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Biomedical subjects

I Hashimoto

Publications and source records attributed to I Hashimoto.

At least 37 records · Page 2Linked to original sources

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

Analysis of left ventricular regional wall motion in normal neonates.

OBJECTIVE: To investigate neonatal circulatory change by quantitative analysis of left ventricular regional wall motion. DESIGN: Random prospective study. SETTING: Department of paediatrics in a teaching hospital. PARTICIPANTS: 66 neonates born after a normal pregnancy, labour, and delivery. INTERVENTIONS: Quantitative analysis of left ventricular regional wall motion was performed on cross sectional echocardiograms. M mode, cross sectional, and Doppler echocardiograms were obtained simultaneously. MAIN OUTCOME MEASURES: Manually traced endocardial contours at end diastole and at end systole were realigned by superimposing the centre of the ventricular mass and the axis. The contours were divided into 24 segments with 24 radii of equal arc from the centre. Then the ratio of the change in area between the outline of the contour and the two hemiaxes was calculated automatically. RESULTS: There was hyperkinesis of the interventricular septum in the first 24 hours after birth which continued until the end of the first week. Simultaneous echocardiographic examination showed evidence of pulmonary hypertension, as indicated by an increase in the ratio of the right pre-ejection period to the right ventricular ejection time (RPEP/RVET) and of the diameter ratio of the pulmonary artery to the aorta and a shortening of the acceleration time of pulmonary arterial blood flow. These features disappeared within a week. CONCLUSIONS: Hyperkinesis of the interventricular septum may reflect circulatory changes that are characteristic of the early neonatal period.

Diastole

[Magnetic resonance imaging: evaluation of the Blalock-Taussig shunts and anatomy of the pulmonary artery].

The morphology and circulation of the pulmonary arteries and shunt vessels were evaluated by magnetic resonance imaging (MRI) in 8 patients with cyanotic heart disease after a Blalock-Taussig shunt operation. Their ages ranged from one month to 17 years. MRI permitted assessment of the size and patency of the Blalock-Taussig shunts, as well as the size and morphology of the pulmonary arteries in all patients. Measurements of the vessel diameters on MRI correlated well with the angiographic measurements (main pulmonary artery, r = 0.98; right pulmonary artery, r = 0.98; left pulmonary artery, r = 0.98; and Blalock-Taussig shunt, r = 0.97). MRI successfully imaged 3 of 4 shunt obstructions and 3 of 4 pulmonary stenoses with high resolution. In assessing peripheral pulmonary stenosis or obstruction, MRI was superior to echocardiography, the latter being unable to image peripheral pulmonary arteries satisfactorily. We concluded that MRI is an excellent noninvasive method for serially evaluating the anatomy and function of Blalock-Taussig shunts and pulmonary arteries, which is particularly useful for children with cyanotic congenital heart disease.

Adolescent

Increased gene expression of matrix metalloproteinase-3 (stromelysin) in skin fibroblasts from patients with severe recessive dystrophic epidermolysis bullosa.

Gene expression of matrix metalloproteinase 3 (MMP-3 = stromelysin) was examined in the skin fibroblasts obtained from patients with severe recessive dystrophic epidermolysis bullosa (RDEB). Steady-state mRNA level of MMP-3 was selectively increased in the unstimulated RDEB cells by a post-transcriptional mechanism. A parallel study on the susceptibility of type VII collagen to MMPs revealed that this type of collagen is degraded by MMP-3, but not by MMP-1 (collagenase). These data suggest that MMP-3 may play an important role in the blister formation fo the skin in RDEB patients by the degradation of anchoring fibrils consisting of type VII collagen.

Blotting, Northern

Multi-unit activity in sensory fibers is related to intensity of sensation evoked by air-puff stimulation of the glabrous hand in man.

An analysis of a multi-unit activity (MUA) recorded from the median nerve at the wrist was undertaken to study intensity coding in the peripheral somatosensory system. Brief air-puff stimuli were applied over the glabrous hand to obtain neural and psychophysical responses. The detection threshold (So) was determined and 6 above-threshold stimulus intensities (So + 0.25 kg/cm2, So + 1.25 kg/cm2, So + 2.50 kg/cm2, So + 3.75 kg/cm2, So + 5.00 kg/cm2, and So + 6.25 kg/cm2) were adopted for magnitude estimation. MUA was recorded for the 6 stimulus intensities and for the threshold (So) level. Response duration, number and frequency of the MUA were evaluated as candidate coding parameters for stimulus intensity. A simple power function with an exponent of 1.03 provided an adequate description of the magnitude estimation function. Similarly, stimulus-response functions of the 3 parameters defining the MUA were well represented by straight lines in double logarithmic plots, with the function of the MUA number having the highest power exponent (0.98) and also the highest correlation coefficient. The results suggest that the total number of MUA, representing spatial recruitment, is the most relevant coding parameter for the subjective magnitude estimation of the stimulus intensity.

Adult

Conduction velocity and temporal dispersion of the nerve volleys evoked by air-puff stimulation of the index finger and palm.

Air-puff stimuli were delivered to 5 successive sites (3 cm increments) over the index finger and palm to record propagating sensory nerve action potentials (SNAPs) from surface electrodes over the median nerve at the wrist. SNAPs consisted of a series of individual peaks (N1, P1, P2, N2 and P3) and the corresponding peaks in the records with stimulation at the various locations could be identified. The apparent conduction velocity of the first peak determined from the stimulation point at the finger tip to the wrist was 38 m/sec. With stimulation of the more proximal locations it became even slower. This paradoxical slowing is due to an increasing effect in the calculation of conduction velocity of the utilization time at the receptors for air-puff stimulation at progressively proximal sites. Segmental conduction velocity estimated between adjacent stimulus sites was 10-20 m/sec faster than the distal conduction velocity between the finger tip and the wrist. Within each segment, the conduction velocities of the individual peaks were not significantly different. These findings, together with invariant durations of the negative components (N1 and N2) in the propagating SNAPs along the ascending digital nerves, lead to the conclusion that the separate peaks are not the result of temporal dispersion due to differences in conduction velocity of skin afferents, but are primarily due to a more peripheral receptor mechanism involving variable delays in activation of different classes of mechanoreceptors.

Action Potentials

Multichannel measurements of magnetic compound action fields of the median nerve in man.

Magnetic compound action fields (CAFs) evoked by electrical stimulation of the median nerve at the wrist were recorded with 7-channel 2nd-order SQUID gradiometers. CAFs measured over the elbow and upper arm were biphasic with field patterns and polarities corresponding to the depolarization and repolarization fronts of the action potential volley.

Action Potentials

Compound activity in sensory nerve fibers is related to intensity of sensation evoked by air-puff stimulation of the index finger in man.

An analysis of a population response recorded from the primary afferents was undertaken to study the neural signs of intensity coding in the peripheral somatosensory system. Short air-puff stimuli were applied to the volar aspect of the tip of the index finger to obtain both neural and psychophysical responses. The detection threshold (So) was first determined and 6 levels of stimulus intensity above threshold (So + 0.25 kg/cm2, So + 1.25 kg/cm2, So + 2.50 kg/cm2, So + 3.75 kg/cm2, So + 5.00 kg/cm2, and So + 6.25 kg/cm2) were adopted for magnitude estimation using the stimulus level of So + 2.50 kg/cm2 as the standard stimulus. The subject was asked to give a numerical estimate of the intensity of a series of stimuli randomly presented. Compound sensory nerve action potentials (SNAPs) were also recorded from surface electrodes over the median nerve at the wrist for the 6 stimulus intensities. Eight SNAP components (4 positive and 4 negative) were recorded within 10 msec following stimulation. A simple power function with an exponent of 0.85 provided an adequate description of the magnitude estimation function, as was verified by the high correlation coefficient (r = 0.89, P less than 0.001). Similarly, stimulus-amplitude functions of individual SNAP components were well represented by straight lines in double logarithmic plots. The function of the late N2-P3 component had the highest power exponent (0.80) and also the highest correlation coefficient (r = 0.59, P less than 0.001). The functions of other SNAP components had considerably lower power exponents with lower correlation coefficients. Thus, a mismatch between neural and psychophysical functions was obvious when individual neural functions were compared with the psychophysical function. Conversely, it was found likely that the total number or time-integral of peaks in the population response was a more pertinent parameter of neural activity and, thus, had a closer correlation with the psychophysical response.

Adolescent

Expression of glutathione S-transferase-pi in malignant skin tumors.

GST-pi has been known to be markedly increased in human (pre) neoplasms of several organs. In this paper, the significance of immunohistochemical detection of GST-pi in human malignant tumors of the skin was studied. In specimens from 40 patients with various skin cancers, malignant melanoma, Paget's disease and undifferentiated squamous cell carcinoma showed strong reactivity in GST-pi staining. The reactions were negative or weak in Bowen's disease, basal cell epithelioma and solar keratosis. In normal melanocytes, eccrine, apocrine, and breast gland cells stained positively but not in keratinocytes, sebaceus gland and fibroblasts. While immunohistochemical detection of GST-pi in the skin was not specific for malignancies, it contributed to aid the distinction of squamous cell carcinoma from other keratinocytic tumors. GST-pi might provide potentially useful information on chemosensitivity of skin cancer, and might serve as a biomarker of disease activity.

Biomarkers, Tumor

Eccrine syringofibroadenomatous hyperplasia in a patient with bullous pemphigoid: a case report and review of the literature.

A 76-year-old man with multiple erythematous lesions on his palms and soles which appeared following bullous pemphigoid (BP) is the subject of this case report. The lesions were not raised above the normal skin level, and there were no nodules on the erythematous lesions. The lesions had the histologic appearance of eccrine syringofibroadenoma. This condition is considered to be not a true tumor but a hyperplasia of eccrine sweat ducts following recurrent subepidermal blister formation in BP.

Adenofibroma

Latencies of peripheral nerve and cerebral evoked responses to air-puff and electrical stimuli.

This study examined the latency relationship between mechanically and electrically elicited sensory nerve action potentials (SNAPs) and the somatosensory-evoked potentials (SEPs) they produce. Brief air-puff and electrical stimuli were applied to the tip of the index finger in separate trials and SNAPs from the median nerve at the wrist and SEPs from the scalp were recorded for each stimulus presentation. Air-puff evoked SNAPs were polyphasic, usually consisting of 2 to 4 separate waves, unlike triphasic activity elicited by electrical stimulation. The SEPs produced by these 2 distinct forms of inputs, however, were similar in morphology. The latencies of the initial components of SNAPs and SEPs were longer for air-puff stimulation. The conduction time, however, of the fastest afferent volleys from the wrist to cortex was not significantly different for air-puff (20.52 +/- 1.06 ms, mean +/- SD) and electrical stimulation (20.17 +/- 0.66 ms). It is therefore concluded that the latency delays for air-puff evoked SNAPs and SEPs are due solely to a transduction time at the skin receptors and not due to differences in conduction velocities as suggested in the previous literature.

Adult

Interleukin-1 induces collagenase production by recessive dystrophic epidermolysis bullosa fibroblasts.

We examined the direct effect of interleukin-1 (IL-1) on the collagenase production by epidermolysis bullosa (EB) fibroblasts. Addition of IL-1 at concentrations of 2.5 x 10(-4) units/ml or below in the culture media greatly enhanced collagenase production by two cell lines of recessive dystrophic EB (RDEB) fibroblasts. They produced 4.82 +/- 0.04 to 5.93 +/- 0.39 units/ml of enzyme, as compared to 0.02 +/- 0.07 units/ml in the absence of IL-1. In contrast, collagenase production by two cell lines of dominant dystrophic EB (DDEB) and normal fibroblasts was not, or only slightly, increased up to 0.69 +/- 0.28 units/ml. IL-1 concentrations of 2.5 x 10(-3) units/ml or higher failed to induce collagenase production by all fibroblasts. 3H-thymidine uptake increased by about 110-376% of control after IL-1 treatment. In addition, these data were obtained using fibroblasts of the 13-15 passages, suggesting that the property might be determined genetically. Although RDEB seems to be a wide heterogeneous group, the present data strongly suggest that the property may be specific to and characteristic of some types of RDEB cells.

Cells, Cultured

[Magnesium deficiency dermatitis--changes in leukotriene levels and effects of azelastine hydrochloride on the dermatitis and leukotriene B4].

To estimate the pathogenesis of magnesium deficiency dermatitis (MDD) in the hairless rats fed with a hypomagnesic diet, plasma concentrations of leukotrienes (LTB4, LTC4, LTD4) were measured. Inhibitory effect of azelastine hydrochloride (AZ), which is known as an inhibitor of 5-lipoxygenase, on MDD was also evaluated. In the hairless rats with magnesium deficiency condition, plasma level of leukotriene B4 was increased, whereas LTC4 and LTD4 showed no changes. In AZ-administered rats, MDD was depressed with the dose-dependent tendency. However, the decrease of LTB4 level did not follow therapeutic effect of AZ for gross appearance of dermatitis. These results indicated that development of MDD associates with increase of LTB4, but its pathogenetic role still remains unknown, and inhibitory effect of AZ against MDD not based on reduction of LTB4 production.

Animals

Interleukin-1 levels in blister fluids of some skin diseases with blister formation.

The interleukin-1 (IL-1) concentrations in 32 blister fluid samples from 26 patients with several bullous dermatoses were determined using a radioimmunoassay technique in order to investigate the relation between IL-1 levels and blister formation. In epidermolysis bullosa, cases with the recessive dystrophic type showed normal levels, but about half of the cases of the simplex type demonstrated high levels. In autoimmune bullous diseases a tendency to higher levels was observed, and especially a patient with herpes gestationis had remarkably high levels. The high IL-1 levels in 25% (3/12) of samples from burn patients are probably related to the severity of inflammation and the duration after bulla formation. Since the IL-1 levels showed no great change in time courses of days, observations in the shorter term, i.e. in the course of hours, will be more useful.

Autoimmune Diseases

Sensory nerve action potentials elicited by mechanical air-puff stimulation of the index finger in man.

Brief air-puff stimuli were applied to the tip of the index finger to record propagating sensory nerve action potentials (APs) from pairs of surface electrodes at successive sites over the median nerve of the distal forearm. Within 10 msec, air-puff stimulation elicited 2-4 separate waves lasting 3-6 msec, in contrast to a single triphasic wave evoked by electrical stimulation. Amplitudes of air-puff evoked APs were much smaller than those of electrically induced APs. However, the amplitude ratio of the initial negative wave (P1-N1) of electrically evoked APs to that of air-puff induced APs declined linearly as a function of recording points along the ascending median nerve. Similarly, the duration ratio of the same component (N1) increased progressively in the proximal direction along the nerve. These results suggest that air-puff evoked afferent volleys undergo considerably less temporal dispersion than those induced by electrical stimulation. Thus, each peak of air-puff evoked APs represents a relatively homogeneous afferent fiber population. The initial P1, N1 and P2 peaks of air-puff evoked APs occurred later than those of electrical induced APs, and the latency included the time of skin indentation and receptor transduction in response to mechanical stimulation. Proximal conduction velocities were faster than distal conduction velocities due to cancellation of the extra delay at the skin mechanoreceptors as well as a true increase in the proximal direction. There were no significant differences between the interelectrode conduction velocities of the fastest fibers activated by the air-puffs and by electrical stimulation. Interelectrode propagation velocities of the different peaks from the same segments had no significant differences for air-puff evoked APs. The presence of multiple peaks may not be the result of temporal dispersion due to difference in conduction velocity of skin afferents but primarily due to a more peripheral receptor mechanism involving transduction and impulse generation.

Action Potentials

Superoxide anion in polymorphonuclear leukocytes of hairless rats suffering from magnesium-deficiency dermatitis.

Clinical and histological studies were made on magnesium-deficiency dermatitis produced on a new strain of hairless rats. Superoxide anion generation in polymorphonuclear leukocytes (PMNs) and the inhibitory effect of some antioxidants and anti-inflammatory agents against the elicited dermatitis were also examined. From the detection of increased superoxide production and effective actions of inhibitors including superoxide dismutase, cepharanthine, 4-4'-diamono-diphenylsulphone and 5,4,11,14-eicosatetraynoic acid (ETYA), it is indicated that superoxide anion or related activated oxygen may be responsible for magnesium-deficiency dermatitis as an inflammatory mediator and that the dermatitis may be related to lipoxygenase metabolites derived from arachidonic acid.

Animals

[Changes in cerebral level of monoamines by Japanese encephalitis virus infection].

The changes in monoamine levels of different brain regions following Japanese encephalitis virus (JEV) intraperitoneal inoculation were examined in experimentally JEV-infected mice. In addition, virus distribution was studied using infectivity assay and immuno-histochemistry of viral antigen. 1) The level of monoamines in brain tissues was not affected by 48 hours after viral inoculation, but marked effects were elicited at 96 hours after the inoculation. The cerebral concentration of 5-hydroxyindole-3-acetic acid (5 HIAA) was increased, while that of dopamine (DA) showed a decrease. Especially these alteration were observed in the cerebral cortex, but not in the cerebellum. 2) The viral growth in the brain was observed at 48 hours after the inoculation. The growth in the cerebellum, however, was found to be lower than those in other cerebral regions. 3) The viral antigen was detected in the cerebral cortex, hippocampus, mesencephalon and diencephalon in addition to the substantia nigra and striatum. From these results, it is presumed that clinical manifestation of JEV infection may involve the changes in the metabolism of neurotransmitter, especially those of DA and serotonin in the brain.

3,4-Dihydroxyphenylacetic Acid