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Biomedical subjects

K M Harris

Publications and source records attributed to K M Harris.

At least 19 recordsLinked to original sources

Dense core vesicles resemble active-zone transport vesicles and are diminished following synaptogenesis in mature hippocampal slices.

Large dense core vesicles (approximately 100 nm) contain neuroactive peptides and other co-transmitters. Smaller dense core vesicles (approximately 80 nm) are known to contain components of the presynaptic active zone and thought to transport and deliver these components during developmental synaptogenesis. It is not known whether excitatory axons in area CA1 contain such dense core vesicles, and whether they contribute to synaptic plasticity of mature hippocampus. Serial section electron microscopy was used to identify dense core vesicles in presynaptic axons in s. radiatum of area CA1 in adult rat hippocampus. Comparisons were made among perfusion-fixed hippocampus and hippocampal slices that undergo synaptogenesis during recovery in vitro. Dense core vesicles occurred in 26.1+/-3.6% of axonal boutons in perfusion fixed hippocampus, and in only 17.6+/-4.5% of axonal boutons in hippocampal slices (P<0.01). Most of the dense core vesicle positive boutons contained only one dense core vesicle, and no reconstructed axonal bouton had more than a total of 10 dense core vesicles in either condition. Overall the dense core vesicles had average diameters of 79+/-11 nm. These small dense core vesicles were usually located near nonsynaptic membranes and rarely occurred near the edge of a presynaptic active zone. Their size, low frequency, locations, and decrease following recuperative synaptogenesis in slices are novel findings that merit further study with respect to small dense core vesicle content and possible contributions to synapse assembly and plasticity in the mature hippocampus.

Animals↗

Dendritic spines disappear with chilling but proliferate excessively upon rewarming of mature hippocampus.

More dendritic spine synapses occur on mature neurons in hippocampal slices by 2 h of incubation in vitro, than in perfusion-fixed hippocampus. What conditions initiate this spinogenesis and how rapidly do the spines begin to proliferate on mature neurons? To address these questions, CA1 field of the hippocampus neurons expressing green fluorescent protein in living slices from mature mice were imaged with two-photon microscopy. Spines disappeared and dendrites were varicose immediately after slice preparation in ice-cold artificial cerebrospinal fluid (ACSF). Electron microscopy (EM) revealed disrupted dendritic cytoplasm, enlarged or free-floating postsynaptic densities, and excessive axonal endocytosis. Upon warming dendritic varicosities shrank and spines rapidly reappeared within a few minutes illustrating the remarkable resilience of mature hippocampal neurons in slices. When membrane impermeant sucrose was substituted for NaCl in ACSF dendrites remained spiny at ice-cold temperatures and EM revealed less disruption. Nevertheless, spine number and length increased within 30 min in warm ACSF even when the extracellular calcium concentration was zero and synaptic transmission was blocked. When slices were first recovered for several hours and then chilled in 6 degrees C ACSF many spines disappeared and the dendrites became varicose. Upon re-warming varicosities shrank and spines reemerged in the same position from which they disappeared. In addition, new spines formed and spines were longer suggesting that chilling, not the initial injury from slicing, caused the spines to disappear while re-warming triggered the spine proliferation on mature neurons. The new spines might be a substrate for neuronal recovery of function, when neurons have been chilled or exposed to other traumatic conditions that disrupt ionic homeostasis.

Animals↗

Effect of endoscopic ultrasonography on the management of 100 consecutive patients with oesophageal and junctional carcinoma.

BACKGROUND: Endoscopic ultrasonography (EUS) offers very accurate tumour and node staging information for oesophagogastric cancer. The aim was to determine whether the addition of EUS directly influenced the definitive management plan for individual patients. METHODS: Personal and staging information from 100 consecutive patients with carcinoma of the oesophagus or oesophagogastric junction were summarized and blinded. Three consultant oesophagogastric surgeons independently made a management decision for each patient, in the presence and absence of the EUS data. All scored their perceived value of the EUS staging data for each patient. RESULTS: EUS was deemed useful in 63-87 per cent of patients and its addition resulted in an increased number of concordant management plans (from 53 to 62 per cent), and increased agreement between surgeons. The greatest change in concordant management was an increased referral of patients for non-surgical palliation. CONCLUSION: The addition of EUS to the staging of patients with oesophageal and oesophagogastric junction cancer significantly altered the management strategy for some of these patients.

Adenocarcinoma↗

Confirmation by DNA analysis that Contarinia maculipennis (Diptera: Cecidomyiidae) is a polyphagous pest of orchids and other unrelated cultivated plants.

The cytochrome oxidase subunit I gene in mitochondrial DNA of 53 larvae of Contarinia maculipennis Felt from flower buds of various host plants, collected from Hawaii, Japan and Thailand was analysed. Monophyly of the clade including C. maculipennis from Hawaii, Thailand and Japan was supported. There was no sequential variation within the specimens from Hawaii and Japan, which differed from one another by 6 bp (1.37%). Three haplotypes were recognized in specimens from Thailand but differences from Hawaiian and Japanese specimens were small. Overall, there were no differences in the 146 deduced amino acid residues. It is therefore concluded that C. maculipennis is a polyphagous species that can develop on plant hosts representing at least seven botanical families. This pest of Dendrobium flower buds in glasshouses is considered to have entered Hawaii, Florida and Japan from Southeast Asia, and was recently intercepted in the Netherlands. Infestations have established and spread in orchid glasshouses, causing concern about the possibility of more extensive damage to orchids and to crops, such as bitter gourd, grown in close proximity to orchid glasshouses in Japan. The potential usefulness of DNA analysis in determining host plant ranges of morphologically identical cecidomyiid species that are currently identified solely on differences of host plant is emphasized.

Animals↗

Three-dimensional comparison of ultrastructural characteristics at depressing and facilitating synapses onto cerebellar Purkinje cells.

Cerebellar Purkinje cells receive two distinctive types of excitatory inputs. Climbing fiber (CF) synapses have a high probability of release and show paired-pulse depression (PPD), whereas parallel fiber (PF) synapses facilitate and have a low probability of release. We examined both types of synapses using serial electron microscopic reconstructions in 15-d-old rats to look for anatomical correlates of these differences. PF and CF synapses were distinguishable by their overall ultrastructural organization. There were differences between PF and CF synapses in how many release sites were within 1 microm of a mitochondrion (67 vs 84%) and in the degree of astrocytic ensheathment (67 vs 94%). However, the postsynaptic density sizes for both types of synapses were similar (0.13-0.14 microm(2)). For both types of synapses, we counted the number of docked vesicles per release site to test whether this number determines the probability of release and synaptic plasticity. PF and CF synapses had the same number of anatomically docked vesicles (7-8). The number of docked vesicles at the CF does not support a simple model of PPD in which release of a single vesicle during the first pulse depletes the anatomically docked vesicle pool at a synapse. Alternatively, only a fraction of anatomically docked vesicles may be release ready, or PPD could result from multivesicular release at each site. Similarities in the number of docked vesicles for PF and CF synapses indicate that differences in probability of release are unrelated to the number of anatomically docked vesicles at these synapses.

Animals↗

Cylindrical diameters method for calibrating section thickness in serial electron microscopy.

UNLABELLED: An estimate of section thickness is required for measuring structures in serial section microscopy. Mean section thickness is estimated reliably by averaging the ratios of the diameters of cylindrical objects, such as mitochondria, to the number of sections they span. This cylindrical diameters method improves the accuracy of section thickness as inferred from the colour of sections floating in water. The cylindrical diameters method gives the same answer as that obtained by the minimal folds METHOD: It is preferable because it can be done in a series that has no folds that can distort and obscure the objects that are being measured.

Animals↗

A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma.

BACKGROUND: Endoscopic ultrasound (EUS) may be used for preoperative staging of gastro-oesophageal carcinoma but performance values given in the literature differ. AIMS: To identify and synthesise findings from all articles on the performance of EUS in tumour, node, metastasis (TNM) staging of gastro-oesophageal carcinoma. SOURCE: Published and unpublished English language literature, 1981-1996. METHODS: Data on the staging performance of EUS were retrieved and evaluated. Summary receiver operator characteristic methodology was used for synthesis, and a summary estimate of performance, Q*, obtained. Multiple regression analysis was used to assess study validity and investigate reasons for differences in performance. RESULTS: Twenty seven primary articles were assessed in detail. Thirteen supplied results for staging oesophageal cancer, 13 for gastric cancer, and four for cancers at the gastro-oesophageal junction. For gastric T staging, Q*=0.93 (95% confidence interval (CI) 0.91-0.95) and for oesophageal T staging, Q*=0.89 (95% CI 0.88-0.92). For gastro-oesophageal T staging, including cancers at the gastro-oesophageal junction, Q*=0.91 (95% CI 0.89-0.93). Inclusion of cases with non-traversable stenosis was found to slightly reduce staging performance. For N staging, Q*=0.79 (95% CI 0.75-0.83). In articles that compared EUS directly with incremental computed tomography, EUS performed better. None of the variables assessed in the regression analysis was significant using a Bonferroni correction. Three variables (anatomical location, traversability, and blinding) showed strong relationships for future research and validation. CONCLUSIONS: EUS is highly effective for discrimination of stages T1 and T2 from stages T3 and T4 for primary gastro-oesophageal carcinomas. The failure rate of EUS from non-traversability of a stenotic cancer may be a limitation in some patient groups.

Confidence Intervals↗

Sibling, peer, neighbor, and schoolmate correlations as indicators of the importance of context for adolescent development.

We use nationally representative data to calculate correlations in achievement and delinquency between genetically differentiated siblings within a family, between peers as defined by adolescents' "best friend" nominations, between schoolmates living in the same neighborhood, and between grademates within a school. We find the largest correlations between siblings, especially identical twins. Grademate and neighbor correlations are small. Peer-based correlations are considerably larger than grademate and neighbor correlations but not larger than most sibling correlations. The data suggest that family-based factors are several times more powerful than neighborhood and school contexts in affecting adolescents' achievement and behavior.

Adolescent↗

The initial United States experience with the ATS mechanical cardiac valve prosthesis.

From January 1, 1997 through June 30, 2000, 224 patients underwent valve replacement with the ATS Medical cardiac valve prosthesis under a USFDA-approved investigational device exemption study. Aortic valve replacement (AVR) was conducted in 152 patients (39 with coronary bypass) and mitral replacement (MVR) in 72 patients (18 with coronary bypass). Overall operative mortality was 1.8% (AVR = 2.8%, MVR = 0%), with only one valve-related death. In 372 patient-years of follow-up, there were an additional four patient deaths, two of which were valve related following a stroke. Valve-related complications included: thromboembolism (linearized rate = 3.8% per patient year), of which 3/11 had chronic deficits (0.8% per patient year); thrombosis (1 MVR = 0.8% per patient year); paravalvular leak (1 AVR = 0.4% per patient year); anticoagulant-related hemorrhage (1 AVR and 5 MVR = 1.6% per patient year) with no patient mortality; prosthetic valve endocarditis (1 MVR = 0.8% per patient year); and valve dysfunction (0%). Echocardiographic gradients were proportional to valve size and did not significantly change over the follow-up period. This study documented the ATS Medical prosthesis to be a valuable addition to the surgeon's armamentarium in the treatment of cardiac valvular disease.

Adult↗

Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy.

BACKGROUND: Sudden death is known to be a possible consequence of hypertrophic cardiomyopathy. Quantification of the risk of sudden death, however, remains imprecise for most patients with this disease. METHODS: We assessed the relation between the magnitude of left ventricular hypertrophy and mortality in 480 consecutive patients with hypertrophic cardiomyopathy. The patients were categorized into five subgroups according to maximal wall thickness: 15 mm or less, 16 to 19 mm, 20 to 24 mm, 25 to 29 mm, and 30 mm or more. Their ages ranged from 1 to 89 years (median, 47). RESULTS: Over a mean follow-up period of 6.5 years, 65 of the 480 patients (14 percent) died: 23 suddenly, 15 of heart failure, and 27 of noncardiac causes or stroke. The risk of sudden death increased progressively and in direct relation to wall thickness (P=0.001), ranging from 0 per 1000 person-years (95 percent confidence interval, 0 to 14.4) for a wall thickness of 15 mm or less to 18.2 per 1000 person-years (95 percent confidence interval, 7.3 to 37.6) for a wall thickness of 30 mm or more and almost doubling from each wall-thickness subgroup to the next. The cumulative risk 20 years after the initial evaluation was close to zero for patients with a wall thickness of 19 mm or less but almost 40 percent for wall thicknesses of 30 mm or more. As compared with the other subgroups, patients with extreme hypertrophy were the youngest (mean age, 31 years), and most (41 of 43) had mild symptoms or no symptoms; of the 12 patients who were less than 18 years old at the initial evaluation, 5 died suddenly. CONCLUSIONS: In hypertrophic cardiomyopathy, the magnitude of hypertrophy is directly related to the risk of sudden death and is a strong and independent predictor of prognosis. Young patients with extreme hypertrophy, even those with few or no symptoms, appear to be at substantial long-term risk and deserve consideration for interventions to prevent sudden death. The majority of patients with mild hypertrophy are at low risk and can be reassured regarding their prognosis.

Adolescent↗

Congenital myasthenic syndrome with sleep hypoventilation.

We report the case of a 13-year-old boy with acetylcholinesterase deficiency, a congenital myasthenic syndrome, who developed sleep hypoventilation syndrome during a period of rapid growth. His symptoms were insidious and life-threatening despite changes in strength or lung volume measurements that were not marked. He responded well to noninvasive nocturnal ventilation, with reversal of symptoms and normalization of blood gases. His lung volumes, but not motor function, improved after treatment.

Acetylcholinesterase↗

Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines.

There has been an explosion of new information on the neurobiology of dendritic spines in synaptic signaling, integration, and plasticity. Novel imaging and analytical techniques have provided important new insights into dendritic spine structure and function. Results are accumulating across many disciplines, and a step toward consolidating some of this work has resulted in Dendritic Spines of the Hippocampus. Leaders in the field provide a discussion at the level of advanced under-graduates, with sufficient detail to be a contemporary resource for research scientists. Critical reviews are presented on topics ranging from spine structure, formation, and maintenance, to molecular composition, plasticity, and the role of spines in learning and memory. Dendritic Spines of the Hippocampus provides a timely discussion of our current understanding of form and function at these excitatory synapses. We asked authors to include areas of controversy in their papers so as to distinguish results that are generally agreed upon from those where multiple interpretations are possible. We thank the contributors for their insights and thoughtful discussions. In this paper we provide background on the structure, composition, function, development, plasticity, and pathology of hippocampal dendritic spines. In addition, we highlight where each of these subjects will be elaborated upon in subsequent papers of this special issue of Hippocampus.

Animals↗

Identifying studies for systematic reviews. An example from medical imaging.

OBJECTIVES: To determine if published figures on the proportion of articles included in systematic reviews and identified in electronic databases are applicable to an example from medical imaging. METHODS: A systematic review was performed. Additionally, sensitivity and precision of a MEDLINE search were compared with values from three published searches, each customized for a specific field. RESULTS: All articles included in the systematic review were in electronic databases. The MEDLINE search had low precision compared with searches in other fields. CONCLUSIONS: In a specific area of medical imaging, electronic databases, including MEDLINE, are reliable sources of articles.

Bibliometrics↗

A case of confirmed nonbacterial thrombotic endocarditis with correlative transesophageal echocardiographic findings.

The diagnosis of nonbacterial thrombotic endocarditis is rarely made during life. We describe a patient with non-Hodgkin's lymphoma with evidence of systemic embolism in which transesophageal echocardiography was useful in establishing the diagnosis. The clinical and echocardiographic features of nonbacterial thrombotic endocarditis should be remembered when a valvular mass is seen on echocardiography.

Adult↗

The mechanisms mediating the effects of poverty on children's intellectual development.

Although adverse consequences of poverty for children are documented widely, little is understood about the mechanisms through which the effects of poverty disadvantage young children. In this analysis we investigate multiple mechanisms through which poverty affects a child's intellectual development. Using data from the NLSY and structural equation models, we have constructed five latent factors (cognitive stimulation, parenting style, physical environment, child's ill health at birth, and ill health in childhood) and have allowed these factors, along with child care, to mediate the effects of poverty and other exogenous variables. We produce two main findings. First, the influence of family poverty on children's intellectual development is mediated completely by the intervening mechanisms measured by our latent factors. Second, our analysis points to cognitive stimulation in the home, and (to a lesser extent) to parenting style, physical environment of the home, and poor child health at birth, as mediating factors that are affected by lack of income and that influence children's intellectual development.

Adolescent↗