A case of Leber's hereditary optic neuropathy with elevated blood levels of lactate and pyruvate.
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Adult↗
Biomedical subjects
H Yamazaki
Publications and source records attributed to H Yamazaki.
Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer's disease as shown by MRI and PET.
OBJECTIVE: To investigate the relation between atrophy of the hippocampus and parahippocampal gyrus (the % hippocampal area) and cerebral metabolic rate for glucose (CMRGlc) in Alzheimer's disease. METHODS: 13 patients with probable Alzheimer's disease by NINCDS-ADRDA criteria (six men; seven women, mean age 71 years, mini mental state 13.8 (SD 4.6)) and age matched controls were studied. T1 weighted MRI (0.5T) images were used for evaluation of the hippocampal area. With a digitiser system, a percentage of the hippocampal area to the brain (the % hippocampal area) was calculated. Eight patients received another T1 weighted MRI (1.5T) for further evaluation of the minimum thickness of the hippocampus. Regional CMRGlc (rCMRGlc) was measured using PET and the FDG technique. RESULTS: The hippocampal area in patients with Alzheimer's disease was significantly lower than that of controls (P < 0.01). All the cortical rCMRGlc values in patients with Alzheimer's disease were lower than those of controls (P < 0.01). A significant correlation (P < 0.05) was found between the % hippocampal area and rCMRGlc in the temporal lobe, temporoparieto-occipital (TPO) region, and frontal lobe in Alzheimer's disease. There was a significant correlation between minimal hippocampal thickness and ipsilateral TPO metabolism on both sides. CONCLUSION: The ipsilateral correlation between hippocampal atrophy and decreased TPO metabolism in Alzheimer's disease suggests a functional relation and the asymmetries show that Alzheimer's disease is an asymmetric disease in its early stages.
Aged↗
A novel mosaic protein containing LDL receptor elements is highly conserved in humans and chickens.
Certain receptors belonging to the LDL receptor (LDLR) gene family appear to constitute a newly identified branch whose members are expressed in brain, in addition to other tissues. In support of this concept, we have now discovered the expression and delineated the molecular structures of a representative of this emerging branch from two such diverse species as human and chicken. This membrane receptor, called LR11 and thus far only known to exist in the rabbit, is a complex seven-domain mosaic protein containing, among other structural elements, a cluster of 11 LDLR ligand-binding repeats and a domain with homology to VPS10, a yeast receptor for vacuolar protein sorting. Cytoplasmic signature sequences define the receptor as competent for endocytosis. The most striking properties of LR11s are their (1) high degree of structural conservation (>80% identity among mammals and birds), with 100% identity in the membrane-spanning and cytoplasmic domains of rabbit and human; (2) lack of regulation by cholesterol and estrogen; and (3) expression in brain. The features of LR11 suggest important roles in intercellular and intracellular ligand transport processes, some of which it may share with other brain-specific LDLR family members.
Amino Acid Sequence↗
Effect of thoracic irradiation on hepatocyte growth factor in rats lung and in bronchoalveolar lavage fluid of patients with thoracic malignancies.
This study aimed to examine the physiological role of hepatocyte growth factor (HGF) after thoracic irradiation. We analysed the changes of HGF protein levels in rat lung following 12 Gy of whole thoracic irradiation. Bronchoalveolar lavage fluid (BALF) was then collected from 11 patients (10 lung cancer and one oesophageal cancer) after completion of radiation therapy. One month after irradiation, the HGF protein level in the lungs of irradiated rats decreased (p<0.05), followed by a remarkable elevation in HGF protein levels 2 (p<0.05) and 3 months (nonsignificant) after irradiation accompanied by the clinical appearance of radiation pneumonitis. Finally, HGF protein levels in the lung returned to their original level 6 months after thoracic irradiation. In humans, HGF protein levels in the BALF in the limited irradiated area were lower than those obtained from unirradiated areas (p<0.05). In conclusion, hepatocyte growth factor production is transiently suppressed in the irradiated area after irradiation.
Aged↗
Renal cortical retention on delayed CT after angiography and contrast associated nephropathy.
The aim of this study was to examine the relationship between renal cortical retention (RCR) of contrast media observed on delayed CT (median delay: 20 h) and contrast associated nephropathy (CAN). We investigated the incidence of both phenomena in 270 patients. CAN was defined as an increase in the creatinine level > 0.5 mg dl-1 (44 mumol l-1) and > 25% on day 1, 3 or 7, while RCR was recognized when CT values for the renal cortex showed either mild RCR (CT value > 50) or severe RCR (CT value > 100). RCR was demonstrated in 127 patients (47%), mild in 78 (29%) and severe in 49 (18%), on delayed CT after angiography. CAN was found in eight patients (3%). Patients with severe RCR showed a higher CAN rate (8%) than other patients (mild RCR: 4%, RCR (-): 1%) (p = 0.02). The type of contrast medium was independently associated with the incidence of RCR (p = 0.0001). Although severe RCR was associated with a higher frequency of CAN than the milder forms of RCR, RCR as such was not always associated with CAN.
Adolescent↗
Molecular genetics of renal diseases.
Recent progress in molecular genetics has strongly influenced nephrology. Gene mutations have been identified which cause various monogenic hereditary renal diseases including Alport syndrome, autosomal dominant polycystic kidney disease, and tubular transporter disorders. The data obtained will be useful not only to develop new methods of diagnosis and treatment of such particular diseases but also to expand the knowledge of renal physiology and pathophysiology. In addition, genetic factors have been investigated which are involved in the development and progression of more common renal diseases such as IgA nephropathy and diabetic nephropathy. There have also been great advances in molecular studies of experimental renal diseases such as Heymann nephritis and in the use of transgenic and knockout mice. In this review we focused on the important achievements made recently in the field of molecular nephrology.
Animals↗
Short-latency somatosensory evoked potentials in patients with brain stem tumor: study of N20 and N18 potentials.
Short-latency somatosensory evoked potentials (SSEPs) elicited by median nerve stimulation were studied in 17 patients with brain stem tumor. A total of 35 SSEP records were obtained and classified into five groups: 13 in Group I, central conduction time (CCT) < 7.56 msec (within the normal limits); eight in Group II, CCT > or = 7.56 msec; nine in Group III, N20 potential was abolished; four in Group IV, N20 and N18 potentials were abolished; and one in Group V, N20, N18, and P14 potentials were abolished. These SSEP groups were correlated with the size and location of the brain stem tumor on magnetic resonance images. N20 potentials were unchanged in latency in patients with small localized gadolinium (Gd)-enhanced lesions. In contrast, the N20 potentials were abolished in patients with tumors extending to the dorsal pons and the upper medulla oblongata. The extent of nonenhanced low-intensity lesion did not correlate with the changes of the N20 potentials. The degree of the impairment of the N20 potentials reflected the severity of the clinical symptoms. The N20 potential can evaluate brain stem dysfunction caused by brain stem tumor. The N18 potentials were abolished in four patients, in whom the tumor extension (one Gd-enhanced lesion, three low-intensity lesions) involved not only the pons but also the medulla oblongata. Therefore, the N18 potentials are probably generated from the medulla oblongata.
Adolescent↗
Characteristics of postural control and locomotion of patients with vascular and Alzheimer-type dementias.
The postural control and locomotion of patients with Alzheimer-type senile dementia (n = 20) or vascular dementia (n = 20) were investigated. Patients with both types of senile dementia, especially patients with vascular dementia, generally showed lower scores than healthy old people (n = 53). Moreover, deterioration of locomotion was more remarkable.
Adult↗
Instantaneous cloth-based enzyme immunoassay for the semi-quantitative visual determination of antibodies.
An antigen-coated cloth segment was placed onto a blotting pad. The cloth was blotted with one drop of an antibody sample, immediately washed with five drops of a washing solution, exposed to one drop of an anti-antibody-peroxidase conjugate, washed, and finally exposed to a peroxidase substrate. The colored peroxidase product was determined either visually or colorimetrically with the color intensity being correlated to the antibody concentration. This rapid assay would facilitate field serodiagnosis of human and animal diseases.
Animals↗
A novel member of the LDL receptor gene family with eleven binding repeats is structurally related to neural adhesion molecules and a yeast vacuolar protein sorting receptor.
We now have discovered and characterized a novel multi-domain protein and classified it as a member of the LDL receptor gene family. The approximately 250 kDa membrane protein, termed LR11, highly conserved in man, rabbit and chicken, contains a cluster of 11 LDL receptor ligand binding repeats, a group of 5 LDL receptor "YWTD" repeats, a large hexarepeat domain of structural elements found in neural cell adhesion molecules, and a domain with similarity to a yeast receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits features typical of endocytosis-competent coated pit receptors. The mosaic, and presumably multifunctional, receptor is expressed abundantly in brain, liver and adrenal glands. Ligand blotting of LR11-transfected cells demonstrated that LR11 binds apolipoproteinE-containing lipoproteins, as well as other members of LDL receptor gene family. In contrast to the LDL receptor, the mRNA levels in rabbit liver is unaffected by hyperlipidemia. The features of this highly conserved and complex mosaic protein suggest the importance of the ever expanding LDL receptor gene family in the evolution and proposed multifunctionality.
Amino Acid Sequence↗
[A study of the clinical effect of hormone replacement therapy for patients with stress incontinence].
BACKGROUND: Our purpose was to clarify the effect of hormone replacement therapy (H.R.T.) for patients with stress incontinence. METHODS: We investigated 25 postmenopausal women, age 54-73 years, with a leakage volume is less than 15 g/day. In this study 0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone acetate were administrated for a total of 4 months. A clinical evaluation, measurement of volume of leakage per day and urodynamic evaluation (urethral pressure profile) were performed three times at pre administration, and at 2 months and 4 months after administration. RESULTS: Five of the 24 patients (20.8%) were improved significantly both clinically and urodynamically. Six patients (25.0%) improved clinically, and two patients (8.3%) improved urodynamically, the remaining 11 patients (45.8%) showed no change. Side effects occurred in eight cases. In one patient, it was necessary to stop administration due to severe irregular genital bleeding and leukorrhea, and in one patient the dosage was reduced due to swelling of breasts. The side effects of swelling of breasts and genital bleeding were relatively mild in the remaining six patients and they could continue H.R.T. administration. CONCLUSIONS: These results suggest that H.R.T. for patients with stress incontinence is not necessarily superior to the other non surgical methods. However, it may provide an alternative treatment method for incontinence.
Aged↗
[Treatment results of radical prostatectomy for localized prostate cancer--biochemical failure analyzed from pathological findings at surgery].
OBJECTIVE: Recurrence is not rare after radical prostatectomy for localized prostate cancer. The treatment results of radical prostatectomy for localized prostate cancer was evaluated in this retrospective study. METHODS: A total of 36 patients with localized prostate cancer (clinical stage: A, B) were treated with radical prostatectomy. Kaplan-Meier product limit method analyzed from biochemical failure was used to study the treatment results of radical prostatectomy, and Cox's proportional hazards model was used to analyze the influence of pathological findings at surgery on biochemical failure. RESULTS: Of all 36 patients, 24 (67%) had pT3 (N0-2) disease, and these patients received adjuvant hormonal therapy after surgery. Overall freedom from biochemical failure at 5 years after surgery was 53% (pT1-2N0; 83%, pT3N0-2; 40%). No significant difference was seen in the freedom from biochemical failure between patients grouped by pathological classification (p = 0.106), tumor grade (p = 0.476), proximal and distal margin involvement (p = 0.095) and regional lymph node metastasis (p = 0.482), but a significant difference was seen between patients grouped by capsule involvement (freedom from biochemical failure at 5 years in cases with positive capsule: 30%, p = 0.023) and seminal vesicle involvement (freedom from biochemical failure at 5 years in cases with positive seminal vesicles: 26%, p = 0.014). Cox's proportional hazards model, on the other hand, showed only that seminal vesicle involvement significantly influenced on biochemical failure (p = 0.031). CONCLUSION: We confirmed a high likelihood of biochemical failure and presumably less favorable prognosis in patients with seminal vesicle involvement. These results indicated that candidates for surgery should be selected pathologically by excluding those with seminal vesicle involvement in the preoperative evaluation.
Aged↗
Effects of freezing, thawing, and storage of human liver samples on the microsomal contents and activities of cytochrome P450 enzymes.
Effects of freezing, thawing, and storage at room temperature of human liver samples on the contents and catalytic activities of individual forms of cytochrome P450 (P450 or CYP) were examined. The stability of liver genomic DNA was also investigated. There were no significant decreases in microsomal levels or catalytic activities of P450 enzymes by storage at -80 degrees C for 5 years. We then examined the effects of freezing/thawing of liver samples. Levels of P450 forms were determined immunochemically and by the activities of typical drug oxidation reactions in liver microsomes of human samples, which were divided into two groups. One group of samples was thawed and kept at 25 degrees C for 6 hr and then frozen again and kept for 1 week at -80 degrees C. In the other group, liver microsomes were prepared at the same time (as those from the other group), but not thawed and refrozen. Thawing the liver samples and storage for 6 hr at 25 degrees C decreased contents of total P450 by about 90% and activities of both NADH-ferricyanide and NADPH-cytochrome c reductases by about 80%. However, the decrease in b5 levels was only about 30%. Spectral studies of P450 suggested that thawing the liver samples and holding them at 25 degrees C produced inactive form P420. P450 proteins were detected by immunoblot analysis with or without thawing, but catalytic activities for individual P450s were decreased drastically by thawing and holding samples for 6 hr at 25 degrees C. Only 10% of tolbutamide methyl hydroxylation activity was present, and there was no detectable ethoxyresorufin O-deethylation activity in such microsomes after thawing and holding samples for 6 hr at 25 degrees C. Genomic DNA from human livers was also found to be degraded after the samples were thawing. These results suggested that thawing and holding the liver samples at 25 degrees C decreased the levels and activities of P450s in microsomes and that there are differences in stabilities in individual forms of P450 proteins. P450 proteins determined immunochemically do not always reflect P450-catalytic functions in human liver microsomes because of difficulties in obtaining fresh liver samples.
Cryopreservation↗
[Induction of cytochrome P-450 IIE1 after chronic ethanol administration in man and in animals].
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Alcoholism↗
Oxidation of xenobiotics by recombinant human cytochrome P450 1B1.
Human cytochrome P450 (P450) 1B1 (CYP1B1) has recently been shown to be an important enzyme in the activation of diverse procarcinogens such as arylarenes, nitroarenes, and arylamines to reactive metabolites that cause DNA damage in the cells. However, it is not known whether this P450 enzyme also plays roles in the oxidation of certain drugs or model substrates commonly used in P450 assays. We examined the substrate oxidation activities of recombinant human CYP1B1 in yeast microsomes and compared these activities with those catalyzed by reconstituted systems containing recombinant CYP1A1 and CYP1A2 which were isolated from membranes of Escherichia coli in which respective cDNAs have been expressed. Catalytic activities towards some of the model substrates of other human P450 enzymes including CYP2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 were also determined and compared. CYP1B1 catalyzed benzo[a]pyrene 3-hydroxylation at rates lower than those of CYP1A1 but higher than those of CYP1A2. The activity towards 7-ethoxyresorufin O-deethylation catalyzed by CYP1B1 was about one-tenth of that of CYP1A1, but the Km values were lower for CYP1B1 than those for CYP1A1 and CYP1A2. CYP1B1 was also able to catalyze the oxidation of theophylline and caffeine, two prototypic substrates for CYP1A2. CYP1B1 did not oxidize other typical P450 substrates such as coumarin, tolbutamide, S-mephenytoin, chlorzoxazone, nifedipine, and testosterone, while low rates of oxidation of bufuralol and 7-ethoxycoumarin were found for CYP1B1. These results indicate that CYP1B1 has catalytic activities overlapping CYP1A1 and CYP1A2 with respect to the oxidation of drugs and model P450 substrates, although the relative catalytic roles in these three P450 enzymes differ depending upon the substrates examined. A distinct marker activity of CYP1B1 has not been identified.
Antibodies↗
HTLV-I pX transgenic rats: development of cytokine-producing mammary carcinomas and establishment of the pX mammary carcinoma cell lines.
In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the HTLV-I pX gene under control of the mouse H-2Kd promoter, mammary carcinomas developed predominantly in females starting at about 5 months of age. The incidence of the tumor reached about 40% when the rats were 12 months old. Histology of the tumor was undifferentiated carcinoma with massive infiltration of granulocytes into the tumor tissue. Systemic granulocytosis and hepato-splenomegaly due to extramedullary granulocytopoiesis were seen in pX rats and nude mice bearing pX mammary tumor. mRNAs of both pX and host genes, Gro and MIP-2, which are granulocyte chemoattractants of the IL-8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene, related with mammary carcinomas, were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats. pX mammary carcinoma cell lines, which have similar characteristics to the primary tumor, were established and the cells underwent apoptosis under the serum deprived conditions. The pX rats and the pX mammary carcinomas appear to be suitable models for analyses of HTLV-I pX oncogenesis and immune pathogenesis in vivo and in vitro.
Animals↗
Models of HTLV-I-induced diseases. Infectious transmission of HTLV-I in inbred rats and HTVL-I env-pX transgenic rats.
To examine the pathogenic roles of HTLV-I in HTLV-I-induced diseases, we developed two models; namely HTLV-I carrier rats and HTLV-I env-pX transgenic rats. Among life long HTLV-I carriers in seven rat strains, only WKAH rats with the RT1k haplotype developed chronic progressive myeloneuropathy, resembling HAM/TSP clinically and histologically in humans, designated as HAM rat disease and after long incubation periods. Apoptosis of myelin forming cells, oligodendrocytes and Schwann cells associated with HTLV-I infection appears to be the primary cause of HAM rat disease. Local activation of the pX gene and TNF alpha gene was evident in these rats. WKAH rats transgenic for HTLV-I env-pX gene were established and at age 5 weeks, swelling of the bilateral ankle joints began to develop and histological features of the affected joints resembled findings in cases of rheumatoid arthritis (RA): high-titers of rheumatoid factors were present in these rats. A series of vascular collagen diseases such as polyarteritis nodosa-like angiitis, polymyositis, myocarditis, and Sjögren's syndrome-like sialodenitis together with RA were present, even in one individual animal. These transgenic rats as well as HAM rats appear to be suitable animal models for elucidating pathogenic mechanisms implicated in HTLV-I-induced diseases and also various demyelinating vascular collagen diseases of unknown etiology.
Animals↗
HTLV-I env-pX transgenic rats: prototype animal model for collagen vascular diseases.
To evaluate the function of HTLV-I env-pX gene in vivo, we developed two lines of transgenic rats (env-pX rats) that expressed env-pX gene products, under control of own LTR promotor. In various tissues of the rats, env and pX mRNAs were constitutively expressed, irrespective of age. At age 5 weeks, swelling of the bilateral ankle joints histologically showing synovial lining hyperplasia, severe chronic inflammation, erosion of the joint cartilage, and bone destruction with pannus formation began to develop in these env-pX rats. These histologic features resemble those of rheumatoid arthritis (RA) in man. High titered rheumatoid factors and low anti-dsDNA antibodies and hyper-gamma globulinemia were detected. Necrotizing arteritis resembling polyarteritis nodosa, polymyositis, myocarditis and Sjögren syndrome-like sialoadenitis developed, together with RA-like arthritis even in one individual animal. Thymic atrophy with low body weight was also observed. The evidence indicates that env-pX rats appear to be suitable animal models for elucidating pathogenetic mechanisms involved in not only HTLV-I related diseases but also various collegen vascular and autoimmune diseases of unknown etiology in man.
Aging↗