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Biomedical subjects

D Owen

Publications and source records attributed to D Owen.

At least 19 recordsLinked to original sources

Maturation of the filaria Litomosoides sigmodontis in BALB/c mice; comparative susceptibility of nine other inbred strains.

When inoculated subcutaneously, the infective larvae of L. sigmodontis undergo complete development and produce a patent microfilaraemia in mice of the BALB background (BALB/c, BALB/K and BALB/B, with respectively the H-2d, H-2k et H-2b haplotypes). The most susceptible strain is BALB/c with all mice harbouring adult filariae and 47% of mice presenting with a patent microfilaraemia. Mice with the B10 background (B10, B10Br and B10D2, with respectively the H-2b, H-2k et H-2d haplotypes) are almost completely resistant to infection. Adult filariae were recovered from all mice of the CBA/Ca, CBA/HN, C3H/HeN, DBA/2N strains. However, the site and structural development of the parasite varied in each strain. Absence of microfilaraemia is associated with absent or abnormal spicules, reduced number of female filariae and small size of female filariae. These results show that the Major Histocompatibility Complex only modulates the developmental pattern of filariae within the limits imposed by background genes. Male CBA/HN and C3H/HeN were more susceptible to infection than female mice. Inverse phenomenon was observed with strains BALB/c; and, no host sex effect was seen in DBA/D2N.

Animals

Analysis of antibody responses directed against two Onchocerca volvulus antigens defined by monoclonal antibodies.

Monoclonal antibodies, reactive with antigens solubilised from the body wall of intact female Onchocerca volvulus using 2% 2-beta-mercaptoethanol, have been characterised. Two IgG1 antibodies, Cam1 and Cam28, recognised antigens of apparent molecular weights of 18,000 and 28,000; and 120,000, respectively. The target antigens of Cam1 and Cam28 could be localised in the cuticle. Inhibition ELISAs showed that target epitopes of both monoclonal antibodies induce an antibody response in onchocerciasis patients. 153 sera from Sierra Leonean patients were tested for their individual antibody levels against antigen epitopes recognised by Cam1 and Cam28. Patients within the age of 5-8 years had the highest levels of antibodies against the Cam28-epitope, whereas patients above 60 years had almost none. Amicrofilaremic patients had higher anti-Cam28 antibody levels than microfilaremic patients and there was a significant difference between groups with no chronic skin disease and those with mild or severe signs. A high percentage of patients (80.4%) recognised the Cam1-epitope, highest antibody levels being found in patients within the age group of 15 to 45 years and in microfilaremic patients. However, levels of antibodies inhibiting monoclonal antibody Cam1 could not be correlated with presence or absence of skin disease.

Adolescent

Is positive diagnostic peritoneal lavage an absolute indication for laparotomy in all patients with blunt trauma? The Montreal General Hospital experience.

The authors review the use of diagnostic peritoneal lavage (DPL) at The Montreal General Hospital between 1982 and 1987. Fifty-two of 254 patients admitted with a diagnosis of blunt abdominal trauma underwent DPL: results of the procedure were negative in 23 and positive in 29 (grossly positive in 27). Twenty-one of the 23 patients with negative findings were managed nonoperatively; the other 2 underwent laparotomy, which revealed no abnormalities. Nineteen of the 29 patients with positive findings were managed by immediate laparotomy; the other 10 were managed conservatively. The mean (+/- standard deviation) injury severity score (ISS) in the latter group was 13.1 +/- 8.01. The group managed by immediate laparotomy had an ISS of 25.91 +/- 12.81 (p = 0.007). The number of patients suffering from class I or class II shock in the group managed nonoperatively was significantly (p = 0.045) larger than those in the group managed by laparotomy. The authors conclude that a positive result DPL is not a sine qua non for immediate laparotomy in all patients with blunt abdominal trauma. A selective approach can be taken in these patients, considering the severity of the associated injuries and the patient's hemodynamic status. Intensive-care monitoring must be available.

Abdominal Injuries

Bolus versus infusion regimens of etoposide and cisplatin in treatment of non-small cell lung cancer: a study of the North Central Cancer Treatment group.

In an effort to test clinically the hypothesis that the duration of cellular exposure to etoposide (VP-16) and cisplatin (CDDP) is an important determinant of cytotoxicity, we performed a phase III randomized trial comparing an outpatient bolus regimen of combined VP-16 and CDDP with a sequential infusion over 72 hours of these same two drugs. All patients had stage IV non-small cell lung cancer, and survival was the primary end point. Of 113 patients randomly allocated to the study, 108 were assessable for response, survival, and toxicity. A major response was observed in 20 (37%) of 54 patients on the bolus regimen and in 16 (30%) of 54 patients receiving infusion therapy. The median time to progression was 61 and 88 days for bolus and infusion therapy, respectively. The median survival time was 148 and 157 days, respectively (P = .71). Study results were not consistent with the possibility that infusion therapy could be associated with a 50% improvement in median survival, i.e. from 5 months to 7 1/2 months. Toxicity was primarily myelosuppression and was significantly greater with the infusion regimen. We conclude that infusion therapy as tested in this protocol with VP-16 and CDDP does not offer any advantage in response rate, time to disease progression, or survival as compared with bolus therapy. In addition, infusion therapy is associated with a greater degree of neutropenia and more treatment-related deaths.

Adult

DNA sequence analysis of the imp UV protection and mutation operon of the plasmid TP110: identification of a third gene.

The sequence of the imp operon of the plasmid TP110 (which belongs to the Incl1 incompatibility group) has been determined, and is shown to contain three open reading frames. This operon, involved in UV protection and mutation, is functionally analogous to the umuDC operon of E. coli and the mucAB operon of the plasmid pKM101, which belongs to the quite unrelated IncN incompatibility group. The umu and muc operons however contain only two open reading frames, coding for proteins of approximately 16kD and 46kD. The high degree of homology between the two 16kD proteins (UmuD and MucA) and between the two 46kD proteins (UmuC and MucB) clearly shows their relatedness. This is shown also to extend to the imp gene products, with ImpA sharing homology with UmuD and MucA, and ImpB sharing homology with UmuC and MucB. However, the two imp genes are preceded in the operon by a third gene, impC, which encodes a small protein of 9.5kD and which has no equivalent in the umu and muc operons.

Amino Acid Sequence

Lymphocytic gastritis in patients with celiac sprue or spruelike intestinal disease.

A distinctive form of gastritis, characterized by lymphocytic infiltration of pit epithelium, has recently been described in association with evidence of Campylobacter pylori infection. We have evaluated simultaneous small bowel and gastric biopsies from 22 patients with diarrhea or malabsorption, all of which showed small bowel changes characteristic of sprue or spruelike disease. In 10 of 22 patients, striking lymphocytic gastritis was identified. Cases positive for lymphocytic gastritis had a mean of 46.5 lymphocytes per 100 epithelial cells, compared with a mean of 3.5 in normal gastric controls and 5.1 in abnormal controls, including cases with Campylobacter gastritis. Concurrent small bowel biopsies had a mean of 47.2 lymphocytes per 100 epithelial cells. Cases without lymphocytic gastritis had means of 10.8 and 39.9 lymphocytes per 100 gastric and intestinal epithelial cells, respectively. Campylobacter organisms were identified in only 1 of the 10 patients with lymphocytic gastritis and in 3 of the 12 patients without lymphocytic gastritis. Intraepithelial lymphocytes in small bowel and stomach were positive for the antibody MT-1, indicating a T-cell infiltrate at both sites. These findings suggest that lymphocytic gastritis may occur as a manifestation of celiac sprue or spruelike disease and that the lymphocytic infiltration of celiac sprue may affect gastric epithelial mucous cells.

Biopsy

Colonic lymphocytosis in patients with celiac sprue.

We examined colonic biopsies from 39 patients with clinical and small bowel biopsy changes of celiac sprue. In 12 of 39 patients (31%), striking lymphocytic infiltration of the superficial colonic epithelium and chronic inflammation of the lamina propria were identified. These 12 cases had a mean of 30.4 lymphocytes per 100 superficial colonic epithelial cells, compared with means of 8.4 in sprue cases without colonic epithelial lymphocytosis, 4.8 in normal controls, and 32.4 in nine cases of lymphocytic colitis without concurrent celiac sprue. No case showed subepithelial collagen layer thickening. Four patients with celiac sprue and colonic lymphocytosis also had gastric biopsies; two showed gastric lymphocytosis. Intraepithelial lymphocytes at all sites were positive for the T-cell marker MT-1. These findings indicate that sprue-associated colonic lymphocytosis and lymphocytic colitis are histologically, quantitatively, and immunohistochemically indistinguishable, that the epithelial T-cell infiltration of celiac sprue occurs in glandular mucosa at all levels of the gastrointestinal tract, and that colonic subepithelial collagen deposition in patients with celiac sprue is an infrequent occurrence. These findings also suggest that gastrointestinal epithelial T-cell infiltration may be an immunologic response that is common in individuals sensitized to absorbed lumenal antigens, and that colonic lymphocytosis may occur as a response to a number of antigens, including gluten.

Celiac Disease

Anal cloacogenic and squamous carcinomas. Comparative histologic analysis using in situ hybridization for human papillomavirus DNA.

In order to evaluate the morphologic and possible etiologic distinctions between anal cloacogenic and squamous carcinomas, we performed histologic examination and in situ hybridization for human papillomavirus (HPV) DNA on anal canal and anal verge carcinomas from 37 patients. Twenty-one neoplasms were invasive or in situ squamous carcinomas, 14 were invasive cloacogenic carcinomas, and two were unclassified. In situ hybridization was positive for HPV types 16/18 in 12 cases and for types 6/11 in two cases of anal squamous carcinoma (67% HPV positivity overall). All 14 cases classified as anal cloacogenic carcinoma were negative for HPV DNA by this technique. One of the two unclassified carcinomas was positive for type 16/18 DNA. We conclude that anal cloacogenic and squamous carcinomas are histologically similar but distinct neoplasms. Differential expression of HPV DNA in these lesions may be a manifestation of separate mechanisms of pathogenesis, or it may be due to varying degrees of tumor cell differentiation.

Anus Neoplasms

New discharge criteria decrease recovery room time after subarachnoid block.

The authors completed a two-phase study to determine criteria that might predict hemodynamic stability during recovery from subarachnoid block (SAB). Patients' supine and sitting (2 min) blood pressures were determined at 30-min intervals in the recovery room (RR). In the first group of 26 patients, retrospective analysis revealed that the orthostatic decrease in mean arterial pressure (MAP) never exceeded 15% following two successive orthostatic decreases of 10% or less. This finding was validated prospectively in a second group of 26 patients. Following two successive orthostatic MAP decreases of 10% or less, none of 65 orthostatic challenges resulted in an MAP decrease of more than 15%; conversely, in the absence of two successive MAP decreases of less than 10%, 5 of 51 orthostatic challenges resulted in an MAP decrease of greater than 15% (P less than 0.02). Had patients been discharged from the RR based on two successive MAP decreases of less than 10%, 35 of 52 patients could have been discharged from the RR 76 +/- 6 min (mean +/- SE) sooner than they would have under usual empirical discharge criteria of supine hemodynamic stability, regression of sensory level to T10, and return of toe movement. Following SAB, hemodynamic stability may return before sensory and motor function; for many patients, orthostatic testing following SAB may safely decrease the amount of time spent in the RR.

Aged

Noncoding 3' sequences of the transferrin receptor gene are required for mRNA regulation by iron.

The cell-surface receptor for transferrin mediates cellular uptake of iron from serum. Transferrin receptor protein and mRNA levels are increased in cells treated with iron chelating agents, and are decreased by treatment with iron salts or hemin. Here we report that expression of human transferrin receptor cDNA constructions in stably transfected mouse fibroblasts is regulated both by the iron chelator, desferrioxamine, and by hemin. We found that sequences within the 3' noncoding region are required for the iron-dependent feed-back regulation of receptor expression, whereas the presence of the transferrin receptor promoter region is not necessary. Regulation by iron is observed when transcription is initiated at either the SV-40 early promoter or the transferrin receptor promoter, but deletion of a 2.3 kb fragment within the 2.6 kb 3' noncoding region of the cDNA abolishes regulation and increases the constitutive level of receptor expression. Furthermore, the 3' deletion does not affect the decrease in receptors which is observed in response to growth arrest, indicating that transferrin receptor expression is controlled by at least two distinct mechanisms.

Animals

Eradication of the pinworm Syphacia obvelata from an animal unit by anthelmintic therapy.

Thiabendazole incorporated in the diet at a rate of 0.1%, fed to all animals over a period of 3 months, successfully eliminated the parasite from the colony. Samples taken 12 months after treatment were still negative for the parasite. During the period between the discovery of the organism and the preparation of the diet a course of piperazine citrate was administered at a rate of 2 g/litre in the drinking water in order to limit the spread of the infection.

Animals