Female sterility in mice lacking the basigin gene, which encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily.

Basigin (Bsg) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Bsg knock-out mice exhibit infertility of both sexes. Based on limited results, defective implantation has been considered to be the cause of the female infertility. We demonstrate here that disruption of the Bsg gene produces the failure of female reproductive processes including not only implantation but also fertilization. Bsg mRNA expression in cumulus cells and basolateral localization of the Bsg protein in the endometrial epithelium further support the importance of Bsg in these processes.

Expression of basigin, a member of the immunoglobulin superfamily, in the mouse central nervous system.

Basigin (Bsg) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Chicken Bsg (HT7/neurothelin/ 5A11) is expressed in neuroblasts, but disappears from neurons after a specific stage of cytodifferentiation, and becomes restrictedly expressed in the capillary endothelium in the adult brain. We show herein by means of in situ hybridization that Bsg mRNA was expressed in neuroblasts in 13.5 day old mouse embryos. In the adult mouse, Bsg was differentially expressed in subregions of the brain. Strong Bsg expression was detected in the limbic system, including the olfactory system, hippocampal formation, septal area, amygdala, thalamic anterior nuclei, hypothalamus, mesencephalic tegmentum, entorhinal cortex, and cingulate gyrus. Bsg was also intensely expressed in the retinal neuronal layers, the Vth layer of the cerebral neocortex, Purkinje cells of the cerebellum, several nuclei of the brain stem, and the gray matter of the spinal cord. Although in situ hybridization showed a weak signal in the brain capillary endothelium, protein expression of Bsg was strong enough to be detected by immunohistochemistry. Northern blot analysis confirmed the strong expression of Bsg in the central nervous system. Taking into account that Bsg knockout mice exhibit abnormalities in behavior, but a normal blood-brain barrier function, the present findings suggest that Bsg functions actively in neuronal interactions in the central nervous system.

Binding of [3H]p-aminoclonidine to two sites, alpha 2-adrenoceptors and imidazoline binding sites: distribution of imidazoline binding sites in rat brain.

Binding sites labeled by [3H]p-aminoclonidine [( 3H]PAC) were investigated by the competitive analysis with imidazoline and non-imidazoline derivatives. Phenylethylamine derivatives displaced only the part of specific sites for [3H]PAC, which was considered as alpha 2-adrenoceptor, whereas imidazoline derivatives, such as clonidine and tolazoline, competed for a further specific binding of [3H]PAC to the non-adrenergic sites, in addition to the alpha 2-adrenoceptor. Because the non-adrenergic sites were specific for the imidazoline structure, they were termed imidazoline sites. The imidazoline sites were not distributed uniformly among rat brain regions. In striatum, hippocampus and medulla oblongata, they occupied 39.6, 33.0 and 36.5% of the specific binding of [3H]PAC, respectively. Saturation isotherms revealed that Kd and Bmax of imidazoline sites for [3H]PAC were 3.09 +/- 0.59 nM, 27.4 +/- 1.7 fmol/mg protein and 2.23 +/- 0.29 nM, 21.0 +/- 1.5 fmol/mg protein in striatum and hippocampus, respectively. Because imidazoline binding sites also displayed weak affinities for imidazole compounds, such as histamine and cimetidine, the imidazoline site may be a subtype of histamine H2-receptor.

Inhibition of cyclic AMP accumulation by alpha 2-adrenoceptors in the rat cerebral cortex.

The effects of alpha 2-adrenoceptor agonist and antagonists on the accumulation of cyclic AMP were examined in rat cerebral cortex slices. Norepinephrine (10(-4) M) caused a 123 +/- 11% increase in the cyclic AMP concentration in the cortical slices, which was greater than the increase (89 +/- 7% increase) caused by isoproterenol (10(-4) M) alone. However, the cyclic AMP response to norepinephrine was completely inhibited by propranolol (10(-4) M), a beta-adrenoceptor antagonist. Yohimbine (10(-7)-10(-5) M), an alpha 2-adrenoceptor antagonist, intensified the cyclic AMP response to norepinephrine by 30%, whereas, clonidine, an alpha 2-adrenoceptor agonist, decreased the response. Treatment with reserpine (3.0 mg/kg) reduced the density of [3H]p-aminoclonidine binding sites (Bmax, 93.8 +/- 18.4 fmol/mg protein) compared to the density in non-treated rats (154.4 +/- 33.5 fmol/mg protein). The potentiating effect of yohimbine and the inhibitory effect of clonidine on the cyclic AMP response to norepinephrine were also reduced. These results suggest that alpha 2-adrenoceptors regulate the accumulation of cyclic AMP in the rat cerebral cortex in an inhibitory fashion. The results also suggest that the accumulation is mediated through beta-adrenoceptors and that this response is intensified by alpha 1-adrenoceptor stimulation.

Prognostic values of preoperative and postoperative CEA and CA19.9 levels in pancreatic cancer.

Preoperative serum levels of carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19.9 (CA19.9) were measured in 90 patients with advanced pancreatic cancer. CEA antigen was above the cutoff levels of 5.0 ng/ml in 51% of patients and CA19.9 was above the cutoff limit of 37 U/ml in 87% of patients. High preoperative CEA and CA19.9 levels were related to a poor prognosis of the patients. In multivariate analysis, the hazard rate was significantly higher in the high-CEA group (> 2.5 ng/ml) compared to the low-CEA group (< 2.4 ng/ml). An increase in CEA and/or CA19.9 within 1 month after the operation was also significantly related to the hazard rate. This study reconfirms the prognostic importance of preoperative and postoperative CEA and CA19.9.

Pancreatic stone protein and lactoferrin in human pancreatic juice in chronic pancreatitis.

Lactoferrin and pancreatic stone protein (PSP) are thought to be closely related to pancreatic stone formation in chronic pancreatitis. However, the results reported so far have not been conclusive. To reevaluate the pathological importance of PSP in chronic pancreatitis, compared to lactoferrin, levels of PSP were determined by applying an immunoassay specific to PSP to pure pancreatic juice taken from a total of 52 patients. The patients consisted of 16 controls, 19 chronic pancreatitis patients (13 noncalcified and 6 calcified), and 17 probable cases of pancreatitis. The monoclonal antibody PSP antagonist used in the study recognizes both forms of the protein, PSP S1 and S2-5, with equal effectiveness. No significant reduction of PSP was observed in either calcified (mean +/- SEM, 111 +/- 30 micrograms/mg and 24 +/- 3 micrograms/mg protein) or noncalcified (305 +/- 133 and 97 +/- 47) chronic pancreatitis patients compared with controls (85 +/- 23 and 34 +/- 16). PSP levels did not decrease, at least not in the complete forms of the protein found in chronic pancreatitis. PSP antibody and assay results indicated that a reduction of PSP S2-5 alone could not be ruled out in chronic pancreatitis either.

Effectiveness of multivariate analysis of tumor markers in diagnosis of pancreatic carcinoma: a prospective study in multiinstitutions.

In 403 patients suspected of having pancreatic cancer, we prospectively studied a combination assay of various serum tumor markers: CA19-9, DUPAN2, tissue polypeptide antigen, elastase 1, gamma-glutamyltranspeptidase, lactate dehydrogenase, lipase, amylase, and alkaline phosphatase. The diagnostic value of each marker was compared with a multivariate analysis (computer-aided multivariate and pattern analysis system for pancreatic cancer examine-1: CAMPAS-PX1). Pancreatic cancer was subsequently identified in 47 patients. CAMPAS-PX1 had higher negative in health and positive predictability than those of each marker used alone in the diagnosis of pancreatic cancer. CAMPAS-PX1 proved the most effective marker for diagnosing pancreatic cancer, but in terms of its cost/benefit ration CAMPAS-PX1 was not superior to CA19-9 used alone. In this prospective trial, we experienced poor generalizability in the statistical models (CAMPAS-PX1). We believe that selection bias was present in samples used for model building. Based on this study a new model has been designed.

Possible involvement of placental proteases in bradykinin (BK) degradation.

The hydrolysis of bradykinin (BK) by human placental subcellular fractions and pregnancy sera was studied in the presence of inhibitors by measuring amino acids liberated from BK by high-performance liquid chromatography. The effects of the inhibitors DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (MGTA, for kininase I), phosphoramidon (for endopeptidase 24.11) and captopril and rentiapril (for angiotensin-converting enzyme [ACE, kininase II]) suggested the essential roles of the above three proteases in BK degradation: among the three proteases, kininase I and endopeptidase 24.11 appeared to be the most important in kininase action in the placenta microsomes, whereas kininase I and ACE appeared to be the most important in kininase action in the placental cytosol, lysosome and pregnancy serum. Measurements of BK concentrations in the umbilical arterial blood, umbilical venous blood and maternal plasma revealed higher concentrations in the mother than in the fetus. The present data suggest that degradation of BK in the placenta and pregnancy serum might contribute to the gradient of BK between mother and fetus.

Serum creatine phosphokinase elevation in patients treated with intravenous magnesium sulfate.

OBJECTIVE: During the treatment of pre-term labor with magnesium sulfate, we noted an abnormal elevation of maternal serum creatine phosphokinase. This study was aimed at evaluating the relationship between tocolysis with MgSO4 and maternal serum CPK elevation, which represents the possible damage of muscles by magnesium sulfate. METHODS: Clinical records of 45 women treated with magnesium sulfate and beta-sympathomimetics for the treatment of pre-term labor were retrospectively examined. RESULTS: Serum CPK was abnormally elevated in 32 out of 45 cases (71.1%), but in only one out of 21 in the control group. In three cases, the decrease of serum creatine phosphokinase after cessation of magnesium sulfate was demonstrated, despite the continuous infusion of beta-sympathomimetics. CONCLUSION: Magnesium sulfate may cause muscular damage and abnormal elevation of maternal serum creatine phosphokinase. Special attention must be paid to patients when drugs acting on muscle cells, for example succinyl choline, are going to be used.

Decrease in severity of intrauterine growth retardation in subsequent pregnancies.

OBJECTIVE: Intrauterine growth retardation (IUGR) is likely to recur in a subsequent pregnancy. We investigated the obstetric features of recurrent cases and the severity of IUGR by comparing initial and subsequent deliveries. METHODS: From a total of 12,567 deliveries, 95 women who were delivered of small-for-gestational-age (SGA) infants and who became pregnant again within 5 years, were enrolled. A retrospective, comparative study of recurrent and non-recurrent groups was performed. RESULTS: Twenty-two of ninety-five women gave birth to SGA infants again, and a relatively high risk of recurrence was confirmed, but no single recurrence-associated features were revealed. Within the recurrent group, the degree of IUGR was more severe in only five cases in the subsequent pregnancy. CONCLUSIONS: IUGR tends to recur, but does not increase in severity in most cases. We conclude that there is no need for excessive concern about the recurrence of IUGR.

The diagnosis of pancreatic cancer by pancreatic juice cytology.

Cytologic examination of pancreatic juice collected during cannulation was performed on 105 patients. Positive results were obtained in 23 of 44 cases (52.3%) of carcinoma of the pancreas. Cytologic specimens were collected by direct suction, washing with saline, aspiration after secretin stimulation and brushing. Washing with saline (63.2%) and aspiration after secretin stimulation (51.3%) gave higher positive results than did the other two methods. Positive results when obtained in carcinoma of the head in 12 of 17 cases (70.6%) and in carcinoma of the body and tail in 9 of 24 cases (37.5%). The results were better in carcinoma of the head, and it is necessary to further improve the method of collection in carcinoma of the body and tail.

Endoscopic cytology of the esophagus, stomach and pancreas.

Cytology and biopsy under direct vision using a fiberscope as microscopic diagnostic procedures for carcinoma of the esophagus and stomach were described, and results of cytology were evaluated as compared with the results of biopsy. The diagnostic accuracy of brushing cytology under direct vision using a fiberscope was 97% in 116 cases of esophageal carcinoma and 78% both in 119 patients with carcinoma of the gastric cardia and in 63 patients with gastric carcinoma exclusive of the cardia. The diagnostic accuracy for cytology of pancreatic juice collected by cannulation in 36 patients with carcinoma of the pancreas was 56%: 79% for carcinoma of the head of the pancreas, but only 35% for carcinoma of the body and/or tail. For the esophagus and stomach, the diagnostic accuracy of direct vision biopsy has become almost as high as with cytology. As such biopsies are easily performed, esophagogastric cytology has become in our clinics a supplementary routine to the biopsy, and is done in a limited number of cases in which the biopsy failed or was not appropriate. However, cytology of the pancreas, in which biopsy is difficult, is important as the only microscopic diagnostic procedure. There, the development of newer instruments and the improvement of techniques of cell collecting are required, as is the development of expertise in the interpretation of cells from pancreatic carcinoma, in which the diagnostic accuracy is still relatively low.

[Early detection of pancreatic cancer by serum markers].

Serum markers such as pancreatic enzymes and tumor markers are useful for the diagnosis of pancreatic cancer. Among 40 cases of pancreatic cancer, elevated values were observed for immunoreactive elastase (IRE) in 70% and for CA19-9 in 73%. Elevated serum IRE was observed more frequently in head cancer and resectable cancer, whereas elevation in CA19-9 occurred more often in body-tail cancer and unresectable cancer. Elevation of serum IRE and CA19-9 are useful for diagnosis of pancreatic cancer but it is not specific for pancreatic cancer. Therefore, we studied the clinical usefulness of a combination assay of various serum markers such as CA19-9, lipase, serum iron, amylase, albumin globulin ratio, tissue polypeptide antigen, immunoreactive trypsin, and CA125 using the logistic regression analysis. This assay showed higher sensitivity and high specificity for pancreatic cancer than CA19-9. This combination assay may be very useful for the diagnosis of pancreatic cancer.