Oral delivery of xeno-antigen combined with non-depleting anti-CD4 monoclonal antibody induces significantly prolonged survival of concordant skin xenograft

Abstract: Oral administration can induce unresponsiveness to protein antigens. Therefore, we examined whether oral administration of xeno-antigen could induce the prolonged survival of xenogeneic skin grafts. CBA mice were given 1 × 10⁷ SD rat splenocytes orally, 7 days before transplantation of a SD rat skin in the presence or absence of a non-depleting anti-CD4 monoclonal antibody (mAb) (YTS177, 200 µg/dose, −8 and −7 days relative to transplantation). All skin grafts survived with a median survival time (MST) of 62 days when xeno-antigens were administered orally in combination with anti-CD4 mAb. Mice treated with anti-CD4 mAb alone or oral administration of xeno-antigen alone induced modest prolonged survival of rat skin grafts (MST = 18 and 19 days, respectively) while naive mice rejected rat skin acutely (MST = 12 days). Oral administration alone or combined with anti-CD4 mAb reduced the level of xeno-antibody production compared with that in untreated mice after transplantation. Xenogeneic mixed leukocyte response was reduced when splenocytes from mice pre-treated with oral administration of xenogeneic cells were used as the responder compared with that in untreated mice. Oral delivery of xeno-antigen plus non-depleting anti-CD4 mAb can induce prolongation of concordant xenogeneic skin grafts.     

Serum immunosuppressive acidic protein as a potent prognostic factor for patients with metastatic renal cell carcinoma

BACKGROUND: Estimation of survival probability of individual patients with metastatic renal cell carcinoma was difficult owing to diverse prognostic factors. We analyzed serum immunosuppressive acidic protein (IAP) levels and the cutoff value, then tested its validity for assessing patients' prognoses. METHODS: Serum IAP was measured longitudinally in 84 patients with metastatic disease. Before therapy, cutoff levels of IAP were tested every 20 microg/ml between 600 and 1200 microg/ml. The prognostic importance of IAP and its cutoff level was estimated. RESULTS: The cutoff level of IAP was set at 800 microg/ml for 40 patients who had metastatic disease with the primary tumor in situ and for 44 patients with recurrent disease. IAP was found to be a significant prognostic factor for both patient groups. CONCLUSIONS: Serum IAP is an important prognostic factor for patients with metastatic renal cell carcinoma. Stratification of patients according to prognosis is feasible using the cutoff level.     

Penetrating keratoplasty and cataract surgery

Of 46 eyes undergoing simultaneous penetrating keratoplasty and cataract extraction, 25 grafts (54%) remained clear with an average follow-up of 37 months. This low success rate can be party explained by the fact that more than 50% of our patients had unfavourable ocular conditions preoperatively. In case of simultaneous procedures, methods of cataract extraction (ICCE or ECCE) did not have any significant affect on the rate of clear grafts. In eyes with favourable ocular conditions preoperatively, the rates of clear grafts were similar (approximately 75%) in cases of simultaneous operation (21 eyes) and separate operation (8 eyes).     

Development Of The Human Mesencephalic Trigeminal Nucleus: A Morphometric Study

Anatomical development of the human mesencephalic trigeminal nucleus was assessed quantitatively and qualitatively, using serial sections of brains, with the help of a computer-assisted image-analyser. Five fetuses at 16, 18, 21, 23 and 27 weeks of gestation; five neonates at 30, 32, 33, 35 and 40 weeks of gestation; a two-month-old infant and a 63-year-old adult were studied. Morphometric analyses of the mesencephalic trigeminal nucleus revealed that orocaudal columnar length and neuronal areas gradually increased with gestational age. Diversity of neuronal areas appeared after 32 weeks of gestation, but neuronal numbers and shapes showed little change throughout prenatal and postnatal life.     

Cytocidal activity of PBL, LAK, and IDEC-C2B8 and expression of HLA class 1, ICAM-1, and CD20 in vincristine-resistant hematologic cell lines.

This study was designed to determine whether the cytocidal activity of immunotherapy such as cytotoxic peripheral blood lymphocytes (PBL), lymphokine-activated killer (LAK) cells, and chimeric anti-CD20 mouse/human monoclonal antibody, IDEC-C2B8, overcome vincristine (VCR) resistance in cultured cell lines derived from human leukemia/lymphoma. In addition, the relation between the susceptibility to these immunotherapies and the expression levels of HLA class 1 and ICAM-1 as well as CD20 on the cell surface was analyzed. Three of six VCR-resistant cell lines were less susceptible to PBL cytotoxicity compared with wild-type cells, whereas the susceptibility was kept in the other three VCR-resistant cell lines. Four of six VCR-resistant cell lines were less susceptible to LAK activity and the other two cell lines were as sensitive to LAK cells as their wild-type counterparts. There was no correlation between the susceptibility for PBL cytotoxicity and the expression of HLA class 1 in both wild and VCR-resistant cells. In contrast, ICAM-1 in the two cell lines that showed decreased susceptibility for LAK cytotoxicity disappeared, although that in one cell line increased. IDEC-C2B8 was effective only against B-cell lines expressing CD20. One cell line in which the expression of CD20 increased was nearly six times more sensitive to IDEC-C2B8 than wild type. Thus, we concluded that the resistance to VCR in some tumor cell lines is associated with modified susceptibility for immunotherapies by the different expression of target molecules from those of wild-type counterparts.     

Functional neural reorganization following ischemic stroke in the precentral knob: an fMRI study]

We evaluated a 63 year-old, right-handed woman by functional MRI (fMRI) in the early and the recovery stages following a cerebral infarction in the right precentral knob. An activated signal in the ipsilateral sensorimotor cortex and contralateral supplementary motor cortex during deteriorated hand grasping (left) was observed in the early stages, whereas being unable to detect in the functionally recovered period. When simultaneous bilateral hand grasping was performed, the activated signal around infarct region was enlarged in recovered period. The functionally neural reorganization processes relating recovered hand movement after localized cortical infarction (precentral knob) was suggested.     

Clinical characteristics of seafood allergy and classification of 10 seafood allergens by cluster analysis]

The aim of this study was to investigate the clinical characteristics of children who showed sensitization to any type of seafood and to classify the 10 seafood allergens based on IgE reactivities by a cluster analysis. In children with bronchial asthma (BA) and/or atopic dermatitis (AD), we defined the 'seafood' group as 23 patients having any type of seafood specific IgE antibody (CAP system). We analyzed the clinical features, the serum total IgE and each allergen specific IgE level. In addition, ten seafood allergens were also classified by a cluster analysis. Three patients revealed immediate hypersensitivity to some seafood. The frequency of patients with AD and the total IgE in the seafood group were high and the patients in this group were tend to be sensitized to multiple allergens. Seafood allergens were classified into 4 groups, 1) salmon, sardine, horse mackerel and mackerel, 2) cod and tuna, 3) octopus and squid, and 4) crab and shrimp, by a cluster analysis. These findings corresponded to the biological classification and the classification by the reported common allergens among various types of seafood. Based on our findings, this classification is therefore considered to be useful when selecting allergens to screen for sensitization to seafood.     

Focal Perivascular Alterations of White Matter in Herpes Simplex Encephalitis —A Histological and Immunocytochemical Study—

Abstract: Several cases of human herpes simplex encephalitis treated with Vidarabin have been investigated with the histological and immunocytochemical techniques. Cases with a subacute evolution revealed areas of focal perivascular myelin destruction in the white matter. The distribution of herpes simplex antigen did not show any preferential localization of the virus in perivascular oligoglia! cells. In contrast, a spatial and temporal relationship has been found between the appearance of immunoglobulin-bearing cells around the vessels and that of areas of focal perivascular myelin damage. Therefore, it is postulated that the areas of focal destruction of myelin are not related to the cytotoxic effect of the virus but are rather dependent on the immune response of the host.     

Myosin light-chain kinase inhibitor, 1-(5-chlornaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), inhibits catecholamine secretion from adrenal chromaffin cells by inhibiting Ca2+ uptake into the cells

For determination of whether myosin light-chain kinase (MLCK) is involved in the secretory mechanism of adrenal chromaffin cells, the effect of a preferential inhibitor of the enzyme, 1-(5-chlornaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), on catecholamine secretion from cultured bovine adrenal chromaffin cells was studied. ML-9 did not affect basal catecholamine secretion, but inhibited catecholamine secretion stimulated by acetylcholine, high K+, veratridine or palytoxin. At similar concentrations to those inhibiting the secretion of catecholamine, ML-9 also inhibited increased [45Ca]2+ uptake by the cells induced by these stimulants. However, it did not inhibit catecholamine secretion induced by the Ca2+ ionophore A23187. Moreover, it did not affect catecholamine secretion from digitonin-permeabilized cells induced by a micromolar Ca2+ concentration in the presence of Mg ATP. These results indicate that ML-9 inhibits catecholamine secretion from adrenal chromaffin cells by inhibiting the transmembrane Ca2+ uptake mechanism, but not by inhibiting the intracellular Ca2+-dependent mechanism. The possible role of MLCK in stimulus-secretion coupling in adrenal chromaffin cells is discussed.