Assessment of the cutaneous immune response during Arthroderma benhamiae and A. vanbreuseghemii infection using an experimental mouse model.

BACKGROUND: Dermatophytoses are common but poorly understood skin infections. Most in vivo studies have been performed using the guinea pig as the experimental animal model, which has several limitations. OBJECTIVES: To develop a mouse model of dermatophytosis suitable for multiple purposes, including the investigation of immunity against dermatophytes. MATERIALS AND METHODS: Two peculiar fungal species, Arthroderma benhamiae and A. vanbreuseghemii, isolated from tinea in humans having contact with rodents were used for epicutaneous inoculation. During the infection, clinical and histopathological follow-up were performed. The recruitment of immune cells was evaluated by immunofluorescence staining and the levels of cytokine mRNA were quantified by quantitative reverse transcriptase-polymerase chain reaction in the skin of infected mice. RESULTS: The skin symptoms and microscopic lesions, including the colonization of keratinized epidermal and follicular structures by both dermatophytes, were highly similar to those observed in guinea pig infection models and in natural infections, mimicking acute superficial tinea in humans. The dermal inflammatory cellular infiltrate consisted of macrophages, dendritic cells and especially polymorphonuclear neutrophils, which are one of the histological 'clues' to the diagnosis of dermatophytosis. The in situ cytokine profile was characterized by the overexpression of transforming growth factor-ß, interleukin (IL)-1ß and IL-6 mRNA during infection, suggesting a role of the T-helper 17 pathway in the establishment of immunity. CONCLUSIONS: Our new reproducible and validated mouse model of dermatophytosis is a modern in vivo tool that allows a more in-depth understanding of the pathogenesis of human dermatophyte infections.

Inhibition of the keratinolytic subtilisin protease Sub3 from Microsporum canis by its propeptide (proSub3) and evaluation of the capacity of proSub3 to inhibit fungal adherence to feline epidermis.

Microsporum canis is a pathogenic fungus that causes a superficial cutaneous infection called dermatophytosis, mainly in cats, dogs and humans. Proteolytic enzymes have been postulated to be key factors involved in the invasion of the stratum corneum and keratinized epidermal structures. Among these proteases, the secreted subtilisin protease Sub3 was found to be required for adherence of M. canis arthroconidia to feline epidermis. This protease is synthetized as a preproenzyme consisting of a signal peptide followed by the propeptide and the protease domain. In order to assess whether the enzymatic activity of Sub3 could be responsible for the role of the protease in the adherence process, we expressed and characterized the propeptide of Sub3 and demonstrated that this propeptide is a strong inhibitor of its mature enzyme. This propeptide acts as a noncompetitive inhibitor with dissociation constants, K(I) and [Formula: see text] of 170 and 130 nM respectively. When tested for its capacity to inhibit adherence of M. canis to feline epidermis using an ex vivo adherence model made of feline epidermis, the propeptide does not prevent adherence of M. canis arthroconidia because it loses its capacity to inhibit rSub3 following a direct contact with living arthroconidia, presumably through inactivation by fungal membrane-bound proteases.

Mechanisms of skin adherence and invasion by dermatophytes.

Dermatophytes are keratinophilic fungi that can be pathogenic for humans and animals by infecting the stratum corneum, nails, claws or hair. The first infection step consists of adherence of arthroconidia to the stratum corneum. The mechanisms and the kinetics of adherence have been investigated using different in vitro and ex vivo experimental models, most notably showing the role of a secreted serine protease from Microsporum canis in fungal adherence to feline corneocytes. After germination of the arthroconidia, dermatophytes invade keratinised structures that have to be digested into short peptides and amino acids to be assimilated. Although many proteases, including keratinolytic ones, have been characterised, the understanding of dermatophyte invasion mechanisms remains speculative. To date, research on mechanisms of dermatophyte infection focused mainly on both secreted endoproteases and exoproteases, but their precise role in both fungal adherence and skin invasion should be further explored.

Increased neuronal nitric oxide synthase dimerisation is involved in rat and human pancreatic beta cell hyperactivity in obesity.

AIMS/HYPOTHESIS: Pancreatic beta cell hyperactivity is known to occur in obesity, particularly in insulin-resistant states. Our aim was to investigate whether changes in neuronal nitric oxide synthase (nNOS) function affect beta cell compensation in two relevant models: the Zucker fa/fa rats and pancreatic islets from obese humans. METHODS: Glucose-induced insulin response was evaluated in the isolated perfused rat pancreas and in human pancreatic islets from obese individuals. Expression of nNOS (also known as NOS1) and subcellular localisation of nNOS were studied by quantitative RT-PCR, immunoblotting, immunofluorescence and electron microscopy. RESULTS: Pancreatic beta cells from Zucker fa/fa rats and obese individuals were found to be hyper-responsive to glucose. Pharmacological blockade of nNOS was unable to modify beta cell response to glucose in fa/fa rats and in islets from obese individuals, suggesting an abnormal control of insulin secretion by the enzyme. In both cases, nNOS activity in islet cell extracts remained unchanged, despite a drastic increase in nNOS protein and an enhancement in the dimer/monomer ratio, pointing to the presence of high amounts of catalytically inactive enzyme. This relative decrease in activity could be mainly related to increases in islet asymmetric dimethyl-arginine content, an endogenous inhibitor of nNOS activity. In addition, mitochondrial nNOS level was decreased, which contrasts with a strongly increased association with insulin granules. CONCLUSIONS/INTERPRETATION: Increased nNOS production and dimerisation, together with a relative decrease in catalytic activity and relocalisation, are involved in beta cell hyperactivity in insulin-resistant rats but also in human islets isolated from obese individuals.

[How to read a screening mammography (mammotest)]. / Comment j'interprète une mammographie de dépistage (mammotest).

The purpose of this chapter is to give to the radiologist some practical information in order to be able to read the mammotests, as they are performed in mass screening for breast cancer in France. The examples shown must help to detect as many small cancers as possible, without inflating the false positive rate. Screening mammotests can be read one by one (first reading), or by large series (second or third reading). To improve both the sensitivity and the specificity, reading technique should be strict, with correct fitting (viewboxes, ambiant light). For each case, a technical evaluation is performed (sharpness, contrast, breast projection), followed by the detection phase (asymmetry, abnormal density or calcifications or distorsion). Then, the image is analyzed (eliminating the typical benign conditions), and finally encoded to formalize the result: normal/suspicious for breast cancer. A good working method and a perfect knowledge of normal and pathologic appearances, allow us to reach the recommended rates for detected cancers and positive tests.

[Preoperative localization of asymptomatic breast lesions by the technique of stereotaxic tattooing and use of a wire. Apropos of 670 cases]. / Repérage pré-opératoire des lésions mammaires infracliniques par la technique du tatouage stéréotaxique et du "harpon". A propos de 670 observations.

OBJECTIVE: To compare the quality of pre-operative analysis of sub-clinical lesions of the breast using a wire and stereotaxic tattooing. METHODS: Between 1983 en 1990, 670 cases were analysed. At first needle or wire localisation techniques were used and then from 1988 onwards stereotaxic tattooing, first with the wire technique combined with it and later by itself from 1989 onwards. PLACE STUDY CARRIED OUT: Oscar-lambret Centre in the Department of Surgery and Radiodiagnosis I, BP 307, Lille Cedex. RESULTS: 190 carcinomas were diagnosed (30.7%) of which 20 were micro-invasive and 46 carcinoma in situ. The efficiency of the analysis was evaluated according to the number of explorations that were necessary to remove healthy tissue around the lesion. The wire technique results were significantly different (15.43% = 339 cases), tattooing with wire (9.13% = 144 cases), and tattooing by itself (6.30% = 135 cases). CONCLUSION: It seems that pre-operative assessment using stereotaxic tattooing is the most reliable of methods because it allows limited excision of the lesion and a more aesthetic approach.

[Preoperative marking of non-palpable breast lesions by the stereotaxic tattooing and "harpoon" technique. 670 cases]. / Repérage pré-opératoire des lésions mammaires infracliniques par la technique du tatouage stéréotaxique et du "harpon". A propos de 670 observations.

OBJECTIVE: To compare the quality of pre-operative analysis of sub-clinical lesions of the breast using a wire and stereotaxic tattooing. METHODS: Between 1983 en 1990, 670 cases were analysed. At first needle or wire localisation techniques were used and then from 1988 onwards stereotaxic tattooing, first with the wire technique combined with it and later by itself from 1989 onwards. Place study carried out: Oscar-lambret Centre in the Department of Surgery and Radiodiagnosis 1, BP 307, Lille Cedex. RESULTS: 190 carcinomas were diagnosed (30.7%) of which 20 were micro-invasive and 46 carcinoma in situ. The efficiency of the analysis was evaluated according to the number of explorations that were necessary to remove healthy tissue around the lesion. The wire technique results were significantly different (15.43% = 339 cases), tattooing with wire (9.13% = 144 cases), and tattooing by itself (6.30% = 135 cases). CONCLUSION: It seems that pre-operative assessment using stereotaxic tattooing is the most reliable of methods because it allows limited excision of the lesion and a more aesthetic approach.

Aminoglutethimide (AG) and hydrocortisone (HC) in bone metastases: a retrospective study.

The response rate in bone metastases in 57 patients treated with aminoglutethimide and hydrocortisone was retrospectively assessed. All the X-rays were reviewed by two senior radiologists. A response was observed in 23% of the patients, a stabilization in 32%. The survival was not different whether a response or stabilization was observed. Conversely, survival was significantly worse in patients who experienced a progressive disease.

[Hypopharyngeal cancer in the Northern region and Pas-de-Calais. Epidemiological factors]. / Cancers de l'hypopharynx dans la région Nord et Pas-de-Calais. Facteurs épidémiologiques.

Authors report results of two epidemiological studies concerning hypopharynx cancer. The first one is a part of the head and neck cancer registry of Northern France from 1984 to 1987. Hypopharynx tumors represent 18% of the 6019 registered tumors, 99% are squamous cell carcinoma; the annual european standardized incidence rate is 17.0 per 100,000 males and 0.5 per 100,000 females. The second one is a prospective study of 339 hypopharynx cancer patients: 1 out of 3 lives alone and 1 out 3 works at the moment of diagnosis. The average daily tobacco and alcohol consumption are 24 g and 128 g respectively, without any difference regarding professional exposures.

[Clinically localized cancers of the breast. Therapeutic consequences of the evaluation of extension]. / Cancers du sein cliniquement localisés. Conséquences thérapeutiques du bilan d'extension.

The therapeutic modifications induced by pretreatment evaluation were studied in a consecutive series of 852 asymptomatic women with newly diagnosed primary breast cancer attending our center between 1980 and 1984. Staging tests included chest X-rays in 851 patients, bone X-rays in 831, alkaline phosphatase in 826, hepatic enzymes in 818, liver echography in 750 and bone scintigraphy in 504. The intended local treatment was changed for a systemic one in 8 patients due to suspicious abnormalities. The follow-up confirmed evidence of metastases in 6 out of 8 patients (bone: 4; liver: 1; lung: 1). Mastectomy, initially avoided in these 6 patients, was subsequently performed in 2 of them owing to slow progression of distant metastases. On the basis of the current study, pretreatment staging in asymptomatic primary breast cancer cannot be recommended due to the low prevalence of detectable metastases.

[Cancer of the upper aerodigestive tract. Global study of 2418 cases]. / Les cancers des voies aérodigestives supérieures. Etude globale de 2418 dossiers.

The authors present the general results of a retrospective study on 2418 patients treated between 1976 and 1980. Primaries were located on buccopharynx in 51% of cases, pharyngolarynx in 45% and nasopharynx or nasal and paranasal cavities in 4%. Two out of 3 tumours were classified T3 T4 (UICC 1979) and 1 out of 2 patients presented with palpable cervical lymph nodes. Taking into account persistent diseases and recurrences, failure at primary sites occurred in 40% of patients, in the neck in 20%, distant metastases in 10%. Synchronous and/or metachronous cancers were observed in 1 out of 3 patients. Actuarial survival rates were 2/3 at 1 year, 1/3 at 3 years, 1/4 at 5 years and 1/7 at 8 years. Endolaryngeal tumours had the best prognosis while hypopharyngeal tumours had the worst prognosis.

Computed tomography of urachal carcinoma.

Urachal carcinoma arises in the clinically silent extraperitoneal space between the bladder apex and the umbilicus. Computed tomography was used to correctly diagnose and stage urachal cancer in two patients. In one case a mass was localized to the bladder wall and immediate juxtavesical region; in the other case an advanced locally invasive lesion was seen to engulf and fisulize loops of small bowel and extend through the umbilicus. Urachal carcinoma has a highly characteristic appearance and location on CT images.

[Ulcerated cancers of the breast: results of modified mastectomy. Apropos of 64 cases]. / Les cancers ulcérés du sein: résultats des mastectomies de propreté. A propos de 64 observations.

Although, happily, at the present time the actual tendency in mammary neoplastic disease is being increasingly orientated towards conservative treatment, a fairly large number of total mastectomies are still being performed in patients diagnosed at a late stage. The frequency, technical aspects and precise local and general prognosis of this affection are discussed in relation to 63 breast cancers treated surgically between 1975 and 1984. These so-called "trimming" mastectomies represent 4.22% of overall total mastectomies performed during the same period. The surgical technic employed was the Patey type total mastectomy with either primary suturing after-wide separation of borders or closure with a thoraco-epigastric fasciocutaneous flap with internal pedicle. Actuarial survival was satisfactory: 58% at 2 years, 34% at 5 years, survival being significantly better in patients with lack of glandular invasion. This surgical technic should be considered, in combination with other therapy, for these patients, who should not be classed as "unrecoverable".

[Registry of cancers of the upper respiratory and digestive tract at the Northern and Pas-de-Calais departments from 1984 to 1986]. / Registre des cancers des voies aérodigestives supérieures des départements du Nord et du Pas-de-Calais 1984-1986.

Northern France is known to have the highest mortality rate for cancers of the upper aerodigestive tract (UADT); a UADT cancer registry was therefore set up in this region in January 1984. Three years of meticulous registration provided some significant information. The incidence of UADT cancer was alarming: 4538 UADT cancers in 4403 patients. Most of the patients were males (93.5%). The annual average incidence was 74 per 100,000 males as against 4.8 per 100,000 females. Comparisons with adjusted rates for the European population (91.3 per 100,000 males, 4.8 per 100,000 females) and the world population (68.3 per 100,000 males and 3.6 per 100,000 females) further justified this conclusion. The accuracy of histopathological diagnosis was high (precise diagnosis in 99.2% of the patients). Squamous cell cancers were the commonest form of tumours (97.8%). Oropharynx (27%), larynx (24%) and the hypopharynx (18%) were the most frequent localizations.

[Preoperative location of deep subclinical breast lesions using the harpoon technic. Apropos of 149 cases]. / Repérage pré-opératoire des lésions mammaires infra-cliniques profondes par la technique du "harpon". A propos de 149 observations.

Since April 1983, harpoon technique was used for limited excision of subclinical mammography-observed anomalies. The procedure involves the insertion of a harpoon-shaped metallic thread, after detection by mammography, to obtain guidance of surgical procedures. The results of 155 procedures in 149 patients included detection of 38 cancers (26%), confirming documented data in this field.

Dilutional effect of increased sebaceous gland activity on the proportion of linoleic acid in sebaceous wax esters and in epidermal acylceramides.

Sebaceous wax esters and epidermal acylceramides were isolated from skin surface lipid obtained from children and from young adults. Fatty acid methyl esters (FAME) were prepared from the esterified fatty acids of these lipid classes and analyzed to ascertain the proportions of methyl linoleate (18:2 delta 9,12), methyl sebaleate (18:2 delta 5,8), and methyl sapienate (16:1 delta 6). On the same subjects, 2 measures of sebum secretion rate were obtained, namely the sustainable wax ester secretion rate (WESR) on the forehead and the ratio of wax esters/(cholesterol + cholesterol esters) [WE/(CH + CE)] in the surface lipid. The proportions of methyl linoleate in FAME from the wax esters decreased, and the proportions of methyl sebaleate increased, with increased rates of sebum secretion. For both methyl linoleate and methyl sebaleate, a better correlation was obtained when the ratio of WE/(CH + CE) was used as a measure of sebum secretion rather than the WESR. The proportions of methyl linoleate in the FAME from the acylceramides were also inversely related to ratios of WE/(CH + CE). In acylceramides, linoleate was replaced by sapienate, a major fatty acid of human sebum. It appears, therefore, that sebum fatty acid composition may change with changes in sebaceous gland activity, and that sebum fatty acids can enter the epidermis and be incorporated into epidermal lipids.

In vivo sustained release of cisplatin from bioresorbable implants in mice.

Two kinds of cisplatin-containing implants were prepared from polylactic acid (type I) and from lactic acid-glycolic acid copolymer (type II). Type I implants were almost unaffected when inserted in the renal parenchyma of mice. In contrast, type II implants evolved clearly after in vivo implantation. X-ray pictures and platinum concentration measurements showed a continuous release of platinum over at least three weeks. The release resulted in high platinum concentrations in the kidney tissues and low plasma concentrations, compared to systemic injection. Type II implants seem adequate for further clinical trials of local treatment by cisplatin.