The role of myosin I and II in cell motility

Summary It has been recognized since the turn of the century that cell motility by non-muscle cells requires virtually continuous restructuring of the cytoskeleton (see refs [1–4]). It is also clear that cell motility requires a mechanism for converting chemical energy into mechanical work [5]. The proteins actin and myosin, two important constituents of the cytoskeleton, have been postulated to act as the chemicomechanical transducer in motile cells. Central to their role as a force generating mechanism in motile cells is the ability of myosin (a) to hydrolyze ATP when it interacts with actin and (b) to form filaments. Recent studies on mammalian cells and on the cellular slime mold Dictyostelium discoideum have shed light and at the same time raised questions regarding the involvement of myosin in cell motility. Moreover, they have demonstrated the presence of two types of myosins, called myosin II and myosin I, that have unique biochemical and regulatory properties and that may play different roles in mediating cell motility. In this chapter we will discuss the properties of these two myosins and then describe what is known about their involvement in Dictyostelium and mammalian cell motility.     

An unusual case of small bowel obstruction: heterotopic gastric mucosa

We report a case of heterotopic gastric mucosa (HGM) causing small-bowel obstruction by occlusion of the jejunal lumen, confirmed at laparotomy. The clinical presentation, radiographic features, and pathological findings are described and a brief review of the literature is cited. It is very rate for HGM to present in this way and the surgical significance is described. Offprint requests to: J. P. A. Lodge     

Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity.

A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate (200 mg/m2) and cisplatin (100 mg/m2) prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy.     

Control of leucocyte function-associated antigen-1-dependent cellular conjugation by divalent cations.

The control of integrin activation is fundamental to an understanding of the integrin-dependent cellular adhesion thought to be important for a plethora of basic cellular functions. Using a cell-cell conjugation assay the role of divalent cations in leucocyte function-associated antigen-1 (LFA-1)-dependent cellular adhesion was further investigated. The conjugation of interleukin-2 (IL-2)-activated lymphocytes to tumour cells was found to be energy dependent and required the presence of various divalent cations, removal of which decreased the level of conjugation. Increased concentrations of calcium, magnesium and manganese ions resulted in a corresponding increase in levels of conjugation. This increase in conjugation was LFA-1 dependent. Interestingly, when calcium ions were first removed from LFA-1, treatment of lymphocytes with magnesium and manganese ions gave significantly higher levels of conjugation than in the presence of calcium. Using a simple displacement study, calcium ions were shown to displace magnesium ions resulting in decreased conjugation. However, calcium ions were unable to displace manganese ions for binding to LFA-1. That manganese was exerting its effect via an LFA-1-dependent mechanism was confirmed using monoclonal antibodies to CD11a which negated the increased conjugation frequency due to manganese.     

The impact of the accident at the Three Mile Island on the behavior and well-being of nuclear workers; Part I: perceptions and evaluations, behavioral responses, and work-related attitudes and feelings.

In order to assess the impact of the accident at the Three Mile Island (TMI), telephone interviews were conducted six months later with 324 nuclear workers assigned to TMI and 298 workers assigned to a comparison plant at Peach Bottom (PB). Examination of PB-TMI differences, stratified by supervisory status, revealed the following: Part I: TMI workers reported greater exposure to radiation at the time of the accident and felt that their health had been thereby endangered. TMI workers experienced more uncertainty and conflict at the time of the accident. Coping responses such as seeing a doctor, taking drugs, and increasing alcohol consumption were quite infrequent. Leaving the area was more common; however, over 40 per cent of TMI workers wished to leave but did not do so because of work obligations. TMI workers reported much lower job satisfaction and much greater uncertainty about their job future.     

Epidermal growth factor receptors in human prostate cancer: correlation with histological differentiation of the tumour

The presence of specific and high affinity epidermal growth factor receptors (EGF-R) has been demonstrated in human prostate cancer (CaP). Scatchard analysis of the binding data revealed a linear plot consistent with a single class of binding sites with a mean dissociation constant (Kd) +/- s.d. = 1.6 +/- 0.4 nmol 1-1. Additionally the binding was specific for EGF since no other competitor than EGF was able to displace the binding of the labelled ligand from its receptor. Comparison of the concentrations of EGF-R in tissues from 19 patients with CaP with those measured in a group of 18 patients with benign prostatic hyperplasia (BPH) reveal that the expression of EGF-R was significantly higher in BPH (mean +/- s.d. = 125 +/- 7 fmol mg protein-1) than in CaP (52 +/- 11 fmol mg protein-1; P less than 0.01). Furthermore, in CaP the expression of EGF-R varied according to the histological grade of the cancer: well differentiated tumours demonstrated more receptors (84 +/- 13 fmol mg protein-1) than poorly differentiated tumours (22 +/- 5 fmol mg protein-1; P less than 0.01). Clearly the depletion in the expression of EGF receptors in CaP is a function of the histological grade of the cancer and as such EGF receptors could be used as a biochemical marker for tumour differentiation.     

Closure of transverse loop colostomy and loop ileostomy.

The aim of a defunctioning stoma is to protect patients from the consequences of faecal leakage and pelvic sepsis, should it occur. A retrospective audit of 77 patients who had undergone closure of a loop stoma between 1988 and 1996 was performed. Sixty patients had either transverse loop colostomy (52) or loop ileostomy (8) to defunction distal colorectal/anal anastomoses or pathology, and 17 patients had a loop ileostomy to defunction an ileoanal pouch. Those who had restorative proctocolectomy experienced a much higher (24%) complication rate than the loop colostomy group (5%), despite similar perioperative care and surgery performed by surgeons of equivalent seniority. The complication rate of ileostomy closure in pouch patients is similar to other published series. As a result of these findings, a selective approach to the use of loop ileostomy to protect pouches has been introduced. The absence of wound infections in our series would suggest that primary closure of the stomal wound without drainage can be achieved.     

Gallbladder polyps: prospective study.

The aim of this study was to describe the natural history of gallbladder polyps. Thirty-eight subjects who had been previously identified as having gallbladder polyps in an epidemiologic study of gallstone prevalence in 627 diabetic subjects and matched controls were followed longitudinally. Follow-up sonograms were obtained on 33 and 22 of the 38 subjects at 2 and 5 years, respectively. Prevalence for gallbladder polyps in this population was 6.7%, with a marked male predominance (odds ratio 2.3). No statistical difference in prevalence was found between diabetic subjects and nondiabetic controls. Ninety percent of the polyps were less than 10 mm in diameter, with no polyp being larger than 12 mm. During the follow-up period no changes suggestive of malignant transformation were observed. In conclusion, we found that gallbladder polyps were relatively common and that few significant changes occurred over a 5 year period. In asymptomatic subjects in whom gallbladder polyps less than 10 mm in diameter are found incidentally, the likelihood of malignant transformation is low.