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Biomedical subjects

S Carpenter

Publications and source records attributed to S Carpenter.

At least 73 records · Page 4Linked to original sources
PubMed1996

Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination.

Hereditary demyelinating peripheral neuropathies consist of a heterogeneous group of genetic disorders that includes hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinical and pathologic variation and overlap between these disorders. We have identified five novel mutations in the myelin protein zero (MPZ) gene, encoding the major structural protein (P0) of peripheral nerve myelin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, but rather represent a spectrum of related "myelinopathies" due to an underlying defect in myelination. Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative).

Adult↗
PubMed1996

Vacuolar myelopathy in transgenic mice expressing human immunodeficiency virus type 1 proteins under the regulation of the myelin basic protein gene promoter.

Vacuolar myelopathy is a common neurological complication in AIDS patients. The pathogenesis of this spinal cord white matter disease remains unclear and it is still debated whether infection of spinal cord with the human immunodeficiency virus type 1 (HIV-1) is causing the disease. We have generated transgenic mice expressing the entire HIV-1 genome under the regulation of an oligodendrocyte-specific promoter. These mice develop spinal cord vacuolar lesions similar to those found in AIDS patients. This animal model provides in vivo evidence linking the expression of HIV-1 proteins in oligodendrocytes to the spinal cord damage found in vacuolar myelopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1996

An atypical T-cell lymphosarcoma in a calf with bovine immunodeficiency-like virus infection.

An 11-month-old Holstein calf experimentally infected with bovine immunodeficiency-like virus (BIV) developed T-cell lymphosarcoma 5 months postinoculation, concurrent with progressive monocytosis. Tumors were found in the thymus, multiple lymph nodes, and brain. Tumor cells were CD2+, CD4-, CD8-T cells. Infectious BIV could be recovered from splenic tissue and blood mononuclear cells. Bovine leukemia virus was not present. Because this calf was part of an ongoing experiment on the pathogenesis of BIV infection, immune function data were also available both before and after lymphosarcoma developed. Neutrophil and monocyte function were normal, but lymphocyte blastogenesis was enhanced before the development of lymphosarcoma. Follicular hyperplasia in lymphoid tissues was also seen. This case raises the possibility that BIV infection may cause or be associated with some cases of atypical T-cell lymphosarcoma, without evidence of immune suppression at the time of tumor onset.

Animals↗
PubMed1996

Prolonged effect of omeprazole on the 14C-urea breath test.

OBJECTIVES: We investigated omeprazole's effect on 14C-urea breath testing. We also determined the duration of omeprazole's effect on the breath test. Finally, we studied whether effects on breath testing were dose dependent. METHODS: Fifty-seven employees and outpatients were screened for Helicobactor infection. Those positive for serology, CLO, or histology were asked to undergo baseline breath testing. Those with a positive breath test took omeprazole 20 mg/day for 14 days followed by repeat breath testing, 1, 3, and 5 days after therapy. Subjects with persistently positive breath tests despite omeprazole 20 mg/day were asked to take omeprazole 20 mg b.i.d. for 14 days. Repeat breath tests were performed as above. RESULTS: Thirteen of 57 had HP infection. Ten of 13 underwent a baseline breath test. Eight of 10 with baseline breath test experienced a significant decrease in expired 14CO2 after omeprazole 20 mg/day. Five of 13 with active HP infection developed a negative breath test after omeprazole. All subjects had a positive breath test within 5 days of stopping omeprazole 20 mg/day. Five of eight with persistently positive breath tests despite omeprazole 20 mg/day took omeprazole 40 mg/day. Four of five developed a significant decrease in 14CO2 excretion after omeprazole. All subjects had a positive breath test within 5 days of stopping omeprazole 40 mg/day. CONCLUSIONS: Recent treatment with omeprazole 20 mg/day led to a false-negative breath tests in 38.5%. This effect appeared to be dose dependent and lasted up to 5 days after cessation of omeprazole.

Anti-Bacterial Agents↗
PubMed1995

Late-onset mitochondrial myopathy.

In the majority of patients with mitochondrial encephalomyopathies, signs and symptoms appear in the first three decades of life. Here we report on a group of 9 older patients (> 69 years old) with late-onset skeletal myopathy characterized by focal accumulations of deleted mitochondrial DNAs (mtDNAs) and altered muscle energy status, suggestive of a primary mitochondrial disease. The clinical phenotype was somewhat variable. However, all patients shared a common feature of insidious moderate proximal muscle weakness; some also showed fatigability and axial muscle weakness. In situ hybridization analysis demonstrated accumulations of messenger RNAs transcribed from deleted mtDNAs in a relatively large number of muscle fibers in the patient group. These fiber segments appeared as ragged red with the modified Gomori trichrome stain and hyperreactive with a modified succinate dehydrogenase stain. Most were negative for cytochrome c oxidase activity. On transverse sections their mean frequency was 0.69% (trichrome) and 1.97% (succinate dehydrogenase) significantly above control levels. Multiple mtDNA deletions were demonstrated by the polymerase chain reaction in both the patients and an age-matched control group, but not in younger control subjects. Phosphorus 13 magnetic resonance spectroscopy of resting muscle showed a decreased phosphocreatine-inorganic phosphate ratio in the patient group. The myopathy in this group of patients appears to result from mitochondrial dysfunction related to the clonal expansion of different mtDNA deletions in individual fiber segments. While the origin of the mtDNA mutations is not clear, the phenotype seems to represent an exaggerated form of what is observed in the normal aging process.

Aged↗
PubMed1995

Temporal lobe epilepsy caused by domoic acid intoxication: evidence for glutamate receptor-mediated excitotoxicity in humans.

We describe the development of temporal lobe epilepsy in an 84-year-old man who had suffered domoic acid intoxication. Following intoxication he had nausea, vomiting, confusion, and coma. Generalized convulsions and complex partial status epilepticus progressively developed. After 3 weeks he improved and was seizure free with severe residual memory deficit. Electroencephalograms initially showed periodic epileptiform discharges, later evolving to epileptic abnormalities over frontotemporal regions with diffuse slow waves. Eight months after the intoxication the electroencephalogram was normal. One year after the acute episode, complex partial seizures developed. Electroencephalograms showed epileptic discharges independently over both temporal lobes, with left-sided predominance. Magnetic resonance imaging revealed a hyperintense T2-weighted signal and atrophy of both hippocampi; a positron emission tomographic scan showed bitemporal decreased glucose metabolism. Pneumonia developed and the patient died 3 1/4 years after the intoxication. Autopsy disclosed severe bilateral hippocampal sclerosis. The seizures following acute domoic acid intoxication, the postmortem pathology, and the fact that temporal lobe epilepsy developed 1 year after intoxication indicate that the human hippocampus is also vulnerable to kainate receptor excitotoxicity, and provide strong evidence supporting the role of excitotoxic injury in epileptogenesis. This report provides a unique human parallel to, and validates the animal model of, kainate-induced epilepsy as an important tool for studying temporal lobe epilepsy.

Aged↗
PubMed1995

Monocyte function in cattle experimentally infected with bovine immunodeficiency-like virus.

The effects of bovine immunodeficiency-like virus (BIV) on monocyte function were examined in experimentally infected cattle and in monocytes infected in vitro. Infection with the R29 isolate of BIV appeared to have relatively little effect on monocyte function in cattle during the first 2 years postinfection (PI). For the first 4 to 8 months post infection, monocyte phagocytosis of Staphylococcus aureus tended to be lower (P = 0.06) in BIV infected calves than in control animals. After 8 months PI, however, phagocytosis became equal between the two groups. Random and chemotactic migration and antibody-dependent cell-mediated cytotoxicity (ADCC) did not appear to be affected by BIV infection. Monocytes from BIV infected cattle were able to respond to in vitro treatment with interferon gamma similarly to monocytes from control cattle. Although experimental infection with BIV R29 resulted in minimal effects on monocyte function, this result could have been due either to a low virus burden in vivo or because BIV is intrinsically unable to affect monocyte function. To distinguish between these possibilities, monocytes from control, uninfected cattle were treated with BIV virus in vitro. Treatment of normal monocytes with cell-free virus significantly (P < 0.05) increased phagocytosis and random and chemotactic migration and decreased ADCC, in a dose-dependent manner. It appears, therefore, that the normal function of peripheral blood monocytes in the BIV R29 infected animals may be due to a low virus burden rather than to the inability of BIV to affect monocyte function. The in vitro infection results also raise the possibility that the function of monocyte derived cells at local sites of BIV replication may be altered.

Animals↗
PubMed1995

Familial myopathy with conspicuous depletion of mitochondria in muscle fibers: a morphologically distinct disease.

Three patients (two of them siblings) presented with easy fatiguability and prominent postexercise pain. Muscle biopsy showed that large areas of about one third of the type II fibers were completely devoid of mitochondria. The remaining mitochondria were unusually large in size, but otherwise normal ultrastructurally. In two patients, 31P in vivo MRS showed low phosphocreatine (PCr), high ADP, low phosphorylation potential at rest and slow ADP and PCr recovery after aerobic exercise. This appears to be a pathologically unique form of metabolic myopathy. The cause of the focal mitochondrial depletion is not known. It should be distinguished from the mtDNA depletion syndrome in which muscle mitochondria are not reduced, but proliferate.

Adenosine Diphosphate↗
PubMed1995

Loss of Gag-specific antibody reactivity in cattle experimentally infected with bovine immunodeficiency-like virus.

The development and persistence of virus-specific antibodies were investigated in eight cattle experimentally infected with the R29 isolate of bovine immunodeficiency-like virus (BIV). By 4 weeks postinoculation (p.i.), antibodies reactive to BIV gag- and env-encoded recombinant fusion proteins were detectable by immunoblotting in all animals. By 40 weeks p.i., seven of eight cattle had dramatically decreased Gag-specific antibodies, and anti-Gag reactivity remained very low or undetectable through 190 weeks p.i. Immunoprecipitation experiments revealed a similar loss of reactivity to nondenatured BIV Gag in these animals. In contrast, antibodies to a recombinant BIV Env protein were readily detectable throughout the study in all eight cattle. During the period of declining Gag antibody, infectious virus was recoverable from peripheral blood mononuclear cells of each animal. However, there was no evidence for sufficient amounts of BIV p26-containing immune complexes to explain the loss of anti-Gag reactivity. Interestingly, the single animal that maintained detectable anti-Gag reactivity throughout the study was repeatedly negative for virus recovery beyond 17 weeks p.i. All animals have remained clinically normal for over 4 years p.i., with no evidence of consistent changes in mononuclear cell subsets. These findings provide evidence that in BIV infection an early decline in Gag-specific antibody reactivity can occur without evidence of increasing viral replication or progression to overt clinical disease.

Animals↗
PubMed1995

Periventricular and subcortical nodular heterotopia. A study of 33 patients.

Grey matter heterotopias, demonstrated by MRI, may present with a broad spectrum of clinical severity. We have studied 33 patients with periventricular nodular heterotopias (PNH); 19 (58%) had unilateral and 14 (42%) bilateral lesions. Thirteen of the 19 patients (68%) with unilateral subependymal nodules of grey matter had, in addition, unilateral focal subcortical heterotopias (SNH), comprising 39% of the entire group. Most had normal intellectual and motor function but some presented with mild mental retardation and neurological deficits. Recurrent seizures were described in 82%, mainly partial attacks with temporo-parieto-occipital auras. Nodular heterotopias led to unilateral or bilateral independent temporal epileptic discharges in 47% of epileptic patients with PNH alone and in 61% of those who had SNH in addition. Extratemporal or multilobar, unilateral or bilateral interictal spiking was present in 10 other patients (36%). Two first degree relatives of patients with seizures were affected but had no seizures, three were investigated for other apparently unrelated neurological symptoms: memory impairment, vertigo or transient ischaemic attacks in one person each. Contiguous ovoid nodules of grey matter, symmetrically lining both lateral ventricles, were described in nine patients. Seven of them were female, including four with familial incidence of PNH. Such lesions may explain the familial occurrence of epilepsy in some families. Seven patients underwent anterior temporal resection: two patients with unilateral subependymal and focal subcortical heterotopias were seizure free or significantly improved. Four patients, three with PNH alone and one with additional subcortical nodules, did not improve significantly after surgery. The remaining patient was followed for less than 6 months.

Adolescent↗
PubMed1995

A screening clinic for relatives of patients with colorectal cancer in a district general hospital.

A family cancer screening clinic was set up to screen and counsel subjects at above average risk of developing colorectal cancer. Criteria for referral were one first degree relative under 50 years or two of any age with colorectal cancer. Pedigree information was used to estimate lifetime risks of developing colorectal cancer and offer appropriate screening: colonoscopy for high risks (greater than 1 in 10), faecal occult blood testing for lower risks. One hundred and eleven subjects from 76 families were seen over four years. Forty two families gave a pedigree consistent with dominantly inherited non-polyposis colorectal cancer syndrome (HNPCC). Three subjects from one family were found to have familial adenomatous polyposis. Ninety two colonoscopies yielded 21 patients with polyps (12 had tubular adenomas, including one with early malignant invasion). Thirty three per cent (four of 12) of the tubular adenomas were beyond the reach of a flexible sigmoidoscope. Three hundred and forty two further high risk relatives were identified from the family history.

Adult↗
PubMed1995

Subacute enlarging cerebral hematoma from amyloid angiopathy: case report.

We report the case of a 74-year-old woman who, during a 36-hour period, developed progressive, focal neurological deficits and eventual coma associated with a spontaneously enlarging intraparenchymal hematoma resulting from cerebral amyloid angiopathy. The subacute, progressive enlargement of the hematoma, confirmed by serial computed tomographic scans, supports the hypothesis that hematomas enlarge in amyloid angiopathy as a result of the replacement of the contractile elements of the arterial wall by noncontractile amyloid protein. This interference with vasoconstriction, the first phase of hemostasis, may be supplemented by local endothelial dysfunction causing alterations in the chemical mediators of hemostasis, thereby promoting hemorrhage and hematoma enlargement.

Acute Disease↗
PubMed1994

Chemiluminescent activation of the antiviral activity of hypericin: a molecular flashlight.

Hypericin is a naturally occurring photosensitizer that displays potent antiviral activity in the presence of light. The absence of light in many regions of the body may preclude the use of hypericin and other photosensitizers as therapeutic compounds for the treatment of viral infections in vivo. The chemiluminescent oxidation of luciferin by the luciferase from the North American firefly Photinus pyralis was found to generate sufficiently intense and long-lived emission to induce antiviral activity of hypericin. Light-induced virucidal activity of hypericin was demonstrated against equine infectious anemia virus, a lentivirus structurally, genetically, and antigenically related to the human immunodeficiency virus. The implications for exploiting chemiluminescence as a "molecular flashlight" for effecting photodynamic therapy against virus-infected cells and tumor cells are discussed.

Animals↗
PubMed1994

Cellular and viral specificity of equine infectious anemia virus Tat transactivation.

Lentiviruses vary in their dependence on a functional tat gene during their viral life cycle. To begin to understand the viral and cellular parameters controlling equine infectious anemia virus (EIAV) transactivation, we investigated Tat function and Tat and LTR structural requirements necessary for successful transactivation. EIAV Tat expression was required for detection of viral antigens from a full-length provirus. The level of transactivation by EIAV Tat as measured by LTR-CAT assays correlated well with viral antigen expression. Using horse/mouse somatic cell hybrids (SCH), a single SCH line which supported EIAV transactivation was identified, indicating that the presence of specific horse chromosomes provided cellular factors required for transactivation. Transformed cell lines from several different species were also tested and found to differ in their ability to support EIAV transactivation. A canine cell line, Cf2Th, which was permissive for EIAV transactivation, and a human cell line, HeLa, which was not permissive for EIAV transactivation, were used to map regions of the LTR and Tat that were important in cell-specific transactivation. As expected, the R region of EIAV LTR was required for transactivation by EIAV Tat in all cell lines studied. Similarly, the R region of HIV LTR was necessary for transactivation by HIV Tat. However, the composition of the U3 region also influenced transactivation in a cell-specific manner. In Cf2Th cells, replacement of EIAV U3 sequences with HIV U3 sequences resulted in high basal (nontransactivated) expression, and as a result, only a twofold increase in expression was observed in the presence of EIAV Tat. Similar studies using HIV Tat demonstrated that transactivation occurred in Cf2Th cells when either EIAV or HIV U3 sequences were present in the LTR. In contrast, transactivation by either HIV or EIAV Tat in HeLa cells required the presence of HIV enhancer sequences. These findings suggested that the ability of transactivation to occur in some cell lines may involve interactions between cell-specific transcription factors and the activation domain of Tat. For transactivation in other cell lines, Tat appeared to require more ubiquitious factors that interact with both EIAV and HIV U3 sequences.

Animals↗
PubMed1994

Unusual evolution and computerized tomographic appearance of a gliosarcoma.

A patient with a remote infarct, seizures, mild hemiparesis, and dysphasia became obtunded over four months and died. Computerized tomography (CT) over 5 years showed a consistent, large, wedge-shaped left hemisphere hypodensity with a central calcification, but without signs of mass effect. This was interpreted as an infarct of the left middle cerebral artery territory. Post-mortem examination of the brain revealed the entire area appearing as infarct on CT was a gliosarcoma. We suspect that the unusual CT appearance of the lesion was likely caused by multiple pathologies: a low grade glioma transforming into a gliosarcoma that was able to spread throughout the area of infarct encephalomalacia without revealing a typical CT appearance of mass effect. The patient's brief period of deterioration probably coincided with transformation of the tumor into a gliosarcoma. The variable CT characteristics of gliosarcomas are reviewed.

Brain Neoplasms↗
PubMed1994

Relationship between atrophy of the amygdala and ictal fear in temporal lobe epilepsy.

Viscerosensory and affective manifestations are often elicited by temporal lobe seizure discharges. They have been reproduced by amygdaloid stimulation in awake patients during stereotaxic exploration or neurosurgical procedures. They are not exclusively reproduced by stimulation of the amygdala, though most commonly they are evoked from it. Ictal fear is frequently, but not invariably, associated with a rising epigastric sensation, palpitations, mydriasis and pallor. We studied 50 patients (mean age 33 years) with intractable temporal lobe epilepsy (TLE): MRI volumetric measurements of amygdala and hippocampus were performed using a protocol previously described by our group (Watson et al., Neurology 1992; 42: 1743-50). All patients had extensive EEG investigation and at least two seizures recorded by video-EEG monitoring. Seventeen patients (34%) had a clear history of fear accompanied by a rising epigastric sensation as the initial manifestation of their habitual attacks. The amygdala volumes in this group were significantly (P = 0.001) smaller (mean 2131.6 mm3) compared with the volumes of the 33 patients without these symptoms (mean 2561.5 mm3). Both patient groups had smaller mean amygdala volumes compared with normal controls (mean 2828.2 mm3). Postoperative pathology correlated well with volumetric atrophy. In addition, we found that patients with more pronounced amygdaloid atrophy more commonly had prolonged febrile convulsions in early childhood and also more frequently secondarily generalized seizures. Results support the finding that ictal fear is related to pathology of the amygdala and that it, like the hippocampus, is an important substrate of TLE.

Adolescent↗