Anterior pituitary hormones in plasma and pituitaries from patients with Cushing's disease

Pituitary adenomas were obtained from eight of nine patients with Cushing's disease, and the surrounding tissues as well were obtained from six of nine patients. ACTH, beta-lipotropin (beta-LPH), beta-endorphin, GH, TSH, LH, and PRL concentrations in these tissues were determined by RIA. Immunoreactive ACTH and beta-endorphin (beta-endorphin + beta-LPH) were present in high concentrations in all adenomas, and low concentrations were found in the surrounding tissues, except for one patient. As compared to levels seen in normal pituitary tissue, the GH concentration in the surrounding tissues was suppressed in five of six cases. TSH and LH concentrations were suppressed in four and three cases, respectively. The PRL concentration was not suppressed in any of the six patients studied. These four hormones were not detected in any adenoma. Plasma GH, TSH, and LH responses to various stimuli which were suppressed preoperatively returned to normal in most of the patients after adenomectomy. Basal plasma cortisol concentrations were normal or subnormal and were suppressed by the administration of 1 mg dexamethasone after adenomectomy, in contrast to the lack of such suppression preoperatively. ACTH and beta-endorphin secretion were stimulated by lysine-8-vasopressin and suppressed by dexamethasone and cyproheptadine in vitro.     

The significance of alpha-subunit as a tumor marker for gonadotropin-producing pituitary adenomas

We studied gonadotropin hormone alpha-subunit and gonadotropin secretion in four patients with gonadotropin-producing pituitary adenomas. All four patients had elevated plasma alpha-subunit levels, ranging from 2.8-8.5 ng/ml (normal, less than 0.5 ng/ml). alpha-Subunit responses to LHRH were less than those in seven patients with primary gonadal failure. The relative proportions of the gonadotropin and alpha-subunit peaks in one patient were the same before and after LHRH administration, based on gel filtration studies of plasma. The alpha-subunit levels decreased little during testosterone treatment in the two adenoma patients so treated. Immunohistochemical study of the adenomas from two patients demonstrated definite staining with alpha-subunit and gonadotropin antisera. Elevated plasma levels of alpha-subunit and its relative unresponsiveness to LHRH stimulation or testosterone suppression suggest that the alpha-subunit originated in tumor tissue and that its measurement is useful for the diagnosis of a gonadotropin-producing tumor in patients with elevated plasma levels of LH and/or FSH.     

The relationship between circulating sialyl Tn antigen and polypoid or nonpolypoid growth characteristics in colorectal cancer

Recent studies delineated two different patterns of tumor growth in colorectal carcinoma characterized as polypoid and nonpolypoid (PG-type and NPG-type, respectively). We quantified serum sialyl Lewis (Le)^a (CA19–9), sialyl Le^x (SLX), sialyl Tn (STN), and carcinoembryonic antigen (CEA) in 269 colorectal cancer patients to establish whether their levels correlated with any biological or clinical differences between PG-type and NPG-type cancer. Patients were divided into high and low antigen groups (higher or lower than a selected diagnostic-based cut-off value) and compared. Statistical testing was by univariate and multivariate (logistic regression) analyses. Forty-seven (17.5%) patients with PG-type and 222 (82.5%) with NPG-type cancer were studied. In contrast to NPG-type, the characteristics of the PG-type cancers included a low rate of lymph node metastasis and a high serum STN level. In contrast to a low STN level, a high STN level was independently related to the presence of distant metastasis in patients with PG-type cancer, and also to the presence of distant metastasis and large-sized tumor in patients with NPG-type cancer. These data suggest that differences in STN levels in the serum of patients with PG-type or NPG-type colorectal carcinomas may be at least partly responsible for different tumor progression behavior. Received: 17 December 1999 / Accepted: 6 March 2000     

Expression of blood group antigens A, B and H in carcinoma tissue correlates with a poor prognosis for colorectal cancer patients

The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy. Received: 20 August 1999 / Accepted: 16 December 1999     

Metabolite 1 of protopanaxadiol-type saponins, an axonal regenerative factor, stimulates teneurin-2 linked by PI3-kinase cascade.

We previously showed that 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (M1), a metabolite of protopanaxadiol-type ginseng saponins by intestinal bacteria had axonal extension activity in degenerated neurons, and improved memory disorder and synaptic loss induced by an active fragment of amyloid beta, Abeta(25-35). It is unknown how M1 shows these effects in neurons. To clarify the signal transduction mechanism of M1-induced axonal extension, phosphorylated proteins by M1 stimulation were identified because most cellular signal pathways are regulated by phosphorylation/dephosphorylation. The combination of immunoprecipitation and MALDI-TOF-MS revealed that teneurin-2 and mPar3 were specifically phosphorylated by M1 stimulation. Because mPar3 is known as an axonal specifying molecule and to be regulated by phosphatidylinositol 3-kinase (PI3-kinase), the involvement of teneurin-2 and PI3-kinase in the M1 signal was studied. In teneurin-2-deficient cortical neurons, M1-induced axonal extension and PI3-kinase activation were significantly inhibited. In addition, treatment with PI3-kinase inhibitor also reduced M1-induced axonal extension. These results suggest that M1 induces axonal outgrowth through the teneurin-2-PI3-kinase cascade.     

Reexamination of 123I-IMP-SPECT at interictal stages in adult partial epilepsy

123I-IMP-SPECT scans at the interictal stages in 13 epileptic patients with normal X-ray CT findings were reexamined at intervals of 1.9 +/- 0.8 years. Interictal scalp EEGs were recorded a few hours after each SPECT scan. All of the SPECT abnormalities indicated focal hypofixation images of 123I-IMP, i.e. zones of a decreased rCBF reflecting a functional inactivation. Among 11 patients with the SPECT abnormalities in the first SPECTs, eight cases had the complete or partial regional reproduction of the abnormalities in the second SPECTs. As changes in the SPECT findings, an alteration from the abnormal SPECT images to normal images (normalization), the reverse change, the enlargement and reduction of hypofixation sites were seen. Also the EEG foci had various changes (right and left regional changes, etc.). Because of these SPECT and EEG changes, the regional relationship between the SPECT abnormalities and EEG foci altered in 7 patients (a change from disagreement to agreement, etc.). The high reproduction rate of SPECT abnormalities appears to increase the reliability or utility of SPECT scans for a regional diagnosis of epileptic foci. The present SPECT changes, especially the normalization or the severse change, suggest that the interictal epileptic focus may have a functional fluctuation. In addition, the causes of regional disagreement between the SPECT abnormalities and EEG foci were discussed on the basis of the present SPECT and EEG changes.     

Acutely administered haloperidol-induced widespread reduction of regional cerebral blood flow observed from subtraction of brain imaging with single photon emission computed tomography using technetium-99m hexamethyl-propyleneamine oxime

Changes in brain images with single photon emission computed tomography (SPECT) using technetium-99m hexamethyl-propyleneamine oxime (99mTc HMPAO) before and after intramuscular injection of haloperidol (0.08 mg/kg) were studied in 2 unmedicated schizophrenic patients and 2 normal controls by a new technique, i.e. subtraction of brain images. The haloperidol injection reduced regional cerebral blood flow extensively in the bilateral cerebral hemispheres in one of the schizophrenics and one of the normal controls, with little or no haloperidol-induced effects in the remaining 2 subjects. The widespread cortical reduction is considered to be due to a nonspecific or indirect effect of haloperidol in view of the broad action sites inconsistent with the known anatomy of the mesocortical dopaminergic system.     

Clinical evaluation of various tumor markers in pleural effusion and in the serum

Various tumor markers and enzymes in the pleural effusion and serum have been measured in 47 patients with carcinoma and in 43 patients with benign disease, by means of a radioimmunoassay and biochemical methods. CEA in the pleural effusion showed a high specificity and sensitivity for the detection of the malignancy. In patients with a lung cancer, measurement of the NSE in the serum was more useful than in the pleural effusion. Further, both CA19-9 and SCC in the pleural effusion showed a high specificity in a differential diagnosis of cancer and benign diseases. On the other hand, CA 125, TPA and IAP in the pleural effusion and in the serum showed a high sensitivity, but a low specificity for diagnosing the malignancy. The levels of ADA were significantly higher in tuberculous pleural effusions than in carcinomatous effusions. Therefore, this suggests that measurement of the various tumor markers in both the pleural effusion and in the serum is useful in achieving a differential diagnosis of malignant and benign diseases.