Effects of hypoxia on urinary organic acid and hypoxanthine excretion in fetal sheep

Severe birth asphyxia leads to a transient organic aciduria and increased hypoxanthine excretion. To investigate its origin and timing, we analyzed urine from 12 late gestation fetal sheep in utero subjected to moderately severe isocapnic hypoxia for 1 h. In six fetuses the carotid sinus nerves were cut to determine whether reflex peripheral vasoconstriction contributed to the changes in excretion. After a control period of 1 h, maternal inspired oxygen was reduced for 1 h so that fetal arterial oxygen tension fell significantly from 2.86 +/- 0.12 kPa (mean +/- SEM) to 1.55 +/- 0.04 kPa. The ewes were returned to normoxia, and monitoring was continued for 1 h. Fetal heart rate, arterial blood pressure, and femoral arterial blood flow (intact fetuses only) were recorded, and arterial pH, blood gases, and lactate were measured. Urine collected via a bladder catheter was analyzed for organic acids and hypoxanthine with gas chromatography-mass spectrometry. In intact fetuses, hypoxia increased excretion of hypoxanthine and several organic acids, notably lactic acid and intermediates of valine catabolism. Changes were apparent by 15 min, significant by 45 min, and maximal after reoxygenation. In denervated fetuses, there were small, significant, increases in organic acids and hypoxanthine by 45 min of hypoxia, but there was no surge in excretion posthypoxia. Hypoxia caused a large, significant, fall in femoral arterial blood flow in intact fetuses. We conclude that the extent of the reflex peripheral vasoconstriction, particularly in skeletal muscle, determines the amount of organic acid and hypoxanthine excretion and may explain similar biochemical disturbances after birth asphyxia. Urinary lactic acid measurement has a potential value for grading birth asphyxia.     

IS-RT-PCR assay detection of MT-MMP in a human breast cancer cell line

The effect of the host system on the pathogenicity, immunogenicity, and antigenicity of infectious bursal disease virus (IBDV) was investigated. One classic (SAL) and one variant strain (IN) of IBDV were passaged separately six times in three host systems, namely BGM-70 continuous cell line, primary chicken embryo fibroblast (CEF) cells, or embryonating chicken eggs (embryos) or one time in the bursa of Fabricius (BF) of specific-pathogen-free (SPF) chickens. Passage in BGM-70 cells or CEF cells resulted in loss of pathogenicity, but viruses passaged in embryos or BF maintained their pathogenicity. For the immunogenicity study, the viruses described above were used to prepare live and inactivated vaccines, containing 10(3) mean embryo infectious doses (EID50s) and 10(5) EID50s respectively. These vaccines induced different levels of protection. It was concluded that the antigen titration methodology employing embryonating chicken eggs was not suitable for titration of viruses propagated in other host systems because of varying degrees of adaptation and/or pathogenicity of the viruses resulting in variability in antigen mass of the tested vaccines. To test this assumption, an antigen-capture enzyme-linked immunosorbent assay was used as a titration system to compare the antigenicity of viruses propagated in BGM-70 cells or BF. Preparations containing similar antigen masses were inactivated then inoculated into two age groups of SPF chickens and antibody titers were monitored. During the experimental period, the geometric mean virus-neutralizing (VN) antibody titers of the vaccinated groups did not differ significantly (P > 0.05).     

The use of intermittent lighting in broiler raising. 2. Effects on the somatotrophic and thyroid axes and on plasma testosterone levels

Male and female broiler chicks were raised separately in nearly continuous lighting [23 h light (L):1 h dark (D), CL] and consumed feed ad libitum. At 7 d of age, the intermittent lighting schedule (1L:3D, IL) was imposed on half of the chicks, whereas the other chicks remained under CL. In addition to performance characteristics, several parameters of the somatotrophic and thyrotrophic axes were studied together with plasma concentrations of testosterone. Males had a higher growth rate than females regardless of the imposed lighting schedule and this pronounced growth difference is reflected by higher plasma concentrations of growth hormone (GH), and a better GH receptor occupancy. Differences in growth rate between sexes could not be attributed to differences in circulating 3,3',5-triiodothyronine (T3) levels or to hepatic deiodination activities. However, from 3 wk of age onwards, males had significantly higher plasma testosterone levels than females. Plasma GH and T3 levels decreased whereas plasma insulin-like growth factor-I and thyroxine levels increased with age in all experimental groups. The age-related decline in plasma GH levels were less pronounced for males than for females. No major changes in other hormonal parameters or deiodination activities could be observed as a result of imposing IL, except for the higher plasma GH levels of IL chickens, and for plasma testosterone concentrations in IL males at Day 41, which were twice the levels found in their CL counterparts. These results therefore suggest that the somatotrophic axis as well as circulating testosterone levels mediate the sex-related differences in growth rate and the compensatory growth as present in males.     

Haemangiopericytoma of the nasal cavity

Haemangiopericytoma of nose and paranasal sinuses is relatively uncommon tumour. It occurs in adults in sixth and seventh decades of life. In view of paucity of intranasal haemangiopericytoma old in Indian literature and young age of patient, we are reporting one case in 28-year-old female who presented with recurrent, profuse epistaxis.     

T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls

Despite the fact that the neuroleptic drugs have been widely used for more than 40 years, one of their most common side-effects, akathisia, has been relatively neglected. There are still no universally agreed diagnostic criteria for akathisia, particularly chronic akathisia, and in this review article, we discuss the controversies surrounding the voluntary nature of its motor features and the importance of the dysphoric component. We also review the published epidemiological studies to show the great variation in frequency of occurrence. Finally, we discuss the possible neurotransmitters involved in the pathophysiology and treatment of this condition.     

A neostriatal habit learning system in humans

Amnesic patients and nondemented patients with Parkinson's disease were given a probabilistic classification task in which they learned which of two outcomes would occur on each trial, given the particular combination of cues that appeared. Amnesic patients exhibited normal learning of the task but had severely impaired declarative memory for the training episode. In contrast, patients with Parkinson's disease failed to learn the probabilistic classification task, despite having intact memory for the training episode. This double dissociation shows that the limbic-diencephalic regions damaged in amnesia and the neostriatum damaged in Parkinson's disease support separate and parallel learning systems. In humans, the neostriatum (caudate nucleus and putamen) is essential for the gradual, incremental learning of associations that is characteristic of habit learning. The neostriatum is important not just for motor behavior and motor learning but also for acquiring nonmotor dispositions and tendencies that depend on new associations.     

Thirteen-year evolution of azole resistance in yeast isolates and prevalence of resistant strains carried by cancer patients at a large medical center

Drug resistance is emerging in many important microbial pathogens, including Candida albicans. We performed fungal susceptibility tests with archived isolates obtained from 1984 through 1993 and fresh clinical isolates obtained from 1994 through 1997 by testing their susceptibilities to fluconazole, ketoconazole, and miconazole and compared the results to the rate of fluconazole use. All isolates recovered prior to 1993 were susceptible to fluconazole. Within 3 years of widespread azole use, we detected resistance to all agents in this class. In order to assess the current prevalence of resistant isolates in our hematologic malignancy and transplant patients, we obtained rectal swabs from hospitalized, non-AIDS, immunocompromised patients between June 1995 and January 1996. The swabs were inoculated onto sheep's blood agar plates containing 10 microg of vancomycin and 20 microg of gentamicin/ml of agar. One hundred one yeasts were recovered from 97 patients and were tested for their susceptibilities to amphotericin B, fluconazole, flucytosine, ketoconazole, and miconazole. The susceptibility pattern was then compared to those for all clinical isolates obtained throughout the medical center. The antifungal drug histories for each patient were also assessed. The yeasts from this surveillance study were at least as susceptible as the overall hospital strains. There did not appear to be a direct linkage between prior receipt of antifungal agent therapy and carriage of a new, drug-resistant isolate. Increased resistance to newer antifungal agents has occurred at our medical center, but it is not focal to any high-risk patient population that we studied. Monitoring of susceptibility to antifungal agents appears to be necessary for optimizing clinical therapeutic decision making.     

Endothelium-dependent potentiation of prostaglandin F2alpha-induced contractions by (+/-)-[6]-gingerol is inhibited by cyclooxygenase- but not lipoxygenase-inhibitors in mouse mesenteric veins

The mechanism of potentiation of prostaglandin (PG) F2alpha-induced contraction of mouse mesenteric veins by (+/-)-[6-gingerol was investigated in vitro. (+/-)-[6]-Gingerol (0.3mM) potentiated the maximal contraction response elicited by PGF2alpha (0.28 mm) in the presence of intact vascular endothelium, but not in its absence (de-endothelialized preparations). The potentiating effect was completely inhibited by cyclooxygenase inhibitors (0.2 mm aspirin and 0.2 mm indomethacin) and partly by calcium antagonists (2 microM verapamil, 8 nM nitrendipine and 1 microM ryanodine), but not inhibited by nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor and ONO-3708, a thromboxane (TX) A2 antagonist. The potentiation by (+/-)-[6]-gingerol is also observed in mesenteric veins of streptozotocin-diabetic mice where the enhancement of PGF2alpha-induced contraction is caused mainly by activation of lipoxygenase. The potentiation of PGF2alpha-induced contraction by (+/-)-[6]-gingerol may be caused by a cyclooxygenase-dependent release of vasoconstrictors, other than PGF2alpha and TXA2, or by inhibiting vasorelaxants released from endothelial cells of mouse mesenteric veins.     

A retroviral vector that directs simultaneous expression of alpha and beta T cell receptor genes

The transfer of alpha/beta T cell receptor (TCR) genes into T lymphocytes or their precursors could provide a means to increase frequency of tumor- or pathogen-specific cytotoxic T lymphocytes. To begin to address this possibility, we have used class I MHC-restricted alpha/beta TCR cDNAs to develop a retroviral TCR expression vector. Alpha- and beta-chain cDNAs were inserted into a derivative of the LN series of retroviral vectors, with the retroviral LTR directing expression of TCR-beta and an internal cytomegalovirus promoter/enhancer driving TCR-alpha expression. The variable region fragments can be replaced using unique restriction sites that have been introduced into the proximal constant regions. We have used this vector system to transfer two different pairs of alpha/beta TCR genes into an alpha- and beta-chain-deficient T cell hybridoma. TCR- hybridoma cells were transduced by coculture with pools of virus-producing cells, and fluorescence-activated cell sorting was used to enrich for cells expressing the transduced TCR. Transduction with either alpha/beta TCR restores stable, long-lived expression of the alpha/beta TCR complex. TCR-mediated signal transduction is also reconstituted, as demonstrated by the ability of transduced cells to secrete IL-2 following stimulation with Vbeta-specific antibodies. Our results suggest that alpha/beta T cell receptor gene transfer could provide a basis for new approaches to immunotherapy, and that further studies examining the in vivo fate of transduced TCR are possible.     

The influence of aging and target motion on the control of prehension

The purpose of this study was to examine age-related differences in reaching behavior when younger (mean age = 26.0 years) and older (mean age = 70.1 years) individuals were required to reach toward and grasp both small and large targets that were either stationary or moving. The older subjects had shorter movement times, and smaller within-subject movement time variability than younger subjects. Also, the deceleration of the reach was shorter for older subjects, indicating that they were not making extensive use of on-line feedback, and were instead utilizing anticipatory control strategies. There were no age differences in the size of the maximum grasp around the target, but the timing of the grasp was influenced by target motion for the younger subjects, suggesting on-line control for the younger subjects only.