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Biomedical subjects

R Hunt

Publications and source records attributed to R Hunt.

At least 19 recordsLinked to original sources

Increased lymphatic pumping ability in pregnant ewes.

OBJECTIVE: Daily the lymphatic system returns several liters of fluid to the systemic circulation. Unlike blood, lymph is pumped against a pressure gradient. Because vessels in the systemic circulation are hyporesponsive to vasoconstrictor hormones during pregnancy, we decided to assess whether lymphatic pumping ability was decreased during pregnancy. STUDY DESIGN: Ten pregnant ewes were chronically catheterized in the left thoracic duct and jugular vein. Four days after surgery thoracic duct pumping ability was determined by measuring the lymph flow rate as a function of outflow pressure by varying the height at which lymph flow drains in an open-flow system. RESULTS: Lymph flow was plotted against outflow pressure, and the value at which lymph flow decreases is defined as the "breaking point." The outflow pressure at which lymph flow equals zero is the "stopflow" pressure; this value defines the pumping ability. The pregnant ewes had a breaking point of -1 +/- 2.7 versus 14.4 +/- 3.0 mm Hg (mean +/- SD) for the nonpregnant sheep. Stopflow pressures were 62 +/- 7.3 versus 23.9 +/- 4.7 mm Hg (mean +/- SD) for the nonpregnant ewes (p < 0.05). CONCLUSIONS: The ability of the lymphatic system to generate pressure is increased during pregnancy, but the breaking point is diminished. Alterations of lymphatic pumping ability could explain fluid retention under pathophysiologic conditions.

Animals

Glucose turnover and its regulation during intense exercise and recovery in normal male subjects.

Intense exercise to exhaustion is expected to be associated with rapid and large changes in glucose production (Ra) and utilization (Rd). To quantify these, and to determine their mechanisms and those of the prolonged postexercise hyperglycemia, we measured circulating metabolic regulators and glucose kinetics, the latter by the method of enriched tracer [3-3H] glucose infusion during exercise. Eighteen fit, lean young male subjects exercised to exhaustion at 80% of maximal workload (approximately 100% VO2max) on a cycle ergometer. Plasma glucose was 4.90 +/- 0.08 mM/L at rest, increased during exercise, then abruptly to 6.91 +/- 0.40 mM/L at 4 min recovery then gradually declined. Plasma insulin was constant during exercise, then doubled to 162 +/- 28 pmol/l until 20 min recovery, before declining. Plasma glucagon increased by 71 +/- 11 pg/mL. Plasma norepinephrine increased 18-fold and epinephrine 14-fold, both declining by 20 min recovery. Ra increased 7-fold by exhaustion to 13.0 +/- 1.18 mg/kg/min, then decreased to 2.43 +/- 0.24 mg/kg/min by 9 min, then to about 2 mg/kg/min the rest of recovery. Rd rose 3-fold (6.61 +/- 0.70 mg/kg/min), and remained lower than Ra to 7 min recovery, but thereafter declined more slowly. Thus, the rapid and extremely large increase in Ra was not matched by the increment in Rd during exercise and early recovery. We suggest that unlike in exercise of lesser intensity, the major mediators of both the increase in Ra and the restraint of the increase in Rd are the catecholamines. The post exercise hyperglycemia and hyperinsulinemia are appropriate to muscle glycogen repletion.

Adult

Detection of breast abnormalities on teleradiology transmitted mammograms.

The authors conducted an observer performance study to compare breast lesion detection of conventional mammography (CM) with teleradiology (TE) transmitted mammograms. One hundred four abnormal, single-projection mammographic images were transmitted by teleradiology. Abnormalities included 11 cases with skin thickening or retraction, 48 cases with microcalcifications, and 52 with parenchymal masses. The CM and TE images were reviewed by four mammographers who indicated the type and location of abnormalities and a level of confidence for their diagnostic decisions. For each of three detection tasks--skin and nipple abnormalities, microcalcifications, and masses--receiver operating characteristic curve analysis was performed for individual readers and all readers as a group. For detecting skin and nipple abnormalities, readers performed significantly better with CM than with TE (z = 2.05, P = less than 0.04). However, no significant differences were found among readers for detection of either microcalcifications or masses. Further improvements in hardware and imaging parameters may improve detection of soft tissue abnormalities. Further evaluation is necessary to determine whether teleradiology might be applicable to breast cancer screening.

Breast Neoplasms

Staphylococcus aureus enterotoxin B challenge of monkeys: correlation of plasma levels of arachidonic acid cascade products with occurrence of illness.

Arachidonic acid cascade products have been shown to be increased in vitro in Staphylococcus aureus enterotoxin B (SEB)-treated epithelial cell cultures in our laboratory. In order to confirm that these products were clinically related to SEB intoxication, monkeys were administered SEB by nasogastric intubation. It caused emesis in five of six monkeys (less than 4 h), and the sixth monkey showed signs of mild illness. The monkeys which vomited continued to display signs of gastrointestinal illness beyond 8 h but were without any apparent signs of illness by 24 h. Blood samples were collected prior to SEB administration, upon first indication of illness, and at twice that time interval. One week prior to SEB treatment, the same monkeys were administered saline by nasogastric intubation and in every way handled similarly in order to serve as their own controls. Blood samples were taken from the control animals at 0, 4, and 8 h. The plasma concentrations of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 5-hydroxyeicosatetraenoic acid (5-HETE) did not vary significantly throughout the 8-h experiment for saline-treated controls, nor did they differ from the concentrations found in the plasma of monkeys just before administration of SEB. When the SEB-treated monkeys showed the first indication of illness (less than 4 h), the mean of the concentration in plasma of PGE2 increased 1.44-fold, that of LTB4 increased 2.23-fold, and that of 5-HETE was essentially unchanged. At twice the time interval of the first display of illness (less than 8 h), PGE2 was still elevated (1.48-fold), LTB4 had decreased slightly to 1.66-fold, and 5-HETE had soared (3,45-fold), suggesting a divergence in the enzymatic utilization of the parent compound of the latter two metabolites, 5-hydroperoxyeicosatetraenoic acid. These studies suggest that arachidonic acid cascade metabolites were a consequence of SEB intoxication and may provide a logical site for metabolic interference in SEB-induced toxicity.

Animals

Absence of any male-specific antigen recognized by T lymphocytes in X/XSxr' male mice.

Previous work has established that whereas X/X mice carrying the sex-reversing chromosomal fragment Sxr are positive for the male-specific transplantation antigen, H-Y, X/X mice carrying the variant Sxr', although they too develop as phenotypic males, are H-Y negative. In this paper we show that X/XSxr' male mice do not express any male-specific antigen that can induce skin-graft rejection.

Animals

Where patients with cancer die in South Australia.

In a sample of 1582 deaths among South Australian patients with cancer (795 deaths in 1981 and 787 deaths in 1985), 67% of deaths occurred in a hospital, 9% of deaths in a hospice, 10% of deaths in a nursing home, and 14% of deaths in a private residence. More patients died in a hospice or nursing home in 1985 than in 1981, and fewer died in a hospital. With increasing age, fewer patients died in a hospital and more in a nursing home. Compared with men, women were less likely to die at a private residence and more likely to die in a nursing home. A greater proportion of men with a living wife died at a private residence than was so among single or widowed men. However, conjugal status was not associated with the place of death of women. Patients who lived in the more affluent metropolitan suburbs tended more to die at a private residence than did those from poorer suburbs or country areas. Patients with haematological malignancies died in major metropolitan public hospitals more frequently than did patients with other tumours. Possible explanations are given for these findings.

Age Factors

Oral nimodipine reduces prostaglandin and thromboxane production by arteries chronically exposed to a periarterial haematoma and the antifibrinolytic agent tranexamic acid.

The calcium antagonist nimodipine blocks the effects of many vasoconstrictors of cerebrovascular smooth muscle and may reduce the incidence of delayed cerebral ischaemia following subarachnoid haemorrhage though not necessarily by inhibiting the development of angiographic cerebral vasospasm. Post-haemorrhagic CSF contains abnormally large quantities of various eicosanoids that partly reflect enhanced production by cerebral arteries. Does nimodipine affect this process? The extra-arterial and intra-arterial production of PG6 keto-F1 alpha, PGE2, PGF2 alpha and TXB2 were measured in perfused common carotid arteries taken from rabbits in which the arteries had been ensheathed by blood clot in vivo for 7 days. All rabbits were given the antifibrinolytic agent tranexamic acid to retard resolution of the clot, and half were given oral nimodipine (2 mg/kg/day) for 10 days. Nimodipine significantly reduced the extra-arterial production of TXB2 during the third and fourth hours of perfusion and, less consistently, the production of PGF2 alpha, PGE2 and PG6 keto-F1 alpha. Lutrol, the solvent for nimodipine, had no such effect.

6-Ketoprostaglandin F1 alpha

Dietary composition and renal function in healthy subjects.

Increments in dietary protein intake can increase glomerular filtration rate (GFR) in humans, and the glomerular hyperfiltration induced by high protein intake has been incriminated in the progression of glomerulosclerosis related to age and a number of renal diseases. GFR (as 51Cr-EDTA clearance) was measured in 18 vegans, 16 lactovegetarians and 18 omnivorous control subjects, matched for age. Omnivores ate significantly more total protein and protein of animal origin than the other two groups. Vegetable protein comprised 100% of the vegans' daily protein intake and 64% of the lactovegetarians', both significantly higher than the omnivores' (32%). Vegans and lactovegetarians also ate more carbohydrate and fibre than omnivores, although fat intake was similar. Mean GFR was significantly lower in the vegans than in the omnivores (100 +/- 13 vs. 113 +/- 16 ml/min/1.73 m2; p less than 0.04) and was intermediate in the lactovegetarians (105 +/- 16 ml/min/1.73 m2). Omnivores had significantly higher mean urinary albumin excretion rate (p less than 0.05) than vegans, and higher mean diastolic blood pressure than both vegans and lactovegetarians (p less than 0.01). The vegan diet is associated with glomerular and systemic haemodynamic changes which may be beneficial in the prevention of glomerular sclerotic changes in health and disease.

Albuminuria

Prevalence and significance of positive Mitsuda reaction in the nine-banded armadillo (Dasypus novemcinctus).

One hundred two armadillos captured from the wild were lepomin tested. Nine of them (8.8%) showed a positive Mitsuda reaction. The histopathological appearance of the reaction had a spectrum showing tuberculoid, borderline tuberculoid, borderline lepromatous, and lepromatous histology. It is possible that armadillos can develop all the different types of leprosy seen in humans. The armadillo is a good animal model to test protective vaccines against leprosy.

Animals

Regulation of accessory cell function by retinoids in murine immune responses.

This study examines the effects of in-vivo immune regulation by vitamin A acetate (VAA) and 13-cis-retinoic acid (13-CRA) on in-vitro accessory cell function. Mice were fed a control diet, or diet containing VAA or 13-CRA, and monitored by body weight gains and diet consumptions at weekly intervals. At 4, 7 and 12 weeks mice were killed, differential blood counts performed and accessory cells isolated from lymphomedullary tissues. Histology confirmed that the chief feature of the lymphomedullary organs of the VAA-fed animals was an expansion of the splenic marginal zone and the paracortical region of the lymph nodes. There was an increase in the number of accessory cells present, and this included both dendritic cells and macrophages. The accessory cell function of these cells was also increased, as evidenced by both alloproliferative and allocytotoxic responses in vitro. In 13-CRA-fed animals the effects were similar to those seen with VAA, but were less pronounced. We suggest that the primary effects of these compounds on in-vivo immunoregulation could be due to their promotion of accessory cell function.

Animals

Early postnatal administration of 5,7-dihydroxytryptamine: effects on substance P and thyrotropin-releasing hormone neurons and terminals in rat brain.

Substance P, thyrotropin-releasing hormone (TRH) and serotonin are putative neurotransmitters which have been proposed to co-exist in some brain neurons. Our previous immunocytochemical and biochemical studies have demonstrated that 85-100% of all serotonin neurons are destroyed following neonatal 5,7-dihydroxtryptamine (5,7-DHT) treatment. In this study, we have determined the effect of neonatal 5,7-DHT and desipramine (DMI) treatment on the biochemical content and immunocytochemical localization of substance P and TRH throughout the brain. Interestingly, we have observed that virtually all substance P- and TRH-immunoreactive cells in the ventral pons-medulla are destroyed by the neurotoxin. However, peptide-containing neurons in other regions were not affected. Additionally, we measured the peptide content and found that TRH is significantly decreased in the spinal cord (-50%) and pons-medulla (-20%), but not in other brain regions. Substance P content was not significantly altered in any region, even after a greater than 90% reduction of serotonin. These data indicate that the co-localized substance P and TRH forms a small proportion of the total peptide in brain.

5,7-Dihydroxytryptamine

T-cell depletion of allogeneic bone marrow prevents acceleration of graft-versus-host disease induced by exogenous interleukin 2.

Highly purified human recombinant interleukin 2 (IL-2) markedly accelerated lethal GVHD in the H-2-identical B10.BR----CBA combination, but had no effect when the donor cells were depleted of mature (Thy-1.2-positive) T lymphocytes, indicating a strong immunopotentiating effect of IL-2 on mature T cells causing GVHD. In the same donor-host combination, IL-2 did not influence the recovery from the post-transplantation bone marrow aplasia. The results suggest that IL-2 could be considered for adjuvant hormonal therapy to enhance immune recovery in recipients of T-cell-depleted allogeneic marrow.

Animals

H-Y status of X/X Sxr' male mice: in vivo tests.

Sex reversed X/X male mice carrying Sxr or the variant Sxr' were typed for expression of the male specific histocompatibility antigen H-Y, by skin grafting and by in vitro cytotoxic and proliferative tests. The X/XSxr males, like X/Y males, were H-Y positive by in vitro testing, and failed to reject semi-syngeneic male skin grafts. In contrast X/XSxr' males, like X/X females, were H-Y negative and rejected semi-syngeneic, male skin. Spleen cells from X/Y males sensitized C57BL/10 female recipients to reject syngeneic male skin rapidly, whilst immunization with X/X female or X/XSxr' male cells failed to stimulate such second-set responses. These data suggest that the H-Y antigen detected by cytotoxic T cells is the same as that detected by graft rejection responses, that the Sxr' variant is not a tissue-specific regulatory mutation, and that X/XSxr' individuals do not express H-Y antigen but nevertheless develop as phenotypic males.

Animals