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Biomedical subjects

J Newman

Publications and source records attributed to J Newman.

At least 145 records · Page 8Linked to original sources

Effects of chemotherapy on ultrastructure of oesophageal adenocarcinoma.

AIMS: To compare and contrast the ultrastructural appearance of resected oesophageal adenocarcinomas treated with preoperative chemotherapy with that of non-treated resected controls; and to determine the usefulness of this method in the assessment of the effectiveness of the chemotherapeutic regimen. METHODS: Ten resected oesophageal adenocarcinomas treated with preoperative chemotherapy--mitomycin-C, ifosfamide, and cisplatin (MIC)--were examined by transmission electron microscopy and their appearance compared with that of 13 concurrent untreated resected oesophageal adenocarcinomas. RESULTS: The treated adenocarcinomas showed cytotoxic damage although complete tumour eradication was not achieved. In all 10 treated cases a variable proportion of the neoplastic cells showed unusual degenerative and necrotic changes not seen in untreated cases. In the most affected carcinomas the stroma contained increased numbers of inflammatory cells. CONCLUSIONS: This ultrastructural method is useful for the assessment of the in vivo effect of MIC.

Adenocarcinoma↗

Inactivation of viruses with photoactive compounds.

The transmission of human immunodeficiency virus (HIV-1) and other enveloped virus by blood transfusion is a major concern. Photosensitive dyes such as hematoporphyrin derivative (HPD), dihematoporphyrin ether (DHE), benzoporphyrin derivatives (BPD), extended ring porphyrins, sapphyrins and texaphyrins, and various cyanines were used with viral cultures to test the feasibility of using those light-excitable dyes to kill virus. A photodynamic flow cell was used to irradiate viral suspensions or viral infected cells in culture media or in whole blood. Herpes virus (HSV-1) was used to screen compounds. Effective compounds were subsequently tested for their ability to kill HIV-1, CMV, and SIV in culture medium and in blood and proved to effectively kill free virus and infected cells at significant viremias. Irradiation was achieved with a filtered xenon light source and/or tunable dye laser. Concentrations of dyes at 10 times viral kill dose were irradiated in blood which was tested for damage to erythrocytes (RBC), platelets, and blood proteins. No damage to RBC, complement factors, and immunoglobulins was evident immediately after photodynamic treatment. Platelet condition is minimally modified with time. Photodynamic treatment of blood appears to be a feasible means of eradicating virus and some protozoans from blood.

Blood↗

Phase I immunotoxin trial in patients with B-cell lymphoma.

Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 micrograms/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (less than or equal to 85 micrograms/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had greater than 50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.

Adult↗

Probe diffusion in solutions of filamentous actin formed in the presence of gelsolin.

Dynamic light scattering was used to characterize the diffusion of monodisperse polystyrene latex spheres (PLS) of different sizes (55-, 105-, and 265-nm radii) in column-purified 0.65 mg/mL actin solutions polymerized with 100 mM KCl in the absence and presence of various amounts of the actin-binding protein gelsolin. The gelsolin and its interaction with actin was initially studied to ensure that the gelsolin could be used to produce filament populations with well-defined mean lengths. Measurements with PLS diffusion probes present showed, in the absence of gelsolin, that the effective local microviscosity in the actin solutions was 5-20 times that of water and that a large fraction of the PLS are trapped within the pores of the actin filament network, as found previously [J. Newman, K. L. Schick, & K. S. Zaner, (1989) Biopolymers 28, 1969-1980]. As the molar ratio of gelsolin to actin was increased, the diffusion coefficients of the PLS approached those in pure water while the degree of PLS trapping went to zero. Measurements of the dependence of the PLS diffusion coefficients on the ratio of actin concentration to the semidilute overlap concentration showed, for the smaller PLS, a transition occurring near the mean global overlap concentration. These results reflect the dissolution of the actin network as the gelsolin concentration is increased and illustrate the role of gelsolin/actin interactions in the control of macromolecular transport within the periphery of cells.

Actins↗

Host-parasite interface of the urinary bladder-inhabiting nematode Trichosomoides crassicauda: changes induced in the urothelium of infected rats.

The urinary bladders of rats infected with Trichosomoides crassicauda were studied by light, scanning and transmission electron microscopy. The bladder epithelium of infected rats showed a diffuse, mild, flat hyperplasia, four to six cells thick. The anterior parts of adult female worms were embedded in tunnels within the hyperplastic epithelium with the posterior portions of the parasites lying free in the bladder lumen. The hyperplastic epithelial cells forming the inner layer of the tunnel wall, adjacent to the parasite, showed degenerative changes. These cells contained single or multiple pycnotic nuclei. Their cytoplasm was fibro-granular in appearance, with few distinct organelles, and the luminal surfaces of the cells were not limited by plasma membranes. Small numbers of granular cells, similar in appearance to mast cells, were seen in, and possibly crossing, the epithelium. There was no infection-related increase in the number or type of inflammatory cells in the lamina propria. Questions of interest emerging from this study relate to the nutrition of an adult nematode occupying an intra-epithelial location, and the absence of a significant chronic inflammatory response to the mature worm. It is suggested that the avascular hyperplastic epithelium of the bladder is an immunologically 'protected site' for the mature female T. crassicauda.

Animals↗

Congenital heart disease, parental stress, and infant-mother relationships.

The effect of congenital heart disease on early social relationships was assessed by observing 42 infants with the disease and 46 healthy infants in a standardized laboratory setting with their mothers. Significantly fewer infants with congenital heart disease, in comparison with healthy peers, were considered to have secure relationships with their mothers. The quality of the infant-mother relationship in the group with congenital heart disease was not related to parents' reports of their own stress or psychologic well-being. Severity of illness did not have a direct effect on the quality of the infant-mother relationship, but securely attached infants showed more subsequent improvement in health than insecurely attached peers showed. Attention to the infant-mother relationship in clinical care may improve the social development of babies with congenital heart disease and may have positive effects on physical health as well.

Adult↗

Pupillometric assessment of excessive daytime sleepiness in narcolepsy-cataplexy.

Ten untreated patients with narcolepsy-cataplexy and age- and sex-matched normals between the ages of 20 and 71 years underwent pupillometric analyses immediately prior to each of five multiple sleep latency test sessions. Although narcoleptics were sleepier as indicated both by their Stanford Sleepiness Scale ratings and by their latencies to sleep onset, the baseline pupil diameter, pupillary light reflex, and pupillary orienting response did not differentiate between groups. Narcoleptics did, however, exhibit a significantly greater frequency of spontaneous oscillations in the dark-adapted state than did controls. These findings indicate that pupillary stability may serve as a supplementary diagnostic tool for narcolepsy-cataplexy. The results are discussed with the view that psychosensory restoration of alertness, among other extraneous variables, must be controlled when utilizing pupillometric techniques. A review of the literature indicates a variety of methodological and statistical shortcomings that must be amended. Suggestions are made for improving the reliability and validity of the pupillometric approach.

Adult↗

Granulomatous prostatitis: a clinicopathological study.

In a clinicopathological study of granulomatous prostatitis, we have found two distinct histological patterns. Approximately one third of cases consisted of localized, often elongated or stellate lesions, resembling rheumatoid nodules. Where clinical details were available, most of these cases had a history of previous transurethral resection. The remaining cases showed more diffuse involvement of the prostate, with lesions centred on ducts and glands, and were not associated with previous prostatic surgery or systemic illness. Immunohistochemical studies of the associated inflammatory infiltrate showed an apparently random distribution of T- and B-lymphocytes in the former group, while in the latter group there was a concentration of T-cells in and around damaged ducts and glands, suggesting a possible immune-mediated destruction of these structures.

Adult↗

Lymphoepithelial cyst of the pancreas.

A case of lymphoepithelial cyst of the pancreas is reported. The unilocular cyst was filled with keratin, lined by mature, keratinizing squamous epithelium and surrounded by lymphoid tissue.

Aged↗

Intestinal graft versus host disease.

An ileocolectomy specimen was examined from a patient with graft versus host disease (GvHD). In addition to the characteristic histological features of this condition, both the small and the large intestine showed extensive destruction of mucosal tissue with survival of clusters of enterochromaffin cells. This appearance has previously been described only in the large bowel. Endocrine cells seem to be less vulnerable to the effects of GvHD than epithelial cells, resulting in their being spared, which is not seen in other types of crypt destruction.

Adult↗