Rare Case of Small-Cell Carcinoma Arising from the Endometrium with Paraneoplastic Retinopathy

We present the fourth known case of endometrial carcinoma, and the second case of endometrial small-cell carcinoma, to be associated with paraneoplastic retinopathy. Initial symptoms were decreased visual acuity and a narrowing of the visual field. Endometrial carcinoma was diagnosed several months later. An antibody to 34-kDa bovine retinal antigen was detected in the patient's serum. Thus, autoimmunity was suspected as the cause of the retinopathy. In patients with endometrial carcinoma with visual disturbance of unknown cause, paraneoplastic retinopathy should be suspected.     

Tumor Response to Neoadjuvant Chemotherapy Correlates with the Expression of P-Glycoprotein and PCNA but Not GST-π in the Tumor Cells of Cervical Carcinoma

Objective.To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas.Methods.We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathioneS-transferase π (GST-π), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied.Results.Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P< 0.005) and low PCNA labeling (P< 0.05), but not GST-π expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-π nor PCNA was correlated with the patient survival.Conclusion.Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.     

The effect of RO15-1788 on cardiovascular depression caused by fentanyl and diazepam

Cardiovascular depression occuring when diazepam is combined with fentanyl has been investigated using the benzodiazepine antagonist RO15-1788 in the dog.After the initial administration of fentanyl (40mcg/kg), the mean arterial pressure (MAP) decreased to 89% of its control value. Following the administration of diazepam (1.2mg/kg), the MAP and the total peripheral resistance (TPR) decreased significantly, to 75% and 83% of their control values respectively. After the administration of RO15-1788 (0.4mg/kg), the MAP increased significantly to 90% and the TPR to 102% of their control values and, lastly, the administration of naloxone (40mcg/kg) increased the MAP to 108% of its control value. No relationship was found between the changes in the catecholamines and the changes in the MAP after the administration of fentanyl, diazepam, and RO15-1788.The mechanism of circulatory depression when diazepam was used with fentanyl is interpreted as being a peripheral vasodilatory effect of diazepam acting by way of the benzodiazepine receptors since RO15-1788 was found to antagonize this effect.(Sone T, Kato T, Tsukahara I et al.: The effect of RO15-1788 on cardiovascular depression caused by fentanyl and diazepam. J Anesth 2: 69–76, 1988)     

Cellular localization of Babesia bovis merozoite rhoptry-associated protein 1 and its erythrocyte-binding activity

The cellular localization of Babesia bovis rhoptry-associated protein 1 (RAP-1) and its erythrocyte-binding affinity were examined with anti-RAP-1 antibodies. In an indirect immunofluorescent antibody test, RAP-1 was detectable in all developmental stages of merozoites and in extracellular merozoites. In the early stage of merozoite development, RAP-1 appears as a dense accumulation, which later thins out and blankets the host cell cytoplasm, but retains a denser mass around newly formed parasite nuclei. The preferential accumulations of RAP-1 on the inner surface of a host cell membrane and bordering the parasite's outer surface were demonstrable by immunoelectron microscopy. An erythrocyte-binding assay with the lysate of merozoites demonstrated RAP-1 binding to both bovine and equine erythrocytes. Anti-RAP-1 monoclonal antibody 1C1 prevented the interaction of RAP-1 with bovine erythrocytes and significantly inhibited parasite proliferation in vitro. With the recombinant RAP-1, the addition of increasing concentrations of Ca(2+) accentuated its binding affinity with bovine erythrocytes. The present findings lend support to an earlier proposition of an erythrocytic binding role for RAP-1 expressed in B. bovis merozoites and, possibly, its involvement in the escape of newly formed merozoites from host cells.     

Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice

We have previously shown that tumor necrosis factor-α (TNF-α), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-α was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-α exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-α, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation.     

Existence of phenol oxidase in the argasid tick Ornithodoros moubata

Phenol oxidase (PO, EC 1.10.3.1) activity was detected in the hemolymph of the fourth instar nymphs of the argasid tick, Ornithodoros moubata, with peak levels corresponding to the days before the majority of the nymphs had molted, suggestive of a protective role of PO during the ecdysial phase. Higher PO activity was detected in plasma relative to the hemolymph and was negligible in hemocytes. The concentration of the hemolymph and plasma assayed clearly influenced the level of PO activity, and was significantly reduced ( P<0.005) after treatment with 1-phenyl-2 thiourea, a specific PO inhibitor. This is the first report of the existence of PO in the hemolymph and plasma of a soft tick species. The regulation of PO activity and its precise role in soft tick immunity, particularly during the ecdysial phase, are interesting and need to be examined further.     

Roles of the Maltese cross form in the development of parasitemia and protection against Babesia microti infection in mice

Babesia microti, a hemoprotozoan parasite of rodents, is also important as a zoonotic agent of human babesiosis. The Maltese cross form, which consists of four masses in an erythrocyte, is characteristic of the developmental stage of B. microti. Monoclonal antibody (MAb) 2-1E, which specifically recognizes the Maltese cross form of B. microti, has been described previously. In the present study, we examined the roles of the Maltese cross form during the infectious course of B. microti in mice. The number of the Maltese cross form increased in the peripheral blood of infected mice prior to the peak of parasitemia. With confocal laser scanning microscopy, MAb 2-1E was found to be reactive with the ring form, with the parasites undergoing transformation to the Maltese cross form and subsequent division, and also with extracellular merozoites. Furthermore, the Maltese cross form-related antigen (MRA) gene was isolated from a B. microti cDNA library by immunoscreening with MAb 2-1E, and the nucleotide sequence was determined. Genomic analyses indicated that the MRA gene exists as a single-copy gene in B. microti. Immunization of mice with recombinant MRA induced significant protective immunity against B. microti infection. These findings indicate that the Maltese cross form plays important roles in both the development of parasitemia and the protective response against the infection.     

Clinicopathologic features and incidence of invasive lobular carcinoma in Japanese women

Intending to clarify the true Incidence of Invasive lobular carcinoma of the breast In Japanese women as well as the frequency of unilateral multlcentriclty, 362 cases of clinically defined monocentrlc breast cancer without pre-operative biopsy (previously fine needle aspiration or needle biopsy were routinely carried out for every case) were examined by whole mammary gland serial sectioning. On the basis of pathology and the World Health Organization classification of breast tumors, each case was assigned to one of two main histologlc types: Invasive lobular carcinoma (ILC) or Invasive ductal carcinoma (IDC). Invasive lobular carcinoma was further separated into classic and variant types by employing previously published criteria. Twenty-one cases of ILC (5.8%) were diagnosed, which Is more than In most previous Japanese studies. Unilateral multicentric breast carcinoma was detected In 9.5% of ILC and 16.1% of IDC (the difference was found not significant). Microscopically, ILC tumors were found to be, on average, larger than IDC. Patients with classic type ILC tended to be younger than those with variant type or IDC. Estrogen receptor expression was found more frequently In variant type ILC than in classic type. These results suggest that the incidence of invasive lobular carcinoma of the breast In Japanese women is low and that unilateral multicentricity Is not significantly higher in ILC than in IDC.     

Fate redirection of hippocampal astrocytes toward neuronal lineage by aggregate culture

Mammalian cells that have been committed to a certain cell lineage cannot be directed to other lineages. However, some astrocytes in the mammalian brains have been reported to represent plasticity to redirect to other cell lineages. We found that mouse hippocampal astrocytes cultured in aggregate forms of "astrosphere", redirected to MAP2-positive immature neurons. In astrospheres, basic HLH factors positively regulating neuronal differentiation were up-regulated and Id3 inhibiting basic HLH factors was down-regulated. Ectopic Id3 induction repressed redirection of astrocytes to a neuronal lineage, suggesting that astrosphere formation induced plasticity of astrocytes by changing the gene expression patterns.