Striatal cells containing the Ca2+-binding protein calretinin (protein 10) in ischemia-induced neuronal injury

The present study concerns the vulnerability of striatal interneurons immunopositive for the Ca²⁺-binding protein calretinin to ischemic neuronal injury. An immunohistochemical study was carried out on the striata of rats which had undergone transient middle cerebral artery occlusion. Two weeks after the ischemia, there was a marked reduction in the number of calretinin-positive neurons in the ipsilateral ischemic lesion, although the striatal interneurons positive for parvalbumin, which are a neuronal population distinct from the calretinin-immunoreactive cells in the striatum, were spared in the insulted areas. The present data indicate that the striatal calretinin-positive neurons are less resistant to transient ischemia, suggesting that there may exist vulnerability differences among the striatal interneurons in ischemia-induced neuronal injury.     

Type of lymphocytes affected by the islet-activating protein (IAP)

By flow cytometric analysis, we identified the subclass of lymphocytes that proliferates in response to islet-activating protein (IAP), both in vitro (human peripheral blood mononuclear cells, MNC, cultured with IAP) and in vivo (peripheral blood MNC derived from A/J mice treated with IAP). IAP caused a preferential proliferation of CD8+ T cells. These cells expressed the IL-2 receptors on their surface. CD4+ CD8+ T cells could also be detected in these cultures, IAP caused human MNC to produce IL-1 and to induce expression of HLA-DR antigen. These effects may play an important role in the T-cell proliferation induced by IAP, although IAP by itself suppressed the proliferative action of IL-1 in mouse thymocytes. IAP induced proliferation of the purified CD4+ cells but had a smaller effect on the purified CD8+ cells. This suggests that the proliferation of CD8+ cells in IAP-treated MNC depends on the function of other types of cell, e.g. CD4+ cell and macrophage.     

Brain metastasis from malignant fibrous histiocytoma of the heart: case report

This is the second reported case of a malignant fibrous histiocytoma of the heart that metastasized to the brain. A 33-year-old woman developed headache, nausea, and ataxic gait 9 months after removal of the tumor from the left atrium of the heart. Computed tomographic and magnetic resonance imaging scans disclosed multiple metastatic tumors in the brain. Although dramatic improvement in her symptoms and signs followed the removal of the brain tumors, she died of tumor recurrence in the left atrium 3 months after the removal of the metastatic brain tumors.     

Metabolic syndrome, C-reactive protein and increased arterial stiffness in Japanese subjects.

The aim of this study was to investigate whether the metabolic syndrome (MS) was associated with an elevated level of C-reactive protein (CRP) and increased arterial stiffness, and to clarify whether combined MS and CRP data had a stronger relation to arterial stiffness than did MS data alone. Brachial-ankle pulse wave velocity (baPWV), CRP, and conventional risk factors were evaluated in 3,412 men and 854 women. Adjusted mean values of baPWV in men with 0, 1, 2, and > or = 3 components were 1,309, 1,372, 1,422, and 1,462 cm/s, respectively (p for trend <0.001). Adjusted mean values of baPWV in women with 0, 1, 2, and > or =3 components were 1,212, 1,292, 1,357, and 1,391 cm/s, respectively (p for trend <0.001). Adjusted geometric mean concentrations of CRP in men with 0, 1, 2, and > or = 3 components were 0.036, 0.049, 0.059, and 0.076 mg/dI, respectively (p for trend <0.001). Adjusted geometric mean concentrations of CRP in women with 0, 1, 2, and > or = 3 components were 0.023, 0.030, 0.057, and 0.077 mg/dI, respectively (p for trend <0.001). In analyses of adjusted mean values of baPWV according to the number of MS components and according to CRP levels within or without top quartile levels, the p value for the trend was significant (<0.001) in both men and women but, in post hoc analyses, comparing high and low CRP levels in each MS component-number group, no significant difference was found. These results suggest that, for prediction of increased arterial stiffness, combining MS and CRP data has little additive effect compared to the use of MS data alone.     

Anterior basal encephalocele of the neonatal and infantile period

Diagnosis of occult basal encephalocele is not difficult if the peculiar clinical and radiological signs of this anomaly are borne in mind. Recent surgery for transsphenoidal encephalocele has had better results than realized. However, high surgical risks may still be encountered in transsphenoidal encephalocele of the early infantile period, because the pituitary-hypothalamic structures are usually incorporated in the herniated encephalocele of this age group. Surgical indications for and operative approaches to transsphenoidal encephalocele in the infantile period are discussed on the basis of the authors' failure in transcranial repair, which resulted in early postoperative death due to hypothalamic dysfunction. Reviewing the reported cases of anterior basal encephalocele, a high correlation between transsphenoidal encephalocele, particularly in the pediatric age group, and allied malformations of the face, eye, and brain was disclosed. This characteristic malformation complex may be explained by a common pathogenetic mechanism operating in the embryonal period at about the stage of the anterior neuropore closure and occurring in the ventral surface of the cephalic end of the neural tube. Three cases of transsphenoidal encephalocele diagnosed in the neonatal period with progressive obstruction in the nasopharyngeal airway are also reported. A characteristic malformation complex consisting of median cleft face syndrome, optic nerve dysplasia, and agenesis of the corpus callosum was associated in two cases; the other patient had an extremely rare combination of septooptic dysplasia. Two patients died pre- and postoperatively, respectively; the other patient did not undergo operation because of grave multiple anomalies.     

Chemotherapy-induced anemia in patients with primary lung cancer.

To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05).     

Phase I Study of Paclitaxel by Three-hour Infusion: Hypotension Just after Infusion Is One of the Major Dose-limiting Toxicities

The primary objectives of this study were to determine the maximum tolerated dose (MTD) of paclitaxel administered by 3-h infusion to patients with solid tumors, and to characterize the pharmacokinetics of a 3-h infusion in comparison with those of a 24-h infusion. Twenty-seven patients each received one of six levels of paclitaxel, 105, 135, 180, 210, 240 and 270 mg/m², with premedication. Two patients given 240 mg/m² and one patient given 270 mg/m² unexpectedly had grade 3/4 hypotension just after finishing the paclitaxel infusion. Peripheral neuropathy was also dose-limiting at 270 mg/m². Although granulocytopenia was significantly less severe than with a 24-h infusion, more than half of the patients experienced grade 4 toxicity at doses of 240 or 270 mg/m². Severe hypersensitivity reactions (HSRs) were not observed. Pharmacokinetic studies using high performance liquid chromatography demonstrated proportionally greater increases in the peak plasma concentration and area under the curve, and decreases in clearance and volume of distribution with increasing dose, suggesting non-linear pharmacokinetics of paclitaxel when given by 3-h infusion. The MTD of paclitaxel given as a 3-h infusion was determined to be 240 mg/m² with dose-limiting toxicities of granulocytopenia, peripheral neuropathy and hypotension. Hypotension just after infusion, induced by 3-h infusion of paclitaxel, is a new observation which has not been reported previously. The recommended dose for phase II study is 210 mg/m². Although hypotension was observed as an unexpected toxic effect, paclitaxel could be administered safely over 3 h with premedication and proper monitoring, resulting in reduced myelotoxicity and with no increase in the incidence of HSRs as compared with a 24-h infusion.     

Synergistic effect of recombinant interleukin-2 on the inhibition of growth of adenocarcinoma 755 by mitomycin

The increase in life-span (ILS) of tumor-bearing mice caused by recombinant interleukin-2 (RIL-2) was studied in the solid tumor adenocarcinoma 755 system. With long-term treatment (Days 5-12), RIL-2 (10(5) U/mouse) showed a weak effect (24% ILS), but short-term RIL-2 treatment (Days 5-8 or 9-12) had hardly any effect. Mitomycin, at 2 mg/kg (maximum nontoxic dose), caused 35% ILS with Days 5-8 treatment and only 12% ILS with Days 9-12 treatment. Sequential treatment with mitomycin (Days 5-8) and RIL-2 (Days 9-12) markedly enhanced antitumor activity (88% ILS). This value is significantly greater than that of mitomycin alone or RIL-2 alone (P less than 0.01). Furthermore, mitomycin followed by RIL-2 markedly augmented killing activity of spleen cells that are cytotoxic in vitro. These results indicate that RIL-2 markedly affects the inhibition of growth of a tumor treated with an antitumor agent.     

Classification of human liver transplant recipients by their preoperative CD8+ T cell subpopulation and its relation to outcome.

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.     

Pharmacokinetic Study of Mitomycin C with Emphasis on the Influence of Aging

Mitomycin C (MMC) at a dose of 8 mg/m² was administered by short intravenous infusion to 14 cancer patients. All patients had normal renal, hepatic, cardiac and bone marrow functions. The plasma level of MMC, which was determined by high-performance liquid chromatography over a 24–h period after the infusion, fitted the 2-compartment model curve except for one patient. There was a significant correlation between the area under the time versus concentration curve (AUC) of MMC and the age of patients ( r = 0.558, P < 0.05). Pharmacokinetic parameters in one of the older (a 69-year-old male) patients were extremely different from those of the other 13 patients. This patient experienced severe myelosuppression, probably due to the markedly increased AUC of MMC. Our results suggest that a patient's age has a significant influence on the pharmacokinetics of MMC in patients with normal major organ functions and that in some patients, MMC pharmacokinetics may be altered, possibly due to interpatient variation in the activation or metabolic pathway of MMC.