Koso Ohama

Anatomic and chromosomal anomalies in 639 spontaneous abortuses

SummaryA total of 639 spontaneous abortuses collected in a maternity hospital were set up in culture. This sample included 565 unselected consecutive abortuses and 74 selected abortuses ascertained by morphology and/or clinical history. Among these, 339 were incomplete specimens with no recovered embryo or fetus, 110 were anatomically apparently normal and 190 were grossly abnormal. In the unselected series, 565 specimens were cultured and 402 were karyotyped; 215 (53.5%) were chromosomally abnormal. In the selected series, 74 specimens were set up in culture and 45 were karyotyped; 26 (57.7%) had an abnormal karyotype. In all, successful karyotyping was done on 447 abortuses (70%), of which 339 were studied with banding. One or more major chromosome abnormalities were detected in 241 (54%) of the karyotyped cases, 230 of which were numerical anomalies and 11 structural anomalies. Numerical anomalies included primary autosomal trisomies (31% of the total karyotyped), 45,X (10%), triploidy (6.5%), and tetraploidy (1.8%). Of the 22 types of autosomal trisomies possible, all except those for 1, 5, 17, and 19 were identified. An abortus with a 49,XX,+2,+5,+8 karyotype was detected. The excess autosomal material present in the triple trisomic abortus corresponded to 10% of the haploid autosomal complement. Of the 11 abortuses with structural abnormalities, seven were inherited while the other four were sporadic. The survival rate of 45,X conceptuses was estimated to be one in 300.

Dental panoramic radiograph as a tool to detect postmenopausal women with low bone mineral density: untrained general dental practitioners’ diagnostic performance.

The detection of postmenopausal women with low bone mineral density (BMD) is an important strategy to reduce the incidence of osteoporotic fracture. Recent studies suggested that incidental findings on dental panoramic radiographs may be used as a tool to detect women with low BMD. However, little is known whether this finding is sufficiently assessed by untrained general dental practitioners (GDPs). The purpose of this study was to investigate: (1) the observer agreement and (2) the diagnostic efficacy in detecting women with low BMD, when untrained GDPs assess the appearance (normal or eroded) of the mandibular inferior cortex on dental panoramic radiographs of postmenopausal women. Twenty-seven GDPs were asked to classify the appearance of the mandibular inferior cortex on dental panoramic radiographs of 100 postmenopausal women who had completed BMD assessments of the lumbar spine and of the femoral neck. Intra-and inter-observer agreements were analyzed with kappa statistics. The diagnostic efficacy (sensitivity, specificity and predictive values) was analyzed by comparing two groups classified by the mandibular inferior cortex (women with normal and women with eroded mandibular inferior cortex) with those classified by BMD (women with normal BMD and women with osteopenia or osteoporosis). The mean sensitivity and specificity were 77% and 40%, respectively, when BMD of the lumbar spine was used as standard and 75% and 39%, respectively, when BMD of the femoral neck comprised the standard. Nineteen untrained GDPs (70%) presented a moderate to almost perfect intra-observer agreement. We conclude that dental panoramic radiograph may be used in clinical dental practice to identify postmenopausal women who have undetected low BMD and should undergo further testing with bone densitometry.

Effect of estrogen replacement therapy on endothelial function in peripheral resistance arteries in normotensive and hypertensive postmenopausal women.

Both menopause and hypertension are associated with endothelial dysfunction and are risk factors for coronary heart disease. We evaluated forearm resistance artery endothelial function in hypertensive postmenopausal women (HPW, n=57) and compared it with endothelial function in normotensive postmenopausal women (NPW, n=67). In addition, we evaluated the effects of long-term estrogen replacement therapy (ERT, conjugated equine estrogen at a dose of 0.625 mg daily for 12 weeks) on endothelial function in HPW (n=10) and NPW (n=35). Forearm blood flow (FBF) was measured by strain-gauge plethysmography during reactive hyperemia to assess endothelium-dependent vasodilation and after sublingual nitroglycerin (NTG) administration to assess endothelium-independent vasodilation. Basal FBF was similar in the NPW and HPW groups. The FBF in the HPW group during reactive hyperemia was significantly lower than that in the NPW group. Increases in FBF after NTG were similar in the 2 groups. ERT decreased the LDL cholesterol concentration and circulating ACE activity and increased estradiol and HDL cholesterol in both groups. Basal blood pressures, heart rate, FBF, and body weight did not change with ERT. After 12 weeks of ERT, the maximal FBF response during reactive hyperemia increased significantly in both groups. The improvement in reactive hyperemia after ERT was significantly greater in the HPW group than in the NPW group (49±8 versus 17±5%, P <0.05). Changes in FBF after sublingual NTG administration were similar before and after 12 weeks of ERT. These findings suggest that continued ERT improves forearm resistance artery endothelial function in postmenopausal women and that this beneficial effect is greater in patients that are hypertensive.

Relationship between dental panoramic radiographic findings and biochemical markers of bone turnover

We investigated whether mandibular cortical measures on dental panoramic radiographs are associated with biochemical markers of bone turnover in 82 postmenopausal women. Mandibular cortical shape was significantly associated with biochemical markers and spinal BMD. Our results suggest that dentists may be able to identify postmenopausal women with low BMD by using dental panoramic radiographs.

Tooth loss is associated with an increased risk of hypertension in postmenopausal women.

Tooth loss has been associated with an increased risk of vascular diseases such as coronary heart disease and cerebrovascular disease. Little is known whether hypertension is an important factor linking 2 phenomena in postmenopausal women. We compared an incidence of hypertension and traditional risk factors for vascular diseases between 2 age-matched groups: 67 postmenopausal women with missing teeth and 31 without missing teeth. In addition to blood pressure, serum concentration of total cholesterol, high- and low-density lipoprotein cholesterol and triglycerides, plasma angiotensin-converting enzyme activity, plasma angiotensin II concentration, plasma renin activity, and resting heart rate were measured as traditional risk factors for vascular diseases. Subjects without missing teeth had significantly lower diastolic blood pressure than did subjects with missing teeth (P = 0.021). The former tended to have lower systolic blood pressure than did the latter (P = 0.058). There were no significant differences in other variables between subjects with and without missing teeth. The odds ratio of having hypertension in subjects with missing teeth was 3.59 (95% confidence interval, 1.10 to 11.7) after adjustment of obesity, hypercholesterolemia, and hypertriglyceridemia. Our results suggest that hypertension may be an important factor linking tooth loss and an increased risk of vascular diseases in postmenopausal women.

Increased MCL–1 Expression Is Associated with Poor Prognosis in Ovarian Carcinomas

To investigate the potential role of the BCL–2 gene family (BAX, BCL–2, MCL–1, and BCL‐XL) in ovarian cancer development and progression, mRNA expression levels of these genes were measured using semi‐quantitative PCR in epithelial ovarian tumor tissues and normal ovaries. The immunohistochemical expression of MCL–1 in ovarian tumors was also examined. The expression levels of BAX and MCL–1 mRNA were significantly higher in ovarian cancers and in adenomas than in normal ovaries (P<0.05). In contrast, the BCL–2 mRNA expression level in ovarian cancers was significantly lower than in ovarian adenomas and in normal ovaries (P<0.05). Expression of BCL‐XL mRNA was no different between normal ovaries and ovarian tumors. Log‐rank testing showed that low BAX mRNA expression and high MCL–1 mRNA expression significantly correlate with poor survival for patients with stage III ovarian carcinomas (BAX, P=0.05; MCL–1, P=0.02). Immunohistochemical analysis showed that diffuse‐positive expression of MCL–1 protein in mucinous carcinomas was significantly higher than in mucinous low malignant potential (LMP) tumors (P=0.03). In ovarian cancer cases, diffuse‐positive expression of MCL–1 protein significantly correlates with advanced clinical stage, high histologic grade, and poor survival (stage, P<0.01; grade, P=0.01; survival, P=0.01). These results suggest that increased MCL–1 expression may play an important role in replacing the functions of increased BAX and decreased BCL–2 in ovarian carcinoma cells, thereby promoting cell survival, and resulting in a poor prognosis for patients with ovarian cancer.

Expression of basic fibroblast growth factor in human gastric carcinomas

SummaryThe expression of mRNA for the basic fibroblast growth factor (FGF) gene was examined in seven human gastric carcinoma cell lines and in tissue from 29 gastric carcinomas together with the adjacent normal mucosa. Among the seven gastric carcinoma cell lines, the MKN45 cell line expressed mRNA for the basic FGF gene. Basic FGF protein production was confirmed by flow cytometric analysis and immunohistochemistry. Among the surgical specimens, 16 (55%) of 29 gastric carcinomas showed higher levels of basic FGF mRNA than the normal mucosa. Interestingly, in scirr-hous gastric carcinomas characterized by their fibrous stroma and rapid growth, 9 (69%) of 13, samples examined revealed higher levels of basic FGF mRNA than normal mucosa, whereas only 3 (33%) of the 9 well differentiated adenocarcinomas studied produced similar results. Immunohistochemically, basic FGF protein was localized in tumor cells. These results suggest that basic FGF produced by tumor cells may play an important role in producing fibrosis and angiogenesis in gastric carcinomas.

Origin of immature teratoma of the ovary

Six cases of immature teratoma of the ovary were karyotyped and analyzed for chromosomal heteromorphisms, enzyme polymorphisms, and HLA specificities to determine their mechanism of origin. Three cases were chromosomally abnormal, with karyotypes of 48,XX, +14, +21; 47,XX, +20; and 47,XXX, respectively. The tumors with 48,XX, +14, +21 and 47,XX, +20 karyotypes were heterozygous for chromosomal heteromorphisms which were identical to those of their host and therefore originated from a premeiotic cell or failure of meiosis I. Both had a poor prognosis. The 47,XXX tumor and the three cases with normal karyotypes were homozygous for chromosome heteromorphisms and either homozygous or heterozygous for enzyme and HLA markers and therefore originated from a failure of meiosis II or duplication of a mature haploid ovum. All four had an uneventful postoperative course. These observations show that immature teratomas are like cystic teratomas in having at least three separate mechanisms of origin. However, they are unlike cystic teratomas in having a high proportion with chromosome abnormalities and a high rate of malignant transformation.

Meiotic segregation analysis of a 14;21 Robertsonian translocation carrier by fluorescence in situ hybridization

Abstract. Meiotic segregation of chromosomes 14 and 21 in sperm from a 14;21 Robertsonian translocation carrier was analyzed with dual-color FISH using two locus-specific DNA probes (Tel 14q and LSI 21). The frequency of normal or chromosomally balanced sperm, resulting from alternate segregation, was 88.42%. The frequency of unbalanced sperm, resulting from adjacent segregation, was 11.25%. These observed frequencies deviated significantly from the theoretical frequencies (33.33% and 66.67%, respectively) based on random chromosome segregation, with sperm resulting from alternate segregation being preferentially produced in the translocation carrier. With respect to the chromosomally unbalanced sperm, the frequency of 21q disomic sperm was 2.45%, which is in agreement with the frequencies of unbalanced fetuses or offspring at the time of amniocentesis or at term (0–4.3%) reported by others. Although the frequency of 14 or 21 nullisomic sperm should be theoretically equal to that of 14q or 21q disomic sperm in both the carrier and controls, the frequency of nullisomic sperm was significantly higher than that of disomic sperm in the carrier (P=0.0009 for chromosome 14, P<0.0001 for chromosome 21) but not in the controls (P=0.091 for chromosome 14, P=0.74 for chromosome 21). This evidence suggests the occurrence of maturation arrest during spermatogenesis of the carrier.

XY and XX complete moles: clinical and morphologic correlations.

The results of clinical, morphologic, and histologic analysis of nine XY complete moles (six karyotyped, three Y-chromatin positive) were compared with the results from analysis of 16 XX moles. Five of the nine XY moles were proved to result from dispermy while all the 16 XX moles studied originated from the doubling of a haploid sperm. At follow-up delayed decrease or rebound of urinary (or serum) human chorionic gonadotropin levels was noted in three of eight women with XY moles and in five of 15 women with XX moles. One woman with an XY mole was treated for lung metastasis, but her condition remained stable over a 4-year follow-up period. No appreciable difference was noted in the gross and microscopic findings between the XY and XX moles. On the other hand, differences were noted between younger (12 weeks or less of menstrual age) and older (13 weeks or more) moles. Younger moles had smaller, elliptic or club-shaped villi with numerous secondary villous sprouts, poorly demarcated central cisternae, and frequent mesenchymal capillaries. Older moles had larger, oval or globular villi with sparse villous sprouts, well-developed central cisternae, and less frequent remnants of capillaries. Trophoblastic hyperplasia was more marked in older than in younger moles.