Search PubMed⌕ Search

Biomedical subjects

M J Merino

Publications and source records attributed to M J Merino.

At least 91 records · Page 5Linked to original sources
PubMed1994

Presence of immunoreactive corticotropin-releasing hormone in normal and polycystic human ovaries.

Recently, we demonstrated the presence of immunoreactive (Ir) CRH and its receptors in the rat ovary. To determine whether CRH is also present in human ovaries, we examined ovaries from normal women and patients with the polycystic ovarian syndrome (PCOS). Immunoreactive CRH in normal human ovaries had a similar distribution to that of rat ovarian IrCRH, as determined by immunohistochemistry. Thus, immunoreactivity was intense in the cytoplasm of thecal cells surrounding the ovarian follicles, in luteinized cells of the stroma, and in a subpopulation of cells within the corpora lutea. No IrCRH was present in oocytes of primordial follicles. Polycystic ovaries also had IrCRH in thecal cells; however, CRH immunostaining was less prominent or completely absent from the stroma or the sparsely present corpora lutea and was clearly detected in oocytes of primordial follicles. Using a specific RIA, the IrCRH content in extracts of normal ovaries was higher than that in polycystic ovaries (mean +/- SD, 0.075 +/- 0.02 vs. 0.038 +/- 0.009 pmol/g wet tissue, respectively; P < 0.05). Human follicular fluid samples collected from women undergoing ovarian hyperstimulation for assisted reproduction had low, but detectable, levels of IrCRH (mean +/- SD, 4.975 +/- 1.179 pmol/L), whereas IrCRH was undetectable in concurrently drawn plasma samples. IrCRH detected in normal and polycystic ovaries and in follicular fluid had similar chromatographic mobility to that of rat/human CRH-(1-41) by reverse phase HPLC. We conclude that IrCRH is present in normal human ovaries and follicular fluid, suggesting that this neuropeptide may play a regulatory role in one or more of the various functions of this gonad, such as ovulation and/or luteolysis, through its proinflammatory properties and/or its auto/paracrine regulation of steroid biosynthesis, in analogy to its action on testosterone secretion by the Leydig cell. Its decreased concentration and localization in primary oocytes of polycystic ovaries may be related to the increased androgen biosynthesis by the theca and stroma and/or to the oocyte dysfunction observed in women with the polycystic ovarian syndrome, respectively.

Adolescent↗
PubMed1994

Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure.

Despite having amenorrhea and markedly elevated serum gonadotropin levels, some women with karyotypically normal spontaneous premature ovarian failure, nevertheless, have ovarian follicles that function intermittently. Graafian follicles capable of responding to these high FSH levels are faced with high serum LH levels as well, which might induce inappropriate luteinization and prevent normal follicle function. We examined this possibility using weekly blood sampling and sonography in 65 patients. Nearly 50% of our patients demonstrated ovarian follicle function [serum estradiol, > 183 pmol/L (50 pg/mL)] during a median of 4 months of observation (range, 2-6 months). However, during this observation, only 16% achieved an ovulatory serum progesterone level [> 9.5 nmol/L (3.0 ng/mL)]. We imaged an antral follicle by sonography in over 40% of patients (27 of 65), and serum estradiol was significantly greater when an antral follicle was present. The follicles in these patients were not functioning normally, however. In contrast to normal women, patients with ovarian failure had poor correlation between follicle diameter and serum estradiol. We biopsied these antral follicles in 6 patients and found luteinized Graafian follicles in all cases. Therefore, luteinized Graafian follicles account for at least 60% of the antral structures imaged (95% confidence limit). Thus, inappropriate luteinization of Graafian follicles appears to be a major pathophysiological mechanism in patients with karyotypically normal spontaneous premature ovarian failure.

Adult↗
PubMed1994

Presence of immunoreactive corticotropin releasing hormone in thyroid lesions.

Corticotropin-releasing hormone (CRH) functions as a regulator of the hypothalamic-pituitary-adrenal axis and coordinator of the stress response. Immunoreactive CRH (IrCRH) is also produced in a variety of inflammatory sites, where this peptide acts as a proinflammatory cytokine. To detect CRH in autoimmune thyroid disease as well as in disorders that may be associated with an inflammatory reaction within this gland, we examined immunohistochemically 45 thyroid lesions, including 12 nodular goiters, 9 cases of Hashimoto thyroiditis, 6 follicular adenomas, 4 follicular and 8 papillary carcinomas, 4 Hürthle cell tumors, 1 medullary cancer, and 1 insular thyroid carcinoma. We also examined the presence of IrCRH in the adjacent normal thyroid parenchyma. The avidin-biotin complex method was employed on formalin-fixed, paraffin-embedded tissue, using a highly specific, affinity-purified polyclonal rabbit anti-CRH antibody. Granular cytoplasmic immunostaining of follicular cells was observed in 100% of the cases of Hashimoto thyroiditis, 77% of the neoplasms and 42% of goiters. The intensity of the staining was more pronounced in Hashimoto thyroiditis and Hürthle cell tumors, whereas the remaining lesions exhibited a heterogeneous staining pattern. No IrCRH was observed in the normal thyroid parenchyma. Using a specific radioimmunoassay, the IrCRH in extracts of simple thyroid goiters, papillary carcinomas, and Hürthle cell tumors ranged between 0.031 and 0.224 pmol/g of wet tissue but was undetectable in normal thyroid parenchyma. The IrCRH molecule in the thyroid gland eluted at the same fraction as synthetic rat/human CRH 1-41 in reverse phase high pressure liquid chromatography. We conclude that IrCRH is present in thyroid lesions, predominantly in those related to autoimmune phenomena, suggesting that this neuropeptide may be directly and/or indirectly involved with inflammatory processes taking place in this gland.

Animals↗
PubMed1994

NM23 protein in neoplastic and nonneoplastic thyroid tissues.

The expression of nm23 gene products has been associated with a lower metastatic potential and better outcome in malignant tumors. We have used immunohistochemistry to study the expression of nm23 protein in thyroid tissues from 101 patients consisting of 78 malignant neoplasms, 13 adenomas, and 10 other benign conditions. Cytoplasmic staining for nm23 protein was identified in normal tissues and in most benign and malignant lesions and did not correlate with either histological type of clinical outcome. Nuclear staining was seen in 93% of normal tissues and in 29% of primary carcinomas of the thyroid and was associated with a longer disease-free survival (P = 0.03). Membranous staining was present in some tumors but absent in normal thyroid. In conclusion, nm23 protein has a combined pattern of distribution among subcellular compartments in thyroid tissues. Although there was no significant association between cytoplasmic or membranous expression and histological type of tumor or survival nm23 nuclear expression may be a useful marker in assessing the evolution of thyroid tumors.

Adolescent↗
PubMed1993

Primary soft tissue sarcomas of the breast: local-regional control with post-operative radiotherapy.

PURPOSE: A retrospective analysis was undertaken to determine the efficacy of postoperative radiotherapy in patients with primary sarcoma of the breast. METHODS AND MATERIALS: Ten patients with high-grade nonmetastatic primary sarcoma of the breast were treated at the National Cancer Institute, NIH, between 1979 and 1989 with mastectomy and adjuvant radiotherapy. Chemotherapy was given to three patients as part of a randomized trial. RESULTS: With a median potential followup of 99 months postoperatively, seven patients remain alive and without evidence of disease 142, 119, 82, 48, 45, 28, and 19 months postoperatively. Three patients died of metastatic disease 7, 25, and 29 months, postoperatively. There were no local or regional failures. Actuarial 5-year disease free and overall survival were 68% and 66%, respectively. CONCLUSION: Sarcomas of the breast have a prognosis similar to that of extremity sarcomas. When adjuvant radiotherapy is used, excellent local control may be achieved.

Adolescent↗
PubMed1993

Age contrast in ovarian pathology.

BACKGROUND. Ovarian cancer accounts for approximately 23% of all gynecologic tumors and is the most common fatal gynecologic malignancy. These tumors can occur in women of all ages, but there are differences in the histologic types during various decades of life. CONCLUSIONS. During infancy and childhood, the predominant type of neoplasms are those of germ cell origin, such as teratomas, dysgerminomas, and endodermal sinus tumors. In adults, epithelial neoplasms, or tumors that originate from the epithelium that covers the ovarian surface, are the most common, accounting for almost 85% of all neoplasms after the age of 50 years. The peak incidence of benign epithelial tumors occurs between the ages of 20 and 40 years. Young women (30 to 40 years of age) are frequently affected by the so-called "tumors of low malignant potential," which have excellent prognosis. Older women, on the other hand, usually have the most aggressive forms of ovarian cancer, present with advanced disease, and have a dismal prognosis.

Adult↗
PubMed1993

Long-term outcome in 87 patients with low-grade soft-tissue sarcoma.

OBJECTIVE: To describe the long-term clinical outcome of patients with low-grade soft-tissue sarcoma and identify factors that may predict or determine their prognosis. DESIGN: Retrospective chart review with multivariate analysis. SETTING: Large research hospital and referral center. PATIENTS: All patients treated between 1975 and 1990 at the National Cancer Institute (Bethesda, Md) who had a confirmed diagnosis of low-grade soft-tissue sarcoma. INTERVENTIONS: Surgery and radiation therapy. MAIN OUTCOME MEASURES: Local recurrence and overall survival. RESULTS: For patients with nonretroperitoneal lesions, overall survival was excellent, with a history of recurrence, a positive surgical margin, and an absence of adjuvant radiation therapy significantly associated with increased risks of local recurrence. Patients with retroperitoneal lesions not only had an increased risk of local recurrence, but significantly poorer overall survival. CONCLUSIONS: Low-grade soft-tissue sarcomas are associated with excellent overall survival, especially those confined to nonretroperitoneal sites. The risk of local recurrence after resection with negative margins and/or adjuvant radiation therapy is very low and most recurrences can be controlled with further therapy.

Adolescent↗
PubMed1993

Case report: wandering intravascular bullet with aortic pseudoaneurysm.

A 26-year-old man received a gunshot wound to the left flank. No exit wound was seen. A plain abdominal film, computed tomography (CT) and angiography were performed. Abdominal aortic pseudoaneurysm with extravasation of contrast into the retroperitoneum and embolization of the bullet to the left iliac artery were shown. The diagnostic value of the CT was considerable, but angiography was still required for definitive localization of the bullet.

Abdominal Injuries↗
PubMed1993

Severe endocrine and nonendocrine manifestations of the McCune-Albright syndrome associated with activating mutations of stimulatory G protein GS.

McCune-Albright syndrome (MCAS) is a sporadic disease classically including polyostotic fibrous dysplasia, café au lait spots, sexual precocity, and other hyperfunctional endocrinopathies. An activating missense mutation in the gene for the alpha subunit of GS, the G protein that stimulates cyclic adenosine monophosphate formation, has been reported to be present in these patients. The mutation is found in variable abundance in different affected endocrine and nonendocrine tissues, consistent with the mosaic distribution of abnormal cells generated by a somatic cell mutation early in embryogenesis. We describe three patients with MCAS who had profound endocrine and nonendocrine disease and who died in childhood. Two of the patients were severely ill neonates whose complex symptoms did not immediately suggest MCAS. A mutation of residue Arg201 of GS alpha was found in affected tissues from all three children. A review of the literature and unpublished case histories emphasizes the existence of other patients with severe and unusual clinical manifestations. We conclude that the manifestations of MCAS are more extensive than is generally appreciated, and may include hepatobiliary disease, cardiac disease, other nonendocrine abnormalities, and sudden or premature death.

Adolescent↗
PubMed1993

Malignant lymphomas involving the ovary. A clinicopathologic analysis of 39 cases.

We report 39 patients with non-Hodgkin's lymphoma who initially presented with ovarian enlargement. Fifteen patients had unilateral (10 left, four right, one unknown) and 24 had bilateral ovarian masses. The median size of the tumors was 8 cm (range, 2 to 23 cm). Histologically, using the Working Formulation, 21 lesions (54%) were classified as small noncleaved cell, Burkitt's type; 12 (31%) as large cell (nine diffuse, three focally follicular); three (8%) as diffuse mixed, small and large cell; two (5%) as large cell immunoblastic; and one (2%) as follicular and diffuse small cleaved cell. Twenty-six tumors were analyzed immunophenotypically, 25 (96%) of which were B-cell neoplasms. However, combining histologic and immunohistochemical findings, 37 neoplasms were of B-cell lineage, one diffuse large-cell lymphoma was not analyzed, and one large-cell immunoblastic lymphoma (with features of anaplastic large-cell lymphoma) was of T-cell lineage with an aberrant immunophenotype. On the basis of staging studies and clinical follow-up, we conclude that only four (10%) of the neoplasms in this study most likely arose in the ovary. The primary neoplasms, three diffuse large-cell and one diffuse mixed small- and large-cell, were B-cell neoplasms. Three of four patients with primary neoplasms were apparently cured at last follow-up following surgical excision and chemotherapy. The remainder of the lymphomas in this study, most commonly of small noncleaved cell, Burkitt's type, appear to be systemic tumors that involved the ovaries secondarily. Approximately 40% of patients with systemic neoplasms were alive without evidence of disease at last follow-up.

Adolescent↗
PubMed1993

The significance of the grooved nucleus in thyroid lesions.

Nuclear grooving has recently been accepted as a useful diagnostic criterion for papillary thyroid carcinoma. In order to determine whether this feature can serve as a reliable cytomorphologic marker of papillary carcinoma we studied, by light microscope, the surgical specimens of 80 nonpapillary thyroid lesions including 35 follicular adenomas, 8 follicular carcinomas, 5 Hürthle cell adenomas, 4 Hürthle cell carcinomas, 4 medullary carcinomas, 2 undifferentiated carcinomas, 5 cases of Hashimoto's thyroiditis, 5 diffuse hyperplasias, 2 adenomatous hyperplasias, and 10 nodular goiters. In each case, 10 random high-power fields (HPF) per slide were reviewed and the frequency of grooved nuclei per microscopic field examined and recorded. Nuclear grooves were found in all but 11 cases (one case of adenomatous hyperplasia and 10 cases of nodular goiter). Overall, 40% of the nonpapillary thyroid lesions contained nuclear grooves in more than 9 HPFs, 42% in 5 to 8 HPFs and 18% in less than 4 HPFs. Twenty four percent of the nonpapillary neoplastic lesions had eight or more grooved nuclei per HPF and 76% had six or less. The latter frequency was recorded for the 50% of the nonneoplastic thyroid conditions. Occasional intranuclear inclusions were seen in two cases of follicular tumors and in one case of Hürthle cell carcinoma. It is apparent from this study that nuclear grooving is not necessarily restricted to papillary thyroid cancer, and that it can be present in a variety of other thyroid lesions.

Cell Nucleus↗
PubMed1993

Ultrastructural histology correlates with results of thallium-201/technetium-99m parathyroid subtraction scintigraphy.

Specimens from 15 scintigraphically true-positive adenomas (golden standard: histology), 15 false-negative adenomas, 15 true-positive hyperplasias, 15 false-negative hyperplasias, 15 true-negative normal glands from patients with hyperparathyroidism, and 15 normal glands from patients without hyperparathyroidism, all selected randomly, were studied. After fixation, sectioning and H and E staining, in all 90 tissues the number of oxyphil, chief, and clear cells was counted in five randomly selected squares (103 x 103 microns). In 30 tissues, the number of mitochondria per cell was counted in five randomly selected cells from each lesion in transmission electron photomicrographs. Total cell counts in each group and number of chief cells showed no correlation with lesion detectability by scintigraphy. However, true-positive lesions had a significantly higher number of oxyphil cells than false-negative or normal glands. Twenty-one of 30 true-positive lesions had a oxyphil-to-clear cell ratio > 1; in contrast to only two of 30 false-negative lesions and 0 of 30 normal glands (p < 0.0005). The number of mitochondria per cell was higher in oxyphil cells in true-positive lesions (adenomas: 155 +/- 58, hyperplasias: 55 +/- 18) than in chief or clear cells in false-negative or normal lesions (30 +/- 15, p < 0.001). Our data suggest that the detectability of abnormal parathyroid glands by 201TI/99mTc subtraction scintigraphy is in part dependent upon the presence of mitochondria-rich oxyphil cells.

Adenoma↗
PubMed1993

Midluteal phase endometrial biopsy does not accurately predict luteal function.

OBJECTIVE: To investigate whether a midluteal phase endometrial biopsy accurately predicts luteal function. DESIGN: One nonpregnant menstrual cycle was evaluated in a prospective fashion. SETTING: Outpatient Clinic of the Clinical Center of the National Institutes of Health. PARTICIPANTS: Fifty healthy, normally cycling women. INTERVENTIONS: Serum progesterone (P) was measured daily throughout the luteal phase. An endometrial biopsy was performed 7 to 9 days after the luteinizing hormone (LH) surge, as detected by rapid plasma assays, and dated histologically according to Noyes' criteria. MAIN OUTCOME MEASURE: To correlate endometrial maturation with luteal P secretion. RESULTS: Mean integrated P measurements were reduced only when the lag between histologic and chronological dating was > or = 3 days or > or = 4 days, depending on whether chronological dates were assigned prospectively from the LH surge or retrospectively from the onset of next menses, respectively. However, these lags did not consistently predict deficient luteal function because subnormal integrated P secretion was seen in only 14% of women with these delays in endometrial maturation. CONCLUSIONS: Midluteal phase endometrial biopsy provides a crude test of luteal function that does not precisely distinguish luteal insufficiency.

Adult↗
PubMed1992

Small cell carcinoma of the endometrium with associated ocular paraneoplastic syndrome.

Small cell carcinomas are well-recognized tumors known to occur predominantly in the lung. These neoplasms occasionally are associated with a variety of symptoms caused by hormones and other products produced by the tumor cells (paraneoplastic syndromes). However, in the gynecologic tract such neoplasms are extremely rare. The authors report the case of an elderly woman who presented with visual disturbances caused by a primary small cell carcinoma of the uterus.

Aged↗
PubMed1992

Molecular and cellular characterization of human renal cell carcinoma cell lines.

Recent studies have suggested that a tumor suppressor gene located in the region 3p21-26 of chromosome 3 is essential to the genesis of sporadic renal cell carcinoma (RCC) and that other tumor suppressor genes located on other chromosomes may be involved with progression of this malignancy. The cellular heterogeneity of solid tumors complicates their analysis. In order to analyze a homogeneous population of tumor cells and identify genetic changes associated with histology in renal cortical tumors, we have established and characterized 35 RCC lines derived from tumor tissue from 31 patients with renal cell carcinomas. The overall success rate in establishing these cell lines from fresh or frozen specimens was 75% (18 of 24) and 35% (17 of 48), respectively. These lines differed in their morphology, growth rates, and tumorigenicity in athymic nude mice. Molecular characterization utilizing DNA fingerprinting and restriction fragment length polymorphism deletion analysis was performed to detect somatic mutations and loss of heterozygosity on the short arm of chromosome 3. Analysis revealed loss of heterozygosity on chromosome 3p in 25 cell lines derived from 28 informative nonpapillary forms of RCC (89%). Deletion-mapping analysis showed the retention of the distal locus, D3S18, in one of the RCC cell lines, which further localized the position of the putative tumor suppressor gene to the region proximal to D3S18. Although deletions on chromosome 3 have been recently suggested to be specific to the clear cell-type phenotype, our results revealed no correlation between loss of heterozygosity and clear or granular cell types.

Animals↗
PubMed1992

Interleukin-1 alpha prevention of the lethality of Escherichia coli peritonitis.

Interleukin-1 (IL-1) is an inflammatory mediator with a variety of described physiologic functions. IL-1 alpha has been shown to confer a survival advantage to experimental animals when administered before a lethal bacterial challenge. The experiments reported here were performed to define the effective pretreatment interval of a single intravenous dose of IL-1 alpha in a murine model of bacterial peritonitis, to examine the differential induction of cytokines in animals with and without IL-1 alpha pretreatment, and to assess differences in histologic evidence of end organ damage. IL-1 alpha (27 micrograms/kg iv) conferred a survival advantage to mice given a lethal challenge of live Escherichia coli (2 x 10(8) CFU/mouse ip) when the pretreatment was given 2 to 24 hr before the bacterial inoculum. Longer pretreatment intervals were not significantly protective. Treatment with IL-1 alpha at 1 hr after bacterial inoculum also did not improve survival. Mice pretreated with IL-1 alpha developed significantly lower peak serum levels of TNF-alpha after E. coli injection than did control mice. Pretreated and control mice had similar peak serum levels of IL-6 after bacterial challenge; however, IL-1 alpha-pretreated mice had a less prolonged elevation of serum levels of IL-6. IL-1 alpha-pretreated animals were protected from the histologic evidence of end organ damage seen in control animals. Thus, in this model of E. coli peritonitis pretreatment with a single intravenous dose of IL-1 alpha confers a significant protective effect when given within a limited time range. Treatment outside this interval has no apparent beneficial effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗