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Biomedical subjects

H McDermott

Publications and source records attributed to H McDermott.

17 recordsLinked to original sources
PubMed1998

A programmable sound processor for advanced hearing aid research.

A portable sound processor has been developed to facilitate research on advanced hearing aids. Because it is based on a digital signal processing integrated circuit (Motorola DSP56001), it can readily be programmed to execute novel algorithms. Furthermore, the parameters of these algorithms can be adjusted quickly and easily to suit the specific hearing characteristics of users. In the processor, microphone signals are digitized to a precision of 12 bits at a sampling rate of approximately 12 kHz for input to the DSP device. Subsequently, processed samples are delivered to the earphone by a novel, fully-digital class-D driver. This driver provides the advantages of a conventional class-D amplifier (high maximum output, low power consumption, low distortion) without some of the disadvantages (such as the need for precise analog circuitry). In addition, a cochlear implant driver is provided so that the processor is suitable for hearing-impaired people who use an implant and an acoustic hearing aid together. To reduce the computational demands on the DSP device, and therefore the power consumption, a running spectral analysis of incoming signals is provided by a custom-designed switched-capacitor integrated circuit incorporating 20 bandpass filters. The complete processor is pocket-sized and powered by batteries. An example is described of its use in providing frequency-shaped amplification for aid users with severe hearing impairment. Speech perception tests confirmed that the processor performed significantly better than the subjects' own hearing aids, probably because the digital filter provided a frequency response generally closer to the optimum for each user than the simpler analog aids.

Biomedical Engineering↗
PubMed1997

Human fertilization with round and elongated spermatids.

Human spermatids from ejaculate and testicular tissue have been utilized for evaluating human fertilization by intracytoplasmic sperm injection (ICSI) and, where possible, compared with spermatozoa utilizing sibling oocytes. Round and elongated spermatids obtained from ejaculates were either prepared through Percoll gradients or isolated and washed individually using subzonal insemination needles (SUZI; 10-14 microm internal diameter). Seminiferous tubules obtained after biopsy were placed into HEPES-buffered Earle's medium and dissected using 21-gauge needles. Spermatogenic cells and spermatozoa were isolated and washed individually using SUZI needles. Spermatozoa were subsequently injected into the ooplasm using 5 microm (internal diameter) ICSI needles, whereas 8-9 microm (internal diameter) needles were used for spermatid injection. Only metaphase II oocytes (n = 207) were injected: 64 with round spermatids, 92 with elongated spermatids and 51 with spermatozoa; the fertilization rate was 30, 24 and 67% respectively. There was a significant (P < 0.001) increase in the fertilization rate using spermatozoa compared with spermatids. The fertilization rate was not different between round and elongated spermatids, although the fertilization rates for round and elongated spermatids in the ejaculate were 33 and 18% respectively, compared with 22 and 38% respectively when testicular spermatids were utilized. In three patients sibling oocytes were used to compare round and elongated spermatids found in the ejaculate with spermatozoa extracted from seminiferous tubules. The fertilization rate was 24% for spermatids and 79% for testicular spermatozoa. This result suggests that, should only spermatids be available in the ejaculate, a testicular biopsy in the hope of obtaining testicular spermatozoa would be worth while.

Cell Size↗
PubMed1995

Immunohistochemical localization of ubiquitin cross-reactive protein in human tissues.

Ubiquitin cross-reactive protein (UCRP) is an interferon-inducible ubiquitin homologue which is constitutively present in cells and can be conjugated to other proteins. Using a characterized polyclonal antiserum to UCRP, immunohistochemical localization of UCRP was performed on paraffin-processed normal human tissues and in human tissues known to contain ubiquitinated intracellular inclusions. The antibody to UCRP immunostained lymphoid cells, striated and smooth muscle, several epithelia, and neurons. The level of staining varied greatly between tissues but was in a consistent punctate pattern. Localization to neuromuscular junctions and striations is similar to that described for antisera to ubiquitin-protein conjugates. Inclusion bodies characterized by immunoreactivity to anti-ubiquitin were not detected by the antibody to UCRP. Importantly, because UCRP may also be detected by antisera to conjugated ubiquitin, future studies on the distribution of ubiquitin in tissue sections must now take account of possible cross-reactivity with UCRP.

Cross Reactions↗
PubMed1995

A positive correlation between expression of beta 1-integrin cell adhesion molecules and fertilizing ability of human spermatozoa in vitro.

The purpose of this study was to investigate firstly whether beta 1-integrin cell adhesion molecules are expressed by human spermatozoa, and secondly whether there is any relationship between the expression of beta 1-integrin cell adhesion molecules and the fertilizing ability of human spermatozoa in vitro. A total of 50 semen samples were examined. The samples were obtained from the male partners of couples undergoing in-vitro fertilization (IVF) for either unexplained, tubal or male factor infertility. A panel of six monoclonal antibodies against beta 1-integrin cell adhesion molecules and immunohistochemical techniques were used to identify the presence of these molecules on the spermatozoa. The percentage of spermatozoa showing strong immunolabelling with each monoclonal antibody was assessed in each sample. The relationship between these results and the aetiology of infertility and incidence of fertilization was examined. beta 1-Integrins, and primarily the ones with alpha 4-, alpha 5- and alpha 6-chains, were expressed by human spermatozoa. Compared with semen samples from unexplained or male factor infertility patients, samples from tubal infertility patients had a significantly higher (P < 0.05) percentage of spermatozoa expressing adhesion molecules. There was a positive correlation between the expression of alpha 4, alpha 5 and alpha 6 adhesion molecules and the fertilizing ability of spermatozoa. The positive correlation between the presence of certain beta 1-integrin cell adhesion molecules and the fertilizing ability of human spermatozoa suggests that integrins may be putative determinants in egg-sperm recognition and interaction.

Adult↗
PubMed1992

alpha B crystallin expression in non-lenticular tissues and selective presence in ubiquitinated inclusion bodies in human disease.

alpha B crystallin is a lens protein which has homology with the small heat-shock proteins and is also expressed in non-lenticular tissues. Polyclonal antibodies have been raised to a synthetic peptide corresponding to residues 1-10 of alpha B crystallin. The antiserum detects a 20 kDa polypeptide on nitrocellulose replicas after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate of extracts of heart muscle known to be rich in alpha B crystallin. Staining of normal human tissues reveals immunoreactivity of lens capsular epithelium, skeletal muscle, cardiac muscle, smooth muscle, renal tubular epithelium, Schwann cells, and glial cells, as has been described by other workers. In addition, positive staining of normal thyroid epithelium, colonic epithelium, and stratified squamous epithelium was seen. Tissues known to contain ubiquitinated inclusion bodies were immunostained with the anti-alpha B-crystallin antiserum. Staining of cortical Lewy bodies, astrocytic Rosenthal fibres, and hepatic Mallory bodies was seen, but only a proportion of inclusions were positive. Neurones containing the ubiquitinated inclusions of Alzheimer's disease were only very rarely immunostained and the ubiquitinated inclusions of motor neurone disease were not detected by the antiserum. Reactive astrocytes in cerebral tissues were strongly immunostained. The results suggest that alpha B crystallin is involved in the formation of ubiquitinated inclusion bodies that have associated intermediate filaments and support previous observations on the localization of a brain-specific ubiquitin carboxy-terminal hydrolase which similarly divides ubiquitinated filamentous inclusions in the central nervous system into two main groups.

Alzheimer Disease↗
PubMed1991

Ubiquitin-protein conjugates and alpha B crystallin are selectively present in cells undergoing major cytomorphological reorganisation in early chicken embryos.

Ubiquitin-protein conjugates and alpha B crystallin are detected immunohistochemically in cells undergoing extensive morphological reorganisation in early chicken embryos. Cytoplasmic ubiquitinated proteins and alpha B crystallin are coordinately found in cells of the lens, notochord and myotome. The antigens appear in the myotome cells precisely at the point at which the cells begin to migrate from the dorsomedial lip of the dermamyotome. The findings indicate that ubiquitin and alpha B crystallin may have a coordinate role in the extensive architectural remodeling which occurs in these developing tissues in the early chick embryo. Some form of functional association between protein ubiquitination and alpha B crystallin in cells may explain why alpha B crystallin is found with ubiquitin-protein deposits in some neurodegenerative diseases.

Amino Acid Sequence↗
PubMed1991

Ubiquitin and the lysosome system: molecular immunopathology reveals the connection.

Considerable advances in our understanding of the molecular pathology of the major human neurodegenerative diseases have been made by the use of ubiquitin immunocytochemistry. The technique demonstrates that filamentous inclusions and vacuoles contain ubiquitin-protein conjugates. The molecular structure of the filaments and the morphological type of vacuoles is not completely understood but there is evidence that some of the filamentous inclusions contain intermediate filaments and the perinuclear distribution of the vacuoles resemble the distribution of intraneuronal lysosomes. Intermediate filaments and lysosomes are involved in the sequestration and degradation of viral membrane proteins in tissue culture cells. Immunogold electron microscopical and biochemical evidence indicates that ubiquitin-protein conjugates are normally considerably enriched in the lysosomes of fibroblasts relative to all other organelles. Immunogold electron microscopy shows a similar enrichment of ubiquitin-protein conjugates in the dense lysosomes of granulocytic precursor cells in the bone marrow. Filamentous inclusions showing several of the features seen in inclusions in the neurodegenerative diseases are seen in Epstein-Barr virus transformed lymphoblastoid cells. Immunohistochemistry shows that the inclusions contain vimentin intermediate filaments, the latent membrane transforming protein of the virus, ubiquitin-protein conjugates, and a heat-shock protein 70 (hsp 70). Immunohistochemistry and immunogold electron microscopy demonstrate that the latent membrane protein, ubiquitin-protein conjugates and hsp 70 are in lysosomes entwined in an intermediate filament cage centred on the microtubule organising centre. The implications of the combined observations for our understanding of the cell stress response in degenerating neurones and in virally infected cells are discussed.

Heat-Shock Proteins↗
PubMed1991

The role of protein ubiquitination in neurodegenerative disease.

Ubiquitin immunocytochemistry with an antiserum which reacts with ubiquitin-protein conjugates demonstrates the presence of ubiquitinated proteins in filamentous inclusions found in neurones in the major human neurodegenerative diseases, i.e. Alzheimer's disease, diffuse Lewy body disease, motor neurone disease. Ubiquitin immunohistochemistry has revolutionized the neuropathological diagnosis of dementia showing that diffuse Lewy body disease is not, as previously supposed, a rare cause of dementia. The filamentous inclusions in neurones in the human neurodegenerative diseases can be divided into at least two types based on recent immunocytochemical studies. We have shown that a ubiquitin-carboxyl terminal hydrolase is present in Lewy bodies but not in neurofibrillary tangles in Alzheimer's disease. This observation is significant since it indicates that molecular pathological mechanisms in neurones in diffuse Lewy body disease are fundamentally different to Alzheimer's disease. Ubiquitin-protein conjugates are also found in vacuoles in areas of granulovacuolar degeneration in hippocampal neurones in Alzheimer's disease and in granulovacuoles in neurones of scrapie infected mouse brain. These locations suggest that ubiquitinated protein are present in the lysosome-related system of neurones. We have recently shown that ubiquitin-protein conjugates are indeed enriched some 12-fold in the lysosomes of normal fibroblasts and lymphocytes.

Brain Diseases↗
PubMed1990

Ubiquitin carboxyl-terminal hydrolase (PGP 9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative diseases.

The recent discovery that brain PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase suggests that the role of this protein should be studied in relation to ubiquitinated cellular inclusions characteristic of several chronic human degenerative diseases. Formalin-fixed, paraffin-processed sections known to contain ubiquitin-protein conjugate immunoreactivity in cortical Lewy bodies, neurofibrillary tangles, Rosenthal fibres, Pick bodies, spinal inclusions in motor neurone disease, and Mallory's hyaline in alcoholic liver disease were immunostained to localize PGP 9.5. The majority of cortical Lewy bodies in diffuse Lewy body disease showed immunoreactivity for PGP 9.5. In Alzheimer's disease, only a minority of loosely arranged globose-type neurofibrillary tangles were immunostained together with a minority of neurites surrounding senile plaques. In cerebellar astrocytomas, the periphery of the majority of Rosenthal fibers was immunostained in addition to strong diffuse cytoplasmic immunostaining in some astrocytes lacking apparent Rosenthal fibers. In Pick's disease, there was no immunostaining of inclusions but there was intense immunostaining of swollen Pick cells. No spinal inclusions in motor neurone disease were stained; however, anterior horn neurones appear to show increased levels of PGP 9.5 compared with those from control cases. No immunostaining of hepatic Mallory's hyaline was demonstrable, which accords with suggestions that PGP 9.5 is a tissue-specific ubiquitin C-terminal hydrolase isoenzyme. The differential detection of a ubiquitin C-terminal hydrolase in different forms of ubiquitinated inclusion body in the nervous system may form the basis of a method for assessment of the staging of inclusion body biogenesis and give insight into the dynamics of inclusion body formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1990

Ubiquitin conjugate immunoreactivity in the brains of scrapie infected mice.

Sections of brain from normal mice or clinically-ill mice infected with either the 87V or the ME7 strains of sheep scrapie were immunostained to show the localization of ubiquitin-protein conjugates or a specific marker of disease, the scrapie-associated fibril protein (PrP). In both scrapie models immunoreactive ubiquitin-protein conjugates were seen in thread-like structures found throughout the neuropil, in inclusion bodies within vacuolated neurones, and in areas surrounding anti-PrP positive amyloid plaques. The PrP protein was visualized in diffuse deposits in highly vacuolated parts of the scrapie-affected brain, and focally in amyloid plaques, microglia and neuronal processes. The ubiquitin-protein conjugate staining of scrapie amyloid plaques is very similar to that seen in the plaques of Alzheimer's disease. The ubiquitinated intraneuronal inclusion bodies seen in scrapie resemble the granulovacuolar lesions also seen in Alzheimer's disease, but appear much larger and possibly correspond to material in giant autophagic vacuoles. We suggest that these inclusions may be the result of ubiquitinated abnormal proteins being directed to the lysosomal system, and that scrapie and Alzheimer's disease share at least some common processes of neurodegeneration.

Amyloid↗
PubMed1989

An advanced multiple channel cochlear implant.

An advanced multiple channel cochlear implant hearing prosthesis is described. Stimulation is presented through an array of 20 electrodes located in the scala tympani. Any two electrodes can be configured as a bipolar pair to conduct a symmetrical, biphasic, constant-current pulsatile stimulus. Up to three stimuli can be presented in rapid succession or effectively simultaneously. For simultaneous stimulation, a novel time-division current multiplexing technique has been developed to obviate electrode interactions that may compromise safety. The stimuli are independently controllable in current amplitude, duration, and onset time. Groups of three stimuli can be generated at a rate of typically 500 Hz. Stimulus control data and power are conveyed to the implant through a single transcutaneous inductive link. The device also incorporates a telemetry system that enables electrode voltage waveforms to be monitored externally in real time. The electronics of the implant are contained almost entirely on a custom designed integrated circuit. Preliminary results obtained with the first patient to receive the advanced implant are included.

Cochlear Implants↗
PubMedDate not supplied

Can we justify spermatid microinjection for severe male factor infertility?

During 1995 and 1996 the first spermatid pregnancies were announced with both round spermatid (ROSI) and elongated spermatid (ELSI) injections. These publications were flanked by live births from ROSI in a number of animal species, with resulting offspring appearing normal, healthy and fertile. However, the live births in humans heralded a scientific and ethical debate on the clinical use of this technology; and in a number of countries nationwide moratoria prohibiting spermatid microinjection were enjoined. Concerns surrounded the biological condition of spermatids and clinical implications of utilizing an immature spermatozoon for conception. Nevertheless, case reports and a few scientific studies on human spermatid conception have been published in recent years, and further polemic on testicular histopathology and prognosis has ensued. This paper reviews the current arguments on the clinical use of ROSI and ELSI, and evaluates the biology of the main contributory components of a spermatozoon to the subsequent embryo, namely the genetic material, the microtubular organizing complex and the putative oocyte activating factor. We also consider the relevant testicular histopathology and likely outcome in the context of the current birth rate from ROSI and ICSI. We conclude by considering the way forward for infertile men who require this technology to become genetic fathers, and whether the time is now appropriate to consider clinical trials.

Clinical Trials as Topic↗