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Biomedical subjects

K Funabiki

Publications and source records attributed to K Funabiki.

At least 37 records · Page 2Linked to original sources

Vestibulo-ocular reflex in patients with Meniere's disease between attacks.

In Meniere's disease, spontaneous nystagmus beating toward the affected ear (ipsilateral nystagmus) is frequently observed especially during vertiginous periods. VOR against horizontal rotation was recorded in 19 patients with Meniere's disease exhibiting ispilateral beating nystagmus, and the dynamic aspect of vestibular function during vertiginous periods was examined by determining VOR gain and directional preponderance (DP). The patients sat on a rotation chair and were passively rotated at about 0.3-0.6 Hz. The maximal head velocity ranged from 80 to 120 deg/s and the duration of rotation from 20 to 30 s. In most patients exhibiting ipsilateral nystagmus, VOR gain toward the affected side was higher than that toward the intact side, indicating that the peripheral vestibular system on the affected side could still respond to head movements and that its dynamic function was increased. This asymmetry disappeared along with disappearance of ipsilateral nystagmus. During the period with contralateral nystagmus, VOR gain toward the affected side became lower than that toward the intact side. These findings indicate that alterations in the dynamic property of the peripheral vestibular system may correlate with the directional change of spontaneous nystagmus. However, the degree of VOR DP (VOR DP%) did not correlate with the slow phase velocity of spontaneous nystagmus, indicating that observation of spontaneous nystagmus alone cannot determine with precision the degree of imbalance in the dynamic aspect of vestibular function.

Adult↗

A new vestibulo-ocular reflex recording system designed for routine vestibular clinical use.

A new vestibulo-ocular reflex (VOR) recording system was developed, which consists of an infrared eye camera, a small velocity sensor and a frequency modulator. Using this system, the head velocity signal was frequency modulated and simultaneously recorded as a sound signal on the audio track of a Hi8 video recorder with eye images. This device enabled recording of the VOR response in routine vestibular clinical practice. The reliability and effectiveness of this system were estimated by recording and analysing the VOR response against manually controlled rotation in normal subjects (n = 22) and in patients with unilateral severe vestibular hypofunction (n = 11). VOR gain on clockwise rotation viewed from the top was defined as R gain, and counterclockwise rotation as L gain. Directional preponderance (DP%) was also calculated. VOR gain towards the diseased side was significantly lower than that towards the intact side, and also significantly lower than that of normal subjects. DP% of unilateral vestibular hypofunction cases was significantly larger than that of normal subjects. These findings indicate that this VOR recording system reliably detects severe unilateral vestibular hypofunction.

Adult↗

Correlations among expression of glomerular intercellular adhesion molecule 1 (ICAM-1), levels of serum soluble ICAM-1, and renal histopathology in patients with IgA nephropathy.

The purpose of the present study was to evaluate the correlations among expression of intercellular adhesion molecule 1 (ICAM-1) in glomeruli, levels of soluble ICAM-1 (sICAM-1) in sera, and renal injuries in patients with IgA nephropathy. The levels of sICAM-1 in sera from 27 patients with IgA nephropathy and 7 healthy controls were measured by the human soluble ICAM-1 immunoassay. The expression of ICAM-1 in glomeruli was detected by indirect immunofluorescence. We observed marked expression of ICAM-1 in glomerular capillary walls and mesangial areas in patients with advanced-stage, but not in those with mild IgA nephropathy. Since the histopathological changes in the advanced stage of this disease were characterized by diffuse mesangial cell proliferation and tubulointerstitial injury, the expression of ICAM-1 in the glomeruli may be of value in evaluating the degree of renal lesions in patients with IgA nephropathy. However, there was no significant change in the levels of serum sICAM-1 among mild-stage and advanced-stage patients and healthy controls. It appears that the measurement of serum sICAM-1 is not useful in evaluating the degree of renal injuries in patients with IgA nephropathy.

Case-Control Studies↗

The role of GABAergic inputs for coincidence detection in the neurones of nucleus laminaris of the chick.

1. Synaptic inputs to nucleus laminaris (NL) neurones were studied in a brainstem slice preparation of chick embryos (E15-20) using the whole-cell patch clamp technique. NL neurones are third order auditory neurones and are proposed to behave as coincidence detectors concerned with interaural timing discrimination. 2. Under voltage clamp conditions, electrical stimuli applied to either ventral or dorsal dendritic layers evoked EPSCs. These fast currents decayed with a time constant of 1.1 ms near the resting potential, reversed close to 0 mV, and were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 microM) or 6, 7-dinitro-quinoxaline-2,3-dione (DNQX, 20 microM). Coincident or near coincident stimulation of the ventral and the dorsal dendritic layers increased the probability of action potential generation (response probability). 3. In the presence of CNQX (40 microM) other postsynaptic currents (PSCs) were observed, which reversed close to the equilibrium potential for chloride (ECl), and were reversibly blocked by bicuculline (20 microM) and, therefore, were mediated by GABAA receptors. Spontaneous GABAergic PSCs were inward going near the resting membrane potential immediately after starting whole-cell recording with a low Cl- (5 mM, ECl = -90 mV) pipette medium, but became outward-going with time. This indicates that GABAergic inputs may generate depolarizing potentials in intact NL neurones. 4. Local GABA (10 microM) application reduced both the EPSP and EPSC amplitude and shortened the EPSP decay time constant (from 5.3 to 2. 1 ms), while the EPSC decay time constant was not affected (from 1.3 to 1.2 ms). These GABA effects were mostly due to the shunting conductance of the postsynaptic GABAA receptors. 5. Depolarizing current injections combined with electrical stimuli to a unilateral axon bundle simulated bilateral synaptic inputs. Response probability increased with decreased interstimulus intervals, while local GABA (10 microM) application to the soma narrowed the time dependence of the response probability. 6. These results suggest that GABAergic inputs to NL neurones may serve to improve coincidence detection of the bilateral excitatory inputs through an increase in membrane conductance.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Differential expression of collagen IV isoforms in experimental glomerulosclerosis.

Expansion of the glomerular mesangial matrix (MM), thickening of the glomerular basement membrane (GBM), and eventually the development of glomerulosclerosis are often seen in immunologically mediated kidney diseases. In addition to quantitative changes in the extracellular matrix (ECM), qualitative changes in ECM molecules may contribute to alterations in the composition of the glomerular matrix. The expression of collagen IV, alpha 1-5(IV) mRNA, and polypeptides was therefore investigated during the development of chronic graft-versus-host disease (GvHD) in mice, a model for lupus nephritis, and in chronic serum sickness (CSS) in rats, a model for membranous nephropathy. Immunohistochemical studies showed increased mesangial expression of alpha 1 and alpha 2 early in the disease, but only late in the GBM. In contrast, alpha 3 and alpha 4 increased in the GBM during disease, but not in the MM. The mRNA levels for all collagen IV chains were increased in isolated glomeruli before morphological alterations were detectable. The mRNA increase was earlier and more profound for alpha 3, alpha 4 and alpha 5 than for alpha 1 and alpha 2. Expression of alpha 3(IV) was greatest in GvHD, whereas expression of alpha 4 was greatest in CSS. As determined by in situ hybridization (ISH), alpha 1 mRNA was observed dispersed in the glomerulus, but alpha 3, alpha 4, and alpha 5 mRNAs were mainly located in cells at the periphery of the glomerular tuft. The changes in the relative abundance of collagen IV mRNA in disease states may perturb the collagen IV network, altering glomerular structure and function, and may thereby play a central role in the development of glomerulonephritis and glomerulosclerosis.

Animals↗

Multicentric Castleman's disease associated with renal amyloidosis and pure red cell aplasia.

A 50-year-old man was admitted suffering from severe anemia and renal dysfunction. He had been admitted for the first time at the age of 49, and was diagnosed with multicentric Castleman's disease (MCD) and secondary amyloidosis. At that time, marked erythroid hypoplasia was demonstrated by both aspiration and biopsy of bone marrow. A diagnosis of pure red-cell aplasia (PRCA) was made. Immunosuppressive agents improved his symptoms and laboratory data. We report here a very rare case of PRCA following MCD and amyloidosis, and with reference to the literature, we discuss the relation between MCD and related diseases.

Amyloidosis↗

A case of multicentric Castleman's disease associated with renal amyloidosis and pure red cell aplasia.

This is the first reported case of multicentric Castleman's disease (MCD) associated with renal amyloidosis and pure red cell aplasia (PRCA). Inguinal lymph node biopsy showed follicular hyperplasia with prominent germinal centers and plasma cell proliferation in the interfollicular areas. Renal biopsy specimens revealed intraglomerular amyloid deposits, defined as AA amyloidosis. Since amyloid deposits were not present in the gastric and rectal mucosal tissues, his renal disorder was found to be an unusual secondary amyloidosis associated with MCD. Following treatment by plasma exchange, there was progressive deterioration of anemia due to PRCA detected by bone marrow aspiration. Subsequently he was successfully treated with steroid pulse therapy not only for anemia but also for renal function.

Amyloidosis↗

Dissociated expression of collagen type IV subchains in diabetic kidneys of KKAy mice.

Diabetic nephropathy is characterized by thickening of the glomerular basement membrane and expansion of the mesangial matrix. The glomerular basement membrane is assembled from at least five genetically distinct collagen IV chains. In patients with diabetic nephropathy, differential distribution of these components has been demonstrated. In order to clarify the relationship between progression of diabetic nephropathy and altered type IV collagen assembly in the renal cortex, we examined steady state mRNA levels encoding collagen IV subchains in the kidney cortices of spontaneously diabetic KKAy mice and nondiabetic C57black mice as controls. They were sacrificed at 4, 8, 16, and 24 weeks of age. Northern and dot blot analyses were performed using 32P-labeled mouse probes for classical alpha1(IV) and alpha2(IV) and for alpha3(IV), alpha4(IV), and alpha5(IV) minor chains. The mRNA levels for all collagen IV chains peaked at 4 weeks of age and declined rapidly thereafter in the nondiabetic mice. At all times, alpha1(IV) and alpha2(IV) mRNA expressions were abundant and almost unchanged in KKAy mice. In contrast, mRNA levels for alpha3(IV), alpha4(IV), and alpha5(IV) progressively changed with age. It appears that the expression of minor collagen IV chains is dissociated from the alpha1(IV) and alpha2(IV) chains in diabetic nephropathy. Moreover, an unbalanced increase in the production may affect collagen IV assembly and contribute to basement membrane thickening in diabetic nephropathy of KKAy mice.

Animals↗

The effect of intravenous lidocaine injection on hearing thresholds.

The effect of intravenous injection of lidocaine on hearing thresholds was studied in normal subjects. Continuous and intermittent tones at 1, 4 and 8 kHz were used as stimuli and the threshold change with lidocaine injection was measured using a self-recording audiometer (Békésy audiometer). Both increases and decreases in the threshold were observed. The former occurred more frequently than the latter. In cases of a threshold increase, lidocaine injection exhibited a frequency specific effect; the higher the frequency, the more often the threshold was increased by lidocaine injection. There was no significant difference in threshold changes between continuous and intermittent tones. The present results suggest that lidocaine may act on the inner ear hair cells.

Adult↗

Light-weight and low-cost infrared CCD eye monitoring system designed for routine vestibular clinic use.

A simple and low-cost eye monitoring system with infrared illumination was developed. This system consists of a small board mounted with an infrared sensitive CCD camera and its control unit and a swimming goggle; it is light-weight and visualizes eye movements by connecting the output lines of the board to the video input on a monitor. We have found the present system useful in the routine vestibular clinic practice.

Costs and Cost Analysis↗

Application of parasagittal surface coil MRI to otoneurological diagnosis.

Parasagittal surface coil magnetic resonance imaging (MRI) of the internal auditory canal and the inner ear was performed in patients with otoneurological diseases. T2-weighted fast spin-echo sequences, plain and enhanced T1-weighted sequences were used to examine the inner ear and the individual nerves in the internal auditory canal. Normal parasagittal images of the inner ear and the internal auditory canal and 4 patients with otoneurological disorders are presented. Precise location of the acoustic tumor was visualized and postoperative status of the internal auditory canal and the inner ear was assessed by the present method. The cochlear nerve was not identified in a patient with long-standing unilateral deafness. A follow-up study with MRI was performed in a patient with Meniere's disease who underwent endolymphatic-mastoid shunt surgery, showing gradual postoperative shrinkage of the shunted endolymphatic sac. The present method provides a new approach to the assessment of otoneurological disorders.

Adolescent↗

Usefulness of magnetic resonance imaging in diagnosing vertebro-basilar insufficiency.

To estimate the usefulness of magnetic resonance imaging (MRI) in diagnosing vertebro-basilar insufficiency (VBI), 41 VBI patients with vertigo or dizziness and 26 subjects without vertigo or dizziness (as control) were examined by MRI. Sixty-eight percent of the VBI group and 12% of the control group showed a large difference between the right and the left vertebral artery diameter, the incidence being significantly higher in the VBI group. Thirty-nine percent of the VBI group and 12% of the control group had lacunar infarction in the brain stem, of which the incidence was significantly higher in the VBI group, MRI can be recommended to diagnose VBI providing information on both blood vessel disorder and ischemic changes in the brain.

Aged↗

Detection of antioxidant enzyme activities in renal tissues of early stage IgA nephropathy in ddY mice.

The purpose of this study was to determine the antioxidant enzyme activities in renal tissues of early stage ddY mice, an animal model for primary IgA nephropathy. Eight- and 40-week-old ddY female mice and normal healthy Balb/c female mice were used in this study. The levels of Cu/Zn-SOD, Mn-SOD, and GSH-PX activities in the renal cortex were significantly higher in 40-week-old ddY mice than in Balb/c control mice of the same age; no change of catalase activity was observed. There were no significant differences in the levels of Cu/Zn-SOD, Mn-SOD, GSH-PX, and catalase activities between the ddY mice and Balb/c mice at 8 weeks of age. Urinary protein was slightly higher in 40-week-old ddY mice. IgA or C3 was deposited at low levels in the glomerular mesangial areas of 8-week-old ddY mice. Marked depositions of IgA and C3 extended from the glomerular mesangial areas to the capillary walls of 40-week-old ddY mice. Expansion of glomerular mesangial matrices and mild mesangial cell proliferation was observed in 40-week-old ddY mice. Antioxidant enzyme activities in the renal cortex were already increased in the early stage IgA nephropathy in 40-week-old ddY mice. These findings suggest that measurements of antioxidant enzyme activities in the renal cortex of 40-week-old ddY mice was useful for evaluation of the pathogenesis of renal involvement in the early stage of IgA nephropathy.

Animals↗

Voltage-gated ionic currents and their roles in timing coding in auditory neurons of the nucleus magnocellularis of the chick.

Avian cochlear neurons of the nucleus magnocellularis (NMC) are known to encode temporal information of sound. The neuron generated only a single action potential at a stable timing even though suprathreshold currents of long duration (> 100 ms) was injected. The threshold for the action potential was -42 mV. In voltage-clamp experiments, a TTX-sensitive Na current was activated at membrane potentials more positive than -50 mV. A low voltage activated (LVA) Ca current and a high voltage activated (HVA) Ca current were observed. The LVA Ca current was activated from -65 mV and showed a voltage dependent inactivation. The HVA Ca current was activated from -40 mV and did not show any inactivation. The LVA Ca current and the HVA Ca current were sensitive to Ni2+ (0.1 mM) and Nifedipine (10-20 mM), respectively. NMC neurons showed a TEA-sensitive K current and a 4-AP-sensitive K current. With 4-AP (0.5 mM) in a bathing medium, the threshold of action potential was decreased to -49 mV and the timing of action potential generation showed a wider distribution than that of control. Ni2+ (0.1 mM) reversed effects of 4-AP on the threshold and the variability of action potential onsets. It is concluded that a 4-AP-sensitive current counteracts the LVA Ca current that facilitates Na spike generation, and sets a threshold to a higher level for generating a single action potential at a precise timing following synaptic inputs from the auditory nerve.

4-Aminopyridine↗

Retarded vestibular compensation in mutant mice deficient in delta 2 glutamate receptor subunit.

The delta 2 subunit of ionotropic glutamate receptors is expressed only in the cerebellar Purkinje cell. In mutant mice deficient in the delta 2 protein, cerebellar long-term depression and motor coordination are impaired. We examined behavioural plasticity in these mutant mice after unilateral vestibular destruction. After intratympanic injection of sodium arsanilate, the mice showed roll head tilt and their righting response under a rotation load was impaired. These symptoms improved with time. However, compensation of the righting response was retarded in the mutant mice. These results suggest that motor learning of the delta 2 mutant mice is disturbed, and that the static and dynamic components of vestibular compensation may be controlled by different neuronal mechanisms.

Animals↗

Developmental changes in seminiferous tubule extracellular matrix components of the mouse testis: alpha 3(IV) collagen chain expressed at the initiation of spermatogenesis.

The temporal expression of type IV collagen, laminin, and entactin in the basal laminae of the seminiferous tubule during development of the mouse testis was determined. Northern blot analysis was used to examine changes in testicular mRNA for alpha 1-alpha 5 type IV collagen (IV) chains in mice ranging in age from newborn to adult (60 days). Levels for mRNA alpha 1(IV) and alpha 2(IV) chains were highest in newborns through Day 5 and remained elevated through Day 10, but then sharply declined to adult values by Day 30. In sharp contrast, alpha 3(IV) and alpha 4(IV) chain levels were low in newborns, peaked at Day 10, and then declined to adult values by Day 30. 5(IV) mRNA was elevated in newborns and at Days 5 and 10 before dropping to adult levels by Day 30. Changes in the deposition of alpha 1, alpha 2, and alpha 3(IV) collagen chains, laminin, and entactin into the inner and outer basal laminae of the seminiferous tubule were determined from the beginning of tubule formation (embryonic Day 12.5) through adulthood by immunofluorescence microscopy using polyclonal antibodies for these constituents. The alpha 1 and alpha 2(IV) chains, laminin, and entactin were deposited into the inner basal lamina at embyronic Day 12.5 and into the newly formed outer basal lamina at Day 5 after birth. The alpha 3(IV) chains were deposited into both the inner and outer basal laminae at Day 5. Thus, testicular alpha 1-alpha 3(IV) mRNA levels coincide with the incorporation of detectable collagen chains into the seminiferous basal laminae, suggesting transcriptional control of these alpha (IV) chains. Expression of of the alpha 3(IV) chain coincides with the initiation of spermatogenesis, suggesting a functional role of this chain in spermatogonial proliferation.

Aging↗

Immunofluorescent analysis of extracellular matrix (ECM) components in glomeruli of the hepatic glomerulosclerosis.

An immunofluorescence study was carried out to evaluate alterations in the distribution and/or intensity of extracellular matrix (ECM) components, immunoglobulins and complement (C3) in the glomeruli of 7 autopsy patients with hepatic glomerulosclerosis. As compared with the findings in normal renal tissues, an increase in type IV collagen, laminin and fibronectin was observed in expanded glomerular mesangial areas and along glomerular capillary walls. Depositions of IgA, mainly IgA1, and C3 in glomeruli were in parallel with those of the ECM components. These ECM components were markedly decreased in glomeruli showing global sclerosis. In contrast, type I collagen was observed at central portions of the sclerotic glomeruli. There was an increase in the type I collagen along Bowman's capsules, especially at the sites of capsular adhesion and crescent formation. It appears that hyperproduction and/or infiltration of glomerular ECM components and interstitial collagen is closely linked to the progression of glomerular sclerosis in patients with liver diseases.

Adult↗

Increased remission of early stage membranous nephropathy on long-term treatment with corticosteroid.

Sixty-five patients with primary membranous nephropathy were examined in order to assess the effects of long-term treatment with corticosteroid. The observation period varied from 8 to 279 months (average, 95 months). The patients were treated with corticosteroid alone or with combinations of corticosteroid and immunosuppressants, nonsteroidal anti-inflammatory drugs (NSAID) and/or dipyridamole. At 6 months after treatment, only 14% of the patients had achieved complete remission. At 24 months after treatment, 46% of the patients showed complete remission. The rate of clinical remission, i.e. complete and incomplete remission, was markedly increased in stage I and II patients with membranous nephropathy by Ehrenreich and Churg's classification but not in stage III patients. The actuarial survival curve indicated that 84% of the patients were alive at 10 years after onset. These data suggest that active treatment with corticosteroid is beneficial for patients with primary membranous nephropathy.

Adolescent↗