Clinical Evaluation of an Immunoradiometric Assay for CA15-3 Antigen Associated With Human Mammary Carcinomas: Comparison With Carcinoembryonic Antigen

Serum levels of CA15-3, a mammary tumor associated antigen recognizedby two different murine monoclonal antibodies (115D8 and DF3),were investigated in patients with mammary carcinoma and otherbenign or malignant diseases. The reference value of the serumCA15-3 level was obtained as 24 units/ml at the 99% confidencelimit among healthy individuals (n = 462). Elevation of serumCA15-3 levels was observed in 24.3% of overall patients withmammary carcinoma. Serum CA15-3 levels in breast cancer patientscorrelated with the clinical stage; higher percentages of positivitywere observed in those with advanced breast cancer (stage IV,64.7%, recurrent, 52.4% and metastatic, 70.3%). Furthermore,elevated serum CA15-3 levels in breast cancer patients respondedwell to the effect of therapy. Although the serum CA15-3 testgave percentages of positivity of breast cancer similar to thosefound by the serum CEA test, the serum CA15-3 test revealedlower percentages of posi-tivity than the serum CEA test amongpatients with benign breast lesions, liver cirrhosis or othercarcinomas. These results suggest that the serum CA15-3 antigenlevel provides a very useful marker for diagnosis and clinicalmonitoring of patients with breast cancer.     

Is a limited lymphadenectomy targeting obturator nodes alone an adequate procedure for Japanese men undergoing radical prostatectomy?

BACKGROUND: The objective of the present study was to investigate the significance of pelvic lymphadenectomy during radical prostatectomy in Japanese men with prostate cancer. METHODS: A total of 178 consecutive patients who underwent radical prostatectomy and standard pelvic lymphadenectomy targeting the external iliac nodes and obturator fossa for clinically localized prostate cancer were studied. The median observation period of this series was 18 months (range: 3-36 months). RESULTS: Lymph node metastases were detected in 13 patients; that is, positive nodes were located in the external iliac nodes alone in seven patients, the obturator fossa alone in four patients, and both external iliac nodes and obturator fossa in two patients. Of these 13 patients, all of the seven with more than one positive node demonstrated biochemical recurrence, whereas five of the six with single node involvement remained without signs of biochemical recurrence. Furthermore, a single positive node was located in the external iliac region in five of the six patients. When a group at high-risk for lymph node metastasis was defined as those meeting more than two of the following three criteria: (i) pretreatment serum prostate specific antigen value > or = 20 ng/mL; (ii) biopsy Gleason sum > or = 8; or (iii) percentage of positive biopsy core > or = 50%, the incidence of lymph node metastasis was 24.5% in the high-risk group and 0.8% in the low-risk group. CONCLUSIONS: These findings suggest that limited dissection of the obturator node alone may not be sufficient for Japanese men undergoing radical prostatectomy; therefore, we recommend performing standard pelvic lymphadenectomy targeting both the external iliac nodes and the obturator fossa for patients at high-risk of lymph node involvement.     

Extremely fast hydrogen exchange of ribonuclease-(1–118) as compared with native RNase A and its implication for the conformational energy state

RNase-(1–118) containing native disulfide bonds is similar in fold to native RNase A but not of lowest Gibbs energy as compared with the isomers containing non-native disulfide bonds. The present n.m.r. studies have indicated a dramatic increase in the exchange rate of all of the ‘protected’ amide protons of RNase-(1–118) over RNase A. A calculation shows a large increase in the rate of ‘opening’ of the structure. The exchange rate of the protected amide protons of RNase-(1–120) is slower than RNase-(1–118) but much faster than RNase A. Binding with a synthetic complementing fragment (114–124) markedly reduces the exchange rate of 20 to 25 amide protons of RNase-(1–118). It has previously been shown that binding with a complementing fragment of RNase-(1–118) generates a lowest Gibbs energy state. Thus, using available thermodynamic information for interpretation, we suggest that a) removal of six carboxy terminal residues of RNase A would disrupt coupling between these residues and those distant in the structure (loss of extra stabilizing energy), b) this would, in turn, alter the enthalpy-entropy compensation in such a way that the magnitude of Gibbs energy change favoring folding is significantly reduced without a large change of fold and c) in this activated state the molecule would be highly motile.     

Spontaneous disappearance of a renal arteriovenous malformation

Abstract We describe herein a case of complete spontaneous disappearance of a congenital arteriovenous malformation (AVM). A 28‐year‐old male was hospitalized for right flank pain and gross hematuria, followed by bladder tamponade. To improve the patient's symptoms, bladder irrigation was performed. Cystoscopy demonstrated bloody urine from the right ureteral orifice. Right selective renal arteriography demonstrated tortuous, coiled vascular channels with early filling of the renal vein. Thus, right renal AVM was diagnosed. However, the patient refused further treatment and was discharged. One year later, massive hematuria recurred with bladder tamponade and the patient was rehospitalized. Renal arteriography did not show any evidence of AVM and there has been no hematuria since.     

Selective effector mechanisms for the expulsion of intestinal helminths

In the middle of the era of molecular biology, much less attention is paid to in vivo phenomena. However, carefully designed experimental systems in vivo still can provide valuable information as to the mechanisms underlying the establishment and maintenance of host-parasite relationships. In this review we describe the advantage of using concurrent infections with appropriately chosen combinations of different genera or different maturation stages of parasites to segregate the cellular responses of the host. By means of simple experimental approaches we have found that mucosal mast cells and goblet cells, both of which have long been considered as non-specific effectors, are in fact highly selective and specific effector cells of the host defence mechanisms capable of acting on the establishment and the expulsion of intestinal helminths.     

Actions of peroxovanadate or tungstate on glucose transport by isolated rat adipocytes

The effects of peroxovanadate or tungstate on 3-O-methylglucose uptake were characterized using isolated rat adipocytes to elucidate the mechanism(s) of their actions. The stimulatory effect of peroxovanadate was observed from 1 μmol/L and reached the maximum at about 100 μmol/L. The concentration showing the half-maximal effect was approximately 16 μmol/L. The maximal response of peroxovanadate was 1.19 times higher than that of insulin significantly (P < 0.01). On the other hand, the stimulatory effect of tungstate was seen only at the higher concentrations of 10–30 mmol/L Judging from the experiments using different tungsten compounds, tungstic acid (WO₄^2-) appeared responsible for the effect. The effects of 20 mmol/L tungstate and 20 nmol/L insulin were not additive. The stimulatory effects of 1 mmol/L peroxovanadate, 20 mmol/L tungstate or 20 nmol/L insulin were not seen in the adipocytes deprived of ATP by exposure to 2 mmol/L KCN. The adipocytes which had been stimulated with insulin and further exposed to 2 mmol/L KCN were used to test whether or not peroxovanadate works directly on the function of glucose transporters. In such cells on which GLUT4-rich transporters were rendered immobile, the effect of peroxovanadate was not observed. These results indicate that the effects of peroxovanadate or tungstate are ATP or energy dependent and may be exerted through the mechanism analogous to that of insulin action, and suggest that peroxovanadate does not directly activate the function of GLUT4.     

A case of tetrasomy 9p

A case of mosaic 9p tetrasomy (46,XX/47,XX, + dic[9] [q21]) is reported. Clinical manifestations of the patient were generalized hypotonia, severe mental retardation and characteristic dysmorphic features of 9p tetrasomy. A brief review of the literature is also included.     

Defective natural killer cell activity and deficient production of interferon-γ in children with acute lymphoblastic leukemia

Natural killer (NK) cell activity, OK-432-augmented-NK cell activity, concentrations of interferon-γ (IFN-γ) in the culture supernatants of lymphocytes stimulated with OK-432, and subsets of NK cells and memory T cells were analyzed in 42 children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy. Natural killer and augmented-NK cell activities, and concentrations of IFN-γ in the supernatants of cultured lymphocytes, were significantly lower in the patients with ALL than in age-matched control children. Among the NK cell subsets, proportions of CD57⁺ cells in the patients with ALL were significantly higher than in the controls, and proportions of a memory T cell subset (CD4⁺ CD29⁺ T cells) in the patients were also significantly higher than in the controls. These results suggest that the function of NK cells and memory T cells that are considered as IFN-γ producing cells, may be defective in ALL, and that CD57⁺ cells and CD4⁺ CD29⁺ cells may be resistant to or recover rapidly from suppression by cytotoxic chemotherapy.     

Mucinous adenocarcinoma of the renal pelvis associated with transitional cell carcinoma in the renal pelvis and the bladder

We report a case of mucinous adenocarcinoma of the renal pelvis associated with bladder carcinoma in situ (CIS). Transitional cell carcinoma (TCC) of the renal pelvis and CIS were also observed adjacent to the adenocarcinoma. Immunohistochemical assessment of the pelvic adenocarcinoma revealed positive expressions for mucin, epithelial membrane antigen, cytokeratin 7, cytokeratin 19 and carcinoembryonal antigen, but not vimentin or chromogranin. Based on the histopathological examinations, the adenocarcinoma of the renal pelvis in the present case may have a similar biological nature to conventional TCC and probably originated by development of pre-existing TCC of the renal pelvis.     

Microscopic venous invasion in renal cell carcinoma as a predictor of recurrence after radical surgery

BACKGROUND: The objective of the present study was to investigate the significance of microscopic venous invasion (MVI) as a prognostic factor for patients with renal cell carcinoma (RCC) who underwent radical surgery. METHODS: The study included a total of 157 consecutive patients with non-metastatic RCC who underwent radical surgery between January 1986 and December 2002. The median follow-up period was 45 months (range 6-162 months). Microscopic venous invasion was defined by the presence of a cancer cell in blood vessels based on the examination of hematoxylin-eosin stained specimens. Other prognostic variables were assessed by multivariate analysis to determine whether there was a significant impact on cancer-specific and recurrence-free survivals. RESULTS: Microscopic venous invasion was found in 70 patients, and of this number, 17 (24.7%) developed a tumor recurrence and 12 (17.1%) died of cancer progression, while only six (6.9%) of the remaining 87 patients without MVI presented with disease-recurrence and three (3.5%) died of cancer. Among the factors examined, the presence of MVI was significantly associated with age, mode of detection, tumor size, pathological stage and tumor grade; however, only pathological stage was an independent predictor for disease-recurrence, and none of these factors were available to predict cancer-specific survival in multivariate analyses. In 120 patients with pT1 or pT2 disease, MVI was noted in 36 patients. In this subgroup, recurrence-free survival rates in patients with MVI were significantly lower than those in patients without MVI, and MVI was the only independent prognostic predictor for disease-recurrence in a multivariate analysis. CONCLUSION: Microscopic venous invasion is not an independent prognostic factor in patients with non-metastatic RCC who underwent radical surgery; however, it could be the only independent predictor of disease-recurrence after radical surgery for patients with pT1 or pT2 disease.