Reproductive effort affects cellular response in the mantle of Nodipecten subnodosus scallops exposed to acute hyperthermia.

In marine ecosystems, temperature regulates the energy metabolism of animals. In the last decades, the temperature increase was related to mass mortality events of marine ectotherms, particularly during high-energy investment for reproduction. In scallops, the mantle has been poorly investigated while this tissue covers more than 40 % of the body mass, contributing to the perception of surrounding environmental stimuli. Our aim was to assess the cellular and molecular responses linked to energy metabolism in the mantle of adult N. subnodosus facing acute hyperthermia during reproductive effort. Scallops collected in spring (late gametogenesis) and summer (ripe gonads) were exposed to a control temperature (22 °C) or acute hyperthermia (30 °C) for 24 h. In spring, increased arginine kinase (AK) activity together with increased pyruvate kinase/citrate synthase ratio (PK/CS) suggested an enhanced carbohydrate, pyruvate, and arginine metabolism to maintain the adenylate energy charge (AEC) in the mantle of scallops coping with acute thermal increase. In summer, animals decreased their AEC (5 %) and arginine phosphate pool (40 %) and increased their anaerobic metabolism as shown by enhanced activities of lactate-dehydrogenase (LDH) and octopine dehydrogenase (ODH), respectively. The abundance of twenty proteins involved in energy metabolism (isocitrate dehydrogenase, ATP synthase subunit ß), protein protection (cognate heat shock protein 70), and cytoskeleton (actins and tubulins) were affected only by season. These results underlie the role of the mantle of N. subnodosus in the seasonal responses of this tissue to thermal fluctuations during reproductive effort with possible implications for the physiological performance of scallops under heat waves in wild or harvest conditions.

Long term follow up of BRCA1 and BRCA2 mutation carriers with unsuspected neoplasia identified at risk reducing salpingo-oophorectomy.

OBJECTIVES: The reported incidence of neoplasia identified at the time of risk-reducing salpingo-oophorectomy (RRSO) in germline BRCA1/2 mutation carriers ranges from 4 to 12% but long-term outcomes have not been described. We evaluated recurrence and survival outcomes of mutation carriers with neoplastic lesions identified at RRSO. METHODS: We identified BRCA1/2 mutation carriers with neoplasia at RRSO at three institutions. Data was collected on clinical variables, adjuvant treatment and follow-up. RESULTS: We identified 32 mutation carriers with invasive carcinomas (n=15) or high-grade intraepithelial neoplasia (n=17) that were not suspected prior to surgery. 26 occurred in BRCA1 and 6 in BRCA2 mutation carriers. Median and mean age for carcinomas were 50 years and 49.3 respectively, significantly younger than for intraepithelial neoplasm, median 53 years, and mean 55 years (p=0.04). For the 15 invasive carcinomas, median follow up was 88 months (range 45-172 months), 7 recurred (47%), median time to recurrence was 32.5 months and 3 have died of disease; 1 additional patient died of breast cancer. Overall survival was 73%, disease specific overall survival was 80% and disease free survival was 66%. For the 17 high-grade intraepithelial neoplasms, median follow up was 80 months (range 40-150), 4 were treated with chemotherapy. One recurred at 43 months and is currently not on therapy with a normal CA125, 16 months later. All patients with noninvasive neoplasia are alive. CONCLUSIONS: BRCA1 and BRCA2 mutation carriers with unsuspected invasive carcinoma at RRSO have a relatively high rate of recurrence despite predominantly early stage, small volume disease. High-grade intraepithelial neoplasms rarely recur as carcinoma and may not require adjuvant chemotherapy.

Steroid sulfatase activity in amnion tissue and amnion cells maintained in monolayer culture.

Phenolic steroid sulfatase activity in amnion tissue, amnion homogenate, subcellular fractions, and amnion epithelial cells in culture was demonstrated with radiolabeled estrone sulfate as the substrate. Sulfatase activity could not be detected in either amnion tissue or cells when evaluated with dehydroisoandrosterone sulfate as the substrate. Phenolic steroid sulfatase activity in amnion tissue was linear with incubation time up to 3 h and with amnion tissue weight up to 800 mg/ml. The rate of estrone sulfate hydrolysis in amnion tissue increased in a linear manner with temperature from 3 to 60 C. The apparent Km of amnion tissue sulfatase for estrone sulfate was 9 microM. The highest specific activity of the enzyme was found in both the mitochondrial-lysosomal and microsomal fractions. In studies with amnion epithelial cells in monolayer culture, phenolic steroid sulfatase activity was linear with incubation time up to 4 h and with cell number up to 2 X 10(5)/ml. The apparent Km of amnion cell sulfatase for estrone sulfate was 5.5 microM. The product of hydrolysis, i.e. estrone, was metabolized in situ to 17 beta-estradiol in both amnion tissue and cells. The hydrolysis of estrone sulfate (and possibly other phenolic steroid sulfates present in amniotic fluid) by amnion cells may be important in providing biologically potent estrogens for in situ action.

Steroid sulfatase activity in human lung tissue and in endothelial pulmonary cells in culture.

The conversion of tritium-labeled estrone sulfate to [3H]estrone was evaluated in human lung tissue in vitro. Under standardized conditions, the rate of hydrolysis of [3H] estrone sulfate to [3H]estrone was linear with time of incubation up to 4 h and with wet tissue weight up to 400 mg/ml. The apparent Km of sulfatase for estrone sulfate was 9 microM, and the maximum velocity was 1.4 nmol substrate hydrolyzed/100 mg lung . h. The lung tissue also metabolized the primary metabolite of [3H]estrone sulfate, [3H]estrone, to 17 beta-[3H]estradiol. The hydrolysis of [3H]dehydroisoandrosterone sulfate to [3H]dehydroisoandrosterone by human lung tissue was also measured. Sulfatase activity with this substrate was linear as a function of wet tissue weight up to 800 mg/ml. The apparent Km of sulfatase for dehydroisoandrosterone sulfate was 7 microM, and the maximum velocity was 1.0 nmol substrate hydrolyzed/100 mg lung . h. The highest specific activity of lung sulfatase for [3H]dehydroisoandrosterone sulfate was found in a microsomal fraction of lung homogenate. The primary metabolite, [3H]dehydroisoandrosterone, was metabolized further by lung tissue to [3H]androstenedione and [3H]5-androstene-3 beta, 17 beta-diol. Although isolated segments of human pulmonary arteries also metabolized both [3H] estrone sulfate and [3H]dehydroisoandrosterone sulfate, cultures of pulmonary arterial endothelial cells lacked sulfatase activity. The cell(s) source of sulfatase activity in human lung tissue and isolated arteries has not yet been identified. Our findings suggest that the metabolism of sulfated steroids by the lung should be considered in evaluating homeostasis.

Concomitant and hormonally regulated expression of trp genes in bovine aortic endothelial cells.

Recent findings have suggested that the vertebrate trp family of channel proteins is the structural basis for Ca2+ influx through the capacitative calcium entry (CCE) pathway. We have discerned, in bovine aortic endothelial cells, the concomitant expression of four such vertebrate genes: trp-1 (two splice variants), trp-3, trp-4 and trp-5. Exogenous hormones rendered dynamic effects on the transcript levels of these genes. Most notably, beta-estradiol significantly down-regulated trp-4 while trans-retinoic acid dramatically up-regulated trp-5; yet these hormones rendered little change in CCE. These findings suggest that the extent of a given trp channel's participation in CCE is not reflected in alterations of its transcript level.

Expression of neurotrophin-3 in the growing velvet antler of the red deer Cervus elaphus.

Antlers are organs of bone which regenerate each year from the heads of male deer. In addition to bone, support tissues such as nerves also regenerate. Nerves must grow at up to 1 cm/day. The control of this rapid growth of nerves is unknown. We examined the relative expression of neurotrophin-3 (NT-3) mRNA in the different tissues of the growing antler tip and along the epidermal/dermal layer of the antler shaft of the red deer Cervus elaphus, using semi-quantitative reverse transcription-polymerase chain reaction. Expression in the tip was found to be highest in the epidermal/dermal layer and lowest in the cartilaginous layer in all developmental stages examined. These data correlate well with the density and pattern of innervation of these tissues. Along the epidermal/dermal layer of the antler shaft, expression was highest in the segments subjacent to the tip and lowest near the base, arguing for differences in the temporal expression of NT-3 in these segments. The expression of NT-3 in cells isolated from the different layers of 60-day antlers did not mirror that observed when whole tissues were used and may suggest regional specificity of NT-3 expression within antler tissues.

Gastric choriocarcinoma and yolk sac tumor in a man: observations about its possible origin.

The case of a 65-year-old man who had a gastric tumor with components of choriocarcinoma and yolk sac tumor is presented. The presence of a small component of adenocarcinoma in the primary tumor and the absence of any gonadal or other primary tumor at autopsy confirm its origin. Despite the common association of embryonal and trophoblastic elements in gonadal tumors, this is the first case in which such an association was clearly depicted in the stomach. This and the usual coexistence of adenocarcinoma with choriocarcinoma in the stomach suggest the possibility of a different mode of development of these tumors in the two sites: forward differentiation of neoplastic germ cells in the gonads and retrodifferentiation (opisthoplasia) of neoplastic mucosal epithelial cells in the stomach.

Fluorescence of Pneumocystis carinii in Papanicolaou smears.

Pneumocystis carinii organisms can be identified in routine cytologic smears stained by the Papanicolaou method and viewed under ultraviolet light in a fluorescence microscope. The organisms can be identified easily in thin, well-preserved cytologic smears. No false-positive results were obtained when 55 Papanicolaou smears of bronchial washings were observed by this method. Twenty-three of these smears were from patients with Pneumocystic carinii pneumonia in whom the acquired immunodeficiency syndrome (AIDS) had been well documented with Gomori's methenamine silver stain. With this method no additional special stains are required, no time delay for special stains is involved, and no additional material for the preparation of extra smears for special stains is needed. An additional advantage is the possibility of the retrospective analysis of smears already stained by the Papanicolaou method.

Distribution of Leu-7 antigen (HNK-1) in thyroid tumors: its usefulness as a diagnostic marker for follicular and papillary carcinomas.

The reactivity of the anti-Leu-7 monoclonal antibody was tested in 39 neoplastic and nonneoplastic thyroid tissue specimens. These included eight colloid goiters, 14 follicular adenomas, nine papillary carcinomas, five follicular carcinomas, two medullary carcinomas, and one metastatic follicular carcinoma in bone. We observed strong cytoplasmic and/or cell membrane positivity in all follicular and papillary carcinomas, in both primary and metastatic tumors. However, the medullary thyroid carcinomas tested were negative. We also observed weak and only occasional staining with anti-Leu-7 antibody in colloid goiter and follicular adenomas. The staining in the benign thyroid lesions was usually focal, less than 10% of the cells; however, in cases of follicular and papillary carcinomas, both in primary and metastatic tumors, the staining was diffuse and strong. Some of the colloid material in colloid goiters and follicular adenomas showed faint homogenous staining with anti-Leu-7 antibody. Our findings suggest that anti-Leu-7 monoclonal antibody is a marker that may facilitate the differentiation between benign and malignant thyroid lesions, with the exception of medullary carcinoma. In addition, caution should be taken when using this antibody to diagnose metastatic lesions, as other metastatic carcinomas have also been reported to be positive. This antibody should be used in conjunction with a panel of antisera to complement a morphologic diagnosis.

Peliosis of the spleen with rupture.

A case of peliosis of the spleen without apparent involvement of the liver or other organs is presented. The peliosis was discovered following rupture of the spleen after minimal trauma and was successfully treated by surgery. None of the common associations of peliosis was present (i.e., tuberculosis or intake of steroid compounds). Drugs addiction and chronic alcoholism were the only coexisting debilitating conditions exhibited by this patient.

Endobronchial metastasis from cancer of the breast.

Endobronchial metastasis is reported to occur in less than 5% of the autopsies of patients dying with extrathoracic malignant neoplasms. Frequently associated primary tumors include those of the kidney, pancreas, colon, ovary, and thyroid. To our knowledge, this is the first report of a case of cancer of the breast which metastasized to the mucosa of a major bronchus. The possible factors involved in the widespread, early unusual spread in this 25-year-old woman are discussed.

17 beta-Hydroxysteroid oxidoreductase: a ubiquitous enzyme. Interconversion of estrone and estradiol-17 beta in BALB/c mouse tissues.

A survey was conducted to define the sites of 17 beta-hydroxysteroid oxidoreductase activity in organs and tissues of male and female BALB/c mice, as well as the favored direction of the oxidoreductase reaction in intact tissues. The enzyme activity was assayed by use of radiolabeled estrone and estradiol-17 beta as substrates. Estrone formation from estradiol-17 beta was demonstrated in all tissues. The formation of estradiol-17 beta from estrone was demonstrated in most tissues, however, it was barely detected or was undetectable in the glandular stomach, small intestine, cecum, and large intestine. Thus, 17 beta-hydroxysteroid oxidoreductase activity is expressed in all BALB/c mouse organs and tissues. Approximately two-thirds of the tissues and organs examined, including those of the reproductive tracts, favored the conversion of estrone to estradiol-17 beta rather than the reverse reaction. The results of this study, however, represent qualitative estimates of 17 beta-hydroxysteroid oxidoreductase activity in BALB/c mouse tissues that are uncorrected for conversion to hydroxylated metabolites. These in vitro findings suggest that the 17 beta-hydroxysteroid oxidoreductase catalyzed reduction of estrone may contribute to the maintenance of physiologic levels of estradiol-17 beta in estrogen responsive tissues.

Spindle cell lipoma of the oral cavity. Report of a rare intramuscular case with fine needle aspiration findings.

BACKGROUND: Spindle cell lipoma (SCL) is a benign neoplasm characterized by a mixture of mature fat, bland spindle cells and wiry collagen in a variably myxoid background. Oral SCLs are rare, and only four cases of intramuscular SCL exist in the literature. We report the first case of intramuscular SCL of the oral cavity with fine needle aspiration (FNA) findings. CASE: A 61-year-old woman presented with a 3-cm mass in the right gingivobuccal sulcus. Papanicolaoustained FNA smears were hypocellular and contained loose collections of spindle cells in a myxoid background, numerous mast cells, rare capillary fragments and portions of skeletal muscle. The spindle cells had mild nuclear enlargement, focal nuclear irregularities, rare intranuclear inclusions and occasional small nucleoli. No lipoblasts or mitoses were identified. There was intermingling of the spindle cells with the skeletal muscle fragments. CONCLUSION: Intraoral SCL is a rare lesion but should be considered in the differential for a benign spindle cell neoplasm in the oral cavity. Clues to diagnosis on cytology include mature fat, bland spindle cells, a myxoid background and mast cells.

"Witch doctor?" A hexing case of dermatitis.

A Mexican-American woman presented with exfoliative dermatitis complicated by a "curse". She was cured by a combination of bland topical therapy and casting off of the spell by a curandero.

Topical tretinoin, hydroquinone, and betamethasone valerate in the therapy of melasma.

Twenty adult female patients with melasma were followed over a ten week clinical trial in which a combination of depigmenting agents was used daily. Past clinical experience and objective assessment point to enhanced efficacy of this simple depigmenting combination. Certainly, most of depigmenting agents at our command to date have been relatively ineffective. Even this new combination is not the final answer. The purpose of this study is to provide the clinician with a simple yet effective and readily accessible combination of commercially-formulated and available depigmentary agents. A stable combination in a single vehicle with greater efficacy remains to be perfected.

Halo congenital nevus.

A case of halo congenital nevus is reported in a fifteen year old Mexican-American girl with pre-existing vitiligo.

Oligosymptomatic Melkersson-Rosenthal syndrome.

A patient with cheilitis granulomatosa and sialopenia is presented herein as a variant of the oligosymptomatic type of Melkersson-Rosenthal syndrome. Evidence is presented to support its possible neurotrophic origin.

Factitious pseudoainhum of the nipple.

A patient with a cosmetically disfiguring swelling of his nipple for many years was found to have factitious mechanical pseudoainhum. The possibility of occult mechanical constriction as the cause of acute or chronic deformities of appendages is emphasized.