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Biomedical subjects

M J Merino

Publications and source records attributed to M J Merino.

At least 145 records · Page 8Linked to original sources

Messenger-dependent action of guanylylimidodiphosphate and translation inhibitors on rat brain polypeptide synthesis.

The effects of the Guanosine 5'-triphosphate analog guanylylimidodiphosphate and several antibiotics on protein synthesis in a cell-free system from rat brain were investigated as a function of the template used. Polypeptide chain elongation was promoted by the analog only in the system coded by the endogenous template but not when coded by polyuridylic acid. The effects of the antibiotics were also dependent on the template used. This suggest that the template conditioned the ribosomal conformation which determine the inhibitory effect of the antibiotics.

Animals↗

Reversal of the toxic effects of cachectin by concurrent insulin administration.

Rats treated with recombinant human tumor necrosis factor-cachectin, 100 micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in body weight gain vs. saline-treated controls. Concurrent neutral protamine hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of these changes to control levels without causing any treatment deaths. The improvement seen with insulin was dose independent. Five days of cachectin treatment caused a severe interstitial pneumonitis, periportal inflammation in the liver, and an increase in wet organ weight in the heart, lungs, kidney, and spleen. Concurrent insulin treatment led to near total reversal of these histopathologic changes. Cachectin treatment did not significantly change blood glucose levels from control values of 130-140 mg/dl, but insulin plus cachectin caused a significant decrease in blood glucose from 1 through 12 h after injection. Administration of high-dose insulin can near totally reverse the nutritional and histopathologic toxicity of sublethal doses of cachectin in rats.

Animals↗

Presence of translational inhibitory activity in partially purified extracts from two Petrocoptis species.

The presence of translational inhibitory activity in partially purified extracts from several paleoendemisms from Spain was investigated. The precipitates from 40-80% (NH4)2SO4 fraction from Petrocoptis glaucifolia and Petrocoptis grandiflora displayed a strong inhibitory activity on the protein synthesis of cell-free extracts from rat liver, rabbit reticulocytes and yeast and to a much lower extent on the protein synthesis in isolated rat liver cells. The inhibitors seem to be proteins since they were precipitated by high salt concentrations, were non-dialysable and were inactivated by heat. Since the partially purified extracts did not show unspecific RNA-A or protease activities, the active compounds can be considered to belong to the plant ribosome-inactivating proteins.

Plant Extracts↗

Synergistic antitumor effects of immunotherapy with recombinant interleukin-2 and recombinant tumor necrosis factor-alpha.

The antitumor activity of combination therapy with recombinant tumor necrosis-alpha (rhTNF-alpha) and recombinant interleukin-2 (rhIL-2) was assessed against established immunogenic (MCA-106) and nonimmunogenic (MCA-102) sarcomas at both s.c. and visceral (hepatic) sites. C57BL/6 (B6) mice were treated with a single i.v. dose of rhTNF-alpha (2, 4, 6, or 8 micrograms) followed by rhIL-2 (25,000 U) i.p. thrice daily for 5 consecutive days. Synergistic effects as measured by regression of tumor, prolongation of survival, and improved cure rates were found using the combination of rhTNF-alpha plus rhIL-2 compared to rhTNF-alpha alone or rhIL-2 alone in the treatment of the immunogenic sarcoma MCA-106. No significant antitumor effects were observed against the nonimmunogenic MCA-102 sarcoma. These findings were similar for both s.c. and large single hepatic tumor models. The effect of the timing of rhIL-2 injections in relation to rhTNF-alpha administration (concurrent, 2, 4, or 6 days post single rhTNF-alpha dose) was also evaluated. Substantial tumor regression and increased survival times were seen in mice with s.c. tumors when rhIL-2 therapy was delayed as much as 48 h after rhTNF-alpha administration. No antitumor response was noted with the combination compared to rhTNF-alpha alone when rhIL-2 was delayed for greater than 4 days. No increase in lethal toxicity during treatment course of the combination of rhTNF-alpha and rhIL-2 was noted at any schedule compared to single agent rhTNF-alpha therapy. A possible role of rhTNF-alpha in regulation of IL-2-dependent antitumor activity in vivo is discussed.

Animals↗

Tolerance to tumor necrosis factor in rats and the relationship to endotoxin tolerance and toxicity.

Treatment of rats with recombinant human TNF initially causes a marked decrease in food intake, a loss of body weight, and a negative nitrogen balance. These alterations normalize with continued twice daily intraperitoneal injections of the same dose. Rats tolerized to TNF in this manner are refractory to a lethal dose of TNF. Also, TNF-pretreated and -tolerized rats have prolonged survival and reversed histopathologic changes after injection of a lethal dose of endotoxin compared with control animals. The TNF-tolerant state is dependent on the dose of TNF used and the length of TNF pretreatment. TNF-induced tolerance is relatively short lived, being present 2-4 d after TNF pretreatment and dissipating by 2 wk. Rats made tolerant to endotoxin are also tolerant to a lethal dose of TNF. A bidirectional crossreacting tolerance exists between TNF and endotoxin. The mechanism of TNF tolerance is unclear, but it does not appear to be due to a humoral immune response or a perturbation of the uptake and clearance of injected TNF.

Animals↗

Borderline ovarian tumors.

Ninety-four patients with borderline ovarian tumors were retrospectively analyzed for clinical features, treatments, and survival characteristics. There were 46 patients with FIGO stage IA cancer, 7 with stage IB, 20 with stage IC, 4 with stage IIB, 5 with stage IIC, 5 with stage IIIA, 3 with stage IIIB, and 4 with stage IIIC tumors. Seventy patients had at least a total abdominal hysterectomy and bilateral salpingo-oophorectomy, 20 patients had conservative surgery including unilateral salpingo-oophorectomy or ovarian cystectomy, and 4 patients had bilateral salpingo-oophorectomy. Fifteen patients with stage I disease received adjuvant melphalan therapy and 2 received external beam radiation for concomitant gynecologic cancers; 7 with stage II tumors received adjuvant melphalan therapy and 1 received external beam radiation; and 5 with stage III tumors received melphalan therapy and 6 patients received cisplatin-based combination chemotherapy. Follow-up ranged from 1 to 117 months, with a median of 33.5 months. Eighty-seven patients were alive. Seven patients died, two of disease. The overall 5-year survival rate was 83.0%; those treated with adjuvant therapy had a 79.5% survival, whereas the others had 84.6% survival. Second-look surgery was performed in 10 patients; six results were negative after melphalan therapy, one was negative after cisplatin combination therapy, and one was negative after no adjuvant treatment. Two patients had positive second-look surgery, one with stage IIIC disease treated with a cisplatin combination and the other with stage IC disease treated with melphalan. This review did not demonstrate that patients with borderline ovarian tumors benefited from adjuvant therapy.

Adolescent↗

Malignant mixed Müllerian tumors of the uterus. An immunohistochemical study.

Malignant mixed müllerian tumors (MMMT) of the uterus have been subdivided into two types: those with heterologous sarcomatous elements (e.g., rhabdomyosarcoma, and chondrosarcoma) and those with only homologous elements (e.g., stromal sarcoma). The distinction, which may have prognostic significance, was based on the identification by light microscopy of cells that exhibited definite cross-striations, cartilage, or osteoid production. We studied 32 cases of uterine MMMT to assess the value of immunohistochemical markers in delineating the sarcomatous and epithelial components. Of 32 cases, 11 showed heterologous sarcoma (6, rhabdomyosarcoma, and 5, chondrosarcoma), and the remaining 21 were homologous MMMT. Six antigens--desmin, myoglobin, S-100, alpha 1-antichymotrypsin (ACT), epithelial membrane antigen (EMA), and monoclonal cytokeratin (AE1 and AE3), (to test for possible myogenic, chondroid, fibrohistiocytic, and carcinomatous differentiation)--were analyzed by the avidin-biotin-peroxidase method. EMA was found in neoplastic cells in all cases; 31 of 32 cases showed keratin. Desmin reactivity was detected in 14 of 32 cases, whereas myoglobin was present in 10 of 32. Three cases exhibited S-100 positivity (two in areas of chondrosarcoma, and one in some stromal sarcoma cells). Twenty-two cases (69%) exhibited ACT reactivity. Several cases displayed a malignant fibrous histiocytoma pattern. These demonstrated ACT positivity in both the neoplastic spindle and giant cells. We conclude that immunohistochemical staining for the above mentioned antigens is a useful diagnostic aid in delineating the sarcomatous and carcinomatous elements in MMMT.

Aged↗

Malignant mixed müllerian tumor of the uterus arising in association with a viable gestation.

Malignant mixed müllerian tumors of the uterus are rare neoplasms occurring predominantly in postmenopausal women. We report the prenatal course and diagnosis of a stage III malignant mixed müllerian tumor at cesarean section in a 35-year-old woman. Despite aggressive radiation and chemotherapy, the patient died 14 weeks after diagnosis and initial surgical therapy. The premature infant had an uneventful course.

Adult↗

Transforming growth factor beta levels in rat wound chambers.

Exogenous TGF-beta accelerates healing in both normal and doxorubicin-treated rats, but whether it plays an intrinsic role in the natural healing process is unknown. Subcutaneous wound chambers in 16 F344 rats were aspirated from postwounding Day 3 through Day 16 for TGF-beta levels and cytology. A soft agar assay and a competitive radioreceptor binding assay were used to determine TGF-beta levels. Papanicolau staining and differential cell counts were used to determine cytology. Results were similar using either method for the determination of TGF-beta levels. With the sensitive radioreceptor assay, low TGF-beta levels on postwounding Day 4, mean 2.6 ng/ml, rose to a peak mean level of 20.4 ng/ml on Day 7 and fell significantly from peak level to a level of 5.4 ng/ml of Day 16. All TGF-beta levels for postwounding Days 6 through 14 were significantly increased over the baseline TGF-beta levels of Days 4 and 5 (P less than 0.05). Day 16 TGF-beta levels were not different from baseline. Cytologic changes were characterized by a liner decrease in total neutrophil count over the exam period and a concurrent linear increase in total lymphocyte and macrophage counts. TGF-beta levels changed in a bell-shaped temporal sequence during healing, apparently unrelated to percentage lymphocyte, macrophage, or neutrophil count. Peak TGF-beta levels occurred during the fibroblast proliferation and collagen synthesis phase of healing. This study presents the first evidence that TGF-beta is present in a healing wound and suggests that it may be an intrinsic mediator of the healing process.

Animals↗

Endometrial stromal sarcoma: a clinicopathologic study of 11 cases with determination of estrogen and progestin receptor levels in three tumors.

Eleven cases of endometrial stromal sarcoma were obtained from the files of Yale New Haven Hospital from 1969 to 1981 for clinicopathologic correlation and determination of the outcome after hormonal therapy with progestational agents. Histologically, nine of the tumors were classified as low grade stromal sarcomas, and two were of a high grade. All of the patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy as the main modality of treatment. Two patients received radiation, three adjuvant chemotherapy, two hormonal therapy (Megace 160 mg qd), three received no therapy at all, and the treatment is not known in one case. Two of the patients who received no therapy had recurrences and were placed on hormonal therapy. The remaining patient was a stage IV and died of disease 3 months after diagnosis. All four of the patients who were treated with hormonal therapy are alive, free of disease, or with stable tumor from 2 to 6 years after diagnosis. The presence of estrogen receptors (ER) and progestin receptors (PR) was demonstrated in the tumor in some of the cases; this may explain the sensitivity of this neoplasm to hormonal therapy.

Adult↗

Solid and papillary epithelial neoplasm of the pancreas. An ultrastructural and immunocytochemical study of six cases.

Solid and papillary epithelial neoplasms of the pancreas from six female patients were studied using immunohistochemistry and electron microscopy to define better their histogenesis. The tumors ranged in diameter from 5 to 15 cm (average: 9 cm), and, on cross section, most had areas of hemorrhage and necrosis, sometimes extensive. Microscopically, there was a solid and pseudopapillary pattern, with tumor cells typically having ovoid nuclei with delicate folding and indistinct nucleoli. Of note were the following: a relatively low mitotic rate (range: 0-6/20 hpf), the presence of hyaline globules (four of six cases), and collections of foam cells (three of six cases). Staining for cytoplasmic argyrophil granules was negative in each case. Ultrastructurally, the solid and papillary epithelial neoplasms of the pancreas showed evidence of acinar or ductular differentiation. Two contained zymogen granules, one had intermediate filaments (probably keratin), and three had abundant rough endoplasmic reticulum and mitochondria. Immunostaining was positive for chymotrypsin (six of six cases), trypsin (four of six), and amylase (three of six). None was positive for alpha-1-antitrypsin, neuron-specific enolase, pancreatic polypeptide, gastrin, glucagon, somatostatin, or insulin. The findings support an origin from exocrine pancreas, and follow-up indicates a low rate of malignancy, with local recurrence in two of the six patients.

Adolescent↗

Corticotroph cell pituitary adenoma within an ovarian teratoma. A new cause of Cushing's syndrome.

A 24-year-old woman with severe Cushing's syndrome was found to have corticotroph cell pituitary adenoma arising within a benign cystic ovarian teratoma. The patient manifested sustained hypercortisolemia and lack of suppression of either adrenocorticotropin (ACTH) or cortisol production. There was no evidence of a pituitary mass or secretion of other hormones. After careful clinical evaluation, no other tumor masses were found. Resection of the ovarian tumor led to normalization of ACTH and cortisol levels. Densely granulated corticotroph tumor cells with prominent Type I microfilaments and intracytoplasmic ACTH immunoreactivity characterized the neoplasm as a pituitary corticotroph cell adenoma. This is, to our knowledge, the first case reported of a functioning pituitary adenoma arising within a benign cystic teratoma.

ACTH Syndrome, Ectopic↗

Adenoid cystic carcinoma of the breast. Data from the Connecticut Tumor Registry and a review of the literature.

The case records of the Connecticut Tumor Registry were reviewed from 1952-1982. There were 37 cases of adenoid cystic carcinoma of the breast (ACC) from a total of 40,350 invasive breast tumors. Patient survival, complications, and pathologic sections were reviewed. Only 14 of 27 surgical pathology slides available for review could be confirmed histologically as ACC. All patients were white females with a mean age of 64 years. The tumor remained localized to the breast in all cases. Nine patients had either radical or modified radical mastectomy, four patients had either simple mastectomy or lumpectomy, and one patient refused treatment. There was no evidence of axillary node involvement, metastases, or local recurrence after excision. At the time of follow-up, nine patients were alive and disease free and four died of disease unrelated to their breast cancer. The one patient who died of breast cancer had a radical mastectomy and survived 11.7 years after diagnosis. It is concluded that ACC has a favorable biologic behavior characterized by a prolonged clinical course and good prognosis. Simple mastectomy is all that is required as initial treatment, and a chest x-ray and thorough physical examination looking for local recurrence is all that is needed for follow-up.

Aged↗

Cerebral endometriosis. Case report.

A 20-year-old woman presented with a 3-year history of intermittent focal headaches and a generalized seizure. Computerized tomography demonstrated a hypodense ring-enhancing cystic right parietal lobe lesion. At operation, a chocolate-colored cyst was excised which on histological examination proved to be endometriosis.

Adult↗

Expression of tumor-associated antigen (DF3) in atypical hyperplasias and in situ carcinomas of the human breast.

The monoclonal antibody (MoAb) DF3 prepared against a membrane-enriched fraction of human breast carcinoma has previously shown a differential reactivity to cytoplasmic antigen in carcinomas versus antigen concentrated on apical borders in benign lesions of the breast. In the present report the cytoplasmic reactivity of MoAb DF3 within a spectrum of benign and malignant breast lesions was studied to define whether the DF3 antigen is expressed in the cytoplasm of potentially premalignant lesions, i.e., atypical hyperplasias, or early malignant lesions, i.e., in situ carcinomas. Biopsy specimens of breast lesions from 108 women, including 28 patients with invasive carcinoma, 12 with in situ carcinoma, 17 with atypical hyperplasia, 25 with proliferative lesions without atypia, and 26 with nonproliferative lesions, were examined for DF3 antigen expression with the use of an indirect immunohistochemical method. Atypical hyperplasias were less reactive with MoAb DF3 than invasive carcinomas (P = .05 by Wilcoxon rank sum test). No significant statistical differences were observed, however, between invasive carcinomas and in situ carcinomas or between in situ carcinomas and atypical hyperplasias on the basis of cytoplasmic DF3 reactivity. Invasive carcinomas, in situ carcinomas, and atypical hyperplasias, however, demonstrated significantly higher reactivity with MoAb DF3 in the cytoplasm than proliferative lesions without atypia and nonproliferative lesions (P less than .01). These studies demonstrate that atypical hyperplasias express elevated levels of a given tumor-associated antigen and thus provide further immunologic evidence that these lesions are premalignant.

Antibodies, Monoclonal↗

The rapid onset of cutaneous angiosarcoma after radiotherapy for breast carcinoma.

Malignant neoplasms known to develop following external beam radiation include squamous cell carcinoma, osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, mixed mullerian tumors, malignant schwannoma, myelogenous leukemia and angiosarcoma. Latency periods of many years characterize the onset of these tumors following the exposure. Cutaneous angiosarcoma following radiotherapy for breast carcinoma has been rarely documented, occurring up to 13 years postirradiation. Two cases of this entity are reported occurring 37 months postradiotherapy at the site of mastectomy performed for mammary duct carcinoma.

Aged↗

Demonstration of myc and ras oncogene expression by hybridization in situ in hydatidiform mole and in the BeWo choriocarcinoma cell line.

With the use of hybridization in situ, c-myc and c-ras oncogene expression has been identified in the cytotrophoblast of hydatidiform mole and in the malignant trophoblast cell line BeWo. Expression was also found in early villous placenta. No expression of these two oncogenes was found in the cytotrophoblast of an 11-week conceptus, nor was it found in term placenta. The significance of these findings is discussed.

Cell Line↗