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Biomedical subjects

H Michael

Publications and source records attributed to H Michael.

At least 37 records · Page 2Linked to original sources

Flow cytometric DNA analysis of extramammary Paget's disease of the vulva.

Vulvar extramammary Paget's disease (EMPD) is an uncommon disease entity that occurs predominantly in postmenopausal white women. The clinical behavior of this neoplasm is extremely variable, reflecting the various histological patterns that have been reported with this lesion. Flow cytometry has been used as a method of obtaining prognostic information about a number of gynecological neoplasms, yet to date there have been no flow cytometric studies performed on this unusual neoplasm. We performed flow cytometric analysis of 14 cases of paraffin-embedded vulvar EMPD in patients ranging from 45 to 86 years of age. We correlated histological features and clinical recurrence risk with DNA analysis. Although we were unable to show a statistically significant correlation between DNA ploidy or S-phase and time to recurrence, we did show a statistically significant correlation between DNA ploidy and histological features. Aneuploidy appears to be associated with in situ sweat gland adenocarcinoma, invasive carcinoma, and lymphatic invasion. These results suggest that Paget's cells with aneuploid DNA stem lines may be associated with the potential for aggressive biologic behavior.

Aged↗

The mating-type region of Schizosaccharomyces pombe contains an essential gene encoding a protein homologous to human modulators of HIV transactivation.

In Schizosaccharomyces pombe, an intrachromosomal crossover between the mating type (MT) expression locus and one of the silent donor cassettes is lethal due to the loss of the intervening L region. The region contains one essential gene, let1. This gene was cloned and sequenced. The deduced amino acid (aa) sequence of let1 shows extensive homologies with SUG1 from Saccharomyces cerevisiae. Significant homologies were also found with the human HIV transactivation modulators, MSS1 and TBP-1, as well as with subunit 4 of the mammalian 26 S protease. The data indicate that let1 is a member of a recently defined multigene family of ATPases.

Adenosine Triphosphatases↗

The swi4+ gene of Schizosaccharomyces pombe encodes a homologue of mismatch repair enzymes.

The swi4+ gene of Schizosaccharomyces pombe is involved in termination of copy-synthesis during mating-type switching. The gene was cloned by functional complementation of a swi4 mutant transformed with a genomic library. Determination of the nucleotide sequence revealed an open reading frame of 2979 nucleotides which is interrupted by a 68 bp long intron. The putative Swi4 protein shows homology to Duc-1 (human), Rep-3 (mouse), HexA (Streptococcus pneumoniae) and MutS (Salmonella typhimurium). The prokaryotic proteins are known as essential components involved in mismatch repair. A strain with a disrupted swi4+ gene was constructed and analysed with respect to the switching process. As in swi4 mutants duplications occur in the mating-type region of the swi4 (null) strain, reducing the efficiency of switching.

Adenosine Triphosphatases↗

Flow cytometric analysis of DNA content and RAS P21 oncoprotein expression in ovarian neoplasms.

Flow cytometric analysis of DNA content and ras p21 expression were studied in paraffin-embedded normal ovary (NO, n = 10), serous cystadenoma (SA, n = 11), serous tumors of low malignant potential (LMP, n = 13), and papillary serous cystadenocarcinoma (SCa, n = 7). Tissue for DNA analysis was processed via a modified Hedley technique; a separate aliquot of the same sample was stained with a monoclonal antibody directed to oncoprotein ras p21 (clone Y13259). NO (10/10) and SA (11/11) demonstrated diploid DNA stemlines; 4/12 LMP and 5/7 SCa were aneuploid. S-phase fraction varied with significant differences (p less than 0.001) for SA (mean = 4.4%), LMP (mean = 9.0%), and SCa (mean = 12.7%). When all cases were evaluated, p21 expression was relatively lower in NO and SA (mean = 4.2%) in contrast to LMP and SCa (mean = 13.0% and 8.1%). Diploid cases were examined separately, and lesions with high p21 expression were associated with a diagnosis of LMP/SCa (p less than 0.001), whereas diploid tissues with low p21 expression were associated with a nonmalignant diagnosis (NO/SA). This study suggests that aneuploidy or diploidy with high p21 expression (greater than 10%) may be associated with LMP or frankly malignant ovarian tumors.

Aneuploidy↗

Flow cytometric DNA analysis of placental-site trophoblastic tumors.

The placental-site trophoblastic tumor is a rare form of gestational trophoblastic neoplasia. Although originally considered benign, it is now apparent that this lesion can be associated with aggressive clinical behavior. Our study examined the DNA ploidy status and clinicopathologic features of four new cases of placental-site trophoblastic tumor. Three cases demonstrated diploid DNA stemlines with S-phase fractions ranging from 6% to 16%. These patients were alive and well at follow-up and had low-serum human chorionic gonadotrophin (hCG) levels. A fourth patient, who had a large tumor, demonstrated a tetraploid DNA peak with a prominent S-phase fraction. This patient exhibited an elevated serum hCG at limited follow-up. Flow cytometric DNA analysis may be a useful adjunct for the identification of placental-site trophoblastic tumors with malignant potential.

Adult↗

An examination of the hemodynamic and metabolic effects of carteolol during different workloads on a bicycle ergometer.

The influence of 10 mg carteolol/day on the serum concentrations of insulin, C-peptide, glucagon, free fatty acids, adrenaline, noradrenaline, blood glucose, blood lactate levels, on heart rate and systolic blood pressure was investigated during different workloads on a bicycle ergometer in a placebo-controlled randomised double-blind study involving twelve male volunteers. The subjects performed standardized increasing exercises until subjective exhaustion as well as three 40-minute endurance exercises of varying intensity, corresponding to a lactate concentration of 1.0 to 2.0 mmol/l, 2.5 to 3.5 mmol/l and more than 3.5 mmol/l in the region of the anaerobic threshold, each exercise being followed by one rest day. The most important findings are: --the ISA of carteolol is of significance for the influence on the heart rate at rest but plays a minor role with respect to the degree of reduction in the heart rate and blood pressure under exercise; --carteolol exerts a minor influence on the metabolic parameters investigated in this study. This can be partly ascribed to the pronounced ISA of carteolol. In the case of endurance exercises, which lead to blood lactate concentrations of more than 3 mmol/l, the blood glucose levels showed a tendency to decrease. However, this was not statistically significant.

Adult↗

Spindle cell tumors resected from male patients with germ cell tumors. A clinicopathologic study of 14 cases.

We identified 14 male germ cell tumor patients (13 of whom had received prior chemotherapy) in whom distinctive neoplasms composed of spindle to stellate cells set in a myxoid to collagenous stroma containing numerous blood vessels developed. These neoplasms were cytokeratin-positive and vimentin-positive and alpha-fetoprotein (AFP)-negative. Ten patients with neoplasms of low cellularity and no mitoses have not had tumor recurrences, whereas four patients with more cellular and mitotically active tumors have experienced either recurrences or death. We recommend simple surgical excision, without additional chemotherapy, for the hypocellular, mitotically inactive cases. The transition from mitotically active spindle cell tumors to frankly sarcomatous areas in three cases indicates that these lesions may be the substratum for the development of sarcomas in some patients with germ cell tumors. Based on their histologic appearance and immunohistochemical profile, as well as preceding evidence of yolk sac tumor (YST) in 11 patients (data incomplete in 3 cases), we speculate that many of these cases represent overgrowth of a spindle cell component of YST that is selected for by chemotherapy.

Adolescent↗

The pluripotential nature of the mesenchyme-like component of yolk sac tumor.

Germ cell neoplasms were reviewed for the investigation of a mesenchyme-like component of yolk sac tumor (YST) characterized by spindle cells with few mitoses in a myxoid, vascular background. Nineteen YSTs with this pattern were identified. The mesenchyme-like component of these YSTs appeared to derive from the epithelial elements of YST, since cytokeratin as well as vimentin positivity occurred in the spindle cells of the mesenchyme-like areas and foci of epithelial-spindle cell transition were present. In some cases the mesenchyme-like component showed differentiated mesenchymal elements (usually skeletal muscle). Similar features were identified in 13 chemotherapy-treated cases of YST that consisted only of this mesenchyme-like component. The mesenchyme-like component of YST appears to represent a chemoresistant, pluripotential cell population arising from metaplasia of YST epithelium; it may give rise to sarcomas occurring in some patients with treated germ cell tumors.

Female↗

Malignant papillary lesions of the endometrium.

In a review of 440 patients treated for endometrial adenocarcinoma at this center since 1974, 21 patients with tumors of papillary histology were identified. Eleven (2.5%) lesions contained histologic changes characteristic of uterine papillary serous carcinoma: complex papillary architecture, high nuclear/cytoplasmic ratio, and irregular epithelial tufting. Ten lesions (2.3%) containing areas of papillary morphology but lacking the criteria for the diagnosis of papillary serous tumors were termed papillary endometrioid adenocarcinoma. Patient age, stage, and the presence of obesity, hypertension, and diabetes were similar in both groups and reflected those characteristics well established for endometrial adenocarcinoma in general. Fewer papillary serous tumors (16.7%) and papillary endometrioid tumors (33.3%) contained progesterone receptors than did other adenocarcinomas (52.3%). In clinical stage I, surgical findings indicating a more advanced stage were present in 40% of patients with papillary serous tumors compared to 10% in papillary endometrioid tumors and 12.5% in nonpapillary adenocarcinomas (P = 0.03, Fisher's exact test). Recurrences were observed in 50% of patients with papillary serous lesions compared to 42.9% in papillary endometrioid lesions and 24.3% in other adenocarcinomas. Survival for clinical stage I papillary serous tumors was worse than that for nonpapillary grade 3 controls (P = 0.042) and survival for papillary endometrioid lesions was not different from that of the same controls. These findings support those of J. L. Chen, D. C. Trost, and E. J. Wilkinson (Int. J. Gynecol. Pathol. 4, 279-288 (1985)) that papillary serous and papillary endometrioid adenocarcinomas represent two distinct subtypes of papillary endometrial neoplasia.

Adenocarcinoma, Papillary↗

Ovarian carcinoma with extracellular mucin production: reassessment of "pseudomyxoma ovarii et peritonei".

Peritoneal implants of mucin and columnar epithelium with variable amounts of free peritoneal mucin complicated 11 mucinous ovarian neoplasms. Slides of the primary ovarian tumors were reviewed in eight cases. Although all contained areas of mucinous cystadenomatous tumor of low malignant potential, the neoplasms displayed additional features not well recognized as manifestations of invasive disease in the ovary. Irregular pools of mucin were present in the ovarian stroma and contained at least rare fragments of columnar epithelium in most cases. The epithelium was often more plentiful in the peritoneal mucin. Cytologic atypia was minimal in all except one case. Goblet cells were present in both the ovarian tumor epithelium and the peritoneal implants in most cases and may have a role in dissemination of the tumor. We propose the term "ovarian carcinoma with extracellular mucin production" for this form of mucinous carcinoma; this term is both descriptive of its histologic appearance and indicative of its malignant behavior. Eight of the 11 patients died of their disease from 8 months to 13.5 years after diagnosis. One additional patient died of chemotherapy-related leukemia. The mean survival was 4.2 years. The short-term prognosis is better than that for mucinous carcinoma in general, but most patients eventually die of their disease.

Adenocarcinoma, Mucinous↗

Invasive and noninvasive implants in ovarian serous tumors of low malignant potential.

Ovarian serous tumors of low malignant potential ("borderline" serous tumors) are classified according to the histologic features of the primary ovarian tumor, without regard to any coexisting extraovarian disease. The peritoneal implants display a range of histologic appearances, ranging from benign glands (endosalpingiosis), to noninvasive papillary glandular proliferations resembling the ovarian neoplasms, to irregular glands associated with a desmoplastic stroma and having features of invasive disease. This review of 16 patients with histologically documented extraovarian tumor implants seen at Indiana University Medical Center, Indianapolis, and 13 patients whose tumor implants have been previously described in the literature indicates that the clinical stage of disease has much greater prognostic significance than does the implant histologic features. There is a tendency for patients with more advanced disease to have invasive implants. However, within a given clinical stage, disease progression or recurrence was not influenced by the presence or absence of invasive histologic characteristics in the tumor implants.

Adult↗

Villous adenoma of the uterine cervix associated with invasive adenocarcinoma: a histologic, ultrastructural, and immunohistochemical study.

An unusual neoplasm of the uterine cervix had the features of a villous adenoma with an adjacent adenocarcinoma. Histologic and electron microscopic features of the lesion are described, as well as immunohistochemical staining of the lesion for carcinoembryonic antigen. Electron microscopic evidence of intestinal differentiation in the villous adenoma suggests a rarely recognized potential for intestinal metaplasia in the uterine cervix. The association of villous adenoma with cervical adenocarcinoma underscores the malignant potential and the need for complete excision of this rare cervical lesion.

Adenocarcinoma↗

Estrogen and progesterone receptors in uterine sarcomas.

Estrogen and progesterone receptors were measured in tissues from 43 patients with various uterine sarcomas using the dextran-coated charcoal assay. Estrogen receptor was present in 55.5% and progesterone receptor in 55.8% of samples, at median estrogen and progesterone receptor concentrations of 10.7 and 15.8 fmol/mg cytosol protein, respectively. These median values are much lower than those in 30 consecutive endometrial adenocarcinomas and 50 breast carcinomas assayed in our laboratory. Progesterone receptor status correlated strongly with estrogen receptor status in uterine sarcomas (P = .001). Estrogen and progesterone receptor levels were not influenced by stage, grade, or mitotic count. Patients 50 years of age or less had significantly higher progesterone receptor than those over 50. No such age effect was seen for estrogen receptor. Endometrial stromal sarcoma had higher estrogen and progesterone receptor levels than other histologic types. Low-grade endometrial stromal sarcomas had higher median estrogen receptors (238.9 fmol/mg) and better survival (all patients alive at 6-12 months) than did high grade (N = 7) endometrial stromal sarcomas (median ER = 6.6 fmol/mg, all dead of disease at 8-27 months). For all histologic types, evaluable patients with stage I or II disease (N = 16) were more likely to survive longer than one year than those with stage III or IV disease (N = 13, P = .003). Evaluable patients with estrogen receptor-positive sarcomas were more likely to survive longer than one year than those with estrogen receptor-negative tumors (P = .006). With one exception, an endometrial stromal sarcoma, hormonal therapy exerted no beneficial effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Minimal deviation endocervical adenocarcinoma: clinical and histologic features, immunohistochemical staining for carcinoembryonic antigen, and differentiation from confusing benign lesions.

Thirteen patients with a diagnosis of very well-differentiated endocervical adenocarcinoma were studied in order to characterize the histological and immunohistochemical features of minimal deviation adenocarcinoma (MDA). Five of these patients had neoplasms composed of structures almost identical to normal endocervical glandular patterns. These five neoplasms, representing MDA, were characterized by a haphazard proliferation of both large, claw-shaped glands, and smaller, slit-shaped, pointed glands. Focal mild cytologic atypia was identified in each case. Immunohistochemical stains displayed focal cytoplasmic carcinoembryonic antigen (CEA) in each neoplasm. Two of the five patients with MDA died of their neoplasms; both presented with advanced disease. Three well-differentiated adenocarcinomas lacked the deceptively bland appearance of MDA. Two of these three well-differentiated endocervical adenocarcinomas also contained CEA. Atypical endocervical gland proliferations originally diagnosed as MDA in five patients were reclassified as benign lesions on the basis of histologic pattern, findings after subsequent surgical procedures, and benign subsequent clinical courses. Of these five benign lesions, only reserve cell hyperplasia was found to contain CEA. Minimal deviation adenocarcinoma should be distinguished from the more common well-differentiated endocervical adenocarcinoma and from atypical benign lesions. Criteria for these distinctions are presented. While the histological appearance of an endocervical gland proliferation is the paramount basis for identifying an MDA, immunohistochemical staining represents a useful diagnostic aid.

Adenocarcinoma↗