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K Toda

Publications and source records attributed to K Toda.

At least 19 recordsLinked to original sources
PubMed1992

The chimeric gene linked to glucocorticoid-suppressible hyperaldosteronism encodes a fused P-450 protein possessing aldosterone synthase activity.

Glucocorticoid-suppressible hyperaldosteronism (GSH) is one variety of primary aldosteronism with hypertension and is inherited in an autosomal dominant mode. A recent report has indicated that GSH is caused by a gene duplication arising from unequal crossing over between the two genes, CYP11B1 and CYP11B2, encoding P-450(11 beta) and P-450C18, respectively (Lifton et al. Nature (1992) 355, 262-265). The nucleotide sequence analysis in the present study has demonstrated that unequal crossing over in the chimeric gene formed by the gene duplication occurs within the region from the 3'-portion of exon 4 through the 5'-portion of intron 4 in Australian GSH patients. Namely, the chimeric gene encodes a fused P-450 protein consisting of the amino-terminal side of P-450(11 beta) (encoded by exons 1-4 of CYP11B1) and the carboxyl-terminal side of P-450C18 (encoded by exons 5-9 of CYP11B2). When a cDNA corresponding to the chimeric gene is transfected into COS-7 cells, the fused P-450 protein expressed in the mitochondria exhibits steroid 18-hydroxylase or aldosterone synthase activity. These results provide the molecular genetic basis for the characteristic biochemical phenotype of GSH patients.

Animals↗
PubMed1992

Characterization of a cis-acting regulatory element involved in human-aromatase P-450 gene expression.

The characteristics of a cis-acting regulatory region involved in the human-aromatase P-450 gene have been examined by transient expression analysis. The region spans from -242 - -166 relative to the cap site of the gene. A fragment containing the region excised from the gene enhances heterologous promoter activity as well as its own promoter activity in a position-independent and orientation-independent manner. The fragment exerts its enhancer activity in human BeWo choriocarcinoma cells in which the aromatase P-450 gene is expressed, but not in other cell lines tested. Deletion of 38 bp from the 3' end of the fragment results in a complete loss of enhancer activity. A gel-retardation assay with nuclear extracts from BeWo cells suggests the existence of a nuclear factor(s) which interacts with the fragment. These results suggest that the regulatory element in the fragment is involved in efficient transcription of the human-aromatase P-450 gene.

Animals↗
PubMed1992

Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans.

A gene encoding steroid 18-hydroxylase (P-450C18) was isolated from a human genomic DNA library. It was identified as CYP11B2, which was previously postulated to be a pseudogene or a less active gene closely related to CYP11B1, the gene encoding steroid 11 beta-hydroxylase (P-45011 beta) [Mornet, E., Dupont, J., Vitek, A. & White, P. C. (1989) J. Biol. Chem. 264, 20961-20967]. The nucleotide sequence of the promoter region of the P-450C18 gene is strikingly different from that of the P-45011 beta gene, although the sequences of their exons are 93% identical. The transient expression in Y-1 adrenal tumor cells of CAT constructs with a series of deletion mutants of promoter regions of both genes indicated that the two genes are regulated differently. P-450C18 as expressed in COS-7 cells exhibits steroid 18-hydroxylase activity to catalyze the synthesis of aldosterone and 18-oxocortisol and exhibits steroid 11 beta-hydroxylase activity as well. In contrast, P-45011 beta as expressed in the cultured cells exhibits steroid 11 beta-hydroxylase activity exclusively but fails to catalyze the synthesis of aldosterone and 18-oxocortisol. These results indicate that P-45011 beta and P-450C18 are products of two different genes and that the former participates in the synthesis of glucocorticoids whereas the latter participates in the synthesis of mineralocorticoids in humans.

Amino Acid Sequence↗
PubMed1992

Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients.

The gene for steroid 18-hydroxylase (P-450C18) has been recently assigned to encode corticosterone methyl oxidases Type I and Type II which were previously postulated to catalyze the final two steps in the biosynthesis of aldosterone in humans. Molecular genetic analysis of the P-450C18 gene is three patients from three different families affected with CMO II deficiency has indicated that a point mutation of CGG----TGG (181Arg----Trp) in exon 3 and one of GTG----GCG (386Val----Ala) in exon 7 occur exclusively in the gene of the patients. Analysis of PCR products by restriction enzymes (HapII and HphI) has indicated that the patients are homozygous and the unaffected parent is heterozygous for both mutations, in accordance with the established concept that CMO II deficiency is inherited in an autosomal recessive manner. These data clearly provide the molecular genetic basis for the characteristic biochemical phenotype of CMO II clinical variants.

Aldosterone↗
PubMed1992

Amyloidosis cutis dyschromica. DNA repair reduction in the cellular response to UV light.

BACKGROUND: Amyloidosis cutis dyschromica, a special type of primary cutaneous amyloidosis, is assumed to be a congenital disorder and sun exposure is thought to be the major causal factor. Herein we report a case of this rare disease and DNA repair characteristics of UV damages in the fibroblasts derived from the patient. OBSERVATIONS: A 24-year-old Japanese woman showed hyperpigmented and hypopigmented xerotic lesions in sun-exposed skin since she was 10 years old; deposits of amyloid material were detected in the papillary dermis. The fibroblasts were hypersensitive to UV-B, but not so sensitive to UV-C. Unscheduled DNA synthesis of the patient's cells after UV-C exposure was lower than that of normal cells at 3 hours and both reached the same level at 6 hours. After UV-B exposure, unscheduled DNA synthesis of the patient's cells was lower than that of normal cells at least until 6 hours after UV exposure. CONCLUSION: Although the origin of amyloidosis cutis dyschromica is unknown, hypersensitivity to UV-B with possible DNA repair defects is suggested to be the cause of this disease.

Adult↗
PubMed1992

Regional cerebral blood flow and P3 variables in patients with multiple lacunar infarcts.

We measured regional cerebral blood flow (rCBF) and event-related potentials (ERPs) in 36 patients with multiple lacunar infarcts and 14 age-matched normal subjects. rCBF was measured by the 133Xe inhalation method. ERPs were recorded during visual discrimination tasks using three kinds of stimuli. The patients showed lower mean cortical blood flow than normal subjects especially for the frontal cortex. Nontarget P3 latency in patients was longer than in normal subjects, while no significant differences could be found in target P3 latency between the two groups. Nontarget P3 latency correlated with frontal CBF. These results show that frontal lobe dysfunction may be particularly marked with multiple lacunar infarcts and suggest that reduction of frontal CBF is related to the impairment of the automatic processing associated with the nontarget P3 component.

Aged↗
PubMed1992

Immunohistochemical distribution of adult T-cell leukemia-derived factor/thioredoxin in epithelial components of normal and pathologic human skin conditions.

Tissues from normal human skin and various skin diseases were studied with the immunoperoxidase technique using an antibody to adult T-cell leukemia-derived factor (ADF), a homologue of human thioredoxin. Normal human skin showed positive immunostaining for ADF/thioredoxin in the outer root sheath of hair follicle, sebaceous glands, and secreting components of apocrine and eccrine sweat units, but not in the unexposed interfollicular epidermis and other parts of both hair follicles and the sweat units. Immunoreactivity of benign skin tumors gave similar distribution to their normal counterparts; trichilemmal cyst, nevus sebaceus, senile sebaceous hyperplasia, and mixed cell tumor were positive for immunostaining, whereas epidermal cyst and pilomatricoma were not. No immunoreactivity was detected in malignant skin tumors such as basal cell carcinoma and poorly differentiated squamous cell carcinoma. Solar keratosis, well-differentiated squamous cell carcinoma, some of metastatic lesions of squamous cell carcinoma, and extramammary Paget's disease reacted with the antibody. These immunoreactivities reflected numerous functions of thioredoxin in higher organisms. Our findings suggest that the expression of ADF/thioredoxin in both normal and abnormal human skin is related to epithelial cell differentiation.

Adult↗
PubMed1992

Event-related potentials in patients with multiple lacunar infarcts.

We studied event-related potentials (ERPs) occurring in response to attended and unattended stimuli in 31 patients with multiple lacunar infarcts. ERPs were recorded during the performance of visual discrimination tasks using three kinds of stimuli. Each component of P300 response to infrequent nontarget stimuli and P300 response to infrequent target stimuli was defined as non-target P3 or target P3. The non-target P3 latency in patients with multiple lacunar infarcts was significantly longer than in 15 age-equivalent normal subjects, while no significant differences could be found in target P3 latency between patients and normal subjects. From the controlled/automatic standpoint these results suggest that multiple lacunar infarcts are related to impairment of automatic processing reflected by non-target P3, although controlled processing reflected by target P3, is less impaired.

Aged↗
PubMed1992

Intracavernous epidermoid tumor presenting with abducens nerve paresis--case report.

An unusual case of a pediatric epidermoid tumor entirely located in the cavernous sinus is reported. A 6-year-old boy presented with left abducens nerve paresis which developed over 2 months. Neuroimaging demonstrated a lesion in the left cavernous sinus. Part of the tumor capsule and the pearly contents were removed by the left pterional approach through Dolenc's anterolateral triangle. No bleeding from the cavernous sinus occurred. The tumor was histologically identified as an epidermoid tumor. Postoperatively, the abducens nerve paresis improved. The presence of dural reflection in the lateral wall of the cavernous sinus and displacement of the intracavernous internal carotid artery are useful indicators for intracavernous lesions.

Abducens Nerve↗
PubMed1992

[Correlation of visual evoked potentials with dementia in Parkinson's disease].

There has been some debate regarding abnormalities in visual evoked potentials (VEP) in Parkinson's disease (PD). To elucidate the mechanism causing abnormal VEP, we investigated the relationship between VEP and mental function in PD patients. Pattern reversal VEP was recorded in PD patients (n = 27) and age-matched control subjects (n = 14). PD patients consisted of two subgroups; PD without dementia (nD-PD; n = 17) and PD with dementia (D-PD; n = 10). Dementia was evaluated according to the criteria for dementia assigned in DSM III-R, and mental faculties were estimated by using the mini-mental state examination (MMSE). In pattern VEP recordings, P100 latency and amplitude were measured for each eye stimulated. No patient or control subject had impairment of corrected visual acuity or ophthalmological disease. There was no significant difference in age among the three groups (D-PD, nD-PD and control subjects). D-PD patients showed significantly prolonged P100 latency compared to nD-PD patients and control subjects (p less than 0.05). With respect to P100 amplitude, no significant difference was shown among the three groups. In PD patients, there was a rough correlation between P100 latency and MMSE score. No correlation was found between P100 amplitude and MMSE score. In control subjects, P100 latency did not correlate with advancing age. In PD patients, nD-PD patients showed a significant correlation between P100 latency and age, whereas D-PD patients presented no correlation. Abnormal VEP in PD has been mostly ascribed to dopaminergic deficiency in the retina.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[A case of idiopathic pulmonary fibrosis with histology of usual interstitial pneumonia that responded to pulse therapy followed by combined immunosuppression with prednisolone and azathioprine].

A 64-year-old woman who was admitted with cough and dyspnea showed severe hypoxemia and interstitial lung shadows. The clinical diagnosis was idiopathic interstitial pneumonia (synonymous with idiopathic pulmonary fibrosis in the United States), since there were no specific immunological or bacteriological findings. No clinical signs or laboratory data compatible with collagen disease were observed. Methylprednisolone pulse therapy was given followed by prednisolone (0.8 mg/kg) and azathioprine (15 mg/kg). Marked improvement of hypoxia, chest X-ray and spirometry results was observed after five weeks. Histological examination of an cases of residual interstitial shadow obtained by open lung biopsy revealed usual interstitial pneumonia. Tapering of the immunosuppressant drugs led to a recurrence 3 months later, which was controlled by reintroduction of the same regimen. Therefore, only prednisolone was tapered, and data obtained in an outpatient clinic 6 months after the recurrence were as follows: %VC 108%, %DLco 72%, PaO2 80 Torr. The value of this regimen for acute IPF or exacerbation of IPF is suggested because of its life-saving effects.

Aged↗
PubMed1992

Age-related changes in attended and unattended P3 latency in normal subjects.

Event-related potentials to visual attended and unattended stimuli were studied in 37 normal subjects between the ages of 19 and 91. The components of the P3 responses to rare nontarget stimuli and rare target stimuli were measured as P3a and P3b, respectively. Both the P3a and P3b latencies were significantly and positively correlated with age. The N2 finding of age-related latency prolongation was comparable to the P3a changes with age. From the standpoint of the theory of automatic and controlled processing, these results suggest that both automatic processing, as reflected by the P3a, and attentional controlled processing, as reflected by the P3b, are impaired with normal aging.

Adult↗
PubMed1992

The mechanism of action of serum immunosuppressive factor in Crohn's disease: it blocks the growth of mitogen-stimulated lymphocytes in early G1 phase through an inhibition of transferrin receptor expression.

The presence of serum immunosuppressive factor has recently been reported in patients with Crohn's disease. We investigated the mechanism of action of this immunosuppressive factor in vitro. The factor in serum fraction from patients with Crohn's disease had an inhibitory activity on the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from healthy volunteers. The growth of tumor cell lines, however, was not inhibited by the factor. While the factor did not influence the production of interleukin 2 (IL2) or the expression of IL2 receptor of PHA-stimulated PBMCs, it inhibited the expression of transferrin receptor. The effect of the factor on cell cycle of PHA-stimulated PBMCs was examined by flow cytometry analysis. The factor kept the cells in quiescent G0/G1 phase and decreased the number of cells in S phase. Prostaglandin E2, an immunosuppressive substance, may not participate in the inhibitory action of the factor, since indomethacin did not affect the inhibitory activity of the factor. These results suggest that the immunosuppressive factor in serum from patients with Crohn's disease is unique in the mechanism of inhibitory action and further clarification of this factor might contribute to the development of a new diagnostic assay for Crohn's disease and the elucidation of the pathogenesis of this disease.

Cell Cycle↗
PubMed1992

[A case of inflammatory breast cancer treated with medroxyprogesterone acetate (MPA) in combination with intra-arterial infusion chemotherapy].

A 55-year-old female with severe inflammatory breast cancer was treated with the combined use of MPA and the intraarterial infusion chemotherapy. One cycle consisted of 4'-epi-adriamycin; 210 mg (day 1, 4 and 8) and daily administration of MPA; 1,200 mg. A marked shrinkage of the tumor was obtained with this treatment. The regressive change was noted not only in the primary lesion but in lymph nodes of the axillary region. Therefore, the combined use of MPA with intra-arterial infusion chemotherapy may well contribute to the treatment of inflammatory breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Effect of serum factors on the differentiation of a colon cancer cell line Caco-2].

A human colon cancer cell line Caco-2 undergoes spontaneous enterocytic differentiation under the standard culture condition. We examined the changes in the proliferative activity of Caco-2 cells during the differentiation, and the effect of serum factors on this spontaneous differentiation. Caco-2 cells cultured in FCS-containing media exhibited the differentiation phenotypes such as dome formation and increase of ALP activity after the 6th day of culture. Cell cycle analysis showed a marked decrease in S phase cell population during the cell differentiation. When Caco-2 cells were cultured in FCS free media, the cell population of S phase remained unchanged during culture period and the differentiation phenotypes were not induced. The addition of FCS to Caco-2 cell cultured in the absence of FCS resulted in the rapid induction of the differentiation phenotypes. These results suggest that differentiation of Caco-2 cells is closely related to the reduction of cell proliferation and requires some factors in FCS.

Animals↗
PubMed1991

Comparisons of the sensation perceived and intradental nerve activity following temperature changes in human teeth.

The relationship between the intradental nerve responses and subjective sensory ratings evoked by thermal stimulation of the teeth was studied in man. Recordings were taken from a total of 12 thermally sensitive units from the inferior dental nerve following thermal tooth stimulation, of which seven responded to both heating and cooling, two were exclusively cold-sensitive and three exclusively heat-sensitive. The early and late sensory responses following both cold and heat stimulation of the tooth were observed. The late sensory responses were more unstable than the early sensory responses. The mean threshold of the early sensory responses to tooth cooling was 13.6 +/- 1.9 degrees C (n = 9) and that to heat stimulation was 48.4 +/- 4.8 degrees C (n = 10). The firing frequency of the heat-sensitive, but not the cold-sensitive, units increased linearly in proportion to the increase in magnitude of the early sensory ratings.

Adult↗
PubMed1991

Membrane-bound respiratory system of Enterobacter cloacae strain HO1 grown anaerobically with chromate.

Chromate has been demonstrated to be an electron acceptor in the respiratory chain of anaerobically grown Enterobacter cloacae strain HO1. By using potentiometric titration and low temperature spectroscopy, the spectral absorption of the anaerobic membrane vesicles of this organism in the presence of chromate was resolved into six peaks at 548, 549, 550, 555, 556, and 558 nm in the alpha band of the reduced minus oxidized spectra. The spectra elicited by chromate are attributed to cytochromes c548, c549, c550, b555, b556, and b558. Among these cytochromes, c548 was found to be specifically involved in electron transfer to chromate.

Anaerobiosis↗