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Biomedical subjects

H Sugimoto

Publications and source records attributed to H Sugimoto.

At least 127 records · Page 7Linked to original sources

Granulocyte colony-stimulating factor ameliorates life-threatening infections after combined therapy with barbiturates and mild hypothermia in patients with severe head injuries.

OBJECTIVE: The objective of this study was to clarify the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on infections in patients with severe head injuries after combined therapy with high-dose barbiturates and mild hypothermia. PATIENTS AND METHODS: Since 1996, we have administered rhG-CSF to eight patients with severe head injuries for 5 days (group G). Their treatment results were compared with those of 22 patients cared for earlier without rhG-CSF treatment (group N). All patients in both groups met the criteria of total leukocyte count (TLC) less than 5,000/mm3, C-reactive protein (CRP) over 10 mg/dL, and the presence of an infectious complication. Changes in the TLC, CRP, respiratory index, intracranial pressure, and infectious condition were evaluated in both groups. In addition, the nucleated cell count and differentiation from bone marrow aspiration, neutrophil functions, serum concentrations of interleukin-6, and plasma concentration of leukocyte elastase were evaluated in group G. RESULTS: In group G, TLC, nucleated cell count, and neutrophil functions significantly increased, whereas CRP, respiratory index, and interleukin-6 decreased reciprocally. There was no deterioration of intracranial pressure and leukocyte elastase. Consequently, seven of the eight patients in group G recovered from life-threatening infections, and none of the eight patients died. However, in group N, CRP and respiratory index remained high and TLC did not increase as much as it did in group G. Infections continued after 5 days in 17 of the 22 patients, 7 of whom died from severe infections during hospitalization. CONCLUSION: Administration of rhG-CSF ameliorated life-threatening infections without causing lung injury or increasing brain swelling in patients with severe head injuries who were treated with combined therapy involving high-dose barbiturates and mild hypothermia.

Adolescent↗

Triolein-induced pulmonary embolization and increased microvascular permeability in isolated perfused rat lungs.

BACKGROUND: The pathophysiologic mechanism of the fat embolism syndrome is poorly understood. This study was designed to determine the effects of fat emboli on pulmonary vasculature. METHOD: Triolein was infused into isolated rat lungs perfused with Krebs-Henseleit buffer. Pulmonary arterial pressure and microvascular permeability (Kf) were measured at baseline and 20 minutes after the triolein infusion. RESULT: The 99% triolein produced dose-dependent increases in both pulmonary arterial pressure and Kf. The 65% triolein, containing free fatty acid, resulted in a greater increase in Kf. Pretreatment with indomethacin attenuated the increase in Kf after 65% triolein but not after 99% triolein. CONCLUSION: Pure triolein induced mainly embolization in the pulmonary vasculature, and 65% triolein caused embolization and subsequently increased vascular permeability, which are, at least in part, mediated by the action of cyclooxygenase products. Free fatty acids might induce permeability edema by means of a cyclooxygenase-dependent mechanism. We conclude that triolein-induced increases in pulmonary arterial pressure and Kf in isolated rat lungs provides a useful model of acute lung injury by fat embolism.

1-Methyl-3-isobutylxanthine↗

Changes in left ventricular performance in patients with severe head injury during and after mild hypothermia.

OBJECTIVE: To evaluate left ventricular (LV) performance in patients with severe head injury during and after mild hypothermia. PATIENTS AND METHODS: Seven consecutive patients who underwent therapeutic mild hypothermia (age, 15 to 70 years; Glasgow Coma Scale score on admission, 4 to 8). LV performance was assessed by using M-mode, color tissue Doppler imaging tracings and pulsed Doppler echocardiography. LV contraction and relaxation were evaluated by using the peak velocity of LV posterior wall movement during systole (Smax) and diastole (Dmax), respectively, in addition to the conventional echocardiographic indices. RESULTS: Mild hypothermia increased LV ejection time and reciprocally reduced LV filling period as indicated by temperature-dependent shortening of the early diastolic filling and the total diastolic inflow time. The indices depending on temporal factors such as ejection time, Smax, or Dmax were significantly affected by mild hypothermia, whereas those depending on spatial factors such as fractional shortening or stroke volume index were not. The attenuated Smax was compensated for the prolonged ejection time resulting in the relatively consistent fractional shortening regardless of body temperature. There was no compensatory mechanism for the decreased Dmax during diastole. CONCLUSION: The effect of mild hypothermia seemed to be predominantly negatively chronotropic. LV diastolic function was more vulnerable to mild hypothermia than LV systolic function was.

Adolescent↗

Differential distribution of insulin-like growth factor-1 and insulin-like growth factor binding proteins in experimental diabetic rat kidney.

Insulin-like growth factor-1 (IGF-1) is a peptide growth factor, and its activity is modulated by interaction with the family of IGF binding proteins (IGFBP-1 to 6). IGF-1 is detected in rat kidney and has metabolic and growth effects. To explore the possible involvement of IGFBPs in glomerular hypertrophy in streptozotocin (STZ)-induced diabetic rat, the immunolocalization of IGF-1 and IGFBPs were investigated. IGF-1 was gradually increased in the glomeruli of diabetic rats and correlated with glomerular hypertrophy. IGFBP-1 was transiently increased at 1 week after the STZ injection and declined to control level during the following period. In contrast, IGFBP-4 was increased in the diabetic glomeruli throughout the observation period. With insulin treatment, the levels of IGF-1, IGFBP-1 and 4 were normalized and glomerular hypertrophy was prevented. Initial glomerular hypertrophy of diabetic nephropathy is a related IGF-1 action, which may be modulated by IGFBP-1 and 4.

Animals↗

Effect of propolis extract on D-galactosamine-induced hepatic injury in rats.

The preventive effect of propolis extract on D-galactosamine-induced hepatic injury was examined in rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased at 24 h after intraperitoneal injection of D-galactosamine (400 mg/kg) in the animals. Propolis extract was administered orally three times in doses of 3 or 30 mg/kg at 18 h and 1 h before and 8 h after D-galactosamine injection. The extract itself and the vehicle alone (dextran) caused no significant changes in serum AST or ALT activities. Treatment with the extract dose-dependently prevented the increases in serum AST and ALT activities induced by D-galactosamine, and significant inhibition was observed at a dose of 30 mg/kg. These results suggested that propolis extract may have an ameliorating effect on hepatic dysfunction.

Alanine Transaminase↗

[Discovery and development of donepezil hydrochloride for the treatment of Alzheimer's disease].

The most consistent change of neurotransmitter in the brain of Alzheimer's patients is the dramatic decrease of cholinergic innervation due to the loss of neurons in the basal forebrain. The most widely studied acetylcholinesterase inhibitors (AChEIs) have been physostigmine and tacrine. Physostigmine has very short duration, and tacrine has liability to hepatotoxicity. These are the defects of the inhibitors. Our objective was to find a new type of AChEIs that would overcome the disadvantages of physostigmine and tacrine. Through a random screening, we incidentally found an N-benzylpiperazine derivative which showed positive cholinergic behavior in rats. We replaced the N-benzylpiperazine moiety with N-benzylpiperidine moiety and found a dramatic increase in anti-AChE activity. Even after the replacement of an amide group with a ketone group the activity was held. Furthermore, the cyclic-amide derivative showed enhanced inhibitory activity. On the basis of these results, an indanone derivative was designed. Among these indanone derivatives, donepazil hydrochloride (E2020), brand name ARICEPT was found to be the most balanced compound. The clinical studies of donepezil hydrochloride demonstrated statistically significant effects on ADAS-cog (Alzheimer's Disease Assessment Scale cognitive sub.) and CIBIC Plus (Clinician's Interview-Based Impression of Change plus).

Acetylcholine↗

Transumbilical embolization of a congenital dural arteriovenous fistula at the torcular herophili in a neonate. Case report.

A neonate, in whom a congenital cerebral vascular anomaly had been diagnosed prenatally, exhibited progressive high-output congestive heart failure soon after birth. Cerebral angiography revealed a congenital dural arteriovenous fistula (AVF) with a huge dural lake located at the torcular herophili. In addition to the meningeal blood supply, an unusual pial blood supply from all cerebellar arteries was observed to feed the fistula. The patient was treated by repeated transarterial and transvenous embolization through the umbilical venous route. To the authors' knowledge, neither the existence of a congenital dural AVF at the torcular herophili presenting with an enormous pial blood supply or the technique of trans-umbilical venous intervention has been reported in the literature.

Arteriovenous Fistula↗

Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure.

OBJECT: This study was performed to determine whether mild hypothermia therapy is essential for the treatment of severely head injured patients in whom intracranial pressure (ICP) can be maintained below 20 mm Hg by using conventional therapies. METHODS: Sixteen consecutive severely head injured patients fulfilled the following criteria: the patient's ICP was maintained below 20 mm Hg by using fluid restriction, hyperventilation, and high-dose barbiturate therapy; and the patient had a Glasgow Coma Scale score of 8 or less on admission. After conventional therapies had been applied, the patients were divided randomly into two groups: the mild hypothermia group (HT group; eight patients) and the normothermia group (NT group; eight patients). The HT group received mild hypothermia (intracranial temperature 34 degrees C) therapy for 48 hours followed by rewarming at 1 degree C per day for 3 days, whereas the NT group received normothermia (intracranial temperature 37 degrees C) therapy for 5 days. Specimens of cerebrospinal fluid (CSF) taken from an intraventricular catheter every 24 hours were analyzed for the presence of excitatory amino acids ([EAAs] glutamate, aspartate, and glycine) and cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, IL-8, and IL-10). The two groups did not differ significantly in patient age, neurological status, or level of ICP. There were no significant differences in daily changes in CSF concentrations of EAAs and cytokines between the two groups. The incidence of pneumonia was slightly higher in the HT group compared with the NT group (p = 0.059). The incidence of diabetes insipidus associated with hypernatremia was significantly higher in the HT group compared with that in the NT group (p < 0.01). The two groups did not differ with respect to their clinical outcomes. CONCLUSIONS: The authors recommend normothermia therapy for the treatment of severely head injured patients in whom ICP can be maintained at lower than 20 mm Hg by using conventional therapies, because mild hypothermia therapy does not convey any advantage over normothermia therapy in such patients.

Adolescent↗

Periarticular calcification in systemic lupus erythematosus.

OBJECTIVE: To describe the radiologic manifestations of periarticular calcification in patients with systemic lupus erythematosus (SLE) and to investigate clinical variables associated with its occurrence. METHODS: Hand radiographs and clinical records of 52 patients who had 4 or more features of the 1982 revised criteria for classifying SLE and who had no other collagen vascular diseases were analyzed retrospectively. RESULTS: Periarticular calcifications were found in 7 patients (13.5%) near the distal and proximal interphalangeal (DIP and PIP) joints and metacarpophalangeal (MCP) joints. No significant association with calcification was noted for the following variables: age at disease onset, duration of the disease, sex, the maximum value of the serum calcium, organic phosphate, and uric acid, Raynaud's phenomenon, lupus nephritis, femoral avascular necrosis, central nervous system lupus, proteinuria, or the use of drugs such as corticosteroids, synthetic vitamin D, and nonsteroidal antiinflammatory drugs. However, a significant association was noted with the use of furosemide (p < 0.01 by chi-square). In 5 patients periarticular calcification was observed during or just after hyperuricemia had developed while taking diuretics. CONCLUSION: Periarticular calcification in patients with SLE was seen in the DIP, PIP, and MCP joints, and appeared to be associated with the use of diuretics. If patients with SLE are prescribed a diuretic regimen, crystal associated arthritis should be considered as a possibility when diagnosing oligoarthritis.

Adult↗

[Diabetic nephropathy--recent advances in its mechanism and treatment].

The elevated glomerular filtration rate that occurs in 25 to 40 percent of insulin-dependent diabetics has been proposed as having a role in the initiation and evolution of diabetic nephropathy. We report that both enhanced NO synthesis by ecNOS in afferent arterioles and glomerular endothelial cells and increased expression of IGF-1 receptor can cause glomerular hyperfiltration, and that upregulated expression of ICAM-1 can promote the intraglomerular infiltration of mononuclear cells, which were prevented by aldose reductase inhibitor. The results of United Kingdom Prospective Diabetes Study (UKPDS) will also be discussed.

Animals↗

[Surgical management of chest wall tumors].

Twenty-four patients with chest wall tumors underwent resection during the past twenty years. There were 12 female and 12 male patients with ages ranging from 7 months to 78 years (mean 44 years). Five patients had primary malignant neoplasms, 7 had metastases, and 12 had benign tumors. The tumor was located in the soft tissue in 14 patients and in the ribs and the sternum in 10. Ninety-two percent of tumors were diagnosed correctly if they were benign or malignant before resection, however the final diagnosis was made in only 25% of benign tumors and 54% of malignant tumors before surgery. Thirty-one operations were performed in 24 patients and 10 reconstruction with prosthetic materials were done. Concerning malignant neoplasms patients with primary tumors had better prognosis than those with metastases and patients underwent reconstruction had better prognosis than those underwent resection only. We conclude that wide resection with reconstruction is potentially curative treatment.

Adolescent↗

[Cystic lesions around the joint: ganglion and bursitis].

Cystic lesions such as ganglion and bursitis around the joint are a common problem. Practitioners now encounter such lesions more frequently than previously, thanks to the increased usage of magnetic resonance (MR) imaging in daily practice. The purpose of imaging for periarticular cystic lesions is to confirm the cystic nature of the lesion, to determine the relationship of the cystic mass to the joint and surrounding structures, and to evaluate associated joint disorders. Because of its superior soft-tissue contrast resolution, multiplanar capability, and non-invasiveness, MR imaging is more suitable for diagnosing cystic lesions around the joint than ultrasound, arthrography, or computed tomography. Diagnoses of ganglion and bursitis are readily established when they develop in typical locations and present characteristic imaging features. However, when they contain debris following hemorrhage or infection, or develop in an atypical location, diagnosis may prove difficult. In analyzing a cystic lesion around the joint, it is important to be aware of the possibility of ganglion or bursitis.

Bone Cysts↗

Cloning and expression of cDNA encoding rat liver 60-kDa lysophospholipase containing an asparaginase-like region and ankyrin repeat.

Mammalian tissues contain small form and large form lysophospholipases. Here we report the cloning, sequence, and expression of cDNA encoding the latter form of lysophospholipase using antibody raised against the enzyme purified from rat liver supernatant (Sugimoto, H., and Yamashita, S. (1994) J. Biol. Chem. 269, 6252-6258). The 2,539-base pair cDNA encoded 564 amino acid residues with a calculated Mr of 60,794. The amino-terminal two-thirds of the deduced amino acid sequence significantly resembled Escherichia coli asparaginase I with the putative asparaginase catalytic triad Thr-Asp-Lys and was followed by leucine zipper motif. The carboxyl-terminal region carried ankyrin repeat. When the cDNA was transfected into HEK293 cells, not only lysophospholipase activity but also asparaginase and platelet-activating factor acetylhydrolase activities were expressed. Reverse transcription-polymerase chain reaction revealed that the transcript occurred at high levels in liver and kidney but was hardly detectable in lung and heart from which large form lysophospholipases had been purified, suggesting the presence of multiple forms of large form lysophospholipase in mammalian tissues.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Molecular cloning of human D-dopachrome tautomerase cDNA: N-terminal proline is essential for enzyme activation.

D-Dopachrome tautomerase converts 2-carboxy-2,3-dihydroindole-5,6-quinone (D-dopachrome) into 5,6-dihydroxyindole. This protein has an amino acid sequence that is highly homologous with that of macrophage migration inhibitory factor (MIF), which has the potential to catalyze D-dopachrome to 5,6-dihydroxyindole-2-carboxylic acid and is an important cytokine for T-lymphocyte activation. We isolated and sequenced a 566 bp-long cDNA encoding human D-dopachrome tautomerase. The cDNA contains an open reading frame encoding 118 amino acids, including the initiator methionine. The amino acid sequence of the protein shares 80% homology with that of the rat enzyme. Northern blot analysis demonstrated that mRNA of D-dopachrome tautomerase is expressed in a large amount in the liver, and to lesser extent in other organs, including the heart, lung and pancreas. After purification of D-dopachrome tautomerase expressed in E. coli, we confirmed that the recombinant protein catalyzes the conversion of D-dopachrome to 5,6-dihydroxyindole. Its catalytic mechanism is not well understood. We found that the protein completely lost the enzyme activity when the N-terminal proline residue was replaced with alanine by site-directed mutagenesis. This fact suggests that the N-terminal proline is essential for the catalytic mechanism. Although the precise pathophysiological function of D-dopachrome tautomerase remains to be elucidated, the present results could contribute to further understanding of isomerase activity in relation to the immune response.

Amino Acid Sequence↗