We report here a familial clustering of elevated serum angiotensin converting enzyme (ACE) levels. The patient was a 58-year-old Japanese female. She had been in excellent health until the age of 45, when she noticed a decrease in visual acuity of her left eye. Despite intensive therapy under the diagnosis of occulusion of the central retinal vein, she lost her visual acuity at the age of 45. Thereafter, she has been in excellent health. The only abnormality found in this case has been a markedly elevated level of serum ACE (625 n mol/min/ml; normal range; 22-40 n mol/min/ml of serum). Her blood pressure was within normal limits (140/80 mmHg). There was no evidence for the diagnosis of sarcoidosis, Gaucher's disease, leprosy, hyperthyroidism, diabetic retinopathy, or liver disease. One of her two sisters also showed a marked increase in serum ACE activity (303 n mol/min/ml), and remarkably high levels of serum ACE (276 and 294 n mol/min/ml) were demonstrated in both of two sons of this sister. All the members of this family have been in excellent health. The serum ACE activity was activated by chloride and cobalt ions, and inhibited by EDTA, captopril and rabbit antiserum to purified human plasma ACE. Thus, our study showed a familial clustering of "hyper-ACE-emia", and the disorder appears to have been inherited as an autosomal dominant trait.

View full abstract

Unique ganglioside components including GM2 and spots No.1 and 2 designated tentatively were increased in content in some cases of cirrhotic liver as well as in all cases of hepatocellular carcinoma (HCC). Tissues of cirrhotic liver in which these components were increased were examined histologially. These components were increased in cirrhotic liver showing many foci of dysplastic nodules and in cirrhotic nodules at the matrix of multicentric HCC. These findings, thus, indicate that the unique ganglioside components are probably related to the histological findings of the cirrhotic liver.

View full abstract

Serum cholesterol level was studied in normal subjects in Kasakake Village. The serum cholesterol levels increased significantly with age, from the third to the fifth decade in males and from the third to the seventh decade in females. Thereafter, the levels were maintained in males while declined in females. The mean peak values (±SD) were 178 ± 31 mg/100 ml in males and 207 ± 37 mg/100mlin females. The presumptive values of the zero-year-old obtained from the regression lines calculated from the plot of serum cholesterol values against age were 129 mg/100 ml and 112 mg/100 ml in males and females respectively. Throughout the age-range examined in females, the serum cholesterol level was well correlated with the relative body weight determined with modified Broca's method. A similar, but less obvious correlation was demonstrated in males. However, there was not comparable change in the relative body weight against the trend of the serum cholesterol level in both sexes. In the babies normally delivered with full term, the mean cholesterol level (±SD) in the umbilical cord blood serum was 65 ± 13 mg/100 ml and it increased to 150 ± 46 mg/100 ml during one to three months after birth which was very close to the presumptive values obtained from the regression lines in the adults. There also was significant correlation between the cholesterol value and the body weight. It is concluded that in normal people, age and relative body weight are major and independent determinants of serum cholesterol level from the start of their life.

View full abstract

With methylene blue dye spraying endoscopy 392 Japanese outpatients with gastric diseases, and 253 Japanese and 84 Canadian outpatients free of gross findings in the stomach were investigated on chronic atrophic gastritis in special reference to intestinal metaplasia. Second, with the same technique 176 asymptomatic healthy residents in Kyoto, Japan, were also investigated, in which 50 residents were followed for two years and 32 subjects for four years. In each population subjects, with increasing age the fundic-pyloric (F-P) border shifted cephalad indicating atrophy of the fundic mucosa. Japanese subjects, however, showed greater variation in location of the F-P border, and also greater in symptomatic outpatients than in asymptomatic healthy subjects. The reduction in fundic gland area with aging was followed by intestinal metaplasia. In addition, our follow-up study indicates that atrophic gastritis was most likely to advance gradually wih increasing age, even in asymptomatic residents.

View full abstract

A multi-center study on the clinical effect of danazol in patients with IgA nephropathy is described. Two different doses of oral administration, including 200 mg or 300 mg per day, were employed in the present study. Urinalysis and measurements of complement components, i.e. C3 and C4, were performed before, and in the eighth and 20th week after the administration of danazol. It was demonstrated that 200 or 300 mg of danazol administration was effective in reducing the amount of proteinuria and in increasing the levels of serum complement components in the patients. It is concluded that the administration of danazol may be useful for treatment of patients with IgA nephropathy.

View full abstract

We defined duodenal ulcers (DUs) not healed within 3 months with H₂-antagonists as "intractable", because the recurrence rate of these DUs is higher than that of DUs healed within the same periods, and etiological differences are suggested to exist among these two groups. To verify the pathophysiological differences, gastric analysis including modified sham-feeding (MSF) were performed in 1 2 intractable, 10 tractable DUs and 5 healthy controls. By MSF stimulation, acid output increased in all subjects and the mean acid output of MSF amounted to about 60% of the tetragastrin maximum.Meanacid output of intractable DU cases was significantly higher than the controls in any stimulatory state and was different only in MSF with tractable DU. No significant changes of serum gastrin were recognized during MSF and both serum pepsinogen I and II are higher in DU cases than the control in basal state, but the two DU groups show no significant difference or increase by MSF or gastrin stimulation. These data suggest that vagal activity of intractable DUs is higher than not only healthy subjects, but tractable DUs and participation of gastrin in the increase of acid output by MSF might be denied.

View full abstract

Eleven patients with adult idiopathic thrombocytopenic purpura (ITP) were treated with bolus methylprednisolone at doses of 1 g/day for 3 days. In nine of eleven patients the platelet count rose to more than 100 × 10⁹/l during 2-9 days. In two other patients, it rose to 81 × 10⁹/l and 43 × 10⁹/l. In six of eleven patients splenectomy was carried out without any platelet transfusion when the platelets rose to more than 100 × 10⁹ /l after bolus mPSL therapy. Bolus mPSL therapy is efficient as a pre-treatment for a planned splenectomy in adult ITP.

View full abstract

Plasma lipids and lipoproteins obtained from different places of the circuit of double filtration plasmapheresis (DFP) were measured and effect of DFP therapy on removal of them was examined. When 2A was used as a second filter, 69.8%, 52.4%, 63.0%, 58.0%, 60.8%, 59.2% and 63.9%, respectively of β- lipoprotein, cholesterol, triglyceride, high density lipoproteins (HDL), phospholipids, free cholesterol and lipoprotein (a) (Lp(a)) were removed from the patient's plasma. When 4A was used as a second filter, 69.0%, 56.8%, 53.2%, 45.4%, 56.0%, 50.9% and 51.7%, respectively of β-lipoprotein, cholesterol, triglyceride, HDL, phospholipids, free cholesterol and Lp(a) were removed from the patient's plasma. In contrast, concentrations of free fatty acids (FFA) after DFP therapy using filter 4A and 2A increased to 222.8% and 256.4%, respectively. Thus, it was shown that except for FFA, DFP therapy using either 2A or 4A as a second filter is effective in reducing concentrations of plasma lipids and lipoproteins.

View full abstract

TAE was performed in 49 cases of HCC for clinical assessment of the usefulness. This procedure was aimed to subside intraperitoneal hemorrhage in 8 cases among them and to provide a possible antitumor effect in the remaining 41 cases. The prognosis in the 8 cases of intraperitoneal hemorrhage was 54.9 ± 41.1 days including one case survived as long as 116 days. The prognosis in the remaining 41 cases was 12.6 ± 8.3 months in group A, 7.8 ± 6.1 months in group B and 1.6 ± 1.3 months in group C according to Child's classification, while it was 2.8 ± 2.5 months in Ist branch occluded, 9.4 ± 6.1 months in IInd branch occluded and 19.2 ± 6.7 months in IIIrd branch occluded group according to the portal vein occlusion due to tumor thrombi suggesting that a more prolonged survival was attained with more favorable degree of Child's classification and less affected portal embolization. The cumulative survival time (by Kaplan-Meier's methods) was 6 months in 89% of the cases examined, 1 year in 59%, 2 years in 34% and 3 years or more in 11%, indicating significantly higher survival as compared to our TAI group. Angiographic re-opening of tumor vessel within 3 months was observed in 46.7%. TAE on HCC was useful both for the purpose of antitumor effect and of hemostasis. The degree of Child's classification and severity of portal occlusion at the initial examination may closely relate to the prognosis. Thus, angiography should be repeated within 3 months following the first TAE at least.

View full abstract

Peptide YY (PYY)-like immunoreactivity was detected in the mucosa and muscle layer of normal human colon and rectum and in well to moderately differentiated adenocarcinoma derived from the mucosa of the colon and rectum, using a sensitive and specific radioimmunoassay for PYY. The content of PYY-like immunoreactivity in the mucosa was markedly higher than those in the muscle layer and adenocarcinomatous tissue of any part of the colon and rectum. A high concentrations of PYY-like immunoreactivity was demonstrated throughout the colon mucosa (ascending colon 94.14 ± 15.34 pmol/g, transverse colon 137.19 ± 13.44 pmol/g, descending colon 168.89 ± 15.63 pmol/g, and sigmoid colon 223.69 ± 35.31 pmol/g), the highest being observed in the rectum (313.15 ± 45.90 pmol/g). The major molecular form of PYY-like immunoreactivity both in the mucosa and muscle layer of normal human colon and rectum and in adenocarcinomatous tissue was judged by gel exclusion chromatography to be identical to pure porcine PYY. This study revealed the presence of PYY-like immunoreactivity not only in normal tissue of the colon and rectum but also in adenocarcinomas with the same elution pattern, and the mucosal concentrations of PYY-like immunoreactivity were found to be increasing distally throughout the colon and rectum.

View full abstract

The purpose of this study is to disclose the molecular basis of type I familial amyloidotic polyneuropathy (FAP) in Japan. Amyloid fibril protein of type I FAP consists of a variant transthyretin (also called prealbumin) with one amino acid substitution of methionine-for-valine at position 30. This variant transthyretin is present in the serum as a precursor protein of amyloid. A radioimmunoassay (RIA) has been established to detect the variant transthyretin. All the 94 patients with FAP who originate from various districts in Japan have the variant transthyretin, but any one of 78 healthy adults of families with FAP do not have it. Half of the symptom-free children of FAP patients have the variant transthyretin even before clinical manifestations appear. The RIA is widely applicable for early diagnosis. The methionine- for-valine substitution is due to a base change from guanine to adenine at the first letter of the valine codon at position 30. Type I FAP in Japan is considered to be a molecular disorder of transthyretin. Since the age of onset ranges from twenties to forties, genetic counseling is recommended to prevent the transmission of this intractable disorder to the next generation.

View full abstract

We investigated a possible effect of doxapram (a respiratory stimulant) on the peripheral chemoreceptors in man (8 control subjects, 11 bronchitics, and 4 emphysematous). In addition, we determined whether infusion of doxapram could augment blunted chemosensitivity to hypoxia or hypercapnia seen in both chronic obstructive pulmonary disease (COPD) patients and normal subjects. Doxapram infusion caused a significant increase in ΔVE/ΔSaO2 (p < 0.05), as well as ΔPo.l/ΔSaO2 (p < 0.05) in control subjects, although the changes in both ΔVE/ΔPAco2 (where, PAco2 = end-tidal Pco2) and ΔPo.l/ΔPAco2 did not attain significant level. Control subjects with low baseline ΔPo.l/ΔSaO2 showed significantly larger changes in both ΔPo.l/ΔSaO2 and ΔVE/SaO2 during doxapram infusion than the patients with chronic bronchitis (0.02 < p < 0.05). We conclude that (1) doxapram increases chemosensitivity to hypoxia and slightly increase chemosensitivity to hypercapnia, indicating its primary action being stimulation of peripheral chemoreceptors, and (2) doxapram stimulates chemoreceptors little in patients with chronic bronchitis, whereas blunted hypoxic response in normal subjects could be increased markedly.

View full abstract

The effect of calcium supplementation on blood pressure was studied in three groups: eight normotensive subjects, 14 borderline essential hypertensive subjects, and 11 established essential hypertensive subjects (EEH). All subjects were outpatients and were given 6 g of calcium lactate (779 mg of elemental calcium) daily for 16 weeks. In EEH, systolic blood pressure was decreased significantly by 6 mmHg, but diastolic blood pressure was not decreased significantly (2 mmHg). In other groups, blood pressure was not reduced significantly. In all groups, urinary excretion of calcium was increased significantly but urinary excretion of other electrolytes, such as sodium, potassium and phosphate did not change. Serum electrolytes, various hormones, such as parathyroid hormone, 1-25(OH)₂D3/sub>, 25OHD₃, plasma renin activity, plasma aldosterone, plasma norepinephrine and epinephine, and cardiac output did not change throughout this study. There were no adverse effects observed during this trial. From these results, it was concluded that daily administration of 6 g of calcium lactate produces a slight antihypertensive effect in EEH, and that this might be useful as a supplementary treatment for essential hypertension, especially in the aged.

View full abstract

In an attempt to clarify the clinical significance of atrial natriuretic peptide (ANP) in man, plasma levels of immunoreactive ANP were studied in patients with heart diseases and in those with chronic renal failure. When ANP concentrations in pulmonary arterial plasma were compared with hemodynamic variables in patients with heart diseases who underwent cardiac catheterization, a significant positive correlation was found between plasma ANP levels and mean pulmonary capillary wedge pressure, while plasma ANP levels were not significantly correlated to mean right atrial pressure (MRAP). After the injection of contrast medium, both MRAP and plasma ANP levels increased and a significant positive correlation was observed between two variables. Plasma levels of ANP were elevated in patients with congestive heart failure according to the severity. In addition, patients associated with atrial fibrillation showed significantly higher plasma ANP levels than those on sinus rhythm. In patients with paroxysmal atrial arrhythmias, plasma ANP levels increased markedly during paroxysms. Patients with chronic renal failure had elevated plasma ANP levels, which fell after hemodialysis. These results suggest that both left and right atrial tissue can secrete ANP as a result of stretching of the cardiocytes in man and that plasma ANP levels are elevated in patients with congestive heart failure and in those with chronic renal failure by increased atrial pressure due to volume expansion. Abnormal atrial contraction per se, in addition, may stimulate ANP secretion.

View full abstract

The effectiveness of high-dose intravenous corticosteroid therapy for acute bouts of multiple sclerosis (MS) was evaluated in comparison with the conventional oral prednisolone therapy. Group I comprised 11 cases of MS treated with oral prednisolone, 30-60 mg daily, and group II comprised 16 cases treated with intravenous corticosteroids; 11 cases given 1000 mg of methylprednisolone for the initia l3 days followed by 100 mg of prednisolone, while the remaining 5 were given 100 mg of prednisolone alone.The initial dosage was maintained for 1 or 2 weeks in each group, tailing off with a period of several weeks of oral prednisolone. The clinical status was evaluated using Kurtzke's expanded disability status scale (EDSS) and functional system scale before and 1, 2 and 4 weeks after the initiation of therapy.EDSS score significantly declined from week 0 (before)to weeks 1, 2 and 4 in group II, respectively, whereas no significant decline of EDSS score was observed in group I. The frequency of improvement (0.5 of an increment in EDSS score) in group II was significantly higher than that in group I at weeks 1, 2 and 4. It was thus suggested that high-dose intravenous corticosteroid therapy might be more useful in acute bouts of MS, especially for obtaining an early improvement, than conventional oral prednisolone therapy.

View full abstract

Short-term prednisolone therapy was instituted on 27 patients with chronic active hepatitis (CAH) type B, in an attempt to induce seroconversion from hepatitis B e antigen (HBeAg) to the corresponding antibody (anti-HBe). Patients with CAH received a four-week regimen of prednisolone with daily dosage tapering from 40 to 10 mg (total 700 mg). Within one year after the withdrawal of prednisolone, 19 (70%) lost HBeAg and 11 of them (41% of the total) developed anti-HBe, at rates significantly higher than 3 (12%) and 1 (4%) who spontaneously showed respective serological changes among 26 matched controls during one year (p < 0.001). Within two years after the withdrawal, 21 (78%) lost HBeAg and 19 (70%) developed anti-HBe, in contrast to 6 (23%) and 2 (8%) of controls who showed respective changes during that period (p < 0.001). Seroconversion to anti-HBe was invariably accompanied by clinical and biochemical improvements along with loss of DNA polymerase from circulation. Elevation in transaminase levels, reflecting the rebound of steroid withdrawal, always heralded and appeared to be required for the seroconversion, but serious aggravation of hepatitis was not encountered in any of the patients.

View full abstract

Myasthenia gravis, malignant thymoma, multiple schwannomas and monoclonal IgA gammopathy coexisted in a 54-year-old Japanese man. Serum acetylcholine receptor antibody activity was located in the IgG fraction, but not in the paraprotein peak. It was speculated that all these disorders might fall under the spectrum of the diseases associated with thymic abnormality or that some growth factors might induce neoplasms and activation of B cell clones of autoantibodies (including acetylcholine receptor antibody) in this case.

View full abstract

A case of pseudoidiopathic hypoparathyroidism is described. The patient, 47-year-old male, developed numbness and muscle spasms in the extremities in July 1980. Physical and laboratory examinations revealed positive Chvostek and Trousseau's signs, hypocalcemea, mild hyperphosphatemia, normal serum magnesium, prolongation of QTc on EKG, normal reaction to Ellsworth-Howard test and high levels of serum PTH. Treatment with calcium lactate and vitamin D was successful. The literature regarding 16 cases reported in Japan was reviewed.

View full abstract

Recently, acute interstitial nephritis (AIN) presenting nephrotic syndrome and renal failure induced by nonsteroidal anti-inflammatory drug (NSAID) has been recognized with increasing frequency. We described here a 43-year-old woman who developed this type of nephropathy after taking NSAID for rheumatoid arthritis. Flurbiprofen (Froben) was assumed to be a causal drug based on a clinical course and a positive result of lymphocyte transformation test. Withdrawal of flurbiprofen therapy led no sufficient improvement, and high-dose steroid therapy done 15 months after the onset resulted in only a minor improvement. So far as we know, this was the second case of AIN associated with flurbiprofen and the youngest in NSAID-induced AIN with irreversible chronic renal insufficiency.

View full abstract

A 43-year-old man with pancytopenia and circulating blast cells was found to have acute megakaryoblastic leukemia. Bone marrow biopsy disclosed reticulin fibrosis with infiltration of blast cells. Cytogenic study showed 48, XY, +15, +18. The megakaryocytic origin of blast cells was confirmed by platelet peroxidase reaction at ultrastructural level. The spleen which had not been felt on admission increased in size rapidly and ruptured abruptly. This appears to be the first reported case of a splenic rupture associated with acute megakaryoblastic leukemia.

View full abstract

A case of lymphangiomyomatosis with marked chylous ascites and persistently elevated CA-125 levels is presented. A 30-year-old woman revealed milky urine, milky ascites and exertional dyspnea about one year after the normal delivery of her second child. The lungs showed bilateral diffuse reticular shadows. No pleural effusion was observed. Pulmonary function tests revealed hypoxemia and obstructive changes of the respiratory tract. The levels of CA-125 in blood and ascites were continuously more than 200 U/ml. The inguinal lymph node biopsy and open lung biopsy confirmed the diagnosis of lymphangiomyomatosis. The patient was first treated with progesterone without effect. Oophorectomy was then performed, resulting in the improvement of respiratory distress, although ascites continued. With addition of Le Veen's peritoneojugular shunt the patient improved with reduction of ascites.

View full abstract

Here we are reporting two cases consisting of a male patient and his elder sister from Kagashima in Gifu City and both suffering from polyneuropathy of dissociation type and skin amyloidosis. In the former, the presence of amyloid was demonstrated not only in the skin, but also in the stomach, liver and gums. He was also diagnosed suffering from chronic hepatitis of inactive type. He responded to DMSO and Cepharanthin. In the patients, no urinary Bence Jones protein nor blood M component was detected and the amyloid exhibited resistance to potassium permanganate treatment. The neuropathy of the patients were slightly different from that of the Portuguese type which starts on lower extremities as well as those conventionally have been reported in Japan.

View full abstract

A patient who had experienced water intoxication despite normal renal function and normal urinary diluting ability was observed during the initiation stage of hyponatremia. Upon the excessive water intake (10 to 15 L) for several days, he developed moderate hyponatremia (121 mEq/L) and headache, an early symptom frequently seen in water intoxication. During this period, his urine was maximally dilute (50 to 60 mOsm/kg H₂O), and his urinary sodium excretion increased. This report suggests that 10 to 15 L of water intake for several days can cause water intoxication in subjects with normal urinary diluting ability and that the increase in sodium excretion is prerequisite for the high urine flow rate.

View full abstract

A 30 years old male presented with acute gastrointestinal symptoms and encephalopathy. History, investigations and the response to chelator therapy led to the diagnosis of lead poisoning. Encephalopathy in an adult resulting from industrial exposure to inorganic lead are the main features of the case.

View full abstract

Three cases of Crohn's disease (CD) which showed an elevation of creatine phosphokinase (CPK) during the course were reported. In two cases, elevations of serum myoglobin and aldolase were also observed which indicated rhabdomyolysis. Rhabdomyolysis occurred unrelated to the activity of CD and it was asymptomatic. It was unable to identify an apparent known cause for rhabdomyolysis. All three cases were under elemental diet (ED) but the causality of ED for rhabdomyolysis was uncertain. So far as we know, there is no report on rhabdomyolysis during ED treatment and there are only two reports in which rhabdomyolysis was documented in CD. The latter was rhabdomyolysis due to electrolyte depletion secondary to malabsorption in CD which was not encountered in our cases. Our department dealt only three cases of CD and all of them had an elevation of CPK which had been measured as one of routine blood chemistry in our hospital. These observations led to a following conclusion that subclinical rhabdomyolysis may be one of extra-intestinal complications of CD.

View full abstract