Serum Alkaline Phosphatase of Large Molecular Weight

Bio-Gel A-5m and Bio-Gel A-150m gel-chromatography of serumalkaline phosphatase was carried out. Large molecular alkalinephosphatase in serum which exhibited alkaline phosphatase activityprior to any treatment was obtained and assumed tobe cell debrisenzyme. By the treatment with Triton X-100, its molecular weightbecame smaller and alkaline phosphatase activity increased.Treatment with DOC also lowered the molecular size, but alkalinephosphatase activity was inhibited. Electron microscopic studyof ultracentrifugation sediment of this material revealed celldebris like features possessing alkaline phosphatase activitythemolecular weight of this meterial may be over ten million witha very broad size distribution.     

Controlled Study of Therapeutic Granulocyte Transfusions in Granulocytopenic Patients with Severe Infections

The effectiveness of therapeutic granulocyte transfusions wasstudied in a controlled trial involving 75 granulocytopenicpatients with severe infections. Patients who had granulocytecounts of less than 200/mm³ and no response to antibiotic therapywere assigned to receive antibiotic therapy alone or granulocytetransfusions plus antibiotic therapy. Granulocytes were collectedby filtration leukapheresis (FL), intermittent flow centrifugeleukapheresis (IFCL) or continuous flow centrifuge leukapheresis(CFCL). Therapeutic effects of granulocyte transfusions wereevaluated on the basis of 20-day survival after entry into thestudy. The patients were divided into three groups: 1) 22 patientsreceived antibiotic therapy alone for 29 infectious episodes(control group); 2) 27 patients received 131 transfusions ofgranulocytes collected by FL for 31 infectious episodes (FLgroup); 3) 26 patients received 139 transfusions of granulocytescollected by IFCL and CFCL for 27 infectious episodes (IFCL& CFCL group). The overall survival of the transfused patientswas not significantly different from that of the untransfusedpatients. Similarly, there was no significant difference insurvival between the transfused and untransfused patients whenthe data concerning septicemia were analyzed. When patientsshowed bone-marrow recovery, which was indicated by recoveryof granulocytes to 500/mm³ or more during the study, 20-daysurvival was observed in 13 of 14 untransfused patients andin all of 26 transfused patients. In contrast, the survivalrate for the patients without bone-marrow recovery was 13% (2/15)in the control group, 39% (7/18) in the FL group and 57% (8/14)in the IFCL & CFCL group respectively. Thus, the survivalrate was significantly higher for the transfused than for theuntransfused patients. These observations suggest that therapeutic granulocyte transfusionsmay be of limited value in improving the outcome of severe infectionsin persistently granulocytopenic patients. Since bone-marrowrecovery is a critical factor for the prognosis of severe infections,therapeutic granulocyte transfusions do not provide any beneficialeffects in granulocytopenic patients whose bone-marrow functionwill recover.     

No association between c-fos gene polymorphisms and sporadic Alzheimer's disease

Abstract Although ApoE ε4 is a major risk factor for sporadic Alzheimer's disease (AD), 20–30% of sporadic AD patients do not have this allele. This indicates that other risk factors are involved in the pathogenesis of sporadic AD. Studies of the genetic association between AD and polymorphisms in the c-fos gene, a candidate gene for AD, were conducted. The polymorphisms of Dsal in exon 2 and Sau3Al in intron 2 were examined in 89 patients diagnosed as sporadic cases of probable AD clinically and radiologically according to the NINCDS-ADRDA criteria. This was also undertaken in 96 controls. There was no significant difference between the groups in allele frequencies or genotype counts. Although c-fos gene as a locus conferring susceptibility to sporadic AD cannot be ruled out, these data could not support the hypothesis that a c-fos allele should be another risk factor for sporadic AD.     

Clinical follow‐up study of adult‐onset Still’s disease

Eighteen patients with adult‐onset Still’s disease have been followed up for 3–22 years in our department. Initial manifestations were fever with skin rash in 14 patients, fever, skin rash and sore throat in two, skin rash in one and arthralgia in one. During the follow‐up period, typical skin rash was seen in all patients, of them five patients (29%) revealed atypical skin rash simultaneously. Atypical rash included persistent erythema with pigmentation in two, persistent plaques and papules with linear erythema in two and edema of the eyelids mimicking dermatomyositis in one. Persistent papules and plaques revealed histologically characteristic features, such as dyskeratotic keratinocyte and liquefaction degeneration as well as a sparse superficial dermal infiltrate containing scattered neutrophils. In patients of chronic articular type and polycyclic systemic type, atypical skin rash, lymphadenopathy and hyperferritinemia were noted to be significantly higher than those of monocyclic type. These factors might be prognostic factors of adult‐onset Still’s disease in our study.     

Primary IgA Glomerulonephritis and Schonlein-Henoch Purpura Nephritis: Clinicopathological and Immunohistological Characteristics

A comparative analysis on clinicopathological and immunohistologicalcharacteristics was performed of 205 cases with primary IgAnephritis and 35 with Schönlein-Henoch purpura nephritis(purpura nephritis). Diagnostic criteria for primary IgA nephritiswere set out so that IgA was either the most prominent immunoglobulinor, at least, equal to IgG and/or IgM, if present, irrespectiveof mesangial or peripheral localization. In primary IgA nephritis,one half of the cases were discovered by asymptomatic proteinuria,and one-third presented recurrent upper respiratory tract infectionand gross hematuria, one-fourth abdominal pain and a few casesjoint pain, while purpura nephritis was associated with a significantlyhigher incidence of such systemic symptoms as abdominal andjoint pains, in addition to purpura. Both diseases shared atendency toward conspicuous hematuria in contrast to the modestproteinuria, with normal renal function in three-fourths totwo-thirds. Moreover, four of 35 with purpura nephritis showedpreceding proteinuria and had been regarded as primary IgA nephritisuntil purpura appeared. The glomerular pathology had a commonfeature in that there was frequent occurrence of mesangial proliferativeand focal and segmental lesions. The immunohistology in thetwo diseases was indistinguishable with regard to the glomerularimmunoglobulins and mediators, whether purpura was present orabsent. Thus, we propose a unifying concept that, by analogywith SLE, primary IgA nephritis may be regarded as ‘sinelupo,’ lying on one side of the nosological spectrum withless systemic symptoms, whereas purpura nephritis may occupythe other side with more systemic aspects. Furthermore, we confirmedthe epimembranous granular deposition of IgA in both diseasesas the most characteristic morphological expression of circulatingimmune complexes.     

Drug Metabolism: Intestinal Bacterial Hydrolysis is Required for the Appearance of Compound K in Rat Plasma after Oral Administration of Ginsenoside Rb1 from Panax ginseng

Ginsenoside Rb₁ from Panax ginseng root is transformed into compound K via ginsenosides Rd and F₂ by intestinal bacterial flora. Among 31 defined intestinal strains from man, only Eubacterium sp. A-44 transformed ginsenoside Rb₁ into compound K via ginsenoside Rd. The ginsenoside Rb₁-hydrolysing enzyme isolated from Eubacterium sp. A-44 was identical to a previously purified geniposide-hydrolysing β-D-glucosidase. When ginsenoside Rb₁ (200 mg kg^?1) was administered orally to germ-free rats, neither compound K nor any other metabolite was detected in the plasma, intestinal tract or cumulative faeces 7 or 15 h after administration. Most of the ginsenoside Rb₁ administered was recovered from the intestinal tract, especially the caeca, and cumulative faeces indicating poor absorption of ginsenoside Rb₁. When ginsenoside Rb₁ was administered orally to gnotobiote rats mono-associated with Eubacterium sp. A-44, a significant amount of compound K was detected in the plasma and considerable amounts were found in the caecal contents and cumulative faeces 7 and 15 h after administration. A small amount of ginsenoside Rb₁ was detected in the caecal contents only 7 h after administration. These results indicate that orally administered ginsenoside Rb₁ is poorly absorbed from the gut but that its metabolite compound K, produced by ginsenoside Rb₁-hydrolysing bacteria such as Eubacterium sp. A-44 in the lower part of intestine, is absorbed.     

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.     

Correlation Between Disappearance of the Intrahepatic Bile Ducts and Histologic Changes in the Liver in Primary Biliary Cirrhosis

Statistical investigations indicate that disappearance of bile ducts, estimated by a histometric method, was more extensive in symptomatic than in asymptomatic patients with primary biliary cirrhosis. The extent and degree of intrahepatic bile duct disappearance in PBC is related to the degree of copper granule deposition in the hepatocytes, the degree of atypical ductular proliferations and the fibrous septa formation. Bile plug formation and chemically determined copper content are not so well related to the bile duct disappearance, while periportal lymphoid cell infiltration is not related to the degree or extent of bile duct disappearance at all.