Biomedical subjects

K M Harris

Publications and source records attributed to K M Harris.

At least 109 records · Page 6Linked to original sources

PubMed1989

Infiltrating lobular carcinoma: mammographic patterns with pathologic correlation.

Of the five identified radiographic patterns of ILC, the most common was a poorly defined asymmetric density with architectural distortion. Areas of ILC frequently are of low density, not much greater than that of the surrounding parenchyma. The mammographic appearance may reflect the behavior of ILC tumor cells, which travel in linear array ("single file") along and around the arborizing ducts that serve as scaffolding for these small, malignant cells that permeate the parenchyma without a central nidus. This feature of ILC may also help explain why tumors may be palpable as areas of vague induration or thickening rather than as discrete masses. When tumors are hidden in dense breast tissue (pattern 3) and not well imaged by mammography or when there are subtle mammographic changes (pattern 1), sonography may help confirm the presence of a solid mass. Most of the suspected tumors imaged by sonography were palpable as discrete masses or areas of induration.

Adult↗

PubMed1989

Carcinoma mimicked by the sternal insertion of the pectoral muscle.

A prospective study of 1843 patients was performed to identify the frequency of imaging the medial portion of the greater pectoral muscle on the craniocaudal projection during routine mammography. This artifact was seen in 14 patients. None of these patients had a palpable abnormality; additional craniocaudal views revealed continuity of the density with the pectoral muscle. Four patients were reexamined in 6 months; no change was seen in the size of the density. The density is thought to represent the medial portion of the pectoral muscle, which is included because of vigorous retraction of the breast and slight external rotation during positioning for the craniocaudal view. Familiarity with the appearance of the medial portion of the greater pectoral muscle on craniocaudal mammograms will help prevent inaccurate interpretations and unnecessary biopsies.

Breast Neoplasms↗

PubMed1989

Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics.

Serial electron microscopy and 3-D reconstructions of dendritic spines from hippocampal area CA 1 dendrites were obtained to evaluate 2 questions about relationships between spine geometry and synaptic efficacy. First, under what biophysical conditions are the spine necks likely to reduce the magnitude of charge transferred from the synapses on the spine heads to the recipient dendrite? Simulation software provided by Charles Wilson (1984) was used to determine that if synaptic conductance is 1 nS or less, only 1% of the hippocampal spine necks are sufficiently thin and long to reduce charge transfer by more than 10%. If synaptic conductance approaches 5 nS, however, 33% of the hippocampal spine necks are sufficiently thin and long to reduce charge transfer by more than 10%. Second, is spine geometry associated with other anatomical indicators of synaptic efficacy, including the area of the postsynaptic density and the number of vesicles in the presynaptic axon? Reconstructed spines were graphically edited into head and neck compartments, and their dimensions were measured, the areas of the postsynaptic densities (PSD) were measured, and all of the vesicles in the presynaptic axonal varicosities were counted. The dimensions of the spine head were well correlated with the area of PSD and the number of vesicles in the presynaptic axonal varicosity. Spine neck diameter and length were not correlated with PSD area, head volume, or the number of vesicles. These results suggest that the dimensions of the spine head, but not the spine neck, reflect differences in synaptic efficacy. We suggest that the constricted necks of hippocampal dendritic spines might reduce diffusion of activated molecules to neighboring synapses, thereby attributing specificity to activated or potentiated synapses.

Animals↗

PubMed1988

The role of ultrasound-guided needle aspiration of breast masses.

Ultrasonically guided aspiration cytology is an accurate and cost-effective method for managing sonographically indeterminate breast masses (masses that do not have all the ultrasonic criteria of simple cysts). Forty-five breast masses were aspirated. Of these, fifteen (33%) were atypical cysts, twenty-one (47%) were benign solid masses, three (7%) were malignant and six (13%) were solid lesions with nondiagnostic aspirate material. Since the tip of the needle is ultrasonically identified within the mass prior to aspiration, the accuracy of tissue sampling is potentially greater than with palpation alone. Lesions over five millimeters in diameter can be reliably sampled for cytology. This method can reduce the number of surgical biopsies performed by distinguishing atypical cysts from benign solid lesions and detecting malignant lesions when small. The simplicity of the technique encourages its use whenever an ultrasound study detects a noncystic mass.

Biopsy, Needle↗

PubMed1988

Dendritic spines of rat cerebellar Purkinje cells: serial electron microscopy with reference to their biophysical characteristics.

We have used serial electron microscopy and 3-dimensional reconstructions of dendritic spines from Purkinje spiny branchlets of normal adult rats to evaluate 2 questions about the relationship of spine geometry to synaptic efficacy. First, do relationships between spine geometry and other anatomical indicators of synaptic activity suggest that spine size and shape might be associated with synaptic efficacy? Reconstructed spines were graphically edited into head and neck compartments; the area of the postsynaptic density (PSD) was measured; the volume of spine smooth endoplasmic reticulum (SER) was computed; and all of the vesicles in the axonal varicosities were counted. Spine head volume and the volume of SER contained in the head are well correlated with the area of the PSD and the number of vesicles in the presynaptic axonal varicosity. Spine neck diameter does not fluctuate with PSD area, head volume, or the vesicle number. These results suggest that the dimensions of the spine head, but not of the spine neck, are likely to reflect differences in synaptic efficacy. Second, does the geometry of cerebellar spine necks reduce the transfer of synaptic charge to the recipient dendrite from the theoretical maximum that could be transferred if the synapse were on a dendritic shaft? Comparison of volume to surface area showed that the spine heads are approximately spherical and the necks are approximately cylindrical. Application of results from a biophysical model that assumed these geometrical shapes for spines (Wilson, 1984) showed that the cerebellar spine necks are unlikely to reduce transfer of synaptic charge by more than 5-20% even if their SER were to completely block passage of current through the portion of the neck that it occupies. We suggest that the constricted spine neck diameter might serve to isolate metabolic events in the vicinity of activated synapses by reducing diffusion to neighboring synapses, without significantly influencing the transfer of synaptic charge to the postsynaptic dendrite.

Animals↗

PubMed1987

Posttransplantation cyclosporine-induced lymphoproliferative disorders: clinical and radiologic manifestations.

Fifteen allograft transplant recipients acquired lymphoproliferative disorders after immunosuppressive therapy with cyclosporine and steroids. Many of these lymphoproliferative disorders regressed or disappeared completely after reduction of cyclosporine dose. This disease has several aspects that distinguish it from usual posttransplantation lymphomas that occur with regimens that do not contain cyclosporine. The time course from transplantation to onset of lymphoma is relatively short, with an average of approximately 8 months. Organs show a wide spectrum of abnormalities typical of other immunosuppression-associated lymphomas, but there is unique sparing of the central nervous system. The tumor is also unique in that it responds to a decrease in the cyclosporine dose.

Adolescent↗

PubMed1986

Protein kinase C mediated regulation of calcium channels in PC-12 pheochromocytoma cells.

Depolarization of PC-12 pheochromocytoma cells with K+ produces an immediate increase in catecholamine release. The stimulation of release is blocked by Co2+, removal of extracellular Ca2+ or by dihydropyridine drugs such as nitrendipine. Release is enhanced by other dihydropyridines such as BAY K8644. Release is accompanied by a voltage dependent uptake of 45Ca2+ which is also blocked by Co2+ or nitrendipine and enhanced by BAY K8644. The phorbol ester phorbol 12-myristate-13-acetate (TPA) in the range 10(-9)-10(-6) M produced little effect by itself but augmented the K+ evoked release of catecholamine. An analog of TPA which does not activate protein kinase C was ineffective. In contrast, TPA in the same concentration range blocked influx of 45Ca2+ induced by 70 mM K+ or 70 mM K+/BAY K8644. 45Ca2+ influx produced by A23187 was not blocked by TPA. The results suggest a system by which protein kinase C may regulate the output of transmitters from secretory cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1986

Clinical and radiographic features of simple and hydatid cysts of the liver.

The advances of hydatid chemotherapy and the non-operative management of simple (epithelial) hepatic cysts make a correct diagnosis of increasing importance. Twenty-six patients with hepatic hydatid cysts and eleven with simple cysts were reviewed. In both groups clinical presentation was most frequently due to pain. Sex, age and size of the cysts were similar. Hydatid serology was negative in six of the hydatid patients (23 per cent). None of the simple cyst patients had positive serology but one had a borderline titre. Ultrasound and computerized tomography identified daughter cysts within the main cyst in only 17 hydatid cysts (65 per cent) and considerable intra-cyst debris was also present in five of the simple cysts. Seven of the simple cysts were deroofed surgically and the remainder underwent percutaneous aspiration. Sixteen of the hydatid cysts were found to have a biliary communication whereas this was not found with any simple cyst. The difficulties in making a precise diagnosis in some patients with a liver cyst should deter the interventional radiologist and restrain the hydatid chemotherapist.

Adult↗

PubMed1986

Membrane structure at synaptic junctions in area CA1 of the rat hippocampus.

In tissue from area CA1 of the rat hippocampus prepared for electron microscopic study by thin-sectioning, asymmetric synaptic junctions were found on dendritic spines, spiny dendritic shafts, and non-spiny dendritic shafts. In freeze-fractured preparations, aggregates of large particles were found on the extracellular half of the postsynaptic membrane at each of these synaptic junctions. Particle aggregate areas were measured and particle packing densities were computed at dendritic spine synapses and dendritic shaft synapses in area CA1, and compared to similar measures of particle aggregates on dendritic spines of cerebellar Purkinje cells. All of these CA1 and cerebellar synapses are excitatory and are thought to use glutamate as a neurotransmitter. There was a tendency for the dispersion of particles within individual aggregates to be less uniform in larger aggregates in both area CA1 and cerebellar cortex. Distinct particle-free zones could be distinguished in the center of particle aggregates on large "mushroom-shaped" spines in area CA1. There was no statistically significant difference between the particle densities at CA1 dendritic spines (2848 +/- 863 particles/micron2) and CA1 dendritic shafts (2707 +/- 718 particles/micron2). However, the average density of particles at cerebellar dendritic spine synapses (3614 +/- 1081 particles/micron2) was significantly greater than at dendritic spine or shaft synapses found in area CA1. Symmetric synaptic junctions were observed on the CA1 pyramidal cell somas and dendritic shafts in thin-sectioned preparations. These synapses typically exert an inhibitory action mediated by gamma-aminobutyric acid. In freeze-fracture preparations, large varicosities were found apposed to the pyramidal somal and dendritic membranes, but there were no specializations of particle distribution on either the extracellular or the cytoplasmic half of the fractured postsynaptic membranes. This finding parallels observations from freeze-fracture preparations of other GABAergic synapses in the central nervous system.

Animals↗

PubMed1985

Ultrastructural study of cholecystokinin-immunoreactive cells and processes in area CA1 of the rat hippocampus.

We used light and electron microscopic immunocytochemical methods to examine the structure of neuronal perikarya and processes containing cholecystokinin-like immunoreactivity (CCK-IR) in area CA1 of the rat hippocampus. The morphology of stained perikarya, their positions within all laminae, and the orientation of their dendrites indicate that CCK-IR is located in interneurons. These cells were seen in the electron microscope to have deeply folded nuclei and to receive both symmetric and asymmetric synaptic junctions on their cell somata and dendritic shafts. Their dendrites are essentially spine-free, but form bulges at the site of some asymmetric synaptic junctions. Axonal varicosities containing CCK-IR make symmetric synaptic junctions with cell somata and dendritic shafts of both pyramidal and non-pyramidal neurons. In addition, CCK-IR varicosities form symmetric junctions with unstained non-pyramidal neurons and with CCK-IR cells, suggesting either recurrent innervation of one cell on itself or interaction between interneurons. The presence of CCK-IR varicosities and synaptic junctions on pyramidal cells is in agreement with physiological data which indicate that CCK has a direct postsynaptic action. The observation of CCK-IR varicosities forming synaptic junctions on non-pyramidal cells suggests that CCK might also modify the response of interneurons.

Animals↗

PubMed1984

Developmental onset of long-term potentiation in area CA1 of the rat hippocampus.

Long-term potentiation (l.t.p.) was studied in area CA1 of rat hippocampal slices during development at post-natal days 1-8, 15 and 60. Tetanic stimulation at 100 Hz for 1 s was delivered to the fibres in stratum radiatum and the time course of potentiation was recorded in stratum pyramidale for 20 min after tetanus. L.t.p. was measured at 20 min post-tetanus as an increase in the amplitude of the population spike. The time course and magnitude of post-tetanic potentiation (p.t.p.) differed with age. For 60-day-old animals p.t.p. was seen as a maximally potentiated response immediately post-tetanus that declined to a smaller potentiated response by 5 min post-tetanus. For animals younger than 15 days the response was also maximally potentiated immediately post-tetanus with subsequent decline. However, the duration of maximal potentiation was shorter and the magnitude was less. A different time course of p.t.p. was observed at 15 days. The maximal potentiation was approximately equal to that seen at 60 days, but instead of declining, the response remained maximally potentiated throughout the entire post-tetanus monitoring period. L.t.p. was first observed at post-natal day 5, and by post-natal days 7 and 8 substantial levels of l.t.p. were seen consistently. The greatest magnitude of l.t.p. was found at 15 days, and was considerably more than that produced at 60 days. When the duration of l.t.p. was monitored for longer than 20 min the response declined back to pretetanus levels by 1-1 1/2 h for animals younger than 15 days. In 15-day-old rats the response remained maximally potentiated for the full 72 min that it was monitored, with no decline. In control experiments of low-frequency stimulation (l.f.s.) at 1/15 s for 100 stimuli, hippocampal slices from 60-day-old animals showed response elevation. In contrast, l.f.s. resulted in response decrement over time for slices from 5-15-day-old animals. Three measures of pretetanus excitability in area CA1 suggested an increase with age. The stimulus intensity required for field excitatory post-synaptic potential (e.p.s.p.) threshold declined, the magnitude of the maximal population spike amplitude increased, and the population spike latency decreased. These results suggest that the magnitude of l.t.p. is not strictly related to the pretetanus excitability of CA1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1983

Evidence for late development of inhibition in area CA1 of the rat hippocampus.

Development of recurrent inhibition in area CA1 of the rat hippocampus was monitored by a paired-pulse stimulation test. Inhibition of the second response was never observed before postnatal day six. In addition, a type of epileptiform activity, referred to as spontaneous unison firing, was observed frequently, only on postnatal days 4 and 5. Together these observations suggest that the inhibitory interneuronal network of area CA1 becomes effective on about postnatal day 6.

Aging↗

PubMed1983

Age differences in a circadian influence on hippocampal LTP.

Data from several experiments on long-term potentiation (LTP) in the rat hippocampus were examined for circadian influence. Incidence and magnitude of LTP produced in both area CA1 and area dentata were analyzed, and a reciprocal light/dark difference was found in the two areas, with pyramidal cells of area CA1 showing more LTP during the light period and granule cells of area dentata showing more LTP during the dark period. In addition, results from experiments on developing animals, suggested that the circadian influence on LTP in either area was not present before postnatal day 20. All of these experiments were from hippocampal slice preparations; therefore, it is important to note that circadian influences on hippocampal LTP are preserved in the in vitro environment where tonic extrahippocampal input has presumably been removed.

Aging↗

PubMed1980

A Golgi impregnation technique for thin brain slices maintained in vitro.

A technique for using routine rapid Golgi impregnation procedures on very thin freshly fixed slices (less than 0.5 mm) of brain tissue is described. The technique was particularly successful with hippocampal slices that were maintained and stimulated in vitro prior to fixation. Thin tissue slices were surrounded by thicker sections of tissue to form a 5 mm thick bundle. The tissue bundle was then processed by a rapid Golgi procedure, 5 days each in chromate osmium and silver nitrate solutions. At the end of this time the thin tissue slices were unwrapped from their thicker protecting tissue sections, embedded in celloidin, cut at 60-100 micrometer thickness on a sliding microtome and mounted in permount under cover glass. Qualitative light microscopic analysis of the rapid Golgi impregnated slices revealed fully impregnated cell bodies, dendrites, dentritic spines, axons and axonal varicosities with minimal background artifact. In contrast, unprotected thin tissue slices showed only a dense black artifact without cells or processes.

Animals↗

PubMed1975

Apparent volumes of distribution of 125-I-lothalamate and inulin in chickens.

The suitability of utilizing 125-I-iothalamate to estimate the volume of extracellular fluid was assessed in ureterally ligated chickens. Subsequent to intravenous administration the movement of labeled iothalamate from the plasma compartment follows closed two-compartment kinetics and equilibration between vascular and extravascular phases is attained in about 20 minutes. The volume of distribution of 125-I-iothalamate prior to and following the influsion of 0.15 M NaCl (equal to 15% of the estimated ECFV) averaged 23.6 plus or minus 0.61 and 28.4 plus or minus 0.22% of the body weight, respectively. The observed postsaline labeled iothalamate space did not differ statistically from the expected value. When administered simultaneously inulin penetrates into an apparent volume that is 75% of the labeled iothalamate space after 60 minutes. The content of 125-I-iothalamate is relatively high in liver and kidney tissue and suggests that these are major sites where removal of the indicator from plasma occur. It is suggested that 125-I-iothalamate, under appropriate conditions, could be used to measure the plasma volume and the extravascular fluid with which plasma is in rapid diffusion equilibrium.

Animals↗

PubMedDate not supplied

The role of transthoracic echocardiography in the management of patients seen in an outpatient cardiology clinic.

Transthoracic two-dimensional (2D) Doppler echocardiography may provide new or additional information in patients, but it is often not known whether the results alter the treatment plan. We investigated whether results of clinically indicated 2D echocardiography were different from the physician's clinical examination or led to changes in management in 200 consecutive outpatients seen in a university-based clinic. A questionnaire was completed by the physician regarding physical findings and treatment plan before 2D echocardiography was performed. After results were known, the physician was asked to report any differences compared with clinical examination or changes in patient management. Most patients (83%) were studied to evaluate left ventricular (LV) or valvular function. 2D echocardiography confirmed clinical assessment in 182 patients (one inadequate 2D echocardiogram) and disclosed a new diagnosis in 17. 2D echocardiography provided additional information, not expected from clinical assessment or history, in 94 patients. Clinical assessment, compared with 2D echocardiography, was concordant in 154 (77%) of 199 patients with regard to LV systolic function but in only 22 (50%) of 44 with valve disease. Alterations in management based on results of 2D echocardiography were instituted in 73 patients (36%), most often manifested by changes in pharmacologic therapy (n = 45; 62%). Results of 2D echocardiography obviated the need for further cardiac evaluation, surgery, or procedures in 30 patients, avoiding additional patient charges of $125,754.00. In contrast, results of 2D echocardiography led to the need for further evaluation, surgery, or procedures in 32 patients, resulting in additional patient charges of $70,860.00. In conclusion, 2D echocardiography provides new or additional information that results in changes in management strategy in one third of patients, and 2D echocardiography offers relative cost savings by avoiding additional procedures.

Adolescent↗

PubMedDate not supplied

Breast cancer screening.

Radiographic imaging of the breast began in the early years of the twentieth century. Continuous advances in film quality, energy sources, targets, grids, and filters have all contributed to superior image resolution. Federal quality standards now regulate screening mammography, and mass screening for breast cancer has become widely accepted in the United States. Wider application of screening has resulted in a dramatic apparent increase in incidence rates of breast cancer; a large proportion of this increase is in ductal carcinoma in situ. During the past 30 years, nine prospective, randomized trials to evaluate the ability of screening mammography to reduce mortality from breast cancer have been completed. These trials show a 30% reduction in mortality for women ages 50-69 years, but the benefit to women aged 40-49 years remains uncertain. This uncertainty is largely attributable to the lack of properly designed and conducted studies to evaluate screening efficacy in younger women. Although there is no biological reason to predict poor screening performance in the younger age groups, the sensitivity of screening mammography is lower in younger women. Additional data suggest that screening intervals longer than 12 months are ineffective in women younger than 50 years. With shorter screening intervals, the cost associated with screening mammography is comparable to other life-saving measures widely applied in the population. New breast imaging techniques hold promise for superior image quality, but they remain investigational as tools for mass screening. Until primary prevention of breast cancer is a reality, mass screening remains available to reduce mortality from breast cancer.

Adult↗

PubMedDate not supplied

Extending unbiased stereology of brain ultrastructure to three-dimensional volumes.

OBJECTIVE: Analysis of brain ultrastructure is needed to reveal how neurons communicate with one another via synapses and how disease processes alter this communication. In the past, such analyses have usually been based on single or paired sections obtained by electron microscopy. Reconstruction from multiple serial sections provides a much needed, richer representation of the three-dimensional organization of the brain. This paper introduces a new reconstruction system and new methods for analyzing in three dimensions the location and ultrastructure of neuronal components, such as synapses, which are distributed non-randomly throughout the brain. DESIGN AND MEASUREMENTS: Volumes are reconstructed by defining transformations that align the entire area of adjacent sections. Whole-field alignment requires rotation, translation, skew, scaling, and second-order nonlinear deformations. Such transformations are implemented by a linear combination of bivariate polynomials. Computer software for generating transformations based on user input is described. Stereological techniques for assessing structural distributions in reconstructed volumes are the unbiased bricking, disector, unbiased ratio, and per-length counting techniques. A new general method, the fractional counter, is also described. This unbiased technique relies on the counting of fractions of objects contained in a test volume. A volume of brain tissue from stratum radiatum of hippocampal area CA1 is reconstructed and analyzed for synaptic density to demonstrate and compare the techniques. RESULTS AND CONCLUSIONS: Reconstruction makes practicable volume-oriented analysis of ultrastructure using such techniques as the unbiased bricking and fractional counter methods. These analysis methods are less sensitive to the section-to-section variations in counts and section thickness, factors that contribute to the inaccuracy of other stereological methods. In addition, volume reconstruction facilitates visualization and modeling of structures and analysis of three-dimensional relationships such as synaptic connectivity.

Algorithms↗