Post-menopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin levels.

BACKGROUND: Serum undercarboxylated osteocalcin (ucOC) is a biochemical bone marker of vitamin K insufficiency. It had been reported that bone resorption inhibitors tend to decrease the serum ucOC level in patients with primary osteoporosis. In rheumatoid arthritis (RA) patients, these results have never been reported. AIM: We investigated risk factors which could change serum ucOC level in post-menopausal women with RA (no.=100). SUBJECTS AND METHODS: Twenty patients received no bone resorption inhibitor (control), 30 received raloxifene (RLX), while 50 received alendronate (ALN). This cross-sectional study was limited to patients with low RA disease activity (Disease Activity Score-28 ≤3.2). We measured serum ucOC, and the data were analyzed by multivariable analysis, including ucOC and the other variables. RESULTS: Scheffe's F test demonstrated a significant difference in serum ucOC levels between controls and the RLX group (p<0.01), and between controls and the ALN group (p<0.01). Serum ucOC levels were low in both treated groups. An adjusted multivariate analysis was performed for the variables: bone resorption inhibitor use, serum alkaline phosphatase, glucocorticoid dose, age, estimated glomerular filtration rate and matrix metalloproteinase 3. As a result, serum ucOC inversely correlated with bone resorption inhibitor use (p<0.01) and oral glucocorticoid dose (p<0.01), which were independent risk factors of lowering ucOC. CONCLUSIONS: Bone resorption inhibitors and glucocorticoids were independent risk factors for lowering serum ucOC levels in post-menopausal RA patients.

Serum undercarboxylated osteocalcin level increases with 48 weeks of teriparatide treatment in pre-treated elderly rheumatoid arthritis patients who use anti-resorptive drugs.

AIM: The serum undercarboxylated osteocalcin (ucOC) level, a biochemical bone marker of vitamin K insufficiency, is often affected by anti-osteoporosis drugs. There have been no reports regarding the relationship between ucOC and teriparatide. SUBJECTS AND METHODS: We conducted a prospective observational study of 26 female rheumatoid arthritis (RA) patients. The patients were divided into 3 groups: those who underwent a direct switch from anti-resorptive drugs to teriparatide (12 cases), those who started teriparatide without pre-treatment (5 cases), and the control patients (9 cases). The median age (interquartile range) of the patients in each group was 75 (67-77), 82 (78-84), and 69 (62-80) yr, respectively. All patients, except controls, received 48-week treatments of teriparatide. We analyzed the median 48-week changes from baseline of the serum ucOC levels with the Steel-Dwass method. RESULTS: The median change from baseline in the direct switch group was higher than that in other groups (p<0.05). CONCLUSIONS: The serum ucOC levels increased with treatment of teriparatide in elderly RA patients, especially when the patients received pre-treatment.

Preemptive therapy with ganciclovir 5 mg/kg once daily for cytomegalovirus infection after unrelated cord blood transplantation.

The efficacy and safety of preemptive therapy using ganciclovir (GCV) 5 mg/kg once daily for CMV infection after unrelated cord blood transplantation (CBT) were studied. The initial preemptive therapy with GCV 5 mg/kg once daily led to resolution of CMV antigenemia in 25 of 34 patients (74%). In the remaining 9 patients (26%), antigenemia resolved after dose-escalation of GCV or change to foscarnet therapy. Recurrence of antigenemia was seen in 18 patients (53%). A total of 12 patients received the second preemptive therapy with GCV 5 mg/kg once daily, which led to resolution of antigenemia in 11 of 12 patients (92%). The remaining 1 patient (8%) required change to foscarnet therapy. None of 34 patients developed CMV disease. Neutropenia with an absolute neutrophil number of less than 1 and 0.5 x 10(9) per liter after GCV therapy occurred in 12 (35%) and 1 (3%) patients, respectively, after the initial therapy, and in 2 (17%) and 0 (0%) patients, respectively, after the second therapy. No patients developed neutropenic fever or secondary graft failure after GCV therapy. There were no deaths directly attributable to GCV therapy. The present study suggests that antigenemia-based preemptive strategy using GCV 5 mg/kg once daily is feasible and effective for CBT recipients.

"Alternative self-diploidization" or "ASD" homothallism in Saccharomyces cerevisiae: isolation of a mutant, nuclear-cytoplasmic interaction and endomitotic diploidization.

A mutant of Saccharomyces cerevisiae representing a novel life cycle, named "alternative self-diploidization" or "ASD" homothallism, was obtained fortuitously. In this life cycle, MAT alpha (or MATa) haplophase and MAT alpha/MAT alpha (or MATa/MATa) diplophase alternate. Germinated cells are haploid and mating. They soon become nonmating and sporogenous as they vegetatively grow. They sooner or later diploidize presumably via endomitosis. The diploid cells haploidize via normal meiosis. A single recessive nuclear mutation, named asd 1-1, is responsible for "ASD" homothallism. In the rho 0 cytoplasm, asd 1-1 cells mate even if at a low efficiency and fail to diploidize. Since pet mutations do not have such effects, we conclude that a certain mitochondrial function other than respiration is required for manifestation of "ASD" homothallism. That is, "ASD" homothallism is the result of some sort of nuclear-cytoplasmic interaction.

A simple method for efficiently establishing 8-azaguanine-resistant mutant human leukemia and myeloma cell lines.

A simple and convenient method for efficiently establishing 8-azaguanine-resistant mutant leukemia and myeloma cell lines (for example, the T cell lines Jurkat and CCRF-CEM, human myeloid/macrophage-like cell lines HL60 and U937, Burkitt lymphoma line Raji and the human myeloma line RPMI 8226), is described. The method relies on culturing the cell lines in RPMI 1640 medium containing 8-azaguanine and supplemented with 15% heat-inactivated fetal calf serum and large amounts of amino acids and vitamins, and removes the necessity for pretreatment with mutagenic reagents such as ethyl methylsulfonate or X-irradiation. The possibility of obtaining mutant cell lines using the method described here is about 15 times greater than using media without high levels of amino acids and vitamins. Hybridomas produced between mitogen-activated human peripheral blood lymphocytes and an 8-azaguanine-resistant Jurkat mutant cell line (established by this method) were shown to produce soluble T cell-derived macrophage activating factor (MAF)-like material.

Herpes simplex virus infection in adult patients after unrelated cord blood transplantation: a single-institute experience in Japan.

Herpes simplex virus (HSV) infection in adult patients who underwent cord blood transplantation (CBT) from unrelated donors was studied. None of nine HSV-seronegative patients developed HSV disease after CBT. Of 28 HSV-seropositive patients, seven (25%) developed HSV disease at a median of 92 days after CBT (range, 52-239 days). The cumulative incidence of HSV disease in HSV-seropositive patients was 27% at 12 months after CBT. The manifestations of HSV disease included gingivostomatitis (three patients), herpes labialis (two patients), localized herpes facialis of the nose (one patient), and disseminated eczema herpeticum (one patient). HSV disease recurred in two patients as gingivostomatitis and disseminated eczema herpeticum. All the patients responded to antiviral therapy. The presence of grade II-IV acute graft-versus-host disease (GVHD) was significantly associated with a higher rate of HSV disease after CBT (51 vs 8%, P=0.015). These results suggest that the recovery of HSV-specific immune responses is delayed in patients who develop grade II-IV acute GVHD after CBT.

Neuroprotective action of a novel compound--M50463--in primary cultured neurons.

The neuroprotective effects of a novel synthetic compound, M50463, have been determined by using embryonic rat neocortical neurons in various culture conditions. M50463 was initially characterized as a potent specific ligand for a voltage-dependent sodium channel by radioligand binding studies. In fact, M50463 inhibited neuronal cell death induced by veratrine and inhibited an increase of the intracellular calcium level in neurons evoked by veratrine. In addition to such expected effects, M50463 had the ability to prevent glutamate neurotoxicity, to promote the neuronal survival in serum-deprived medium and to prevent nitric oxide-induced neurotoxicity. These results suggested that M50463 is not a simple sodium channel blocker, but a neuroprotective agent which has some crucial mechanism of action on neuronal death occurring in various situations, and it is a novel, innovative candidate for neuroprotective therapy for various neurodegenerative disorders.

Immuno-chemotherapy of malignant lymphoma using OK-432, a streptococcal agent.

Clinical trials of immuno-chemotherapy were conducted on malignant lymphoma patients. Patients during the period from 1972 through 1977 were allocated to two groups retrospectively according to the mode of treatment, i.e., chemotherapy alone (historical control group, 35 patients) and chemotherapy with OK-432 (treated group, 15 patients). Comparisons were made of the two groups, which were homogeneous with regard to induction chemotherapy, maintenance chemotherapy, stage and histologic type of disease. The treated group had a higher remission rate, and a longer remission duration and survival than the control groups, especially in patients with Hodgkin's disease but the difference was not statistically significant owing to the limited number of cases.

Correction of CAPD catheter displacement using gastric biopsy forceps: the push-pull method.

We corrected malpositioned continuous ambulatory peritoneal dialysis catheters in six patients using a new technique named the "push-pull method". A gastric biopsy forceps was advanced through the catheter to near its tip. After manipulating the tip of the forceps through the abdominal wall, the forceps was opened and pulled out slowly. Repeated insertion and removal of the forceps induced the catheter to return to the pelvic cavity. This push-pull method was successful for Swan neck straight (n=2) and coiled (n=4) catheters in all patients. The time required for the procedure was only 5-10 minutes and there were no complications.

Dose escalation induces tolerance to side-effects of erythropoietin in a patient with dialysis anaemia: case report.

A 51-year-old woman began haemodialysis for chronic renal failure in February 1981. Symptomatic anaemia required treatment with recombinant human erythropoietin (rHuEPO) in February 1990 (3000 IU, twice weekly, intravenously). She developed influenza-like symptoms and treatment was withdrawn. In June 1994 rHuEPO was resumed at a very low dose of 100 IU subcutaneously three times weekly, and was increased gradually to 500 IU, without inducing any side-effects. At this dose the haematocrit was maintained at 22.0-25.0% and the symptoms of anaemia improved. In patients like ours, with influenza-like symptoms caused by rHuEPO therapy, dose escalation starting from an ultra-low dose may be effective in avoiding side-effects.

[Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate on low density lipoprotein in rabbits].

The hypolipidemic effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on cholesterol diet-fed rabbits were studied. EPA-E (300 mg/kg, p.o. x 4 weeks) decreased total cholesterols in the lipoprotein fractions of very low-density lipoprotein and intermediate lipoprotein+low-density lipoprotein (LDL), but not in high-density lipoprotein. Furthermore, the properties of LDL were investigated in rabbits given EPA-E (300 mg/kg, p.o. x 2 weeks). EPA-E had no influence on the lipid composition in LDL, and the cholesterol accumulation into macrophages was not increased by the incubation with EPA-E-treated LDL. However, the omega 3 polyunsaturated fatty acids contents of LDL were increased by the administration of EPA-E. EPA-E-treated LDL was also studied on the binding to the hepatic membranes. The binding of EPA-E-treated LDL to the hepatic membranes was higher than that of ordinary LDL. These results suggest that EPA-E causes a modification of LDL, such that EPA-E has an enhancing effect on the hepatic uptake of LDL. These effects may contribute to the hypolipidemic action of EPA-E.

Note: application of UF-4 emulsion films to detect low-energy ions from plasmas produced by laser ablation.

Detection of low-energy ions via Thomson parabola mass analyzer in the absence of any additional electrical systems is examined. Numerous low-energy ions were recorded on UF-4 solid state emulsion films. Kinetic energies between 1 and 4 keV of ions generated by YAG laser focused on Al and Ti targets were obtained using Thomson parabola measurements. Characteristics of ion tracks on the UF-4 detector are discussed in terms of pressure ranges of vacuum chamber. Moreover, differences in charges of ions between this study and previous spectroscopic measurements are discussed.

D-penicillamine-induced glomerulonephritis with crescent formation: Remission following drug discontinuation.

We report a 71-year-old female who presented with rheumatoid arthritis complicated by proteinuria. She had been receiving D-penicillamine (D-Pc) for two years prior to presentation. A urinalysis showed proteinuria and hematuria which disappeared within 3 months after D-Pc was stopped. The renal histological findings showed focal proliferative glomerulonephritis with crescent formation. A total of 10 cases of D-Pc-induced glomerulonephritis with crescent formation without alveolar hemorrhage have previously been reported in the literature. To the best of our knowledge, this is the first case report in which the patient did not require any treatment.