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Biomedical subjects

J Diamond

Publications and source records attributed to J Diamond.

At least 91 records · Page 5Linked to original sources
PubMed1994

Effects of irrigation solutions on corneal endothelial function.

Rabbit corneas were perfused in vitro with an irrigation solution for 90 minutes. This was followed by 6 hours of perfusion with tissue culture medium TC199 during which endothelial function was assessed by monitoring rates of swelling during a period of perfusion in the absence of bicarbonate ions, and subsequent rates of thinning when bicarbonate ions were restored to the perfusate. Corneal thickness (measured with an ultrasonic pachymeter) immediately following excision was 401 microns (SD 19, n = 23). During the 90 minute perfusion at 35 degrees C, corneas exposed to balanced salt solution (BSS), Hartmann's solution or 0.9% NaCl (all initially at room temperature) swelled, respectively, at 14 (SD 2.3, n = 4), 11 (SD 2.6, n = 4), and 70 (SD 4.3, n = 4) microns/h. Cold Hartmann's solution (initially at 4 degrees C) caused corneas to swell at 9 (SD 2.3, n = 4) microns/h. On the other hand, corneas perfused with BSS Plus thinned at 9 (SD 3.4, n = 4) microns/h and TC199 with Earle's salts had little effect on thickness. Rates of swelling and thinning during the following assessment perfusion showed no apparent effects of prior exposure to any of the irrigation solutions on the barrier properties or pump function of the endothelium. Despite this, the increased thickness of corneas exposed initially to BSS, cold Hartmann's solution, or 0.9% NaCl was not fully reversed, even by the end of the 6 hour assessment perfusion. In contrast, the swelling observed in corneas exposed to Hartmann's solution at room temperature was reversed and these corneas had returned to their normal thickness by the end of the assessment period. All corneas, even those exposed to 0.9% NaCl, had an intact endothelial mosaic with no evidence of damage or cell loss, although morphological differences in cell shape and the appearance of cell borders were evident compared with freshly isolated cornea.

Animals↗
PubMed1994

Rapid upregulation of snake intestine in response to feeding: a new model of intestinal adaptation.

Mammalian guts exhibit numerous adaptive responses to feeding. However, response magnitudes are often inconveniently modest for experimental analysis, because mammals feed often and their intestines are rarely empty. We anticipated larger responses in sit-and-wait foraging snakes, because they consume huge meals at long intervals. Hence, we studied metabolic rates, brush-border nutrient transport, and intestinal morphometrics in the rattlesnake, Crotalus cerastes, as a function of time since feeding. O2 consumption by the whole snake, a reflection of the cost of digestion and of rebuilding the starved gut, peaked after 2 days at eight times fasting values. Activities of brush-border glucose, leucine, and proline transporters peaked after 1-3 days at 5-22 times fasting values. Ratios of amino acid to glucose uptake rates peaked at 104, reflecting snakes' extreme adaptation to carnivory (a high-protein low-carbohydrate diet). Intestinal mass increased more than twofold within 1 day, primarily because of mucosal growth. After defecation, the intestine atrophied, brush-border transporters were downregulated, and O2 consumption returned to basal. These rapid and large responses reduce costs of gut maintenance during long bouts of quiescence between meals. Hence sit-and-wait foraging snakes may furnish advantageous model species for studying gut regulation and adaptation.

Adaptation, Physiological↗
PubMed1994

Lack of reciprocal translocation in BCR-ABL positive Ph-negative chronic myeloid leukaemia.

We used fluorescence in situ hybridization (FISH) to metaphase chromosomes with BCR and ABL cosmid probes in conjunction with the polymerase chain reaction (PCR) to study the mechanism by which the ABL proto-oncogene is inserted into a morphologically normal chromosome 22 in patients with Ph-negative chronic myeloid leukaemia characterized by the BCR-ABL chimeric gene. In control patients with Ph-positive CML the ABL probe localized to 22q- and the 3' BCR probe localized to 9q+. In nine Ph-negative CML patients the ABL probe localized to one normal chromosome 9 and to one 'normal' chromosome 22. Both 5' and 3' BCR probes localized exclusively to the chromosomes 22. By PCR all had evidence of BCR-ABL transcripts, but none had evidence of the reciprocal ABL-BCR gene product that is seen in 70% of the Ph-positive CML patients. These data confirm the view that Ph-negative CML results from insertion of ABL-containing DNA sequences into a normal-appearing chromosome 22 without reciprocal translocation of sequences from chromosome 22 to chromosome 9.

Adult↗
PubMed1993

Times to extinction for small populations of large birds.

A major practical problem in conservation biology is to predict the survival times-"lifetimes"-for small populations under alternative proposed management regimes. Examples in the United States include the 'Alala (Hawaiian Crow; Corvus hawaiiensis) and Northern Spotted Owl (Strix occidentalis caurina). To guide such decisions, we analyze counts of all crow, owl, and hawk species in the most complete available data set: counts of bird breeding pairs on 14 European islands censused for 29-66 consecutive years. The data set yielded 129 records for analysis. We define the population ceiling as the highest number of breeding pairs observed from colonization to extinction, within a consecutive series of counts for a given species on a given island. The resulting distributions of population lifetimes as a function of population size prove to be highly skewed: most small populations disappear quickly, but a few last for a long time. Median (i.e., 50th percentile) lifetimes are calculated as only 1-5 yr for hawk, owl, and crow populations with ceilings of one or two breeding pairs. As expected if demographic accidents are the main cause of extinction for small populations, lifetimes rise by a factor of 3-4 for each additional pair up to three pairs. They rise more slowly thereafter. These observations suggest that lifetimes of the 'Alala (now reduced to about three pairs in the wild), and of populations of Northern Spotted Owl in the smallest forest fragments, will be short unless active management is implemented.

Journal Article↗
PubMed1993

Pertussis immunisation and serious acute neurological illnesses in children.

OBJECTIVE: To determine long term outcome in children who had a severe acute neurological illness in early childhood associated with pertussis immunisation. DESIGN: Follow up study of cases and matched controls. SETTING: Assessment of children at home and at school throughout Britain. SUBJECTS: Children recruited into the national childhood encephalopathy study in 1976-9 were followed up, with one of their two original matched controls, in 1986-9. MAIN OUTCOME MEASURES: Performance in educational attainment tests; behaviour problems reported by teachers and parents; continuing convulsions; evidence of other neurological or physical dysfunction. RESULTS: Over 80% of cases and controls were traced. Case children were significantly more likely than controls to have died or to have some form of educational, behavioural, neurological, or physical dysfunction a decade after their illness. The prevalence of one or more of these adverse outcomes in case children who had been immunised with diphtheria, tetanus, and pertussis vaccine within seven days before onset of their original illness was similar to that in case children who had not been immunised recently. The relative risk for recent diphtheria, tetanus, and pertussis immunisation in children who had died or had any dysfunction in comparison with controls was 5.5 (95% confidence interval 1.6 to 23.7). However, the number of cases associated with vaccine (12) was extremely small and statistically vulnerable, and other possible agents or predisposing factors could not be excluded. CONCLUSIONS: Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis immunisation supports continued use of the vaccine.

Acute Disease↗
PubMed1993

Distribution and colocalization of choline acetyltransferase immunoreactivity and NADPH diaphorase reactivity in neurons within the medial septum and diagonal band of Broca in the rat basal forebrain.

NADPH diaphorase histochemistry and choline acetyltransferase immunocytochemistry were used to assess quantitatively the presence of nitric oxide synthase in the cholinergic neurons of the magnocellular basal forebrain complex. Virtually all (97%) NADPH diaphorase reactive magnocellular neurons in the medial septum and the vertical and horizontal limbs of the diagonal band of Broca were choline acetyltransferase immunoreactive, whereas only a proportion of the choline acetyltransferase immunoreactive neurons were NADPH diaphorase reactive. Thus NADPH diaphorase histochemistry identified a subpopulation of the magnocellular cholinergic neurons. Occasionally, NADPH diaphorase reactive neurons were observed within the medial septum and diagonal band of Broca that were not choline acetyltransferase immunoreactive, and in general were morphologically distinct from the magnocellular neurons; such neurons are probably representatives within the medial septum and diagonal band of more widely distributed phenotypically distinct populations of NADPH diaphorase reactive neurons. The proportions of the neurons in which choline acetyltransferase and NADPH diaphorase colocalized in the medial septum and in the diagonal bands of Broca were similar in any one coronal section, but there was a considerable difference in the proportions throughout the rostrocaudal extent of these nuclei. In the most rostral sections of the medial septum and diagonal band, approximately 70% of the choline acetyltransferase immunoreactive neurons were NADPH diaphorase reactive, whereas the proportion decreased progressively to about 30% at the level of the decussation of the anterior commissure. To examine further the extent of colocalization throughout the magnocellular basal forebrain complex, sections of the magnocellular preoptic nucleus, substantia innominata, and nucleus basalis magnocellularis were examined. While there was little total colocalization of choline acetyltransferase immunoreactivity and NADPH diaphorase reactivity in any particular section (approximately 18%), almost all of the double labelled neurons were in the substantia innominata, with very few in the other nuclei. Thus although there is a caudal to rostral gradient of the proportion of magnocellular cholinergic neurons that are NADPH diaphorase reactive throughout the entire basal forebrain magnocellular complex, subregions, such as the substantia innominata and magnocellular preoptic nucleus, may not follow this trend. The recent demonstration that the NADPH diaphorase histochemical reaction localizes a nitric oxide synthase suggests that attention should be given to the NADPH diaphorase subpopulation in pathological and experimentally induced alterations of the basal forebrain.

Animals↗
PubMed1993

Characterization of insulin-stimulated seryl/threonyl protein kinases in rat skeletal muscle.

Post-insulin receptor signal transduction is mediated by a cascade of seryl/threonyl protein kinases which includes a family of mitogen-activated protein (MAP) kinases, ribosomal protein S6 kinases, and casein kinase-2. Previous studies have characterized these kinases primarily in cultured or isolated cells. We have demonstrated that intravenous injection of insulin into fasted rats significantly stimulated the activities of MAP kinases and S6 kinases in skeletal muscle, independently of the blood glucose levels in these animals. Anion exchange chromatography on Mono Q afforded the resolution of at least five peaks of insulin-stimulated myelin basic protein kinase activity. By immunological criteria, these myelin basic protein kinases included the p42mapk and p44erk1 as well as other potentially novel 44-kDa MAP kinases. Insulin-activated ribosomal S6 kinases were resolved into two major peaks by Mono Q chromatography, the latter of which contained a 100-kDa isoform of p90rsk as revealed by immunoblotting with an anti-rsk-peptide antibody. A 32-kDa S6 kinase in the earlier peak may represent a novel protein kinase in this tissue. Skeletal muscle casein kinase-2 was not significantly stimulated following insulin injection into rats under our experimental conditions. These results indicate that the intact rat can serve as a useful model system to investigate the mechanisms of insulin signal transduction.

Amino Acid Sequence↗
PubMed1993

Role of cyclic GMP in airway smooth muscle relaxation.

The evidence in favor of a role for cyclic GMP as a mediator of relaxation in airway smooth muscle is reviewed. All of the criteria usually used to decide whether a cyclic nucleotide is the mediator of a particular response appear to have been satisfied, at least to some extent, for a causal relationship between cyclic GMP elevation and relaxation of airway smooth muscle.

Animals↗
PubMed1993

NADPH-diaphorase histochemistry identifies isolated endothelial cells at sites of traumatic injury in the adult rat brain.

In addition to labelling endothelium, some ependymal cells (including tanycytes), and a subpopulation of neurons, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry of stab lesion sites in the neocortex revealed a large population of cells concentrated within several hundred micrometers of the lesion site. To determine the identity of these cells, NADPH-diaphorase reactivity was compared to binding with either the I-B4 isolectin from Bandeiraea simplicifolia (which has previously been shown to identify endothelial cells and activated mononuclear phagocytes), or a monoclonal antibody (OX-42) that recognizes activated mononuclear phagocytes. Many I-B4 lectin-labelled cells were also NADPH-diaphorase reactive, and other I-B4 lectin-labelled cells were also OX-42 immunoreactive, but co-existence of OX-42 immunoreactivity and NADPH-diaphorase reactivity was not observed. Only a small minority of NADPH-diaphorase-reactive cells did not exhibit I-B4 lectin binding. In contrast to the simple somatic morphology of the majority of NADPH-diaphorase-reactive cells, the I-B4 lectin-negative cells had a ramified appearance, and while readily observed at two days postlesion, they were only rarely seen at three days postlesion. Primary cultures of bovine aortic endothelial cells also exhibited NADPH-diaphorase reactivity which occupied most of the cytoplasm in a filamentous web pattern. Endothelial cells possess a constitutive form of nitric oxide synthase which, as demonstrated in NADPH-diaphorase-reactive neurons, may be the basis of their NADPH-diaphorase reactivity. These findings indicate that NADPH-diaphorase-reactive cells observed at lesion sites are probably angiogenic endothelial cells not associated with extant blood vessels. Thus, NADPH-diaphorase histochemistry offers an effective method of visualizing neovascularization in the brain and other tissues.

Animals↗
PubMed1993

Outpatient management of small traumatic hyphaemas: is it safe?

In this prospective study patients with small traumatic hyphaemas were managed as ambulatory outpatients. No routine systemic or topical treatment was given. The patients were reviewed daily in the Casualty Department until the blood had cleared, after which they were examined fully. The incidence of rebleeding and the number of days for the blood to clear were comparable to figures for hospitalised bed-bound patients. Nine patients (21%) defaulted from follow-up. Outpatient management of small traumatic hyphaemas is safe in compliant patients and may save valuable resources.

Adolescent↗
PubMed1993

Increased NGF mRNA expression in denervated rat skin.

Using a coupled reverse transcription and competitive polymerase chain reaction protocol, we have measured Nerve Growth Factor (NGF) mRNA expression in adult rat skin following its denervation. By 2-4 days, levels of NGF mRNA were increased approximately 5-10 fold over levels in innervated skin, remaining increased for up to at least 2 weeks. In situ hybridization carried out on skin samples revealed that the NGF message was expressed not only in the distal nerve pathways but also in non-nerve associated cells, such as dermal fibroblasts, and in the basal epidermal layer. Denervated skin evokes a NGF-dependent collateral sprouting from neighbouring intact sensory axons. The new findings indicate that an increased NGF production is associated with the increased availability of NGF in such skin, and that cutaneous nerves have a role in regulating this NGF production.

Animals↗
PubMed1993

Lesion-induced NADPH-diaphorase reactivity in neocortical pyramidal neurones.

Pyramidal neurones of the rat neocortex do not normally express NADPH-diaphorase reactivity. However, after stab lesions which extended through the entire depth of the neocortex, strong NADPH-diaphorase reactivity was observed in pyramidal neurones at 7 and 14 days post-lesion. At 3 and 21 days post-lesion fewer and less reactive pyramidal neurones were observed, and no reactive pyramidal neurones were seen at 2 and 26 days post-lesion. The great majority of reactive pyramidal neurones were in layers V and VI and most were situated medial to the lesion. The induction of NADPH-diaphorase implies that the capability to synthesize nitric oxide may be a component of the pyramidal neurones' response to traumatic injury.

Animals↗
PubMed1993

Leukotriene D4 receptors are not negatively coupled to adenylyl cyclase in guinea-pig lung parenchyma.

1. The possibility that receptors for the peptide-containing leukotrienes may be negatively coupled to adenylyl cyclase in guinea-pig lung parenchyma was investigated by comparing the effect of leukotriene D4 (LTD4) on the intracellular cyclic nucleotide (cyclic AMP and cyclic GMP) content and on the activity of cyclic AMP-dependent protein kinase (PKA). In addition, the potential association between changes in the cyclic nucleotide content and the ability of LTD4 to increase lung parenchymal tone was also evaluated. 2. Non-cumulative challenge of parenchymal lung strips with LTD4 elicited concentration-dependent contractions (pD2 = 8.23) that were paralleled by concentration-related increases in the intracellular level of cyclic AMP and cyclic GMP, and in the activation state of PKA (Kact = 33 nM). Temporally, these biochemical effects of LTD4 were transient, peaking after approximately 5 min drug contact thereafter decaying, despite the continued generation of tone. Both the biochemical and mechanical effects of LTD4 were antagonized by the LTD4-receptor blocking drug, ICI 198,615 (1 microM for 60 min), indicating that they were receptor-mediated events. 3. Challenge of guinea-pig lung with LTD4 (200 nM; EC100 for tension generation) stimulated a 150 and 70 fold increase in the elaboration of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) respectively, relative to that generated spontaneously. 4. Pretreatment of lung strips for 60 min with an irreversible inhibitor of cyclo-oxygenase, flurbiprofen,at a concentration (8 microM) that abolished both basal and LTD4 (200 nM)-induced TXB2 and 6-keto-PGF1alpha release, relaxed rapidly the spontaneous tone of the tissues, reduced the cyclic AMP content by ~50%and lowered the PKA activity ratio from 29% to 17%. In addition, flurbiprofen abolished the ability of LTD4 (200 nM) to increase the cyclic AMP content and to activate PKA. Functionally, the magnitude of LTD4 (200 nM)-induced tone and the increase in cyclic GMP content were attenuated by approximately 20% and 50% respectively in flurbiprofen-treated tissues.5. In flurbiprofen-treated tissues, isoprenaline (10 microM for 10 min) increased the cyclic AMP content(from 4 to 27 pmol mg-1 protein) and activated PKA (from 15% to 26%). Preincubation (30 s or 5 min)of lung with LTD4 (200 nM) did not inhibit (or enhance) these isoprenaline-induced effects.6. Pretreatment of lung strips for 60 min with the thromboxane synthetase inhibitor, dazmegrel (10 microM),relaxed the spontaneous tone of the tissues, abolished the LTD4 (200 nM)-stimulated release of TXB2 and significantly enhanced (~two fold) the elaboration of 6-keto-PGF1alpha. In addition, dazmegrel attenuated (by ~50%) LTD4 (200 nM)-induced cyclic GMP accumulation but approximately doubled both the cyclic AMP content and PKA activity ratio. LTD4-induced contractions, in contrast, were not affected by dazmegrel.7. EP 092 (1 microM for 60 min), a selective TP-receptor blocking drug, had no effect on spontaneous tone,eicosanoid formation or on the cyclic GMP content of guinea-pig lung parenchymal strips. Likewise,EP 092 exerted no significant mechancial effect in lung challenged with LTD4 (200 nM) although it did potentiate, to a small extent, the ability of LTD4 (200 nM) to increase the cyclic AMP content.8. It is concluded that LTD4 can increase the intracellular level of cyclic AMP in guinea-pig parenchyma and activate PKA by a leukotriene-receptor-mediated mechanism sensitive to ICI 198,615. However,these biochemical actions of LTD4 are induced indirectly by an arachidonic acid-derived cyclo-oxygenase product(s) other than TXA2. Thus, contrary to reports of other investigators, no evidence was found to corroborate the finding that stimulation of leukotriene receptors on guinea-pig lung parenchyma results in a rapid lowering of the cyclic AMP content even in cyclo-oxygenase-blocked tissues. These data,therefore, do not support the hypothesis that leukotriene-induced tension generation is dependent upon a prior reduction in the cyclic AMP content.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

A novel method for rapid enrichment of lactotrophs from dispersed anterior pituitary cells of the rat.

A polyclonal antibody to the rat D2 dopamine (DA) receptor was rapidly and covalently attached to surface-activated polystyrene cultureware (MicroCEL-Lector plates). Addition of a suspension of dispersed rat anterior pituitary cells resulted in the rapid (within 1 h) selection of cells possessing D2 DA receptors (i.e. lactotrophs). Four-fold enrichment (from about 20% in the suspension to about 80%) was routinely obtained, as judged by prolactin (PRL) immunostaining. The enriched cells were virtually free of fibroblasts and were much more homogeneous in appearance than untreated cells after 3 days in culture. Lactotroph-enriched cell cultures displayed similar functional characteristics as untreated cells when assessed by determining dose-response curves for inhibition of PRL secretion by the DA agonist N-propylnorapomorphine. This method may be generally applicable for the selective enrichment and purification of desired cell types from heterogeneous mixtures in tissue dispersions.

Amino Acid Sequence↗
PubMed1993

Professional satisfaction and dissatisfaction of family physicians.

BACKGROUND: Physicians' satisfaction with their professional life influences the quality of patient care they provide and helps to determine the number and type of students attracted to the various fields of medicine. In this study, we sought to delineate areas of satisfaction and dissatisfaction among family physicians. METHODS: A self-administered questionnaire was sent to all physicians in the state of Pennsylvania who were included in the 1990 directory of the American Board of Family Practice (N = 1944). RESULTS: Completed questionnaires were received from 1066 family physicians in full-time practice. Sixty-five percent were satisfied with their professional lives. Patient relationships, a sense of clinical competence, and their relationships with their partners were among the most satisfying aspects of practice for all family physicians. Problems identified included regulations by third-party payers and government agencies and the large amount of paperwork encountered in practice. There were significant (P < .001) differences in satisfaction between physicians in different practice arrangements. Significant differences between practice types were also found in the degree of dissatisfaction with third-party payers and government agencies, paperwork, isolation from other physicians, and the threat of a malpractice suit. CONCLUSIONS: Almost two thirds of family physicians are satisfied with their general professional lives. Conversely, one third are not. Clear areas of satisfaction and dissatisfaction have been defined for family physicians in general as well as for family physicians in various practice environments. This information may be useful in the development of policy to structure a medical system that meets the needs of both patients and physicians.

Adult↗