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Biomedical subjects

I Hashimoto

Publications and source records attributed to I Hashimoto.

At least 145 records · Page 8Linked to original sources

Mouse 230-kDa bullous pemphigoid antigen gene: structural and functional characterization of the 5'-flanking region and interspecies conservation of the deduced amino-terminal peptide sequence of the protein.

The 230-kDa bullous pemphigoid antigen is a hemidesmosomal protein of the cutaneous basement membrane zone. The primary sequences deduced from full-length human cDNAs predict that this molecule consists of a central rod region and flanking globular domains. To get insight into regulation of the 230-kDa bullous pemphigoid antigen gene (BPAG1), and to evaluate evolutionary conservation of the amino-terminus of the protein, we screened a mouse genomic DNA library with a 0.3-kb cDNA corresponding to the 5' end of the human 230-kDa bullous pemphigoid antigen cDNA. A positive clone was isolated, and Southern analysis of the clone with the 0.3-kb cDNA allowed isolation of a 3.0-kb Hind III fragment containing the 5' end of the coding sequence. Alignment of the sequences of this subclone and human BPAG1 sequences revealed that this fragment contained 2466 bp of 5'-flanking DNA, upstream from the ATG translation initiation site, and 258 bp of translatable sequences that encode a putative polypeptide of 86 amino acids at the amino-terminus of the protein. This deduced polypeptide showed 91% homology with the corresponding human sequence. The TATAAA and CCAAT consensus sequences, as well as several putative cis-regulatory elements, were identified in the 5'-flanking region of the mouse DNA. To test the functional promoter activity of the 5'-flanking DNA, three mouse BPAG1 promoter/CAT reporter gene constructs, with the promoter segments spanning from -1133, -525, and -213 to -1, were developed. Transient transfections of mouse transformed keratinocytes (Pam 212 cells) with these constructs revealed clearly detectable CAT activities, indicating that the 5'-flanking region contains a functional promoter. Furthermore, these experiments suggested that the upstream sequences contain upregulatory elements, as well as elements that confer, at least in part, tissue specificity to the expression of the mouse 230-kDa BPA gene.

Amino Acid Sequence↗

Melanosis Riehl-like facial pigmentation in a Japanese case of AIDS.

An AIDS patient with the cardinal complaint of severe pigmentation on the face is reported. Hyperpigmentation is an unusual symptom of AIDS. This is a Japanese patient who presented melanosis Riehl-like discoloration. The importance of pigmented lesions in patients who have not been given any anti-HIV agents has not been emphasized in the literature.

Acquired Immunodeficiency Syndrome↗

Epidermolysis bullosa simplex with transient erythema circinatum.

A 4-week-old male infant who developed blisters on the face, hands and buttocks immediately after birth was diagnosed as suffering from generalized epidermolysis bullosa (EB) simplex (Köbner). At 6 months of age, centrifugally expanding erythema circinatum suddenly appeared on the trunk and limbs. Blood tests showed transient elevation of liver enzymes. An intercurrent illness such as a bacterial or viral infection, or an adverse reaction to a drug was suspected, but no supportive evidence was obtained. The circinate or arciform pattern of the eruption, and the ultrastructural findings of basal cell cytolysis and some tonofilament aggregation suggested a possible diagnosis of epidermolysis bullosa herpetiformis (Dowling-Meara) [DM-EB]. However, the predominant feature of this child's dermatosis was erythema circinatum, with a small number of blisters limited to the areas affected by erythema. The erythema resolved spontaneously after 8 months. Round or whisk-like clumping of tonofilaments, a typical finding in DM-EB, was not demonstrated on electron microscopy. These observations were not consistent with classical DM-EB, and we consider that this case is an unusual form of EB simplex showing transient erythema circinatum.

Child, Preschool↗

Bullous pemphigoid sera induce bullous-pemphigoid-like lesions in neonatal mice pretreated with a limited dose of ultraviolet B irradiation.

The role of bullous pemphigoid (BP) autoantibodies (Abs) in the pathogenesis of BP is unclear. Lack of a confirmed experimental animal model prevents studies of the pathogenetic role of BP Abs. We hypothesized that some alterations of BP antigens (BP Ags) will be necessary for causative binding of BP Abs to the Ags. To cause an artificial and reproducible alteration, neonatal mice were irradiated with ultraviolet B (UVB). After the irradiation of 600 mJ/cm2 of UVB, BP serum was intraperitoneally injected. When the BP sera, which recognized only the 230-kD BP Ag, or both 230- and 180-kD BP Ags, were transferred into the UVB-treated mice, erosions and vesicles appeared in 14-78% of the animals. Histopathological examination revealed subepidermal blister formation in the mice treated with UVB and BP sera. Electron microscopy demonstrated that the separation occurred at the level of the lamina lucida. Human IgG and C3 were deposited at the dermal-epidermal junction. Control animals to which healthy sera were injected after the same dose of UVB irradiation showed degeneration of the upper epidermis but no apparent dermal-epidermal cleft formation histopathologically. These results suggest that BP antibodies play a pathogenetic role in vivo. This animal model can contribute to a study of the pathogenesis of BP.

Animals↗

Coronary arterial lesions due to Kawasaki disease: selective coronary angiography in five cases with difficult-to-detect localized stenosis.

We report five cases of localized stenosis in coronary arterial lesions due to Kawasaki disease which were difficult to demonstrate by routine selective coronary angiography. Of these cases, three had localized stenosis overlapping the aneurysm, one had localized stenosis overlapping another adjacent branch, and the fifth had localized stenosis at the proximal left main trunk of the coronary artery. The reasons for difficulty in demonstrating the stenoses by routine study include: the localized stenosis was often superimposed on the aneurysm and/or the other adjacent branches, and the catheter was pushed into the inlet of the aneurysm on the proximal left main trunk. For a precise demonstration of a localized stenosis by selective coronary angiography, many angiograms from different perspectives should be taken. In addition, when a large aneurysm exists in the left main coronary artery, selective coronary angiography should be taken without pushing the catheter into the inlet of the aneurysm, and each frame of the cine coronary angiography should be carefully examined. Care should also be taken to compare with the initial view of the projection.

Child↗

Gene expression of collagenase and stromelysin in skin fibroblasts derived from dystrophic epidermolysis bullosa.

We studied expression of collagenase gene and stromelysin gene in skin fibroblasts derived from patients with recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Northern blot analyses revealed that collagenase gene expression was markedly increased in two of four RDEB cells, as compared with three normal control cells. Moreover, stromelysin gene expression was also markedly increased in two RDEB cells, as compared with normal controls. In contrast, collagenase and stromelysin gene expression levels in three DDEB cells did not show any significant difference from those of normal controls, except one cell line which showed mild increase of both collagenase and stromelysin mRNA. Quantitative estimates of collagenase mRNA (U/micrograms RNA) determined by slot blot hybridizations showed that those of RDEBs: 0.92-1.81 (mean 1.3 +/- 0.45); DDEBs: 0.18-0.73 (mean 0.60 +/- 0.37); normal controls: 0.26-0.93 (mean 0.64 +/- 0.34). Stromelysin mRNA levels showed that those of RDEBs: 1.75-6.62 (mean 4.06 +/- 2.00); DDEBs: 0.55-3.78 (mean 1.69 +/- 1.81); normal controls: 1.27-2.08 (mean; 1.55 +/- 0.45). These data demonstrated that collagenase and stromelysin gene expression was increased in some, but not all, RDEB cell lines. Our data suggested that collagenase and/or stromelysin could play a certain role for blister formation in RDEB, coordinately or in a distinct manner.

Adolescent↗

Simultaneous and separated culture of keratinocytes and fibroblasts on each side of a collagen membrane.

We have developed a new cell culture system which is of benefit for the research of dermal-epidermal interaction. In this system, normal human keratinocytes are cultured on the upper surface of a permeable collagen membrane, on the undersurface of which human fibroblasts are simultaneously and separately cultured in a lifted condition. Both the keratinocytes and fibroblasts showed good proliferation and differentiation which were revealed by phase contrast microscopy as well as light and electron microscopies. A permeability test of the collagen membrane used in the present study showed that peptides of less than 30 kDa are able to penetrate through the membrane. Using this system, we estimated the total protein content and cornified envelope formation in the keratinocytes cultured with or without fibroblasts. We found that the total protein and cornified envelope formation were significantly increased when keratinocytes were cultured together with fibroblasts. When keratinocytes were cultured with fibroblasts in the condition of air-liquid interface, synthesis of the cornified envelope was further enhanced. These results indicate that fibroblasts really effect not only the proliferation but also the differentiation of keratinocytes, and the air-liquid interface enhances their effect on differentiation. This bi-phase separated cell culture system is a useful tool for the study of keratinocyte-fibroblast interaction.

Cells, Cultured↗

End results of 114 extended "commando" operations for retromolar trigone carcinoma.

Retromolar trigone carcinomas invade the mandible and the pterygoid and/or masseter muscles in a large number of cases. There is also a significant risk of ipsilateral lymph node neck metastasis. The purpose of this retrospective study was to report the survival results of 114 consecutive patients who underwent an extended "commando" operation (retromolar operation) from 1960 to 1991. The technique is a variation of a composite resection. The operation consists of hemimandibulectomy with resection of the pterygoid and masseter muscles, with an ipsilateral neck dissection (radical classical, modified, or supraomohyoid). The oral cavity and oropharyngeal defects were closed primarily in 83 patients. In the remaining 31 patients (27.2%), it was reconstructed by a tongue flap (12 patients), pectoralis major myocutaneous flap (10 patients), and other flaps (9 patients). There were 104 men and 10 women, with a median age of 55 years. All patients had squamous cell carcinoma. Tumor stages were T1 (5 patients), T2 (44 patients), T3 (24 patients), T4 (28 patients), and Tx (13 patients). The metastases were predominantly in levels I and II. Only patients with positive nodes at levels I and/or II had histologically positive nodes at levels IV or V. Complications occurred in 51.8% of the patients (wound infection in 21 patients, 18.4%). Sixty-six patients underwent postoperative irradiation (4 to 70 Gy, median: 50 Gy). To date, 41 patients have presented with 50 tumor recurrences: 31 local, 9 in the dissected neck, 3 in the contralateral neck, and 7 distant. The 5-year actuarial overall survival rate was 80.0% in patients with T1 tumors, 57.8% in those with T2 tumors, 46.5% in those with T3 tumors, and 65.2% in those with T4 tumors. In conclusion, the retromolar operation can be performed with acceptable morbidity, and it is effective (5-year overall survival rate of 55.3%). The rate of local recurrences (27.2%) suggests that radiotherapy as an adjunctive modality should be indicated in patients in whom recurrences are likely.

Adult↗

Clinical criteria for differentiating between recessive and dominant forms of dystrophic epidermolysis bullosa, elaborated from an analysis of 119 cases.

We attempted to establish clinical criteria which differentiated between recessive dystrophic epidermolysis bullosa (RDEB) and dominant DEB (DDEB), since these two groups show prominent differences in prognosis, genetic recurrence risk and response to some types of treatment. The total of 119 cases examined consisted of our own 9 cases (2 of RDEB and 7 of DDEB) and 110 cases (26 of RDEB and 84 of DDEB) collected from the medical literature. They were analyzed by calculating the sensitivity and specificity of ten clinical features. We concluded that, syndactyly, presence of complications, dental lesions, remission-less course, and oral lesions are strongly indicative of RDEB (more than 70% specific). Intractable skin ulcer is suggestive of RDEB (more than 55% specific). Nail lesions, scar and atrophy, milia and pigmentation are not helpful in the differentiation because of their commonality. The proposed criteria are simple, reliable, and practical, providing us with a useful tool for differentiation of RDEB and DDEB in daily practice.

Child↗

Analyses of serum copper and zinc levels and copper/zinc ratios in skin diseases.

With the objective of comprehending abnormal metabolisms of the essential metals of zinc (Zn) and copper (Cu) in three groups of skin diseases, skin cancer, inflammatory diseases, and non-inflammatory disease, we measured serum levels of Zn and Cu in 151 cases of various cutaneous manifestations and estimated the significance of the ratios between the two metals (Cu/Zn). The serum level of Zn was significantly decreased in cases of bullous pemphigoid, decubitus ulcer, and alopecia areata. The serum level of Cu was elevated in cases of psoriasis, decubitus ulcer, and skin cancer. We observed no elevation of serum Zn level or abnormally depressed serum Cu level. The Cu/Zn ratio showed significantly different values among these three groups of the diseases, suggesting the utility of measuring Cu/Zn ratios for differential diagnosis over that of determining the serum level of Zn or Cu alone. It was also demonstrated that, in each skin disease, the Cu/Zn ratio clearly reflects the severity of the progress.

Adult↗

[Relation of habitual exercise to basal metabolic rate and energy expenditure during exercise in older people].

The relation between habitual exercise and the basal metabolic rate, energy expenditure during exercise (lactic threshold and maximal oxygen uptake) was examined in 291 older people. Metabolic rate was highest in old players of gatebowl (a form of croquet) (male; 23.3 +/- 2.3, female; 22.7 +/- 3.0 kcal/kg/day), higher in old untrained people (male; 21.9 +/- 2.5, female; 20.8 +/- 2.4 kcal/kg/day), and lower in old people in a home for the aged (male; 20.6 +/- 3.5, female; 20.8 +/- 3.7 kcal/kg/day). Energy expenditure while walking at a speed of less than 100 m/min was similar in trained and untrained old people aged 60-69 years. However, lactic threshold was higher in trained (30.2 +/- 4.8 ml/kg/min) than in untrained (20.9 +/- 2.8 ml/kg/min) females aged 60-69 years. Maximal oxygen uptake was higher in trained (male; 50.4 +/- 4.1, female; 36.6 +/- 3.9) than in untrained (male; 30.9 +/- 3.7, female; 26.8 +/- 2.8) old people aged 60-69 years. It was suggested that a higher basal metabolic rate, lactic threshold and maximal oxygen uptake resulted in higher daily physical activity and larger daily energy consumption in trained old people.

Aged↗

[Effect of training fitness on obesity, hypertension, hyperlipidemia and disorders in glucose metabolism].

Effects of physical training on obesity, hypertension, hyperlipidemia and disorders of glucose metabolism were investigated in 359 males, 30-59 years of age. Body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and fructosamine (FA) were measured before and after the 2 month period of physical training at intensities of about 50% of maximal O2 uptake. Results are summarized as follows; 1. Means of BMI, SBP, DBP, TC and FA after the training were significantly lower than before the training. Mean of HDL-C was significantly higher than before the training. 2. In subjects with high BMI (n = 124), high SBP (n = 129) and high DBP (n = 128), means of BMI, SBP and DBP decreased with increase of training time per week. In subjects with low HDL-C (n = 104), high TC (n = 135) and high FA (n = 66), changes in means of TC, HDL-C and FA after the training did not show a relationship to training time per week. 3. Differences observed for measured values before and after the training of 2-3 hours per week were 0.4 kg/m2 in BMI, 15 mmHg in SBP and 10 mmHg in DBP, suggesting that training of 2-3 hours per week was effective in intervention of obesity and hypertension.

Adult↗

Association of annexin V with prolactin in the rat anterior pituitary gland.

When pituitary extracts were subjected to non denaturing polyacrylamide gel electrophoresis, an unknown protein was found to associate with a proportion of the prolactin. This protein was dissociated from prolactin by sodium dodecyl sulfate. The protein was purified and sequenced. As the amino terminus was blocked, the amino acid sequences of three peptide fragments were determined. The obtained sequences of 41 amino acids were identical to partial sequences of a known protein, rat Annexin V. The molecular mass, 36 kDa, was also the same as the molecular weight of Annexin V. The existence of Annexin V mRNA in rat pituitary glands was also confirmed by polymerase chain reaction. These results show that Annexin V, a member of the calcium-dependent phospholipid binding proteins, is synthesized in the rat pituitary gland, and suggest its association with prolatin in the gland.

Animals↗

Somatosensory evoked potential correlates of psychophysical magnitude estimations for air-puff stimulation of the foot in man.

Short air-puff stimuli were applied to the sole of the right foot to obtain both psychophysical and neurophysiological responses. The detection threshold (So) was first determined, and six levels of stimulus intensity above threshold were adopted for magnitude estimation. Somatosensory evoked potentials (SEPs) were also recorded over the foot projection area (2 cm posterior to Cz) for the six stimulus intensities. Six components (N40, P45, N55, P70, N80 and P90) were recorded within 100 ms following stimulation. A power function with an exponent of 0.94 provided an adequate description of the magnitude estimation values as a function of stimulus intensity, as was verified by the high correlation coefficient (r = 0.87; P < 0.001). Similarly, stimulus-amplitude functions of P45-N55, N55-P70 and P70-N80 SEP components were well represented by power functions with exponents of 0.62, 0.63 and 0.78, respectively. The SEP latencies as a function of stimulus intensity had negative power functions. The latency functions of the P45 and N55 components had the largest negative power exponents (-0.17 and -0.15) and showed the highest negative correlations (r = -0.70 and -0.71, respectively) with the stimulus intensity. These results suggest that both the amplitude and the latency information encoded in the SEPs may contribute to the magnitude estimation of the stimulus.

Adult↗

Somatosensory evoked potential correlates of psychophysical magnitude estimations for air-puff stimulation of the face in man.

Air-puff stimuli were applied to the skin of the face to obtain psychophysical and neurophysiological responses. Six levels of stimulus intensity above threshold were adopted for numerical magnitude estimation and for recording somatosensory evoked potentials (SEPs). A power function with an exponent of 0.71 provided an adequate description of the magnitude estimation values as a function of stimulus intensity, as was verified by the high correlation coefficient (r = 0.86, P less than 0.001). Six SEP components (N15, P20, N30, P40, N50 and P65) were recorded during the 100 ms following stimulation. Stimulus-amplitude functions of the various SEP components were well represented by power functions. The P20-N30 component had the highest power exponent (0.66) and also the highest correlation coefficient (r = 0.55, P less than 0.001). The SEP latencies as a function of stimulus intensity had negative power functions. The latency function of the P20 component had the largest negative power exponent (-0.10) and showed the highest negative correlation (r = -0.62) with the stimulus intensity. These results suggest that processing of intensity information occurs at a relatively early stage within the central nervous system, and that both the amplitude and latency information encoded in the SEPs may contribute to stimulus processing.

Adult↗

Input-output relation of the somatosensory system for mechanical air-puff stimulation of the index finger in man.

This study examined input-output relation of the somatosensory system in response to mechanical air-puff stimuli applied to the volar aspect of the tip of the index finger. Compound sensory nerve action potentials (SNAPs) from the median nerve at the wrist and cerebral somatosensory evoked potentials (SEPs) were simultaneously recorded at six levels of stimulus intensity above threshold. Using the time-integral of the SNAPs and SEPs as measures of peripheral and central neural activity, a strongly accelerating power function with an exponent of 1.35 was found to describe peripheral neural function, while central neural function was described by a negatively accelerating function with a power exponent of 0.50, suggesting suppression of SEPs by recruitment of units with increasing stimulus intensity. It was concluded that input-output relation of the somatosensory system can be described by a decelerating power function with the exponent of 0.37.

Action Potentials↗

Inhibitory effect of the leukotriene B4 receptor antagonist against hypomagnesic diet-induced dermatitis in hairless rats.

In vivo experiments have shown that magnesium deficiency elicits characteristic skin lesions in the hairless rat. However, the mechanism of the involvement is not clarified. From the results of previous studies, a product derived from arachidonic acid, but not via the cyclooxygenase pathway, has been considered as an etiological cause. In this study, the inhibitory effect of newly produced leukotriene B4 (LTB4) receptor antagonist (LTBRA) against these skin manifestation was examined in hairless mutants given a hypomagnesic diet. Control animals with treatment of LTBRA developed eruptions on their bodies with increasing serum levels of LTB4, but LTBRA-treated animals did not suffer from the cutaneous disorder. Increased serum levels of LTB4 in control rats were significantly higher than those in the pre-treated condition. The diminution of skin lesions by LTBRA strongly indicated that magnesium deficiency dermatitis may involve a lipoxygenase-mediated metabolite of arachidonic acid, presumably LTB4, and that the cutaneous changes in hairless rats fed with hypomagnesic diet might provide an easily identifiable indicator of LTB4-mediated dermatitis.

Animals↗