[Gamma-heavy chain disease associated with MALT lymphoma of the duodenum].

We report a case of a 63-year-old woman with gamma heavy chain disease (HCD) associated with mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum. She was suffering from drug-resistant tonsillitis with high fever. Examination on admission showed leukocytopenia and thrombocytopenia. Bone marrow aspirate revealed granulocytosis and a hypocellular marrow with no increase in plasma cells or atypical lymphocytes. Serum electrophoresis disclosed, in addition to hypogamma-globulinemia, an abnormal band due to the presence of gamma HCD protein. This abnormal protein was a molecular weight of approximately 40 kd as determined by Western blots technique, and belonged to the IgG1 subclass as determined by ELISA with monoclonal antibodies against IgG. An endoscopic examination of the patient's duodenum found a small tumorous lesion, which was confirmed pathologically to be MALT lymphoma. HCD is known to be associated with lymphoproliferative diseases. In this case, gamma HCD had developed as a secondary complication of MALT lymphoma. gamma HCD associated with MALT lymphoma of the duodenum is rare in the literature.

[A case of relapsing polychondritis with IgA nephropathy].

We report a case of a 37-year-old man with relapsing polychondritis and IgA nephropathy. He visited our hospital with high fever and the swelling of his ears and eyelids. His symptoms and the results of the biopsy of his right auricle fulfilled the Damiani's criteria. Laboratory examination on admission showed an increase of serum IgA level, a presence of immune complex, remarkable hematuria (grade III) and proteinuria (grade II). Most of his symptoms were improved by the administration of antibiotic and NSAIDs, however, urinary findings still remained unchanged. The biopsy of his right kidney led to a diagnosis of IgA nephropathy (group II). Although relapsing polychondritis is known to associate rarely with renal involvement, it is very rare to associate with IgA nephropathy. This case indicates that immune disorders including IgA nephropathy should be investigated in patients with relapsing polychondritis.

[A study on antiprothrombin antibodies in antiphospholipid syndrome].

In this study we investigated the frequency and the type of manifestations of antiprothrombin antibodies (aFII) in patients with antiphospholipid syndrome (APS). In 16 (84.2%) of 19 patients with lupus anticoagulant (LA) and either anticardiolipin antibodies or antiphosphatidylserine antibodies, two types of abnormal patterns were shown on a crossed immuno-electrophoresis technique using anti-human prothrombin murine IgG. The slow-moving peak of prothrombin was detected in 8 patients, while a peak in the other patients had the slow-moving shoulder. These slow-moving materials might represent prothrombin-aFII complexes. In 13 patients who were studied on Western blots, IgGs of 11 patients (84. 6%) bound to human purified prothrombin, and the IgGs of 7 (53.8%) of these patients also bound to human purified alpha-thrombin. Our results indicate that aFII detected in patients with APS may explain part of the mechanism of LA.

Protection by alpha2-macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor-1.

Tissue plasminogen activator (tPA) is widely used in the treatment of acute myocardial infarction (MI). However, its thrombolytic efficacy does not correlate with the dose administered. The interactions between tPA, alpha2-macroglobulin (alpha2-M), and plasminogen activator inhibitor-1 (PAI-1) were investigated both in vitro and in patients undergoing tPA therapy for MI in an attempt to identify variables that might affect the clinical efficacy of tPA. Purified alpha2-M (5.4 mg/ml) protected 16.0% or 22.4% of tPA (12.5 IU/ml) activity from inhibition by PAI-1 at 4 or 8 IU/ml in vitro. Of nine patients treated with 5-20 mega IU of tPA for MI, the plasma activity of tPA remained increased for 15-30 min after the cessation of infusion in eight; the patient who failed to exhibit a persistent increase in tPA activity had a low plasma concentration of alpha2-M. Total tPA activity, derived from the area under the activity-versus-time curve (AUC), showed a significant inverse correlation with the ratio of the plasma PAI-1 activity to the plasma alpha2-M concentration. Total tPA activity did not correlate with plasma PAI-1 activity or plasma alpha2-M concentration alone. Results suggest that alpha2-M, by binding to tPA, protects the latter against inhibition by PAI-1.

[Henoch-Schönlein nephritis with nephrotic syndrome during pregnancy].

We report a 33-year-old female with nephrotic syndrome associated with Henoch-Schönlein nephritis (HSN) during pregnancy. She presented purpura in the legs at 20 weeks in her third pregnancy. A biopsy of her purpuric skin lesion showed leukocytoclastic vasculitis. After a month she was admitted to Sapporo City General Hospital because of development of a nephrotic syndrome. She was treated with heparin as anticoagulants therapy and delivered of a healthy girl by Cesarean section at 34 weeks. Renal biopsy, carried out beyond a month after delivery, revealed diffuse proliferative glomerulonephritis with prominent IgA deposits, which made the diagnosis of HSN (grade III of classification of the renal histopathology of HSN from the International Study of Kidney Disease in Childhood). Prednisolone 40 mg, dipyridamole 300 mg per day and pulse doses of steroid were administrated. Two months later proteinuria was not detected. A sister of the patient had also Henoch-Schönlein Purpura in her childhood. They shared HLA DR 4, DQ 4 which are known to be associated with IgA nephropathy. Fifty percent of pregnant women with chronic glomerulonephritis shows increased proteinuria. Pregnancy may have influence on the increased proteinuria in this case.

[Massive ascites as an initial sign, plasmacytoma of the cervical supine, and hyperammonemic consciousness disturbance in a patient with biclonal type multiple myeloma].

A 69-year-old male presented with fever, ascites and leg edema in February, 1994. He had a pathological fracture of cervical supine in October. Pathological findings at operation showed plasmacytoma. Bone marrow aspiration showed 16.2% myeloma cells. So he was diagnosed as multiple myeloma presenting biclonal gammopathy of IgA-L and IgD-K. Ascites was massive and drainage of 2 to 4 liter per week was required. Ascites was supposed to be related to multiple myeloma, because the IL-6 level in the ascites was increased (2,440 pg/ml), although repeated cytologic studies were negative. After the operation, he developed hyperammonemic drowsiness. It was also suggested that hyperammonemia was associated with multiple myeloma. In addition to radiation therapy for the cervical lesion, MP therapy, Interferon-alpha, VAD therapy and intraperitoneal cyclophosphamide infusion were administered. But no improvement of ascites or hyperammonemia were noticed. Here we described a case of multiple myeloma with very notable clinical features.

EM523L, a nonpeptide motilin agonist, stimulates gastric emptying and pancreatic polypeptide secretion.

We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

[Hemophagocytic syndrome with syndrome of inappropriate secretion of antidiuretic hormone (SIADH)].

A 69-year-old female was admitted to the hospital because of fever, hyponatremia and anemia. Laboratory data showed hemoglobin 8.6 g/dl, indirect bilirubin 1.9 mg/dl and Na 122 mEq/l. Urine osmolality was elevated and urinary excretion of sodium was increased. Furthermore, antidiuretic hormone (ADH) level was elevated. Renal function and hormonal data were within normal limit. Therefore, she was diagnosed as having syndrome of inappropriate secretion of antidiuretic hormone (SIADH). On the other hand, bone marrow aspiration showed hemophagocytosis and the diagnosis of hemophagocytic syndrome (HPS) was also made. High dose prednisolone and pulse therapy of cyclophosphamide were administered, nevertheless high grade fever persisted. Fever alleviation was acquired by Etoposide. But she died of pneumonia. An autopsy revealed hemophagocytosis in bone marrow, lymphnodes and spleen, but malignant tumor was not detected. And hypophysis was intact. The pathogenesis of SIADH in this case was not clarified. This report is seemed to be the first case of HPS associated with SIADH.

HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression.

HLA-DRB1 allele typing was performed by the PCR-RFLP method on 59 ulcerative colitis (UC) patients and 136 healthy controls. Phenotypic frequencies of HLA-B52 and DR2 were significantly increased among the UC patients, serologically. DNA typing of HLA-DRB1 revealed that the genotypic frequency of DRB1*1502 was higher in UC than in the controls (49.2% vs 17.6%; P < 0.0001). In the analysis of clinical parameters, 82.8% of patients bearing DRB1*1502 were treated with corticosteroids. DRB1*1501 and DRB1*1502 differ in only one amino acid at residue 86 (valine vs glycine), and 66% of the UC patients carried two glycines at position 86 in the HLA-DR beta-chain (vs 51% of control; P < 0.05). These observations suggest that the presence of Gly-86 in the HLA beta-chain and surrounding amino acid sequence of HLA-DRB1*1502 is strongly associated with susceptibility to UC.

[Primary biliary cirrhosis, rheumatoid arthritis and Sjögren's syndrome following implantation of ventriculoperitoneal shunt tube--an aged male case report].

A 73-year old male was received implantation of ventriculoperitoneal shunt tube (made with silicone) following subarachnoid hemorrhage in March 1991. Alkaline phosphatase was elevated gradually and he was diagnosed as having primary biliary cirrhosis by antimitochondria antibody and liver biopsy. He had been taking urso acid after that time on. He was admitted to our hospital because of stiffness and edema of both hands in November 1993. He was diagnosed as rheumatoid arthritis by morning stiffness with duration of few hours bilateral swelling of metacarpal, proxymal intrapharangeal and wrist joints and positive rheumatoid factor. In addition he felt dry mouth and laboratory data revealed that antinuclear antibody was 640x, centromere type, anti-SS-A antibody positive and elevation of circulating immune complex. A salivary gland disfunction was showed by gum test and salivary gland scintigraphy. Therefore the diagnosis of Sjögren's syndrome was made also. Connective tissue diseases have been reported to occur following cosmetic surgery with injection of the foreign substances paraffin and silicone. Now it is supposed to be the first case tcat connective tissue disease following ventriculoperitoneal shunt tube implantation.

[Bronchial hypersensitivity in Sjögren's syndrome].

It has been reported that Sjögren's syndrome has various pulmonary involvement including lymphoid interstitial pneumonia, lung fibrosis and various pulmonary manifestation. And some abnormalities in respiratory function have been pointed out. Bronchial hypersensitivity has been indicated in patients with bronchial asthma. It has been revealed that it plays an important role in pathogenesis of bronchial asthma. Recently, some authors reported bronchial hypersensitivity in patients with Sjögren's syndrome. We studied bronchial responsiveness to methacholine by using astograph in patients with Sjögren's syndrome. The patients are 25 subjects with Sjögren's syndrome. Bronchial hypersensitivity was seen in 15 patients (60%). And it's pattern was more slight than it of bronchial asthma patients. Our results show bronchial hypersensitivity in Sjögren's syndrome which has been pointed out recently. It may be due to an alteration of bronchial epithelium secondary to lymphocytic inflammation and damage of bronchial glands.

[Effective regimen for eradication of Helicobacter pylori].

There is now substantial evidence that Helicobacter pylori (H. pylori) is both a frequent cause of chronic gastritis and an important factor in the recurrence of duodenal ulcer. However, to achieve the eradication of H. pylori is very difficult and although a number of treatment regimens suppress this organism, the stomach usually becomes recolonized shortly after the cessation of treatment. Many reports have shown that polytherapy is more effective than monotherapy. And so, the best results have been achieved with triple therapy using combination of bismuth, metronidazole, or tinidazole, and amoxicillin or tetracycline. The factor influencing effectiveness of triple therapy is compliance with the prescribed medications. And so, short term triple therapy is highly effective and well tolerated.

Effect of trimebutine maleate on emptying of stomach and gallbladder and release of gut peptide following a solid meal in man.

We investigated the effect of orally administered trimebutine maleate on gastric and gallbladder emptying and on the release of gut peptide, pancreatic polypeptide (PP), and gastrin in humans for 120 min after ingestion of a solid meal. Gastric emptying was measured by a radionuclide technique. Gallbladder emptying was estimated by real-time ultrasonography. The oral administration of 200 mg of trimebutine maleate significantly shortened the lag time in starting gastric emptying (P < 0.05). Considering gallbladder emptying, trimebutine significantly inhibited the fasting emptying induced by neural reflex. Postprandially, there was a tendency toward an accelerated gallbladder emptying in the early phase. Neither the maximal percentage of gallbladder emptying nor the time of peak gallbladder emptying were affected. Trimebutine significantly blunted the post-prandial PP response in the cephalic and gastric phases, reflecting a vagal-cholinergic activity (P < 0.05). The PP response in the intestinal phase was also blunted. Gastrin release was significantly augmented only during the period of fasting after drug administration (P < 0.05). The major effect of trimebutine maleate appears to be a shortening of the lag time at the start of gastric emptying probably via its anticholinergic activity.

Effect of synthetic prostaglandin E1 analog (ornoprostil) on gastric emptying and pancreatic polypeptide release after solid-meal ingestion in man.

The effect of orally administered ornoprostil, 17S,20-dimethyl-6-oxoprostaglandin E1 methyl ester, on gastric emptying and on pancreatic polypeptide (PP) release after solid meal ingestion, was investigated in man. A radionuclide technique was used to measure gastric emptying of eight healthy volunteers. In addition, four parameters [SI (starting index): the lag time in the start of emptying; K value: the emptying rate; T1/2: the half emptying time; 120 min RR: the percent retention at 120 min] were determined for evaluation. Also, the PP response was analyzed according to two parameters: IPPRSI the integrated PP response for periods up to SI, and IPPR120, the integrated PP response for 120 min. The results demonstrated that 5 micrograms of orally administered ornoprostil significantly reduced the gastric emptying rate of solid meal (T1/2 and 120 min RR, P less than 0.05). However, ornoprostil affected neither the basal PP concentrations nor the cephalic phase of PP secretion which was determined as IPPRSI. This thus suggests that ornoprostil affects the gastric motor function without interfering with the vagal-cholinergic pathway to the stomach.

[Acute lymphocytic leukemia with thrombophlebitis of lower limbs and translocation (4;11)].

On November 22, 1985, a 54-year-old male was admitted to the cardiovascular department of our hospital suffering from thrombophlebitis, with redness, swelling and pain around the right ankle and left knee. He was transferred to our department on Nov. 26, because of hyperleukocytosis. Peripheral blood examination revealed hyperleukocytosis with 93.0% blastic cells and thrombocytopenia. The bone marrow aspirate was hypercellular and almost all cells were consistent with peroxidase negative blastic cells. The blastic cells were Leu M1 positive and Leu M2, M3 and lymphocytic markers were negative. The patient was diagnosed to have acute lymphocytic leukemia with Leu M1 positive blast cells. BH-AC/DMP therapy was began on the 1st hospital day but he died of cerebral haemorrhage on the 4th hospital day. An autopsy revealed systemic infiltration of leukemic cells including thrombophlebitis of the legs. Chromosome analysis of the bone marrow cells showed t(4;11)(q21;q23).

[Kaposi's sarcoma developing during corticosteroid therapy in idiopathic thrombocytopenic purpura].

A case of Kaposi's sarcoma developing during corticosteroid therapy for idiopathic thrombocytopenic purpura is reported. The patient is a 58-year-old female who was admitted to Sapporo City General Hospital for bleeding tendency in March 1987. She had been treated before admission with prednisolone (over 40 mg/day) for idiopathic thrombocytopenic purpura since October 1986, but her platelet count was below 40,000/microliters. In April 1987, several dark red or blue nodules appeared on the tip of her nose, left forearm, right shoulder, trunk and tongue. These nodules rapidly grew. Biopsy specimens from the nodule of the left forearm showed the histologic changes of Kaposi's sarcoma. She was treated with irradiation. Splenectomy was done in May 1987 and prednisolone was decreased to 5 mg/day. Her platelet count was continually kept 50,000/microliters or more. Her Kaposi's sarcoma completely regressed in January 1988. The relationship of immunosuppressive therapy to Kaposi's sarcoma is discussed.

Generation of monoclonal anti-dermatan sulphate antibodies cross-reacting to calf thymus DNA.

Monoclonal anti-dermatan sulphate antibodies were produced with hybridization after immunizing BALB/c mice with dermatan sulphate (DS). These antibodies were tested for cross-reactivity to double-stranded DNA (dsDNA) and heat-denatured DNA (ssDNA). Five clones had binding activity to DS, dsDNA and ssDNA in enzyme-linked immunosorbent assay, but no clones binding to DS alone were produced. Two (2H8 and 3C4) of the five clones were selected for analysis. Their binding activity to DS, ssDNA and dsDNA were inhibited by DS, dsDNA and ssDNA. DNase I treatment abolished the binding activity to dsDNA and ssDNA, completely, but had no effect on the binding activity to DS. On the other hand, chondroitinase ABC treatment of the solid-phased DS augmented the binding to DS. The inhibition assay using digested fractions suggested that the epitope recognized by 2H8 and 3C4 clones could not be in delta Di-4S or delta Di-diSB but in the linkage regions of DS.