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Background/Aims--Non-melanoma skin cancers frequently harbour multiple human papillomavirus (HPV) types. A recent report suggests that a polymorphism of the p53 tumour suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in HPV associated malignancies. This study aimed to determine the following: (1) the relation between HPV infection and the development of cutaneous squamous cell carcinoma (SCC), and (2) whether there is a correlation between p53 codon 72 polymorphism and the development of SCC.Methods--Blood samples were taken from 55 patients with skin cancer (both renal transplant recipients and immunocompetent patients with skin cancer) and 115 ethnically matched volunteers. A polymerase chain reaction based assay was used to determine p53 codon 72 genotypes. In addition, 49 benign and malignant lesions from 34 of the patients with skin cancer and 20 normal human skin samples from 20 of the control volunteers were examined for HPV.Results--The proportions of p53 codon 72 genotypes found were 78% arginine homozygous, 2% proline homozygous, and 20% heterozygous among patients with skin cancer and 79% arginine homozygous, 3.5% proline homozygous, and 17.5% heterozygous among the control population. Statistical analysis showed no significant differences in the distribution of the two p53 isoforms between the patients with skin cancer and the control population. The predominant viral types detected in both the patients and the control group were EV associated HPVs, although the incidence was lower in normal skin samples than in malignant lesions or viral warts.Conclusions--These results suggest that in a Celtic population there is no correlation between the presence of HPV, the p53 codon 72 arginine polymorphism, and the development of skin cancer.

Background/Aims--Loss of function of the retinoblastoma (Rb) tumour suppressor gene, located on chromosome 13, is common in many inherited and sporadic forms of cancer. Inactivation of its gene product by oncogenic human papillomaviruses (HPV) plays a key role in the genesis of cervical cancer. It has been shown previously that non-melanoma skin cancers of renal transplant recipients and immunocompetent patients with skin cancer also frequently harbour potentially oncogenic HPV types. This study aimed to examine the integrity of the Rb gene in histologically confirmed squamous cell carcinomas (SCCs) from renal transplant recipients and immunocompetent patients with skin cancer.Methods--Loss of heterozygosity (LOH) at the Rb locus was examined in 13 histologically confirmed SCCs using the D13S153 microsatellite marker, which is located in exon 2 of the Rb gene. Loss of a second marker, D13S118, distal telomerically to the Rb gene at 13q14.3 was also analysed.Results--Of the 13 HPV associated SCCs examined 11 were informative (two SCCs were homozygous for both microsatellite markers). LOH at the D13S153 locus was found in four of the 10 informative SCCs and LOH at the D13S118 locus was found in five of the 11 informative cases. Overall, seven of the 11 informative cases showed LOH at one or other locus. This represents a high degree of chromosomal instability in these tumours. The expression of the Rb gene product in the 11 informative cases was analysed immunohistochemically. Expression of Rb was detected in 10 of the 11 SCCs examined. No correlation between the HPV status of the tumours and the expression of Rb was found. Although the only SCC not to express Rb also demonstrated LOH at the D13S153 locus, the remaining SCCs that had LOH at 13q14 were able to express Rb.Conclusion--Another tumour suppressor gene located at 13q14 might be responsible for the genesis of these tumours.

The conventional smear has been very useful in detecting pre-cancerous lesions of the cervix. In recent years the UK screening programme has resulted in a 7% reduction annually in invasive cervical carcinoma. However the conventional smear has many limitations including a significant false negative and false positive rate and a significant unsatisfactory rate. Specimen quality is a problem with conventional Pap smears, with the presence of blood, inflammation and mucus often obscuring potential diagnostic cells leading to an unacceptably high unsatisfactory and suboptimal rate. In an attempt to address these limitations associated with the conventional smear various new techniques of smear preparation and screening have been developed.

The study of ageing and cell senescence has led to the recent interest in telomeres and telomerase. Telomeres are known to play a role in chromosomal replication and each time cells divide these telomeres shorten. Telomere shortening occurs with increased age. Telomerase is the main factor involved in the preservation of telomere length and therefore its activation is mooted to play a role in the immortalisation of cells. It is in this that our interest lies as it is thought that telomerase has a role to play not only in cell immortalisation but also in the development of neoplasia. Much research has been carried out in this exciting field with the aim of elucidating the role telomerase plays in carcinogenesis. This review is an attempt to summarise the recent advances in this area, which is striving to establish if telomerase does indeed have a role to play in either the early diagnosis of carcinoma or as a marker of prognosis.

Multielectrode sensor arrays are made of soft and wet materials not easily examined by most microscopic techniques. In this paper, we have demonstrated that lowvacuum scanning electron microscopy LVSEM and energydispersive Xray analysis EDX are adequate for studying the hydration, swelling, and possible delamination of multielectrode sensor arrays. We found that the LVSEM environment had no detectable effect on the morphology of Na, K, and Casensors, and EDX analysis indicated that all three membranes have similar compositions. However, once hydrated, the sensors exhibited different behaviors. The Kand Casensors swelled more than the Nasensor did. This swelling is due principally to water sorption in the membrane. We believe that the larger thickness of the Kand Camembrane is partly responsible for the observed swelling effect. A simple Griffith analysis of the interface rupture confirms the experimental evidence that these thicker membranes also are more prone to delamination failure. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 50, 313–321, 2000.

Objective.CD44, an integral membrane glycoprotein, may have an important role in early tumorigenesis, specifically, facilitating early tumor progression. Reports of the expression of CD44 in early uterine cervical squamous carcinogenesis are conflicting. We examined the expression of CD44 in microinvasive carcinoma of the cervix (MIC), as yet unreported, and compared it to that in cervical intraepithelial neoplasia (CIN) 1 and CIN 3 to further elucidate its role in early squamous carcinogenesis.

Cell suicide, or apoptosis, is a process essential for survival. It is an error-free method of programmed cell death whereby cells damaged by a variety of genotoxic insults are eliminated. The exact process of apoptosis is not completely understood and the control mechanisms are variable in different tissues. Much information on ultraviolet radiation induction of apoptosis has been accumulated from cell culture and animal model studies. This paper provides evidence of the role of sunlight. A variety of complex pathways are known to be involved. The p53 protein, a product of the tumour suppressor gene is involved in the process; however, parallel p53 independent pathways do exist. The knowledge learnt regarding apoptosis has been applied clinically to treat a variety of dermatological conditions. The importance of this exacting procedure is recognized by the fact that malignancy is related to mutations leading to impairment of the process of apoptosis.

The pressure dam bearing is a type of fluid film bearing in widespread use for enhancing rotor stability. Analytical refinements have been made to existing theory for predicting its performance characteristics and optimizing designs. This paper describes experiments conducted for evaluating the theory. Four designs were tested, with the basic for comparison being the static pressure generated at the dam. Measured differences from the refined theoretical predictions were generally less than 16% and are attributed to manufacturing errors which caused deviations from the theoretical model.

This study documents the reactions of the monoclonal antibody KP-1, which detects histiocytes in paraffin sections, with 137 sarcomas, 48 lymphomas, 28 carcinomas, 7 malignant melanomas and 8 cystosarcoma phyllodes. The soft tissue sarcomas had been previously immunophenotyped. Positive staining was obtained in all categories of sarcoma except clear-cell sarcomas. Most categories of sarcoma showed staining in less than 10% of tumour cells although a minority of leiomyosarcomas showed more extensive staining. Five of 7 malignant melanomas were also positive while all lymphomas and carcinomas were negative. We conclude that KP-1 positivity is not helpful in supporting the histiocytic origin of a tumour and is of limited value in the differential diagnosis of soft tissue sarcomas or their separation from other categories of malignancy.

Objective To determine the efficacy of DNA flow cytometric analysis of testicular percutaneous fine-needle aspirates in the assessment and follow-up of testicular function after torsion, and to determine the relationship between the duration of torsion and testicular injury.

Theoretically predicted instability onset speeds are compared to the experimental instability threshold speeds for a simple three mass flexible rotor supported by five geometrically different sets of step journal bearings and a set of two axial groove bearings. The near optimum step bearing designs increase the instability onset speed by around 109 percent in one case and 41 percent in another compared to two axial groove bearings. The off optimum designs increase the instability speed by 18, 30 and 35 percent. The theoretical stability analysis predicts the general trends in the experimental data.

This retrospective study reports the incidence of hydatidiform mole in a population of 19,457 pregnancies over a 3-year period. During the study period all “products of conception” from first and second trimester abortions were referred for pathological examination. Coded histologic sections were reviewed using the published histologic criteria for hydatidiform mole. Ploidy was estimated by DNA flow cytometry. Clinical data were retrieved from maternal case notes. Thirty-eight cases were confirmed as hydatidiform mole, 10 (26) as complete mole, and 28 (74) as partial mole. Twenty-three cases of partial mole (88) were triploid, and nine of 10 complete moles were diploid. The incidence of hydatidiform mole was 1:512 pregnancies, (complete mole, 1:1,945; partial mole, 1:695). Only one case (3.5) of partial mole was suspected clinically. One case of persistent gestational trophoblastic disease occurred following a complete mole. No sequelae were encountered following partial mole. We conclude that hydatidiform mole is a common condition and the majority of cases are partial moles. Quantitatively imprecise morphologic criteria contribute to the inaccuracy in reporting of partial mole; analysis of ploidy is useful in the evaluation of problem cases. Follow-up of partial mole is warranted because its true biological potential is as yet unclear.

Feulgen-DNA content of sperm was quantified in fresh semen samples of 20 consecutive couples during preparation for in vitro fertilization to measure the condensation state of sperm chromatin. Results were expressed as a percentage of expected haploid DNA value (lc). No significant differences were found between those who did not get pregnant, those who went full term, and those who aborted. Because fertilization can occur with a minority of normal sperm, it is concluded that the present findings do not provide useful clinical information about pregnancy outcome and in vitro fertilization.

OBJECTIVE: To assess the importance of iron overload as a risk factor for porphyria cutanea tarda (PCT). DESIGN: Prospective study during a 4-month period. SETTING: Departments of emergency care, gastroenterology, and dermatology in a tertiary referral center. PATIENTS: Patients were deemed eligible for inclusion in the study if serum ferritin levels were greater than 500 μg/L (normal range: females, <125 μg/L; males, <325 μg/L). MAIN OUTCOME MEASURES: Porphyrin excretion profiles were analyzed on all patients included in the study, where clinically relevant. A diagnosis of PCT was confirmed biochemically in all cases. The HLA typing was then performed on newly diagnosed cases of PCT. RESULTS: Of 4127 patients tested, 240 patients with an elevated serum ferritin level were identified, of whom 74 had an elevated serum ferritin level of more than 500 μg/L. Of the latter group, 17.5% had hemochromatosis and 6.7% had PCT. The incidence of PCT in the hemochromatosis group was 23%; HLA typing revealed the presence of at least 1 of the hemochromatosis markers. CONCLUSIONS: A high serum ferritin level in the absence of evident cause should prompt investigation for both hemochromatosis and PCT. The HLA heterozygosity for hemochromatosis in some patients with PCT may be a cause of hepatic siderosis.Arch Dermatol. 1997;133:1098-1101

The DNA content of 168 consecutive T3,NO,MO (Dukes' B, Astler-Coller B2) colorectal cancers was studied using image analysis on formalin-fixed paraffin-embedded tissues. 72 cases (43%) were classified as diploid and the remaining 96 (57%) as non-diploid. After a median follow-up period of 6.7 years, a significant survival advantage was found for diploid compared with non-diploid cases (logrank test; P= 0.008). The long-term (8 year) survival rate was 70% for diploid and 46% for non-diploid tumours. Subgroup analysis showed that the survival advantage conferred by tumour diploidy was greatest in large (⩾ 5 cm) cancers and was found both in colonie and rectal cancer cases. These data indicate that tumour ploidy status measured by image analysis might be useful in determining risk of colorectal cancer recurrence and death in patients following resection of early colorectal cancer.

Background:: Kidney transplant recipients have an increased incidence of skin cancer, the cause of which is likely multifactorial. Inactivation of the tumor suppressor gene p53 protein may be important. Chemoprophylaxis of skin cancer with retinoids is beneficial in these patients. Objective:: Our purpose was to investigate the immunohistochemical expression of p53 protein in premalignant and malignant cutaneous lesions in kidney transplant recipients and the effect of low-dose etretinate on p53 expression. Methods:: Paraffin sections were stained with the monoclonal antibody DO-7. Results:: Immunoreactivity of p53 was observed in 59% of basal cell carcinomas and more than 60% of squamous cell carcinomas, Bowen's disease, dysplastic lesions, and viral warts. No demonstrable effect of etretinate on p53 expression could be determined. Conclusion:: The high prevalence of p53 immunoreactivity in premalignant and malignant skin lesions of kidney transplant recipients supports a role for p53 protein in skin cancer. This could be caused by mutation of the p53 gene, inactivation, or failure of degradation of p53 protein.

Tumour markers now have an established role in tumour diagnosis and patient management. However, antibodies used to detect these tumour markers have in some instances proved unreliable, with a low rate of sensitivity and specificity. In this study we wished to evaluate the role of a commercial antibody to myoglobin as a marker of rhabdomyosarcomas. The purpose of this investigation was to assess the sensitivity and specificity of myoglobin antiserum as a marker of rhabdomyosarcomas. This was performed by reacting a large number of tumours (sarcomas, carcinomas and melanomas) with a polyclonal anti human myoglobin antiserum. Staining was demonstrated in 60% of rhabdomyosarcomas. Only two tumours from a total of 226 non-skeletal muscle tumours showed a positive reaction (0.88%). One was a leiomyosarcoma and the other had been classified as an undifferentiated sarcoma but a rhabdomyosarcoma was included in its differential diagnosis. It is of interest that both had been earlier irradiated. This antiserum was therefore a specific but not a very sensitive tumor marker. Its rate of staining of rhabdomyosarcomas is compared with the results in the literature. A great disparity is found and the reasons for this are discussed.

The response of a flexible rotor mounted in six bearing sets has been experimentally determined. One set of axial groove bearings and five sets of pressure dam bearings were tested. Conventional synchronous tracking was used in the analysis and other techniques utilizing an FFT analyzer were developed. The stability of the system was seen to strongly depend on the design of the step bearings. The dam bearings were also noted to lock into subsynchronous whip during deceleration after the system went unstable. The response of the system with varying degrees of unbalance is also analyzed and several structural resonances of the rotor system are discussed.

Background: Sodium diphenylhydantoin (DpH) (phenytoin) was first introduced as an antiepileptic in 1938. One of its side effects, gingival hyperplasia, prompted investigation into the possible application of this drug as a promoter of wound healing. Since the late 1950s phenytoin has been used in a variety of clinical situations. However, its exact mechanism of action is still debated. The aim of this study was to determine the effect of DpH on wound healing in an incisional rat model. Methods: A four dorsal wound model was used, and each cephalad wound had a polyvinyl alcohol sponge placed in a subcutaneous pocket just above its cephalad end. Caudal and cephalad wounds were treated with 10 mg DpH in 200 @ml carrier, and the other two wounds received an equal volume of the saline vehicle as controls on the day of wounding and on the third and sixth postoperative days. The animals were killed on the tenth postwounding day. Tensile strength of fresh and fixed scars was determined using constant speed tensiometry, and wound hydroxyproline was determined spectophotometrically. Results: There was a highly significant increase in both fresh and fixed wound tensile strength of all DpH-treated wounds compared with controls (p < 0.001). This was reflected by a significant increase in polyvinyl alcohol sponge hydroxyproline in DpH-treated wounds compared with saline-treated wounds (p = 0.002). Histologic examination of these wounds was performed at 3 and 6 days after wounding. There was moderate fibroblast infiltration with a marked inflammatory infiltrate and neovascularization in the DpH-treated wounds compared with controls at 3 days. By day 6, the inflammatory infiltrate had almost totally receded in the treated wounds, but fibroblast infiltration and angiogenesis were still persistently marked. In comparison, the saline-treated wounds still had moderate inflammatory and fibroblast infiltrate and mild angiogenesis. Conclusions: DpH alters the natural course of wound healing and may be of benefit in clinical situations where defective wound collagen deposition may lead to poor wound healing and consequent morbidity and mortality. (Surgery 1998;123:287-93.)

Clinical reports of increased graft primary non function in patients receiving cyclosporine in whom the anastomosis time is prolonged (>30 minutes) suggest a synergism between the nephrotoxic effects of cyclosporine and the ischaemia occurring during transplantation. Using unilaterally nephrectomised greyhound dogs, sixty minutes ischaemia and cyclosporine 10mg./kg./day we have produced an animal model of cyclosporine enhanced ischaemia renal failure. Structural and functional data suggests the proximal tubule is the main site of injury.

Cyclosporine is associated with an increased incidence of graft primary non function and poorer long term graft function in patients with prolonged ischaemia times. We evaluated the role of hypothermia in preventing this synergism between the nephrotoxic effects of cyclosporine and ischaemia in a canine model. Induced renal hypothermia prevented this synergism.

SUMMARY In a three-dimensional study of the distribution of anterior horn cells in the C8 segment of the human spinal cord we have recognized lateral and medial zones of motor neuron groupings, but have not been able to recognize subgroups of neurons within these groupings resembling the anatomical columns described by earlier investigators. This observation does not invalidate the concept of functional groupings within these anterior horn cell pools In studies of the same segment in cords obtained at autopsy from patients with motor neuron disease, zones of focal loss of motor neurons were identified, without consistent severity or distribution at different sectional levels. These findings imply varying resistance to the disease in different pools of motor neurons.