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Biomedical subjects

J Diamond

Publications and source records attributed to J Diamond.

At least 55 records · Page 3Linked to original sources
PubMed1998

Automated histometry in quantitative prostate pathology.

OBJECTIVE: To review progress on the development of machine vision and image understanding in prostate tissue histology and to discuss the problems and opportunities afforded to pathology through the use of these techniques. STUDY DESIGN: A variety of concepts in machine vision are explored, and methodologies are described that have been developed to deal with the complexities of histologic imagery. The theory of human vision and its impact on machine vision are discussed. Software has been specifically developed for the analysis of prostate histology, allowing accurate gland segmentation, basal cell identification and measurement of vascularization within lesions. RESULTS: Image interpretation can be achieved using knowledge-based image analysis and the application of local object-oriented processing. This successfully allows an automated quantitative analysis of histologic morphology in the diagnosis of prostate intraepithelial neoplasia and invasive prostatic cancer. The use of low-power image scanning, based on textural or n-gram mapping, permits the development of fully automated devices for the rapid detection of tissue abnormalities. High-power, knowledge-guided scene segmentation can be carried out for the quantitative analysis of cellular features and the objective grading of the lesion. CONCLUSION: Automated tissue section scanning and image interpretation is now possible and holds much promise in prostate pathology and other diagnostically demanding areas. Issues of standardization still need to be addressed, but the development of such systems will undoubtedly enhance our diagnostic capabilities through the automation of time-consuming procedures and the quantitative evaluation of disease processes.

Humans↗
PubMed1997

Nerve growth factor accelerates seizure development, enhances mossy fiber sprouting, and attenuates seizure-induced decreases in neuronal density in the kindling model of epilepsy.

Recurrent seizure activity induced during kindling has been reported to produce a functional synaptic reorganization of the mossy fibers in the hippocampus. To date, it is unclear whether this kindling-induced growth is secondary to decreases in hilar neuron density, which are presumed to reflect hilar neuronal cell loss, or whether it is related specifically to an activation-dependent plasticity. We recently demonstrated that blocking nerve growth factor (NGF) biological activity retards seizure development and inhibits the sprouting of mossy fibers. We now demonstrate that intraventricular administration of NGF itself accelerates the progression of kindling epileptogenesis, increases mossy fiber sprouting in the CA3 region and in the inner molecular layer (IML), but reduces seizure-induced decreases in hilar cell density. These findings provide support for a role of NGF in kindling and kindling-induced mossy fiber sprouting. In addition, the results dissociate this form of epileptogenesis from hilar cell loss or decreases in hilar cell density attributable to increases in hilar area, thereby supporting seizure-induced mossy fiber sprouting as being primarily attributable to the combined effects of neuronal activation and the activation-induced upregulation of growth factors.

Animals↗
PubMed1997

Maximal sustained energy budgets in humans and animals.

Why are sustained energy budgets of humans and other vertebrates limited to not more than about seven times resting metabolic rate? The answer to this question has potential applications to growth rates, foraging ecology, biogeography, plant metabolism, burn patients and sports medicine.

Animals↗
PubMed1997

Assessment and management of chemotherapy-induced mucositis in children.

Oral mucositis is one of the most common side effects of cancer treatment. The oral mucosa is comprised of membranes of a high mitotic index with rapid epithelial turnover and maturation rates. This causes the mucosa to be vulnerable to the adverse effects of chemotherapy. Chemotherapy alters the integrity of the mucosa, the microbial flora which normally inhabit the oral cavity, salivary quantity and composition, as well as the epithelial maturation. As a result, the child receiving chemotherapy may experience significant pain, dysphagia, alteration in nutritional status, and risk of infection. Severe mucositis can also delay therapy that may compromise the child's treatment and chance for cure. Not all chemotherapy-induced mucositis can be prevented. However, with proper management, the severity and duration of oral complications can be minimized.

Antineoplastic Agents↗
PubMed1997

Cyclic GMP-dependent protein kinase activation in the absence of negative inotropic effects in the rat ventricle.

1. It has been suggested that activation of cyclic GMP-dependent protein kinase (PKG) is a necessary step in the chain of events leading to the production of negative inotropy by muscarinic receptor agonists in mammalian ventricles, and that some cyclic GMP-elevating agents, such as sodium nitroprusside (SNP), fail to exert a negative inotropic effect because they elevate cyclic GMP levels in a pool that does not activate the kinase. This hypothesis was tested in the present study by monitoring the effects of carbachol, SNP and atrial natriuretic peptide (ANP) on contractility, cyclic GMP content and PKG activity in rat intact ventricular preparations and freshly isolated ventricular cardiomyocytes. 2. The presence of PKG in both the intact vehicle and in isolated ventricular cardiomyocytes was confirmed by MonoQ anion exchange chromatography and Western blotting. The elution profile indicated that the conditions of the PKG assay were selective for measuring PKG activity. 3. Carbachol induced a marked negative inotropic effect in intact, perfused hearts and ventricular strips in the presence of isoproterenol. The negative inotropic effect of carbachol was not associated with significant changes in cyclic GMP content or PKG activity in intact ventricular tissue, or in PKG activity in isolated cardiomyocytes. 4. SNP and ANP significantly increased cyclic GMP levels and activated PKG in intact ventricular preparations. Both drugs also activated PKG in isolated cardiomyocytes. However, neither drug had any negative inotropic effect in isoprenaline-stimulated perfused hearts and ANP did not change the contractility of isoprenaline-stimulated isolated cardiomyocytes. 5. The results of this study demonstrate that the negative inotropic effects of muscarinic receptor agonists can occur in the absence of significant activation of PKG. Conversely, marked increases in ventricular cyclic GMP content and PKG activity caused by SNP or ANP were not accompanied by a negative inotropic effect. 6. These results suggest that increases in cyclic GMP levels and activation of PKG do not play important roles in the regulation of rat ventricular contractility by muscarinic receptor agonists.

Adrenergic beta-Agonists↗
PubMed1997

Effects of meal size on postprandial responses in juvenile Burmese pythons (Python molurus).

Pythons were reported previously to exhibit large changes in intestinal mass and transporter activities on consuming meals equal to 25% of the snake's body mass. This paper examines how those and other adaptive responses to feeding vary with meal size (5, 25, or 65% of body mass). Larger meals took longer to pass through the stomach and small intestine. After ingestion of a meal, O2 consumption rates rose to up to 32 times fasting levels and remained significantly elevated for up to 13 days. This specific dynamic action equaled 29-36% of ingested energy. After 25 and 65% size meals, plasma Cl- significantly dropped, whereas plasma CO2, glucose, creatinine, and urea nitrogen increased as much as a factor of 2.3-4.2. Within 1 day the intestinal mucosal mass more than doubled, and masses of the intestinal serosa, liver, stomach, pancreas, and kidneys also increased. Intestinal uptake rates of amino acids and of D-glucose increased by up to 43 times fasting levels, whereas uptake capacities increased by up to 59 times fasting levels. Magnitudes of many of these responses (O2 consumption rate, kidney hypertrophy, and D-glucose and L-lysine uptake) increased with meal size up to the largest meals studied; other responses (Na+-independent L-leucine uptake, plasma Cl-, and organ masses) plateaued at meals equal to 25% of the snake's body mass; and still other responses (nutrient uptake at day 1, passive glucose uptake, and plasma protein and alkaline phosphatase) were all-or-nothing, being independent of meal size between 5 and 65% of body mass. Pythons undergo a wide array of postprandial responses, many of which differ in their sensitivity to meal size.

Acclimatization↗
PubMed1997

Regulation of intestinal sugar transport.

The recent surge in knowledge of cellular and molecular mechanisms of intestinal sugar transport has fueled an enormous interest in adaptive mechanisms regulating sugar transport. We first review several functional considerations that help us interpret the different patterns of adaptation for different nutrients. We then distinguish nonspecific adaptive mechanisms leading to parallel changes in transport of different nutrients from specific adaptive mechanisms only affecting the transport of a single nutrient. Nonspecific adaptive mechanisms include changes in mucosal surface area and in the ratio of transporting to nontransporting cells; specific mechanisms include changes in site density of transporters and in affinity constants. We also enumerate the patterns of regulation and describe how sugar transport is affected by changes in diet, energy budgets, and environmental salinity as well as by intestinal resection, starvation, stress, and age. We relate the various signals linking these stimuli to adaptive mechanisms and make predictions about the nature of these signals. Finally, we describe the significance of the interactions among sugar, fluid, and electrolyte transport mechanisms and of the paracellular pathway to transepithelial transport of sugars. We close by drawing attention to promising directions for future research.

Animals↗
PubMed1997

The ultrasonic evaluation of the carotid intima-media thickness and its relation to risk factors of atherosclerosis in normal and diabetic population.

High-resolution ultrasound provides an excellent tool for the non-invasive assessment of the severity of atherosclerosis. It allows the measurement of the common carotid artery (CCA) intima media thickness (IMT) which has been found to be a feasible and reliable method for the evaluation of the progression and regression of the disease. The aim of this study was to evaluate the influence of risk factors of atherosclerosis on the mean CCA IMT in both normal and non-insulin dependent diabetic (NIDDM) individuals and to determine the effect of diabetes as a major atherosclerotic risk factor on the CCA IMT. Four hundred and eighty-four subjects were studied, 244 normal individuals and 240 non insulin dependent diabetic patients. The right and left CCA IMT were measured using high resolution ultrasonography. Both in the normal and diabetic individuals, the mean CCA IMT was found to increase linearly with age (p < 0.01), was directly related to total serum cholesterol and triglyceride and inversely related to HDL-cholesterol (p < 0.01). Multiple linear regression analysis showed the most important risk factor influencing the CCA IMT and hence early athrosclerosis to be the presence of diabetes, followed by serum HDL-cholesterol (inverse relation), total cholesterol, age and serum triglyceride. This study has shown that high resolution ultrasonography can be used to evaluate the effect to risk factors on early atherosclerosis and could be used to monitor future clinical trails aiming to modify the progression of atherosclerosis in the population.

Adult↗
PubMed1997

Activation of guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase in rabbit aorta by nitroglycerin and sodium nitroprusside.

It is generally accepted that cGMP mediates the vascular relaxant effects of nitrovasodilators such as sodium nitroprusside (SNP) and nitroglycerin (NTG). It has been suggested that the relaxant effects of cGMP are mediated via activation of a specific, cGMP-dependent protein kinase (PKG). The objective of this study was to determine whether PKG can be activated by SNP and by NTG in intact strips of rabbit aorta and, if so, whether a good correlation exists between activation of PKG and relaxation of the arteries by the nitrovasodilators. PKG activity was measured by means of a recently described assay using a peptide substrate, BPDEtide, that exhibits good sensitivity and specificity for PKG compared with other protein kinases. Verification of the specificity of the assay for PKG was obtained using MonoQ chromatography to resolve soluble extracts of the rabbit aorta and subsequent immunoblotting to identify the kinase by means of a PKG-specific antibody. The role of PKG in vascular relaxation was investigated by simultaneously monitoring the effects of SNP and NTG on cGMP levels, PKG activity ratios and tension in isolated strips of rabbit aorta exposed to varying concentrations of the nitrovasodilators for varying times. The results indicate that PKG can be activated in a concentration- and time-dependent manner by both SNP and NTG in intact vascular preparations and that reasonably good correlations exist between PKG activation and relaxation in these experiments. Although a causal relationship between the two parameters has not been definitely established, these results are consistent with the proposed role for PKG as a mediator of the vascular relaxant effects of cGMP-elevating agents such as SNP and NTG.

Animals↗
PubMed1997

Activation of guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase in rat vas deferens and distal colon is not accompanied by inhibition of contraction.

There is good evidence that in vascular smooth muscle, the relaxant effects of sodium nitroprusside (SNP) are mediated by increases in cGMP levels and activation of cGMP-dependent protein kinase (PKG). However, in rat vas deferens and rat distal colon, cGMP-elevating agents such as SNP and atrial natriuretic factor (ANF) have been shown to elevate cGMP without inducing relaxation. The lack of relaxation might be explained by either lack of activation of PKG by these agents or low levels of PKG in these tissues. The object of the present study was to investigate these possibilities by simultaneously monitoring cGMP levels, PKG activity and contractility in isolated strips of rat vas deferens, rat proximal colon and distal colon exposed to high concentrations of SNP or ANF. Verification of the specificity of the assay for PKG was obtained using MonoQ chromatography to resolve soluble smooth muscle extracts, followed by immunoblotting with a PKG-specific antibody to identify the kinase. In rat vas deferens, 5 mM SNP increased cGMP levels (14-fold) and PKG activity ratios (3.4-fold) but did not inhibit phenylephrine-induced contractions. In both rat proximal and rat distal colon, 100 nM ANF significantly elevated cGMP levels and PKG activity ratios, but only in the proximal colon was inhibition of spontaneous contractions observed. Total PKG activity was much lower (approximately 16 pmol PO4/min/mg protein) in rat vas deferens, which was not relaxed by SNP, than in rabbit aorta (approximately 148 pmol PO4/min/mg), which was relaxed. However, in the rat proximal colon, despite low PKG levels (approximately 11 pmole/min/mg), ANF did inhibit contractions. Thus the inability of the cGMP-elevating agents SNP and ANF to inhibit contractions in rat vas deferens and rat distal colon cannot be explained by either of the possibilities suggested above.

Animals↗
PubMed1997

Does adjunctive fluoxetine influence the post-hospital course of restrictor-type anorexia nervosa? A 24-month prospective, longitudinal followup and comparison with historical controls.

A 24-month naturalistic, prospective longitudinal followup study was conducted on 33 patients with anorexia nervosa who had participated in an intensive, multidisciplinary inpatient treatment program and were receiving fluoxetine as part of their continuing treatment regimen. Data on course, outcome, and treatment exposure in this cohort were obtained using standardized, comprehensive interviews administered at 6-month intervals after hospital discharge. Longitudinal course data for these patients were compared with data for matched historical controls who had received identical inpatient and followup treatment but without adjunctive fluoxetine. Analyses failed to show that fluoxetine had a significant effect on the cumulative probability of remaining at target weight during the followup period, the risk of sustained weight loss, or other clinical measures of outcome. Thus, adjunctive treatment with fluoxetine may not have additive long-term therapeutic benefit when measured against the effects of sustained and intensive followup treatment.

Adolescent↗
PubMed1996

Delayed effects of epidermal growth factor after extensive small bowel resection.

Epidermal growth factor (EGF) is produced in the gastrointestinal tract and has been shown to have a transient stimulatory effect on mucosal growth and uptake of glutamine. This study investigated the delayed effects of EGF on mucosal brush-border membrane enzymes and glutamine uptake after extensive small bowel resection. Twenty-four New Zealand White rabbits underwent a 50% to 60% midjejunoileal enterectomy. One group of 12 had a subcutaneous osmotic pump inserted, delivering EGF at 0.3 microgram/kg/h for the first 7 postoperative days. The other group of 12 served as controls. Six rabbits from each group were killed at 3 weeks, and the remaining 12 were killed at 6 weeks. Six additional rabbits served asd nonsurgical controls. There was a twofold increase in mucosal dry weight at 3 weeks without EGF, and an almost fourfold increase with EGF, over control rabbits. This effect of EGF on the mucosa persisted for 6 weeks. Enzymatic activity per gram of protein in each group of rabbits was similar between the four groups of rabbits, although maltase activity increased approximately fourfold over that of nonoperative control animals. However, enzyme capacity of maltase and aminooligopeptidase (AOP) increased threefold and twofold (respectively) at 3 weeks without EGF, and sixfold and fourfold with EGF. Functional capacity is a measure of the load of nutrients that the intestine can digest and absorb, and therefore the derivable benefit to the animal. Glutamine uptake capacity increased 60% in 3 weeks without EGF, then declined by 6 weeks. However with EGF it increased 200% by 3 weeks, and further increased 400% by 6 weeks over control levels. The authors conclude that EGF markedly increases the functional capacity of the small intestine in rabbits that have undergone extensive small bowel resection; this effect persists for up to 6 weeks after a small initial dosage of EGF.

Animals↗
PubMed1996

Simultaneous manipulation of intestinal capacities and nutrient loads in mice.

To study the relationship between capacity and load in the small intestine, we simultaneously varied dietary nutrient load and intestinal capacity in mice. Intestinal transection alone caused an increase in intestinal mass, because of increased serosal mass. Because virgin mouse intestine possesses 180% reserve uptake capacity before resection and the intestine regenerates after resection, resection of up to 50% had no effect on food intake, digestive efficiency, intestinal brush-border glucose uptake rate, or mass of all organs measured except the cecum. Regeneration of intestinal mass and glucose uptake capacity was quantitatively complete, because intestinal mass 10 wk after resection was similar to that in unresected mice. Resected intestinal mass in lactating mice was four times larger than that immediately after resection in virgin mice. Cecal mass increased in 50%-resected lactating mice with high food intakes, suggesting nutrient spillage into the distal gut as a signal for regeneration. Mice failed to survive 70% resection of the intestine, possibly because intestinal reserve uptake capacity was exhausted immediately after surgery, making regeneration impossible.

Animals↗
PubMed1996

Is mammary output capacity limiting to lactational performance in mice?

Using lactation in mice as a model, we sought to determine whether ceilings on sustained energy expenditure reside in the capacities of energy-acquiring and input organs (such as the intestine) or of energy-expending and output organs (such as the mammary glands). To distinguish between these possibilities experimentally, we surgically varied the teat number of lactating mother mice while simultaneously varying their litter size. The energy burden on each teat (i.e. the pup/teat ratio) could thus be varied independently of the energy burden (i.e. litter size) on the mother herself or on her intestine. At each teat number, pup mass proved to be maximal at intermediate litter sizes. At a given pup/teat ratio, mothers with five teats weaned pups no larger than the pups of normal (10-teat) mothers, even though the total energy burden on the former mothers was only half as large. Mothers with only two teats could not wean any pups. Litter size controlled maternal food intake, which in turn controlled intestinal mass and nutrient uptake capacity. Disproportionately high food intake for the smallest litters appears to reflect capital start-up costs of lactation. Pup mass is evidently limited by inadequate suckling stimulation of mammary glands.

Animals↗
PubMed1996

Reverse transcription/polymerase chain reaction (RT/PCR) amplification of very small numbers of transcripts: the risk in misinterpreting negative results.

Technical modifications of the reverse-transcription/polymerase chain reaction (RT/PCR) amplification method now permit its use to detect amplified products from as few as one abnormal cell, either isolated or mixed with a larger number of normal cells. We studied the reproducibility of such results using as targets low numbers of cells from chronic myeloid leukaemia (CML) patients and CML cell lines in quintuplicate two-step RT/PCR designed to amplify BCR-ABL sequences. When one K562 or KYO1 cell was diluted in 10(3) non-CML HL60 cells, an amplification product was obtained in each test; at greater dilutions BCR-ABL transcripts were detected erratically. Titration of cDNA synthesised from 5 x 10(7) cells from four CML patients showed that whereas positive BCR-ABL sequences could be amplified in some tests starting with as little as a 1 in 10(7) dilution of cDNA template (corresponding to 5-10 cells), the dilution threshold for reproducible amplification was around 1 to 5 in 10(5) (100-500 cells). Quantitative PCR analysis revealed that reactions from 1 in 10(7) diluted cDNA contained less than 10 BCR-ABL transcripts as the starting template. The stochastic nature of the amplification from such small numbers of transcripts was illustrated by results of 10 replicate PCR tests on cDNA from a patient expressing both b3a2 and b2a2 transcripts: dilutions of cDNA up to 1 in 10(5) yielded dual transcript amplification in all 10 tests, but the 1 in 10(7) cDNA dilution resulted in b3a2 and b2a2 products in three tests, b3a2 only in three, b2a2 only in one and no amplification in three tests. We conclude that this 'sampling effect' may yield false-negative results and thus misinterpretation of data regarding assessment of gene expression when the quantity of target material available for study is very small.

False Negative Reactions↗
PubMed1996

An interactive decision support system for breast fine needle aspiration cytology.

OBJECTIVE: To develop a computerized system to assist in the diagnosis of malignancy in breast fine needle aspiration cytology. STUDY DESIGN: A Bayesian belief network was designed to control uncertainty and allow a diagnostic decision to be reached based on the sequential collection of cytologic information. Ten cytologic features were defined as clues that contribute to the diagnostic discrimination of benign and malignant aspirates. The impact of each feature on the diagnostic decision was quantified by a conditional probability matrix. RESULTS: For the assessment of a new case, the computer guides the user through the diagnosis, prompting him or her for information on each of the diagnostic features in turn. For each feature, the user is presented with a series of digitally stored color microscopic images that have been selected to represent good examples of the different feature grades-e.g., pleomorphism: none, mild, moderate and severe. Each image is mapped to an overlapping curve, and by positioning a line on the spectrum where the user feels the case lies, a membership function vector is calculated and entered as evidence into the network. This results in an update in the belief in the diagnostic alternatives. After all the clues have been assessed, a final diagnostic probability is reported. In addition, a cumulative belief curve can be drawn that maps the change in the diagnostic probabilities after each piece of evidence has been submitted, providing unique insight into the diagnostic process. CONCLUSION: Systems like this represent an important step forward in the use of descriptive classifiers. They impose consistency in terminology, improve reproducibility in the grading of cellular abnormalities and remove subjectivity in interpreting the significance of pvisual clues to diagnosis. As such, they represent a necessary tool in pathologic decision making.

Biopsy, Needle↗
PubMed1995

NGF-dependent and NGF-independent recovery of sympathetic function after chemical sympathectomy with 6-hydroxydopamine.

To help clarify the distinction between the nerve growth factor (NGF)-dependent collateral sprouting of sympathetic nerves and their NGF-independent regeneration after crush, we used 6-hydroxydopamine (OHDA) to destroy the sympathetic terminals in adult rats; this leaves the axons damage-free. Would recovery occur by regeneration and/or collateral sprouting? A single 6-OHDA injection abolished the sympathetic pilomotor field revealed by electrical stimulation of a cutaneous nerve. Recovery began within 2 days, and by 20 days the field was reestablished. If the field was "isolated" by adjacent denervations at the time of 6-OHDA treatment, the recovering pilomotor field expanded extensively into the surrounding territory. In the presence of anti-NGF, however, the pilomotor field expansion ceased at about 60% of its former size; if anti-NGF treatment was discontinued, expansion recommended and extended into the surrounding skin. We suggest that the latter, NGF-dependent, growth phase corresponds to collateral sprouting, and the initial NGF-independent one to regeneration. After simple nerve crush, however, such regeneration can triple the normal sympathetic field size. This difference between crush- and 6-OHDA-induced regeneration might relate to the "cell body reaction" (CBR); the CBR is reduced with increasing distance of the lesion and is undetectable after a 6-OHDA lesion. Since the CBR and the vigor of regeneration are both increased by repeated axonal injury, we tested the effects of multiple 6-OHDA treatments; this significantly increased the initial NGF-independent expansion. We hypothesize that regeneration is regulated largely by mechanisms associated with the CBR, and that neurotrophin-dependent collateral sprouting occurs independently of these.

Animals↗