Saccharomyces cerevisiae exhibits a sporulation-specific temporal pattern of transcript accumulation.

Cultures of the yeast Saccharomyces cerevisiae that are heterozygous for the mating type (MATa/MAT alpha) undergo synchronous meiosis and spore formation when starved for nitrogen and supplied with a nonfermentable carbon source such as acetate. Haploid and homozygous MAT alpha/MAT alpha and MATa/MATa diploid cells incubated under the same conditions fail to undergo meiosis and are asporogenous. It has not yet been firmly established that gene expression during sporulation is controlled at the level of transcript accumulation. To examine this question, we used cloned genes that encode a variety of "housekeeping" functions to probe Northern blots to assay the appearance of specific transcripts in both sporulating and asporogenous S. cerevisiae. In sporulating cells, each transcript showed a characteristic pattern of accumulation, reaching a maximum relative abundance at one of several different periods. In contrast, in both asporogenous haploid MATa and diploid MAT alpha/MAT alpha cells, all transcripts accumulated with similar kinetics. These results suggest a sporulation-specific pattern for transcript appearance. During these studies, high levels of several different transcripts were observed at unexpected times in sporulating cells. Histone (H)2A and (H)2B1 transcripts, although most abundant during premeiotic DNA synthesis, remained at one-third to one-half maximal levels after its end and were found in mature ascospores. Their appearance at this time is in sharp contrast to vegetative cells in which these histone transcripts are only found just before and during the period of DNA synthesis. Furthermore, transcripts from GAL10 and CDC10 genes, which are believed to be dispensable for sporulation, were much more abundant in sporulating cells than in asporogenous cells and vegetative cells grown on glucose or acetate. The presence of these transcripts did not appear to be due to a general activation of transcription because each accumulated with different kinetics. In addition, the transcript for at least one gene, HO, that is also dispensable for sporulation was not detected. The increased abundance of transcripts from some genes not required for sporulation leads us to propose that genes preferentially expressed during sporulation need not be essential for this differentiation.

Mycobacterium malmoense septic arthritis.

We report a case of septic arthritis of an interphalangeal joint and osteomyelitis of the phalanx due toMycobacterium malmoense in a 61-year-old man with a 20 year history of rheumatoid arthritis treated with steroids and azathioprine. This was successfully treated with ethambutol, rifampicin and clarithromycin. To our knowledge this is the only reported case of septic arthritis due to this pathogen which is usually associated with respiratory disease or cervical lymphadenitis.

Cement burns and their treatment.

Twenty patients with cement burns presenting to Stoke Mandeville Hospital Burns Unit between 1981 and 1989 are described. They represent 1.8 per cent of the total adult patients treated at this unit. Fifteen (75 per cent) had surgery for full thickness skin burns. A questionnaire sent to all the accident and emergency officers employed within the catchment area of the Burns Unit at Stoke Mandeville Hospital showed important gaps in their knowledge of the subject. It is suggested that further publicity be given to this uncommon but potentially serious injury.

An unusual cause of anuria in a burned child.

When treating children with burns we avoid catheterization whenever possible since the complications may outweigh the benefits. We present the case of a 1-year-old infant with 13 per cent burns who required catheterization. The catheter knotted in the bladder, obstructing urine outflow. A general anaesthetic was required to remove it.

Dupuytren's disease in children.

Although Dupuytren's disease of the hand has been reported in teenagers, it is generally considered to be a disease of adults. A series of nine children who developed Dupuytren's disease of the hand before the age of 13 years is presented. Eight had surgical removal of the diseased tissue and histological confirmation of the diagnosis before the age of 13 years and one at 14 years of age. The presence of the condition in young children and teenagers is discussed and the literature summarized.

Primary repair of dog bites to the face: 40 cases.

Dog bites to the face can be life-threatening if major infection occurs, and traditional management consists of wound toilet and debridement, with repair only when the possibility of infection has been eliminated. Surgical opinion is now swinging towards earlier repair. We have analysed retrospectively the outcome of 40 cases that, irrespective of time delay between injury and presentation, underwent primary repair or reconstruction after wound toilet, debridement and administration of prophylactic antibiotics. The victims were 17 males and 23 females with ages ranging from 2 to 76 years (mean 25). Median delay between the injury and presentation in the emergency department was 60 minutes (range 7 minutes to 5 days). All patients received surgical treatment within 24 hours of admission, 18 being operated on within 6 hours. 31 had primary repairs and 9 patients had reconstructive procedures with local skin flaps or skin grafts. Primary healing was achieved in all but 2 patients, of whom one developed minor wound infection and one had necrosis of a composite graft. These results support the view that, for dog bites to the face, primary repair is the method of choice.

Primary repair of zone I flexor tendon injuries.

Eighty-two patients who were treated by suture repair for zone I flexor tendon injuries over a ten-year period were identified, to determine the incidence of post-operative surgical complications and subsequent re-operations. Eighty-five percent of patients completed 12 weeks follow-up post-surgery. Of these patients almost all had good to excellent outcome in terms of total active movement (TAM). However when assessing the range of motion at the distal interphalangeal joint (DIPJ), only 23% could be classified as having good or excellent results at final follow-up. A total of six patients (7.32%) required surgery for tendon repair complications. This study illustrates that DIPJ ROM is more indicative of functional recovery after tendon repair in flexor zone I. Given the DIPJ is important in providing a fine pinch and a span pinch grip movements, patients should be counselled for inability to perform these functions post-tendon repair.

The button-over-nail technique for Zone I flexor tendon injuries.

The "button over the nail" is the most commonly used technique in order to re-insert the flexor digitorum profundus tendon into the distal phalanx in the management of Zone 1 injuries. Recent evidence in the literature has highlighted an associated morbidity with the technique. In this study, 37 patients were identified that had been treated using the "button technique", for which outcome data is collected by hand therapists as part of a prospective flexor tendon injury audit. Retrospective case note review was performed to determine incidence of post-operative surgical complications. There were limited complications with the use of the "button technique" overall. However, functional outcome when compared to other studies are relatively poor with mean range of motion at the distal interphalangeal joint being 37.5 degrees. The authors would recommend any decision to change technique for the management of these injuries should consider functional outcome in the presence of a low surgical complication rate.

Assessment of the severity of hand injuries using "hand injury severity score", and its correlation with the functional outcome.

INTRODUCTION: Objective assessment of hand injuries is a complex subject. However, an objective assessment, leading to a score, can help in predicting outcome and can be used as a research tool. Campbell and Kay have devised one such score known as "hand injury severity score" or HISS [J. Hand. Surg. [Br.] 21 (3) (1996) 295]. A study on this score has been carried out in our institute. The idea was to see if the hand injury severity score, correlates with the functional outcome as measured by disability arm shoulder and hand score (DASH), after a period of minimum 2 years. METHOD: All the hand injury patients admitted in the hospital were assessed at the time of admission, and objective information was documented on a hand injury documentation form. The form captured all the data required to calculate "hand injury severity score" . A sample of 70 patients admitted during the first 6 months of 1999 was taken and their scores were calculated. The sample was selected such, that it had a reasonable representation of hand injuries of all severities. After obtaining a due approval from ethics committee, all these 70 patients were sent a DASH questionnaire. A total of 23 patients replied. Spearman's rank correlation test was used to analyse the correlation between the severity of hand injury as assessed using HISS, and functional outcome as measured using DASH. Correlations between the outcome and skeletal component score, outcome and motor component scores, and outcome and Integument component scores, were assessed separately. RESULTS: The study shows a statistically significant association ( r = 0.7182, P = 0.000165) between the severities of injury and the functional outcome. The functional outcome also shows a statistically significant association with the severity of injury to skeletal component (r = 0.5151, P = 0.014083) and motor component (r = 0.6797, P = 0.000507). However, the severity of injury to integument component, as measured by HISS, does not show any association with the outcome (r = 0.3571, P = 0.102736). This study supports the overall structure of the HISS. However an improvement in the integument component scoring is required to improve overall accuracy.

Pseudoainhum in chronic psoriasis.

Pseudoainhum is a term used to describe the presence of constricting bands of the extremities due to a variety of underlying causes. Progression of the lesions can cause irreversible damage and autoamputation of the affected digit. This report documents a rare association of pseudoainhum and psoriasis and emphasizes the importance of recognizing this condition.

Accessory palmaris longus muscle causing ulnar nerve compression at the wrist.

An accessory palmaris muscle that arose from the base of the fifth metacarpal passed proximally and inserted into the palmaris longus tendon. In its course it compressed the ulnar nerve and vessels. It was detached proximally and folded on itself to provide hypothenar bulk. The entrapment symptoms were relieved.

Textured or smooth implants for breast augmentation? Three year follow-up of a prospective randomised controlled trial.

Silicone breast implant surface texturing has been shown to reduce the short-term incidence of adverse (Baker III/IV) capsular contracture in augmentation mammaplasty in double-blind randomised controlled trials. It is, however, undetermined whether the textured surface merely delays the onset of severe contracture or its effect on capsular contraction is persistent. The current study reviewed, after three years, 49 of the 53 patients who had undergone subglandular breast augmentation mammaplasty in a randomised double-blind study with textured or smooth silicone gel-filled implants in 1989. The incidence of adverse capsular contracture was 59% for smooth implants and 11% for textured ones (P = 0.001; chi 2 = 10.60). Eight patients (31%) with smooth prostheses underwent breast implant exchange for severe capsular contracture between the one and three year assessments, compared with a revisional surgery rate of only 7.4% (2/27 patients) for the textured group (P < 0.04). These adverse capsular contracture and revisional breast implant surgery rates clearly demonstrate that the effect of textured implants in reducing capsular contracture in augmentation mammaplasty found at one year is maintained at three years, and suggest that it may be long lasting.

Hand injuries from leading horses.

An estimated 3.5 million people ride horses in the United Kingdom (Cannon, 1989). Injuries consequent to falls are common (Edixhoven et al., 1981), but those sustained while leading horses are less well recognized. In eight cases inappropriate grip of the reins or halter rope while leading a horse or pony resulted in an avulsion injury to a finger or thumb. It is suggested that people at risk be informed of such injuries.

Bizarre parosteal osteochondromatous proliferation with cortical invasion.

A 15-year-old male presented with an 18-month history of increasing swelling on the radial aspect of his left forearm. Radiographs and MR images showed a partly calcified mass on the lateral border of the radius with erosion of the underlying cortex. Following a CT-guided needle biopsy, the mass was excised by segmental resection of the radial shaft with replacement by a vascularised fibular graft. Histological examination of the resected specimen showed many features typical of a bizarre parosteal osteochondromatous proliferation (BPOP) but with destruction of the underlying cortical bone by cellular spindle cell tissue. Although there were no cytological signs of malignancy, we believe that this unusual disease should be regarded as a particularly aggressive form of BPOP and treated by wide excision. Clinical follow-up of our patient at 2 years shows no sign of local recurrence or metastasis.

An enzyme-linked immunosorbent assay for the Raf/MEK1/MAPK signaling cascade.

The Ras-MAPK signaling cascade transmits mitogenic stimuli from growth factor receptors and activated Ras to the cell nucleus. Inappropriate Ras activation is associated with approximately 30% of all human cancers. The kinase components of the Ras-MAPK signaling cascade are attractive targets for pharmaceutical intervention. Therefore, we have developed a high-throughput, nonradioactive ELISA method to monitor Raf and MEK1 kinase activity. In this assay system activated Raf phosphorylates and activates MEK1, which in turn phosphorylates MAPK. Antibodies that specifically detect phosphorylated MAPK (vs. nonphosphorylated MAPK) made enzyme-linked immunosorbent assay (ELISA) development possible. This assay detects inhibitors of Raf and/or MEK1 and has been used to screen large numbers of random compounds. The specific target of inhibition in the Raf/MEK1/MAPK ELISA can be subsequently identified by secondary assays which directly measure Raf phosphorylation of MEK1 or MEK1 phosphorylation of MAPK.

MEK (MAPKK) inhibitors. Part 2: structure-activity relationships of 4-anilino-3-cyano-6,7-dialkoxyquinolines.

A series of 4-anilino-3-cyano-6,7-dialkoxyquinolines with different substituents attached to the 4-anilino group has been prepared that are potent MEK (MAP kinase kinase) inhibitors. The best activity is obtained when a phenyl or a thienyl group is attached to the para-position of the aniline through a hydrophobic linker, such as an oxygen, a sulfur, or a methylene group. The most active compounds show low nanomolar IC(50)'s against MEK (MAP kinase kinase), and have potent growth inhibitory activity in LoVo cells (human colon tumor line).