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P A Mitchell

Publications and source records attributed to P A Mitchell.

12 recordsLinked to original sources
PubMed1998

Cervical cancer in the elderly treated with radiation therapy.

OBJECTIVES: The aim of this study was to evaluate the tolerance and outcome of elderly cervical carcinoma patients treated with radiation therapy (RT). METHODS: Three hundred ninety-eight patients with stage I-III cervical carcinoma treated with definitive RT were analyzed. Patients were divided into nonelderly (ages 35-69) (n = 338) and elderly (ages >/= 70) (n = 60) groups. A comparison of patient, tumor and treatment factors, morbidity, and outcome was performed. Median follow-up was 81 months. RESULTS: Elderly patients had a higher rate of comorbid conditions including diabetes (P = 0. 02), coronary artery disease (P = 0.003), and hypertension (P = 0. 001) than younger patients. Comorbid conditions in the elderly resulted in more frequent treatment breaks and less ability to undergo definitive treatment with intracavitary RT (ICRT). While the 5-year actuarial disease-free (DFS) and cause-specific (CSS) survival rates were comparable between the two groups, disease recurrence and death from cervical cancer were more common beyond 5 years in the elderly group. When patients not undergoing ICRT and those with treatment protraction were excluded, differences in the DFS and CSS curves were no longer evident. The frequency and severity of acute and chronic sequelae were similar. CONCLUSIONS: Elderly cervical carcinoma patients have an equivalent overall outcome following radiation therapy to younger patients when comparable treatment is delivered. Age per se is not associated with a higher rate of acute or chronic sequelae. Comorbid conditions adversely impacted on the quality and delivery of RT in the elderly group and help explain observed differences in outcome based on age.

Adult↗
PubMed1995

Wave collation visual speech display: design and evaluation.

The wave collation display is a pitch-synchronous, time-domain visual speech display. Collation processing maps the speech waveform into a planar array, condensing the waveform and making speech information, including pitch contour and formant transitions, salient. Evaluation included both analytic evaluation and training. Analytic evaluation was based on a perceptual sorting task using untrained subjects. Subjects sorted printed speech display tokens by visual similarity in a match-to-exemplar design. Stimuli included vowels, with single speaker, multiple speakers, and multiple phonemic contexts, and voiceless consonants. Results for untrained subjects ranged from 73% correct (consonants) and 71% correct (vowels) for single speaker tokens to 46% correct (multiple speaker vowels). For comparison, analytic evaluation using spectrograms was also performed for vowels with single and multiple speakers. Overall results were statistically equivalent to the collation display, with 76% correct (single speaker vowels) and 44% correct (multiple speakers). In the training component, four subjects were trained on collation display sorting tasks as above; after mastering these tasks, generalization to novel stimuli was tested. The tasks were mastered in a few hours, and generalization to novel tokens from a familiar speaker was nearly perfect; generalization to unfamiliar speakers was imperfect.

Color Perception↗
PubMed1991

Colloidal gold localization of type IV collagen in the extracellular matrix of rat gastric mucosa: influence of alcohol and prostaglandin.

The effect of acute alcohol exposure on the gastric mucosal basal lamina, and its major structural protein type IV collagen, was assessed by transmission electron microscopy (TEM) and immunogold (IG) labeling of this collagenous material. Fasted rats orally received either 50% or 100% ethanol. Five or 60 minutes later animals were sacrificed and mucosal samples were obtained from the glandular epithelium for TEM or IG localization of type IV collagen. For IG studies, the number of gold particles/area lamina densa was quantified in interfoveolar, pit, and gland regions as an index of the molecular integrity of type IV collagen. Both ethanol concentrations induced epithelial exfoliation with pleating of the denuded lamina densa. Absolute ethanol, and to a lesser extent 50% ethanol, caused frequent rupture of a thickened, precipitated lamina densa. Immunolabeling of type IV collagen varied with the experimental protocol. In control tissues exposed to oral saline, binding was greatest in the interfoveolar zone. Low binding occurred with 100% ethanol in all regions when compared with controls, but 50% ethanol evoked significantly higher binding in interfoveolar regions, in a similar fashion to controls. In additional studies in which 16,16 dimethyl prostaglandin E2 (PGE2) (10 micrograms/kg) was injected subcutaneously prior to oral ethanol exposure, PGE2 pretreatment prevented the large decrease in IG binding induced by absolute ethanol, but the level still remained significantly less than with corresponding controls. In contrast, pretreatment with PGE2 prior to 50% ethanol exposure restored type IV collagen immunolabeling to control levels. These results indicate that ethanol induces a concentration-dependent lowering of IG binding to type IV collagen which also effects its reversibility by PGE2.

Animals↗
PubMed1990

Effects of alcohol on lectin binding affinity in rat gastric mucosa.

Fluoresceinated lectins were employed to qualitatively evaluate cell surface carbohydrates, with and without ethanol exposure, in rat stomach mucosae. Rats received 1 ml of saline, or 50% or 100% ethanol orally. After 30 min, tissue samples of the glandular stomach were retrieved, cryosectioned, and incubated with one of a panel of lectins. Another set of sections was preincubated with neuraminidase to remove sialic acid residues. Qualitative evaluation of lectin binding showed that although several different sites stained, concanavalin A was the only lectin to stain the extracellular matrix, and soybean agglutinin the only lectin to stain chief cells. Neuraminidase preincubation enhanced lectin binding to both stained and previously unstained sites. Ethanol, both 50% and 100%, produced changes in both neuraminidase-treated and untreated tissues, increasing the specific binding of concanavalin A, Ulex europaeus agglutinin I, and wheat germ agglutinin, while decreasing Helix pomatia agglutinin and soybean agglutinin. These results suggest that ethanol can, through unknown mechanisms, alter carbohydrate binding affinity.

Animals↗
PubMed1987

Ultrastructural and freeze fracture localization of multilamellar liposomes containing a lipophilic cisplatin analogue in normal tissues and liver metastases of M5076 reticulosarcoma.

The tissue localization of multilamellar vesicles (MLV) (size 0.5-5.0 microns) composed of dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG) (molar ratio 7:3) containing a lipophilic cisplatin analogue (NDDP) was studied in mice by freeze fracture (FF) and transmission electron microscopy (TEM). Liposomes were observed within cytoplasmic vacuoles of hepatocytes and Kupffer cells in normal mice as early as 5 minutes after intravenous (iv) administration of MLV-NDDP. Liposomes within hepatocytes were more numerous but smaller in diameter (0.5-2.0 microns) than those within Kupffer cells (2.0-4.0 microns). In normal lung examined by FF or TEM at 5 minutes after MLV-NDDP administration, liposomes were only observed in the intravascular space. Liposomes could not be identified within Type I or II pneumocytes nor within the alveolar space. Two hours after iv administration, the distribution within the liver showed an increased number of liposomes in the hepatocytes with some evidence of liposome decomposition. The distribution in the lung was virtually identical to that observed at 5 minutes. The pattern of tissue localization within lung and liver of empty MLV 5 minutes and 2 hours after iv administration was identical to that of MLV-NDDP. In mice bearing gross liver metastases of M5076 reticulosarcoma, liposomes were present in the cytoplasm of tumor cells as well as normal cells 5 minutes and 2 hours after the iv administration of MLV-NDDP. These studies suggest that MLV composed of DMPC and DMPG containing NDDP are able to cross the liver sinusoidal capillaries and gain access to both hepatocytes from normal liver and malignant cells of M5076 reticulosarcoma from liver metastases.

Animals↗
PubMed1987

Gap junction modulation in rat uterus. III. Structure-activity relationships of estrogen receptor-binding ligands on myometrial and serosal cells.

A number of steroidal and nonsteroidal estrogen receptor-binding ligands were tested for their ability to affect the formation and internalization of gap junctions in hypophysectomized rat uterine myometrial and serosal cells. Potent estrogen, including diethylstilbestrol, estradiol benzoate (EB), estradiol-17 beta, and the weak estrogens, estriol and estrone, stimulate formation of macular and annular gap junctions in myometrium in a dose-dependent fashion when administered in daily injections over 5 days. Induction of annular gap junctions in the uterine serosal epithelium follows a similar dose-dependent pattern of estrogen stimulation but requires lower levels of hormone to initiate the response. In myometrium, differential stimulation of circular and longitudinal myometrial cell layers was observed, with 3 to 5 times more gap junctions detected in the circular than in the longitudinal layer. Progesterone, estriol, or estrone suppress the myometrial gap junction response to EB when administered concurrently with EB. However, the EB-stimulated appearance of myometrial cell gap junctions was blocked when the progesterone-to-estrogen ratio exceeded 100:1. The estrogen receptor-binding androgens, 5 alpha-androstane-3 beta,17 beta-diol (Adiol) and delta 5-androstene-3 beta,17 beta-diol failed to induce myometrial gap junctions at doses up to 5 mg/day for 5 days, whereas Adiol did induce annular gap junctions in the serosal cells at the highest dosage tested. Of the triphenylethylene derivatives and related compounds evaluated, including mixed isomers of tamoxifen and CI 628, the cis (zuclomiphene, ZUC) and trans (enclomiphene) isomers of clomiphene citrate, and a fixed-ring antiestrogen, nafoxidine, only ZUC was able to induce gap junctions in myometrial and serosal cells. These studies indicate that induction of gap junctions in rat uterine myometrial cells is an estrogen-dependent response that requires higher levels of estrogen than other estrogen-dependent target cell responses in the rodent uterus.

Animals↗
PubMed1987

Taurodeoxycholate and the developing rabbit distal colon: absence of secretory effect.

Failure to absorb bile acids by the ileum leads to fluid secretion by the colon and diarrhea in adults. The infant ileum, however, does not actively transport bile acids. Therefore, we investigated the effect of taurodeoxycholic acid (TDCA) on ion transport in the colon of rabbits 7-10 days old. We mounted distal colon from infant and adult rabbits in modified Ussing chambers and exposed the mucosal or serosal surfaces to TDCA. In the adult, 50 microM TDCA produced an increase in short-circuit current (delta Isc = 1.0 +/- 0.3 mu eq . h-1 . cm-2, P less than 0.05) and Cl secretion. In the infant, the effect was different, Isc was reduced (delta Isc = -1.1 +/- 0.2 mu eq . h-1 . cm-2, P less than 0.01) and ion flux was not altered. Microscopy demonstrated that the infant epithelium was not significantly damaged by exposure to TDCA at these concentrations. The infant colon was, however, capable of a secretory response to a variety of agonists including theophylline, carbachol, bradykinin, serotonin, and 12,13-dibutyryl phorbol ester. The infant rabbit distal colon lacks a secretory response to TDCA during that period when the ileum cannot transport bile acids.

Animals↗
PubMed1987

The protective effects of a prostaglandin without antisecretory properties against ethanol-induced injury in the rat stomach: a histologic study.

This study examined the effect of 2-acetyl-2-decarboxy-15(S)-15 methyl PGF2 alpha (PGF2 alpha) on ethanol (EtOH) induced injury in the rat stomach to determine if a PG analogue devoid of antisecretory properties could confer full or partial gastric mucosal protection. Rats were orally administered saline or PGF2 alpha in a dose of 0.5 or 5.0 mg/Kg. Thirty minutes later animals received varying concentrations (i.e. 25%, 50%, and 100%) of EtOH orally. Five minutes following EtOH exposure, they were killed and samples taken from identical regions of the glandular mucosa for microscopic evaluation. All concentrations of EtOH tested damaged the gastric epithelium. The injury induced by 25% EtOH was almost exclusively confined to the surface epithelium and was not altered by either dose of PGF2 alpha pretreatment. In contrast, both 50% and 100% EtOH elicited comparable damage to the gastric mucosa involving both the deep and superficial mucosa of virtually the entire epithelium. The deep injury induced by these two EtOH concentrations was prevented by both the low and high dose of PGF2 alpha. Of particular importance the 5.0 mg dose of PGF2 alpha provided complete protection (i.e. both superficial and deep) to as much as 50% of the mucosa exposed to 50% or 100% ethanol. These findings indicate that PGF2 alpha possesses "cytoprotective" properties involving both the superficial and deep epithelium that are dose related.

Administration, Oral↗
PubMed1986

The ontogeny of nexuses (gap junctions) in the ovary of the fetal mouse.

Nexuses (gap junctions), the morphological correlates of direct cell-to-cell communication, were consistently detected between granulosa cells of primordial follicles in the ovaries of adult cycling, juvenile, or neonatal mice. To examine the ontogeny of these intercellular channels, the cellular interactions occurring during the fetal stages of folliculogenesis, which culminate in the formation of primordial follicles, were analyzed in ovaries from fetal days 13, 15, 17, and 19. On fetal day 13, the ovary is characterized by clusters of germinal cells and invading rete ovarii cells. The rete cells progressively penetrate the ovary and wall off clusters of oocytes by fetal day 17, at which time rete cells can be recognized as presumptive granulosa cells. Gap junctional contacts can be recognized between rete cells on day 13 and these contacts persist as the cells become recognizable as presumptive granulosa cells throughout ovarian histogenesis. Quantification of junctional contacts from days 15-19 indicated that the number of gap junctions increases with fetal age. In addition heterocellular gap junctional contacts were detected between oocytes and presumptive granulosa cells as early as fetal day 17, indicating that the potential for direct intercellular communication between granulosa cells and oocytes is established from the earliest contact.

Animals↗
PubMed1984

Gap junction modulation in rat uterus. II. Effects of antiestrogens on myometrial and serosal cells.

The ability of several triphenylethylene antiestrogens to affect the modulation of gap junctions in rat uterine myometrial and serosal cells was examined in animals 60 days following hypophysectomy. Five daily injections of enclomiphene, zuclomiphene, tamoxifen, nafoxidine, CI 628 or CI 680 (500 micrograms per injection) promote uterine luminal epithelial cell hypertrophy characteristic of exogenous estrogen administration. These same compounds, however, fail to induce myometrial cell or increase the number of serosal cell gap junctions, respectively, which is also characteristic of exogenous estrogen treatment. Pretreatment of animals with antiestrogens blocks the ability of estradiol benzoate (E2 B) to induce gap junction formation in myometrial cells when followed by combined injections of E2 B and antiestrogens (both 250 micrograms) administered daily for 5 days. Therefore, with respect to the parameter of myometrial cell gap junction stimulation, all of the antiestrogens examined act as pure estrogen antagonists. These same antiestrogen pretreatments only weakly antagonized the ability of E2 B to modulate serosal cell gap junction membrane. These studies indicate the presence of different mechanisms for the estrogenic modulation of gap junctional membrane in myometrial and serosal cells.

Animals↗