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Biomedical subjects

H Moriya

Publications and source records attributed to H Moriya.

At least 19 recordsLinked to original sources

Increased sensitivity to acute and persistent pain in neuron-specific endothelin-1 knockout mice.

Endothelin-1 (ET-1) exists in endothelial cells as well as a variety of other cell types. The presence of ET-1 and its receptors in neurons suggests its possible role as a neurotransmitter and/or neuromodulator. Studies utilizing exogenous ET-1 have suggested that ET-1 affects pain transmission. This study was designed to examine the possible role(s) of neuronal ET-1 in pain processing. We produced neuron-specific ET-1 knockout mice using the Cre/loxP system with a synapsin I promoter and examined the effects produced by the lack of neuronal ET-1 on pain behavior using common pain models and a model of stress-induced analgesia. In acute nociceptive pain models, paw withdrawal thresholds to radiant heat and mechanical stimuli applied with von Frey hairs were significantly lower in the knockout mice compared with control. This indicated that the absence of neuronal ET-1 leads to greater sensitivity to acute nociceptive stimuli. After inflammation was produced by intraplantar injection of carrageenan, there was a significantly greater degree of thermal hyperalgesia and mechanical allodynia in the knockout mice even after the difference in baseline values was compensated. Furthermore, in a neuropathic pain model produced by spinal nerve ligation, there was also a greater degree of mechanical allodynia in the knockout mice. Finally, in a swim-stress model, the magnitude of stress-induced analgesia was less in the knockout mice, indicating the involvement of neuronal ET-1 in stress-induced analgesia. The results suggest that there is a basal release of ET-1 from neurons that affect baseline pain thresholds as well as an additional release during persistent pain states that acts to suppress the pain. The involvement of neuronal ET-1 in stress-induced analgesia further suggests its role in endogenous pain inhibitory systems. To confirm that ET-1 is released in persistent pain states and to determine which part of the CNS is involved, we measured the concentrations of ET-1 before and after inducing peripheral inflammation in different parts of the CNS involved in endogenous pain inhibitory systems in normal mice. We found that ET-1 was increased in the hypothalamus while no significant increase was observed in the midbrain, medulla and spinal cord. The results of the present study suggest that neuronal ET-1 is involved in endogenous pain inhibitory control likely via pathways through the hypothalamus.

Acute Disease↗

A proposed prognostic formula for Perthes' disease.

UNLABELLED: We retrospectively reviewed 145 patients with unilateral Perthes' disease and compared a quantitative analysis of early radiographic signs with a predicted prognosis at long-term followup. The average age of the patients at followup was 18.7 years (range, 16.2-27.5 years). We used the age at onset and three radiographic factors as independent variables for multiple regression analysis. The final radiographic results were based on a modified Stulberg's classification as the dependent variable. Fifty patients (35%) had a good outcome, 33 patients (23%) had a fair outcome, and 62 patients (42%) had a poor outcome. The most reliable formula in the stepwise multiple regression analysis was calculated as: y = -0.697 + 0.418 (age score) + 0.860 (involvement score) + 0.248 (subluxation score). The radiographic stage at first visit had no influence on the final results. Multifactorial assessment by combination of age at onset and two radiographic factors (epiphyseal involvement and subluxation) was the most reliable for predicting the prognosis. A score of 1.5 points or less predicted a good prognosis and a score of 2.6 or more indicated a poor prognosis. LEVEL OF EVIDENCE: Prognostic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Adolescent↗

Intervertebral disc degeneration associated with lumbosacral transitional vertebrae: a clinical and anatomical study.

We studied 52 patients, each with a lumbosacral transitional vertebra. Using MRI we found that the lumbar discs immediately above the transitional vertebra were significantly more degenerative and those between the transitional vertebrae and the sacrum were significantly less degenerative compared with discs at other levels. We also performed an anatomical study using 70 cadavers. We found that the iliolumbar ligament at the level immediately above the transitional vertebra was thinner and weaker than it was in cadavers without a lumbosacral transitional vertebra. Instability of the vertebral segment above the transitional vertebra because of a weak iliolumbar ligament could lead to subsequent disc degeneration which may occur earlier than at other disc levels. Some stability between the transitional vertebra and the sacrum could be preserved by the formation of either an articulation or by bony union between the vertebra and the sacrum through its transverse process. This may protect the disc from further degeneration in the long term.

Adolescent↗

Supplement nephropathy due to long-term, high-dose ingestion of ascorbic acid, calcium lactate, vitamin D and laxatives.

A 48-year-old Japanese woman previously in good health was found to have severe proximal tubular dysfunction with a high serum level of ascorbic acid (57.3 microg/ml, reference range: 1.9 - 15.0 microg/ml). Renal biopsy specimen showed marked tubulointerstitial damage, i.e. tubular atrophy, dilatation of tubular lumen with flattened tubular epithelial cells, vacuolization of proximal and distal tubular epithelial cells, and severe interstitial fibrosis with mild infiltration of mononuclear cells. Calcified lesions, which caused tubular obstruction or stenosis, were also seen in interstitial area adjacent to degenerated proximal tubuli. Hypokalemic nephropathy, probably due to long-term use of laxatives, was clearly shown. However, calcified lesions seemed to be caused by inappropriate excessive daily ingestion of ascorbic acid (6 000 mg/day), calcium lactate, and vitamin D because of the patient's misunderstanding that these supplements could keep her in a good health. This condition may be clinically called "supplement nephropathy".

Ascorbic Acid↗

Surgery for Dupuytren's disease in Japanese patients and a new preoperative classification.

The surgical outcome of Dupuytren's disease was evaluated in 73 hands of 57 patients in a Japanese population. Subtotal fasciectomy was performed in all cases. Surgical results were evaluated using the percentage improvement of extension in each finger joint. Statistical analyses were performed on the risk factors associated with recurrence and extension. The surgical outcome depended on the degree of contracture of the proximal interphalangeal joint. Recurrence of disease occurred in eight patients (14%) and extension occurred in nine (16%). Recurrence and extension frequently occurred in those who had ectopic lesions or involvement of the radial side of the hand. The present results suggested that the Dupuytren's diathesis had an influence on recurrence and extension. We proposed a new classification of Dupuytren's disease that might help to predict the surgical outcome and facilitate surgical planning.

Adult↗

Dupuytren's disease on the radial aspect of the hand: report on 135 hands in Japanese patients.

We studied 135 hands in 77 Japanese patients to assess the frequency of radial involvement and its association with recurrence and the Dupuytren's diathesis. The radial aspect of the hand was affected in 22% of the hands. Diseased cords were observed in ten patients who underwent surgery on the radial aspect of the hand. Longitudinal cords on the radial side of thenar eminence and distal transverse interdigital cords were common. The radial aspect of the hand was the most common site of disease extension, though recurrence never occurred after excision of a radial lesion. Ectopic lesions, bilateral hand involvement, and recurrence were significantly more frequent in patients with the radial side involvement. Thus the results of this study suggest that radial side disease is associated with the Dupuytren's diathesis and is a risk factor of recurrence.

Adult↗

An objective method to evaluate the risk of recurrence and extension of Dupuytren's disease.

This study was undertaken to assess the influence of the factors related to Dupuytren's diathesis on the rates of recurrence and extension of Dupuytren's disease after surgery. The records of 65 patients who underwent surgery for Dupuytren's disease were retrospectively studied and the presence of factors related to diathesis were recorded. The sensitivity and specificity of each factor for predicting recurrence and extension were calculated. Odds ratios and 95% confidence intervals were also calculated and a discriminant analysis was performed to explore correlations between recurrence and extension and the significant variables. Our results confirmed the prognostic value of diathesis. The results have been used to develop a new scoring system for evaluating the risk of recurrence and extension.

Adult↗

Reduced inflammatory pain in mice deficient in the differential screening-selected gene aberrative in neuroblastoma.

Differential screening-selected gene aberrative in neuroblastoma (Dan) protein is produced in small neurons of dorsal root ganglia. Thermal and mechanical allodynia and Fos expression in the spinal dorsal horn evoked by inflammation and neuropathic pain were investigated using Dan-deficient mice. Mice showed pain reactions induced by the introduction of complete Freund's adjuvant (CFA) into their hind paw (inflammatory pain model) and after sciatic nerve ligation (neuropathic pain model). In the inflammatory pain model, thermal and mechanical pain thresholds in Dan-deficient mice were significantly higher than those of wild-type mice. The number of Fos-immunoreactive cells in the dorsal horn during the inflammatory period was significantly less in Dan-deficient mice. However, in the neuropathic pain model, no differences in thermal hypersensitivity, mechanical allodynia, or the number of Fos-immunoreactive cells in the dorsal horn were observed between the mice. These data suggest that Dan may be a neuromodulator in inflammatory pain.

Animals↗

Rotation of the spinal cord in idiopathic scoliosis.

We undertook a radiographic analysis with pre-operative computed tomographic myelography in 78 patients with idiopathic scoliosis in order to analyse rotation of the spinal cord and to investigate its clinical significance. The angle of rotation of the cord had a statistically significant relationship to both that of the apical vertebra and the size of the primary curve. The relationship between the rotation of the cord and that of the apical vertebra was divided into three types. The cord rotated in the same direction as the apical vertebra in 55 patients and rotated in the opposite direction in the remaining 23 patients. In the first group, the angle of rotation of the cord was more than that of the vertebra in six patients, but less than it in 49 patients. These results suggest that the neuraxis in idiopathic scoliosis may be under tension in the axial dimension.

Adolescent↗

A paired study of Perthes' disease comparing conservative and surgical treatment.

We performed a paired study of mature patients with Perthes' disease to compare the radiological results after treatment between conservatively- and surgically-treated groups. One patient was selected from each group to create the pairs for this study. Each pair was strictly matched for gender, body mass index, age at onset, stage at the first visit, necrotic area and radiological at-risk signs and each was assessed by comparing the values of six radiological measurements. Eighteen pairs (36 hips) fitted the criteria. The radiological measurements which showed a statistically better result in the surgical groups were Mose's method, the acetabular-head index and leg-length discrepancy. There were no statistical differences in the slope of the acetabular roof and the articulotrochanteric distance. Four hips in the conservative group were in Stulberg class II, five in class III and nine in class IV. In the surgical group, 13 were in Stulberg class II, four in class III and one in class IV. We conclude that surgical treatment improved the sphericity of the femoral head and provided greater acetabular cover, but did not reform the acetabular roof. It was noteworthy that a greater leg-length discrepancy and a smaller articulotrochanteric distance were not seen in the surgical group. Our study suggests that surgical treatment is preferable in patients with severe Perthes' disease.

Child↗

Increased procollagen alpha1(I) mRNA expression by dermal fibroblasts in melorheostosis.

We report a patient with melorheostosis in whom increased procollagen alpha1(I) mRNA expression and alpha1(I), alpha2(I) and alpha1(III) collagen secretion were observed in dermal fibroblasts obtained from a skin biopsy overlying the involved bone. The patient was a 53-year-old man with melorheostosis lesions over the left knee joint. Multiple pigmented macules were present on the medial aspect of the lower left leg. Hyperpigmentation of the basal keratinocytes, thick-walled vessels in the reticular dermis, and proliferation of normal-appearing collagen around the hair follicles were observed histologically.

Fibroblasts↗

Dorsal root ganglion neurones with dichotomising afferent fibres to both the lumbar disc and the groin skin. A possible neuronal mechanism underlying referred groin pain in lower lumbar disc diseases.

Dorsal root ganglion neurones with dichotomising axons are present in several species and are considered to play a role in referred pain. Clinically, patients with lesions in the lower lumbar discs occasionally complain of pain in the groin. We investigated the existence of dichotomising afferent neurones projecting axons both to the lumbar disc and to the groin skin, using the double fluorescent-labelling technique in rats. We observed neurones labelled with a tracer applied at the ventral portion of the LS-L6 disc and another tracer placed on the groin skin in L1 and L2 dorsal root ganglia. Our results showed that the double-labelled neurones had peripheral axons which dichotomised into both the LS-L6 disc and the groin skin, indicating the convergence of afferent sensory information from the disc and groin skin. Our findings provide a possible neuroanatomical mechanism for referred groin pain in patients with disc lesions.

Animals↗

Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal dorsal horn.

Differential screening-selected gene aberrative in neuroblastoma (DAN) belongs to a novel gene family that includes the Xenopus head-inducing factor, Cerberus and the dorsalizing factor, Gremlin. It has been suggested that members of this family control diverse processes in growth, development and the cell cycle.Here, we demonstrate that the DAN protein is produced in the small neurons of the dorsal root ganglion and is transported to the nerve terminals in the spinal dorsal horn in adult rats. Furthermore, intrathecal injection of an antibody to the DAN protein suppressed inflammatory pain caused by the introduction of complete Freund's adjuvant or carrageenan into the rat hindpaw. The amount of mRNA for DAN in dorsal root ganglion neurons and of its expressed protein in the spinal dorsal horn were both increased in inflammatory models.Together, these data suggest that the DAN protein may be a novel neuromodulator in primary nociceptive nerve fibers.

Afferent Pathways↗

Natural history of infantile tibia vara.

We have observed the natural history without treatment of 46 limbs in 29 patients with infantile tibia vara and a metaphyseal-diaphyseal angle (MDA) of more than 11 degrees. The femorotibial angle (FTA) and MDA were measured, and Langenskiöld's classification of radiological changes in the proximal medial metaphysis of the tibia was used. In 22 limbs which were not in Langenskiöld stages II to III the condition resolved spontaneously without treatment. Of the remaining 24 which were in stages II to III, in 18 it resolved spontaneously by the age of six years, but six showed little or no improvement at the latest follow-up. It was impossible to differentiate by measuring the FTA or MDA whether spontaneous resolution could be expected before the age of four years. There was no difference in the rate of resolution of the deformity between those patients who had been treated by a brace and those who had received no treatment. We advise no initial treatment but review at six-monthly intervals until the age of four years, even in patients with Langenskiöld stage-II to stage-III deformity. When a deformity persisted or progressed we carried out a corrective osteotomy after the age of four years.

Bone Malalignment↗

Deterioration of long-term clinical results after the Elmslie-Trillat procedure for dislocation of the patella.

We examined 39 patients (45 knees) who had undergone an Elmslie-Trillat procedure for recurrent or habitual dislocation of the patella with a follow-up of more than ten years. The mean age at the time of surgery was 18.4 years; the mean follow-up was 161 months (120 to 238). Using Fulkerson's functional knee score, 41 knees (91%) had an excellent or good result at a mean follow-up of 45 months, and this was maintained in 29 (64%) at the final review. The main cause of deterioration in the clinical results was the onset or worsening of patellofemoral joint pain, not patellar instability.

Adolescent↗

Brain-derived neurotrophic factor and vanilloid receptor subtype 1 immunoreactive sensory DRG neurons innervating the lumbar facet joints in rats.

The rat L5/6 facet joint is innervated from L1 to L6 by the dorsal root ganglia (DRG). The presence of substance P- and calcitonin gene-related peptide-immunoreactive (ir) DRG neurons innervating the L5/6 facet joint has been demonstrated. However, the presence of brain-derived neurotrophic factor (BDNF)-ir and the vanilloid receptor subtype 1 (VR1)-ir DRG neurons, which relate to inflammatory and burning pain innervating the L5/6 facet joint, has not. Fluoro-gold (FG)-labeled neurons innervating the L5/6 facet joint were distributed throughout the DRGs from T13 to L6 levels. Of the FG-labeled neurons, the proportions of BDNF-ir in L1, L2, L3, L4 and L5 DRG neurons were 9%, 15%, 21%, 17% and 20% and the proportions of VR1-ir L1, L2, L3, L4 and L5 DRG neurons were 8%, 9%, 15%, 16% and 15%, respectively.

Animals↗