Parvalbumin in rat cerebrum, cerebellum and retina during postnatal development

Radioimmunoassay and immunohistochemical studies were performed on the occurrence and distribution of parvalbumin-like immunoreactivity (PA-LI) in developing rat cerebrum, cerebellum and retina. No PA-LI was detected in the nervous tissues of the newborn animals. In the cerebrum, the PA-LI appeared in non-pyramidal neurons at the 2nd postnatal week and increased linearly until the 8th week. In the cerebellum, a rapid increase in the PA-LI took place at the 2nd week, with an enrichment of the antigen to Purkinje neurons. In the retina, amacrine cells contained PA-LI, the levels of which increased from the 2nd to 4th week. Regulation of intracellular Ca²⁺ concentration may be one of the important factors for the maturation of the central nervous system.     

Hypoxia-ischemic insult in neonatal rats induced slowly progressive brain damage related to memory impairment

The present study was designed to determine potential associations between the brain damage induced by hypoxic-ischemic (HI) insult and spatial learning impairment in an eight-arm radial maze task. We first determined the pathological outcomes after 2, 5, 9, and 17 weeks of recovery following the HI insult. The results show that the brain damage progressed from 2 up to 17 weeks of recovery. To clarify the time course of the brain damage changes, we investigated the histological changes of the same individual with magnetic resonance imaging (MRI) after 5, 9, and 57 weeks of recovery following the HI insult. The MRI changes were similar to the histological changes, and the brain damages were exacerbated in the contralateral hemisphere after 57 weeks of recovery following the HI insult. To investigate whether alteration in brain function was correlated with MRI and histological changes, the rats were made to find their way through an eight-arm radial maze was performed at either 7th or 16th weeks of recovery. According to the results, the spatial learning impairments of rats in the maze starting at 16 weeks of recovery were more severe than those at 7 weeks of recovery, indicating that the impairments were progressive and depended on the degree of brain damage. The results of the present study are the first demonstration that the evolutional and specific brain damage following the HI insult is slowly and progressively exacerbated to the contralateral hemisphere and rats who experience the HI are at risk for showing a late impairment of brain function.     

Hereditary pressure-sensitive neuropathy: demonstration of "tomacula" in motor nerve fibers.

By studying intramuscular nerves in 2 patients from 2 families with hereditary pressure-sensitive neuropathy (HPSN), the occurrence of abnormal thickening of myelin sheaths ("tomacula") was for the first time demonstrated in motor nerve fibers. Furthermore, the tomacula were found to line up on certain axons instead of being randomly distributed. These results indicate that the recurrent mononeuropathies of HPSN arise from an underlying asymptomatic motor and sensory polyneuropathy. It is also suggested that some signals emanating from the axons might be related to the formation of tomacula on the basis of the genetically determined myelination disorder.     

CD98 regulates the phosphorylation of HER2 and a bispecific anti-HER2/CD98 antibody inhibits the growth signal of human breast cancer cells

Human epidermal growth factor receptor (HER) family proteins are currently major targets of therapeutic monoclonal antibodies against various epithelial cancers. However, the resistance of cancer cells to HER family-targeted therapies, which may be caused by cancer heterogeneity and persistent HER phosphorylation, often reduces overall therapeutic effects. We herein showed that a newly discovered molecular complex between CD98 and HER2 affected HER function and cancer cell growth. The immunoprecipitation of the HER2 or HER3 protein from lysates of SKBR3 breast cancer (BrCa) cells revealed the HER2-CD98 or HER3-CD98 complex. The knockdown of CD98 by small interfering RNAs inhibited the phosphorylation of HER2 in SKBR3 cells. A bispecific antibody (BsAb) that recognized the HER2 and CD98 proteins was constructed from a humanized anti-HER2 (SER4) IgG and an anti-CD98 (HBJ127) single chain variable fragment, and this BsAb significantly inhibited the cell growth of SKBR3 cells. Prior to the inhibition of AKT phosphorylation, BsAb inhibited the phosphorylation of HER2, however, significant inhibition of HER2 phosphorylation was not observed in anti-HER2 pertuzumab, trastuzumab, SER4 or anti-CD98 HBJ127 in SKBR3 cells. The dual targeting of HER2 and CD98 has potential as a new therapeutic strategy for BrCa.     

Studies of effects of anticancer agents in combination with/without hyperthermia on metastasized human bladder cancer cells in chick embryos using the polymerase chain reaction technique

Cultivated T24 cells derived from a human bladder cancer were inoculated into the chorioallantoic membrane vein of chick embryos. Hyperthermic treatment was performed following injection of anticancer agents 3 days after the inoculation of the T24 cells. DNA samples were obtained from the livers of the chick embryos, and the polymerase chain reaction technique was used to amplify a DNA fragment specific to the human -globin gene. The Southern hybridization method was used to evaluate the inhibitory effects of anticancer agents in combination with/without hyperthermia on T24 cells metastasized to the liver. The hyperthermia exerted an inhibitory effect on the growth of the T24 cells in the livers of the chick embryos, and this was dependent on the thermal dose. The antitumor effects of hyperthermia performed at 42.5° C for 20 min and at 43.0° C for 10 min were evidenced by 69.2% an 82.0% inhibition of the growth of the metastasized T24 cells, respectively, as compared with the growth of untreated T24 cell. Hyperthermia performed at 42.5° C for 10 min alone produced 26.7% tumor growth inhibition, and these conditions for hyperthermia were subsequently used as a criterion for evaluating the effects of its combination with various anticancer agents. Adriamycin (20 g/egg) alone, mitomycin C (10 g/egg) alone, carboplatin (10 g/egg) alone, and cisplatin (10 g/egg) alone produced 13.5%, 58.9%, 27.3%, and 29.1% tumor growth inhibition, respectively. Adriamycin and mitomycin C applied in combination with hyperthermia showed additive inhibitory effects on the growth of the metastasized T24 cells in this chick embryo model.     

Disseminated intravascular coagulation in a man with metachronous bone metastasis from gastric-cancer - case-report

We report on a case of multiple bone metastasis and disseminated intravascular coagulation (DIG) in a 49-year-old Japanese man. He underwent total gastrectomy for advanced gastric cancer in July 1992, He was diagnosed as a case of multiple bone metastasis in August 1993. Severe anemia, thrombocytopenia, and elevated fibrinogen degradative products were indicative of DIG. He was treated with sequential i.v. administration of methotrexate (MTX) and 5-fluorouracil (5-FU) and continuous i.v. infusion of heparin and gabexate mesilate. After two weeks of treatment with MTX combined with 5-FU, the findings of DIC disappeared and his general condition improved dramatically.