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Biomedical subjects

M Tsumura

Publications and source records attributed to M Tsumura.

At least 19 recordsLinked to original sources

Atypical alkaline phosphatase isozymes in serum and urine of patients with renal failure.

BACKGROUND: Alkaline phosphatases (ALPs) originating from different organs are frequently detected in the serum and urine of patients with renal failure. METHODS: We investigated the characteristics of ALPs in the serum and urine of 108 patients with chronic renal failure (CRF) and of 106 healthy control subjects. RESULTS: In polyacrylamide gel electrophoresis, three atypical ALP bands in serum of patients were designated as atypical-s1, -s2 and -s3, respectively. In contrast, five atypical bands (u1, u2, u3, u4 and u5) were detected in the urine of patients. The atypical ALPs were electrophoretically isolated and assayed to determine their biochemical properties, i.e., neuraminidase sensitivity, heat stability, reactivity to anti-intestinal or anti-tissue nonspecific ALP antibodies, molecular sizes and sugar chain heterogeneities. From these results, we found that atypical-s1 and -s2 were the intestinal-type ALP, while s3 was the tissue-unspecific type ALP. Atypical-u1, -u2 and -u3 were high-molecular type ALPs, which we suggested as the ones that originated from the intestine. Atypical-u4, a tissue-unspecific type ALP, was detected with considerable frequency in the urine of patients. In patients with CRF, the appearance of these atypical ALPs was accompanied by a deterioration of the creatinine clearance. CONCLUSIONS: The appearance of atypical ALPs in the serum and urine of patients with CRF may be a useful marker for renal disease.

Adult↗

Serum lipid metabolism abnormalities and change in lipoprotein contents in patients with advanced-stage renal disease.

BACKGROUND: Arteriosclerosis is the major cause of death in patients with chronic renal failure. There is much interest in the lipid metabolism of patients treated with hemodialysis. METHODS: We analyzed low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in chronic renal failure (CRF) patients according to patients on hemodialysis (HD), patients with diabetic nephropathy before initiation of dialysis (DN), and patients with chronic glomerulonephritis in the conservative stage (CGN); and compared the lipid metabolic abnormalities in patients on hemodialysis and those not yet on hemodialysis. We also analyzed the qualitative abnormalities of LDL and HDL and their relationship with the pathological stages. RESULTS: Electrophoretic patterns identified small LDL particles and small HDL particles in the three groups, and the degree of denaturation was more enhanced in CRF patients in the conservative stage than in HD patients. For LDL susceptibility to oxidation LDL (oxLDL) by addition of Cu(2+), the lag time was approximately 57 min in healthy controls and CGN patients, but was prolonged to approximately 75 min in HD and DN patients. For HDL susceptibility to oxidation HDL (oxHDL), HD, DN and CGN patients showed lag times shorter than those found in healthy control subjects. These results showed that LDL and HDL in the serum of CRF patients were in a state of enhanced susceptibility to oxidative modification. In Western blot analysis using anti-human-denatured LDL and anti-human-oxidized HDL monoclonal antibodies, bands of low molecular oxLDL at 150-197 kDa were detected in all CRF patients, with marked tailing in CGN patients. Similarly, bands of small oxHDL particles at 110 and 120 kDa were found in HD, DN and CGN patients. CONCLUSIONS: Oxidative modification of both LDL and HDL occurs in patients with advanced CRF resulting in small lipoproteins. Increased production of oxLDL and oxHDL is the main cause of lipid metabolic abnormality in CRF patients.

Aged↗

[Subependymoma of the lateral ventricle: a case report].

We report a case of subependymoma of the right lateral ventricle in a 59-year-old man. CT revealed a mass lesion in the right lateral ventricle. No calcification was seen in the tumor, and the right lateral ventricle was dilated dominantly by the tumor. The tumor showed intermediate intensity on T1-weighted MR images and high intensity on T2-weighted MR images. On contrast study, the tumor showed heterogeneous enhancement. We suspected this to be a case of central neurocytoma, and surgical resection was performed. The histological diagnosis was subependymoma, but we considered it difficult to differentiate from astrocytoma, central neurocytoma, and ependymoma.

Aged↗

Decreased plasma levels of fibronectin in amyotrophic lateral sclerosis.

OBJECTIVES: Fibronectin (FN) possesses a wide range of biological functions. However, the role of plasma FN in vivo has not yet been established and there have been no published studies of plasma FN in ALS. The aim of this study was to measure plasma FN in ALS patients. MATERIAL AND METHODS: We measured plasma FN levels in 28 ALS patients, 18 control subjects with other neurologic or muscular diseases (control group A) and 21 healthy adults (control group B). The age and sex distributions among the 3 groups were comparable. RESULTS: Plasma FN levels were significantly lower in ALS patients than in control groups A and B. There was also a significant negative correlation between plasma FN levels and duration of illness in ALS patients. CONCLUSION: These data suggest that a metabolic alteration of FN may take place in ALS and that the measurement of plasma FN may serve as an indicator of clinical progression of this disorder.

Amyotrophic Lateral Sclerosis↗

Increased serum hyaluronic acid in amyotrophic lateral sclerosis: relation to its skin content.

BACKGROUND: Abnormalities of hyaluronic acid (HA) of skin have been reported in patients with amyotrophic lateral sclerosis (ALS). However, little is known concerning the changes of serum HA in ALS. The purpose of this study was to investigate skin HA content and serum HA levels in ALS patients. METHODS: We measured skin HA content and serum HA levels in patients with ALS, and compared the results with those of control subjects. RESULTS: Skin HA content in ALS patients was significantly higher than in diseased control subjects and control subjects without neurological disorders, and increased significantly, the longer the duration of illness. Serum HA concentrations in patients with ALS were significantly higher than in diseased control subjects and in healthy control subjects, and were positively and significantly associated with duration of illness. There was an appreciable positive correlation between serum HA concentrations and skin HA content in ALS patients. CONCLUSION: These data suggest that a metabolic alteration of HA may take place in ALS and increased levels of serum HA may reflect an increased content of skin HA in ALS.

Adult↗

Increased expression of insulin-like growth factor I in skin in amyotrophic lateral sclerosis.

OBJECTIVES: Insulin-like growth factor I (IGF-I) has potent effects on motor neuron survival and is being studied as a possible therapeutic agent for ALS. However, little is known concerning IGF-I in the skin of patients with amyotrophic lateral sclerosis (ALS). The aim was to evaluate IGF-I immunoreactivity of skin in patients with ALS. METHODS: IGF-I immunoreactivity of skin from 18 patients with ALS and 16 controls was examined. RESULTS: IGF-I immunoreactivity was markedly positive in the epidermis and dermal blood vessels and glands and was moderately positive in the reticular dermis in all patients with ALS. On the other hand, the epidermis and dermal blood vessels and glands and the reticular dermis showed a weak IGF-I immunoreactivity in controls. The optical density for IGF-I immunoreactivity of the epidermis and dermal blood vessels and glands, and the reticular dermis in patients with ALS was significantly higher than in diseased controls, and was significantly increased with duration of illness. CONCLUSIONS: These data suggest that a metabolic alteration of IGF-I may take place in the skin of patients with ALS.

Aged↗

Serum markers of type I collagen synthesis and degradation in amyotrophic lateral sclerosis.

Collagen abnormalities in the skin and spinal cord have been reported in amyotrophic lateral sclerosis (ALS) patients. Serum carboxyterminal propeptide of type I procollagen (PICP) and the carboxyterminal cross-linked telopeptide of type I collagen (ICTP) reflect type I collagen synthesis and degradation, respectively. However, there has been no study concerning PICP or ICTP in ALS. We studied collagen contents of the skin and measured serum levels of PICP and ICTP in patients with ALS and control subjects. Serum PICP levels were significantly lower in ALS patients than in controls. Serum ICTP levels were significantly higher in ALS patients than in controls, and there was an appreciable positive correlation between serum ICTP levels and the duration of illness in ALS patients. In ALS patients, the collagen content of the skin was significantly smaller than in controls and indicated a progressive decrease in relation to illness. In addition, there was a significant negative correlation between serum ICTP concentrations and the collagen content of the skin in ALS patients. These data suggest that increased ICTP levels and decreased serum PICP levels may reflect unique changes in the skin, with a predominance of degradation compared to the synthesis of type I collagen in ALS.

Adult↗

Novel potassium channel opener prodrugs with a slow onset and prolonged duration of action.

(-)-(3S,4R,1'R,6'S)-4-(4-Benzyl-5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2 -yloxy)-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbo nitrile and its derivatives with a modified benzyl group were synthesized with the objective of discovering novel ATP-sensitive potassium channel openers (PCOs) with a slow onset of action and a reduced tendency to induce tachycardia. Among the compounds synthesized, 4-(2-chlorobenzyl) derivative 5bB had potent hypotensive activity in spontaneously hypertensive rats (SHRs). In addition, compound 5bB showed the desired pharmacological profile with a slow onset and long duration of action and induction of only mild tachycardia. Compound 5bB was found to be quantitatively metabolized in rats to give active des-2-chlorobenzyl derivative 6B. These results suggest that the incorporation of an N-benzyl group is a useful method for the preparation of prodrugs, the function of which is to delay the onset and prolong the duration of action of the active substance.

Administration, Oral↗

[Inter-examiner reliability of nerve conduction measurements].

A total of 122 patients were performed motor and sensory nerve conduction studies of the upper limb by two examiners (1. doctor, 2. medical technician) to know the inter-examiner reliability of nerve conduction measurements. Subjects contained normal individuals and various types of neuropathy patients. Motor nerve conduction studies were carried out in the median nerve, and antidromic sensory nerve conduction studies were performed in the median and ulnar nerves. F-wave latency of the median nerve and sensory conduction velocity between finger and wrist of the median and ulnar nerves presented the equal mean value between two examiners. A relatively good correlation between two examiners was pointed out in the distal motor latency and F-wave latency. Inappropriate measurements were caused by the differences in the site of placement of stimulating or recording electrodes and effects of submaximum stimuli or stimulus spread to other nerves. In sensory nerve conduction studies, especially in the ulnar nerve, careful attention should be paid to avoid the influence of motor artifact in giving supramaximum stimuli. Amplitude measurements showed larger inter-examiner difference than latency or velocity measurements. We reported the present condition of measurement reliability. We should do our best to minimize the error.

Humans↗

Identification of major biliary and urinary metabolites of ecabapide in rats.

1. The structures of major biliary and urinary metabolites of ecabapide in rat were identified by comparison with authentic standards using lc-ms and 1H-nmr spectrometry. 2. A major metabolite was found in the bile obtained from rat after an oral dose of 14C-ecabapide and identified as the amidaldehyde derivative. In the urine, two polar metabolites were characterized as the phenolic sulphates. Further, two lipophilic metabolites were identified as alcohol derivatives, and two others as oxamic acids. 3. From these results, it was estimated that the first step in the metabolism of ecabapide in rat was oxidative N-dealkylation to produce the amidaldehyde. This amidaldehyde was further metabolized by two routes, one by reduction of the amidaldehyde into the corresponding alcohol followed by mono-demethylation and subsequent aromatic O-sulphation, the second by oxidation of the amidaldehyde into the oxamic acid followed by mono-demethylation and subsequent aromatic O-sulphation.

Animals↗

[Expression of CD44 variant 6 and its metastatic potential in squamous cell carcinoma of the oral cavity].

Using antihuman CD44 variant 6 monoclonal antibody (2F10), immunohistochemical screenings were performed for 38 oral squamous cell carcinoma cases and 10 oral mucosa in healthy cases as normal counterpart. Normal epithelium in the oral surface was stained intensely by the antibody. The reactivity was particularly strong in the spinous layers of stratified squamous epithelium. Cells in the basal layers exhibited moderate staining. In contrast, expression of CD44v6 tended to be downregulated in 38 oral squamous cell carcinoma materials. Interestingly, more faint or no staining by the anti-CD44v6 monoclonal antibody was found in the primary squamous cell carcinomas involving regional lymphnode metastasis. Downregulation of CD44v6 isoform was suggested to occur during regional lymphnode metastasis on oral squamous, cell carcinomas.

Carcinoma, Squamous Cell↗

[A case of tuberculous pyothorax with retroperitoneal gravitation abscess].

A 65-year-old woman being treated under the diagnosis of pneumonia was subjected to further evaluation for right back tenderness. Chest radiography revealed a granular, net-like shadow in the right lower lung field, and right pleural thickening with pleural fluid retention. Ultrasonography demonstrated a cystic mass of uniformly low echo density, corresponding to the site of tenderness. This lesion was located on the right renal dorsal, right iliopsoas muscle ventral side. Based on CT findings of internal water density and marginal enhancement, the lesion was diagnosed as an abscess. With the suspicion of right tuberculous pyothorax with retroperitoneal gravitation abscess, puncture was attempted. The diagnosis was confirmed by the presence of Mycobacterium tuberculosis in the specimen. Antituberculosis chemotherapy was initiated, with drainage for symptom relief and lesion range definition. The abscess cavity communicated with the right pleural cavity via s stalk. The stalk path was confirmed by CT, and surgical curettage was performed. Tuberculous pyothorax with retroperitoneal gravitation abscess is rare and is not discussed in standard textbooks. In large series of cases it is not mentioned. In this patient we assumed that retroperitoneal gravitation abscess occurred as a result of the advanced state of tuberculous pyothorax.

Abdominal Abscess↗

Cloning and nucleotide sequencing of a novel 7 beta-(4-carboxybutanamido)cephalosporanic acid acylase gene of Bacillus laterosporus and its expression in Escherichia coli and Bacillus subtilis.

A strain of Bacillus species which produced an enzyme named glutaryl 7-ACA acylase which converts 7 beta-(4-carboxybutanamido)cephalosporanic acid (glutaryl 7-ACA) to 7-amino cephalosporanic acid (7-ACA) was isolated from soil. The gene for the glutaryl 7-ACA acylase was cloned with pHSG298 in Escherichia coli JM109, and the nucleotide sequence was determined by the M13 dideoxy chain termination method. The DNA sequence revealed only one large open reading frame composed of 1,902 bp corresponding to 634 amino acid residues. The deduced amino acid sequence contained a potential signal sequence in its amino-terminal region. Expression of the gene for glutaryl 7-ACA acylase was performed in both E. coli and Bacillus subtilis. The enzyme preparations purified from either recombinant strain of E. coli or B. subtilis were shown to be identical with each other as regards the profile of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were composed of a single peptide with the molecular size of 70 kDa. Determination of the amino-terminal sequence of the two enzyme preparations revealed that both amino-terminal sequences (the first nine amino acids) were identical and completely coincided with residues 28 to 36 of the open reading frame. Extracellular excretion of the enzyme was observed in a recombinant strain of B. subtilis.

Amidohydrolases↗

[A case of traumatic diaphragmatic hernia presenting a distinct thoracic abnormal shadow after a long course of disease].

A 43-year-old man came to our hospital for further examination of a thoracic abnormality pointed out on a check-up examination. Chest X-ray revealed a protruding tumor shadow on the right diaphragm. The patient had a history of right precordial contusion due to a traffic accident about 2 years previously, and after the injury a shadow appeared which gradually became larger, suggesting traumatic right diaphragmatic rupture-induced hernia. Chest CT scan revealed middle hepatic vein within the tumor without changes such as deviation and/or stenosis and hepatoparenchymatous tumor. Ultrasonography revealed the tumor to comprise a part of the liver (S4, S8) with the normal internal echo and the right diaphragm dividing the liver parenchyma in two, intrathoracically and intraperitoneally. The above led to the diagnosis of right diaphragmatic hernia, which probably was caused by the traffic injury and gradually increased during approximately 2 years. In cases of suspected traumatic right hemidiaphragmatic hernia, ultrasonography is regarded as useful.

Adult↗

Clinical values for an index predicting postoperative residual liver function by pre-operative liver-scintigraphy in patients with liver disease.

Hepatic resection is essential in treating hepatocellular carcinoma. However, before an operation, it is difficult to predict the functional reserve in the remnant following massive resection. We devised an original method by which effective liver volume was measured by liver scintigraphy. In order to predict the residual liver function before hepatic resection in a preoperative radiocolloid study, we obtained a predictive index by combining the K values with effective liver volumes which seemed to have the estimated residual liver function. Twenty-one patients with liver or biliary tract disease were selected at random for the present study. We divided them into 3 groups in accordance with prognosis after hepatic resection. There were statistically significant difference between the deceased group who died from hepatic failure and the group who died from causes other than hepatic failure; and between the deceased group who died from hepatic failure and the living group in the preictive index (p less than 0.01). Our data suggest that if the predictive index is above 0.45, the probability of hepatic failure after hepatic resection is low. We concluded that our predictive index is useful to use in preoperative prediction of post-hepatectomic residual liver function.

Aged↗

[A case of gastric carcinoid tumor with coexisting adenocarcinoma in the same tumor].

A case of a gastric carcinoid tumor with a coexisting adenocarcinoma in the same tumor is reported. The patient was a 71-year-old man who complained of epigastralgia. His physical examination and routine laboratory data were unremarkable. An upper GI x-ray series and the gastroendoscopic findings, however, demonstrated a Borrmann 2-like tumor of the antrum. An endoscopic biopsy specimen from the tumor revealed that it was a gastric adenocarcinoma. Therefore, a subtotal gastrectomy with a lymph node dissection was performed. The resected specimen showed a Borrmann 2-like tumor, but also that infiltration was limited to within the submucosal layer. The pathological findings revealed that the tumor contained two differential component structures (a carcinoid and an adenocarcinoma). The carcinoid and adenocarcinoma structures coexisted with transitional changes that connected both structures. Pathohistologically, it was thought that these two differential components developed from a common origin.

Adenocarcinoma↗

Enhancement of antitumor effects of 1-hexylcarbamoyl-5-fluorouracil combined with hyperthermia on Ehrlich ascites tumor in vivo and Nakahara-Fukuoka sarcoma cell in vitro.

1-Hexylcarbamoyl-5-fluorouracil (HCFU) was found to be hydrolyzed to 5-fluorouracil (5-FU) depending on temperature. In this study, the antitumor effects of HCFU with hyperthermia were studied on Ehrlich ascites in tumor-bearing CD-1 mice and Nakahara-Fukuoka sarcoma cells. Concurrently, the change of 5-FU concentration in the Ehrlich tumor was also observed. In vivo, Ehrlich cells were transplanted in the foot pads of mice. HCFU (80 mg/kg) and 5-FU (40 mg/kg) (same molarity) were administered orally on the 3rd, 6th, and 9th days after transplantation and simultaneously hyperthermia (43.5 degrees C, 45 min) was induced. The antitumor effect was evaluated by the tumor volume. On the 9th day after transplantation, HCFU (150 mg/kg) and 5-FU (75 mg/kg) were administered with or without hyperthermia (43.5 degrees C, 45 min) and the tumor tissues were taken for 5-FU concentration analysis. In addition, Nakahara-Fukuoka sarcoma cells were incubated (42 degrees C various times) with our without HCFU and 5-FU (both 1 x 10(-4) M) in vitro. The cytotoxicity was evaluated by colony forming assay. The most effective condition was found to be the combination of HCFU with hyperthermia in vitro and in vivo. The highest 5-FU concentration was observed by the treatment of HCFU combined with hyperthermia in vivo. Hence, HCFU could be clinically useful in thermochemotherapy.

Animals↗