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Biomedical subjects

K Kendall

Publications and source records attributed to K Kendall.

At least 37 records · Page 2Linked to original sources

Monoclonal antibody-porphyrin conjugate for head and neck cancer: the possible magic bullet.

Although photodynamic therapy in the treatment of large head and neck cancers showed some initial promise, the results in the final analysis have been somewhat disappointing. Lack of specificity and nonhomogeneous uptake of the porphyrin by the tumor are only some of the problems. The conjugation of a monoclonal antibody (UCD/AB 6.01) with hematoporphyrin derivative that preferentially binds to tumor cells offers promise as a therapeutic agent that will not only improve specificity, but vastly enhances tumor cell kill when exposed to light in its photodynamic range. The application of the monoclonal antibody-hematoporphyrin conjugate (AB:HPD) to A-431 squamous cell carcinoma cells in vitro, followed by exposure to light in the 630 nm range, increases the kill ratio by a factor of 10(5) times. The active tumor cell binding site on the cell surface has been found to be on the microvilli, a site at which a 52 kDa protein that is very similar to keratin 8 is found. The clearance of the conjugate from nude mice who have grown an A-431 tumor shows a retention of AB:HPD of approximately 15% and less than 1% in skin and internal organs when measured at 48 hours. Direct application of AB:HPD to fresh pathology specimens containing human squamous cell carcinomas shows binding exclusively limited to the tumor.

Animals↗

Spontaneous mutations in the galactose operons of Streptomyces coelicolor A3 (2) and Streptomyces lividans 66.

Mutations can be divided into two classes: point mutations (base changes, frame shifts) and DNA rearrangements (deletions, insertions, inversions etc.). In Escherichia coli K 12, DNA insertions account for up to 40% of spontaneous mutations that inactivate genes (for review, see CULLUM 1985) and the Insertion Sequences involved can also mediate deletions and inversions. We started to study spontaneous mutations in Streptomyces in the expectation of isolating transposable elements and chose the galactose genes as convenient system. When selection is made for resistance to the galactose analogue 2-deoxygalactose (2dgalR), gal K mutants are obtained that are defective in the enzyme galactokinase (Kendall et al. 1987). We isolated spontaneous 2dgalR mutations in the closely related strain S. coelicolor A 3 (2) and S. lividans 66 and cloned the gal K gene of the former strain. Adams et al. (1988) have cloned and sequenced the gal genes of S. lividans 66 and shown that they form an operon, the restriction map appears to be identical to that of S. coelicolor A 3 (2). In this paper we describe the characterisation of spontaneous 2 dgalR mutants in S. coelicolor A 3 (2) and S. lividans 66.

Chromosome Deletion↗

Identification and characterization of a locus inhibiting extrachromosomal maintenance of the Streptomyces plasmid SLP1.

We report here the existence and initial characterization of a genetic locus (imp) that inhibits maintenance of SLP1-derived plasmids as extrachromosomal replicons in a manner distinct from normal incompatibility between autonomous SLP1 replicons. The trans-acting imp function has been localized to a 1.8 kb Eco47III restriction fragment present on integrated SLP1 elements. At least part of this DNA segment is absent from SLP1-derived plasmids. DNA sequence analysis of the imp region indicates that it contains three overlapping open reading frames (ORFs) that may constitute a polycistronic operon. The effects of insertions within the imp region indicate that uninterrupted transcription through all three ORFs is necessary for imp activity.

Amino Acid Sequence↗

The medical and social impact of nonaccidental injury.

To determine the medical and economic impact of nonaccidental trauma at a regional trauma and emergency care facility, a prospective patient database was used to follow up all victims of intentional injury admitted during one year. Specific patient data were combined with financial data to determine the medical outcome, expenditure, and hospital reimbursement. We found that 17% of the 2451 trauma patients admitted to our facility were victims of nonaccidental injury. The majority of these patients were severely injured, with an average hospital stay of six days. Hospital charges averaged $13,000 per patient. Three fourths of these individuals required governmental funding for medical care. Six months after completion of the review, only two thirds of all expenditures had been reimbursed. These patients represent a high medical services use group and consume a disproportionately high percentage of medical resources.

Alcohol Drinking↗

The aftermath of rape. Profiles of immediate and delayed treatment seekers.

Seventy-eight sexual assault victims who sought treatment within 1 month of their assaults were compared with 40 victims who delayed seeking treatment. Demographic, rape situation, and psychiatric history characteristics were examined as were postrape symptom profiles and responses to treatment. More of the delayed treatment seekers were raped by a "friend," and fewer used physical means to defend themselves against the assailant. With respect to symptomatology, delayed treatment seekers reported considerable rape-related distress and were more anxious and significantly more fearful than were recent rape victims. Implications for clinical practice and for the tailoring of services for victims of sexual assault are suggested.

Anxiety Disorders↗

Cloning of the galactokinase gene (galK) from Streptomyces coelicolor A3(2).

Streptomyces coelicolor A3(2) and Streptomyces lividans 66 strains were shown to be sensitive to the galactose analogue 2-deoxy-D-galactose. Spontaneous resistant mutants were isolated that were Gal- and lacked the enzyme galactokinase. The galK gene (structural gene for galactokinase) from S. coelicolor was cloned into S. lividans using the low copy number vector pIJ922. The resulting plasmid (pMT650), which contained a 14 kb insert, complemented gal mutations in both species. The presence of the galK gene on a 2.8 kb EcoRI fragment was confirmed by expressing it in Escherichia coli where it complemented a well characterized galK mutation.

Cloning, Molecular↗

Tolerability of timolol and betaxolol in patients with chronic open-angle glaucoma.

Twenty-four patients with bilateral chronic open-angle glaucoma received three treatments: (1) artificial tears (control) in both eyes, (2) artificial tears in one eye and one drop of timolol (0.05%) in the other, and (3) artificial tears in one eye and one drop of betaxolol (0.05%) in the other. Twelve patients always received the test medication in the left eye and 12 in the right eye. The patients were examined and questioned about ocular symptoms at the time of drug administration and at 1, 5, 30, and 60 minutes. Irritation was noted in five treated eyes after artificial tears, in three after timolol, and in 11 after betaxolol. The incidence of irritation after initial treatment was significantly lower than expected for timolol than for artificial tears or betaxolol (P less than 0.01).

Adrenergic beta-Antagonists↗

Identification of a DNA sequence associated with plasmid integration in Streptomyces coelicolor A3(2).

We identified a DNA element of length about 1 kb that is present in two copies in the chromosome of Streptomyces coelicolor A3(2) and is also present on the plasmid SCP1 which has been carefully defined genetically, but never isolated as extrachromosomal DNA. A copy of the element is close (within 5 kb) of a gene coding for an extracellular agarase in the chromosome of S. coelicolor A3(2) and in an NF strain, in which SCP1 has integrated into the chromosome, the agarase gene has been deleted. The element has properties reminiscent of Insertion Sequences in Escherichia coli, but it is not yet know if it can transpose.

DNA Restriction Enzymes↗

From lesbian heroine to devoted wife: or, what the stage would allow.

Plays written by English women on the same historical subject appeared in 1696 and 1841. The earlier play, written in a period of active feminism, features Agnes de Castro as a lesbian heroine, probably the first in English stage history. The second, written in the age of Solomon Grundy, characterizes de Castro as a self-sacrificing, devoted heterosexual wife. Since both plays were written by women who would now be defined as lesbians, the treatment of the heroine seems more a reflection of audience than author. Study of the two plays with their sources and their authors' lives reveals much about audiences and the pressures a homophobic society can exert on lesbian artists who write for a living.

Drama↗

Cloning and expression of an extracellular-agarase from Streptomyces coelicolor A3(2) in Streptomyces lividans 66.

An extracellular agarase gene was cloned from Streptomyces coelicolor A3(2) strain M130 into S. lividans 66 using the multicopy plasmid vector pIJ702. Various deletion derivatives of the initial clone (pMT605) were obtained by in vitro and in vivo methods. This allowed the gene to be localised to a 1.9-kb segment of DNA. The agarase enzyme was overproduced (up to 500 times) and exported efficiently into the medium. The agarase protein was identified as a 28-kDal band after sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE); in the case of one derivative, pMT608, this band accounted for nearly 50% of the total extracellular protein. Differences in agarase production between the deletion derivatives correlated well with plasmid stability.

Chromosome Mapping↗

Increased activity of rat intestinal lactase due to increased intake of alpha-saccharides (starch, sucrose) in isocaloric diets.

The adaptability of intestinal microvillar alpha-disaccharidases to the variation of alpha-saccharide content in the diets is well established, but the influence of these sugars on the activity of microvillar lactase (neutral beta-galactosidase) has heretofore been considered negligible or non-existing. In two experiments rats were fed isocaloric diets where the carbohydrate (starch or sucrose) content versus fat content was varied. (High carbohydrate diets: 71% of calories as carbohydrate and 5% of calories as fat; low carbohydrate diets: 6 and 73% calories, respectively). Experiment 1: male and female rats had access to experimental diets only from day 12 postnatally and were killed at age 56 days. Experiment 2: male rats were fed experimental diets starting on day 73 postnatally and killed 3, 7, 14 and 28 days later. Rats fed the high carbohydrate diets exhibited a significant increase in activity (specific and total per segment) of lactase in all three intestinal segments compared to rats fed the low carbohydrate diets. Changes in the activity of sucrase and maltase paralleled those of lactase activity. These experiments have thus demonstrated clearly the influence of variation in alpha-saccharide content in the diet upon lactase activity. Further experiments are needed to determine the active principle of this dietary adaptation.

Adaptation, Physiological↗

Differences in the development of jejunum and ileum as observed in fetal rat isografts. Possible implications related to the villus size gradient.

Previous studies have shown that villus size in the small intestine decreases from the duodenum toward the ileum. Villus-enlarging and villus-reducing factors have been found in the gastric, pancreatic, and duodenal secretions, and in bile (Altmann and Leblond, '70; Altmann, '74). We here explore the role of intrinsic factors present in the individual sections of the small intestine by following the development of villus height in fetal (21-day old) jejunal and ileal segments implanted under the kidney capsule of syngeneic adult rats. Twenty-eight and 45 days after implantation, the jejunal villi contained significantly more columnar epithelial cells than did the ileal villi, but the jejunoileal gradient was even greater in small intestine of corresponding ages, developing in situ. Our experiments, thus, show that the jejunoileal gradient is already programmed in rats 1 day before birth, while other factors contribute postnatally to regulation of its magnitude.

Animals↗

Development of fatty acid esterification mechanisms in rat small intestine.

Fatty acid esterification was measured in fetal jejunal and ileal isografts implanted under the kidney capsules of adult host rats and compared to the age-controlled intestine grown in situ. Studies were conducted on the 21st, 35th, 49th, and 63rd postconceptional days, corresponding to prenatal, suckling, weaning, and weaned rats. Substantial fatty acid esterification activity was found in prenatal jejunum but not in ileum. A proximal-distal gradient of fatty acid esterification was observed in all groups grown in situ, but not in isografts. The monoglyceride pathway (MG-P) accounted for about one-third of total fatty acid esterification (TFAE) in jejunum grown in situ and remained constant through the study. In the ileum, MG-P was the major esterification pathway during the first 4 postnatal weeks, but decreased progressively after weaning to become insignificant in adult rats. TFAE fell in the jejunal isografts, whereas it increased in the ileum. MG-P remained as the major pathway in the implanted jejunum and ileum. Our studies suggest that luminal contents are probably the most important modulator for the development and maintenance of intestinal fatty acid esterification, and "fetal programming" manifested by changes in fatty acid esterification mechanisms in the isografts is less important.

Animals↗

Development of jejunoileal differences of activity of lactase, sucrase and acid beta-galactosidase in isografts of fetal rat intestine.

Jejunal and ileal segments from preterm rat fetuses were implanted under the kidney capsula of adult rats. Sucrase, lactase and acid beta-galactosidase activities were determined in the isografts at different times after implantation, and in corresponding segments developing in situ. Whereas fetal intestine contains considerable activity of acid beta-galactosidase and lactase, no sucrase activity is detectable. Similarly -- as in situ -- 4 weeks after the implantation the jejunal segment exhibited higher activity of sucrase and lactase than the ileal segment. Acid beta-galactosidase was more active in ileal than in jejunal segments -- both growing in situ as well as isografts. Experiments have thus demonstrated that the expression of the jejunoileal gradient of activity of the 3 enzymes studied does not depend on direct contact with food or gastric, pancreatic and biliary juices. This gives validity to the suggestion that the gradient may already be programmed in fetal intestinal tissue, but other factors active in situ might be responsible for its magnitude.

Animals↗