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Biomedical subjects

J Lucas

Publications and source records attributed to J Lucas.

At least 19 recordsLinked to original sources

Defecatory disorders, anorectal and pelvic floor dysfunction: a polygamy? Radiologic and manometric studies in 41 patients.

A consecutive series of 41 patients with defecatory disorders was prospectively studied by anal manometry and evacuation proctography to determine the relationship between abnormalities and symptoms. The patients (29 female, 12 male, aged 41 +/- 2.3 years) all complained of difficulty in evacuation. All had normal colonoscopy and biochemistry. There was no evidence of megacolon or megarectum, and no symptoms had been previously treated by pelvic floor surgery. All subjects completed detailed questionnaires related to gastrointestinal symptoms with special reference to excessive straining and discomfort, digital manipulations during defecation, a sense of pelvic heaviness and incomplete evacuation. Each patient underwent clinical examination, anal manometry and defecography during a single outpatient visit. Rectocele (16 patients) was significantly associated with vaginal digitation, lower stool frequency, delayed rectal emptying and decreased rectal sensation to distension. Increased anal pressure on straining (14 patients) was also related to a poor rectal emptying in 13 patients. Neither perineal descent (24 patients) nor external rectal prolapse (12 patients) was related to objective obstruction. Nevertheless there was an association with pelvic heaviness and lower anal manometric recordings. Five among 16 patients with rectocele had manometric anismus. Forty percent of patients with intussusception also had a paradoxical sphincter response during defaecation. Furthermore, associated abnormalities were extremely common (34 of 41 patients), accurate interpretation of which was necessary for planning effective therapy.

Adult

Susceptibility of myelin proteins to a neutral endoproteinase: the degradation of myelin basic protein (MBP) and P2 protein by purified bovine brain multicatalytic proteinase complex (MPC).

Multicatalytic proteinase complex (MPC) was isolated from bovine brain and the susceptibility of myelin basic protein (MBP) and P2 protein of bovine central and peripheral nervous system was examined. SDS-polyacrylamide electrophoretic analysis of purified MPC revealed protein bands of molecular weight ranging from 22-35 kDa. The enzyme is activated by SDS at a concentration less than 0.01%. Upon incubation with MPC, purified MBP and P2 proteins were degraded into smaller fragments. There was a 57% and 100% loss of MBP at 2 and 6 hours of incubation. The P2 protein which is not susceptible to any endogenous non-lysosomal enzyme thus far studied was digested into small peptide fragments only in the presence of SDS (0.01%) and not in its absence. These results indicate that MPC which is active at physiological conditions may have a role in the turnover of myelin proteins and in demyelinating diseases.

Amino Acid Sequence

Factors that determine the in vivo dose-response relationship for stable chromosome aberrations in A-bomb survivors.

An overview is given of the dose-response relationship for stable chromosome aberrations (i.e., translocations and inversions) in the peripheral blood lymphocytes of A-bomb survivors in Hiroshima. Special emphasis is placed on (i) the overdispersion of survivor cases with either unexpectedly high or low aberration frequencies relative to the estimated DS86 kerma values assigned to individual survivors, termed "cytogenetic outliers", and (ii) the correlation of chromosome aberration frequencies with other biological endpoints, such as acute radiation symptoms (severe epilation). A new molecular biological technique, known as fluorescence in situ hybridization (FISH) with composite, whole-chromosome probes to paint differentially the target chromosomes, has facilitated rapid, efficient, and extensive scoring of translocation-type chromosome aberrations in which the target chromosomes are involved. Using this methodology, the observed findings on translocation frequencies in A-bomb survivors have shown that the frequency of stable chromosome aberrations, which have persisted for years without change in frequency in irradiated persons, is indeed useful as an indicator for biological dosimetry.

Chromosome Aberrations

Novel biodosimetry methods applied to victims of the Goiânia accident.

Two biodosimetric methods under development at the Lawrence Livermore National Laboratory were applied to five persons accidentally exposed to a 137Cs source in Goiânia, Brazil. The methods used were somatic "null" mutations at the glycophorin A locus detected as missing proteins on the surface of blood erythrocytes and chromosome translocations in blood lymphocytes detected using fluorescence in-situ hybridization. Biodosimetric results obtained approximately 1 y after the accident using these new and largely unvalidated methods are in general agreement with results obtained immediately after the accident using dicentric chromosome aberrations. Additional follow-up of Goiânia accident victims will 1) help provide the information needed to validate these new methods for use in biodosimetry and 2) provide independent estimates of dose.

Accidents

Emmetropisation, squint, and reduced visual acuity after treatment.

In a sample of children used to assess the value of optical correction of hypermetropia from the age of 6 months the refraction of the most hypermetropic meridian frequently became less than 3.5 D as the children grew. When this occurred, the incidence of squint was significantly less (p less than 0.001) and the last known acuity after treatment was significantly better (p less than 0.001) than when it did not. This process of emmetropisation appears to have been impeded by the consistent wearing of hypermetropic spectacle correction from the age of 6 months.

Eyeglasses

[Periodic disease and pregnancy].

The authors report a case of familial Mediterranean fever in a pregnant woman treated with Colchicine. She delivered normally at term. A review of the literature shows that colchicine does not have a teratogenic effect which it was long thought to have. All the same it is best to carry out fetal karyotype examination using early amniocentesis. Furthermore, colchicine improves fertility which is disturbed in these patients and pregnancy has a good effect on the disease.

Adult

Applications of fluorescence in situ hybridization in biological dosimetry and detection of disease-specific chromosome aberrations.

Dual color FISH with whole chromosome and pan-centromere probes facilitates rapid detection of stable structural aberrations such as translocations. This approach should allow analysis of translocations for assessment of genetic damage at long times after exposure or as a result of chronic exposure during a long period of time. Multi-color FISH with locus specific probes allows assessment of the frequency of cells carrying specific aberrations known to be associated with tumorigenesis, analysis of the series of genetic changes that occur during tumor evolution and correlation between genotype and phenotype. The power of FISH for analysis of random and tumor related events will increase steadily as informative probes are developed during the course of the International Human Genome Project.

Chromosome Aberrations

Alterations in the expression of colony-stimulating factor-1 and its receptor during an acute graft-vs-host reaction in mice.

During the course of an acute graft-vs-host reaction in the mouse we observed a progressive increase in the concentration of CSF-1 in serum and liver, peaking at day 14. In contrast, there was a progressive decrease in the splenic CSF-1 concentration. In vivo studies of 125I-CSF-1 uptake and degradation and in vitro studies of 125I-CSF-1 binding by splenic cells demonstrated that within 24 h of the reaction the number of CSF-1 receptor+ cells had increased by 2-fold and their capacity to express the CSF-1 receptor by approximately 3-fold, resulting in a approximately 2.5-fold increase in the splenic clearance of CSF-1 from the circulation. Inasmuch as at 24 h, serum CSF-1 was not significantly altered, these results are suggestive of an increased rate of release of CSF-1 into the circulation early in the response. The splenic CSF-1-receptor bearing cells were in a Mac-1+ fraction that is consistent with a role for CSF-1 in the generation of host-derived splenic macrophages in acute graft-vs-host reaction.

Animals

Preparative separation of pyrogens from proteins by isoelectric focusing using a multicompartment electrolyser with Immobiline membranes.

Due to the nature of lipopolysaccharide endotoxin structures of bacterial pyrogens, their removal from solutions containing therapeutic proteins is often a problem in the pharmaceutical industry. In this report we describe the application of electromotive force to dislodge lipopolysaccharide endotoxins from proteins. This was performed by employing a multicompartment electrolyzer fitted with Immobiline membranes of specified pIs. A thousand-fold reduction of endotoxin could be achieved in the model test system described. This contribution describes the use of a new recycling isoelectric focusing approach without the use of carrier ampholytes.

Isoelectric Focusing

Left recurrent laryngeal nerve paralysis: an unusual presentation of histoplasmosis.

A case of histoplasmosis seen as left recurrent laryngeal nerve paralysis in a 49-year-old man is described. The patient had roentgenographic findings of a solitary, noncalcified left upper lobe mass and mediastinal adenopathy. Tissue diagnosis of histoplasmosis was obtained using a thoracotomy, allowing institution of appropriate treatment.

Histoplasmosis

Factors relating to visual acuity in children who have been treated for convergent squint.

Retrospective analysis of a selected sample of children who presented with convergent squint has shown that abnormal meridional hypermetropia (3.5 D or more) at age 1 was the principal factor associated with severe amblyopia (6/24 or less) remaining after conventional treatment. Neither the reported age of onset nor delay in presentation influenced the final visual outcome.

Amblyopia

Results of a randomised trial of treating abnormal hypermetropia from the age of 6 months.

Children who were abnormally hypermetropic at the age of 6 months were randomly allocated treatment with spectacles or no treatment. The eventual incidence of squint was the same in both groups (approximately 24%). The last known visual acuity of the two groups was not significantly different either. Therefore there is no indication to screen infants with a view to preventing squint/amblyopia by optical correction of hypermetropia. If, however, the children allocated treatment are divided into two subgroups--those who wore glasses consistently and those who probably or certainly did not do so--the incidence of squint was the same, but the last known acuities of those who consistently wore glasses may be better than those who did not do so. This suggests that it may yet prove possible to prevent severe amblyopia.

Eyeglasses

Intestinal metaplasia is age related in Barrett's esophagus.

The correlation among cellular characteristics of Barrett's esophagus, patient age, and malignant neoplasm is not well documented. This study, which describes a population of 66 patients with Barrett's esophagus spanning 1 to 80 years of age, analyzes the cellular constituents of their lesional tissues by endoscopic biopsy and histochemical and morphometric studies. Goblet cell metaplasia, identified in 50% (n = 14) of pediatric patients, increased significantly to involve 84% (n = 32) of biopsy specimens from adult patients with Barrett's esophagus. This increase was exponential by linear regression analysis (R2 = .64) between the ages of 5 and 29 years. Pediatric patients usually had 25 or less goblet cells per square millimeter of Barrett mucosa with no identifiable epithelial dysplasia or cancer; Nissen fundoplication lessened esophageal inflammation, but the Barrett mucosa persisted. Goblet cell metaplasia maintained a plateau (mean of 57 cells per square millimeter of Barrett mucosa) between the ages of 41 and 80 years. Dysplasia, in situ carcinoma, or invasive carcinoma was found in patients with Barrett's esophagus who were aged 41 years or older. This study demonstrates persistence of Barrett mucosa, increased incidence of goblet cell metaplasia, and predictable changes in goblet cell number with advancing patient age. The relationship between Barrett mucosa and malignant neoplasm remains uncertain, but the goblet cell may serve as a marker of disease chronicity in which setting neoplasia evolves.

Adolescent

Immunomodulation by low-dose methotrexate. I. Methotrexate selectively inhibits Lyt-2+ cells in murine acute graft-versus-host reactions.

We have studied the effect of methotrexate in murine acute graft vs host (GvH) disease at concentrations analogous to those used in human rheumatoid arthritis. The GvH reaction was induced by i.v. injection of parental spleen cells into a normal F1 recipient. The acute suppression of T cell function in GvH mice was prevented by methotrexate given orally for 10 days at 1.0 or 0.5 mg/kg but not at 0.25 mg/kg. T cell mitogen response and IL-2 secretion that were inhibited in GvH mice were restored by methotrexate. Protection from immunosuppression in drug-treated GvH mice lasted at least 3 wk after drug dosing was stopped. The mechanism of the protective effect appears to be a preferential inhibition of donor and host Lyt-2+ Ts cell proliferation. In mixing experiments we found that methotrexate inhibited Ts function in GvH mice. By dual fluorescence labeling we showed that the engraftment of donor Lyt-2+ cells was prevented by drug treatment. This was not true of donor L3T4+ cells which were clearly present in the spleens of GvH mice after methotrexate treatment. These donor L3T4 cells were functional in that they induced the production of anti-DNA autoantibodies in the methotrexate-treated GvH mice.

Acute Disease

The effect of 3,6-bis(2-piperidinoethoxy) acridine trihydrochloride (CL 246, 738) on acute graft vs host reactions in mice.

3,6-Bis (piperidinoethoxy) acridine trihydrochloride (CL 246, 738) prevented the development of graft vs host (GVH) disease in normal BDF1 mice injected with C57BL/6 parental spleen cells. A single oral dose (50 mg/kg) given on day 0 or day -1 of GVH induction prevented the day 10 GVH-associated suppression of mitogen responsiveness and IL-2 production. The drug was ineffective if given later (days 3-7) in the reaction. The protective effect of CL 246,738 was neutralized by injecting drug-treated GVH mice with antibody to asialo GM-1 (ASGM-1). This suggested that the protective mechanism was not due to a direct effect of the drug on donor cells but rather was achieved indirectly through the activation of host ASGM-1+ cells which then rejected donor lymphocytes. This hypothesis was supported by immunofluorescence which showed that the donor-host chimerism seen in control GVH mice was not found in drug-treated GVH mice. Direct verification of this hypothesis was provided by data which showed that the transfer of CL 246, 738-activated large granular lymphocytes from normal F1 mice can prevent donor-induced immunosuppression in GVH mice. The results suggest that CL 246,738 is a potent immunostimulant which can boost natural resistance of normal unirradiated mice.

Acridines

Fringe-scan flow cytometry.

We describe the development of a scanning flow cytometer capable of measuring the distribution of fluorescent dye along objects with a spatial resolution of 0.7 micron. The heart of this instrument, called a fringe-scan flow cytometer, is an interference field (i.e., a series of intense planes of illumination) produced by the intersection of two laser beams. Fluorescence profiles (i.e., records showing the intensity of fluorescence measured at 20 ns intervals) are recorded during the passage of objects through the fringe field. The shape of the fringe field is determined by recording light scatter profiles as 0.25 micron diameter microspheres traverse the field. The distribution of the fluorescent dye along each object passing through the fringe field is estimated from the recorded fluorescence profile using Fourier deconvolution. We show that the distribution of fluorescent dye along microsphere doublets and along propidium iodide stained human chromosomes can be determined accurately using fringe-scan flow cytometry. The accuracy of fringe-scan shape analysis was determined by comparing fluorescence profiles estimated from fringe-scan profiles for microspheres and chromosomes with fluorescence profiles for the same objects measured using slit-scan flow cytometry.

Chromosomes