RETARDED MESANGIAL TRANSPORT AND ITS PATHOMORPHOLOGIC SEQUELAE IN HUMAN AND EXPERIMENTAL RENAL DISEASES

Human renal biopsy specimens (472 cases) from varied kidney diseases, especially minimal glomerular change group and other idiopathic glomerular diseases having nephrotic manifestation of mainly juvenile individuals, showed morphologic evidence of paraarterial deposits of afferent arterioles at the glomerular entrances in more than 50% of examined cases. Because these deposits were often accompanied with concomitant mesangial, intraarterial and subendothelial deposits of afferent arterioles, it was felt that retarded mesangial transport which is ordinarily associated with certain glomerular diseases might be an important factor to produce these particular paraarterial deposits. The referred deposits of minimal glomerular change group cases were thought to predispose the occurrence of focal sclerotic capillary lesions at the vascular poles of glomeruli. The experimental chronic nephrotic rats produced by daily administration of aminonucleoside of puromycin revealed mesangial dysfunction with increased uptake and retarded disposal of secondarily overloaded aggregated human gamma globulin at mesangial areas in glomeruli. Besides, the increased deposits of autologous serum proteins in mesangial areas and arteriolar walls were common findings in those rats, and these deposits were observed to be always preceded to the occurrence of segmental sclerotic changes of glomeruli, which were often associated in the later stage of this experiment. ACTA PATHOL. JPN. 33: 219∼236, 1983.     

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).     

TREATMENT OF GOUT WITH ALTERNATE-DAY HYPO-URICAEMIC DRUGS

In the treatment of gout, an alternate-day hypo-uricaemic drugwas tried in order to reduce the amount of hypo-uricaemic drugprescribed and to lessen its possible side-effects. The serumurate level in the alternate-day therapy with benzbromarone(100 mg/day) was higher than that found with daily therapy,but was conversely lower than that in half-dose daily therapy.The serum urate level in alternate-day therapy with five hypo-uricaemicdrugs increased by 0.7 mg to 1.4 mg/100 ml, compared with thatin the daily therapy. The incidence of hyperuricaemia (serumuric acid over 7 mg/100 ml) in alternate-day therapy with along-acting hypo-uricaemic drug was relatively low (0 % forbucolome, 20 % for probenecid and 25.0 % for benzbromarone).The incidence of hyperuricaemia in alternate-day therapy withsulphinpyrazone and allopurinol was 42.9 % and 66.7 %, respectively.The frequency of gouty attacks in alternate-day therapy withfive drugs was not significantly different, when compared withdaily therapy.     

Cardiac responses to hypoxia and hypercapnia in spinal man

The purpose of this study was to evaluate the effect of interruptionof the descending supraspinal sympathetic outflow on heart ratecontrol during exposures to chemical stimuli. We investigatedthe heart rate responses to progressive isocapnic hypoxia andhyperoxic hypercapnia using the rebreathing technique and quantifiedthe relationship between heart rate (HR), oxygen saturation(SaO₂), alveolar PCO₂ (P_ACO₂), and minute ventilation (V_E) in16 chronic tetraplegic subjects with low cervical spinal cordtransection. The HR responses were determined from the linearslopes of HR on SaO₂ and HR on P_ACO₂. We found that mean restingheart rate was within normal range; 66 ±3 (SEM) beatsmin^–1. HR increased as oxygenation fell or CO₂ tensionrose. The mean tetraplegic HR/SaO₂ was 0.83 ± 0.14 beatsmin^–1 per 1% fall in SaO₂ and that of HR/P_ACO₂ was 0.30± 0.13 beats min^–1 per mmHG rise in P_ACO₂. TheHR and V_E responses to either hypoxia or hypercapnia were relatedin the tetraplegic subjects. We conclude that the stimulatoryHR reponses to chemical stimuli are not suppressed by cervicalspinal cord transection. Thus, the descending sympathetic activitydoes not underlie the HR acceleration by chemical stimuli.     

Pancreatic Arteriovenous Malformation in a Patient with Gastrointestinal Hemorrhage

A 39-year old woman, with a pancreatic arteriovenous malformation (AVM) which ruptured into the pancreatic duct, was treated successfully with distal pancreatectomy and splenectomy. Histological examinations revealed an AVM with extravasation into the pancreatic ducts. A review of the cases reported to date emphasizes the importance of physical signs, individual histories and angiographic studies for early diagnosis and surgery.     

Transient low level of IgG3 induced by sepsis

Staphylococcus aureus sepsis developed in a 14 year old girl. Immunological evaluation revealed low level of IgG3, although total IgG level was normal. The level of IgG3 increased gradually along with the recovery from sepsis. Immunoglobulin replacement therapy might have been useful in this patient, even though the total immunoglobulin level was within normal limits.     

A case of West syndrome with atypical massive gray matter heterotopia that is well controlled by ACTH therapy

A 4 month old female infant with atypical asymmetrical massive gray matter heterotopia diagnosed as West syndrome is described. Her seizure initially appeared as afebrile general tonic and clonic convulsion and progressed to typical West syndrome consisting of clusters of myoclonic spasms of the extremities, mainly on the left side, accompanied by head and eye deviation to the right side. Electroencephalogram (EEG) presented typical hypsarrhythmia and cranial computerized tomography (CT) and magnetic resonance imaging (MRI) showed massive heterotopic gray matter in the right hemisphere with the same density or intensity as cortical gray matter. Single photon emission computed tomography (SPECT), using N-isopropyl-p-¹²³I-iodoamphetamine (¹²³I-IMP), demonstrated decreased blood flow in the ectopic lesion. Although clinical response to several anti-epileptic drugs was poor, her seizures were well controlled by relatively low dose adrenocorticotropic hormone (ACTH) therapy of 0.015 mg/kg per day followed by a combination of valproic acid and clonazepam.     

CHERRY RED MACULAR DEGENERATION

ABSTRACT. Cherry red macular degeneration was presented in a 6-month-old Japanese girl suffering from classical features of the diencephalic syndrome. The association of cherry red macular degeneration with the diencephalic syndrome was previously undescribed.     

HLA‐haploidentical nonmyeloablative stem cell transplantation: induction to tolerance without passing through mixed chimaerism

There are few reports of unmanipulated HLA‐haploidentical nonmyeloablative stem cell transplantation (NST) using only pharmacological acute graft‐vs.‐host disease (GVHD) prophylaxis. We present here a successful case of unmanipulated HLA‐haploidentical NST for mediastinal large B cell lymphoma that was resistant to autologous peripheral blood stem cell transplantation (PBSCT). The conditioning regimen consisted of fludarabine, busulfan and rabbit anti‐T‐lymphocyte globulin (ATG) in addition to rituximab. GVHD prophylaxis was performed using tacrolimus and methylprednisolone 1 mg/kg. The patient had rapid engraftment, with 100% donor chimaerism in the lineages of both T cells and granulocytes on day +12, but developed no GVHD clinically. The patient is still in complete remission past day +1020, with no sign of chronic GVHD without receiving immunosuppressive agents. HLA‐haploidentical NST may be performed without utilizing mixed chimaerism.     

Flow cytometric analysis of platelet activation markers CD62P and CD63 in patients with coronary artery disease

We investigated whether platelet activation could be quantitatively detected in patients with coronary artery disease using flow cytometric analysis of the expression of CD62P and CD63, which are activation-specific antigens on the platelet surface. Platelet samples were obtained from 16 healthy control subjects and 65 patients, of whom 25 had angiographically normal coronary arteries and 40 had at least one major coronary artery stenosis (≥ 50% narrowing). In both patient groups, CD62P expression was significantly higher than in the control group, but the difference between the two patient groups was not significant. In contrast, CD63 expression did not differ among the three groups. We also compared expression of these antigens after stratifying the patients according to the number of significant coronary artery stenoses. Patients with three-vessel disease had significantly increased CD62P and CD63 expression compared with the other subgroups. Our findings indicate that platelet activation occurs in patients with severe coronary artery stenosis.