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Biomedical subjects

J K Robinson

Publications and source records attributed to J K Robinson.

At least 19 recordsLinked to original sources

Comparative studies of transcytosis and assembly of secretory IgA in Madin-Darby canine kidney cells expressing human polymeric Ig receptor.

Epithelial transport of polymeric IgA (pIgA) from its site of synthesis to the mucosal lumen is mediated by the polymeric Ig receptor (pIgR). During transcytosis, a disulfide bond forms between pIgR and pIgA, resulting in secretion of a covalently linked complex. To dissect further the intracellular processing and functions of pIgR, we have expressed the entire coding sequence of human pIgR cDNA in Madin-Darby canine kidney (MDCK) cells. Cloned transfected cells express human pIgR, as detected by immunofluorescence and by quantification of the cleaved extracellular domain of pIgR in culture supernatants. The function of transfected pIgR was confirmed by measuring vectorial transcytosis of 125I-labeled pIgA and its disulfide bonding to pIgR. Species specificity of transcytosis was determined by comparing transport of human, rat, and mouse pIgA in MDCK cells expressing either human or rabbit pIgR. pIgA from all three species was transported by both human and rabbit pIgR, with rat pIgA being transported to the greatest extent in each case. However, disulfide bonding was observed only with human pIgR, and was found to occur mainly inside the cell. Our results suggest that conformational differences between human and rabbit pIgR may account for differences in disulfide bonding to pIgA, and show that efficient transcytosis of pIgA is correlated better with noncovalent than covalent binding to pIgR.

Animals

Skin cancer risk and sun protection learning by helpers of patients with nonmelanoma skin cancer.

BACKGROUND: Knowledge-based skin cancer risk and prevention educational interventions by physicians and nurses were directed to subjects who had a nonmelanoma skin cancer. These high-risk patients asked relatives or friends to assist with postoperative care rendered after surgical removal of the skin cancer. The patient's experience with the nonmelanoma skin cancer was expected to raise the awareness of the helper. The study examined whether the patient became a source of information, risk assessment, and skills training for his or her helper. METHODS: Sequential patients between 30 and 60 years of age and their designated helpers completed a self-report questionnaire prior to the intervention and 1 year after the intervention. The questionnaire examined: (a) knowledge of skin cancer and sun protection; (b) individual susceptibility as determined by ease of sunburning or tanning; (c) attitudes about self-esteem, sun exposure, and health locus of control; (d) intentions to use sun protection; and (e) behaviors of sun protection used. RESULTS: Over the course of 1 year, 200 pairs were entered into the study. Both patients and helpers demonstrated an increase in knowledge after the educational intervention with the patients. There was a change in the self-reported intention to use sun protection and the behaviors of sun protection used in both patients and helpers after the intervention; however, there was no attitudinal change demonstrated in pre- and post-tests for either patients or helpers. Among both patients and helpers, gender-specific differences in attitudes, intentions, and behaviors existed. Women expressed a greater likelihood of taking precautions, including the use of sunblock; however, men reported the protective strategy of wearing a hat more than women did. Men valued a tan more than women and had greater outdoor exposure, which they restricted after the intervention. Women helpers ceased using indoor tanning devices after the intervention. Behavioral change in use of sun protection measures, including protective clothing or sunblock use and decrease in hours of outdoor sun exposure or use of indoor tanning devices, was dependent upon the patient or helper's own reported susceptibility as determined by his or her history of poor tanning and ease of sunburning. CONCLUSION: Patients transferred knowledge to their helpers. Intention to change behavior and behavioral change were strongly correlated with the individual's reported susceptibility to easy sunburning and poor tanning. Despite a lack of change in attitudes, changes in both intention to change behavior and behavior itself occurred in those who perceived themselves to be at risk. While the attitudes of participants in this study reflected popular beliefs, targeted education of high-risk adults with a nonmelanoma skin cancer caused changes in sun protection behaviors in both the patients and their helpers.

Adult

Socioeconomic status and attitudes of 51 patients with giant basal and squamous cell carcinoma and paired controls.

BACKGROUND: Giant nonmelanoma skin cancers are disfiguring and clearly visible. This prospective study examined tumor characteristics, ie, location, tumor type, duration, and the socioeconomic status and attitudinal characteristics of these patients and their interactions with the medical community. DESIGN: From 1979 through 1993, preoperative questionnaires about age, sex, tumor duration, prior treatment, socioeconomic status, and attitudinal concerns were completed by 51 patients with giant tumors and randomly matched controls. Additional data completed by the physician included tumor type, location, and preoperative clinically apparent diameter of the tumor. RESULTS: Giant tumors were more frequent on the scalp in men. Lower socioeconomic status and infrequent physician visits were characteristic of those with giant lesions. Those with giant lesions were less concerned about their general health, had a greater sense of shame about their appearance, had greater belief that since prior treatment did not help the problem then nothing else would, and had an increased frequency of perceived prior reassurance. Women and those younger than 65 years of both sexes were more concerned about economic costs and/or the time lost from work or caring for others. CONCLUSIONS: Health promotion by early detection and treatment of these nonmelanoma skin cancers in elderly men could prevent extensive surgical efforts later in the course of the disease. Skin screening examinations by all physicians and better public awareness of the signs of skin cancer, especially among elderly men, would enhance early detection; however, it is not clear that early detection by physicians enables treatment. Strategies to assist individuals in overcoming their barriers to accessing care need to be provided.

Adult

Analysis of anatomical sites at which galanin impairs delayed nonmatching to sample in rats.

Galanin, a neuropeptide that coexists with acetylcholine in the septohippocampal pathway of the rat, impairs operant delayed nonmatching to sample (DNMTS) when administered intracerebroventricularly. Microinjection experiments were conducted to determine the anatomical site or sites at which galanin acts to disrupt DNMTS. Galanin (0.1, 0.4, or 1.6 nmol) was microinjected into the ventral hippocampus, amygdala, nucleus basalis magnocellularis, prefrontal cortex, or entorhinal cortex. Galanin disrupted DNMTS in a dose-dependent manner when microinjected into the ventral hippocampus but not at the other sites tested. These findings are consistent with the ability of galanin to inhibit physiological and biochemical actions of acetylcholine in the ventral hippocampus.

Acetylcholine

Galanin antagonists block galanin-induced feeding in the hypothalamus and amygdala of the rat.

Galanin significantly increased food intake when microinjected into the region of the central nucleus of the amygdala as well as into the paraventricular nucleus of the hypothalamus. In the amygdala this effect was specific to feeding; no change in grooming, resting, or other behaviour was observed after galanin treatment. These results provide evidence that the amygdala may be an important site in the mediation of galanin-induced feeding. The galanin receptor antagonists, C7 and M40, antagonized galanin-induced feeding, while having no effect alone on food consumption in free-feeding rats. These new galanin receptor antagonists provide useful tools for further investigating the role of endogenous galanin in the regulation of feeding.

Amino Acid Sequence

Galanin receptor antagonists M40 and C7 block galanin-induced feeding.

Two peptide antagonists of the galanin receptor, M40 (galanin[1-13]-Pro-Pro-[Ala-Leu]2-Ala amide) and C7 (galanin[1-13]-spantide amide), significantly inhibited galanin-induced consumption of a palatable wet cookie mash, when microinjected intraventricularly to satiated rats. Antagonists were effective at doses equimolar to or less than the active doses of galanin. Feeding induced by an overnight fast was not significantly different in rats microinjected with saline as compared to M40 or C7, at doses which inhibited galanin-induced feeding. The activity of the chimeric compound, C7, did not appear to be linked to the properties of its C-terminal spantide-like sequence, as C7 did not induce barrel rolling at doses which inhibited galanin-induced feeding. The IC50 for displacement of 125I-[Tyr26]-porcine galanin 1-29 binding in rat hypothalamic membranes was 15 nM for M40, and 0.2 nM for C7, as compared to 0.8 nM for unlabelled porcine galanin(1-29). These two structurally different galanin antagonists, both demonstrating antagonist activity in vivo in awake, behaving rats, provide promising tools for further analyses of the functional activity of galanin in the mammalian brain.

Amino Acid Sequence

The role of galanin in cholinergically-mediated memory processes.

1. Galanin, a 29 amino-acid neuroactive peptide, has been shown to affect diverse processes throughout the nervous system and to coexist with several "classical" neurotransmitters, including norepinephrine, serotonin, and acetylcholine. 2. Galanin coexists with acetylcholine in neurons of the medial septum, diagonal band, and nucleus basalis of Meynert, cells which degenerate during the course of Alzheimer's disease. 3. In the ventral hippocampus, galanin inhibits the release of acetylcholine and inhibits carbachol stimulated phosphatidyl inositol hydrolysis. 4. Galanin impairs choice accuracy in learning and memory paradigms in rats, and is therefore hypothesized to be a contributory factor in the memory and cognitive disabilities found in Alzheimer's patients. 5. Newly developed galanin antagonists, by eliminating putative inhibitory effects of endogenous galanin on cholinergic function, may serve as useful therapies for memory disorders.

Animals

Intraventricular galanin impairs delayed nonmatching-to-sample performance in rats.

Galanin is a neuroactive peptide that coexists with acetylcholine in the basal forebrain region. Galanin inhibits cholinergic functions in vitro and in vivo and has been shown to impair performance in some memory tasks. The present study compared the effects of galanin with the effects of scopolamine (a muscarinic antagonist) and ketamine and MK-801 (both NMDA receptor antagonists) on performance of an operant, spatial, delayed nonmatching-to-sample task in rats. Choice accuracy was impaired in a dose-dependent but delay-independent manner by galanin, scopolamine, and MK-801 but was not systematically influenced by ketamine. Measures of session duration, trials completed, discrimination accuracy, preservation, within-trial error distribution, and operant lever pressing were also analyzed. These results support observations that galanin disrupts performance in memory tasks requiring delayed responding but that the disruption is not specific to mnemonic capabilities.

Animals

Intraseptal galanin potentiates scopolamine impairment of delayed nonmatching to sample.

Galanin coexists with ACh in the basal forebrain and medial septal region. The present study investigated the interactions of the muscarinic receptor antagonist scopolamine and the neuropeptide galanin on an operant spatial delayed non-matching to sample task (DNMTS) in rats. Scopolamine administered both intraperitoneally and microinjected into the medial septum impaired performance on DNMTS. Galanin administered alone into the medial septum did not disrupt DNMTS, but potentiated the disruptive effects of intraperitoneal administered scopolamine. These findings raise the possibility that endogenous galanin may exacerbate cognitive impairments associated with forebrain cholinergic deficits.

Acetylcholine

Compensation strategies in sun protection behaviors by a population with nonmelanoma skin cancer.

BACKGROUND: Initiation of sun protection strategies can be promoted, to some extent, by educational efforts, but little is known about the merit of continuing education interventions in sustaining the desired behaviors or adding new behaviors. This prospective study clarifies the choices individuals make among the four strategies that allow them to maintain lifestyle changes. METHODS: From 1983 to 1987, the population received education about sun protection coupled with the removal of a nonmelanoma skin cancer. One year later, their choice of sun protection methods was determined. Then annually from 1985 to 1989, they received written recommendations about sun protection for a period of 2-6 years after the initial education. The maintenance, cessation, and addition to the initial sun protection behaviors were ascertained by a questionnaire, as was the intention to change. Frequency of physician visits and development of subsequent nonmelanoma skin cancer were evaluated by medical chart review for the 2-6 year phase of continued education. RESULTS: One percent of the population consisting mostly of women described ceasing tanning after 2-6 years of education. The population related a greater use of protective clothing and/or sunscreen with an SPF of 15 or greater as their reported restrictions on outdoor activities ceased. An emerging new strategy of some of the population (n = 185) was the use of sunscreens with an SPF less than 15 in association with attempts to deliberately tan and longer daily outdoor exposure. Neither frequency of physician visits nor numbers of subsequent nonmelanoma skin cancers influenced continuation or addition of sun protection behaviors. CONCLUSIONS: While the greatest reported change in behavior was temporarily associated with educational intervention linked to removal of the skin cancer, continued educational efforts may have recruited some individuals to cease tanning and encouraged others to adopt the use of protective clothing or more frequent sunscreen use as they were unable to maintain the limitations on outdoor activities. It is not possible to structure a control group restricted from mass media education; therefore, the effectiveness of specific behavior-directed education cannot be precisely determined. Nonetheless, the population described using knowledge to develop compensation sun protection strategies that preserved lifestyle.

Choice Behavior

Delayed-nonmatching-to-sample performance is impaired by extensive, but not by limited, lesions of the thalamus in the rat.

Two experiments were conducted to determine whether lesions affecting limited areas of the thalamus can impair the performance of rats on a spatial delayed-nonmatching-to-sample (DNMTS) task trained before surgery. In Experiment 1, DNMTS was not affected by lesions produced by injecting 5 microliters of 1 mM N-methyl-D-aspartate into either the midline thalamus (n = 16) or bilaterally 1.0 mm from the midline (n = 16). In experiment 2, radio-frequency lesions were made 1.0 mm lateral to the midline at 3 anterior-posterior locations that destroyed the full rostral-caudal extent of the lateral internal medullary lamina (L-IML; n = 8), or at single anterior-posterior locations that destroyed either the anterior (n = 8) or posterior (n = 8) portions of the L-IML site. Although complete L-IML lesions disrupted DNMTS performance to an extent comparable to that of another study (Mair & Lacourse, 1992), lesions that were restricted to either the anterior or posterior portion of the L-IML site had no significant effect on this task.

Animals

Alteration in keratinocyte ganglioside content in basal cell carcinomas.

We examined the ganglioside content of normal human keratinocytes and basal cell carcinomas (BCC). The total ganglioside content of the epidermis was 0.098 +/- 0.01 microgram lipid-bound sialic acid/mg dry weight. GM3 was the predominant ganglioside of epidermis. GM2 and GD3 were also found in significant amounts. Polysialylated gangliosides were identified in only small amounts. In contrast to all other body locations, breast epidermis showed large amounts of GM1. The total ganglioside content of nodular and sclerosing facial BCC was approximately 3.5 times that of normal facial epidermis. This marked elevation of total ganglioside was not affected by dermal ganglioside contamination, because the total ganglioside content of the dermis was similar to that of the epidermis. The relative percentage of GM2 was significantly decreased, whereas the relative percentage of GM3 was slightly decreased in BCC. 9-O-acetyl-GD3 was present in the BCC, but not in normal epidermis or dermis. 9-O-acetyl-GD3 may be a surface marker for BCC. Furthermore, the alterations in amount and composition of individual gangliosides on neoplastic membranes may lead to novel therapeutic interventions.

Basal Cell Carcinoma

Relative importance of prior basal cell carcinomas, continuing sun exposure, and circulating T lymphocytes on the development of basal cell carcinoma.

This 36-month prospective study of a group of 61 people at high risk to develop multiple basal cell carcinomas (BCC) examined the circulating lymphocyte subsets of the population, patterns of sun exposure, and the longitudinal development of basal cell carcinoma. Sun exposure status was highly correlated with immune status defined by the CD4/CD8 T-lymphocyte ratio. There were significantly more BCC at 18 and 36 months in the 35 patients with high sun exposure and low CD4/CD8 ratio than in the 20 patients with low sun exposure and high CD4/CD8 ratio. A multivariate analysis assessed the relative importance of prior basal cell carcinoma, sun exposure, and immune status on the development of the skin cancer. Basal cell carcinoma developing in the previous 18 months and sun exposure during those 18 months were the first and second most important variables in determining development of basal cell carcinoma during the next 18 months. CD4/CD8 ratio had no additional predictive ability once prior skin cancers and sun exposure were accounted for. A low ratio of CD4/CD8 cells correlated with high sun exposure during the preceding 18 months.

Aged

Trichloroacetic acid peel of molluscum contagiosum in immunocompromised patients.

Seven human immunodeficiency virus-(HIV) positive patients with biopsy proved extensive facial molluscum contagiosum were treated with trichloroacetic acid peels. Peels were performed with 25 to 50% trichloroacetic acid (average 35%) and were repeated every 2 weeks as needed. A total of 15 peels were performed with an average reduction in lesion counts of 40.5% (range 0 to 90%). No spread of molluscum lesions, scarring, or secondary infection developed at 2 months' follow-up. Trichloroacetic acid peeling in concentrations of 35% or less appears to be a safe, effective, adjuvant therapy in the treatment of extensive molluscum contagiosum in immunocompromised patients.

Chemexfoliation

Recognizing malignant skin changes following breast cancer.

Estimates are that 180,000 cases of breast cancer will be diagnosed in 1992. Breast conservation therapy is becoming the treatment of choice for many women. Physicians providing long-term care for these women must be aware of the cutaneous presentations of local metastatic or recurrent disease, including inflammatory, nodular, telangiectatic and scirrhous variants. In addition, radiation changes, as well as the development of a secondary malignancy at the site of previous radiation therapy, must be distinguished from metastatic breast lesions.

Adenocarcinoma

MK-801 prevents brain lesions and delayed-nonmatching-to-sample deficits produced by pyrithiamine-induced encephalopathy in rats.

Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task and assigned by block randomization to one of four treatments: pyrithiamine-induced thiamine deficiency (PTD), PTD with administration of MK-801 after 12 days, control with MK-801 treatment, and control without MK-801. After 15 days of treatment followed by 21 days of recovery, the PTD rats showed significant deficits for DNMTS accuracy at retention intervals (RI) that ranged from 3.0 s to 15.0 s, the RIs that produced 75% accuracy on DNMTS in staircase training, and the rate at which a novel radial arm maze task was learned. The PTD-treated rats had consistent lesions in the thalamus and the mammillary bodies. MK-801 protected rats from both behavioral deficits and brain lesions (assessed quantitatively and qualitatively) that were produced by the PTD treatment.

Alcohol Amnestic Disorder