Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease

Immunohistochemistry using both a newly developed polyclonal, and a commercially available monoclonal, anti-insulin receptor antibody was done on the midbrain from cases of idiopathic Parkinson's disease (PD), Alzheimer's disease, amyotrophic lateral sclerosis, vascular parkinsonism and non-neurological controls. Both antibodies gave indentical patterns of neuronal staining. The neurons of the oculomotor nucleus were immunopositive in all the brains. However, the neurons in the pars compacta of the substantia nigra, paranigral nucleus, parabrachial pigmental nucleus, tegmental pedunculopontine nucleus, supratrocheal nucleus, cuneiform nucleus, subcuneiform nucleus and lemniscus medialis, which were positive in other diseases and in non-neurological controls, were not stained by these antibodies in PD brains. These results suggest that, in PD, a dysfunction of the insulin/insulin receptor system may precede death of the dopaminergic neurons.The work in the Kinsmen Laboratory was supported by the MRC of Canada and the Parkinson Society of Canada     

Behavioral analysis of internal memory states using cooling-induced retrograde amnesia in Limax flavus.

Temporal evolution of internal memory states in a terrestrial mollusk, Limax flavus, was studied using cooling-induced retrograde amnesia. The slug was conditioned to avoid carrot odor by temporally correlated presentation of carrot juice and a bitter-taste stimulus of quinidine sulfate. We could induce retrograde amnesia by cooling of the conditioned slug immediately after the training trial. Thus, we studied the memory states in the slug using the retrograde amnesia according to strategies used in the studies of memory states in mammals or insects. In the early process of memory acquisition, at least two distinctive memory states were observed, short-term memory and long-term memory (LTM). For LTM, two states were also observed. One was a reactivated state of LTM, which was sensitive to the cooling used to induce the amnesia. The other was a so-called resting state of LTM, which was insensitive to cooling. A few days after memory acquisition, further evolution was observed in that the amnesia could not be induced even if the memory trace was reactivated. The results obtained in Limax flavus was comparable with those obtained in a variety of animals.     

Placental alkaline phosphatase as a tumor marker for primary intracranial germinoma

A sensitive enzyme-linked immunosorbent assay (ELISA) was used in a retrospective study of placental alkaline phosphatase (PLAP) levels in serum, cerebrospinal fluid (CSF), and intratumoral cyst fluid in primary intracranial germinoma. The ELISA showed no cross-reactivity with intestinal alkaline phosphatase except in very high concentrations, after samples had been heat-treated. Three patients with germinoma were studied for serum PLAP levels and in all the levels were elevated (3.78, 0.52, and 2.11 IU/liter). Two of the germinoma patients were studied for PLAP levels in the CSF, and both had elevated levels (0.83 and 9.83 IU/liter). The intratumoral cyst fluid in one case of germinoma was tested for PLAP and the level was found to be very high (603 IU/liter). These PLAP levels decreased concomitantly with the reduction in tumor size during irradiation. Serum PLAP levels were measured in 40 control adult male individuals and in the CSF of 20 nonpregnant patients with subarachnoid hemorrhage. The upper normal limits were 0.20 and 0.11 IU/liter in the serum and the CSF, respectively. All PLAP levels measured in the serum of patients with various brain tumors were 0.18 IU/liter or less. This study strongly suggests that PLAP is a clinically useful tumor marker for primary intracranial germinoma.     

Evaluation of image-diagnosing methods of enlarged parathyroid glands in chronic renal failure

Three noninvasive image-diagnosing methods, computed tomography (CT), scintigraphy with²⁰¹T1C1 and^99mTcO_h4 ^–, and ultrasonography (US), were preoperatively performed on 50 patients with chronic renal failure and secondary hyperparathyroidism who underwent total parathyroidectomy and parathyroid autograft. The detection rates of the 3 methods on the 191 excised parathyroid glands were compared according to weight and location. CT detected 57.1% of all glands and 78.6% of 103 glands weighing over 500 mg. Scintigraphy detected 51.8% and 75.7%, and US detected 42.4% and 53.4%, respectively. The detection rate of upper glands was best with CT at 58.9% and 89.1%; that of lower glands was best with scintigraphy at 65.3% and 80.4%. Although the combination of the 3 methods diagnosed 69.6% and 89.5%, CT and scintigraphy, the best 2 combinations, visualized 67.5% and 88.3%.

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Resumen Tres métodos diagnósticos no invasivos, la tomografía computadorizada (TC), la centelleografía con²⁰¹T1C1 y^99mTcO₄ y la ultrasonografía (US) fueron realizados preoperatoriamente en 50 pacientes con falla renal crónica e hiperparatiroidismo secundario sometidos a paratiroidectomía y autotransplante paratiroideo. Las tasas de detección de los 3 métodos fueron comparados sobre las 191 glándulas paratiroideas resecadas en relación a los pesos y a los sitios de ubicación. La TC detectó el 57.1% del total de glándulas y el 78.6% de aquellas glándulas (103) con pesos superiores a 500 mg. La centelleografía detectó 51.8% y 75.7%, y la US 42.4% y 53.4% respectivamente. La tasa de detección para las glándulas superiores fue optima con TC, con 58.9% y 89.1%; la de las glándulas inferiores fue óptima con centelleografía, con 65.3% y 80.4%. Aunque la combinación de los 3 metodos diagnosticó el 69.6% y 89.5%, la TC y la centelleografía, la mejor de las combinaciones, visualizó el 67.5% y el 88.3% respectivamente.

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Résumé Trois méthodes d'imagerie non invasives, la tomodensitométrie, la scintigraphie (avec T1C1²¹⁰ et TcO₄ ^99m), et l'ultrasonographie ont été pratiquées avant l'intervention chez 50 malades qui présentaient une insuffisance rénale chronique compliquée d'hyperparathyroïdisme secondaire et qui furent traités par parathyroïdectomie totale et autogreffe parathyroïdienne. Les taux de détection de ces 3 méthodes concernant 191 glandes parathyroïdes réséquées ont été évalués en fonction du poids et du siège des lésions. La tomodensitométrie a permis de découvrir 57.1% de toutes les glandes et 78.6% des glandes dont le poids dépassait 500 mg; la scintigraphie 51.8% et 75.7%; l'ultrasonographie 42.4% et 53.4%. Le taux de détection des glandes supérieures fut plus élevé avec la tomodensitométrie: 58.9% et 89.1%; celui des glandes inférieures le fut avec la scintigraphie: 65.3% et 80.4%. Si la combinaison des 3 méthodes permet le diagnostic dans 69.6% et 89.5% des cas la tomodensitométrie associée seulement à la scintigraphie donne des résultats très voisins, les taux respectifs étant de 67.5% et de 88.3%.

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Presented at the International Association of Endocrine Surgeons in Paris, September 1985.     

Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteoclastogenic potentials in mice.

To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. INTRODUCTION: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. MATERIALS AND METHODS: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. RESULTS: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. CONCLUSION: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone.