Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA: Implication for L‐DOPA‐induced dyskinesia in Parkinson's disease

The medial globus pallidus plays a crucial role in generation of L‐DOPA‐induced dyskinesia in patients with Parkinson's disease. The 6‐hydroxydopamine‐lesioned rat exhibiting behavioral sensitization to L‐DOPA is one useful animal model for examining L‐DOPA‐induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA were examined. Intermittent L‐DOPA treatment induced hypertrophy of the lesioned‐side of medial globus pallidus and substantia nigra reticulata of 6‐hydroxydopamine‐lesioned rats with behavioral sensitization to L‐DOPA. Additionally, coadministration of a 5‐HT_1A receptor agonist, 8‐hydroxy‐2(di‐n‐propylamino)tetralin with L‐DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L‐DOPA in 6‐hydroxydopamine‐lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L‐DOPA‐induced dyskinesia in patients with Parkinson's disease.     

An immunodominant haptenic epitope of carbamazepine detected in serum from patients given long-term treatment with carbamazepine without allergic reaction

An anticarbamazepine antibody was detected in the serum of a patient with severe carbamazepine-induced serum sickness. We found that the patient's T cells and IgG antibody recognized an epitope which appeared in subjects showing an allergic reaction, as well as that in subjects who showed no allergic reaction, after long-term carbamazepine therapy. These results show that an anti-carbamazepine immune response does not occur in the majority of subjects who undergo long-term carbamazepine therapy without developing allergic symptoms, although the immunodominant haptenic epitope of carbamazepine is present in their sera.     

Neural cell adhesion molecule contributes to hemopoiesis-supporting capacity of stromal cell lines

To clarify mechanisms underlying cell-to-cell interactions between hemopoietic stem cells (HSCs) and stromal cells, we established a stromal cell line (FMS/PA6-P) from day-16 fetal bone marrow (BM) adherent cells using an anti-PA6 monoclonal antibody (mAb) specific for BM stromal cells. Importantly, this FMS/PA6-P cell line, showing homogenous fibroblastic morphology, is absent from hematolymphoid and endothelial lineage markers and maintains a high level of expression of PA6 molecule, recognized by the anti-PA6 mAb, for approximately 20 passages. Further, the cell line expressing a high level of PA6 molecule has a better hemopoiesis-supporting capacity in vitro than other stromal cell lines such as PA6 and MS-5. In fact, the PA6 molecule is closely related to the hemopoiesis-supporting capacity of the stromal cells because the proliferation of HSCs was suppressed to a great extent by the anti-PA6 mAb. Affinity chromatography and mass peptide fingerprinting revealed that the protein reacting with the anti-PA6 mAb is neural cell adhesion molecule (NCAM). The frequencies of long-term cobblestone area-forming cells and long-term culture-initiating cells were significantly suppressed by repression of NCAM in the FMS/PA6-P cells using NCAM small interfering RNA. Our findings clearly indicate that NCAM functions on the maintenance of HSCs.     

Intra-bone marrow-bone marrow transplantation facilitates hemopoietic recovery including dendritic cells

In this report, we provide evidence using a serial bone marrow transplantation (BMT) protocol that intra-bone marrow (IBM)-BMT (IBM-BMT) can efficiently reconstitute the hemopoietic system with cells of donor origin, in contrast to conventional intravenous (IV)-BMT (IV-BMT). Furthermore, the hematolymphoid system of secondary recipients that had received bone marrow cells (BMCs) from primary recipients treated with IBM-BMT recovered earlier than that of the secondary recipients of BMCs from primary recipients treated with IV-BMT. This was the case when the Lin-/c-kit+ progenitor cells of the secondary and tertiary recipients were examined. These findings indicate that IBM-BMT can facilitate the development of not only cells of various lineages but also the effective generation and, more importantly, the maintenance of the progenitor cells. Furthermore, we show that IBM-BMT can reconstitute the dendritic cell (DC) subsets (myeloid and lymphoid DCs), which are critical for the initiation of both adaptive and innate immune responses. The frequency of both myeloid and lymphoid DC subsets was approximately equal to that of normal age-matched untreated controls and, after second and third BMT, this ratio was close to that observed in the normal controls. However, the lymphoid DCs were clearly reduced in the secondary and tertiary recipients of BMCs from mice that had received IV-BMT. Therefore, the development of DC subsets is also normally maintained in the IBM-BMT group.     

Purine phosphoribosyltransferase activities in guinea pig epidermis

Purine phosphoribosyltransferase activities in normal and experimental hyperkeratotic epidermis of guinea pig skin were demonstrated quantitatively by a new microassay method. The ratio of HGPRTase with hypoxanthine as a substrate to APRTase activity in normal and hyperkeratotic epidermis was found to be 0.94 and 0.60, respectively. The HGPRTase and APRTase activities expressed as micromoles per gram wet weight per min. were increased in experimental hyperkeratotic epidermis and it is suggested that the salvage pathway for purine nucleotide biosynthesis is activated in experimental hyperkeratotic epidermis. The pH optimum of these enzymes and their stability in the frozen state were also demonstrated.     

Regional myocardial perfusion and metabolism assessed by positron emission tomography in children with Kawasaki disease and significance of abnormal Q waves and their disappearance

To clarify the significance of newly appearing abnormal Q waves and their disappearance in patients with Kawasaki disease, regional myocardial perfusion and glucose metabolism at rest in the fasting condition were assessed by positron emission tomography (PET) with ¹³N-ammonia and ¹⁸F-fluorodeoxyglucose (FDG), and regional wall motion by left ventriculography in regions with persistent and transient abnormal Q waves in 14 patients. PET identified 3 groups of abnormal myocardial segments: segments with hypoperfusion without increased FDG uptake, those with hypoperfusion and increased FDG uptake, and those with normal perfusion and increased FDG uptake. Almost all the segments with persistent or transient abnormal Q waves had abnormal PET findings. PET demonstrated evidence of metabolic activity in 57% of segments with persistent abnormal Q waves and 67% of those with transient abnormal Q waves. Regional wall motion, scored from 0 (normal) to 4 (dyskinesia), was not significantly different between segments with persistent and transient abnormal Q waves (2.3 ± 1.3 vs 2.2 ± 1.2). The persistence of abnormal Q waves on serial electrocardiograms was significantly shorter in metabolically active than in inactive segments (19 ± 17 vs 92 ± 27 months). In conclusion, in patients with Kawasaki disease, the new appearance of abnormal Q waves is a reliable clue to the presence of ischemic myocardial injury and a high proportion of them are associated with metabolically active myocardial regions. The disappearance of abnormal Q waves does not necessarily mean the normalization of regional myocardial perfusion, metabolism or function, and their early disappearance may imply “viability” in the associated myocardial region.     

Electrophysiologic properties of atrial muscle in paroxysmal atrial fibrillation

The electrophysiologic properties of atrial muscle were studied by programmed atrial stimulation in 42 patients with paroxysmal atrial fibrillation (PAF) and in 53 control patients without PAF. Single premature atrial stimulation was given at the right atrial appendage following 8 basic stimuli with a basic cycle length of 500 ms. Repetitive atrial firing (RAF) was defined as the occurrence of 2 or more successive premature atrial activations following single premature atrial stimulation. Fragmented atrial activity (FAA) was defined as an increase by more than 75% of the duration of the atrial electrogram in response to a single premature stimulation. Interatrial conduction delay was defined as an increase of the conduction time by more than 50 ms in response to a single premature stimulation. RAF was induced in 26 of 42 patients (61.9%) with PAF and in 14 of 53 control patients (26A%). FAA and interatrial conduction delay were elicited in 69.0 and 80.9% of patients with PAF and in 34.0 and 56.6% of control patients, respectively. In 16 patients with PAF in whom RAF was not induced, FAA developed in 11 patients (68.8%). In 88.1% of 42 patients with PAF and in 41.5% of 53 controls, RAF or FAA, or both, were elicited by atrial premature stimulation. It is concluded that the incidence of RAF and FAA were significantly higher in patients with PAF than in the control group, and the induction of RAF or FAA, or both, was closely related to the vulnerability of the atrial muscle to atrial fibrillation.     

Diagnosing infection of extracardiac conduit in children

Summary Between August 1985 and July 1992, at our center, 142 Japanese children had an extracardiac conduit operation to reconstruct the right ventricular outflow tract. The study group consisted of 22 of these 142 children who had a persistent fever and whose serum was positive for acute-phase reactants after the operation. We present the diagnostic findings for 10 children with infection of an extracardiac conduit that had been placed to restore the continuity of the right ventricle-pulmonary artery. They were part of the group of 22 children who were followed over the past 7 years with blood cultures, echocardiography, and⁶⁷Ga imaging. All 10 developed a persistent fever and were seropositive for acute-phase reactants. Conduit infection was diagnosed in only 2 patients by the detection of vegetation on echocardiography and was diagnosed in 9 of the 10 patients by an abnormal⁶⁷Ga uptake in the area of the artificial vessels used to reconstruct the pulmonary artery. The present study compared the use of blood cultures, echocardiography, and⁶⁷Ga imaging in diagnosing an infection of the extracardiac conduit. The sensitivity of blood cultures in diagnosing an extracardiac conduit infection was 70% (7/10), and the specificity was 92% (1/12).⁶⁷Ga imaging showed a higher sensitivity than echocardiography in diagnosing infection of an extracardiac conduit.