Antibody-dependent neutrophil-mediated parasite killing in non-lethal rodent malaria

The effects of administrating recombinant human granulocyte colony-stimulating factor (rhG-CSF) and passively transferring immune serum on infection with an attenuated variant of Plasmodium berghei XAT (Pb XAT), in severe combined immunodeficiency (SCID) mice were examined. In immune competent (C.B-17) mice, the attenuated parasite infection was inevitably self-resolving and degenerating forms inside erythrocytes appeared, coinciding with the drop in parasitaemia, whereas SCID mice were unable to control parasite growth and all the mice died. Continuous administration with rhG-CSF caused neutrophilic granulocytosis in both SCID and C.B-17 mice. The effect of rhG-CSF on the infection in C.B-17 mice was to suppress the course of the parasitaemia at an early phase whereas it had no effect in SCID mice. When immune serum was transferred on the day of infection, the prepatent period was prolonged two days in both SCID and C.B-17 mice. When administration with rhG-CSF was combined with transfer of immune serum, SCID mice showed four days delay in patency and degenerating parasites were seen during the course of parasitaemia, although the infection was ultimately fatal. C.B-17 mice similarly treated showed a seven day delay in the onset of the patent parasitaemia which was of a lesser magnitude and shorter in duration compared with control mice. On the other hand, when C.B-17 mice were splenectomized three weeks before infection and then treated with rhG-CSF and immune serum, no degenerating parasites were seen during the infection and all mice died with high parasitaemias. These results show that antibody-dependent neutrophil-mediated parasite killing may occur in the spleen of mice infected with P. berghei XAT.     

Relationship between severity and symptoms of reflux oesophagitis in elderly patients in Japan

Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.     

Cyclic peptides

In order to explore the route for the preparation of cyclodepsipeptide by cyclization through an ester bond formation, two analogs of AM-toxin II, cyclotetradepsipeptide, were synthesized. As a preliminary experiment, synthesis of [L-Phe³, L-Ser(Bzl)⁴]-AM-toxin II, containing L-Phe and L-Ser(Bzl) in place of L-App (2-amino-5-phenyl-pentanoic acid) and ΔAla (α,β-dehydroalanine), respectively, was attempted. Cyclization of H-L-Hmb-L-Phe-L-Ser(Bzl)-L-Ala-OH in CH₂CI₂ at 10mM concentration using water-soluble carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) successfully gave a cyclic monomer in 16% yield. Cyclization of H-L-Hmb-L-App-L-Ser(Bzl)-L-Ala-OH under the same conditions also afforded a cyclic monomer, [L-Ser(Bzl)⁴]AM-toxin II, in 19% yield. Analytical parameters of these cyclic monomers obtained were identical to those of the authentic samples obtained by cyclization through a peptide bond formation.     

Prevalence of use of medically prescribed hypnotics among adult Japanese women in urban residential areas

Abstract Based on a population survey on insomnia among 3600 adult Japanese women living in urban areas, the prevalence of use of medically prescribed hypnotics is determined. The prevalence of use of medically prescribed hypnotics increases with an increase in age (<1.0% for those aged 49 or younger, while 14.3% for those aged 70 or older), in agreement with the results reported in many Western nations. The current sleep disturbance is mild in nearly half of these hypnotics users. More than one-third of the hypnotic users are receiving health care not for sleep problems but for depression, anxiety, or other reasons. More than one-third of the hypnotic users are found to be receiving hypnotics from non-psychiatrists. The percentage of this group is particularly high among those aged 60 or over, probably reflecting the fact that they are often consulting physicians for physical reasons. On the other hand, more than 80% of insomniacs are suggested to be untreated. Future public health research should focus on the quality of life and health care behaviors of untreated insomniacs and hypnotic users, especially among the elderly people, in order to assess the need for primary health care to prevent accidents, mortality, and psychiatric disorders related to sleep problems.     

PREPARATION AND PROPERTIES OF Nα-9-FLUORENYLMETHYLOXYCARBONYLAMINO ACIDS BEARING TERT.-BUTYL SIDE CHAIN PROTECTION

The preparation is described of several Nα-9-fluorenylmethyloxycarbonylamino acids and derivatives bearing tert.-butyl type side-chain protection of amine, carboxyl, guanido, hydroxyl, imidazol, and sulfhydryl functionalities. Physicochemical properties of these compounds have been determined. Cleavage of the Fmoc group by various amines appears to depend on the base strength and steric hindrance. Premature deblocking of Fmoc group by amine on solid support is very slow and may be negligible under the conditions of solid-phase synthesis.     

The Transduodenal Endoscopic Treatment of Acute Cholangitis

Mortality due to acute cholangitis (AC) has been tremendously reduced by the advent of endoscopic sphincterotomy (EST). This study investigates whether EST is really a curative procedure for the treatment of AC, or not. Diagnosis of AC, in 159 out of 1,061 cases in which EST was performed, had been made by infected bile which was recognized as green or pyobile collected during ERCP. Emergency drainage by EST was performed immediately after AC was diagnosed. The causes of AC were attributable to benign diseases in 128 cases (80.5%) and malignant diseases in the remaining 31 cases. Clinical symptoms included abdominal pain, fever, and obstructive jaundice, but Charcot's triad was noticed in 66 cases (43.3%) and Reynolds pentad in only 7 cases (4.6%). As to the relation between clinical symptoms and properties of bile, pyobile was more likely to be recognized in patients with severe symptoms. Four patients treated at our hospital died of AC (2.5%). All were over 80 years old, and their conditions were already complicated by disseminating intravascular coagulation (DIC) syndrome. Compared with the results obtained in patients treated with percutaneous transhepatic biliary drainage (PTBD), the resulting mortality rate was less. Therefore, we feel the best approach for treating AC, which progresses to acute obstructive suppurative cholangitis (AOSC) in the final stage of the disease, is to diagnose early, by ERCP, and to promptly obtain decompression by subsequent EST, or to perform radical surgery.     

Cyclic peptides

Four cyclic dehydrodipeptides, cyclo (-Δaminoacyl-L-Ala-), in which aminoacyl is Phe, Apb (2-amino-4-phenylbutanoic acid), App (2-amino-5-phenylpentanoic acid) and Aph (2-amino-6-phenylhexanoic acid), were prepared by condensation of cyclo (-N-Ac-Gly-N-Ac-L-Ala-) with the corresponding aldehydes. Among them, the yield of cyclo (-ΔApb-L-Ala-) was exceptionally low. Each compound was hydrogenated in the presence of Pd black at various temperatures and chiral induction in hydrogenation was evaluated. Low chiral induction at high temperature (50d?) was observed in the case of cyclo (-ΔPhe-L-Ala-). Optically pure L-Apb, L-App and L-Aph were obtained from the corresponding cyclic dehydrodipeptides, respectively, by hydrogenation and subsequent acid hydrolysis.     

Phase I and Preliminary Phase II Studies on Aclacinomycin A in Patients with Acute Leukemia

Eight patients with acute nonlymphocytic leukemia (ANLL) andfive patients with acute lymphocytic leukemia were treated withaclacinomycin A. It was given daily by one-hour infusion indoses ranging from 0.33 to 0.70 mg/kg for seven to 20 days withoutother antileukemic agents. Two patients with ANLL achieved completeremission and one with ANLL achieved partial remission. Itsmajor toxic effects were myelosuppression and gastrointestinalsymptoms.     

Endoscopic Hemostasis in Patients with Dieulafoy Ulcer

Abstract: Dieulafoy ulcer was defined based on endoscopic findings as an ulcer (1) of 10 mm or less in diameter, (2) of grade Ul-ll or less and (3) showing vascular protrusion in its floor. We evaluated the clinical background and endoscopic findings of Dieulafoy ulcer and studied the usefulness and problems of endoscopic hemostasis. Patients with Dieulafoy ulcer accounted for 8.7 % of 321 patients with diseases treated by endoscopic hemostasis excluding sclerotherapy. The patients were predominantly males, and their average age was 61 years. An association with other diseases was noted in 21 patients (75%). Therefore, more than 50 % of the patients were treated with NSAIDs such as aspirin. The most frequent site of this disease was the posterior wall of the upper gastric body. In particular, the ulcer was located in the superior duodenal angle. In six of the 28 patients, the ulcer and the exposed vessel were similar in size. Endoscopic hemostasis was successful in 25 patients (89%). Hemostasis was acheived by emergency surgery in two and by transcatheter arterial embolization (TAE) in one. No patient showed recurrence. Most Dieulafoy ulcers can be conservatively treated by endoscopic hemostasis. However, a few cases can not be managed conservatively and shock develops due to fatal massive bleeding. In such patients, the timing of TAE or surgery must be carefully considered.     

Interferon-gamma and the induction of protective lgG2a antibodies in non-lethal Plasmodium berghei infections of mice

Mice treated with anti-IFN-gamma monoclonal antibodies were unable to recover from infection with an attenuated variant of P. berghei (Pb XAT) which causes non-lethal malaria in normal mice. On the other hand, treatment with anti-lL-4 monoclonal antibodies had no effect on the course of infection. IFN-gamma was produced by spleen cells in vitro during the early phase of the infection. Treatment with anti-IFN-gamma suppressed development of an anti-plasmodial IgG2a immunoglobulin isotype in the serum of infected mice whereas anti-IL-4 interfered with the IgGl response. An lgG2a fraction of immune serum collected from mice that had recovered from Pb XA T transferred immunity to naive mice but the IgGl fraction did not. When glutaraldehyde fixed parasitized erythrocytes were incubated with immune serum in suspension, specific IgG2a antibodies were detected by fluorescein staining on the membranes of cells infected with mature stages of parasites. These results indicate that IFN-gamma is a key to inducing B cells to produce the protective anti-plasmodial IgG2a immunoglobulin isotype. Antibody-dependent cell-mediated parasite killing seems to be involved in the mechanism of recovery from infection with Pb XAT.