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Biomedical subjects

J Lowe

Publications and source records attributed to J Lowe.

At least 163 records · Page 9Linked to original sources
PubMed1991

Megaduodenum due to hollow visceral myopathy successfully managed by duodenoplasty and feeding jejunostomy.

A 29 year old man with a history of childhood polymyositis developed insulin dependent diabetes and was found coincidentally to have chronic intestinal pseudo-obstruction due to visceral myopathy. Multiple full thickness biopsy specimens showed severe disease in the duodenum and the proximal jejunum only, with less involvement distally. Total parenteral nutrition has been avoided for more than a year by enteral feeding through a fine bore jejunostomy catheter positioned with its tip in the distal jejunum.

Adult↗
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↗
PubMed1991

Reflex sympathetic dystrophy of the patellofemoral joint.

Eighteen patients with a diagnosis of reflex sympathetic dystrophy (RSD) affecting the knee were reviewed. Minor isolated injuries and operations about the knee triggered the original episode. The symptoms, regardless of location and mechanism of injury, occurred in the patellofemoral joint. Roentgenographic features of patchy demineralization and abnormal uptake on a 99mTc scan were typically located in the patella and corresponding femoral articular surface. At the initial stage of the syndrome, pain, hypersensitivity to touch, and inhibition of the quadriceps muscle were the most prominent features. In the later stages of the syndrome, functional instability due to quadriceps weakness created dependence on a knee brace or crutch support. Six patients whose RSD was initially misdiagnosed underwent numerous unsuccessful surgical procedures. In three of these patients, the knee was ultimately fused. All patients had an initial isolated knee injury (usually after minor trauma), and prolonged periods of immobilization and a cast, and 12 of the 18 patients were involved with workers' compensation. Early diagnosis and prompt treatment with an epidural block, followed by intensive physiotherapy, are recommended. A personal doctor/patient relationship that offers guidance and encouragement is key to successful management of this syndrome.

Accidents, Occupational↗
PubMed1991

Pyogenic vertebral osteomyelitis with paralysis. Prognosis and treatment.

In the interval between 1983 and 1988, 14 patients were treated for pyogenic spondylitis complicated by neurologic compromise. There were nine males and five females aged 39-80 years. The average time between onset of symptoms and diagnosis was 2.8 months. Predisposing factors were diabetes mellitus in four patients and urinary tract infections in five patients. The infection was blood borne in all 14 patients. In two patients, the infection was superimposed on a recent vertebral fracture. The cervical spine was involved in one patient; the thoracic spine in seven; and the lumbar spine in six patients. Six patients presented with a Frankel B paralysis, six with a Frankel C paralysis, and two with grade D paralysis. The neurologic symptoms lasted between one day and six weeks before surgery. Twelve patients had anterolateral decompression. Two of the 12 patients had a second stage posterior stabilization. Two patients were deemed inoperable. All surviving patients were managed by parenteral antibiotics for three to six weeks followed by enteral route for a total of three to six months. All 12 operated patients had a significant neurologic improvement (one grade or more on the Frankel scale) with solid interbody fusion.

Adult↗
PubMed1990

Neurodevelopmental performance of very-low-birth-weight infants with mild periventricular, intraventricular hemorrhage. Outcome at 5 to 6 years of age.

The neurodevelopmental outcome of 38 very-low-birth-weight neonates (birth weight, less than 1501 g) was followed up prospectively from birth to 5 to 6 years of age to assess the neurodevelopmental sequelae of mild periventricular, intraventricular hemorrhage (grades I and II). All neonates were screened for periventricular, intraventricular hemorrhage at 5 to 10 days of age. Eleven incurred a mild periventricular, intraventricular hemorrhage (group 1) and 27 had no periventricular, intraventricular hemorrhage (group 2). Each of the infants was neurodevelopmentally normal at 1 to 2 years of age. The 38 children were matched by race, age, sex, and socioeconomic status with control children (group 3) who had been born at term. On outcome measurements at 5 to 6 years of age, groups 1 and 2 scored significantly lower than group 3 on the combined test measurements and on three of the four individual measurements. Group 1 scored significantly lower than group 2 on the combined test measurements only. These data indicate that very-low-birth-weight infants are at risk for learning problems. Although children with mild periventricular, intraventricular hemorrhage did not demonstrate a significant deficit on individual test scores, the significant difference on the combined battery suggests that mild periventricular, intraventricular hemorrhage has an adverse effect on global performance.

Cerebral Hemorrhage↗
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↗
PubMed1990

Characterization of new IgG lambda myeloma plasma cell line (EJM): a further tool in the investigation of the biology of multiple myeloma.

A new IgG lambda myeloma plasma cell line known as EJM was established from a peritoneal effusion from a patient with extramedullary myeloma. The EJM cells have a plasmablastic morphology with abundant rough endoplasmic reticulum and grow in liquid culture with a doubling time of 72 h and a labelling index of 36%. In addition to cytoplasmic IgG lambda, the cells are positive for CD9, 20, 32, 38, 44, 54, 71, 78, MHC Class II DR, DP and DQ. Studies on the control of the cell line proliferation by cytokines have demonstrated stimulation with interleukin 6. In contrast interferon alpha produces marked inhibition of proliferation in doses of greater than 100 units/ml. The culture conditions and the importance of accessory cells and cytokines in supporting myeloma plasma cell growth in vitro are discussed.

Ascitic Fluid↗
PubMed1990

Subepithelial basement membrane deposition and intermediate filament expression in choroid plexus neoplasms and ependymomas.

The pattern of basement membrane deposition was investigated in benign and malignant choroid plexus tumours using an immunocytochemical method to detect laminin, an intrinsic basement membrane component. The results were compared with intracranial ependymomas and myxopapillary ependymomas of the filum terminale. Expression of the intermediate filaments cytokeratin and glial fibrillar acidic protein (GFAP) and the epithelial marker carcino-embroyonic antigen (CEA) was also assessed. Laminin was detected in a subepithelial location in all the choroid plexus tumours but in none of the ependymomas, although basement membrane fragmentation was seen in the choroid plexus carcinomas. In contrast, GFAP was present in all the types of tumour examined. Cytokeratin (as detected by CAM 5.2) was present in all the choroid plexus lesions and also in the ependymomas arising in the spinal canal. CEA was not detected. We conclude that immunostaining for laminin assists distinction between choroid plexus tumors and papillary ependymomas and between benign and malignant choroid plexus tumours.

Basement Membrane↗
PubMed1990

Ubiquitin, cell stress and diseases of the nervous system.

Cells, including those of the nervous system, respond to damage by an increase in the synthesis of a family of proteins called 'stress proteins' which are amongst the most conserved gene products in evolution suggesting fundamental roles in cell metabolism. Stress-induced proteins have functions in normal cells, particularly for the importation of protein into membrane-limited organelles, and their up-regulation following stress is thought to be cytoprotective, by protecting proteins and organelles from damage. Ubiquitin is an important protein induced by cell stress. It is only found in nucleated cells and has several known functions; the most investigated being as a co-factor for the non-lysosomal intracellular degradation of abnormal or short lived proteins. Morphological studies using immunohistochemistry to localize ubiquitin protein conjugates have revealed that ubiquitin is a component of many of the filamentous inclusion bodies characteristic of neurodegenerative diseases, suggesting activation of a common neuronal response in this type of disease process. Immunohistochemical localization of ubiquitin conjugates has provided a new tool for the sensitive detection of such inclusions and has resulted in the identification of novel inclusion bodies in all cases of motor neuron disease. Preliminary work on enzymes involved in ubiquitin metabolism suggest that there are several possible mechanisms for the formation of inclusion bodies and may provide indirect evidence for the dynamics of inclusion body formation. Work in other areas of pathology indicate important roles for the stress proteins in immune surveillance and autoimmunity and it is likely that the general principles which are currently evolving will also have an impact in neuropathology.

Animals↗
PubMed1990

Esmolol for treatment of intraoperative tachycardia and/or hypertension in patients having cardiac operations. Bolus loading technique.

Esmolol, administered as a bolus followed by continuous infusion, was used to treat the occurrence of transient tachycardia and hypertension or tachycardia alone before cardiopulmonary bypass in 45 patients. The study was conducted in two phases. Phase I (15 patients) was a dose-finding study and phase II (30 patients) was a randomized, double-blind, placebo-controlled efficacy study. All patients received the last dose of their usual beta-adrenergic blocker the night before the operation and were anesthetized with midazolam, vecuronium, and enflurane in oxygen. Treatment criteria were either a systolic blood pressure greater than 140 mm Hg and a heart rate greater than 70 or a heart rate greater than 80 beats/min. In phase I, graduated doses of esmolol were given to successive patients. A dose of 80 mg followed by a 12 mg/min infusion was declared effective. Phase II patients were randomized to receive esmolol (n = 16) or placebo (n = 14). Hemodynamic data were collected at baseline and 1, 3, 5, and 10 minutes after the administration of esmolol. Plasma norepinephrine was measured at baseline, 1, and 10 minutes. Esmolol significantly (p less than 0.05) reduced heart rate at 1, 3, 5, and 10 minutes but did not change blood pressure, pulmonary artery diastolic pressure, right atrial pressure, cardiac output, or systemic vascular resistance. Our results show that a bolus loading dose of esmolol is safe and effective in the treatment of tachycardia in patients with ischemic heart disease and that esmolol rapidly blocks the beta-adrenergic effects of norepinephrine associated with surgical stress.

Adrenergic beta-Antagonists↗
PubMed1990

Intraventricular neurocytoma: a clinical and pathological study of three cases and review of the literature.

Three patients with a recently described tumor of neuronal origin, intraventricular neurocytoma, are presented. These tumors occur as intraventricular lesions in young patients, and the prognosis after surgical treatment is favorable. The initial pathological diagnosis of intraventricular neurocytoma may be difficult because of the striking resemblance of these tumors to oligodendroglioma and, to a lesser extent, ependymoma on light microscopic examination. Despite the use of wide-ranging panels of monoclonal antibodies, previous authors have not found any characteristic immunohistochemical staining patterns, but in our three patients, the use of synaptophysin, glial fibrillary acidic protein, and Leu-7 demonstrated staining patterns that may be useful in the diagnosis of this tumor. The monoclonal antibody Ki-67 was used to stain one tumor and showed a low cell proliferation rate. We have reviewed the clinical, radiological, and pathological features of these 3 patients and 17 previously described patients in an attempt to determine the important diagnostic features of intraventricular neurocytoma. Intraventricular neurocytoma should be considered in any young patient with symptoms of raised intracranial pressure and radiological evidence of an intraventricular lesion. Pathological diagnosis requires the use of electron microscopy to show features of neuronal differentiation; however, immunohistochemical demonstration of a neuronal phenotype is also a useful adjunct to diagnosis. Failure to use specialized techniques for pathological diagnosis will lead to misdiagnosis of these lesions as oligodendrogliomas, as was the initial diagnosis in 2 of our patients before review.

Adolescent↗
PubMed1989

Inclusion bodies in motor cortex and brainstem of patients with motor neurone disease are detected by immunocytochemical localisation of ubiquitin.

Histological sections of cerebral motor cortex, brainstem, and spinal cord from 10 cases of clinically diagnosed motor neurone disease (MND) and 10 control cases were examined by conventional histology and immunocytochemical methods to localise ubiquitin. Intracytoplasmic inclusion bodies were identified in motor neurones of hypoglossal nuclei and appeared specific for MND. Similar inclusions were found in both large pyramidal cells and small neurones in the motor cortex, and were restricted to 4 cases having the amyotrophic lateral sclerosis form of MND with severe degeneration of corticospinal tracts. As reported in earlier studies, cellular inclusion bodies were identified in motor neurones of spinal cord from cases of MND but not in control material. Ubiquitin inclusions in motor neurones appear to be markers for the degenerative process causing neuronal loss in MND and there appears to be a close association between the anatomical location of inclusions and clinical manifestations of disease.

Aged↗