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Biomedical subjects

T Iizuka

Publications and source records attributed to T Iizuka.

At least 163 records · Page 9Linked to original sources

Mechanisms of nitroso compound-induced inhibition of superoxide generation in neutrophils: fluorescence quenching of perylene by nitroso-compounds in the membrane fractions of neutrophils.

To investigate the mechanism of nitroso compound-induced inhibition of the respiratory burst in neutrophils, we studied fluorescence quenching of perylene by nitroso-compounds in the membrane fractions of neutrophils at 17, 27, and 37 degrees C and the reagent-induced inhibition of superoxide generation at 28 and 37 degrees C. With increasing temperature, the quenching of perylene fluorescence and inhibition of superoxide generation by nitrosobenzene (NB) were both diminished, while those by 2-nitrosotoluene (NT) were both enhanced. The temperature dependence of the inhibition constants and the quenching constants indicates that the binding of NB is exothermic (deltaH= -27 kJ/mol for inhibition and deltaH= -29 kJ/mol for quenching) and essentially enthalpy-driven. On the other hand, that of NT is endothermic (deltaH= +16 kJ/mol for inhibition and quenching) and essentially entropy-driven. Quenching studies of perylene fluorescence in synthetic vesicles made of endogenous polar lipids of neutrophils showed that the enthalpy changes of NB- and NT-binding with perylene in lipids were similar to each other. Moreover, their values were in good agreement with that of NT, but not of NB, in the membrane fractions, an assembly of proteins and lipids, of neutrophils. These results suggest that NB inhibits the activity by binding to proteins in the membrane, whereas inhibition by NT occurs through hydrophobic interaction with lipids and/or proteins.

Animals↗

A case of Ollier's disease of the hand.

Enchondroma is a benign growth of cartilage arising in the bone metaphysis as a solitary or multiple primary lesions. The form of multiple enchondromatosis with unilateral predominance is termed Ollier's disease. We have recently treated a case of Ollier's disease with the chief complaint of deformity of the left hand. The patient was an 11-year-old boy. Radiographic examination showed honeycombed clear spaces in the metaphyses of the middle and proximal phalanges of the left ring and little fingers as well as of the fourth and fifth metacarpals, and thinning of the cortex of these bones, but with no evidence of pathological fracture. The tumors of the left fourth and fifth metacarpal bones and of the phalanges of the left ring and little fingers were removed, and the metacarpophalangeal joint of the little finger was capsulotomized. The patient was free from recurrence 19 months after surgery. With regard to the prognosis of Ollier's disease, malignant transformation into chondrosarcoma or osteosarcoma has been reported of the chondroma. Since Ollier's disease is self-limited in that it usually stops spontaneously as the patient grows, and since the cartilaginous lesions in occasional cases may regress or even disappear, any cartilaginous lesions that are still active or painful after termination of the growth period should be examined thoroughly under suspicion of undergoing malignant transformation.

Child↗

Depressed contractile response to exercise in diabetic patients in the absence of cardiovascular disease: relationship to adrenergic cardiac dysinnervation.

We investigated the presence of subclinical left ventricular dysfunction by determining left ventricular diastolic filling at rest and the left ventricular ejection fraction (LVEF) response to exercise with radionuclide angiography. The subjects were 40 patients with non-insulin-dependent diabetes who showed no evidence of cardiovascular disease based on clinical findings, electrocardiography and 201T1 perfusion scintigraphy. We also used 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy to investigate whether subclinical left ventricular abnormalities were related to adrenergic cardiac dysinnervation. The change on LVEF in response to exercise (delta LVEF) was < 5% in 1 of 20 normal controls and in 22 of 40 diabetic patients (P < 0.01). The peak filling rate was within normal limits in all controls but was abnormal (< 2.3 EDV s-1) in 5 of 40 patients (P = N.S.). Of the clinical and scintigraphic variables that correlated significantly with delta LVEF, the heart-to-mediastinum 123I-MIBG uptake ratio on the late planar images was the most important and independent predictor. Nearly half of the patients with non-insulin-dependent diabetes without apparent cardiovascular disease exhibited a depressed LVEF response to exercise. This subnormal response was significantly associated with diminished myocardial 123I-MIBG uptake, suggesting a causal relationship.

3-Iodobenzylguanidine↗

Immunohistochemical distribution of lymph capillaries and blood capillaries in the synovial membrane in cases of internal derangement of the temporomandibular joint.

The distribution of lymph capillaries and blood capillaries in the synovial membrane was examined immunohistologically with anti-human collagen IV antibody and anti-human von Willebrand factor in 26 human temporomandibular joint (TMJ) samples comprising discs with adjoining synovial membrane from 10 control TMJs and from 16 TMJs with internal derangement. Three different distribution types were observed in the synovial membrane. In the control samples, the occurrence of blood capillaries and lymph capillaries was rare. In mildly hyperplastic synovitis, lymph capillaries were observed just beneath the surface of the synovial membrane, whereas blood capillaries occurred in a little deeper layer of the synovial membrane. In a severely hyperplastic synovitis, both lymph and blood capillaries were observed frequently. The present results suggest that the different distribution patterns of lymph capillaries and blood capillaries reflect the degree of synovitis but can not be attributed to specific clinical symptoms.

Adult↗

Nitric oxide and aneurysm formation in Kawasaki disease.

The objective of this study is to show that nitric oxide plays a role in the development of coronary artery abnormalities in Kawasaki disease. We examined nitrite+nitrate, biopterin and neopterin in 316 urine samples of 34 patients with Kawasaki disease, those of 24 patients with other diseases, and those of 25 healthy children acting as a control group, because urinary nitrite + nitrate are reportedly useful as markers of nitric oxide generation in vivo, and pathways for neopterin-biopterin synthesis and nitric oxide generation are tightly coupled. In our study, the children with Kawasaki disease excreted more urinary nitrite + nitrate and neopterin than did the healthy control group children and excreted abnormally high quantities more often than did the patients with other diseases. Good relationships were found between the urinary nitrite + nitrate levels and the urinary biopterin levels, and between these biopterin levels and the urinary neopterin levels. Nitric oxide is therefore thought to be generated in abnormally high quantities, and to be closely related to the pathology of Kawasaki disease and to the development of coronary artery abnormalities. The role of nitric oxide in Kawasaki disease should be further studied to elucidate the pathophysiology of the disease and to aid in the development of new treatments.

Biomarkers↗

Cloning of novel enterotoxin genes from Bacillus cereus and Bacillus thuringiensis.

A novel enterotoxin gene was cloned from Bacillus cereus FM1, and its nucleotide sequence was determined. Previously, a 45-kDa protein causing characteristic enterotoxin symptoms in higher animals had been isolated (K. Shinagawa, p. 181-193, in A. E. Pohland et al., ed., Microbial Toxins in Foods and Feeds, 1990) from the same B. cereus strain, but no report of cloning of the enterotoxin gene has been published. In the present study, a specific antibody to the purified enterotoxin was produced and used to screen the genomic library of B. cereus FM1 made with the lambda gt11 vector. An immunologically positive clone was found to contain the full protein-coding region and some 5' and 3' flanking regions. The deduced amino acid sequence of the cloned gene indicated that the protein is rich in beta structures and contains some unusual sequences, such as consecutive Asn residues. In order to clone enterotoxin genes from Bacillus thuringiensis, two PCR primers were synthesized based on the nucleotide sequence of the B. cereus gene. These primers were designed to amplify the full protein-coding region. PCR conducted with DNA preparations from the B. thuringiensis subsp. sotto and B. thuringiensis subsp. israelensis strains successfully amplified a segment of DNA with a size almost identical to that of the protein-coding region of the B. cereus enterotoxin. Nucleotide sequences of the amplified DNA segments showed that these B. thuringiensis strains contain an enterotoxin gene very similar to that of B. cereus. Further PCR screening of additional B. thuringiensis strains with four primer pairs in one reaction revealed that some additional B. thuringiensis strains contain enterotoxin-like genes.

Amino Acid Sequence↗

Predictive value of left ventricular response to exercise in patients with dilated cardiomyopathy--assessment by radionuclide ventriculography.

The objective of this study was to determine noninvasively the likelihood of recovery of the left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy (DCM) verified by radionuclide ventriculography. Twenty patients with DCM were classified into two groups according to the LVEF by M-mode echocardiographic findings two years after ventriculographic examination. The LVEF recovered to > or = 50% in 10 patients (Group A), while it was sustained at < 50% in 10 patients (Group B). The clinical features of each group were compared, based on results of physical examination, radionuclide ventriculography, and other diagnostic tests performed on their referral to hospital. Only the systolic blood pressure differed significantly between the two groups, being slightly, but significantly, increased in Group A over that in Group B (P < 0.05). LVEF at rest by radionuclide did not differ (Group A: 31.5 +/- 10.3% vs Group B: 26.5 +/- 9.4%). Peak exercise EF-EF at rest (peak delta EF) in Group A was apparently increased (3.4 +/- 4.0%), while that in Group B was decreased (-4.4 +/- 5.2%). The positive peak delta EF had a highly predictive value of 90% for patients with DCM whose LVEF will recover to more than 50%. The recovery EF-EF at rest did not differ significantly between groups (Group A: 8.4 +/- 4.7 vs Group B: 3.9 +/- 2.3, P < 0.05). Other clinical parameters such as functional class, cardiothoracic ratio, LVEF by echocardiography, cardiac index by Swan-Ganz catheter examination, and histologic examination of biopsied endocardium were indistinguishable in the two groups. The authors conclude that peak delta EF of radionuclide ventriculography on exercise indicates a preservation of LVEF and predicts a good clinical recovery in patients with DCM.

Blood Pressure↗

Myocardial contractile reserve as prognostic determinant in patients with idiopathic dilated cardiomyopathy without overt heart failure.

To assess the prognostic significance of myocardial contractile reserve in patients with idiopathic dilated cardiomyopathy (DCM) without overt heart failure (New York Heart Association functional class I or II), seventy-one patients underwent exercise radionuclide angiography in addition to clinical, radiographic, hemodynamic, and echocardiographic evaluations. Myocardial contractile reserve was assessed as left ventricular ejection fraction (LVEF) during peak exercise minus LVEF at rest (delta LVEF). During an average of 49 months, 18 patients died of the disease. Cox's proportional-hazards regression analysis showed that the delta LVEF was the most powerful and independent discriminator for survival (p = 0.0002). Ejection time (p = 0.0029) and cardiothoracic ratio (p = 0.017) were the second and third most predictive variables, respectively. Evaluation of the delta LVEF, which reflects residual myocardial contractile reserve, can provide important information about the prognosis of patients with DCM and mild symptoms.

Adolescent↗

Clinical trial of low density lipoprotein-apheresis for treatment of diabetic gangrene.

A 68-year-old man with a 28-year history of non-insulin dependent diabetes mellitus (NIDDM) was admitted to our hospital because of foot gangrene. He had previously suffered from cerebral infarction resulting in right hemiplegia and his right foot was amputated because of right femoral lesion presenting diabetic foot gangrene 5 years previously. The diabetic foot gangrene gradually became worse, although he had received various medications. Then, we attempted to treat the patient with low density lipoprotein (LDL)-apheresis ten times a month. The foot gangrene itself and the local circulation around the gangrene lesion were remarkably improved after treatment with LDL-apheresis. We present here the first case of diabetic foot gangrene improved by LDL-apheresis. LDL-apheresis therapy is anticipated to be a new therapeutic approach for treatment of fatal foot gangrene associated with diabetes mellitus.

Aged↗

[In-111-labeled leukocyte brain SPECT imaging in acute ischemic stroke in man].

This study was performed to investigate the role of leukocyte accumulation in human cerebral infarction and its association with neurological functional outcome. A total of 42 patients diagnosed as acute ischemic stroke (22 embolism, 17 thrombosis, 3 TIA) were examined. Leukocyte accumulation was studied using indium-111-labeled leukocyte brain single-photon emission computed tomography (SPECT). Volume of brain infarction was evaluated by CT and/or MRI. The data were compared with the cerebral blood flow (CBF) imaging. Immediately after CBF study by SPECT using either technetium-99m hexamethylpropyleneamine oxine (Tc-99m-HMPAO) or technetium-99m ethyl-cysteinate dimer (ECD), In-111-labeled autologous leukocytes were injected intravenously. Brain scan for leukocytes was performed after 48 hours. The European Stroke Scale was used for neurological assessment. Thirteen patients with cerebral embolism and three patients with cerebral thrombosis showed intensive accumulation of leukocytes in the region of low flow. Leukocyte's accumulation was not seen in patients with TIA. The accumulation of leukocytes was more noticeable in the central zone of the ischemia. Patients who showed negative leukocyte accumulation revealed clinically mild functional outcome and the size of infarction on CT and/or MRI was small. The regional accumulation of leukocytes was seen in all the patients with hemorrhagic infarction, but the degree of hemorrhage on CT did not have significant influence on the amount of leukocyte accumulation. Abnormal accumulation of leukocytes was associated with reduced CBF during the acute embolic stroke. The present clinical study revealed that leukocyte accumulation correlated with the poor neurological functional outcome in patients with acute embolic stroke. The present study confirms that leukocytes contribute to the ischemic tissue damage of the brain and demonstrates a clinical evidence that the regional accumulation of leukocytes has a deleterious effect on the brain following ischemia.

Adult↗

[TNM classification of carcinoma of the esophagus].

TNM classification of esophageal carcinoma was first described in the supplement to the first edition of the TNM classification in 1973. In the second edition, the classification was changed based on the data of 1,000 cases from the Task Force on Esophagus of American Joint Committee. In this edition, only the clinical classification was described, but the third edition included both clinical and post-surgical histopathological classification. But the criteria for T and pT classification differed. Before the fourth edition, specialists from Japan and the United States met in Hawaii in 1984. Data of the Japanese Nationwide Registration, including 7,742 patients from 1969 to 1978, were presented. After discussion based on these data, T was classified according to the depth of invasion, and perigastric lymph nodes were included in Regional Nodes in the fourth edition. Then, the TNM Research Committee of ISDE collected patient data of esophageal carcinoma from seven countries, and they were studied according to many factors. Based on these data, two proposals were made to the UICC TNM Committee. First, T1 should be divided into two categories: T1a, Tumor invasion of lamina propria; and T1b, Tumor invasion of submucosa. Second, metastases to distant lymph nodes should be grouped into the N classification instead of M classification. The first was accepted in the TNM Supplement of 1993, and the second will be accepted in the Fifth Edition, which will appear in 1997. It is important to accumulate data on many patients using the uniform registration form and to follow these patients very closely in the discussion of revisions to the TNM classification.

Esophageal Neoplasms↗

Transient sick sinus syndrome associated with immunoblastic lymphadenopathy.

We describe a very rare case of immunoblastic lymphadenopathy (IBL) accompanied with a sick sinus syndrome (SSS) in a 64-year-old male. SSS presented with progression of the IBL and subsided with improvement of the IBL following high dose prednisolone (PSL) therapy. The clinical course of this patient strongly suggested cardiac involvement in IBL and being the cause of the transient SSS. To our knowledge, this is the first case of IBL demonstrating SSS as a possible complication of the disease. This case may provide further information for the treatment of similar patients with IBL.

Electrocardiography↗

Intracellular generation of amyloid beta-protein from amyloid beta-protein precursor fragment by direct cleavage with beta- and gamma-secretase.

Two amyloid beta protein precursor (beta APP) fragments involving Met and 103 amino acids of C-terminus of beta APP (delta NOR-beta) and its KM-NL substitution (delta NL-beta) were expressed in COS-7 cells to clarify the proteolytic cleavages to generate amyloid beta protein (A beta). The 4.5-kD protein, A beta with additional N-terminal amino acids, and 4-kD A beta were directly produced and released from 12.5-kD expression proteins without any production of 11.4-kD C-terminal fragment starting at N-terminus of A beta and 3-kD "p3" A beta derivative. Intracellular 4-kD A beta was also detected. The substitution of KM-NL of beta APP found in Swedish familial Alzheimer's disease (AD) promoted the production of intracellular A beta and its release with no increase in level of 11.4-kD C-terminal fragment. These results suggested the presence of a distinct pathway in which A beta is directly cleaved at both N- and C-termini from beta APP fragment intracellularly to release A beta. Since KM-NL substitution enhanced intracellular A beta generation, this pathway may be associated with amyloidogenesis in AD.

Alzheimer Disease↗

Effects of immunoglobulin and gamma-interferon on the production of tumour necrosis factor-alpha and interleukin-1 beta by peripheral blood monocytes in the acute phase of Kawasaki disease.

In order to study the in vitro effects of intact immunoglobulin (Ig) and gamma-interferon (INF-gamma) in patients with Kawasaki disease, the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) was measured in peripheral blood monocytes (PBM) both before and after intravenous immunoglobulin (IVIG) therapy. Spontaneous production of TNF-alpha and IL-1 beta both before and after IVIG therapy was significantly higher than in healthy controls. Intact Ig enhanced in vitro the production of TNF-alpha and IL-1 beta both before and after IVIG therapy approximately 3-4 times as compared to the spontaneous production. INF-gamma did not affect the production of the two cytokines. Ig enhanced IL-1 beta mRNA expression in PBM of KD by 3-8 times more than that of spontaneous production.

Acute Disease↗

Tension-band laminoplasty of the cervical spine.

A new laminoplasty of the cervical spine has been developed using preserved ligaments as a tension-band. The laminae were enlarged in an open-door fashion and spacers inserted to maintain the spinolaminoligamentous complex intact. The stretched ligaments exerted a tension-band effect on the spacers and stabilised them so that neck movements could be started as soon as bleeding stopped. The spacers were iliac grafts, or were made of a bioactive ceramic which proved more satisfactory. The results of 102 cases with ceramic spacers showed an average preservation of preoperative movement between C2 and C7 to be 79% in cervical spondylotic myelopathy and 67% in ossification of the posterior longitudinal ligament at 3 years after operation. No spacer became displaced. CT showed new bone formation in the lamina-ceramic gap in 59% of the spacers used in cervical spondylotic myelopathy by sixth months and in 63% in cases of ossification of the posterior longitudinal ligament by the third month. Neurological recovery was comparable to that after other types of laminoplasty, but the new method allows better function of the neck and more new bone formation around the spacers.

Bone Transplantation↗

Insecticidal activity of the protein encoded by the cryV gene of Bacillus thuringiensis kurstaki INA-02.

A new host specificity was discovered with the insecticidal protein encoded by the cryV gene. The cryV gene was cloned from the Bacillus thuringiensis kurstaki INA-02 strain, which was selected among a number of B. thuringiensis isolates because of its high activity against Spodoptera litura. Analyses by polymerase chain reaction (PCR) revealed that INA-02 contained the cryIA(a) and cryV genes. Since no Spodoptera activity was observed with B. thuringiensis sotto, which contained only cryIA(a), insecticidal activity of the protein encoded by the cryV gene was investigated with several insect species including S. litura. For bioassay, the cryV gene was highly expressed in an acrystalliferous B. thuringiensis strain, BT51. The CryV protein from BT51 was assayed against larvae of three lepidopteran species, Bombyx mori, S. litura, and Plutella xylostella. The protein was highly active against S. litura and P. xylostella, suggestive that the protein contributes to the unique activity of INA-02.

Animals↗

Induction of adenocarcinomas in the submandibular salivary glands of female Wistar rats treated with 7,12-dimethylbenz(a)anthracene.

In 12 male and 12 female Wistar rats, 7-9 weeks of age, a solution of 0.05 ml of 1% 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in acetone was injected directly into the submandibular glands biweekly, after the gland had been injured. In some rats the carcinogen was injected 1 week after the injury. Each rat received six to seven injections. Swelling was observed in the submandibular gland region as early as 4 weeks after the last injection. The animals were killed 4-8 weeks after the last injection and glands with tumour tissues were processed for light microscopy. The control rats of the same age that received a corresponding amount of acetone only (three male, three female), carcinogen injection alone (three male, five female), and injury only (four male, four female) were killed at the same time. Histological examination revealed adenocarcinomas of the submandibular gland in 12/12 (100%) female rats, six of which were associated with fibrosarcomas. The adenocarcinomas basically consisted of ductal and glandular structures. Sometimes tubular, cystic, papillary-cystic and cribriform-like structures were also observed. Male rats mainly developed fibrosarcomas, although there was one squamous-cell carcinoma. The reasons for the sex difference are not known. One adenocarcinoma developed in the submandibular gland of a female rat (1/5) that received carcinogen injections alone. Thus direct injections of DMBA into the submandibular gland produce adenocarcinomas in female Wistar rats.

9,10-Dimethyl-1,2-benzanthracene↗

Analysis of CAG trinucleotide expansion associated with Machado-Joseph disease.

There are currently some types of autosomal dominant cerebellar ataxias such as Machado-Joseph disease (MJD), spinocerebellar ataxia types 1-5 (SCA1-5), or hereditary dentatorubropallidoluysian atrophy. It is very important for these ataxias to be clinically differentiated, but that is sometimes difficult. In particular, the differential diagnosis between MJD and SCA1 is thought to be the most difficult. Recently, both MJD and SCA1 have been proven to be related to expansions of CAG trinucleotide in their causative genes. In this study, 20 cases of MJD in 13 unrelated Japanese families were genetically and clinically examined in comparison with 20 cases of age at onset- and duration-matched Japanese SCA1. The CAG repeat number of expanded MJD and SCA1 alleles was 72.2 +/- 3.1 (mean +/- SD, n = 20) and 47.3 +/- 4.4 (n = 20), respectively, and each repeat size was inversely correlated with age at onset in both MJD and SCA1. The repeat number in leukocytes increased from parents to children with acceleration of age at onset (anticipation) in MJD. In MJD, the number of CAG repeats in the expanded allele was lower in sperm than that of leukocytes, but was more in SCA1. However, the number of peaks in the expanded allele was greater in sperm than in leukocytes in both MJD and SCA1 (increased mosaicism level). MJD was clinically characterized by a relatively higher frequency of ocular signs such as eyelid retraction, bulging eyes, ophthalmoparesis, and nystagmus, spasticity in lower limbs, and sensory and urinary disturbances in contrast to the SCA1 patients except for slow eye movement. These results indicate that the expanded CAG repeat and clinical features are correlated in both MJD and SCA1, and MJD can be differentiated from SCA1 by clinical characteristics mentioned above as well as DNA analysis.

Adolescent↗