A Comparative Study of DCMP versus DCcMP Combination Chemotherapy for Adult Acute Leukemia

An experimental study using L-1210 mouse leukemia indicatedthat daunomycin, cyclocytidine, and 6-mercaptopurine (DCcM)combination chemotherapy was more effective than daunomycin,cytosine arabinoside, and 6-mercaptopurine (DCM). Based on theseresults, a clinical study comparing daunomycin, cytosine arabinoside,6-mercaptopurine, and predni-solone (DCMP) combination chemotherapywith daunomycin, cyclocytidine, 6-mercaptopurine, and prednisolone(DCcMP) in the treatment of adult acute nonlymphocytic leukemiawas conducted. Patients were randomly allocated to receive eitherregimen. Ten of 15 patients treated with DCMP had complete remissionfor a median duration of 43 weeks and one had partial remission.Seven of 15 patients treated with DCcMP had complete remissionfor a median duration of 18 weeks and two had partial remission.The patient characteristics before chemotherapy, the toxicityof the chemotherapeutic regimens and the causes for differencesin antitumor activity between the experimental study and theclinical study are discussed.     

Multiple Dural Arteriovenous Fistulas Causing Rapid Progressive Dementia Successfully Treated by Endovascular Surgery: Case Report

A 67-year-old female presented with multiple dural arteriovenous fistulas (AVFs) manifesting as dementia rapidly progressing over 2 months. The initial diagnosis was Creutzfeldt-Jakob disease based on the acute clinical course. However, angiography eventually revealed multiple dural AVFs involving the bilateral convexities to the superior sagittal sinus and the right transverse-sigmoid sinus. Endovascular treatment combining arterial and venous embolization in multiple stages proved to be effective, as the hemodynamic pathology improved, and the patient recovered from dementia. The cause of the dementia was thought to be venous hypertension in the deep white matter induced by the dural AVFs. Dural AVFs should be included in the differential diagnosis of rapidly progressive dementia.     

Distribution of EGF receptor expressing and DNA replicating epidermal cells in psoriasis vulgaris and Bowen''s disease

We have examined the localization of DNA replicating cells and EGF receptor-expressing cells in the epidermis of psoriasis vulgaris, a benign hyperproliferative skin disease, and Bowen's disease, a pre-malignant hyperproliferative skin disease, and normal skin. DNA replicating cells were detected by anti-BrdU monoclonal antibody after incubating tissue sections with BrdU, and EGF receptors were detected by the anti-EGF receptor monoclonal antibody B4G7. In normal skin, DNA replicating cells were localized exclusively in the basal and suprabasal layers. EGF receptor expression was observed most strongly in the basal and parabasal layers, but diminished gradually towards the upper squamous layer. In psoriatic skin, DNA replicating cells were also localized in the basal and parabasal layers, but the number of these mitotic cells was about 10 times higher than in normal skin. In this case, more EGF receptors were detected in all viable layers of the epidermis. Apparently normal skin adjacent to psoriasis lesions showed persistent expression of EGF receptors in the upper squamous layer without an increased number of DNA replicating cells in the basal and parabasal layers. In Bowen's disease, DNA replicating cells and EGF receptor expressing cells were distributed in all layers of the epidermis. These findings indicate that the increased production of EGF receptors may be, in part, responsible for the hyperproliferative state of the epidermis and that cells in the upper squamous layer of psoriasis may have lost a mechanism by which EGF receptor expression is diminished thus allowing differentiation. This altered process of EGF receptor production may be involved in the onset of psoriasis vulgaris.     

Possible Involvement of Hypothyroidism as a Cause of Lithium-Induced Sinus Node Dysfunction

Although several reports have stated that even therapeutic levels of lithium can induce sinus node dysfunction, the mechanism has not been fully elucidated. We present here two patients with sinus node dysfunction after long-term lithium therapy. Following lithium discontinuation, sinus node function recovered completely. After resuming lithium, however, irreversible sinus node dysfunction recurred and a permanent pacemaker was implanted in one patient. The serum concentration of lithium was within therapeutic levels. Nevertheless, hypothyroidism was associated with the sinus node dysfunction in both patients. Thus, thyroid function may play an important role in sinus node dysfunction induced by lithium. (PACE 1999; 22[Pt. I]-.954-957) lithium, sinus node dysfunction, hypothyroidism, sick sinus syndrome     

Jak3 expression in glomerular epithelia of IgA nephropathy (IgA-N) patients

Jak3 is a member of the Janus kinase family which plays an important role in cytokine signal transduction. Jak3 associates the γ_c chain of receptors for IL-2, IL-4, IL-7, IL-9 and IL-15, and is essential for the signal transduction of these cytokines. We have isolated Jak3 kinase from renal mesangial cells and demonstrated the constitutive expression of Jak3 in glomeruli in vivo. To investigate the physiological and pathological role of Jak3 in glomeruli, we prepared anti-Jak3 antibody and analysed the localization of Jak3 in glomeruli of renal biopsy samples from various nephritis patients and normal subjects. Among 61 nephritis patients and four normal subjects investigated in the present study, Jak3 was selectively localized to glomerular epithelia of IgA-N patients (14/34 cases) and focal glomerulosclerosis patients (1/5 cases), but not detected in minimal changes (n = 6), membranous glomerulonephropathy (n = 7), crescentic glomerulonephritis (n = 4), lupus nephritis patients (n = 5), and normal subjects (n = 4). The intense immunoreactivity for Jak3 is significantly associated with the decrease in creatinine clearance (81.5 ± 10.4 ml/min versus 104.3 ± 29.6 ml/min; P < 0.05, Student’s t-test) and the increase in level of serum creatinine (1.13 ± 0.33 mg/dl versus 0.75 ± 0.23 mg/dl; P < 0.01, Student’s t-test) in IgA-N patients. Furthermore, γ_c chain was concomitantly expressed with Jak3 in glomerular epithelia in vivo and in vitro, suggesting that signal transduction via γ_c-Jak3 cascade may be involved in the pathogenesis of glomerular injury of IgA-N. Taken together with the recent findings that IL-4-secreting T lymphocytes in affected glomeruli injure glomerular epithelium, the responsiveness of glomerular epithelium for IL-4 may be pathologically enhanced in IgA-N.     

Reduced amount of intestinal mucus by treatment with anti-CD4 antibody interferes with the spontaneous cure of Nippostrongylus brasiliensis-infection in mice

Mechanism of spontaneous cure was studied in mice infected with mouse-nonadaptive Nippostrongylus brasiliensis. Adult BALB/c mice were cured spontaneously of infection with this strain of N. brasiliensis by Day 7 post-infection. Expulsion of intestinal worms was delayed dose-dependently by a treatment with anti-CD4 antibody. However, the treatment had no significant effect on larval recovery from the lungs. Treatment of mice with anti-IL-5 antibody suppressed intestinal tissue eosinophilia induced by the infection, but did not affect intestinal worm recovery. Antigen specific IgE antibody was not detected in the sera obtained from Days 5 to 15. Therefore, IL-5 and specific IgE antibody are probably not important in the spontaneous cure. Treatment of mice with anti-CD4 antibody had no significant effect on number of intestinal goblet cells or on expression of terminal sugars of goblet cell mucins. However, histological and quantitative analyses revealed that significantly less intestinal mucus was released in anti-CD4 antibody treated mice than in control mice. These results suggest that CD4+ lymphocytes control the amount of intestinal mucus and consequently the reduced mucus interferes with the spontaneous cure. Quantity of mucus released in the intestinal lumen may have an essential role in the spontaneous cure ofN. brasiliensis-in/fcfio/i of mice.