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Biomedical subjects

Y Tsuboi

Publications and source records attributed to Y Tsuboi.

At least 73 records · Page 4Linked to original sources

Elevated bradykinin and decreased carboxypeptidase R as a cause of hypotension during tryptophan column immunoabsorption therapy.

Tryptophan column immunoabsorption therapy is beneficial to the patient with a neuroimmunological disease, but some complications have been attributed to this treatment. There have been some instances of an abrupt shock state along with severe decreases in blood pressure. In regards to this shock state, it has been reported that plasma bradykinin levels increase during tryptophan column immunoabsorption therapy. In this study, we examined the correlation between plasma bradykinin levels and either blood pressure or the levels of its degrading enzymes, angiotensin converting enzyme (ACE) and carboxypeptidase R (CPR) in 6 patients. Increased concentrations of bradykinin were present in the latter half of the therapeutic interval, and plasma bradykinin levels were found to be inversely correlated to CPR activity. The decreased CPR level could augment the activities of bradykinin. We speculate that bradykinin could be responsible for the hypotension occurring in patients during tryptophan column immunoabsorption therapy and that the metabolism of bradykinin could be caused by the decreased activity of CPR.

Blood Pressure↗

Primary somatosensory cortical neuronal activity during monkey's detection of perceived change in tooth-pulp stimulus intensity.

To elucidate the functional properties of primary somatosensory cortical neurons for the perception of tooth-pulp sensation, neuronal activity was recorded from the primary somatosensory cortex (SI) in awake behaving monkeys. Monkeys were trained to detect changes in tooth-pulp stimulus intensity applied to the upper canine or incisor tooth pulp. Stimulus intensities applied to the tooth pulp were multiples of the threshold intensity for the jaw opening reflex (1.0 T) elicited by tooth-pulp stimulation. When monkeys pressed a button, baseline electrical pulses (V1: 0.5 T, 1.0 T, 2.0 T, or 3.0 T) were applied to the tooth pulp. After 4-8 s, a V2 stimulus (0.3 T, 0.5 T, 1.0 T, or 2.0 T) was added to V1. Percent escapes at V1 stimulus intensity of 0.5 T and 1.0 T were approximately 10%, 22% at 2.0 T, and 40% at 3.0 T (total of 1,997 trials). A total of 862 single units were recorded from the SI. Thirty-seven SI neurons responded to electrical stimulation of the tooth pulp (tooth-pulp-driven neurons; TPNs), 139 SI neurons responded to tactile stimulation of the lateral face area, 90 to upper lip and 99 to lower lip, 44 to tongue and 102 to periodontal membrane, whereas 351 SI neurons were not responsive to tactile stimulation of the orofacial regions. Thirty of 37 TPNs were recorded long enough to test with V1 stimuli ranging from 0.5 T to 3.0 T. Eleven of 30 TPNs linearly increased their firing frequency following increases in stimulus intensity (encoding TPNs), whereas 19 did not (nonencoding TPNs). Mean first spike latency of encoding TPNs was 24.8 +/- 1.7 ms (n = 11), that of nonencoding TPNs was 23.6 +/- 1.5 ms (n = 19), and that of unclassified TPNs was 24.7 +/- 3.7 ms (n = 7). TPNs were distributed in the areas 1-2, 3a, and 3b within the oral projection area and the transition zone between the face and oral projection areas of the SI. All of them received inputs from the intraoral structures, facial skin, or both. The firing frequency of eight encoding and nonencoding TPNs was correlated with detection latency at stimulus intensities of 0.5 and 1.0 T. On the other hand, when the baseline stimulus was increased to 2.0 T and 3.0 T, the discharge of most TPNs did not increase in firing frequency with the reduction in detection latency. These results indicate that the discharge rates of some SI TPNs are correlated with detection latency at near-noxious threshold and noxious stimulus intensities. These findings suggest that some TPNs are involved in the sensory-discriminative aspect of tooth-pulp sensation in the near-pain threshold and pain ranges.

Animals↗

Mesencephalic projections from superficial and deep laminae of the medullary dorsal horn.

The mesencephalic projection pattern of axons arising from the medullary dorsal horn (MDH) was studied on the basis of axonal transport of Phaseolus vulgaris Leucoagglutinin (PHA-L). After large injections of PHA-L into both the superficial and deep laminae of the MDH, labeled fibers were observed in the anterior pretectal area (ATP), internal gray matter of the superior colliculus (InG), and rostral linear raphe nucleus (RLi) in the contralateral mesencephalon, and also in the ipsilateral parabrachial nucleus (PBA). Restriction of PHA-L to only the superficial laminae resulted in heavy axon labeling and varicosity in the APT and little labeling in the lateral part of the InG of the contralateral mesencephalic nuclei and the dorsal part of the ipsilateral PBA. On the other hand, after injections into the deep laminae, labeled axons were distributed mainly in the contralateral InG and RLi. Therefore, it is concluded that there are two different major pain pathways from the superficial and deep laminae of the MDH to the mesencephalic nuclei, processing nociceptive information in the trigeminal system.

Animals↗

[A case of HTLV-I associated polyradiculoneuropathy and cerebral white matter lesions with smouldering type adult T cell leukemia].

A 45-year-old female was admitted to our hospital complaining of abnormal sensation in the upper and lower extremities. She was given a diagnosis of smouldering type adult T cell leukemia 9 months before admission. On admission, neurological examination revealed sensory disturbance of polyneuropathy type, and generalized hyporeflexia. Nerve conduction study demonstrated decreased F wave appearance rate. Motor unit potentials in electromyelography had long duration and high amplitude. MR imaging of the brain showed multiple abnormal lesions in the periventricular and subcortical white matter. CSF protein was mildly increased, and anti-HTLV-I antibody was positive. Treatment with corticosteroid was effective, resulting in disappearance of sensory symptoms and normalization of F wave appearance. The present case is different from HAM, and the above clinical features may fit to the disease entity of HTLV-I associated polyradiculoneuropathy and cerebral white matter lesions.

Anemia, Refractory, with Excess of Blasts↗

Astroglial expression of hepatocyte growth factor and hepatocyte growth factor activator in human brain tissues.

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and also has multifunctional effects on some other cells in various organs. A HGF activating protease, HGF activator (HGFA) has recently been identified as a key enzyme that regulates the activity of HGF in vivo. HGFA appears to be associated with the cell surface. We examined HGFA immunolabelling in the brains of neurologically normal and Alzheimer disease (AD) cases. Furthermore, we identified the expression of the mRNA for HGF and HGFA by in situ hybridization histochemistry. The HGFA antibody stained only astrocytes in the white matter in all the brain tissues. Expression of the mRNAs of HGF and HGFA was also seen in white matter astrocytes. These results suggest that, in human brain, secreted pro-HGF from astrocytes might be activated by HGFA on/or near the astrocytic cell surface.

Aged↗

Inhibitors of cyclic nucleotide phosphodiesterase isozymes block renal tubular cell proliferation induced by folic acid.

In previous studies we observed that inhibition of cyclic 3',5'-nucleotide phosphodiesterase (PDE) isozymes, namely isozyme PDE3, suppresses proliferation of rat renal glomerular mesangial cells in vitro and in vivo. To determine whether activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway coupled to specific PDE isozymes modulates accelerated proliferation of renal epithelial cells, we investigated the effect of selective PDE isozyme inhibition on renal epithelial cell proliferation induced in rats by injection of folic acid (FA). In extracts from suspensions of renal cortical tubules, cAMP was metabolized predominantly by isozyme PDE4; activity of PDE3 was about three times lower. The increase in proliferative activity of renal cortical tissue from FA-injected rats, evaluated by immunostaining with Mib-1 antibody, was limited to tubular epithelial cells. Administration of the PDE3 inhibitors cilostazol or cilostamide together with the PDE4 inhibitor rolipram blocked mitogenic synthesis of DNA, as determined by (3H)-thymidine incorporation into renal cortical DNA, in FA-treated rats. FA injection caused an increase of more than 10-fold in proliferating cell nuclear antigen (PCNA) in renal cortical tissue; administration of the potent PDE3 inhibitor lixazinone or, to a lesser degree, cilostazol suppressed these high PCNA levels, whereas rolipram alone had no effect. The results indicate that FA-stimulated in vivo proliferation of renal tubular epithelial cells is down-regulated by activation of a cAMP-PKA signaling pathway linked to PDE3 isozymes. These observations are consistent with the notion that negative crosstalk between cAMP signaling and mitogen-stimulated signaling pathways regulates mitogenesis of renal cells of different terminal differentiation, including tubular epithelial cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves' thyrotoxicosis.

OBJECTIVE: Abnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time-course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis. DESIGN: Two year prospective follow-up study in patients with Graves' disease. PATIENTS: Ten consecutive patients with Graves' disease (seven males and three females, of mean (+/-SEM) age 39.3 +/- 3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex- and age-matched patients with the disease in remission served as controls. MEASUREMENTS: Bony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and alkaline-phosphatase (ALP) as markers of bone formation. RESULTS: Initial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89 +/- 0.16 before therapy, higher than those of 0.49 +/- 0.12 in the controls (P < 0.0001); the indices gradually decreased to 1.00 +/- 0.20 (12 months) and 0.48 +/- 0.12 (24 months). Lumbar BMD Z-scores increased from -0.22 +/- 0.46 to 0.21 +/- 0.47 (12 months) and 0.68 +/- 0.48 (24 months) (P = 0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, -396%, P < 0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months. CONCLUSIONS: Bone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4-8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.

Adolescent↗

[Prolonged antegrade amnesia due to left anterior thalamic infarct, and SPECT findings].

A 60-year-old right-handed man developed disorientation, antegrade amnesia and transient mild clouding of consciousness. The antegrade amnesia persisted for more than one year after its onset. T2-weighted MR images showed high signal intensity in the left anteromedial thalamus. 99mTc-HM-PAO SPECT revealed decreased uptake in the left frontal and temporal lobes. These SPECT findings were still observed a year later. These findings suggest that functional involvement of the frontal and temporal lobe connections with the dorsomedial nucleus, anterior nucleus, and the mamillothalamic tract in the anteromedial part of thalamus were responsible for the prolonged antegrade amnesia. We think that SPECT findings are important for evaluating the outcome of thalamic amnesia.

Amnesia↗

Morphological and electrophysiological properties of ACCx nociceptive neurons in rats.

A total of 33 neurons with cutaneous receptive fields were recorded from the anterior cingulate cortex (ACCx) and successfully injected with neurobiotin. All neurons were in area 24 of the ACCx. Neurons from the ACCx had large receptive fields (RFs), usually bilateral, and some had RFs covering the whole body surface. Most of the neurons were in the deep laminae and had a pyramidal soma with thick apical dendrites and many spines. Thirteen of 33 neurons were classified as pyramidal nociceptive specific (NS) neurons and 12 as noxious-tap neurons, 3 neurons received inhibitory input and were in lamina V. Two non-pyramidal noxious-tap neurons were located in lamina V and 1 pyramidal noxious-tap neuron was located in lamina VI, and 2 pyramidal NS neurons were in lamina III. Axon collaterals of NS neurons were mainly distributed around the soma, whereas those of noxious-tap neurons were also distributed far from the soma. A large number of varicosities were observed on the axon collaterals of both NS and noxious-tap neurons. Our results suggest that NS neurons in the ACCx send information locally to the vicinity of the soma, while noxious-tap neurons send information to a wider area of the ACCx.

Animals↗

Suppression of mesangial proliferative glomerulonephritis development in rats by inhibitors of cAMP phosphodiesterase isozymes types III and IV.

Excessive mesangial cell (MC) proliferation is a hallmark of many glomerulopathies. In our recent study on cultured rat MC (Matousovic, K., J.P. Grande, C.C.S. Chini, E.N. Chini, and T.P. Dousa. 1995. J. Clin. Invest. 96:401-410) we found that inhibition of isozyme cyclic-3',5'-nucleotide phosphodiesterase (PDE) type III (PDE-III) suppressed MC mitogenesis by activating cAMP-dependent protein kinase (PKA) and by decreasing activity of mitogen-activated protein kinase (MAPK). We also found that inhibition of another PDE isozyme, PDE-IV, suppresses superoxide generation in glomeruli (Chini, C.C.S., E.N. Chini, J.M. Williams, K. Matousovic, and T.P. Dousa. 1994. Kidney Int. 46:28-36). We thus explored whether administration in vivo of the selective PDE-III antagonist, lixazinone (LX), together with the specific PDE-IV antagonist, rolipram (RP), can attenuate development of mesangioproliferative glomerulonephritis (MSGN) induced in rats by anti-rat thymocyte serum (ATS). Unlike the vehicle-treated MSGN rats, rats with MSGN treated with LX and RP did not develop proteinuria and maintained normal renal function when examined 5 d after injection of ATS. In PAS-stained kidneys from PDE-antagonists-treated MSGN-rats the morphology of glomeruli showed a reduction in cellularity compared with control rats with ATS. Compared with MSGN rats receiving vehicle, the MSGN rats receiving PDE-antagonists had less glomerular cell proliferation (PCNA delta -65%), a significantly lesser macrophage infiltration (delta -36% ED-1) and a significant reduction of alpha-smooth muscle actin expression by activated MC; in contrast, immunostaining for platelet antigens and laminin were not different. The beneficial effect of PDE inhibitors was not due to a moderate decrease (approximately -20%) in systolic blood pressure (SBP); as a similar decrease in SBP due to administration of hydralazine, a drug devoid of PDE inhibitory effect, did not reduce severity of MSGN in ATS-injected rats. We conclude that antagonists of PDE-III and PDE-IV administered in submicromolar concentrations in vivo to ATS-injected rats can decrease the activation and proliferation of MC, inhibit the macrophage accumulation, and prevent proteinuria in the acute phase of MSGN. We propose that PDE isozyme inhibitors act to block (negative "crosstalk") the mitogen-stimulated intracellular signaling pathway which controls MC proliferation due to activating of the cAMP-PKA pathway. These results suggest that antagonists of PDE-111 and IV may have a suppressive effect in acute phases or relapses of glomerulopathies associated with MC proliferations.

3',5'-Cyclic-AMP Phosphodiesterases↗

A case of muscle subclavius posticus with special reference to its innervation.

A subclavius posticus muscle was found in the left side of a Japanese male cadaver. This muscle arose from the first costal cartilage, inserted to the upper margin of the scapula, and was innervated by a branch from the nerve to the subclavius. This excess intermediary muscle between the subclavius and the inferior belly of the omohyoid appears to be more closely related to the subclavius, based on detailed examination of the innervation of this muscle. A possible schematic model of the origin of this muscle is proposed.

Humans↗

Tl-201 SPECT in Kimura's disease involving the parotid glands and cervical nodes.

Kimura's disease is a chronic inflammatory condition producing subcutaneous tumor-like nodules, mainly in the head and neck region. Most patients have involvement of regional lymph nodes and major salivary glands. The authors present two cases of Kimura's disease with parotid gland and postauricular lymph node involvement. With Tl-201 SPECT, elevated uptake was noted on early and delayed images. Kimura's disease should be included in the differential diagnosis when increased Tl-201 uptake in head and neck mass lesions is noted.

Adult↗

Involvement of arginine vasopressin and renal sodium handling in pathogenesis of hyponatremia in elderly patients.

The present study was undertaken to determine the pathophysiological role of arginine vasopressin (AVP) in elderly patients with hyponatremia, and the efficacy of fludrocortisone acetate in treating their hyponatremia. Eleven hospitalized patients aged 65 years or older whose serum sodium levels were less than 130 mEq/l were examined. The hyponatremic patients included two groups of patients: syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and central salt-wasting syndrome. And 24 healthy, young subjects aged 20 to 34 years, and 24 healthy, elderly subjects age 65 to 80 years were recruited by community announcement. The elderly subjects had decreased urinary concentrating ability and exaggerated response of AVP secretion to osmotic and nonosmotic stimuli, as compared to the young subjects. All the patients had hyponatremia, with the exaggerated urinary loss of Na. Plasma AVP levels were elevated despite hypoosmolality in all the 2 groups of hyponatremic, elderly patients. Plasma renin activity and plasma aldosterone concentrations were low in the patients with SIADH and central salt-wasting syndrome. Fludrocortisone acetate therapy was effective in the patients with central salt-wasting syndrome and 3 patients with SIADH whose hyponatremia remained unchanged after water restriction. Water restriction therapy normalized serum Na levels in only 3 patients with SIADH. These results indicate that AVP is involved in the mechanism for hyponatremia in the elderly patients with SIADH and central salt-wasting syndrome. Severe hyponatremia associated with SIADH and central salt-wasting syndrome responds well to mineralocorticoid therapy. Both the secretion of AVP and renal sodium handling may be involved in the mechanism of action of the disorders. The diagnostic criteria for SIADH in the elderly patients may have to be reevaluated and should be considered to indicate fludrocortisone acetate therapy.

Adult↗

[Middle ear cholesteatoma caused by cannonball foreign bodies impacted in the bony eustachian tube: a case report].

We present a 76-year-old male patient with adhesive-type cholesteatoma and with metal foreign bodies which were shown to be located in the bony eustachian tube by computed tomography. He sustained a burn injury of the left tympanic membrane when he was struck by a bomb 52 years ago, during World War II. The cannonball fragments that entered the tympanic cavity were apparently transported to and stuck in the eustachian tube isthmus by mucociliary action after spontaneous closure of the tympanic membrane perforation. Persistent tubal obstruction due to the impacted foreign bodies and surrounding granulation tissue seems to have caused chronic adhesive otitis, leading to cholesteatoma which developed in the attic and mastoid antrum. No foreign bodies became visible after cholesteatoma removal by an intact canal wall technique in conjunction with anterior tympanotomy for wide exposure of the supratubal recess and the tympanic osteum of the eustachian tube. Therefore, anterior tympanotomy was further extended anteriorly to open the enlarged bony eustachian tube, allowing visualization and safe removal of two cannonball-fragments firmly impacted within it. We call this surgical approach to the bony eustachian tube "extended anterior tympanotomy". The transmastoidal accessibility of the bony eustachian tube produced by this technique should be assessed by preoperative computed tomography.

Aged↗

Fos induction in the medullary dorsal horn and C1 segment of the spinal cord by acute inflammation in aged rats.

In order to elucidate the effect of aging on nociceptive neurons in the central nervous system, c-fos was used as a marker of excitability of neurons in the medullary dorsal horn (MDH) and the first spinal segment (C1) following noxious stimulation of the lateral face of young and aged rats. The distribution of c-fos-positive cells was dense in the superficial laminae and sparse in the deep laminae of the MDH and C1 in both young and aged animals following subcutaneous injection of formalin into the lateral face, whereas few c-fos-positive cells were labeled after saline injection. The distribution of c-fos-positive cells in the superficial laminae of the aged rats was found to be denser and more rostro-caudally expanded compared to that in the young rats. C-fos-positive cells were distributed more rostro-caudally in aged than in young rats. There was no difference between young and aged rats in the distribution of c-fos-positive cells in the deep laminae. Substance P (SP), 5-HT and calcitonin gene-related peptide-like immunoreactive (CGRP-LI) fibers and varicosities showed similar distribution density in the MDH and C1. Furthermore, many 5-HT-LI aberrant fibers and varicosities were observed in the MDH and C1 of the aged rats. The SP-LI and CGRP-LI cells in the trigeminal ganglion of aged rats were larger than those of young rats. These findings suggest that a deficit of the descending 5-HT inhibitory system produces the increment of c-fos-positive cells in the MDH and C1 of aged rats, resulting in the recruitment of a larger number of neurons in the superficial laminae of the MDH and C1 for conveying nociceptive sensory information to the central nervous system.

Age Factors↗

Possible pre-Cushing's syndrome due to an adrenal adenoma incidentally discovered.

We demonstrated the functional evaluation of adrenal incidentaloma in 8 patients who had no abnormal finding associated with Cushing's syndrome. Adrenal tumors were incidentally discovered by abdominal echogram in 5 patients and by computed tomography (CT) in 3 patients. Serum cortisol levels and urinary excretion of 17-hydroxycorticosteroids (17-OHCS) were within normal limits in four of 8 patients. Urinary excretion of free cortisol was also within normal limits except for patient 8. Urinary excretion of 17-OHCS, however, was not suppressed by dexamethasone administration in five of 8 patients. Excretion of urinary 17-OHCS did not increase in response to metyrapone in 3 of 4 dexamethasone-insuppressible patients, but increased in 3 dexamethasone-suppressible ones. Serum cortisol increased in response to exogenous ACTH in all 6 patients examined. 131I-Adosterol accumulation was found in only the tumor side in 7 patients and bilaterally in one patient. Adrenalectomy was done in 7 patients, and microscopic findings showed adrenocortical adenoma. Serum cortisol was significantly suppressed in response to dexamethasone in the post-operative stage in all 7 patients examined. These results indicate that these adrenal incidentalomas seem to have a cortisol over-production which is dexamethasone-insuppressible and ACTH-dependent, and that they can be classified as "Pre-Cushing's Syndrome."

17-Hydroxycorticosteroids↗