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Biomedical subjects

K Robertson

Publications and source records attributed to K Robertson.

18 recordsLinked to original sources

Tolerance of self induced in thymus organ culture.

F liver protein occurs in serum at low concentration, and therefore induces tolerance of self only in T cells. T cells which mature in cultured thymus lobes in the absence of this protein become reactive towards it but can be prevented from doing so by exposure to the protein while in culture. The threshold of tolerance induction for this soluble antigen is estimated in this way at approximately 1 microgram/ml, which is slightly less than the threshold of response of primed T cells in a proliferation assay. Freshly isolated thymocytes do not display reactivity to self-F protein, indicating that T cells normally become tolerant while still within the thymus.

Animals

Identification and characterization of a novel high-molecular-weight form of the integrin alpha 3 subunit.

The integrin alpha 3 beta 1 is a multiligand extracellular matrix receptor found on many cell types. Immunoprecipitations of 125I-surface-labeled prostate carcinoma cell lines, DU145 and PC-3, with the anti-alpha 3 integrin monoclonal antibodies J143 or PIB5, resulted in the coimmunoprecipitation, along with the expected alpha 3 beta 1 heterodimer, of a polypeptide with a molecular mass of 225 kDa. This protein could also be copurified with the 155-kDa alpha 3 and 115-kDa beta 1 subunits upon affinity chromatography of 125I-surface-labeled cell extracts on anti-alpha 3 antibody-Sepharose columns. Upon reduction, this 225-kDa protein generated 130- and 95-kDa polypeptides, while the 155-kDa alpha 3 subunit generated 130- and 25-kDa polypeptides. The 225-kDa protein did not generate a 25-kDa polypeptide. Deglycosylation and reduction of the 225-kDa protein resulted in the generation of 110- and 95-kDa polypeptides, while deglycosylation and reduction of the 155-kDa alpha 3 resulted in a 110-kDa polypeptide identical in size to the 110-kDa polypeptide generated from the 225-kDa protein. Peptide maps generated from the 110-kDa components of the 225-kDa polypeptide and the 155-kDa alpha 3 integrin subunit were identical, as were their N-terminal amino acid sequences. An antibody directed against the cytoplasmic domain of the alpha 3 subunit immunoprecipitated the 225-kDa polypeptide in addition to the 155-kDa alpha 3 subunit. Furthermore, Northern blot analysis of RNA from DU145 and PC-3 cells with a human alpha 3 cDNA probe identified an mRNA species of 6.2 kb in addition to a major mRNA species of 4.3 kb. The larger mRNA species, which is of an appropriate size for encoding a polypeptide of approximately 220-kDa, was not detectable in cells which did not express the 225-kDa protein. These data demonstrate that the 225-kDa polypeptide represents a novel integrin alpha 3 subunit consisting of the alpha 3 integrin heavy chain disulfide-bonded to a 95-kDa polypeptide which may represent an alternative "light" chain to the 25-kDa light chain of the alpha 3 subunit.

Amino Acid Sequence

Induction of expression of the alpha v beta 1 and alpha v beta 3 integrin heterodimers during retinoic acid-induced neuronal differentiation of murine embryonal carcinoma cells.

All-trans-retinoic acid, an endogenous morphogen, induced neuronal differentiation of P19 murine embryonal carcinoma cells. Peak differentiation, as judged by the elaboration of neuronal processes, occurred 8 days after exposure of the cells to 0.5 mM retinoic acid, a concentration known to induce neuronal differentiation. An examination of the expression of the extracellular matrix receptors, integrins, during this retinoic acid-induced differentiation period, demonstrated a specific and strong induction of expression of two polypeptides (130 and 115 kDa) immunoprecipitated with an anti-human vitronectin receptor antiserum. The expression of a 90-kDa polypeptide, also immunoprecipitating with this antiserum was induced as well, but to a much smaller extent. The expression of a 96-kDa polypeptide immunoprecipitated by this antiserum and present in the untreated cells was not induced by retinoic acid. The increase in the expression of these polypeptides paralleled the neuronal differentiation of the P19 embryonal carcinoma cells. The expression of these integrins was not induced in a variant of the P19 cells, P19RAC65, which are resistant to differentiation induction by retinoic acid. Utilizing integrin subunit-specific anti-cytoplasmic peptide antibodies together with immunoprecipitation and Western blot analysis, the 130- and 115-kDa polypeptides were identified as the integrin alpha v and beta 1 subunits, respectively. The 90-kDa polypeptide, also induced by retinoic acid, was identified as beta 3, whereas the identity of the uninduced 96-kDa polypeptide remains unclear as yet. Peptide map analysis of deglycosylated polypeptides demonstrated that the 90- and 96-kDa polypeptides are distinct proteins and that the 115-kDa polypeptides immunoprecipitated with either anti-alpha v or anti-beta 1 antibodies are identical, further establishing that the 115-kDa polypeptide associating with alpha v is beta 1. The retinoic acid-induced expression of beta 1 occurred at the level of mRNA expression which also paralleled neuronal differentiation, but peaked slightly ahead of the cell surface expression of beta 1. The expression of other beta 1-associated alpha subunits was not induced by retinoic acid in these cells. These data demonstrate that retinoic acid strongly induces the expression of the integrin heterodimer alpha v beta 1 and also, to a smaller extent, the expression of alpha v beta 3. The retinoic acid-induced, high level surface expression of the alpha v beta 1 heterodimer is tightly correlated with the induction of neuronal differentiation by retinoic acid. This finding suggests an important role for the alpha v beta 1 heterodimer in the neuronal differentiation process.

Amino Acid Sequence

Risk factors in onychocryptosis.

A study is described in which the normal toes of 50 patients with unilateral ingrowing toenails were compared with those of 50 healthy subjects matched for age and sex. Twenty-one potential risk factors were compared between the groups. All measurements on patients were derived from unaffected toes in order to avoid anatomical distortion due to the disease process. Statistical analysis revealed significant differences between the groups for three anatomical measures, namely nail fold width (P less than 0.001), medial rotation (eversion) of the great toe (P less than 0.02) and nail thickness (P less than 0.03). Possible discriminating variables were assessed using linear discriminant function analysis and a mathematical equation was derived based on these three factors. This equation was found to possess a potentially high predictive value in that it correctly classified 86 per cent of the patients and 77 per cent of the controls. A further group of 62 unselected patients presenting with unilateral onychocryptosis and 35 unaffected controls were assessed for these three parameters. Of these, 80 per cent of controls and 85 per cent of patients could be classified correctly by the equation. It is thus proposed that, in the majority of subjects with onychocryptosis, a discrete anatomical predisposition exists and that the other factors act only as triggers in the development of the condition. This study provides a rationale for less traumatic surgical approaches to ingrown nail than nail avulsion, with or without nail bed ablation and may also provide a means of identifying high-risk groups.

Adolescent

Some effects of sex-linked clothing and gender schema on the stereotyping of infants.

Two predictions were evaluated: first, that given minimal information about an infant, individuals would use sex-related cues (i.e., clothing) to categorize, evaluate, and make attributions about the infant, and second, that gender schematic individuals would be more likely than gender aschematic individuals to use such sex-related cues. On the basis of the Bem Sex Role Inventory, American college students were classified as either gender schematic (masculine or feminine) or gender aschematic (undifferentiated or androgynous). The students categorized, evaluated, and made trait attributions about an infant dressed in male, female, or ambiguous clothing. Both gender schematic and gender aschematic individuals relied on sex-related cues in their perceptions of the infant.

Adolescent

Effect of pH-adjustment of bupivacaine on onset and duration of epidural analgesia in parturients.

Previous studies have reported that elevation of the pH of local anaesthetics is associated with enhanced quality and duration of block. This study investigated the effect, on time to onset and duration of analgesia, of pH adjustment of 0.25 per cent bupivacaine immediately prior to injection into the epidural space in parturients. Addition of 0.1 ml of 8.4 per cent sodium bicarbonate to 20 ml of 0.25 per cent bupivacaine consistently raised the pH of the local anaesthetic from 5.65 to 7.26 (mean values). Thirty parturients received an epidural injection of 8 ml of pH-adjusted 0.25 per cent bupivacaine and a control group of 30 parturients received 8 ml of the standard commercial preparation of 0.25 per cent bupivacaine. Elevation of the pH of the local anaesthetic significantly increased the speed of onset of analgesia from 6.0 minutes to 3.2 minutes and the duration of analgesia was significantly lengthened from 79.4 minutes to 96.5 minutes. There was no significant influence on time to peak effect, nor on mean maternal plasma levels of bupivacaine.

Adult

Alcohol use and abuse: heavy drinking among methadone clients.

This paper discusses alcohol use among methadone maintenance clients and narcotics users not in treatment. The data are derived from the Tri-State Ethnographic Project, a study of four methadone maintenance clinics in three states. Data indicate that methadone clients consume more alcohol than comparable age groups in the general population, but not more alcohol than narcotics users not in treatment. For a portion of the treatment population, however, heavy drinking presents significant problems. Sixteen percent of the treatment sample were found to be abusive pattern drinkers; that is, persons who report not only drinking heavily but also spending a great deal of time hanging out on the street, getting high, and consuming many other additional drugs. These abusive pattern drinkers reflect a pattern of polydrug use which began in their early teens and report multiple unsuccessful treatment attempts.

Adult

Visual function and academic performance.

Evaluation of 1,910 first-, second-, and third-grade students indicated that visual function and academic performance as measured by reading were not positively related. Visual function tests included visual acuity, muscle balance, preferred eye and hand, color vision, refraction, sensory and motor function, and a writing and drawing task. Academic tests included the Metropolitan Readiness Test, the Cognitive Abilities Test, the Iowa Test of Basic Skills, and the teacher's assessment of reading level. A simple test which can be completed during the office visit and interpreted by the ophthalmologist in the office included drawing, copying, and writing. A segment of this test, the "draw a bicycle test," can be used by an ophthalmologist to demonstrate the difference between vision and performance when examining a child up to third-grade level who is referred because of school failure.

Accommodation, Ocular

Epidural fentanyl, with and without epinephrine for post-Caesarean section analgesia.

Using a double-bolus technique, the efficacy and safety of epidural fentanyl with and without epinephrine 1:400,000 for post-Caesarean section analgesia was examined in 30 patients. The addition of 25 micrograms epinephrine to the fentanyl (100 micrograms) did not potentiate the speed of onset but did significantly prolong the duration of action of the second dose. The only side effect encountered was pruritus, which was significantly increased (from 17-44 per cent) when epinephrine was added. The results indicate a clinical advantage of prolonging the duration of action of fentanyl for post-Caesarean Section analgesia with the addition of epinephrine, but the cumbersome and time-consuming nature of a double-bolus technique limits its clinical value. The relative safety of epidural fentanyl with and without epinephrine was confirmed by the absence of respiratory depression, drowsiness or hypotension in all patients.

Adult

Response of plasma proenkephalin peptide F to exercise.

Plasma proenkephalin Peptide F immunoreactivity was measured in the plasma of endurance trained and untrained males at various exercise intensities. Significantly different levels were found between the two groups at rest and at 54% maximum oxygen consumption (VO2 max). Maximum levels were at 5 min of recovery for the untrained group and at 54% VO2 max and at recovery 5 min for the trained group. These data suggest an adaptation in the trained group fro the release of this peptide and further suggest it may play a role in recovery since the highest levels are following the termination of the exercise period.

Adult

Non-enzymatic glycosylation of keratin from the stratum corneum of the diabetic foot.

Non-enzymatic glycosylation of keratin from the stratum corneum of the sole of the foot was measured by the thiobarbituric acid technique in thirty diabetic and thirty control subjects. A significant increase in the level of glycosylation was demonstrated in the diabetic subjects (P less than 0.001). HbA1 levels were measured in a further eighteen subjects at the same time as keratin was removed, and in this group a significant association between non-enzymatic glycosylation of that protein and diabetic control was demonstrated (P less than 0.01). In vitro incubation of keratin in the presence of free glucose produced increased non-enzymatic glycosylation (P less than 0.01) and this effect was blocked by incubation in the presence of increasing concentrations of aspirin (P less than 0.01). Measurement of non-enzymatic glycosylation of keratin in a further group of twenty diabetics with neuropathic ulceration showed a significant increase in levels when compared with a group of diabetics without ulcers (P less than 0.05). As keratin is the principle structural protein of the stratum corneum of the sole of the foot, it is possible that changes in this protein associated with non-enzymatic glycosylation may contribute to abnormalities seen in the skin of the feet of diabetics.

Adult

Enterochromaffin cells in the duodenal mucosa of children with coeliac disease.

A cell counting technique was used to count enterochromaffin (EC) cells in the duodenal mucosa of 10 children with coeliac disease and 10 controls, and significantly greater numbers of EC cells were found in children with coeliac disease. In four children with a clinical history suggestive of coeliac disease, but with minor histopathological changes in the duodenum, gluten challenge resulted in increased numbers of EC cells. Abnormalities of 5-hydroxytryptamine metabolism in coeliac disease may result from hyperplasia of EC cells in the small intestine.

Celiac Disease