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Biomedical subjects

H Imamura

Publications and source records attributed to H Imamura.

At least 307 records · Page 17Linked to original sources

Paraneoplastic syndrome of hypercalcemia and leukocytosis caused by squamous carcinoma cells (T3M-1) producing parathyroid hormone-related protein, interleukin 1 alpha, and granulocyte colony-stimulating factor.

Previously we reported that a clonal squamous cell carcinoma cell line (T3M-1) derived from a lower jaw cancer of a patient with marked leukocytosis and hypercalcemia produced factors containing a potent bone-resorbing activity (BRA) (Mr 15,000-20,000) and a colony-stimulating activity. To elucidate the pathogenesis of this humoral hypercalcemia, BRA and colony-stimulating activity in both the conditioned medium and cells were characterized. The conditioned medium, when eluted at neutral pH, contained colony-stimulating activity and thymocyte proliferation-stimulating activity, the latter of which comigrated with BRA. Upon elution with acetic acid (pH 2.0), the conditioned medium contained no interleukin 1-like activity but potent parathyroid hormone-like activity, which comigrated with BRA. Northern blot hydridization analysis revealed that T3M-1 cells produced constitutively mRNA for parathyroid hormone-related protein and granulocyte colony-stimulating factor. Furthermore, primer extension analysis revealed that the cells also produced mRNA for interleukin 1 alpha (IL-1 alpha). Since parathyroid hormone-related protein and IL-1 alpha (osteoclast-activating factor) synergistically increase the concentration of serum calcium, and since IL-1 alpha (hemopoietin 1) potentiates granulocyte colony-stimulating factor-induced granulocytopoiesis, we speculate that parathyroid hormone-related protein, granulocyte colony-stimulating factor, and IL-1 alpha are synergistically involved in a paraneoplastic syndrome of hypercalcemia and leukocytosis, at least in some patients with solid tumors.

Animals↗

Effect of interleukin-1 (IL-1) on thyroid hormone metabolism in mice: stimulation by IL-1 of iodothyronine 5'-deiodinating activity (type I) in the liver.

To elucidate the mechanism by which the low T3 and low T4 syndrome occurs in patients with infection, recombinant human interleukin-1 (IL-1) was administered to mice, and their thyroid hormone metabolism was studied. Continuous sc infusion of IL-1 alpha or IL-1 beta at a dose of 0.015-1 microgram/day for 3 days decreased food intake and serum T4, T3, and rT3 concentrations in a dose-dependent manner. In pair-fed control (PFC) mice, serum T4 and T3 also decreased, but rT3 was reciprocally increased. The T3/T4 ratio was greater in IL-1-treated mice than in PFC mice. Although food intake was decreased by 65% in IL-1-treated mice (1 microgram/day) compared with that in fed control mice, type I iodothyronine 5'-deiodinating activity in liver was significantly increased compared with that in fed control mice. Furthermore, the T3 and T4 responses to TSH were greatly diminished in IL-1-treated mice. These findings suggest that IL-1 directly inhibited the effect of TSH on the thyroid gland and decreased the serum concentrations of T4 and T3, and that an increase in type I iodothyronine 5'-deiodinating activity in livers of IL-1-treated mice may account for the greater T3/T4 ratio and lower serum rT3 concentration than those in PFC mice. Since tumor necrosis factor-alpha has a similar effect, we speculate that both cytokines may be synergistically involved in the altered thyroid hormone metabolism in mice (decreased serum T4, T3, and rT3 concentrations) and hypercatabolism in a febrile state.

Animals↗

Parathyroid hormone-related protein and interleukin-1 alpha synergistically stimulate bone resorption in vitro and increase the serum calcium concentration in mice in vivo.

To elucidate the mechanism of humoral hypercalcemia elicited by human esophageal carcinoma cells (EC-GI), which constitutively produced interleukin-1 alpha (IL-1 alpha) and PTH-like factor, the effects of IL-1 alpha and PTH-related protein (PTH-rP) on bone resorption in vitro and on serum calcium concentrations in vivo were investigated. Nude mice transplanted with EC-GI cells invariably developed hypercalcemia, although their urinary cAMP excretion remained within the normal range. IL-1 alpha or PTH-rP-(1-34) stimulated 45Ca release from prelabeled fetal mouse forearm bones in a concentration-dependent manner, and when combined, IL-1 alpha and PTH-rP-(1-34) synergistically stimulated bone resorption in vitro. Injection of PTH-rP-(1-34) into mice three times a day for 2 days increased the serum calcium concentration in a dose-dependent manner. Continuous infusion of IL-1 alpha occasionally increased the serum calcium concentration. Simultaneous administration of IL-1 alpha at rates of 1-2.7 micrograms/day and PTH-rP-(1-34) at doses of 15-30 micrograms/day synergistically increased the serum calcium concentration in vivo. These findings suggest that PTH-rP and IL-1 alpha produced by the tumor cells were synergistically responsible for the humoral hypercalcemia observed in both the original patient and the tumor-bearing nude mice, and that at least two bone-resorbing factors [PTH-rP and another nonadenylate cyclase-stimulating bone-resorbing factor(s)] are active in patients with malignancy-associated hypercalcemia, in whom nephrogenous cAMP excretion is neither increased nor decreased.

Animals↗

[A study of aphasia caused by putaminal hemorrhage].

Aphasia was evaluated in 21 right-handed patients (39-74 years old) with putaminal hemorrhage, and compared with that caused by thalamic hemorrhage. The patients were divided into three groups by the volume of the hematoma: small hematoma (I, n = 6), middle hematoma (II, n = 8) and large hematoma (III, n = 7) groups in computed tomographic findings. Aphasia examination was performed 8-37 days (mean 21 days) after the onset. In group I, aphasia was not seen or just transient, if any. In group II, aphasia was mainly a mixed type, and the prognosis was excellent in many patients. In group III there were expressive type at anterior lesion, receptive type at posterior lesion and global aphasia at anterior-posterior lesion, and the prognosis was not good. It is suggested that the putamen itself does not participate in language behavior, and that aphasia caused by putaminal hemorrhage is due to destruction of the surrounding tissue of the putamen. The type of aphasia and prognosis are varied by the site of a lesion and a hematoma volume. It is also suggested that the thalamus is related to language behavior in a circle of thalamus-cortical language area-thalamus. Aphasia caused by putaminal or thalamic hemorrhage was observed to be different from classical cortical aphasia. But there was no significant difference between aphasia caused by putaminal lesions and that by thalamic lesions.

Adult↗

[Pharmacokinetic and clinical studies of clarithromycin in the pediatric field].

Pharmacokinetic and clinical studies on clarithromycin (TE-031, A-56268), a new macrolide antibiotic, were performed in the pediatric field. 1. Pharmacokinetic investigation We studied serum concentrations and urinary excretions after single oral administration of TE-031 granules and tablets. Doses were 1, 5, 10 and 15 mg/kg body weight in case of granules (10% TE-031) and 150 mg/kg body weight in case of tablets (50 mg TE-031, 3 tablets). As results, Tmax's were 1-2 hours after administration in case of both granules and tablets. Cmax's in cases of granules were 0.29 +/- 0.15 micrograms/ml in 1 mg/kg administration, 2.53 +/- 0.71 micrograms/ml in 5 mg/kg, 4.11 +/- 1.37 micrograms/ml in 10 mg/kg, 6.28 +/- 1.48 micrograms/ml in 15 mg/kg showing a dose dependency. T 1/2's were 1.8-6.5 hours in cases of 1, 5, 10, 15 mg/kg of granules and tablets. T 1/2's became longer with increased doses. Urinary recoveries were 9.4 +/- 2.4% to 31.6 +/- 19.0% in 6 hours after administration. 2. Clinical investigation Clinical study was carried out in 24 patients of respiratory infections. Clinical efficacies were excellent in 11 patients, good in 12 patients and fair in 1 patient. The clinical efficacy rate was 95.8%. No side effects were observed. The above results suggest that TE-031 is a useful oral antibiotic for treating pediatric respiratory infections, especially those due to Mycoplasma pneumoniae.

Adolescent↗

Five-year clinical course of aortic regurgitation without coronary aneurysm following Kawasaki disease.

Kawasaki disease has recently been considered as a major cause of acquired valvular diseases in infants and children. But there have been few reports on the clinical course of the lesions caused by this disease, particularly aortic regurgitation. In February 1982, we examined a six-month-old male infant who had Sellers third degree aortic regurgitation (AR) and Sellers first degree mitral regurgitation (MR) without discernible dilatation, aneurysm formation or stenosis of the coronary arteries, and in January 1987 we performed a second cardiac catheterization in order to estimate the progress of these lesions. The results were: 1) His AR showed no apparent worsening; 2) His MR had completely recovered; 3) His volume and pressure studies were almost normal. The catheterization data were compatible with those of other clinical examinations. He no longer had cardiac enlargement as seen on a chest roentgenogram, and there were no signs of left ventricular hypertrophy on an electrocardiogram (ECG).

Aortic Valve Insufficiency↗

[Carpal tunnel syndrome in acromegaly--4-case report and review of literature].

Four cases of carpal tunnel syndrome in acromegaly were reported. These 4 cases were found in 21 acromegalies (19%). Besides change of features, they complained bilateral sensory disturbances of their hands. After transsphenoidal removal of pituitary adenoma, GH levels returned to the normal range and sensory disturbances were improved in all cases. Mechanism of carpal tunnel syndrome in acromegaly is that edematous synovial tissues compress the median nerve because oversecretion of growth hormone causes increase of sodium and water retention in the extracellular fluid. The patient who showes high basal level of growth hormone and/or acromegalic pattern by various tolerance tests does not always have the carpal tunnel syndrome. But this syndrome is apt to be found in active acromegaly. So the detection of the symptom showed by this activity such as hypersudation in our cases leads to the early diagnosis of acromegaly.

Acromegaly↗

[Pharmacokinetic and clinical studies on sulbactam/ampicillin in the pediatric field].

Pharmacokinetic and clinical studies of sulbactam/ampicillin (SBT/ABPC) were conducted and the obtained results are summarized as follows. For pharmacokinetic investigation, SBT/ABPC at 30 or 60 mg/kg was administered by intravenous drip infusion over 30 minutes. The maximum blood concentration was reached just after the completion of the drip infusion in both groups. The mean peak serum concentrations of SBT and ABPC were 22.4 +/- 0.8 micrograms/ml and 32.8 +/- 1.0 micrograms/ml, respectively, in the 30 mg/kg group, and they were 54.2 micrograms/ml and 93.8 micrograms/ml, respectively, in the 60 mg/kg group. The concentrations were dose-related. The mean half-lives of SBT and ABPC following 30 mg/kg SBT/ABPC administration were 0.91 +/- 0.04 hour and 0.90 +/- 0.05 hour, respectively, and those following 60 mg/kg SBT/ABPC were 1.08 hours and 0.84 hour, respectively. The highest urinary concentration occurred 0-2 hours after the 30 minutes drip infusion. Mean urinary excretion rate of SBT and ABPC over 6 hours were 71.4 +/- 2.5% and 54.6 +/- 3.3%, respectively, in the 30 mg/kg group, and they were 80.0% and 63.7%, respectively, in the 60 mg/kg group. In the clinical investigation conducted with a total of 24 patients (15 with respiratory tract infections, 3 with urinary tract infections, 2 with lymphadenitis, and others), SBT/ABPC was found to be excellent in 14 cases, good in 9, fair in 1. The efficacy rate was, therefore, 95.8%. In the bacteriological evaluation, 9 out of 11 clinically isolated strains were eradicated, 1 unchanged and 1 unknown. The elimination rate was 90.0%. Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, a slight elevation of GOT was observed.

Adolescent↗

[Aneurysm of the left sinus of Valsalva producing obstruction of the left main coronary artery and aortic regurgitation].

A 50-year-old male was admitted with dyspnea on exertion and palpitation. On physical examination, a grade 2/6 aortic regurgitant murmur was heard at the left sternal border. A chest roentogenogram showed an oval shadow on the left cardiac border. Digital subtraction angiogram, aortogram and coronary arteriogram revealed an unruptured-large aneurysm of the left sinus of Valsalva, which compressed the left main coronary artery and produced aortic regurgitation. Surgical correction consisted of obliteration of the orifice of the aneursym with woven Dacron graft patch, aortic valve replacement using SJM23A, and a saphenous vein bypass from the ascending aorta to the left anterior descending coronary artery. Postoperative studies showed complete obliteration of the orifice of the aneurysm, a patent aorto-coronary bypass graft and no perivalvular leakage. This aneurysm was considered congenital in origin, because of no inflammatory and infectious evidence, negative serologic test for syphilis and no aneurysmal dilatation of the ascending aorta.

Aortic Aneurysm↗

[Laboratory and clinical studies on cefodizime in the pediatric field].

Laboratory and clinical studies on cefodizime (CDZM, THR-221), a newly developed cephem antibiotic, were done. The results obtained are summarized as follows: 1. Absorption and elimination were examined in a total of 5 cases including a case of 10 mg/kg intravenous drip infusion for 30 minutes, 2 cases of 20 mg/kg rapid intravenous injection and 2 cases of 40 mg/kg drip infusion for 30 minutes. Maximum serum levels were attained immediately after drip infusion or rapid injection. Cmax's were 119.2 micrograms/ml for 10 mg/kg, 374.9 micrograms/ml or 255.7 micrograms/ml for 20 mg/kg, and 321.3 micrograms/ml or 431.8 micrograms/ml for 40 mg/kg. These values were determined using an high performance liquid chromatography (HPLC) method. In general, values using the bioassay were higher than those with the HPLC method. T 1/2 (beta)'s were between 1.74 and 1.93 hours using HPLC, and between 1.77 and 2.24 hours using bioassay. Urinary recovery rates were examined in 3 out of 5 cases. Cumulative urinary recovery rates were 57.9-90.6% with HPLC method and 50.4-88.0% with bioassay in a period of 0-8 hours after administration. 2. Clinical efficacy was evaluated in a total of 22 cases including 14 cases of respiratory tract infections, 5 cases of urinary tract infections and 3 cases of cellulitis. Clinical efficacy rate was 95.2%. Bacteriologically, pathogenic organisms were eradicated in 90.0%. As adverse reactions, 1 angular stomatitis, 1 diarrhea and 1 loose stool were noted. Abnormal laboratory test values detected were 1 case of increased GPT and 1 case of increased GOT and GPT.

Adolescent↗

[Histopathological study on the safety of conservative breast surgery in terms of the degree of axillary dissection for breast cancer].

The subjects were 15 patients with primary mammary cancer who underwent radical mastectomy. Axillary dissection (level I, II and III) with an incision 7 cm below the axilla was performed. After radical mastectomy, the presence/absence of remaining lymph nodes and fatty tissue was determined. All operations were performed by the same surgeon. The number of lymph nodes dissected by means of subaxillary incision ranged from 10 to 32 (mean 20.4). The proportion of remaining lymph nodes found after radical mastectomy was 0/142 (0%) for level I, 0/113 (0%) for level II and 3/54 (5.6%) for level III. In the subclavian Halsted area, fatty tissue partially remained in 60.0% of the patients and more than half in 13.3%. It was shown that complete dissection of level III lymph nodes is difficult when this surgical technique is employed. Although fatty tissue did remain in some cases after level II dissecting, this technique presented hardly any problems in the case of level I and II dissection. Therefore, from the viewpoint of axillary dissection alone, the present technique can achieve results similar to those obtained by radical mastectomy, suggesting its applicability to mammary cancer at a relatively early stage.

Adipose Tissue↗

[A very rare autopsy case of metastatic brain tumor originating from ureteral cancer].

We report here a very rare case of metastatic brain tumor originating from ureteral cancer which was verified at autopsy. An 88-year-old elderly woman was admitted to our department because of recurrent convulsions which started in March, 1987. Following this episode, right hemiparesis and speech disturbance appeared on June 6, 1987. Neurological examinations at admission on August 12, 1987 showed slightly disturbed consciousness, motor dominant aphasia, and dysphasia. Enhanced CT scan demonstrated a large tumor in the left frontal lobe with perifocal edema, and a small mass in the right frontal lobe (Fig. 1). Left carotid angiogram showed downward displacement of the middle cerebral artery complex at the Sylvian portion. After admission, she developed marked distention of the abdomen, with occurrence of hematuria followed by aggravation of respiration and consciousness. She died on September 2, 1987. Removal of metastatic brain tumor had not been performed due to the poor general condition of the patient. An autopsy was permitted. A coronal section of the cerebrum clearly demonstrated a large tumor in the left frontal lobe with small mass in the right frontal lobe (Fig. 2). Kidney and the ureter at the right side showed hydronephrosis and hydroureter because of the presence of ipsilateral ureteral tumor at the distal end (Fig. 3). Microscopical findings verified that the metastatic brain tumor was a transitional cell carcinoma, which was, histologically, completely the same as the ureteral tumor (Fig. 4, 5). No case of metastatic brain tumor originating from ureteral cancer has yet been reported, as far as the authors know.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Clinical study of prostatic cancer].

Eighty patients with prostatic cancer, who first visited Kyorin University School of Medicine from January 1976 through December 1986, were analyzed. Incidence of prostatic cancer was 3.9% among male inpatients. Age distribution was between 55 and 88, with an average of 72 years old. The most common symptoms were dysuria followed by pollakisuria, hematuria, lumbago and lower extremity pain. Duration from onset of symptom to examination ranged from 6 to 84 months, with an average of 22 months. Clinical stage was A in 7.5%, B in 10%, C in 11.3% and D in 71.3%. According to histological grade, well, moderately, and poorly differentiated adenocarcinomas were observed in 29.9, 29.9 and 40.2%, respectively. According to the General Rules for Clinical and Pathological Studies on Prostatic Cancer, clinical T classification were T0 in 8.7%, T1 in 3.8%, T2 in 47.5%, T3 in 27.5% and T4 in 12.5%. In the correlation between stage and grade, the largest number of poorly differentiated adenocarcinoma cases was in stage D. There was no correlation between stage and T classification. Of the 80 patients, 71.25% were treated with antiandrogen therapy, 16.25% with radiation therapy chiefly, 7.5% by surgery chiefly, and 5% with chemotherapy. Survival rate was calculated by the Kaplan-Meier method. Overall survival rate of the 80 patients was 54.4% at 5 years. Survival rate by stage were 100% in stage A at 4 years, and 100% in B, 87.5% in C and 40.5% in D at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

3,3',5'-Triiodothyronine inhibits ontogenetic development of iodothyronine-5'-deiodinase in the liver of the neonatal mouse.

To elucidate the effect of rT3 on iodothyronine-5'-deiodinating activity (I-5'-DA) in the liver of neonatal mice, rT3 was injected sc on the 5-8th day after birth and I-5'-DA in the liver was determined. A single injection of rT3 (0.01-1 microgram/g) inhibited the ontogenetically developing I-5'-DA in a dose- and time-dependent manner. The inhibitory effect was reversible and specific for I-5'-DA. Lineweaver-Burk analysis revealed that the time- and dose-dependent decrease in the enzyme activity was due to a decrease in Vmax with no alteration in Km values (5 x 10(-8) mol/l). The maximal inhibitory effect was observed at a dose of 1 microgram rT3/g, whereas the inhibitory effect was diminished at greater doses (4-10 micrograms/g), probably owing to a contamination with T4 of the rT3 preparation administered. Furthermore, consistent with our previous in vitro findings, rT3 inhibited the I-5'-DA induced by T3 in the liver of neonatal mice. These findings suggest that rT3 inhibited I-5'-DA in the liver of neonatal mice by decreasing the amount of enzyme available to the substrate and that rT3 also elicited an antagonistic effect against T3 in the induction of I-5'-DA in vivo.

Animals↗

[Pharmacokinetic and clinical studies of sultamicillin fine granules in children].

Sultamicillin (SBTPC) is a semi-synthesized beta-lactam antibiotic consisted of ampicillin (ABPC) and a beta-lactamase inhibitor, sulbactam (SBT), linked with an ester linkage. Pharmacokinetic and clinical studies using SBTPC 10% fine granules were performed in pediatric patients with a variety of infections. 1. Pharmacokinetic investigation: SBTPC was given at 30 minutes after meal at a dose of 10 mg/kg. Peak serum levels were attained at 1 hour after dosing with average levels of 3.83 +/- 0.27 micrograms/ml for ABPC and 2.73 +/- 0.30 micrograms/ml for SBT. The average half-life of ABPC was 1.52 +/- 0.25 hours and that of SBT was 1.13 +/- 0.09 hours. The urinary recovery rate of ABPC during 6 hours after dosing was 58.2 +/- 4.9% and that of SBT was 59.7 +/- 6.4%. 2. Clinical investigation: Enrolled in the study were a total of 26 patients including 12 with tonsillitis, 6 with pharyngitis, 5 with urinary tract infections, and 1 each with bronchitis, with Salmonella enteritis and a case with fever of unknown case. Responses were excellent in 15 patients, good in 8, fair in 2 and poor in 1 with an efficacy rate of 88.5%. In the assessment of the bacteriological efficacy, 11 out of 14 strains of organisms isolated previous to the treatment were eradicated, 1 strain was found reduced in number and 2 strains remained unchanged with an eradication rate of 78.6%. One patient (3.8%) out of the 26 had diarrhea as side effects and 3 patients (16.7%) of 18 showed eosinophilia in laboratory examinations.

Adolescent↗