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Biomedical subjects

K Newell

Publications and source records attributed to K Newell.

32 records · Page 2Linked to original sources

The potential of lactate and succinate to kill nutrient deprived tumor cells by intracellular acidification.

We have investigated the ability of the weak acids, lactate, succinate, and the monomethylester of succinate, to cause intracellular acidification of EMT-6 and MGH-U1 cells. Each of the three substances caused a decrease of intracellular pH (pHi) when the cell lines were exposed at low extracellular pH (pHe) in the range 6.0-6.5. Only monomethylsuccinate caused intracellular acidification at neutral pHe. The fall in pHi increased with increasing dose of each agent and with decreasing pHe. The pHi recovered to almost normal values after exposure of 30 minutes to 50 mM lactate, but there was little or no recovery of pHi in the presence of succinate or monomethylsuccinate. Succinate and its methylester were toxic to cells at low pHe (less than 6.5), and cell killing increased with exposure time and with dose of the agents used. Lactate did not cause cell death at low pHe, and none of the three substances exhibited any cytotoxicity at neutral pHe. Solid tumors are known to have an acidic microenvironment, and pHe may be particularly low in regions of hypoxia. Succinate and its monomethylester may have the potential to kill cells in acidic regions of tumors and might therefore enhance the effect of radiation.

Acid-Base Equilibrium↗

Functional consequences of CD4-TCR/CD3 interactions.

The relative positions of CD4 and of the T cell receptor complex for antigen (TCR/CD3) determine whether signalling through the antigen receptor results in T cell growth. The following discussion focusses on those central observations which demonstrate that CD4 and the associated protein tyrosine kinase p56lck provide critical signals modulating the biological responses induced through the TCR/CD3 complex. Based on the available evidence, we suggest that antigen-mediated co-aggregation of CD4/Lck and TCR/CD3 is an obligate activation signal and that, in its absence, signalling through TCR alpha beta induces T cell death. The role of CD4 in self-non-self discrimination would therefore be critical and would provide a mechanism for the maintenance of peripheral T cell tolerance to non-major histocompatibility complex-related self-antigens.

Animals↗

Developing a strategy for understanding adolescent nutrition concerns.

Disseminating nutrition information that adolescents will incorporate into their lives has been a difficult challenge for nutrition educators. The communication of such information has often been a "one-way street"; adolescents are given information that educators feel they need to have. Researchers contend that a more effective way to communicate is for adolescents to describe what they need to know in order to relate nutrition messages to their own worlds. A research model based on Brenda Dervin's work with the "sense-making" theory of communication was used to better determine adolescents' perceived nutrition concerns. Adolescents aged 14 to 16 across six states were interviewed to record personal situations they experienced concerning food, nutrition, and/or eating. Situation "movement states" were identified to determine the qualitative ways in which the adolescents perceived themselves as dealing with the situations they described. Data indicate that this theoretical base may be used by nutrition educators to identify adolescents' nutrition needs and to design appropriate education materials.

Adolescent↗

Adult nesidioblastosis. An unusual cause of fasting hypoglycemia.

Laidlaw coined the term nesidioblastosis in 1938 to characterize the neodifferentiation of the islet cells of Langerhans from pancreatic duct epithelium. It is well recognized in the pediatric population as a frequent cause of persistent neonatal hypoglycemia. However, its occurrence in adults is presumed to be rare and, therefore, it is not appreciated as a cause of hyperinsulinism. Three women, aged 29, 42, and 63, with adult onset hyperinsulinism secondary to nesidioblastosis are reported. All three patients required near-total pancreatectomy. The preoperative findings were consistent with hyperinsulinemic hypoglycemia as with insulinomas. Results of pancreatic imaging studies were normal in two patients and one patient had a pancreatic examination by computerized tomography and magnetic resonance imaging, with false-positive results. Two of the three patients had previously undergone a 50 per cent distal pancreatectomy in which the resected specimens were interpreted as normal in one patient and consistent with nesidioblastosis in the second. Both patients subsequently developed recurrent symptomatic hyperinsulinemic hypoglycemia that persisted despite dosage adjustments in diazoxide therapy. The oldest patient underwent a 95 per cent pancreatectomy at the initial surgical exploration because an insulinoma could not be identified. The other patients underwent a completion 95 per cent pancreatectomy. In both, histochemical examination of each specimen disclosed nesidioblastosis, characterized by clusters of islet cells interspersed throughout the exocrine tissue.

Adult↗

The way ahead for district health systems.

The weakest level in most health systems is probably that of the district, and the failings of district services have been cited in attempts to discredit the whole notion of primary health care. A district health system cannot function properly in isolation: in particular it should have firm links with its provincial authorities, and should benefit from the comprehensive involvement of the community it serves.

Community Health Services↗

The sense-making approach for audience assessment of adolescents.

The purpose of the research was to test the methodology used to identify how adolescents approach their nutrition concerns and questions. The methodology was based on Dervin's sense-making theory. Using a time-line interview technique, 305 adolescents 14 to 16 years of age detailed a situation involving their most important nutrition concerns. Other pertinent information was obtained. Cluster analysis was chosen as the appropriate analysis to identify groups of adolescents who responded similarly to the technique. Discriminant analysis was then used to determine which variables maximally separated the groups. Four groups were identified, two of which described action-oriented approaches to dealing with nutrition situations and differed in terms of how much outside help they wanted. The remaining two groups perceived barriers to dealing with situations and also differed in how much help they wanted. A fifth group indicated no nutrition concerns or questions. The results will be used to develop and test the effectiveness of nutrition education when it is focused on the different approaches.

Adolescent↗

Circulating concentrations of porcine ileal peptide but not hexosaminidase are elevated following 1 hr of mesenteric ischemia.

Porcine Ileal Peptide (PIP) is located in the mucosa of the small bowel. We hypothesized that PIP may be useful as a marker for early intestinal ischemia or other acute processes of the mucosa. To test this hypothesis we developed a model of acute reversible intestinal ischemia in the pig. Following isolation of a 100-cm segment of ileum on a vascular pedicle baseline, serum and tissue samples were obtained. The vessels were then occluded for 60 min and the segment was reperfused. Serial serum samples were taken and analyzed for PIP and hexosaminidase (HEX). HEX enzyme activity in serum is known to be elevated in animals having intestinal necrosis. The Student t test for paired data was used. In preliminary studies we found that circulating HEX activity became elevated following 3 to 4 hr of vessel occlusion followed by reperfusion. In the current experiments, following 1 hr of ischemia, PIP rose significantly in the peripheral circulation, being 153.8 +/- 76.8, 909.0 +/- 150.4, and 898.3 +/- 128.1 ng/ml (P less than 0.001) at 0, 60, and 360 min after reperfusion of the segment. HEX on the other hand did not change significantly throughout the experiment, having been 766.0 +/- 28.1, 752.0 +/- 71.3, and 780.1 +/- 53.7 nM/liter (ns) at 0, 60, and 360 min following reperfusion of the segment. Histology demonstrated some clubbing, shortening and fracturing of villi with thinning of the tips of the villi in many cases. Immunospecific staining for PIP was present along the intact borders of the villi.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pheochromocytoma crisis.

Of 26 patients with pheochromocytoma treated between 1974 and 1986, two presented with pheochromocytoma crisis. This unusual presentation consists of hyper- and/or hypotension, high fevers (greater than 40 degrees C), encephalopathy, and multiple organ system failure. Both patients had large tumors associated with markedly elevated levels of epinephrine. Although hypertension was adequately controlled in both patients with phenoxybenzamine, phentolamine (1 patient) and nitroprusside, both patients deteriorated rapidly. The first patient expired during attempts to identify a source of sepsis. None was found at autopsy. The second patient underwent urgent adrenalectomy which reversed the multiple organ system failure and resulted in patient survival. We conclude from review of these patients and three others in the literature that (a) crisis is an unusual presentation of pheochromocytoma; (b) its manifestations include vascular lability, high fever, encephalopathy and multiple organ system failure; (c) it may be the result of increased epinephrine secretion; (d) successful treatment of pheochromocytoma crisis demands prompt diagnosis, vigorous medical therapy and emergent tumor removal if the patient continues to deteriorate.

Adrenal Gland Neoplasms↗

A seroepidemiological study of the prevalence of hepatitis B infections in a hyperendemic New Zealand community.

The prevalence of hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) were studied in 93% of the population of the New Zealand township of Kawerau. Sera were collected from 7901 subjects over six months old, and 3318 (42%) had markers of hepatitis B virus (HBV) infections. Five hundred and nineteen (6.6%) were positive for HBsAg and 485 (96.4%) of 503 retested were confirmed as chronic carriers. HBsAg prevalence was 5.4% in the 0-4 years age group but only 1 of 66 children under one year old was positive suggesting that later cross infection, rather than perinatal transmission was the major factor responsible for the high pre-school carrier rate. Total HBV marker prevalence increased dramatically in early school years and peak marker prevalence was 67.7% in the 15-19 year age group. Prevalence of HBsAg was more than four times higher in non-europeans than in Europeans (Caucasians). Other factors significantly associated with hepatitis B virus marker prevalence in children were: number of years spent in Kawerau, which was associated with anti-HBs prevalence; and size of household, which was associated with HBsAg prevalence. Number of siblings was not a significant risk factor over and above the effect of size of household. Factors associated with marker prevalence in adults were: number of years spent in Kawerau, which was associated with anti-HBs; birth in the Northern half of the North Island, which was associated with both HBsAg and anti-HBs; size of household, which was more strongly associated with HBsAg prevalence; and amateur tattoos, which were associated with anti-HBs prevalence but not with HBsAg prevalence.

Adolescent↗

Choosing the right inhaler for patients with asthma.

This article assesses the suitability of inhaler devices for patients with asthma according to their individual needs. Three main types of inhalers are discussed: pressurised metered dose inhalers, breath-actuated inhalers and dry powder inhalers. The advantages and disadvantages of these devices are discussed in relation to lifestyle, ability and suitability for individuals.

Activities of Daily Living↗