GLOMERULAR TISSUE INJURY IN IgA NEPHRITIS

The glomerular lesions In 129 cases of IgA nephritis were analyzed. The development of glomerular injury occurred in two ways, one being a chronic mesangial depositive and sclerosing lesion commonly found in most glomeruli, and the other an acute but local injury initiating from the local peripheral glomerular basement membrane abnormality, i.e., thinning and/or splitting, which was seen at least in one third of all cases. The activation of the local coagulatory process could add segmental glomerular changes including small crescents, adhesion, and local tuft necrosis to the mesangial lesion. ACTA PATHOL. JPN. 33; 367–380, 1983.     

Development and Validation of Scoring Indication of Surgical Clipping and Endovascular Coiling for Aneurysmal Subarachnoid Hemorrhage from the Post Hoc Analysis of Japan Stroke Data Bank

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II–V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III–V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model’s scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.     

Clinical Outcome of Cytoreductive Surgery Prior to Bevacizumab for Patients with Recurrent Glioblastoma: A Single-center Retrospective Analysis

Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient’s condition.     

GENOTYPES OF ALDH2 RELATED TO LIVER AND PULMONARY DISEASES AND OTHER GENETIC FACTORS RELATED TO ALCOHOLIC LIVER DISEASE

Genetic factors related to the development of alcoholic liverand pancreatic diseases (ALD and APD) and of alcohol-inducedasthma were analyzed. The development of ALD is geneticallycontrolled and is directly associated with the polymorphismsof the genes of acetaldehyde (Ac-CHO) and ethanol-metabolizingenzymes, aldehyde dehydrogenase-2 (ALDH2) and cytochrome P4502E1.The development of ALD and APD may also be genetically linkedwith the induction of gamma-glutamyl transferase (GTT) by alcohol.Alcohol-induced asthma is related to the genotypes of ALDH2and is caused by rapid elevation of blood Ac-CHO. ALDH1 playsa very important role in the oxidation of Ac CHO in blood.     

ATP sparing effect of isoflurane during ischaemia and reperfusion of the canine heart

Sustained dysfunction of myocardial contractility after shortperiods of coronary artery occlusion and reperfusion has beentermed "stunned myocardium". Isoflurane may improve the recoveryof regional myocardial contractility in stunned myocardium.The purpose of the present study was to determine if isofluraneprevents depletion of high energy phosphates after myocardialischaemia-reperfusion and if the reduction in cardiac work duringisoflurane anaesthesia contributes to the preservation of highenergy phosphate metabolism in an acute canine model. Mongreldogs were allocated to one of three groups: controls, anaesthetizedwith urethane and chloralose; ISO group, isoflurane administeredbefore ischaemia; and ISOc group, heart rate and mean arterialpressure controlled to approximately match baseline values.The left anterior descending (LAD) coronary artery was occludedfor 15 min and then reperfused for 60 min during 1.5% end-tidalisoflurane anaesthesia. Full thickness samples of myocardiumwere obtained from the reperfused area (supplied by the LAD)and the non-ischaemic area (supplied by the left circumflexcoronary artery). The concentrations of adenosine monophosphate(AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP),creatine phosphate (CP) and lactate in the endocardial portionof the myocardium were measured. Arterial pressure, aortic flowin the ascending aorta and rate-pressure product decreased significantlyafter isoflurane. Although the concentration of ATP of the reperfusedarea in the control group showed a significant reduction 60mm after reperfusion, the ISO and ISOc groups had significantlygreater concentrations. Isoflurane anaesthesia maintained myocardialhigh energy phosphate metabolism in reperfused myocardium. Weconclude that the reduction in cardiac work played only a minorrole in the ATP-sparing effect of isoflurane. (Br. J. Anaesth.1995; 74: 563–568)     

SECONDARY AMYLOIDOSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS: DIAGNOSTIC AND PROGNOSTIC VALUE OF GASTRODUODENAL BIOPSY

Upper gastrointestinal endoscopy was performed in patients withrheumatoid arthritis (RA) during the period 1989–1991,and biopsy specimens were obtained from the stomach and fromthe duodenum for examining amyloid deposits. Among 407 patients,gastrointestinal amyloidosis was confirmed in 54 (13.3%). Twenty-twopatients were regarded as having slight amyloid deposits, while32 patients were categorized as having marked amyloid deposits.The incidence of clinical manifestations suggestive of systemicamyloidosis was more frequent in the marked deposits group thanin the slight deposits group (47% vs 14%, P < 0.05). Amongthe patients who died of manifestations associated with amyloidosis,the survival period following endoscopy was shorter in the markeddeposits group than in the slight deposits group. These findingssuggest that gastroduodenal biopsies may be useful for diagnosingsecondary amyloidosis and that the degree of amyloid depositsseems to be correlated with the clinical manifestations of RA. KEY WORDS: Rheumatoid arthritis, Complications, Secondary amyloidosis, Diagnosis, Endoscopy, Biopsy, Prognosis     

Characteristics of juvenile dermatomyositis in Japan

Questionnaires were sent to 1290 hospitals in Japan asking for data on patients with juvenile dermatomyositis (JDM) diagnosed between June 1984 and May 1994. Of the 204 patients identified by these questionnaires, 102 met the criteria for JDM. JDM is categorized into three subtypes: Banker-type JDM , Brunsting-type and fulminant-type; patients with the latter exhibit markedly elevated serum levels of creatinine phosphokinase (> 10 000 U/mL) and appear to be at risk of renal failure. Cutaneous manifestations were present in 98% of patients and preceded the appearance of other symptoms. This tendency is one of the reasons for the difficulty in some cases in diagnosing the onset of JDM. Better criteria for early treatment of JDM are needed. The results of the present study suggest that itching and calcinosis are factors that indicate a poor prognosis in patients with JDM. Muscle enzyme levels do not always reflect disease activity, suggesting that methods other than measurement of muscle enzymes, such as measurement of the levels of neoprerin and von Willebrand factor antigen, as well as magnetic resonance imaging should be used to be evaluate disease severity. Patients with Brunsting-type JDM who exhibit dysphagia and antinuclear antibody positivity and patients with Banker-type JDM should be treated aggressively. Pulse therapy should be selected as the initial therapy in patients with fulminant-type JDM.     

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients

We conducted molecular analysis of two candidate genes for spinal muscular atrophy (SMA), the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP), in 16 Japanese patients with SMA and compared the phenotypic features of SMA in these patients with the corresponding genotypes. Exons 7 and/or 8 of SMN were homozygously deleted in 11 SMA type I (Werdnig-Hoffmann disease) patients, two SMA type II patients and one SMA type III patient. Exons 5 and 6 of NAIP were homozygously deleted in six SMA type I patients. No patient had a deletion in NAIP without a deletion in SMN. Mechanical ventilation was required during the first 7 months of life in the SMA type I patients who had a deletion in both SMN and NAIP. Ventilatory support was initiated within 2 years after birth in patients who had a deletion in SMN but not in NAIP. We detected homozygous deletion of exon 5 of NAIP in the unaffected mothers of two SMA type I patients. In these families, the patients exhibited a deletion in both SMN and NAIP. The parents and unaffected siblings of these patients did not have a deletion in SMN. The present findings support the hypothesis that SMN deletion plays an important role in the development of SMA and suggest that combined deletion of both SMN and NAIP may be relevant for determining the disease severity.     

Phagocytosis of heat‐killed Staphylococcus aureus by eosinophils: comparison with neutrophils

Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16‐coated immunomagnetic beads and centrifugation through a Ficoll‐Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti‐FcγRIIa mAb (CD32 mAb), anti‐FcγRIIIb mAb (CD16 mAb), anti‐CR3 (CD11b mAb), or anti‐CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat‐killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2′,7′‐dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat‐inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35).