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The suc22+ gene of Schizosaccharomyces pombe encodes the small subunit of ribonucleotide reductase. Two transcripts that hybridise to suc22+ have previously been described: a constitutive transcript of 1.5 kb, and a transcript of approximately 1.9 kb that is induced when DNA replication is blocked by hydroxyurea. In this paper we show that both transcripts derive from the suc22+ gene, are polyadenylated, and have transcription initiation sites separated by approximately 550 nucleotides. The absence of translation initiation codons and predicted intron splice sites within this 550 nucleotide region suggests strongly that both transcripts encode the same protein. Under normal growth conditions, the larger suc22+ transcript is present at a very low level. This low level expression is periodic during the cell cycle, showing a pattern similar to that of other genes under regulation by MCB elements with a maximum in G1/S phase. Consistent with this, there are MCB elements upstream of the initiation site of the transcript. This pattern of expression contrasts with the continuous expression, at a much higher level, of the smaller suc22+ transcript. The larger suc22+ transcript is induced by exposure of cells to 4-nitroquinoline oxide (4-NQO),a UV-mimetic agent that causes DNA damage. The transcriptional response to 4-NQO is observed in cells previously arrested in G2 by a cdc2ts mutation, demonstrating that induction can occur outside S phase. We show that the rad1+ gene, part of the mitotic checkpoint, is required for induction of the large transcript. Exposure of cells to heat shock also induces the suc22+ large transcript: a consensus heat shock element has been identified upstream of the large transcript start site.

In this paper we describe properties of the cdc10-C4 mutant of the fission yeast Schizosaccharomyces pombe. The cdc10+ gene encodes a component of the DSC1Sp/MBF transcription complex, which is required for cell-cycle regulated expression at G1-S of several genes via cis-acting MCB (MIuI cell cycle box) elements. At permissive temperatures cdc10-C4 causes expression of MCB-regulated genes through the whole cell cycle, which in asynchronously dividing cells is manifested in overall higher expression levels. This overexpression phenotype is cold sensitive: in cdc10-C4 cells, MCB genes are expressed offprogressively higher levels at lower temperatures. In heterozygous cdc10-C4/cdc10+ diploid strains, MCB-regulated genes are not overexpressed, suggesting that loss, rather than alteration, of function of the cdc10-C4 gene product is the reason for unregulated target gene expression. Consistent with this, the cdc10-C4 mutant allele is known to encode a truncated protein. We have also overexpressed the region of the cdc10 protein absent in cdc10-C4 under the control of an inducible promoter. This induces a G1 delay, and additionally causes a reduction of the overexpression of MCB genes in cdc10-C4 strains. These results suggest that DSC1Sp/MBF represses, as well as activates, MCB gene expression during the cell cycle.

Microsomal aryl hydrocarbon hydroxylase (AHH) activity and inducibility were measured in jejunal mucosa, liver, and lesion-free epidermis of patients with psoriasis. In all three tissues AHH activity and inducibility were less than in controls. This demonstration of a generalised enzymatic abnormality in the tissues of patients with psoriasis is in keeping with the suggestion that it may be close to the underlying genetic defect.

A family pedigree is described in which the propositus has tricho-dental syndrome. Evidence is presented that the short hair frequently observed in this condition is due to a short anagen phase of the hair cycle.

The feasibility of clinical trials involving the surgical management of primary melanoma was assessed through a survey of Canadian surgeons who treat this disease. Surgeons were polled as to their current practice regarding node dissection and margins of resection of the primary lesion. Their interest in randomized trials addressing these practices was also assessed. Two hundred and forty questionnaires were distributed to 20 centres across Canada. The total number of patients with melanoma seen annually by the 131 surgeons who responded was 790 - of the approximately 1000 new cases of melanoma diagnosed in Canada each year. Of responding surgeons, 63% currently perform wide excision (taking 3 to 5 cm of normal tissue) for lesions less than 1.5 mm in depth and 37% perform limited excision (including 1 to 2 cm of normal tissue). Of all surgeons responding, 76% were interested in a randomized trial comparing wide and limited excision in these superficial lesions. Currently, 90% of surgeons perform wide excision of lesions 1.5 mm or more in depth and 10% perform limited excision. Fifty-nine percent were interested in a randomized trial comparing wide and limited excision in these deeper lesions. Twenty-four percent of surgeons routinely perform prophylactic node dissection on all patients with lesions 1.5 mm or more in depth; 66% wait until there is clinical suspicion of nodal metastases and 9% follow some other policy. The results of this survey indicate that (a) surgical management is varied, (b) radical surgery remains common practice and (c) surgeons are interested in randomized trials that will determine optimal treatment.

Of 107 patients with cancer of the head and neck region in whom sensitization with dinitrochlorobenzene (DNCB) was attempted at the time the patient first presented, 57 became positive while 50 remained negative. These two groups were similar with respect to age, sex, involved sites and extent of tumour at presentation, but the mortality in the DNCB-negative group (38%) was twice as high as that in the DNCB-positive group (17.5%). Since both groups were treated in a similar fashion and have been followed-up for equal periods of time, the difference in mortality suggests that DNCB skin testing is of prognostic value in patients with cancer in the head and neck region.

The purpose of this study was to determine the value of staging and serial follow-up investigations in newly diagnosed patients with completely excised primary cutaneous malignant melanoma. We reviewed the records of the 393 patients with completely excised primary malignant melanoma who were referred to the Ontario Cancer Institute and the Toronto-Bayview Regional Cancer Centre between 1 January 1978 and 31 March 1982. Initial investigations included history and physical examination in all 393 patients, complete blood count (199 patients), liver function tests (198 patients), urinary melanins (159 patients), chest X-rays (345 patients), whole lung tomography (182 patients), radionuclide liver-spleen scans (207 patients), and bone scans (116 patients), bipedal lymphangiograms (78 patients), CT scans of the chest (59 patients), and CT brain scans (51 patients). The clinical stage of ten patients was changed as a result of history and physical examination or lymphangiogram. All other investigations failed to detect metastatic melanoma. Follow-up investigations included history and physical examinations, complete blood counts, liver function tests, radionuclide liver spleen and bone scans. History and physical examinations, chest X-rays and patients' awareness of abnormalities were responsible for detection of subsequent melanoma recurrences. All other tests failed to identify metastatic melanoma at the time of its occurrence. Therefore, we recommend that initial staging investigations be limited to history and physical examination with clinical photographs, and baseline chest X-ray. We recommend that subsequent follow-up include only history and physical examinations and chest X-rays.