Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

The distribution of lectin bindings in the testis of babirusa, Babyrousa babyrussa (Suidae) was studied histochemically using 10 biotinylated lectins, Peanut agglutinin (PNA), Ricinus communis agglutinin (RCA I), Dolichos biflorus agglutinin (DBA), Vicia villosa agglutinin (VVA), Soybean agglutinin (SBA), Wheat germ agglutinin (WGA), Lens culinaris agglutinin (LCA), Pisum sativum agglutinin (PSA), Concanavalin A(Con A) and Ulex europaeus agglutinin (UEA I). Nine of 10 lectins showed a variety of staining patterns in the seminiferous epithelium and interstitial cells. The acrosome of Golgi-, cap- and acrosome-phase spermatids displayed various PNA, RCA I, VVA, SBA and WGA bindings, indicating the presence of glycoconjugates with D-galactose, N-acetyl-D-galactosamine and N-acetyl-D-glucosamine sugar residues respectively. No affinity was detected in the acrosome of late spermatids. LCA, PSA and Con A which have affinity for D-mannose and D-glucose sugar residues were positive in the cytoplasm of spermatids and spermatocytes. DBA was positive only in spermatogonia. In addition to DBA, positive binding in spermatogonia was found for VVA, WGA and Con A, suggesting the distribution of glycoconjugates with N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, D-mannose and D-glucose sugar residues. Sertoli cells were stained intensely with RCA I, WGA and Con A. In Leydig cells, RCA I and Con A were strongly positive, while WGA, LCA and PSA reactions were weak to moderate. The present findings showed that the distribution pattern of lectin binding in the testis of babirusa is somewhat different from that of pig or other mammals reported previously.

A B S T R A C T Plasma ACTH and corticosteroid concentrations were measured by radioimmunoassay in chronically catheterized fetuses of 32 pregnant sheep. Fetal plasma ACTH levels 38+5 pglml (means±SEM) were slightly (P < 0.05) lower than maternal 54±4 pg/ml levels. No general rise in fetal plasma ACTH concentration was noted before 140 days gestation; however, fetal plasma corticoid levels began to increase after about 125 days. This suggested that an increase in fetal adrenal responsiveness to endogenous ACTH occurred during gestation.Hemorrhage of 15% of estimated blood volume decreased mean arterial pressure from 54+3 to 36±3 torr and increased plasma ACTH from 30±5 to 130 ±30 pg/ml in fetuses older than 0.80 gestation. In fetuses younger than 0.67 gestation, 15% hemorrhage caused no change in plasma ACTH levels despite a significant fall in mean arterial pressure. This suggests that system(s) subserving the ACTH response to mild hemorrhage are either absent or nonfunctional in the younger fetuses. The hemorrhage-induced increase in plasma ACTH levels was associated with a small rise in plasma corticoids in fetuses younger than 0.94 gestation. In older fetuses, a similar increase in plasma ACTH was associated with a pronounced increase in plasma corticoid levels. This also suggests that an increase in adrenal responsive-

The quality of blood salvaged at operation and prepared with the Dideco Autotrans BT 795 autotransfusion device was compared with that of donor blood in 41 patients having cardiac surgery involving cardiopulmonary bypass. Saved blood had a higher haemoglobin concentration (17.3 v. 13.1 g dl-1; P less than 0.001), a higher 2,3-diphosphoglycerate concentration (5.3 v. 1.1 mmol litre-1; P less than 0.00001), higher white cell count (17.1 X 10(9) litre-1 v. 4.1; P less than 0.00001), higher pH (7.5 v. 6.6; P less than 0.00001) and a more physiological potassium concentration (5.4 v. 8.8 mmol litre-1; P less than 0.00001) than donor blood. Saved blood platelet count was 34.5 X 10(9) litre-1 compared with 146.24 X 10(9) litre-1 (P less than 0.00001) and its heparin concentration was 0.64 u. ml-1. We conclude that this autotransfusor is a useful aid to blood conservation, producing good quality red cells with relatively normal pH and potassium values. However, modification of the centrifugation and washing is required to lessen the high white cell count and heparin concentrations found in the saved blood.

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The distribution and relative frequency of endocrine cells in the gastrointestinal tract of the babirusa were studied immunohistochemically using the avidin-biotin-peroxidase complex method. Thirteen types of gut endocrine cells were detected; they were immunoreactive for chromogranin, serotonin, somatostatin, gastrin, bovine pancreatic polypeptide (BPP), glucagon, secretin, cholecystokinin (CCK), methionine-enkephalin-Arg6-Gly7-Leu8 (MENK8), motilin, gastric inhibitory polypeptide (GIP) and peptide tyrosine tyrosine (PYY). Cells that were immunoreactive for chromogranin, serotonin, somatostatin and glucagon were found in all portions of the gastrointestinal tract. MENK8-immunoreactive cells were observed in the stomach and small intestine. Gastrin-immunoreactive cells were detected in the pyloric region and duodenum. PYY-immunoreactive cells were found in the small and large intestine. Cells immunoreactive for motilin, CCK, GIP, and secretin were observed in the proximal small intestine and those immunoreactive for neurotensin were found only in the ileum. Although the distribution pattern of endocrine cells in the gastrointestinal tract of babirusa was similar to those reported for pig, restricted distribution of several endocrine cells, gastrin, BPP, MENK8, motilin, CCK, GIP, secretin and neurotensin and wider distribution of glucagon and PYY were observed in the babirusa. The unexpected presence of MENK8 in all glandular regions of the stomach and PYY in the small intestine was also noted. The distribution of gut endocrine cells might be related to the regulatory characteristics of the babirusa digestive tract.

Scanning electron microscopy was used to examine the microstructure of the maternal and fetal placenta from 25 pregnant ponies (Equus caballus) throughout the second half of gestation. Samples of placenta, 2-6 cm(2)in area, were collected from the antimesometrial region of the pregnant horn at 105 days (n=1), 165-219 days (n=5), 260 days (n=3), 270-277 days (n=3), 313-337 days (n=11) and immediately after spontaneous delivery at term (n=2). The maternal microcaruncle appears to be created from a clustering of about 16 uterine crypts encapsulated in a connective tissue sheath. There is a gestational increase in the depth of the microcaruncle during the second half of pregnancy. The fetal microcotyledon appears to be formed by a clustering of individual fetal villi. The length and branching of the villi increased considerably during the last 2-3 months of gestation. Tufts of from three to six branches were seen arising from close to the base of a villous stem. Branching of the villous stem occurred not only at the base but also along the secondary and tertiary branches. There was evidence of continued branching at the tips of the villi in the few days before birth.