptoms of recurrent endometriosis caused by functioning ovarian remnants. DESIGN: Retrospective study (case report). PATIENT(S): A woman with recurrent endometriosis of 14 years' duration. INTERVENTION(S): After hysterectomy and bilateral oophorectomy, hormonal management, and multiple explorations for recurrent endometriosis, cycling ovarian remnants were confirmed histologically. Pelvic irradiation was used to ablate this tissue. A dose of 15 Gy in 10 daily fractions was given through anterior and posterior opposed fields using 18-mV photons. RESULT(S): The patient had a prompt increase in FSH levels associated with castration levels of serum E2. A review of the literature on the use of radiotherapy in this clinical situation is presented. CONCLUSION(S): Radiotherapy should be considered in selected patients when ovarian castration is not a viable surgical option and hormonal therapies have failed.     

Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis

Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV 2) into BALB/cN and C57BL/6N mice was carried out to induce experimental myelitis. The myelitis was clearly observed in C57BL/6N mice following intraperitoneal inoculation. Within 24 hours before death, the mice showed urinary and rectal incontinence and paraplegia of the hind legs. Randomly distributed, severe necrosis was demonstrated in the spinal cord, mainly at the lower cord. In BALB/cN mice the clinical symptoms were not clearly observed, as the mice died shortly after their onset. Although spinal cord necrosis was more prominent in C57BL/6N mice than BALB/cN mice, brain necrosis was only found in the latter, and not in the former. Both strains of mouse showed marked nuclear pyknosis of the nerve cells and slight nuclear pyknosis of the astrocytes in the brain where HSV 2 antigen was demonstrated immunohistochemically. The antigen was also detected in the necrotic spinal cord. In contrast, intracranial inoculation of the virus into both strains did not cause myelitis. Spinal cord necrosis was not demonstrated and virus DNA was not detected, by PCR, in spinal cord samples. In the brain, however, the virus was demonstrated by both PCR and immunohistochemistry.