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Biomedical subjects

C Morris

Publications and source records attributed to C Morris.

At least 109 records · Page 6Linked to original sources
PubMed1997

HLA-DR antigens associated with major genetic risk for late-onset Alzheimer's disease.

Hla-dr antigen types were determined from DNA isolated from post-mortem brain tissue of age-matched groups of 78 patients with pathologically confirmed late-onset Alzheimer's disease (AD) and 50 controls. The results suggest that for individuals with no apolipoprotein E epsilon 4 alleles the presence of either DR1, 2 or 3 antigens is associated with a significantly increased risk for development of late-onset AD. Conversely the DR4 or 6 antigens are associated with a decreased risk of similar magnitude. This DR effect, rather than prolonged use of non-steroidal anti-inflammatory drugs, could be responsible for the reported lower prevalence of AD in rheumatoid arthritis (a condition associated with an increased frequency of DR-4).

Age of Onset↗
PubMed1997

Isolation of diabetes-associated kidney genes using differential display.

Differential Display was used to isolate genes that show transcriptional changes in the kidney during the development of diabetes in the GK rat. Eight candidate diabetes-associated cDNA fragments, CDK1-8, were isolated and characterised. cDNA sequencing and subsequent database analysis revealed that CDK2, 4, 5 and 6 showed no significant sequence similarity to previously reported genes, suggesting that they represent novel genes, whereas CDK 1, 3, 7 and 8 showed significant similarity with rat lactate dehydrogenase, rat amiloride sensitive sodium channel, EST109013 and mouse ubiquitin-like protein respectively. The differential mRNA expression of CDK1-8 was confirmed using differential screening of slot blots. CDK1, 2, 4 and 8 mRNAs appeared to increase whereas CDK3, 5, 6 and 7 mRNAs decreased in the kidneys of GK rats with increasing hyperglycaemia. The altered renal mRNA expression of these genes in association with increased hyperglycemia in the GK rat suggest that they are candidates for a role in the development of diabetic nephropathy.

Animals↗
PubMed1997

Comparative genomic hybridization reveals previously undescribed amplifications and deletions in the chronic myeloid leukemia-derived K-562 cell line.

We used comparative genomic hybridization (CGH) to identify a number of previously undescribed chromosomal imbalances in K-562, a spontaneously transformed cell line originally derived from leukemic cells of a chronic myeloid leukemia (CML) patient in blast crisis. Noteworthy were a discrete amplification in band 13q31, increased copy number of chromosome arms 1q, 5p, 6p, and 16q, and loss of material from 8p, 9p, 10q, and 17p. Amplification within bands 9q34 and 22q11.2 was consistent with previous descriptions of increased copy number of the CML-specific 5'BCR-3'ABL fusion gene in K-562. However, amplification of a large distal segment, 9q31-->9q34, mostly proximal to the ABL locus, was unexpected and is unlikely to be related to BCR-ABL recombination. Previous karyotype studies are reviewed in detail and compared with the CGH findings.

Female↗
PubMed1997

Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia.

Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervous system where the extracellular domains of ion channels and receptors are especially vulnerable targets. We present here a novel means of detecting autoantibodies where the genes of the suspected target proteins are known, and use it to detect specific autoantibodies in acquired neuromyotonia (Isaacs' syndrome), a disorder characterized by hyperexcitable motor nerves and sometimes by central abnormalities. We expressed different human brain voltage-gated potassium channels in Xenopus oocytes by injecting the relevant alpha-subunit complementary RNA, and detected antibody binding by immunohistochemistry on frozen sections. Antibodies were detected to one or more human brain voltage-gated potassium channel in 12 of 12 neuromyotonia patients and none of 18 control subjects. The results establish neuromyotonia as a new antibody-mediated channelopathy and indicate the investigative potential of this molecular immunohistochemical assay.

Autoantibodies↗
PubMed1997

Klinefelter syndrome and non-Hodgkin lymphoma.

Patients with a 47,XXY karyotype (Klinefelter syndrome) appear to have an increased risk of developing cancer, especially male breast cancer and germ cell tumors, but rarely malignant hematologic disorders. We report a patient with a low grade B-cell non-Hodgkin lymphoma with a 47,XXY karyotype in both the tumor and constitutional cells. This is only the 13th reported case of malignant lymphoma in a patient with Klinefelter syndrome. Although some authors postulate that the 47,XXY karyotype may be a predisposing factor in the development of hematological malignancies, the lack of reported cases suggests that such associations may be no more than chance findings.

Aged↗
PubMed1997

Presence of inflammatory mediators in the tears of contact lens wearers and non-contact lens wearers.

The present studies have demonstrated the levels of N-methyl histamine in tears from normal physiological states, pathological states and contact lens wear. Histamine was significantly increased in closed eye tears compared with both open and reflex tears. Tears from other ocular conditions had low levels of histamine except for environmental hypersensitivity, which contained significantly elevated levels compared to normal tear types. Interestingly, tears from asymptomatic contact lens wearers had significant levels of histamine whereas tears from contact lens adverse events had lower levels, possibly reflecting a change in histamine metabolism.

Analysis of Variance↗
PubMed1997

Protection by 4-methylthiobenzoic acid against cisplatin-induced ototoxicity: antioxidant system.

This study was undertaken in order to determine the changes in auditory brainstem-evoked responses relationship with the changes in the levels of GSH, lipid peroxidation and antioxidant enzymes activity in cisplatin-induced ototoxicity and otoprotection by 4-methylthiobenzoic acid (MTBA). Male Wistar rats in different groups were treated as follows: 1) saline control; 2) cisplatin (16 mg/kg, intraperitoneally); 3) MTBA (250 mg/kg, intraperitoneally), and 4) cisplatin plus MTBA. Post-treatment auditory brainstem-evoked responses were performed after three days and the rats were sacrificed and cochleae harvested. The cochleae were analyzed for glutathione (GSH), antioxidant enzyme activity, and malondialdehyde levels. The cisplatin injected rats showed a threshold elevation of 31.9 +/- 16.0 dB above the pretreatment thresholds using click stimulus. Rats treated with MTBA plus cisplatin did not show significant elevation of hearing threshold. Cisplatin plus MTBA administration showed a higher levels of cochlear GSH (5.59 +/- 0.35 nmoles/mg protein) compared to cisplatin alone (4.46 +/- 0.13 nmoles/mg protein). Cisplatin treated rats showed a decrease in superoxide dismutase, catalase, glutathione peroxidase (GSH-peroxidase), and glutathione reductase (GSH-reductase) activities (57%, 83%, 78% and 58% of control). Cochlear superoxide dismutase, catalase and GSH-reductase activities and MDA levels were restored in the rats injected with cisplatin plus MTBA, compared to cisplatin alone. It is concluded that the protection conferred by MTBA against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant system.

Acoustic Stimulation↗
PubMed1997

Rapid and specific detection of Sin Nombre virus antibodies in patients with hantavirus pulmonary syndrome by a strip immunoblot assay suitable for field diagnosis.

To develop a rapid antibody test for Sin Nombre hantavirus (SNV) infection for diagnosis of hantavirus pulmonary syndrome (HPS) in field settings where advanced instrumentation is not available, a strip immunoblot assay bearing four immobilized antigens for SNV and a recombinant nucleocapsid protein antigen of Seoul hantavirus (SEOV) was prepared. The SNV antigens included a full-length recombinant-expressed nucleocapsid (N) protein (rN), a recombinant-expressed G1 protein (residues 35 to 117), and synthetic peptides derived from N (residues 17 to 59) and G1 (residues 55 to 88). On the basis of the observed reactivities of hantavirus-infected patient and control sera, we determined that a positive assay requires reactivity with SNV or SEOV rN antigen and at least one other antigen. Isolated reactivity to either viral rN antigen is indeterminate, and any pattern of reactivity that does not include reactivity to an rN antigen is considered indeterminate but is unlikely to represent hantavirus infection. Fifty-eight of 59 samples from patients with acute SNV-associated HPS were positive according to these criteria, and one was initially indeterminate. Four of four samples from patients with HPS due to other hantaviruses were positive, as were most samples from patients with SEOV and Puumala virus infections. Of 192 control serum samples, 2 (1%) were positive and 2 were indeterminate. Acute SNV infection was distinguishable from remote SNV infection or infection with hantaviruses other than SNV by the presence of G1 peptide antigen reactivities in the former. The strip immunoblot assay shows promise for the detection of SNV antibodies early in the course of HPS.

Antibodies, Viral↗
PubMed1996

Effect of aluminium on expression and processing of amyloid precursor protein.

The environmental agent aluminium has been extensively investigated for a potential role in the aetiology of Alzheimer's disease. Despite many investigations there is at present no definite proof for any involvement. If aluminium is involved it is possible that its action is mediated through interaction with the synthesis or processing of amyloid precursor protein (APP). The present study compared aluminium loaded IMR-32 neuroblastoma cells and rat brains with control cells and brains to determine if aluminium affected APP expression and/or processing. In the IMR-32 model system aluminium had no effect on steady-state APP mRNA levels or on the ratio of individual isoforms. It also had no quantitative or qualitative effect on APP-immunoreactive bands detected in protein extracts from conditioned medium of these cells. In total cell extracts, aluminium reduced the intensity of APP-immunoreactive bands between 120-105 kDa but had no effect on a 9 kDa band. In rat brains, aluminium had no effect on APP-immunoreactive bands from soluble or insoluble-membranous extracts. The results, in general, provide no evidence for any effect of aluminium on APP expression or processing.

Aluminum↗
PubMed1996

Carcinogenesis by methylbenzylnitrosamine near the squamocolumnar junction and methylamylnitrosamine metabolism in the mouse forestomach.

We repeated and extended a 1973 study by Sander and Schweinsberg on forestomach tumorigenesis in mice by methylbenzylnitrosamine (MBZN). Groups of 80 adult CD-1 mice of both sexes received 96 mg/kg of MBZN subdivided into 24 doses of 4 mg/kg, 12 doses of 8 mg/kg or 6 doses of 16 mg/kg (groups 1-3, respectively). The mice were injected i.p. twice weekly with MBZN in 30% dimethylsulfoxide and 6-8 mice/group were killed every 4 weeks up to 40 weeks. Ten untreated control mice did not develop forestomach tumors. Forestomach papillomas occurred in 35-53% of the treated mice, with the highest incidence and shortest latency (mostly <24 weeks) in group 3. Squamous carcinomas of the forestomach were found in 31% of group 1 and 4-6% of groups 2 and 3. Ninety-two percent of the carcinomas and 94% of the papillomas in the 8-mm wide forestomach occurred < or = 1 mm from the squamocolumnar junction (SCJ) with the glandular stomach. This is interesting in view of the rising incidence of human adenocarcinoma near the gastroesophageal SCJ. Methyl-n-amylnitrosamine (MNAN) yields 2-, 3- and 4-hydroxy-MNAN (HO-MNAN) in a 1:3:2 ratio when incubated with rodent tissues for which MNAN is carcinogenic. This metabolism may be due to cytochrome P450 isoform believed responsible for MNAN and, probably, MBZN activation. When freshly excised mouse forestomach and esophagus were incubated for 2 h with 23 microM MNAN, total HO-MNAN yields were 0.79 +/- 0.05 and 1.81 +/-0.08 nmol/100 mg tissue per h (mean +/- SE), respectively, with about 1:3:2 ratios between 2-,3- and 4-HO-MNAN. This compares with published mean HO-MNAN yields in nmol/100 mg per h of 1.2 for rat esophagus (where MNAN and MBZN are strongly carcinogenic) and <0.1 for rat forestomach. These findings may explain why MNAN and MBZN induce forestomach tumors in mice but not in rats and why MNAN induces esophageal tumors in mice, but does not explain why MBZN given i.p. fails to induce esophageal tumors in mice. Three sections of the mouse forestomach (closest-to to furthest-from the SCG) showed total HO-MNAN yields from MNAN of 0.61+/-0.05, 0.38+/-0.03 and 0.48+/-0.02 nmol/100 mg per h (mean +/-SE), respectively. This may help explain why the MBZN-induced forestomach tumors were non-centrated near the SCJ.

Adenocarcinoma↗
PubMed1996

BCR gene recombines with genomically distinct sites on band 11Q13 in complex BCR-ABL translocations of chronic myeloid leukemia.

We have analysed a cloned 11q13/3'BCR junction fragment, one recombination product of a complex t(9;11;22) translocation in a patient with chronic myeloid leukemia. 3'M-Bcr recombined with chromosome band 11q13 at a specific point between two Alu elements lying in opposite orientation. We present new molecular data comparing the genomic location of the 11q13 breakpoint in our patient with that of one other recently reported to lie within the GSTP1 gene. This is the first time that specific breakpoint sites within a chromosomal region highly involved in complex Ph translocations have been relatively mapped. These early results argue against a precise site in 11q13 with which M-Bcr preferentially recombines and favour instead a larger recombination-prone domain. Both of the 11q13 breakpoint regions show Alu repeat elements in close proximity to the site of recombination.

Base Sequence↗
PubMed1996

4-methylthiobenzoic acid protection against cisplatin nephrotoxicity: antioxidant system.

This study investigates the changes in renal antioxidant system after cisplatin administration and the nephroprotection with 4-methylthiobenzoic acid (MTBA). Male Wistar rats were injected with (1) vehicle control, (2) cisplatin, (3) MTBA, and (4) cisplatin plus MTBA. Rats were euthenized 3 days post-treatment and kidney was isolated and analyzed for platinum concentration, malondialdehyde (MDA), glutathione (GSH and GSSG), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Plasma creatinine increased 508% following cisplatin administration alone, which decreased to 189% with MTBA. Cisplatin-treated rats showed a depletion of renal GSH levels (53%), while cisplatin plus MTBA-injected rats had GSH values close to those of the controls. SOD, CAT, and GSH-Px activities decreased 36, 29, and 38%, respectively, and MDA levels increased 212% following cisplatin administration, which were restored to control levels after MTBA treatment. The renal platinum level depleted significantly with MTBA treatment. The data suggest that cisplatin nephrotoxicity is mediated by depletion in GSH concentration and by impaired activities of SOD, CAT, and GSH-Px, increased lipid peroxidation, and plasma creatinine levels. The protection offered by MTBA against cisplatin nephrotoxicity is related to the reduction in plasma creatinine levels, prevention of GSH depletion and lipid peroxidation, and restoring antioxidant enzyme activity in the kidneys of rats.

Animals↗
PubMed1996

Photoacoustic Fibrinolysis: Pulsed-Wave, Mid-Infrared Laser-Clot Interaction.

Objectives: The purpose of this study was to determine whether a mid-infrared laser can induce selective fibrinolysis and to analyze the effect of altered fibrin structure (thin vs. thick fibers) on laser-clot interaction. Background: Mechanical disruption of thrombus can be achieved with balloon angioplasty, sonication, and thermal energy. Thrombi avidly absorb light in the mid-infrared optical spectrum due to their high water content. This phenomenon provides a potential for mid-infrared lasers as a source for selective thrombolysis. As fibrin is the essential component of clot, a study of mid-infrared laser-fibrin interaction is warranted. Methods: Clots of varying fibrin structure were lased in cuvettes with a solid-state, pulsed-wave, mid-infrared laser (2.1 micron, 500 mJ/pulse, 250 msec pulse length). Total pulse energies of 5 Joules (J), 10 J, 37.5 J, 75 J, and 112.5 J were tested. Protein content of the extruded fluid was measured by optical density absorbance at 280 nm. Th e amount of released material was studied as a function of lasing energy and clot structure. SDS-polyacrylamide gel electrophoresis was applied for analysis of protein bands in order to identify unique protein bands released by the selective effect of laser fibrinolysis. Results: A threshold for mid-infrared laser induced fibrinolysis was found; application of up to 20 J of energy did not result in dissolution. As lasing energy was increased above 37.5 J, the structure of these gels was mechanically destroyed and 12.4 +/- 6.7% (mean +/- SEM) of the original content of protein was released. Electrophoresis revealed that lased gels did not release any unique protein band. Lased, thin fibers released significantly less protein than thick fibers, indicating that they are more resistant to the effect of this wavelength of energy. Conclusions: Mid-infrared laser can induce in-vitro photoacoustic dissolution of fibrin clots. However, this wavelength laser achieves fibrinolysis by me chanical destruction of the target clot rather than by a selective effect, as induced by the pulsed-dye laser. A threshold exists for energy levels required. Thin fibrin fibers, with their high elastic modulus (i.e., gel rigidity) appear more resistant than thick fibers to the effect of lasing at this wavelength.

Journal Article↗
PubMed1996

Medium aperture meso-caval shunts reliably prevent recurrent variceal hemorrhages.

BACKGROUND: Objectives of partial medium aperture mesocaval shunts (MCS) include reduction of portal hypertension to prevent recurrent variceal hemorrhage, preservation of portal flow through liver while maintaining an intact porta hepatis to facilitate a future liver transplant (OLTx). PATIENTS AND METHODS: Fifteen patients were retrospectively analyzed to review the indications for the procedure, its short- and long-term complications as well as patency and functional status of the shunt. They were followed for a period of 21 months. RESULTS: The perioperative and long-term mortality rate was 0%. Rebleeding rate perioperatively and in follow-up was 0%. Early shunt nonfunction was 13% and post-shunt encephalopathy (PSE) was 20%. The encephalopathy was grade I to II and controlled medically. Abdominal ultrasound and Doppler confirmed 13 patent shunts (2 patients did not agree to ultrasound) with preserved hepatopetal flow in 10. CONCLUSIONS: Medium aperture MCS utilizing ringed polytetrafluoroethylene (PTFE) grafts safely and reliably prevent recurrent variceal hemorrhage. Encephalopathy is infrequent and mild. This technique preserves the portal venous anatomy making a future OLTx technically easier.

Adult↗
PubMed1996

Sudden death in Williams syndrome: report of ten cases.

Williams syndrome (WS) is a recognizable pattern of malformation with mental retardation, mild growth deficiency, characteristic facies and temperament, and cardiovascular disease. Sudden death is a recognized complication of WS; however, it is thought to be rare. The clinical features of 10 children with WS who died suddenly are reported here, doubling the number of unexpected deaths reported in the literature. We suggest that sudden death is a more common complication than has been assumed previously. Pathologic findings on the seven autopsy cases implicate two anatomic abnormalities that predispose individuals with WS to sudden death: coronary artery stenosis and severe biventricular outflow tract obstruction. The mechanisms for sudden death for both anatomic subgroups include myocardial ischemia, decreased cardiac output, and arrhythmia. We believe these observations warrant the development of strategies for monitoring patients with WS in an attempt to identify those at increased risk of sudden death.

Aortic Valve↗