Long-term survival after brain metastasis from endometrial cancer

A case is reported of prolonged survival after radical hysterectomy for poorly differentiated adenocarcinoma of the endometrium and resection of metastatic carcinoma of the brain followed by radiation therapy. The 43-year-old patient has survived for seven years after hysterectomy and six years 10 months after excision of the brain metastasis. Our results show that the surgical excision of a single metastatic lesion of the brain with postoperative irradiation offers hope of prolonged survival in patients with a solitary brain metastasis and no evident systemic disease.     

Entactin: ultrastructural localization of an ubiquitous basement membrane glycoprotein in mouse skin

Summary Entactin is a recently described sulfated glycoprotein component of mouse endodermal cell-derived extracellular matrix and is present in a number of basement membranes. It has been ultrastructurally localized to both lamina densa and adjacent epithelial cell membranes in rodent kidney. In the present study, we have sought to determine the localization of entactin in mouse skin. Indirect immunofluorescence and immunoelectron microscopy (the latter via immunoperoxidase technique) were performed on both intact and NaCl-separated mouse skin, using a well-characterized IgG class entactin-specific ratxmouse monoclonal antibody. At the light microscopic level, entactin was present in all skin basement membranes. On NaCl-split skin, staining was noted solely on the dermal portion. At the electron microscopic level, in intact skin, entactin was primarily localized to the lamina densa and adjacent upper papillary dermis. However, smaller amounts of immunoreaction products were also detectable within the lamina lucida and in close apposition to overlying hemidesmosomes. In partially separated skin, immunoreactants were similarly noted above the level of the lamina densa. However, in completely separated areas, hemidesmosomal or cell membrane staining was no longer visible. We conclude that entactin is an ubiquitous component of mouse skin basement membranes. Similar to previous findings in rodent kidney, entactin is present in multiple regions of skin basement membrane, although its primary localization remains within and directly beneath the lamina densa.Presented in part at the annual Southern Regional meeting of the Society for Investigative Dermatology, New Orleans, Louisiana, February 3, 1989. Supported in part by the National Institutes of Health (NIAMS AR34861, JDF; NIAMS AR36457 & AF39741, JRC)     

Gastric acid response to graded dose of pentagastrin in duodenal ulcer]

To characterize gastric acid response and its age distribution in the patients with duodenal ulcer (DU), we conducted pentagastrin (PG) dose-response study and calculated maximal response (Vmax-c), half maximal dose of PG (Km-c), and the mean response to 0.22 microgram/kg/hr of PG as percent of highest observed response (SI). The mean values of basal secretion (BAO), Vmax-c, and SI in DU were significantly greater than those of normal subjects (N). The mean values of Km-c were significantly less than those of N. The greater BAO, Vmax-c, and SI, and less Km-c were observed in all age groups of DU. The results indicate that DU patients not only secrete more acid but also are more sensitive to stimulation by pentagastrin than N, and that the characteristics are common in all age groups of DU.     

A case of a solitary metastasis on the surface of the liver by dissemination after resection of an ovarian tumor

A 46-year-old woman underwent total hysterectomy and bilateral salpingo-oophorectomy for a granulosa cell tumor of the ovary ten years ago. Six years later, she underwent a resection of the retroperitoneal tumor because of a retroperitoneal metastases of the ovarian tumor. Four years after, a second operation was carried out for a solitary metastasis on the surface of the liver of the right subphrenic space. It proved to be a disseminated metastasis from the ovarian tumor. The angiography showed that the tumor was being fed by the hepatic artery and, one month later, the tumor was resected. Such a case history of a disseminated solitary metastasis is very rare and seldom reported in the literature.     

Effect of an orally active Na+/H+ exchange inhibitor, SMP-300, on experimental angina and myocardial infarction models in rats.

The effects of SMP-300, an orally active, potent, and selective Na+/H+ exchange inhibitor, were evaluated and compared with those of nifedipine, propranolol, and nicorandil on three experimental angina models and on myocardial infarction in rats. SMP-300 (0.1-1 mg/kg, p.o.) reduced isoproterenol-induced ST segment depression in a dose-dependent manner. Its maximal effect was comparable to that reported for propranolol and greater than that of nifedipine. SMP-300 (0.3-1 mg/kg) reduced vasopressin-induced ST segment depression in a dose-dependent manner, and its maximal effect was comparable to those of nifedipine and nicorandil. SMP-300 (0.3-1 mg/kg, p.o.) and propranolol (100 mg/kg, p.o.) inhibited coronary artery occlusion-induced T-wave elevation, but nifedipine (3 mg/kg, p.o.) did not. SMP-300 (1 mg/kg, p.o.) reduced myocardial infarct size after 40 min of coronary artery occlusion followed by 24 h of reperfusion, but nifedipine (3 mg/kg, p.o.) or propranolol (100 mg/kg, p.o.) did not. This study provides support for the future use of a Na+/H+ exchange inhibitor as an anti-anginal drug with a novel mode of action.     

Antibodies to GAD in Japanese patients classified as Type 2 diabetes at diagnosis. High titre of GAD Ab is a predictive marker for early insulin treatment--report of west Japan (Kyushu, Yamaguchi, Osaka) study for GAD Ab(+) diabetes.

AIM: We evaluated the prevalence of GAD Ab in Japanese Type 2 diabetic patients treated with oral hypoglycaemic agents (OHA) and/or diet and followed GAD Ab(+) patients to assess the usefulness of GAD Ab as a marker for future insulin treatment prospectively. METHODS: A total of 2658 Japanese Type 2 diabetic patients treated by OHA and/or diet were randomly selected between April 1996 and December 1998. The clinical characteristics at entry were assessed and patients were followed for 1-3 years. RESULTS: The overall prevalence of GAD Ab among Type 2 diabetic patients was 2.0%. Forty-five had a history of diabetes of < or = 5 years (short history) while those with duration > 5 years (long history) totalled nine. Among them, 47% of patients with a short history did not require insulin in the follow-up period. However, none of those with a long history required insulin treatment within 2 years. Comparison of patients based on GAD titre in those with short history showed that 33% of patients in the high-titre group (> or = 20 U) required no insulin treatment in the first year of follow-up. In contrast, this proportion was 80% in the first and 67% in the second year in the low-titre group (< 20 U). CONCLUSIONS: The prevalence of GAD Ab in Japanese patients with a short and long history of diabetes was 2.8% and 0.9%, respectively. The presence of GAD Ab in Japanese Type 2 diabetic patients with a short history of diabetes is a marker for early insulin treatment.     

Establishment of a cell line with phenotypes of chondrocyte from a human osteogenic sarcoma of the mandible

We have succeeded in transplanting a human osteogenic sarcoma of the mandible into athymic mice. The transplanted tumor showed marked chondrogenesis and mineralization. Recently, a cell line (USAC) with phenotypes of chondrocyte has been established from the transplanted tumor. USAC cells were stellate or spindle-shaped in sparse culture, but polygonal or spherical at sub-confluency to confluency. In long-term culture, the cells were condensed and calcified nodules were formed. Production of types I, II and X collagen were detected by immunohistochemical staining and Western blot analysis. Type I collagen was strongly expressed in the stellate or spindle-shaped cells. Although type II collagen was usually present in all cells during culture, it was strongly stained in polygonal cells at confluency. Type X collagen was seen in large polygonal cells around calcified nodules. Marked [35S]-sulfate uptake and metachromasia were seen at the confluent stage and in the nodule. The cells around the nodules were positive for alkaline phosphatase, and the center of the nodules was stained with alizarin red. The potentiality of cartilage formation was confirmed by in vivo experiments using a diffusion chamber in athymic mice. These observations indicate that USAC cells maintain characteristics of chondrocyte progenitor cells and thus may serve as a useful model to study the sequential events of chondrogenesis and the process of morbid endochondral calcification. This experiment also demonstrated that transplantation of tumor tissue into athymic mice is a convenient strategy for establishment of a cell line.     

Radiation risk to low fluences of α particles may be greater than we thought

Based principally on the cancer incidence found in survivors of the atomic bombs dropped in Hiroshima and Nagasaki, the International Commission on Radiation Protection (ICRP) and the United States National Council on Radiation Protection and Measurements (NCRP) have recommended that estimates of cancer risk for low dose exposure be extrapolated from higher doses by using a linear, no-threshold model. This recommendation is based on the dogma that the DNA of the nucleus is the main target for radiation-induced genotoxicity and, as fewer cells are directly damaged, the deleterious effects of radiation proportionally decline. In this paper, we used a precision microbeam to target an exact fraction (either 100% or < or =20%) of the cells in a confluent population and irradiated their nuclei with exactly one alpha particle each. We found that the frequencies of induced mutations and chromosomal changes in populations where some known fractions of nuclei were hit are consistent with non-hit cells contributing significantly to the response. In fact, irradiation of 10% of a confluent mammalian cell population with a single alpha particle per cell results in a mutant yield similar to that observed when all of the cells in the population are irradiated. This effect was significantly eliminated in cells pretreated with a 1 mM dose of octanol, which inhibits gap junction-mediated intercellular communication, or in cells carrying a dominant negative connexin 43 vector. The data imply that the relevant target for radiation mutagenesis is larger than an individual cell and suggest a need to reconsider the validity of the linear extrapolation in making risk estimates for low dose, high linear-energy-transfer (LET) radiation exposure.     

Splenectomy for hypersplenism caused by adult T-cell leukemia: Report of a case

A 45-year-old woman with previously diagnosed chronic type adult T-cell leukemia (ATL) presented with abdominal discomfort and red eruptions on her arms and legs. Anemia, thrombocytopenia, hypercalcemia, and splenomegaly indicated progression to acute-type ATL. Combined chemotherapy resulted in normalization of the serum calcium level and improvement in her symptoms. However, the severe anemia and thrombocytopenia persisted, necessitating transfusions of red blood cells (RBC) and platelets three times a week. We performed splenectomy in an attempt to reduce the total volume of malignant cells and improve the hypersplenism. After the operation, the RBC and platelet counts increased gradually, and the transfusions were stopped on postoperative day (POD) 3. Splenectomy should be considered as an optional treatment for hypersplenism caused by ATL when hypersplenism cannot be controlled by chemotherapy in patients without a high surgical risk.