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Biomedical subjects

M Hurd

Publications and source records attributed to M Hurd.

11 recordsLinked to original sources
PubMed1997

Inactivation of Cryptosporidium parvum oocysts and Clostridium perfringens spores by a mixed-oxidant disinfectant and by free chlorine.

Cryptosporidium parvum oocysts and Clostridium perfringens spores are very resistant to chlorine and other drinking-water disinfectants. Clostridium perfringens spores have been suggested as a surrogate indicator of disinfectant activity against Cryptosporidium parvum and other hardy pathogens in water. In this study, an alternative disinfectant system consisting of an electrochemically produced mixed-oxidant solution (MIOX; LATA Inc.) was evaluated for inactivation of both Cryptosporidium parvum oocysts and Clostridium perfringens spores. The disinfection efficacy of the mixed-oxidant solution was compared to that of free chlorine on the basis of equal weight per volume concentrations of total oxidants. Batch inactivation experiments were done on purified oocysts and spores in buffered, oxidant demand-free water at pH 7 an 25 degrees C by using a disinfectant dose of 5 mg/liter and contact times of up to 24 h. The mixed-oxidant solution was considerably more effective than free chlorine in activating both microorganisms. A 5-mg/liter dose of mixed oxidants produced a > 3-log10-unit (> 99.9%) inactivation of Cryptosporidium parvum oocysts and Clostridium perfringens spores in 4 h. Free chlorine produce no measurable inactivation of Cryptosporidium parvum oocysts by 4 or 24 h, although Clostridium perfringens spores were inactivated by 1.4 log10 units after 4 h. The on-site generation of mixed oxidants may be a practical and cost-effective system of drinking water disinfection protecting against even the most resistant pathogens, including Cryptosporidium oocysts.

Animals↗
PubMed1995

Split tolerance in spleen chimeras.

Transferring small doses of T cells to heavily irradiated F1 mice expressing isolated MHC class I or class II differences invariably leads to rapid death from graft-vs-host disease (GVHD). Paradoxically, GVHD is mild or absent when irradiated F1 mice are reconstituted with large doses of unseparated parental strain spleen cells. This applies when bulk populations of B6 spleen cells are transferred to irradiated class II-different (B6 x bm12)F1 mice or class I-different (B6 x bm1)F1 mice. In this study, we examined whether the donor T cells in long-term spleen chimeras become tolerant to host MHC Ags. On the basis of skin-allograft rejection and induction of GVHD on adoptive transfer, the results show that the donor T cells display strong tolerance to host antigens; this applies to CD4+ cells in class II-different chimeras and to CD8+ cells in class I-different chimeras. In marked contrast to the profound tolerance seen by these in vivo parameters, little or no tolerance is observed in standard in vitro assays. The results illustrate that typical in vitro tests for alloreactivity are an imprecise guide to physiologic tolerance of T cells in vivo.

Animals↗
PubMed1994

Profound atrophy of the bone marrow reflecting major histocompatibility complex class II-restricted destruction of stem cells by CD4+ cells.

The effector functions of CD4+ cells in vivo are presumed to reflect a combination of lymphokine-mediated bystander reactions and direct cytotoxic T lymphocyte activity. To assess the relative importance of these two mechanisms, we studied the effects of transferring small doses of purified unprimed CD4+ cells to lightly irradiated (600 cGy) recipients expressing major histocompatibility complex class II (Ia) differences. Within the first week after transfer, the host marrow was rapidly repopulated with hemopoietic cells. Thereafter, however, the donor CD4+ cells caused massive destruction of hemopoietic cells, both in marrow and spleen. Marrow aplasia did not affect stromal cells and was prevented by coinjecting donor but not host bone marrow. The use of allotypic markers and fluorescence-activated cell sorter analysis indicated that the destructive effects of CD4+ cells were directed selectively to host Ia+ hemopoietic cells, including stem cells; donor hemopoietic cells and Ia- host T cells were spared. No evidence could be found that the ongoing destruction of host cells impaired the capacity of donor stem cells to repopulate marrow, spleen, or thymus. Moreover, CD4+ cells failed to destroy host-type hemopoietic cells from Ia-deficient mice. Tissue destruction by CD4+ cells thus did not seem to reflect a bystander reaction. We conclude that, under defined conditions, CD4+ cells can manifest extremely potent Ia-restricted CTL activity in vivo, probably through recognition of covert Ia expression on stem cells and/or their immediate progeny.

Animals↗
PubMed1991

Mature murine B and T cells transferred to SCID mice can survive indefinitely and many maintain a virgin phenotype.

To seek information on the potential lifespan of normal B and T lymphocytes, lymph node (LN) cells from unprimed mice were transferred to H-2-identical severe combined immunodeficiency (SCID) hosts. At a population level, the donor B and T cells survived for at least 10 mo post-transfer with no reduction in their numbers. In terms of antibody production, LN-injected SCID mice remained responsive to several different antigens and contained unprimed precursors of memory cells for greater than or equal to 6 mo post-transfer. Most of the B and T cells recovered from LN-injected SCID mice expressed the typical virgin phenotype of mature lymphocytes from young mice. These findings suggest that many of the transferred lymphocytes might have remained in interphase as virgin cells from the time of injection. This did not apply to all of the transferred cells, however, because 20-40% of CD4+ cells from long-term SCID hosts displayed a memory phenotype, 7% incorporated 2-bromodeoxyuridine over 5 d, and total numbers of B and T cells increased gradually (twofold) over a 10-mo period. Collectively, the data favor the view that the pool of mature B and T cells in adult mice is largely self sufficient: some of the cells proliferate, presumably in response to environmental antigens, but many mature cells can remain quiescent for prolonged periods. Input of new cells from the primary lymphoid organs continues, but at a much reduced rate relative to young life.

Animals↗
PubMed1991

Interactions between body temperature and wheel running over the estrous cycle in rats.

Female rats were housed in Wahmann wheels under a 12:12 light-dark (LD) photoperiod for 36 days and then were switched to LD 10:14 for 36-64 days. Running was 95-100% nocturnal. Overall amounts of running were higher in LD 12:12, but changes over the estrous cycle were similar. On the night of proestrus running increased by 64% in LD 12:12 and 123% in LD 10:14 (p less than 0.0001) compared to the first night of diestrus. Nighttime Tb's were correlated with running levels. In LD 12:12 Tb on proestrus was higher by 0.3 +/- 0.0 degrees C (p less than 0.0001); in LD 10:14 it was higher by 0.2 +/- 0.0 degrees C (p less than 0.001) compared to diestrus-1. During L, Tb was lowest on proestrus and highest on estrus. Half of the rats exhibited a consistent phase advance of at least 30 min in both Tb and activity on proestrus. The advanced Tb acrophase was correlated with both the activity acrophase (r = .91; p less than 0.0001) and the amount of running (r = .60; p less than 0.01). The wheels of 6 rats were then locked at night in LD 10:14. There were no significant Tb changes from diestrus-1 across the cycle. However, Tb acrophase was delayed a mean of 76 +/- 16 min (p less than 0.01) in these rats. Also, the Tb acrophase across all days of the estrous cycle was delayed by 94 +/- 18 min (p less than 0.001) compared to when the wheels were open.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Phentolamine and thermoregulation in rats.

Phentolamine (PHEN), a nonselective alpha-adrenoceptor antagonist, causes a dose and ambient temperature (Ta)-dependent fall in body temperature (Tb) when injected intraperitoneally. In this paper, we investigated whether this was caused by integrated behavioral and autonomic thermoregulatory responses and whether it was due to a central action of the drug. Male rats were trained to press a bar for warm air in the cold or cold air in the heat. Rats were tested in both conditions near their Tb peaks and troughs after injections of saline or PHEN (5 and 10 mg/kg, IP). Tb fell significantly within the first 30 min post-PHEN, and after that, in the cold, the rats worked to increase Ta. In the heat they did not change Ta. To determine what was responsible for the Tb fall, we measured heat loss and heat production after saline or PHEN (10 mg/kg; IP) at Ta 2, 20, and 30 degrees C. Decreases in Tb at 2 and 20 degrees C were caused by increased heat loss during the first 15-30 min post-PHEN. At 2 degrees C, heat production increased after the drop in Tb. We conclude that the main reason the rats do not start to work immediately to prevent their core temperature from falling is that skin temperature is high, due to peripheral vasodilation, and that skin temperature is the major stimulus for regulating preferred Ta. We believe these effects are mediated by peripheral mechanisms because intracerebro-ventricular injections of PHEN did not cause a fall in Tb.

Animals↗
PubMed1991

Elevated body temperature in female rats after exercise.

Female Sprague-Dawley rats living in basin cages (sedentary rats) under a 12:12 light-dark cycle normally have body temperatures (Tb; measured via telemetry) that vary from a mean peak of 38.1 +/- 0.1 degrees C in the dark to a mean trough of 36.0 +/- 0.1 degrees C C in the light. We have found that if rats are housed in activity wheels, their mean peak Tb in the dark, when they run in the wheels, rises to about 39.5 degrees C. Mean trough Tb in the light also rises, to about 36.5 degrees C, although they never or very rarely run in the wheels in the light. Other rats were rotated through two cycles of wheel-open (WO) and wheel-locked (WL) conditions. During the first WO cycle their mean Tb in the dark gradually rose over the first 2 wk, and their mean Tb in the light gradually fell. In the first WL, mean Tb in the dark fell immediately to sedentary levels, and mean Tb in the light fell more gradually. In the second WO condition, both dark and light Tb rose almost immediately. Since rats in locked wheels have Tb similar to sedentary controls, these results support the hypothesis that steady exercise at night results in an upward resetting of a thermoregulatory set-point during the day.

Animals↗
PubMed1982

Uterine and peripheral blood concentrations of vasodilator prostaglandins in conscious pregnant rabbits.

The concentrations of prostaglandin E2 (PGE2) and prostacyclin (PGI2) were estimated in blood obtained from the uterine venous effluent and a peripheral artery of conscious pregnant and nonpregnant rabbits. The blood was analyzed both with a superfusion bioassay and radioimmunoassays. PGE2, but not PGI2, was detected in a very high concentration in the uterine venous effluent of the pregnant rabbit. The peripheral blood of pregnant animals also revealed increased levels of only PGE2. The results of both assay techniques correlated closely. These studies suggest that the uteroplacental unit is the source of the increased peripheral level of the potent vasodilator PGE2. In contrast, these data fail to support the notion that PGI2 is the primary systemic-acting vasodepressor prostaglandin in rabbit pregnancy.

Animals↗