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Biomedical subjects

P Robins

Publications and source records attributed to P Robins.

At least 55 records · Page 3Linked to original sources

Radiotherapy of periocular basal cell carcinomas: recurrence rates and treatment with special attention to the medical canthus.

Basal cell carcinomas of the eyelids, especially those in the medial canthal area, may cause extensive local destruction. Recurrent tumours are more aggressive and become progressively more difficult to treat; this is especially true for postirradiated recurrent, medial canthal, basal cell carcinomas. Tumours in this area should thus be treated by a technique which allows tissue sampling in order to gauge the adequacy of the treatment, with the goal being complete extirpation of the tumour. Excision monitored by frozen section control or Mohs' surgery is our recommendation based on a retrospective analyses of 631 eyelid basal cell carcinomas, half of which were primary tumours and half recurrent.

Adult↗

Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis.

The inducible resistance to alkylation mutagenesis and killing in Escherichia coli (the adaptive response) is controlled by the ada gene. The Ada protein acts both as a positive regulator of the response and as a DNA repair enzyme, correcting premutagenic O6-alkylguanine in DNA by suicidal transfer of the alkyl group to one of its own cysteine residues. We have determined the DNA sequence of the cloned ada+ gene and its regulatory region. The data reveal potential sites of ada autoregulation. Amino acid sequence determinations show that the active center for the O6-methylguanine-DNA methyltransferase is located close to the polypeptide COOH terminus and has the unusual sequence -Pro-Cys-His-, preceded by a very hydrophobic region. These same structural features are present at the active site of thymidylate synthase, suggesting a common chemical mechanism for activation of the cysteine.

Alkylation↗

Mohs surgery for periocular basal cell carcinomas.

Cure rates for 631 periocular basal cell carcinomas treated by Mohs surgery proved to be 98.1% for primary lesions and 93.6% for previously treated lesions. All recurrences of primary lesions post-Mohs surgery were located in the medial canthus. Among lesions previously treated, recurrence rates after Mohs surgery were twice as high for medial canthal lesions as for other periocular basal cell carcinomas, 9.5 and 4.5%, respectively. A threefold increased risk of recurrence was observed for medial canthal lesions (post-Mohs surgery) previously treated by radiation as compared to all other treatment modalities. This high recurrence rate may reflect past practices of treating large medial canthal basal cell carcinomas with radiation rather than by other means. Results of our study indicate that primary basal cell carcinomas in the medial canthus can be treated by microscopically controlled excision with excellent results.

Adult↗

A multivariate analysis of factors affecting wound-healing time.

For post-Mohs surgical defects of the head and neck, the width of the defect is the best predictor of the length of that time it will take the wound to heal. This conclusion is based on a multivariate analysis, testing the effect of the following factors on wound-healing time: (1) age, (2) sex, (3) sound location, (4) wound width, (5) wound length, and (6) wound length X wound width. After accounting for wound width, none of the other factors significantly influenced the rate of wound healing. The 64 wounds evaluated were dressed daily with one of five bandages. When compared with the controls, and after correcting for wound width, each of the test bandages shortened wound-healing time. Among the treatment groups, no significant differences were found in the cultures or in the appearance of the wounds.

Aged↗

Cross-linking of DNA induced by chloroethylnitrosourea is presented by O6-methylguanine-DNA methyltransferase.

The DNA repair enzyme O6-methylguanine-DNA methyltransferase has been used as a reagent to analyse the initial reaction sites of alkylating agents such as chloroethylnitrosourea that cross-link DNA. The transferase can be employed for this purpose because it removes substituted ethyl groups from DNA, as shown by its ability to act on O6-hydroxyethylguanine residues in DNA. The enzyme counteracts the formation of interstrand cross-links induced by bis-chloroethylnitrosourea, but not those induced by nitrogen mustard. Once formed, chloroethylnitrosourea-induced cross-links are not broken by the enzyme. In agreement with deductions from experiments with living cells, it is concluded that chloroethylnitrosourea act by forming reactive monoadducts at the O6 position of guanine and/or the O4 position of thymine, which subsequently generate -CH2CH2- bridges to the complementary DNA strand. A new method for quantitating interstrand cross-links in DNA has been employed.

Alkylation↗

Repair of alkylated DNA in Escherichia coli. Physical properties of O6-methylguanine-DNA methyltransferase.

An inducible methyltransferase of Escherichia coli acts on O6-methylguanine in DNA by conveying the methyl group to one of its own cysteine residues. The protein has now been purified to apparent homogeneity from a constitutively expressing strain. The homogeneous methyltransferase exhibits no DNA glycosylase or endonuclease activity on alkylated DNA. Further, the methyltransferase activity is strikingly resistant to heat inactivation under reducing conditions. The protein has Mr = 18,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while the sedimentation coefficient and Stokes radius of the native enzyme yield Mr = 18,400. The amino acid composition of the purified protein shows 4 to 5 cysteine residues/transferase molecule. The methylated, inactive form of the transferase has an unaltered molecular weight.

Amino Acids↗

Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase.

The O6-methylguanine-DNA methyltransferase of Escherichia coli acts rapidly and stoichiometrically to convert a mutagenic O6-methylguanine residue in DNA to unsubstituted guanine. Even at low protein concentrations and in the absence of any cofactors, the transfer of a methyl group to one of the protein's own cysteine residues occurs in less than 2 s at 37 degrees C. The entire kinetic process can be followed experimentally at 5 degrees C. Formation of S-methylcysteine in the protein is accompanied by loss of activity and accounts for the exceptional suicide kinetics of this enzyme as well as for the sharp saturation of O6-methylguanine repair observed in vivo. The enzyme can remove greater than 98% of the methyl groups from O6-methylguanine present in alkylated DNA, but leaves N-alkylated purines untouched. Single-stranded DNA containing O6-methylguanine is a poor substrate, with the methyl transfer occurring at approximately 0.1% of the rate for duplex DNA. This latter observation may explain the high frequency of mutations induced by alkylating agents at DNA replication forks.

Chromatography, High Pressure Liquid↗

The effect of two new dressings on epidermal wound healing.

The effects of a Polyethylene oxide hydrogel dressing and a co-polymer starch hydrogel dressing upon the rate of re-epithelization were evaluated in a study using Yorkshire pigs. The polyethylene oxide hydrogel dressing significantly promoted re-epithelization by 44% as compared to untreated control wounds, while the copolymer starch hydrogel dressing significantly promoted epidermal healing by 24%. A possible mechanism of action is presented for the quicker healing induced by these dressings.

Animals↗

Risk factors for local recurrence of primary cutaneous squamous cell carcinomas. Treatment by microscopically controlled excision.

Four hundred fourteen primary cutaneous squamous cell carcinomas were treated by microscopically controlled excision. A five-year mortality-table adjusted cure rate of 93.3% was achieved. The following six parameters were analyzed for correlation with the local recurrence rate: sex, age, lesion diameter, history of previous therapy, anatomic site, and number of stages of Mohs' surgery required for treatment. Only the number of stages correlated significantly with the recurrence rate. However, subpopulations at high risk for recurrent disease could be identified. These consisted of male patients younger than 60 years of age, male patients requiring five or more stages of Mohs' surgery, and patients of either sex with carcinoma of the lower extremity. Modifications of microscopically controlled excision may be warranted in selected patients.

Adolescent↗

Squamous-cell carcinoma treated by Mohs' surgery: an experience with 414 cases in a period of 15 years.

From their experience in treating squamous-cell carcinomas by microscopically controlled surgery, the authors found that such lesions in men, particularly in young men, on the extremities and of sizes larger than 5 cm or requiring more than four stages of excision had highest recurrence rates. They recommend one more stage of excision beyond an apparent plane free of malignancy as an insurance in selected cases.

Age Factors↗