Vermis lesions in acute cerebellar ataxia: a sequential imaging study

We report a case of acute cerebellar ataxia (ACA) with discrete paleocerebellar clinical symptoms who underwent serial cranial magnetic resonance images not only with conventional spin echo sequences but also fluid attenuated inversion recovery (FLAIR) sequences. The images with the latter sequences demonstrated more conspicuously the high signal intensity lesions in the superior cerebellar vermis and cerebellar peduncle than those with the former sequences. In the convalescent phase, the lesions became markedly atrophic. Thus, the causative lesions for ACA were demonstrated on MRI, and FLAIR provided clear images of the lesion in the vermis.     

Clinical study of penile cancer]

Recent progress in molecular biology suggests a certain relationship between penile cancer and human papilloma virus infection. However, the treatment for penile cancer has not been established since each institute has experienced only a small number of patients. We analyzed the result of our treatment for 14 penile cancer patients during past twenty years. Ten of the 14 patients were initially treated for the primary lesion with a combination of peplomycin (PEP) or bleomycin (BLM) and radiation therapy. Of these, 9 were found not to have residual viable cancer cells in their primary lesions. No local recurrence was found in all 7 patients in whom the penis was preserved. This result suggests that combination of PEP (BLM) and radiation preserves the penis without increasing the risk of local recurrence. Penile cancer-related death did not occur in patients without lymph node metastasis. However, this cancer death did occur in 4 out of 7 patients with lymph node metastasis, suggesting that metastasis is one of the important prognostic factors. PEP (BLM) and radiation therapy with or without regional lymph node dissection did not improve the prognosis of patients with advanced penile carcinoma, such as with pN2, pN3 or distant metastasis. More effective management may be necessary for these patients.     

Unilateral sudden deafness as a primary symptom of brainstem and cerebellar infarction]

We report a case with a unilateral sudden sensorineural hearing loss caused by an infarction of brainstem and cerebellum. The patient was a 74-year-old male presented with a sudden onset of hearing loss and tinnitus in the right ear and dizziness. Steroid was administered on suspicion of idiopathic sudden deafness. However, the initial symptoms were deteriorated approximately 2 weeks later. He newly complained of the numbness of the right face and double vision, and he was transferred to our hospital for further evaluation. Neurological examination demonstrated horizontal nystagmus, diminution in the right facial sensation, right peripheral facial palsy, right hearing loss and cerebellar ataxia. Urgent MRI disclosed fresh infarctions of the right middle cerebellar peduncle and cerebellum localized in the territory of anterior inferior cerebellar artery. In general, idiopathic sudden deafness and Meniere's disease are frequent diagnosis in cases of sudden hearing loss with vertigo, but these symptoms may rarely be caused by cerebrovascular disorder. In patients with risk factors for arteriosclerosis, cerebrovascular disorder should be taken into consideration even if idiopathic sudden deafness may be suspected clinically. We emphasize the diagnostic importance of careful observation on neurological findings and early detection of radiological abnormalities on MRI.     

Disposition and excretion of Irgasan® DP300 and its chlorinated derivatives in mice

The distributions of radioactivity were examined by whole body autoradiography and liquid scintillation spectrophotometry in male ddY mice following oral administration of tritium-labelled Irgasan^® DP300 (2,4,4-trichloro-2-hydroxydiphenyl ether) (I) and its three chlorinated derivatives; 2,3,4,4-tetrachloro-2-hydroxydiphenyl ether (II), 2,4,4,5-tetrachloro-2-hydroxydiphenyl ether (III) and 2,3,4,4,5-pentachloro-2-hydroxydiphenyl ether (IV). The autoradiograms at 6 or 24 hr showed that the radioactivity distributed in the gall, liver, lung, heart, and kidneys. Among these tissues the radioactivity was most concentrated in the gall, suggesting the enterohepatic circulation of these compounds. A much higher level of radioactivity in each tissue was observed in mice receiving [³H]-III than the other compounds tested. Most of the radioactivity disappeared from each tissue in 24 hr due to [³H]-Irgasan DP300, [³H]-II or [³H]-IV, but in 96 hr it was due to [³H]-III.The cumulative radioactivity excreted in urine after administration of these compounds was in the order of [³H]-Irgasan DP300, [³H]-II, [³H]-IV and [³H]-III while that in feces was in the order of [³H]-IV, [³H]-III, [³H]-II and [³H]-Irgasan DP300,This work was presented at the 106th Annual Meeting of the Pharmaceutical Society of Japan (1986).     

Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs

We investigated the relative effects of 0.5, 1.0, 1.5, 2.0 MAC halothane and enflurane, and concurrent noxious stimulus on hepatic blood flow and oxygen consumption in 14 mongrel dogs randomly divided into groups of seven each. Hepatic arterial and portal venous blood flow (HABF and PVBF, respectively) were measured continuously using ultrasonic transit time flow meter. Mean arterial blood pressure (MAP), cardiac index (CI), hepatic oxygen supply, and hepatic oxygen consumption (H _{O 2}) were measured. Halothane significantly deceased HABF, but not PVBF in a dose dependent manner. Enflurane did not affect HABF and PVBF significantly. MAP and CI decreased in both groups, with halothane producing more marked decreases than enflurane. H _{O 2} did not change with enflurane, but did with halothane, producing significant differences, with halothane being greater at 1.5, 2.0 MAC. A noxious stimulus only caused minor change in blood flow. The results suggest that liver blood flow and oxygen consumption are affected differently by halothane and enflurane and that halothane has a stronger tendency to cause an imbalance between liver oxygen supply and consumption than dose enflurane.(Masaki E, Yasuda N, Tanifuji Y et al.: Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs. J Anesth 3: 118–122, 1989)     

Perforin-dependent killing of tumor cells by Vgamma1Vdelta1-bearing T-cells

The T-cell subset expressing Vdelta2 paired primarily with Vgamma2 comprises a majority of gammadelta T-cells in human adult peripheral blood and expands significantly during a variety of infectious diseases. In contrast, the other subset of gammadelta T-cells that express Vdelta1 is rare among circulating T-cells and its function is poorly understood. Here, we show that a Vgamma1Vdelta1(+) T-cell line, 3-D, established from human peripheral blood by immortalization with Herpesvirus saimiri was able to specifically recognize tumor cells, such as K562 cells, and release cytotoxic granules containing perforin for target cell killing. Some tumor cells, including Daudi cells that are known to be susceptible to killing by Vdelta2(+) T-cells, were resistant to 3-D killing, implicating distinct pathways for tumor cell control by Vdelta1(+) and Vdelta2(+) T-cells. The 3-D T-cell receptor (TCR):CD3 complex reconstituted in TCR-deficient Jurkat cells was capable of transmitting signals, evidenced by activation of the interleukin 2 (IL-2) gene following ligation with anti-CD3 antibody, yet the TCR-reconstituted cells failed to produce IL-2 in response to the target cells. Thus, these results raise the possibility that some Vgamma1Vdelta1(+) T-cells could potentially be stimulated and lyse tumor cells via ligation of TCR/CD3-unassociated molecules.     

Anti-idiotypes to oxidized LDL antibodies in intravenous immunoglobulin preparations--possible immunomodulation of atherosclerosis

OBJECTIVE: The aim of this study was to examine whether intravenous immunoglobulin (IVIg) preparations contain anti-oxLDL and anti-anti-oxLDL antibodies. BACKGROUND: Oxidized low-density lipoprotein (oxLDL) is one of the major players in atherogenesis. IVIg can reduce atherosclerosis in experimental animal models. METHODS: Six commercial IVIg preparations were tested for the presence of anti-oxLDL antibodies by EIA. Inhibition studies were performed with the different IVIg preparations and IgGs purified from a pool of sera from patients with high anti-oxLDL antibody levels. Absorption assays were carried out to evaluate the presence of anti-idiotypes against anti-oxLDL antibodies in IVIg preparations. RESULTS: IVIg preparations tested had various degrees of reactivity towards oxLDL. Absorption experiments suggested that the reactivity was specific because it could be effectively absorbed by oxLDL and not by an irrelevant antigen PPD. The reactivity was smaller than that observed with the IgG from the pool with high anti-oxLDL antibody levels. Inhibition studies with IVIg demonstrated 20-45% inhibition of anti-oxLDL binding to oxLDL, compared to 76% inhibition by the pool with high anti-oxLDL levels. To investigate the presence of anti-idiotypes against anti-oxLDL antibodies within IVIg, F(ab')2 fragments of IVIg IgG were used to absorb IgG F(ab')2 fragments from the pool of sera with high anti-oxLDL levels. The decreased binding to oxLDL of the absorbed supernatants shows that IgG F(ab')2 fragments of the IVIg preparations had high inhibitory capacities ranging from 65 to 90%. CONCLUSIONS: IVIg preparations contain both anti-oxLDL and anti-anti-oxLDL activity. This finding may explain the immunomodulating effect of IVIg in atherosclerosis.     

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.     

Evaluation of anti-parvovirus B19 activity in sera by assay using quantitative polymerase chain reaction

Human parvovirus B19 (B19) infects cells of erythroid lineage. Production of neutralizing antibodies (Abs) is indispensable for recovery from B19-related disease state. In this study, we used a convenient method to measure neutralizing activities in human sera by using a real-time quantitative PCR based assay. Erythroid cell line KU812Ep6 was incubated with test sera before infection with B19 virus. The copy number of B19-DNA in cultures was decreased in the presence of the sera from patients who recovered from acute B19 infection, whereas no decrease in B19-DNA was in cultures incubated with sera from healthy volunteers who had no B19 infection. The decrease in B19-DNA copy number was calculated and the inhibition percentage was expressed as neutralizing activity to B19. A clinical study showed that the levels of neutralizing ability were high in patients who recovered soon after acute B19 infection, but were low in some patients with a prolonged clinical course for recovery from B19 infection. This method is simple and convenient compared with methods described previously, showing its usefulness to evaluate the neutralizing activity to B19.