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Biomedical subjects

H Bond

Publications and source records attributed to H Bond.

18 recordsLinked to original sources

Artificial perfusion of the fetal circulation of the in situ mouse placenta: methodology and validation.

Here we present methodology and validation (including measurement of unidirectional maternofetal clearance (Kmf) of (45)Ca and (14)C-mannitol) for in situ perfusion of the mouse placenta. On day 18 of gestation (term=19 days) mice were anaesthetised and the uterus delivered into a saline bath (40 degrees C). A fetus was selected, the umbilical artery and vein catheterised and perfused with Krebs Ringer (pH 7.4) at 60 microl/min. (45)Ca/(14)C-mannitol (2 microCi/5 microCi in 50 microl saline) was injected via maternal tail vein. Perfusate samples were collected every 5 min for 45 min. Maternal carotid artery pressure was monitored throughout perfusion. A terminal maternal cardiac blood sample was taken and analysed. Placentas were immersion fixed and processed for electron microscopy. Kmf for (45)Ca and (14)C-mannitol was calculated as perfusate [(45)Ca or (14)C-mannitol] x perfusion rate/maternal plasma [(45)Ca or (14)C-mannitol]xplacental weight. Maternal cardiac blood chemistry at termination (n=8-15, mean+/-SEM) was as follows: pH 7.153+/-0.016, PCO(2) 45.48+/-2.06 mmHg, PO(2) 66.47+/-7.10 mmHg, Na(+) 151.4+/-1.2 mmol/l, K(+) 5.54+/-0.17 mmol/l, Ca(2+) 1.15+/-0.03 mmol/l, glucose 7.2+/-0.5 mmol/l, and lactate 1.76+/-0.77 mmol/l. A successful 45 min perfusion in which perfusate recovery was >95% occurred in >50% of animals. Perfusion did not alter placental morphology or carotid pressure. Kmf (microl/min/g placenta) for (45)Ca (66.0+/-8.4 (n=7)) was significantly higher than Kmf for (14)C-mannitol (20.0+/-2.4 (n=5)) (p<0.01). These data demonstrate physiological perfusion of the mouse placenta in situ and its usefulness for measurement of solute transfer.

Animals↗

Altered plasma and pituitary arginine vasotocin and hypothalamic provasotocin expression in flounder (Platichthys flesus) following hypertonic challenge and distribution of vasotocin receptors within the kidney.

Plasma AVT concentration, pituitary AVT content, hypothalamic provasotocin mRNA expression and other osmoregulatory parameters were measured in euryhaline flounder 4, 8, and 24 h after the hypertonic challenge of transfer from fresh water (FW) to seawater (SW). Osmolality and the concentration of major plasma ions, sodium and chloride, were significantly higher in fish transferred to SW by comparison with time matched controls, an effect evident within 4 h. By comparison with time matched controls, pituitary store of AVT was lower while plasma AVT concentration was higher 8 and 24 h after transfer to SW. Higher provasotocin mRNA expression in the hypothalamus was also seen at 4 and 8 h in flounder transferred from FW to SW compared with time matched controls. The lower pituitary store and higher circulating levels imply substantial AVT secretion occurs in the early phase response to this hypertonic challenge. Changes in the regulation of AVT synthesis and secretion appeared quickly following movement to SW, consistent with the rapid osmoregulatory response, including reduced urine production that fish require to accommodate the dehydrative water losses and salt loading on exposure to the new hyperosmotic environment. qPCR measures of whole kidney vasotocin receptor mRNA expression indicated similar levels in SW and FW. Immunohistochemistry for the vasotocin receptor in flounder kidney showed localisation on the afferent and efferent arterioles of the glomerulus and on the capillary bed that extends from the efferent arteriole to the smooth muscle surrounding the collecting duct. Localisation of the vasotocin receptor was comparable in SW and FW fish.

Animals↗

Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring.

AIMS/HYPOTHESIS: We tested the hypothesis that diabetes in pregnancy can result in the in-utero reprogramming of renal calcium and magnesium handling and of bone formation in the offspring, which persists into adulthood. METHODS: Male offspring of streptozotocin-treated diabetic rats (OD rats) and of control non-diabetic animals (OC rats) were investigated as neonates and at 8, 12 and 16 weeks of age. RESULTS: Compared with OC rats, urinary calcium and magnesium output was significantly reduced in OD rats at every age studied; Na+ and K+ outputs were unaffected. The renal expression of proteins involved in the tubular reabsorption of calcium (calcium ATPase, calbindin-D28k and epithelial calcium channel) was increased in OD animals compared with that in OC animals. Additionally, we observed that adult OD rats had lower trabecular and higher cortical femoral bone volumes, explained by deposition of bone on the endosteal surface. CONCLUSIONS/INTERPRETATION: These data show that diabetes in pregnancy has profound effects on male offspring in terms of renal tubular calcium and magnesium reabsorption and the normal pattern of bone formation. These effects persist into adulthood. Such long-lasting effects of diabetes on kidney and the skeleton were not suspected and could have important implications for the health of children born to diabetic women.

Aging↗

Plasma concentrations of arginine vasotocin and urotensin II are reduced following transfer of the euryhaline flounder (Platichthys flesus) from seawater to fresh water.

Plasma concentrations and stored levels of the neuroendocrine peptides arginine vasotocin (AVT) and urotensin II (UII) were measured in the euryhaline flounder (Platichthys flesus) following the acute hypo-osmotic challenge of direct seawater (SW) to fresh water (FW) transfer. Hormone measures, plasma osmolality, and ion concentrations and tissue water content were determined 1, 4, 8, 24, 72, and 144 h after transfer. Plasma AVT concentration fell initially following FW transfer but then returned toward pretransfer levels by day 6. Plasma UII concentration decreased while urophysial UII content was increased following hypo-osmotic challenge relative to SW time-matched controls, suggesting down regulation of the UII system during the initial stages after FW transfer. These changes in neuroendocrine activity were associated with a significant fall in plasma osmolality and major plasma ions. Positive correlations were observed between plasma AVT and osmolality and Cl- and Mg2+ concentrations, suggesting functional association of these plasma parameters with AVT action and/or control of AVT secretion. The initial response to hypotonic challenge involves reduced plasma AVT and UII levels consistent with the proposed role for these hormones, supporting flounder osmoregulation in hypertonic media.

Animals↗

The caudal neurosecretory system: control and function of a novel neuroendocrine system in fish.

The caudal neurosecretory system (CNSS) of fish was first defined over 70 years ago yet despite much investigation, a clear physiological role has yet to be elucidated. Although the CNSS structure is as yet thought to be confined to piscine species, the secreted peptides, urotensins I and II (UI and UII), have been detected in a number of vertebrate species, most recently illustrated by the isolation of UII in humans. The apparent importance of these peptides, suggested by their relative phylogenetic conservation, is further supported by the complex control mechanisms associated with their secretion. The CNSS in teleosts is known to receive extensive and diverse innervation from the higher central nervous system, with evidence for the presence of cholinergic, noradrenergic, serotonergic, and peptidergic descending inputs. Recent observations also suggest the presence of glucocorticoid receptors in the flounder CNSS, supporting previous evidence for a possible role as a pituitary-independent mechanism controlling cortisol secretion. The most convincing evidence as to a physiological role for the CNSS in fish has stemmed from the direct and indirect influence of the urotensins on osmoregulatory function. Recent advances allowing the measurement of circulating levels of UII in the flounder have supported this. In addition, there is evidence to suggest some seasonal variation in peptide levels supporting the notion that the CNSS may have an integrative role in the control of coordinated changes in the reproductive, osmoregulatory and nutritional systems of migratory euryhaline species.

Amino Acid Sequence↗

Safety and effectiveness of nurse telephone consultation in out of hours primary care: randomised controlled trial. The South Wiltshire Out of Hours Project (SWOOP) Group.

OBJECTIVE: To determine the safety and effectiveness of nurse telephone consultation in out of hours primary care by investigating adverse events and the management of calls. DESIGN: Block randomised controlled trial over a year of 156 matched pairs of days and weekends in 26 blocks. One of each matched pair was randomised to receive the intervention. SETTING: One 55 member general practice cooperative serving 97 000 registered patients in Wiltshire. SUBJECTS: All patients contacting the out of hours service or about whom contact was made during specified times over the trial year. INTERVENTION: A nurse telephone consultation service integrated within a general practice cooperative. The out of hours period was 615 pm to 1115 pm from Monday to Friday, 1100 am to 1115 pm on Saturday, and 800 am to 1115 pm on Sunday. Experienced and specially trained nurses received, assessed, and managed calls from patients or their carers. Management options included telephone advice; referral to the general practitioner on duty (for telephone advice, an appointment at a primary care centre, or a home visit); referral to the emergency service or advice to attend accident and emergency. Calls were managed with the help of decision support software. MAIN OUTCOME MEASURES: Deaths within seven days of a contact with the out of hours service; emergency hospital admissions within 24 hours and within three days of contact; attendance at accident and emergency within three days of a contact; number and management of calls in each arm of the trial. RESULTS: 14 492 calls were received during the specified times in the trial year (7308 in the control arm and 7184 in the intervention arm) concerning 10 134 patients (10.4% of the registered population). There were no substantial differences in the age and sex of patients in the intervention and control groups, though male patients were underrepresented overall. Reasons for calling the service were consistent with previous studies. Nurses managed 49.8% of calls during intervention periods without referral to a general practitioner. A 69% reduction in telephone advice from a general practitioner, together with a 38% reduction in patient attendance at primary care centres and a 23% reduction in home visits was observed during intervention periods. Statistical equivalence was observed in the number of deaths within seven days, in the number of emergency hospital admissions, and in the number of attendances at accident and emergency departments. Conclusions Nurse telephone consultation produced substantial changes in call management, reducing overall workload of general practitioners by 50% while allowing callers faster access to health information and advice. It was not associated with an increase in the number of adverse events. This model of out of hours primary care is safe and effective.

Adolescent↗

CD69 expression on primitive progenitor cells and hematopoietic malignancies.

CD69 is an early activation antigen of peripheral blood lymphocytes and is constitutively expressed on a wide variety of bone marrow-derived cells. To further characterize the distribution and understand the potential biological role of the molecule in normal and malignant hematopoiesis, we used a novel high affinity anti-CD69 mAb (UN6) and analyzed hematopoietic progenitor cells together with a panel of myeloid and lymphoid malignancies. We report that mobilized peripheral blood CD34+ cells display detectable levels of CD69 and that the density of membrane expression correlates with the immature phenotype CD34bright Thy-1bright cells. Furthermore, during cytokine-induced differentiation, the expression of CD69 is moderately down-regulated. Analysis of hematopoietic malignancies revealed that CD69 expression correlates with the immature myeloid phenotype. Taken together these data suggest a role of CD69 during the early phase of hematopoiesis and in the leukemic transformation.

Aged↗

Effectiveness of knee replacement surgery in arthritis.

This study examined the effectiveness of knee replacement surgery in an elderly population suffering from arthritis. Four questionnaires which measured pain, mobility, anxiety, depression and social isolation were completed by the study group before and after surgery to assess changes in physical function, psychological state, social interaction and somatic sensation. A statistically significant difference was found in pain which was reduced from a median score of 3 before the operation to 0 afterwards on an intensity scale of 0-5. Statistically significant improvements were also found in the mobility/dependency scores and in the level of anxiety and depression following the operation. It was concluded that knee replacement is a highly effective treatment for arthritis of the knee, reducing pain, increasing mobility and improving the persons emotional state, thus improving the quality of life of the recipient. The use of separate questionnaires to measure single dimensions of quality of life as opposed to a single health profile is also discussed.

Activities of Daily Living↗

UN1, a murine monoclonal antibody recognizing a novel human thymic antigen.

A murine monoclonal antibody (mAb) UN1 was produced on the basis of selective reactivity with human thymocytes. Characterization of UN1 by immunofluorescence gave a high intensity of labeling with the majority of human thymocytes. Expression was preferentially associated with immature thymocytes (CD3dim) compared to mature cells, whereas only a subpopulation of peripheral blood lymphocytes was weakly stained. No specific binding to monocytes or granulocytes was detected. The T-cell lines HPB-ALL, H9 and MOLT-4 were all positively bound by UN1. Immunohistological staining of thymic tissues showed that mAb UN1 detected cells in both the cortex and medulla of fetal thymus, whereas the reaction in thymus samples from young children was mainly with medullar cells. By western blotting analysis, the antigen recognized by mAb UN1 corresponds to a membrane polypeptide with a molecular weight of approximately 120 kDa present on thymocytes and HPB-ALL cells. The mAb UN1 was submitted to the 5th International Workshop and Conference on Human Leukocyte Differentiation Antigens, Boston, 1993. UN1 did not cluster in any of the old or new clusters of differentiation discussed at the conference, indicating its unique reactivity. Together with the data presented in this paper, this suggests that the UN1 antibody defines a previously undescribed molecule present on the cell surface of thymocytes and a minority of peripheral blood lymphocytes.

Animals↗

UN-1, a murine monoclonal antibody recognizing a human thymocyte undescribed antigen.

A monoclonal antibody (MoAb), UN-1, specific for a human thymocyte cell surface antigen was produced. The same MoAb recognized in immunofluorescence also cells of the human T line HPB-ALL, while did not bind human peripheral blood cells and cells of some T, B and myeloid lines. Western blotting analysis of thymocyte membranes with MoAb UN-1 revealed a structure with a molecular weight of 150 kDa. Therefore both the pattern of expression and the size of the antigen recognized by MoAb UN-1 did not correspond to any previously described cell surface molecule.

Animals↗

Five-year follow up of patients treated with inpatient psychotherapy at the Cassel Hospital for Nervous Diseases.

Twenty-eight patients who were admitted consecutively to a single-adult unit of the Cassel Hospital in 1977/8 were followed up 5 years after discharge. Those who were found to have improved at the end of treatment remained well 5 years later. These could be distinguished by their combination of neurotic psychopathology, considerable depression, superior intelligence, and lack of a chronic outpatient history. Patients who had improved 5 years after discharge did not show these characteristics, but had all spent at least 9 weeks on the waiting list and had the capacity to form close and helpful relationships. Patients who were judged to have improved were less dependent on the Health Service and their economic productivity was improved, often as a consequence of returning to education or training. Those who did not improve clinically continued to be admitted to hospital and tended to become less economically productive.

Adult↗

Medical services provided to 2,394 patients at methadone programs in three states.

The type and amount of medical services provided to 2,394 patients in methadone maintenance programs in three states was studied. Data were obtained from on-site confidential interviews with the entire treatment staff at seven programs. It was found that there were marked differences in the number and type of medical staff. Thus, there was ten times more coverage by physicians at some programs than others. In general, there were notable differences in the treatment staff available. Comparable variations among the programs were found with respect to the actual provision of medical services. Thus, the number of patients seen by the medical staff on a weekly basis varied from a high of 185 patients to a low of 36 patients. Similarly, the proportion of each program's patients receiving medical treatment per week varied from 53 to 14 percent. Reasons for those variations in medical services are considered.

Ambulatory Care Facilities↗

Experimental induction of hypoparathyroidism with parathyroid hormone antibodies.

This study describes the effect of a single injection of parathyroid hormone antiserum on the serum calcium, serum phosphate, urinary cyclic AMP, and urinary phosphate levels in the intact perfused rat. A significant decline in serum calcium level with concomitant elevation in serum phosphate level and decreased urinary excretion of phosphate and cyclic AMP was noted. These findings strongly suggest that a transient hypoparathyroid state was induced by the parathyroid hormone antiserum.

Animals↗