Clinicopathologic Study of Angiogenesis in Japanese Patients with Breast Cancer

p = 0.0007) and tumor necrosis (TN) (HMC: p = 0.0050). Univariate analysis showed that AMC or HMC was a statistically significant predictor of overall survival in all patients ( p = 0.0086 and p = 0.0307, respectively). Multivariate analysis showed that AMC was an independent predictor of node status when we fitted a model with node status, BVI, and either AMC or HMC; but HMC was not independent. However, when we fitted a model including all 11 of the other indicators and AMC or HMC, the node status, HG, and LI were independent predictors, but AMC and HMC were not. Although AMC was a better method than HMC for evaluating angiogenesis, we cannot confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients.     

A case of primary malignant lymphoma of the uterine body]

A 70-year-old female was found to have class V cytology on an endometrial smear, and a histological diagnosis of malignant lymphoma was made by endometrial biopsy. The pathological diagnosis was malignant lymphoma, diffuse large cell-type according to the Working Formulation classification. Immunohistochemical staining showed lymphoma cells to be positive for CD 20 (B 1), indicating B cell lineage. Two cervical lymph nodes were palpable, and swelling of a para-aortic lymph node was also found by abdominal CT scan. The clinical stage was determined to be III according to the Ann Arbor classification. After three courses of CHOP chemotherapy, lymphoma cells could no longer be detected by endometrial biopsy, and the para-aortic and cervical lymphadenopathy also disappeared. Primary malignant lymphoma of the uterus, especially of the uterine body, is very rare. Only eight cases of primary malignant lymphoma of the uterine body were reported in the literature. The cell lineage was decided in only one case, which was B cell type.     

Pharmacokinetics of amitriptyline and its demethylated metabolite in serum and specific brain regions of rats after acute and chronic administration of amitriptyline

The concentrations of amitriptyline (AMT) and its demethylated metabolite nortriptyline (NRT) in the serum and in specific brain regions were determined periodically after acute or chronic administration of 20 mg/kg of AMT in rats. Both AMT and NRT declined from the serum in a biexponential manner and were eliminated monoexponentially from the brain regions, with no significant difference in elimination among the eight brain regions examined. In the brain, both AMT and NRT were unevenly distributed after chronic administration, whereas an even distribution was observed after acute administration. The AUCbrain:AUCserum ratio of AMT was higher than that of NRT, indicating greater transport of AMT into the brain regions. The AUCAMT value in the serum increased 1.6 times after chronic administration, whereas no significant changes were observed in the brain regions. The AUCNRT values increased 9.0 times in the serum and 6.8 times in the brain, with the increase in the serum being greater. These results suggest inhibited distribution of the drugs into the tissues, including the brain regions, and enhanced metabolism of AMT.     

Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain

In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 ± 0.38, 2.12 ± 0.37, and 1.38 ± 0.24 (μg/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50 % more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus. Received: 12 August 1996 Accepted: 17 December 1996     

Detection of platelet-activating factor in exudates of rats with phorbol myristate acetate-induced pleurisy

PAF-likely activity, detected as aggregation of washed platelets, was found in the exudate of rats with pleurisy induced by phorbol myristate acetate (PMA, 1 nmol). At 30 min after the injection of PMA, 400-500 pg of PAF was detected in the pleural exudate. An extract of the exudate was made and analysed by HPLC and by rabbit platelet aggregation. The activity was characterized as that of PAF as a result of the inhibition seen with the PAF-antagonist CV-3988 and the loss of activity by treatment with phospholipase A2. Indirect evidence was previously reported in that CV-3988 suppressed the pleural fluid accumulation in the pleurisy induced by PMA. Taken together these facts it indicates that PAF could be an important mediator of acute inflammation, especially of the plasma exudation resulting from an increase in vascular permeability. Evidence that pleural cells produce PAF was also examined in an in vitro experiment. PAF was found in the supernatant and cellular fractions of the incubation mixture of the pleural cells from normal rats when stimulated by PMA (1 microM) or A23187 (5 microM), and the results indicate that the pleural cells produce PAF and release a portion of it.     

An immunocytochemical comparison of the glia-associated proteins glial fibrillary acidic protein (GFAP) and S-100 protein (S100P) in human brain tumors

Immunostaining patterns of two glia-associated proteins, glial fibrillary acidic protein (GFAP) and S-100 protein (S100P), were compared using the peroxidase-antiperoxidase (PAP) method on adjacent paraffin sections in 100 brain tumors including 52 astroglial tumors, 13 oligodendrogliomas, 14 ependymomas, 13 choroid plexus papillomas and 8 medulloblastomas. Most astroglial tumors showed similar immunoreactivity for both proteins. Fibrillary processes, however, showed a stronger and more crisp staining with anti-GFAP than with anti-S100P, whereas cell nuclei were labeled only for S100P. Focal dissociation of immunoreactivities for the two proteins was prominent in several malignant astroglial tumors including giant cell glioblastoma, and in subependymal giant cell astrocytoma. In oligodendrogliomas, GFAP-positive neoplastic oligodendrocytes also showed immunoreactivity for S100P; a smaller number of tumor cells were immunoreactive only for S100P, comparable to normal mature oligodendroglia. Most ependymomas were characterized by a similar distribution of cells immunoreactive for both proteins. In choroid plexus papilloma, absent or only focal immunoreactivity for GFAP contrasted with diffuse labeling for S100P in all cases; this seems of value for a differential diagnosis of papillary CNS tumors. In medulloblastoma, some tumor cells of a classical type were immunoreactive only for S100P; on the contrary, GFAP positive tumor cells with sparse or absent immunoreactivity for S100P were found in desmoplastic medulloblastomas. Similar immunoreactivities for both proteins in most tumors suggest a generally parallel production of both proteins by glial tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

A Possible Role of the Pineal Gland in Acute Immobilization-Related Suppression of Naloxone-Induced LH Release in Ovariectomized Estrogen-Primed Rats

It has been recently reported that acute immobilization stress almost completely suppresses the luteinizing hormone (LH) release induced by naloxone, a μ-opioid antagonist, in ovariectomized estrogen-primed rats. The present study examined the possible involvement of the pineal gland in the acute immobilization-related suppression of the naloxone-induced LH release. An intraventricular (ICV) injection of 15 μg naloxone produced an abrupt increase in circulating LH concentrations in non-stressed rats. The naloxone-induced LH release was completely eliminated when tested 60 min after the end of a 30 min session of acute immobilization. The same stress conditions did not affect LH-releasing hormone (LHRH)-induced LH release, suggesting that the stress-related suppression of the naloxone-induced LH release was a suprapituitary event. In chronically-pinealectomized rats, but not in sham-pinealectomized rats, naloxone injected 60 min after the end of the stress session evoked a significant increase in serum LH concentrations. However, naloxone injected ICV during the acute immobilization did not elicit LH release in either pinealectomized or sham-operated rats. Under non-stressed conditions, the LH secretory response to naloxone was similar in pinealectomized and sham-operated animals. The same stress (30 min immobilization) significantly increased pineal melatonin content as well as plasma melatonin concentrations in rats bearing intact pineal glands, indicating that stress actually affected the pineal function. These results provide evidence for a role of the pineal in the suppression of the LH response to naloxone after stress, but not during stress.     

Effects of Long-Term Glucocorticoid Therapy on Bronchoalveolar Cells in Adult Patients with Bronchial Asthma

The effects of long-term glucocorticoid therapy on airway inflammation were examined in 84 asthma patients. The proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid was significantly decreased in patients with steroid-dependent intractable asthma (SDIA) compared to results in non-SDIA patients, while BAL neutrophils were significantly increased in SDIA patients compared to results in non-SDIA patients. Regarding age, in patients under the age of 69 (except those between 30 and 39), BAL lymphocyte number was significantly decreased in SDIA compared with non-SDIA subjects, and in patients between 50 and 69, BAL neutrophils were significantly increased in SDIA compared with non-SDIA subjects. The number of BAL lymphocytes was significantly lower in patients with serum cortisol levels of less than 5.0 μg/dl than in those with levels of more than 5.1 μg/dl. BAL lymphocyte number was also significantly lower in patients who had received glucocorticoid therapy for more than 6 years than in those who had received such therapy for 2 years. These results show that long-term glucocorticoid therapy decreases the number of lymphocytes and increases neutrophil numbers in the airways.