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Biomedical subjects

M Isaacson

Publications and source records attributed to M Isaacson.

At least 19 recordsLinked to original sources
PubMed2003

Brain responses to micro-machined silicon devices.

Micro-machined neural prosthetic devices can be designed and fabricated to permit recording and stimulation of specific sites in the nervous system. Unfortunately, the long-term use of these devices is compromised by cellular encapsulation. The goals of this study were to determine if device size, surface characteristics, or insertion method affected this response. Devices with two general designs were used. One group had chisel-shaped tips, sharp angular corners, and surface irregularities on the micrometer size scale. The second group had rounded corners, and smooth surfaces. Devices of the first group were inserted using a microprocessor-controlled inserter. Devices of the second group were inserted by hand. Comparisons were made of responses to the larger devices in the first group with devices from the second group. Responses were assessed 1 day and 1, 2, 4, 6, and 12 weeks after insertions. Tissues were immunochemically labeled for glial fibrillary acidic protein (GFAP) or vimentin to identify astrocytes, or for ED1 to identify microglia. For the second comparison devices from the first group with different cross-sectional areas were analyzed. Similar reactive responses were observed following insertion of all devices; however, the volume of tissue involved at early times, <1 week, was proportional to the cross-sectional area of the devices. Responses observed after 4 weeks were similar for all devices. Thus, the continued presence of devices promotes formation of a sheath composed partly of reactive astrocytes and microglia. Both GFAP-positive and -negative cells were adherent to all devices. These data indicate that device insertion promotes two responses-an early response that is proportional to device size and a sustained response that is independent of device size, geometry, and surface roughness. The early response may be associated with the amount of damage generated during insertion. The sustained response is more likely due to tissue-device interactions.

Animals↗
PubMed2001

Image reconstruction from electron and X-ray diffraction patterns using iterative algorithms: experiment and simulation.

The hybrid input-output iterative algorithm, which solves the phase problem for scattering from non-periodic objects, is reviewed for application to X-ray and electron diffraction data. Desirable convex constraints, including the sign of the scattering potential for electrons, and compact support, are discussed. The cases of complex and real exit-face wavefunctions, strong and weak phase objects, various supports, and the use of coherent focussed radiation are reviewed. Reconstruction of general complex objects requires accurate knowledge of the support, which should consist of two holes or a triangle in an opaque mask. The support boundaries should be as sharp as possible. Strong phase objects without absorption can be recovered if the support consists of one hole, is accurately known and has sufficiently sharp boundaries. Real and weak phase objects with absorption can be recovered without accurate knowledge of the support area if the support boundaries are sufficiently sharp and the support consists of one or more holes. A sign constraint on the scattering potential is used to recover weak phase objects. The experimental realization of theoretically desirable support conditions is discussed. A two-stage method of finding the support for complex objects is proposed. Experimental results from applying the Gerchberg-Saxton-Fienup HiO-algorithm to coherent electron diffraction patterns are presented, using specially made e-beam lithographed support structures. Images with a resolution of about 5 nm are thus recovered from the intensities alone in coherent electron diffraction patterns from non-periodic objects. Limitations of the present experiments are identified and suggestions made for development of both X-ray and electron work.

Journal Article↗
PubMed2000

Attachment of astroglial cells to microfabricated pillar arrays of different geometries.

We studied the attachment of astroglial cells on smooth silicon and arrays of silicon pillars and wells with various widths and separations. Standard semiconductor industry photolithographic techniques were used to fabricate pillar arrays and wells in single-crystal silicon. The resulting pillars varied in width from 0. 5 to 2.0 micrometer, had interpillar gaps of 1.0-5.0 micrometer, and were 1.0 micrometer in height. Arrays also contained 1.0-micromter-deep wells that were 0.5 micrometer in diameter and separated by 0.5-2.0 micrometer. Fluorescence, reflectance, and confocal light microscopies as well as scanning electron microscopy were used to quantify cell attachment, describe cell morphologies, and study the distribution of cytoskeletal proteins actin and vinculin on surfaces with pillars, wells, and smooth silicon. Seventy percent of LRM55 astroglial cells displayed a preference for pillars over smooth silicon, whereas only 40% preferred the wells to the smooth surfaces. Analysis of variance statistics performed on the data sets yielded values of p > approximately.5 for the comparison between pillar data sets and < approximately.0003 in the comparison between pillar and well data sets. Actin and vinculin distributions were highly polarized in cells found on pillar arrays. Scanning electron microscopy clearly demonstrated that cells made contact with the tops of the pillars and did not reach down into the spaces between pillars even when the interpillar gap was 5.0 microm. These experiments support the use of surface topography to direct the attachment, growth, and morphology of cells. These surfaces can be used to study fundamental cell properties such as cell attachment, proliferation, and gene expression. Such topography might also be used to modify implantable medical devices such as neural implants and lead to future developments in tissue engineering.

Actins↗
PubMed2000

Aligned microcontact printing of micrometer-scale poly-L-lysine structures for controlled growth of cultured neurons on planar microelectrode arrays.

We describe a method for producing high-resolution chemical patterns on surfaces to control the attachment and growth of cultured neurons. Microcontact printing has been extended to allow the printing of micron-scale protein lines aligned to an underlying pattern of planar microelectrodes. Poly-L-lysine (PL) lines have been printed on the electrode array for electrical studies on cultured neural networks. Rat hippocampal neurons showed a high degree of attachment selectivity to the PL and produced neurites that faithfully grew onto the electrode recording sites.

Animals↗
PubMed1999

Cerebral astrocyte response to micromachined silicon implants.

The treatment of neurologic disorders and the restoration of lost function due to trauma by neuroprosthetic devices has been pursued for over 20 years. The methodology for fabricating miniature devices with sophisticated electronic functions to interface with nervous system tissue is available, having been well established by the integrated circuit industry. Unfortunately, the effectiveness of these devices is severely limited by the tissue reaction to the insertion and continuous presence of the implant, a foreign object. This study was designed to document the response of reactive astrocytes in the hope that this information will be useful in specifying new fabrication technologies and devices capable of prolonged functioning in the brain. Model probes fabricated from single crystal silicon wafers were implanted into the cerebral cortices of rats. The probes had a 1 x 1-mm tab, for handling, and a 2-mm-long shaft with a trapezoidal cross-section (200-microm base, 60microm width at the top, and 130 microm height). The tissue response was studied by light and scanning electron microscopy at postinsertion times ranging from 2 to 12 weeks. A continuous sheath of cells was found to surround the insertion site in all tissue studied and was well developed but loosely organized at 2 weeks. By 6 and 12 weeks, the sheath was highly compacted and continuous, isolating the probe from the brain. At 2 and 4 weeks, the sheath was disrupted when the probe was removed from the fixed tissue, indicating that cells attached more strongly to the surface of the probe than to the nearby tissue. The later times showed much less disruption. Scanning electron microscopy of the probes showed adherent cells or cell fragments at all time points. Thus, as the sheath became compact, the cells on the probe and the cells in the sheath had decreased adhesion to each other. Immunocytochemistry demonstrated that the sheath was labeled with antibodies to glial fibrillary acidic protein (GFAP), an indicator for reactive gliosis. The tissue surrounding the insertion site showed an increased number of GFAP-positive cells which tended to return to control levels as a function of time after probe insertion. It was concluded that reactive gliosis is an important part of the process forming the cellular sheath. Further, the continuous presence of the probe appears to result in a sustained response that produces and maintains a compact sheath, at least partially composed of reactive glia, which isolates the probe from the brain.

Animals↗
PubMed1999

Medical information on the internet

Caveat lector et viewor - Let the reader and viewer beware! Thus sayeth Silberg et al.1 in their brief account of the apparent incompatibility between freedom of the press and accuracy of medical information. They point out that the problem is too much, rather than too little information. The Internet, where every Tom, Dick and Harry can be their own author, editor and publisher, is widely available to both lay and professional browsers. This has brought about a situation where a multitude of information seekers equipped with one or other search engine, wallow through a morass of material that ranges from first class research data to profound garbage. Without a medical background it is well-nigh impossible for the average person-in-the-street to sort the wheat from the chaff.

Journal Article↗
PubMed1995

Neisseria meningitidis with decreased susceptibility to penicillin in Saskatchewan, Canada.

Moderately penicillin-resistant Neisseria meningitidis is rare in North America. We report an outbreak of meningococcal disease in Saskatoon, Saskatchewan, Canada, with serogroup C N. meningitidis. The MICs of penicillin ranged from 0.12 to 0.25 micrograms/ml, and all isolates showing decreased susceptibility had identical genomic fingerprints when they were compared by pulsed-field gel electrophoresis. Our data indicate that N. meningitidis that is moderately resistant to penicillin is prevalent in Saskatchewan, Canada.

Adolescent↗
PubMed1995

Evaluation of the Cult-Dip Plus dip slide method for urinary tract infection.

AIM: To evaluate the Cult-Dip Plus (Merck, Germany), a bacteriological culture test for detecting uropathogens. METHODS: Cult-Dip Plus consists of Brolacin (CLED) and MacConkey agar, each containing methylumbelliferylglucuronide (MUG). Using 1022 urine samples, this product was compared with the routine method of calibrated loop inoculated CLED and blood agar for screening urine for uropathogens. The MUG test for identifying Escherichia coli was also evaluated. RESULTS: Compared with the routine method, Cult-Dip Plus has a sensitivity, specificity, positive predictive value and negative predictive value of 88.3%, 98.0%, 91.9%, and 97.1%, respectively. The MUG test correctly identified 92% of E coli isolates with a sensitivity, specificity and positive predictive value of 91.6%, 95.2%, and 93.6%, respectively. CONCLUSION: Cult-Dip Plus appears to be an alternative method to the calibrate loop method for detecting uropathogens. The MUG test permits rapid, reliable and inexpensive identification of E coli.

Bacteriological Techniques↗
PubMed1994

Evaluation of the Urotest AB antibacterial substance detection test.

The Urotest AB was used to detect antimicrobial substances in urine samples. Of 1022 urine specimens evaluated, Urotest AB detected inhibitors in 38.9%. Of 159 urine specimens from patients thought to be taking an antibiotic, inhibitors were detected in 80.5%. This test may help to explain culture negative urine samples from symptomatic patients, and could help elucidate treatment failures and the epidemiology of antibiotic resistance.

Anti-Bacterial Agents↗
PubMed1987

A radioimmunoassay for the diagnosis of malaria.

A newly developed radioimmunoassay for the diagnosis of malaria has been tested in South Africa. The radioimmunoassay is an antibody binding-inhibition assay, based on a monoclonal antibody (D5) cross-reacting with Plasmodium berghei and P. residual binding activity was tested on antigen-coated microtiter plates. A sample was considered positive if it inhibited binding of the antibodies to an extent exceeding that of the microscopically negative blood samples. Blood was collected on 3 separate occasions from a total of 530 individuals living in a malaria-endemic area and was examined by radioimmunoassay and microscopy. Group 1, consisting of 194 samples, yielded 12 samples positive by microscopy and 10 of these (83%) were also positive by radioimmunoassay. One sample in this group was "positive" in the radioimmunoassay but negative on microscopy (false positive). In the 320 samples of group 2, 13 were positive by microscopy and 6 (46%) by radioimmunoassay. Group 3, which included 16 samples preselected as positive by microscopic examination and 16 controls, was examined after 4 weeks storage at -20 degrees C. Twelve samples (75%) were positive by radioimmunoassay. Tests carried out to determine the effect of blood storage on the activity of the antigen indicated that activity was preserved with little loss over a 3-month period.

Animals↗
PubMed1983

Viral haemorrhagic fever surveillance in Kenya, 1980-1981.

Following two cases of Marburg virus disease in Kenya in 1980, viral haemorrhagic fever surveillance was undertaken in western Kenya. Over a 21-month period investigations, including virus isolation attempts, patient and contact serology, visits to areas where suspected cases occurred, interviewing family members and neighbours of suspected cases and following up any additional illnesses in these areas, were carried out. During the study two cases were found that were likely to have been Ebola haemorrhagic fever based on rising antibody titres or positive serology in contacts. Diagnoses of hepatitis A, hepatitis B, malaria, bacterial septicaemia or other causes were arrived at in 24 cases. No diagnosis could be made in 26 instances. 741 human sera were tested for antibodies against Marburg, Ebola, Congo haemorrhagic fever, Rift Valley fever or Lassa fever viruses by indirect fluorescence. Eight sera were positive for Ebola virus antibodies, all of which were from suspected cases or contacts of suspected cases. Two sera were antibody positive to Congo virus and one had antibodies against Rift Valley fever virus. No Marburg or Lassa virus antibodies were detected.

Adolescent↗
PubMed1979

Plague antibody in large African mammals.

Plague hemagglutinating antibodies to a titer of 1:1,024 were demonstrated in 6.6% of buffalo and 0.3% of elephant sera tested 1 year after a plague epidemic in the same area.

Animal Diseases↗
PubMed1978

The use of electron energy loss spectroscopy for studying membrane architecture: a preliminary report.

Some initial measurements of interest with respect to the use of energy loss spectroscopy (ELS) in the electron microscope are reported. We have obtained energy loss spectra in the region less than 15 eV energy loss for three components of biological components; lecithin, cholesterol and spectrin. Some indications of the effect of electron beam damage on the cholesterol spectrum are shown. In addition, energy loss pictures of erythrocyte membrane fragments are demonstrated for various energy losses less than 40 eV (taken with 0.75 eV width window) and it is shown that an individual ferritin molecule can be identified on the basis of its iron MII-III excitation line. From the results of the preliminary data we have discussed the possibilities of ELS for studies of biological membranes.

Carbohydrates↗