Hirohisa Ueno

Enhanced production and activation of matrix metalloproteinase-7 (matrilysin) in human endometrial carcinomas.

We examined production and tissue localization of 7 different matrix metalloproteinases (MMP‐1, ‐2, ‐3, ‐7, ‐8, ‐9 and ‐13) and 2 tissue inhibitors of metalloproteinases (TIMP‐1 and ‐2) in human endometrial‐carcinoma tissues. Sandwich enzyme immunoassays showed enhanced production of MMP‐7, MMP‐8 and MMP‐9 as well as TIMP‐1 in the carcinoma tissues compared with non‐carcinoma endometrial tissues. Among these MMPs, only the amount of MMP‐7 correlated with clinicopathological factors of the carcinomas. The level was significantly 6.8‐fold higher in the patient group with lymph‐node metastases than in that without metastases (p < 0.05), and also increased with the progress of the clinical stage. MMP‐7 was immunolocalized predominantly to the carcinoma cells in 73% of the cases, while MMP‐8 and MMP‐9 were immunostained in the inflammatory cells infiltrated in the carcinoma tissues. Immunoblotting revealed a definite band for the zymogen of MMP‐7 (proMMP‐7) of 28 kDa in 82% of the carcinoma samples, while only a faint band for proMMP‐7 was seen in 57% of the non‐carcinoma endometrial samples. Active MMP‐7 species of 19 kDa and its activity were demonstrated in the carcinoma samples with proMMP‐7 production by immunoblotting and zymography, respectively. RT‐PCR using a specific primer pair for MMP‐7 demonstrated expression in 86% of the carcinoma tissue and in 57% of the control tissue samples. In situ hybridization showed carcinoma cells selectively expressing MMP‐7 mRNA. These data suggest that, among the 7 MMPs examined, MMP‐7 may play a key role in invasion and lymph‐node metastasis of human endometrial carcinomas. Int. J. Cancer (Pred. Oncol.) 84:470–477, 1999.

Matrix metalloproteinase-9 and Tensile strength of fetal membranes in uncomplicated labor

Objective To analyze the relation between tensile strength and levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 at a number of sites in human fetal membranes. Methods Tensile strengths of fetal membranes from five women who delivered vaginally at term were measured by the method of modified force application. A piece of membrane at each measured site was then dissected, and the levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 were measured by sandwich enzyme immunoassay. The relationship between tensile strength and enzyme levels was evaluated by Scheffé F test at a total of 81 sites on the five membranes. Results The mean tensile strength of the membranes was 45.3 ± 19.8 (mean ± standard deviation) mmHg/0.3 mm2 (n = 81). When the measured sites were divided according to tensile strength into four groups (<25, 25–49, 50–74, and ≥75 mmHg/0.3 mm2), the level of matrix metalloproteinase-9 (0.72 ± 0.82 nmol/g protein, n = 12) in the less than 25 mmHg/0.3 mm2 group was significantly higher than the other groups (0.35 ± 0.22, 0.28 ± 0.15, and 0.15 ± 0.08 nmol/g protein; n = 39, 23, and 7, respectively). The significance level was still higher when the molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 was used for comparison. Conclusion An increased molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 might be related to decreased tensile strength of human fetal membranes in uncomplicated labor.

A congenital lethal form of hypophosphatasia: Histologic and ultrastructural study

Hypophosphatasia ( 1) is a rare metabolic disorder (2) characterized by low alkaline phosphatase in serum and tissues, by excretion of phosphorylethanol amine in urine, by rickets-like changes of the bone, and by autosomal recessive inheritance (3). The disease is classified into lethal perinatal (3), childhood and adulthood phenotypes. It is generally recognized that the earlier the disease appears, the poorer the prognosis. We diagnosed a congenital lethal hypophosphatasia at the 20th week of pregnancy by fetal ultrasonography, by roentgenography, and by serum levels of alkaline phosphatase of the parents.

Reduced Levels of MMP-2 and TIMP-1 in Dyssegmental Dysplasia†

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were measured in a mild case of dyssegmental dysplasia. X‐ray pictures of a female baby born vaginally at 39 weeks of gestation showed short, bent, dumbbell‐shaped long bones of the limbs and profound dyssegmental ossification in the spine, findings characteristic of dyssegmental dysplasia. When the levels of MMP‐1, MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2 were measured, the levels of MMP‐2 and TIMP‐1 were significantly reduced. This case might provide a clue to disclose the etiology of dyssegmental dysplasia.

Cord presentation with posterior placenta praevia

Symptomatic PE 110 (15%) 20 (31%) <0·001 130 (16%) Previous history of 224 (30%) 21 (33%) 0·65 245 (30%) venous thrombosis Risk factor for thrombosis 489 (65%) 41 (64%) 0·80 530 (65%) Cancer diagnosed 16 (2·1%) 10 (15·6%) <0·0001 26 (3·2%) PE=pulmonary embolism. *Statistical comparison between the unilateral thrombosis group and the bilateral thrombosis group.

Choriocarcinoma secondary to isthmic tubal pregnancy

A choriocarcinoma of the fallopian tube developed from normal trophoblasts which appear to have invaded and remained in the muscle layer of the pars mterstitialis of the uterine tube following an ante

A cause of pre-eclampsia?

A 30-year-old woman was admitted to hospital in the 19th week of pregnancy in June, 1999, because of a slight rise in blood pressure. She had previously had a preterm delivery of a girl weighing 1600 g by caesarean section in the 31st week of pregnancy in September, 1995, because of abruption of normally implanted placenta due to preeclampsia. From the 25th to 30th weeks of the previous pregnancy she had had an abrupt weight gain from 60·8 kg to 68·5 kg, deterioration in proteinuria from negative to ++++, and a rise in blood pressure to 160/108 mm Hg. Her postpartum course had been uneventful and signs of pre-eclampsia disappeared completely within a month. In the early weeks of her second pregnancy, blood pressure, monitored at home, was normal, and systolic blood pressure measured in the clinic fluctuated between 110 mm Hg and 130 mm Hg. There was no proteinuria or oedema at the time of admission. During the first 3 weeks in hospital, her blood pressure was fairly stable between 100 mm Hg and 130 mm Hg systolic and 70–90 mm Hg diastolic, and there was no oedema or acute weight gain. Serum concentrations of epinephrine, norepinephrine, and dopamine at admission were within normal ranges, though renin activity was 6·1 ng mL h (normal range, 0·4–2·7). From the middle of the 22nd week her blood pressure gradually rose up to 220/120 mm Hg, even after treatment with hydralazine, methyldopa, prazosin, nifedipine, and magnesium sulphate. Her bodyweight remained at 68 kg, but proteinuria increased to 8·3 g/day by the 26th week of pregnancy. About 80% of urinary protein was albumin. Urinary concentrations of 2-microglobulin and N-acetyl-D-glucosaminidase increased to three to five times the normal upper value. There was slight elevation of serum creatinine and blood urea nitrogen to 80 mol/L and 6·8 mmol/L respectively. At 26 weeks and 4 days the fetus died in utero. The stillborn girl was severely underweight at 464 g. Within 2 weeks of delivery, the patient’s blood pressure, proteinuria, and renin activity had returned to normal. CASE REPORT