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Biomedical subjects

D Morgan

Publications and source records attributed to D Morgan.

At least 37 records · Page 2Linked to original sources
PubMed1991

Evolution of in vitro transformation and tumorigenesis of HPV16 and HPV18 immortalized primary cervical epithelial cells.

Cervical carcinoma develops through a progressive spectrum of premalignant intraepithelial lesions (CIN I-III), the majority of which are associated with human papillomavirus (HPV) types 16 and 18. We established HPV16 and HPV18 immortalized human cervical epithelial cell lines and used them as a model to investigate the genesis and progression of cervical malignancy. The cell lines when cultured in vitro in a system mimicking their in vivo environment exhibit cytologic atypia and a variety of defects in morphologic differentiation at early passage compared to their normal counterparts. With increased passage, these alterations progress to more severe grades, histologically similar to CIN III; however only a limited number of the cell lines are tumorigenic, mimicking the epidemiologic evidence on the rate of conversion from premalignant to invasive carcinoma. The observed changes are not associated with alterations of viral DNA integration or expression and may reflect specific cellular events or changes in virus-host interactions associated with malignant progression.

Cell Transformation, Neoplastic↗
PubMed1990

Prostaglandin E1 bladder instillations to control severe hemorrhagic cystitis.

Severe hemorrhagic cystitis developed in 6 children after marrow transplantation, 3 of whom had a viral etiology. All 6 patients received instillations of prostaglandin E1 directly into the bladder and 5 of the 6 had complete resolution of hematuria. This finding contrasts with our previous experience with severe hemorrhagic cystitis, particularly the type due to a viral infection, persisting in the face of numerous bladder manipulations. We encourage the use of this nontoxic treatment to gain further information regarding its effect on the bladder epithelium. The mechanism of action remains completely unknown.

Administration, Intravesical↗
PubMed1990

Human papillomavirus type 6b DNA required for initiation but not maintenance of transformation of C127 mouse cells.

We describe the transformation of C127 mouse fibroblasts with human papillomavirus type 6b (HPV-6b) DNA, which is associated primarily with benign tumors of the human genital tract. The major transformed phenotype of the HPV-6b-transfected cells lines, which had been G418 selected, pooled, and maintained without subsequent selection, was tumorigenicity in nude mice. We found that, unlike that reported for other HPVs or papovaviruses, the transformed phenotype was expressed after a delay, in which the cells had undergone extensive culture passages (about 20 passages or 100 generations). Interestingly, the HPV-6b DNA had become reduced or nondetectable in copy number in the cells by the time the transformed phenotype was expressed and in most of the tumors induced by the cells in nude mice, indicating that high levels of HPV-6b DNA were not required for maintenance of the transformed phenotype. Clonal cell lines gave similar results. When continued G418 selection was used to maintain high-copy-number HPV-6b DNA, the cells were tumorigenic, indicating that high levels of HPV-6b DNA did not suppress tumorigenesis. These studies suggest that HPV-6b DNA initiates transformation of C127 cells but is dispensable for expression or maintenance of the transformed phenotype. Transformation by HPV-6b DNA in vitro may provide insights into the HPV type-specific association with benign versus malignant lesions in vivo and may elucidate some of the oncogenic processes involved in tumor progression.

Animals↗
PubMed1990

Signature patterns of DNA restriction fragments of Helicobacter pylori before and after treatment.

The genomic DNA of Helicobacter pylori was studied by electrophoretic analysis of restriction endonuclease fragments. Twenty seven isolates from eight patients in the United Kingdom, obtained before and after treatment with nitrofurantoin, and two reference strains from Australia and Peru were investigated. Digestion of DNA with HaeIII, which gave the clearest band pattern of the 20 enzymes tested, showed that each set of isolates from a single patient had a unique band pattern. The DNA signature band patterns of strains from different patients were less than or equal to 62% similar (average 43%); similarities of patterns from the same patient were generally greater than or equal to 86%. Some minor but reproducible polymorphisms (less than or equal to five bands) in the signature region were detected in most consecutive isolates. Plasmid DNA was detected in isolates from five patients, but major pattern differences were attributed to genomic variation. It is concluded that the HaeIII DNA digest signature fingerprints provide a reproducible and sensitive method of discriminating between isolates of H pylori.

Campylobacter↗
PubMed1990

Nature of defibrillation: determinism versus probabilism.

The gradual transitions that are found between unsuccessful and successful shock strengths in percent success or dose-response curves suggest that defibrillation is a probabilistic phenomenon. This concept appears to be reinforced by the fact that a frequency distribution is observed in defibrillation threshold data and that a dose-response relationship is also obtained by integration of the frequency distribution. The purpose of this study was to investigate whether a deterministic threshold model (based on experimental results) could produce 1) gradual transitions in dose-response curves, and 2) a threshold frequency distribution for individual subjects. In the experimental phase of the study, a linear deterministic relationship was found between transthoracic threshold current and defibrillation episode number (other variables held constant) in pentobarbital-anesthetized dogs. The correlation coefficient for each dog was between 0.77 and 0.98 (P less than 0.01), and both positive and negative slopes were found. Based on these results, threshold current was modeled for computer simulation as a linear function of episode number. The model was thus purely deterministic with no random variability. For each simulated experiment, several parameters were varied: order of shocks (increment, decrement, random order), slope of threshold function, and percent error of the initial threshold. Several hundred computer simulations were performed to determine the effect of varying these parameters. In all cases, threshold-frequency distributions and sigmoidal dose-response curves with gradual transitions were produced. The results of this investigation demonstrate that the apparent probabilistic behavior of defibrillation can be produced by a deterministic relationship.

Animals↗
PubMed1990

Induction and autocrine receptor binding of transforming growth factor-beta 2 during terminal differentiation of primary mouse keratinocytes.

Primary cultures of mouse keratinocytes maintain a basal cell phenotype in 0.05 mM Ca2+ medium, while culture in 1.4 mM Ca2+ results in terminal differentiation and inhibition of DNA synthesis. Induction of differentiation by Ca2+ results in a 10- to 20-fold increase in the expression of transforming growth factor-beta 2 (TGF-beta 2) mRNA and peptide, but a decrease in the expression of TGF-beta 1. In contrast, binding and cross-linking analyses show that the number of available surface 80 kilodalton (kDa) and 65 kDa TGF-beta receptor types decrease during differentiation. However, a mild acid wash significantly increases the number of available receptor sites on the differentiated keratinocytes, indicating that the TGF-beta receptors are unavailable for binding due to masking by endogenous ligand. A significant level of TGF-beta 2 secretion and receptor binding occur before the decrease in DNA synthesis, suggesting that the inhibition of DNA synthesis associated with differentiation of keratinocytes is mediated through the production and autocrine action of TGF-beta 2.

Animals↗
PubMed1990

Immunological studies on onchocerciasis in Sierra Leone. 1. Pretreatment baseline data.

Cellular immune responses were tested in vitro using peripheral blood mononuclear cells from 203 individuals resident in an area of Sierra Leone where onchocerciasis is hyperendemic, and 32 individuals (Gambians) with no history of contact with Onchocerca volvulus. Mean reactivity to the mitogen, Concanavalin A, did not differ between these two groups, but responses to PPD were markedly lower in those with onchocerciasis. Proliferative responses to adult female O. volvulus antigen in the latter group were generally low although elevated reactivity was found in certain sub-groups. Higher responses were evident in infected 10-14 year olds, and there was an association between elevated reactivity to O. volvulus antigens and acute reactive dermatological signs, with individuals in the latter group also carrying higher dermal microfilarial loads. A sub-group presenting with lymphadenopathy showed the strongest associations of these three parameters. These results suggested the requirement for a threshold density of dermal microfilariae for induction of acute reactivity. The presence of immunosuppressive factors in soluble O. volvulus antigen was indicated by the ability to suppress, at low concentrations, the cellular responses to PPD of a proportion of individuals.

Adolescent↗
PubMed1990

Digital spot-film fluorography.

Initial assessment of the DSI unit proved the ergonomic advantages of the system compared with a conventional fluoroscopic/fluorographic system. Also, a decrease in radiation dose levels proved encouraging. Savings in respect of hard copy expenditure and higher patient throughout area which the DSI technique can exploit. However, spatial resolution is still not equal to that of conventional film/screen imaging, but the 1024 matrix option and the facility for post-processing of the images in terms of contrast, brightness and edge enhancement have produced diagnostically acceptable images for all examinations undertaken (see figures 4 and 5).

Adult↗
PubMed1990

Dislocated arytenoid: an intubation-induced injury.

Three reports describing the morbidity resulting from intubation-induced arytenoid cartilage dislocation are presented. Significant factors contributing to such an injury are: retrognathia, dental malocclusion, a large tongue base and intubation inexperience. We advise that in all patients who undergo a difficult intubation the possibility of arytenoid dislocation should be considered. A ventilating bronchoscope should be readily available upon extubation, to deal with any acute airway problem that may arise. Treatment modalities are discussed and the advantages of a combined anaesthetic and ENT approach highlighted.

Arytenoid Cartilage↗
PubMed1979

Intestinal absorption of 25-hydroxyvitamin D3 in unanesthetized rat.

We investigated the mechanism and characteristics of 25-hydroxyvitamin D3 (25-OH-D3) absorption in the unanesthetized rat by using a single-pass intestinal perfusion technique. The rate of 25-OH-D3 absorption remained linear for a wide range of concentrations (2-900 nM). Absorption rate of 25-OH-D3 increased as the pH, the bile acid concentration, and thickness of the unstirred water layer were decreased. Absorption did not change after the additions of fatty acids of varied chain lengths and degrees of saturation. In rats with lymph and bile fistulas, 18.5% and 16.3% of the infused radio-activity appeared in the lymph and bile drainage, respectively. These experiments indicate that 25-OH-D3 is absorbed by a passive diffusion mechanism that is influenced by the intestinal pH, bile acid concentration, and thickness of the unstirred water layer, but not by the presence of fatty acids. Approximately equal fractions of the infused hydroxylated vitamin are recovered from the lymphatic and biliary fluids.

Animals↗
PubMed1979

Recurrent intracerebral blastomycotic granuloma: diagnosis and treatment.

We present a patient with a recurrent intracerebral blastomycotic granuloma. The computerized tomographic scan appearance of this lesion is illustrated. Of the 81 reported cases of intracranial blastomycosis, only 35 have represented solid intracerebral lesions; the other patients have had spinal lesions or meningitis. This patient represents the first reported recurrence of an intracerebral blastomycotic granuloma. The treatment utilized, surgical resection combined with intravenous and intraventricular amphotericin B, represents a unique approach to this problem. The diagnosis and currently advocated treatment of intracranial blastomycosis is reviewed, particularly in regard to the potential for recurrence of blastomycosis.

Adult↗
PubMed1979

Subclinical effects of chronic increased lead absorption--a prospective study. II. Results of baseline neurologic testing.

This report summarizes the results of baseline neurologic testing in a group of apparently healthy workers from a secondary lead smelter and a group of controls from nearby aluminum processing plants. The test battery included a standard neurologic examination nerve conduction measurements, quantitative oculomotor function tests and detailed audiologic studies. Lead workers and controls were intermixed so that the examiners were unaware of the status of any individual being tested. Although the lead workers reported significantly more neurologic symptoms than the controls, relatively few differences were found on quantitative neurologic testing. Decreased deep tendon reflexes occured more frequently in the lead workers than in the controls (22% vs. 11%) but the difference was of borderline significance (p=0.06) and other signs of peripheral neuropathy occurred with equal frequency in both groups. The mean motor conduction velocity and sensory latency measurements were not significantly different in the lead workers and in the controls and, of the six oculomotor function measurements, only the mean accuracy of saccadic eye movements was significantly (p less than 0.01) different in the two groups. High frequency hearing loss occurred with equal frequency and severity in both groups, consistent with the level of noise exposure in the lead and control plants.

Absorption↗