Graft Versus Host Disease with Mixed Chimerism

We report a patient with graft versus host disease (GVHD) with mixed chimerism (MC). The patient had chronic myelogenous leukemia and received bone marrow transplantation (BMT) from his elder sister. Eighty days after BMT, erythematous lesions appeared on his chest. Histological examination from the skin lesion revealed lymphocytic infiltration into the upper dermis. Eosinophilic necrotic keratinocytes were scattered through the epidermis. Liquefaction degeneration was also recognized. Sicca syndrome appeared from 110 days after BMT. Detection of host origin Y-chromosome-specific DNA by polymerase chain reaction (PCR) method in bone marrow and peripheral blood showed that all bone marrow samples obtained 6 months from BMT were positive for Y-specific DNA, while peripheral blood became positive in the 60th month after BMT. The host origin normal karyotype (46,XY) in the bone marrow samples was identified for the first time in the 60th month after BMT. These results indicate that host-origin hematopoietic cells survived after BMT.     

Radiographic study of osteoarthritic elbows in professional basebal pitchers

We examined radiographs of the elbows of the pitching arms of 79 professional baseball pitchers (mean age, 25.1 years; mean duration of professional career, 4.7 years) and noted the frequency and size of spurs, bone fragments, and intra-articular loose bodies according to site. The influence of duration of professional baseball career on these osteoarthritic changes was also investigated. The olecranon tip was the most frequent site of spurs (62/79; 78.5%), and fragmentation of the spur was detected in 17 joints. The frequency of spurs was also high at the medial margin of the olecranon, the tip of the coronoid process, the medial margin of the sigmoid notch, the medial margin of the trochlea and the olecranon fossa. In 38 subjects, spurs were observed at the distal portion of the radial notch of the ulna. However, few pitchers had osteoarthritic changes in the humeral capitellum or radial head. Intra-articular loose bodies were detected in 4 of 79 joints (5.1%), and bone fragments were present below the medial humeral epicondyle in 25 of 79 joints (31.6%). Osteoarthritic changes in the elbow joint appeared to be attributable mainly to traction stress and impingement associated with extension and valgus strain. Significant osteoarthritic changes were often found in professional pitchers whose careers exceeded 5 years.     

Effects of calcium channel blockers and hydralazine on plasma glucose levels in streptozotocin-induced diabetic rats in vivo

Effects of calcium channel blockers from structurally different classes and hydralazine on plasma glucose levels were examined in streptozotocin-induced diabetic rats in vivo. Non-dihydropyridine calcium channel blockers (verapamil, diltiazem, 1.0-10 mg/kg, i.p.) did not significantly affect the basal plasma glucose level, and dihydropyridine calcium channel blockers (nifedipine, 0.1-0.3 mg/kg, i.p,; nicardipine, 0.35-0.70 mg/kg, i.p.) caused mild hyperglycemia, which was blocked by the administration of the beta-adrenoceptor antagonist propranolol. In contrast, hydralazine markedly produced hyperglycemia, which was also inhibited by the combined administration of propranolol. The selective alpha 1-adrenoceptor antagonist prazosin greatly potentiated the hydralazine-induced hyperglycemia. Isoproterenol alone showed hyperglycemia similar to that of hydralazine. Hexamethonium (40 mg/kg, i.p.), a ganglionic blocker, blocked the hydralazine-induced hyperglycemia. There was a negative correlation between the hyperglycemic effect and the blood pressure lowering effect by different doses of hydralazine in streptozotocin-diabetic rats, but not in normal rats. These results suggest that endogenous catecholamines are involved in the hydralazine-induced hyperglycemia through the interaction with beta-adrenoceptors in streptozotocin-diabetic rats in vivo.     

AUGMENTATION OF ANGIOTENSIN II RELEASE FROM ISOLATED MESENTERIC ARTERIES OF WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS FOLLOWING NEPHRECTOMY

1. We previously reported that angiotensin II release from the mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) increased in a time-dependent manner as a result of the isolation of the arteries and perfusion. This phenomenon appeared to be due to the withdrawal of circulating angiotensin II (AII). 2. The purpose of the present study was to test the hypothesis that vascular AII generation may be negatively regulated by circulating AII in WKY and SHR, and to clarify the role of this vascular angiotensin II in the sustained hypertension of SHR following nephrectomy. 3. The mesenteric arteries from kidney-intact and nephrectomized WKY and SHR were perfused and the amount of AII released into the perfusate was measured. The effects of the angiotensin converting enzyme inhibitor, captopril, and the effects of supplementation of renal renin and circulating angiotensins to nephrectomized rats, by blood exchange between kidney-intact and nephrectomized rats, on AII release were examined to clarify the pathway of vascular AII generation after nephrectomy. 4. Nephrectomy caused augmentation of vascular AII release both in WKY and SHR in spite of the abolishment of circulating renin. Captopril reduced this enhanced release of AII, but blood exchange did not affect it. There was no significant difference in these responses between WKY and SHR. 5. These results suggest that WKY and SHR have in common a potent pathway for production of vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension of SHR after nephrectomy. The precise pathophysiological role of this pathway remains to be elucidated.     

Glued Carbon Fiber Electrodes for Diaphragm Pacing

Carbon fibers with fibrin glue were used as electrodes for diaphragm pacing. The electrodes were applied to three mongrel dogs and the effectiveness was tested. The carbon leads were glued to phrenic nerves by means of the fibrinogen and thrombin bilaterally. The tidal volumes and threshold current level for stimulation were measured at various time up to 9 weeks after implantation. Effective contraction of diaphragm were observed for 9 weeks. By using this electrode, the exfoliation of the nerve is not necessary, the nerve can be maintained in an intact state, and the risk of the implanting operation can be minimized.     

Practical guidelines for physicians in the management of febrile seizures

Recent studies have shown that adequate medication can prevent the recurrence of febrile seizures (FS). It has also been clarified that the vast majority of, though not all, FS patients follow a benign course. Then, questions arise as to whether or not FS should be prevented, particularly in light of the risks of side effects from drugs. Which kinds of FS can be prevented, if necessary? The guidelines presented here are aimed primarily at helping general practitioners in considering how to manage FS most appropriately. The guidelines stress that judgements should be individualized, while referring to a few specific ‘warning factors’. The guidelines follow a ‘laissez-faire’ principle for the majority of FS cases, whereas intermittent therapy with diazepam and continuous medication with either phenobarbital or valproate are indicated in other limited cases meeting respective definite criteria.     

Gene polymorphism of myospryn (cardiomyopathy-associated 5) is associated with left ventricular wall thickness in patients with hypertension.

We examined a gene polymorphism of a novel Z-disc-related protein, myospryn (cardiomyopathy-associated 5). We focused on one haplotype block associated with a tag single nucleotide polymorphism (SNP) that covered 16 of 27 coding SNPs with linkage disequilibrium (minor allele frequency 0.413). Screening a myospryn polymorphism (K2906N) in a general health check-up of a rural Japanese population revealed an association with cardiac diseases (p=0.0082). In further analysis of the interaction between K2906N and cardiac function in patients, K2906N was associated with the anteroseptal wall thickness of the left ventricle in a recessive model (p=0.0324) and with the ratio of the peak velocity of the early diastolic filling wave to the peak velocity of atrial filling (A/E) (p=0.0278). In an association study based on left ventricular wall thickness, we found a significant difference in the K2906N genotype between controls and patients with cardiac hypertrophy. These results suggest that the K2906N polymorphism could be clinically associated with left ventricular hypertrophy and diastolic dysfunction independent of known parameters. Although the precise mechanism underlying this association remains to be elucidated, treatment with angiotensin II induced an increase in heart myospryn mRNA level in vitro and in vivo. Our results suggest that the polymorphism of myospryn is associated with left ventricular hypertrophy, and an association between a Z-disc protein and cardiac adaptation in response to pressure overload.     

Effects of proton pump inhibitor on gastric mucosa hemodynamics and tissue oxygenation in anesthetized rats.

Proton pump inhibitors have been reported to have a cytoprotective action in addition to the anti-secretory action of acid. The precise mechanism, however, remains obscure. In this study, the effects of proton pump inhibitors (omeprazole and NC-1300) on gastric mucosa hemodynamics and tissue oxygenation were investigated using organ reflectance spectrophotometry in a hemorrhagic shock-reperfusion model involving anesthetized rats. Neither drug affected gastric mucosa hemodynamics nor tissue oxygenation in the basal state before hemorrhage. During the hemorrhagic shock state, however, these drugs maintained tissue oxygenation and reduced ulcer formation, although they did not show a significant effect on gastric mucosa blood volume. The results suggest that both proton pump inhibitors have an anti-ulcer action by maintaining mucosal oxygenation in addition to the anti-secretory activity of acid.     

Presence of circulating suppressive factor for muscarinic acetylcholine receptor in senile dementia

Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acetylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acetylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean +/- SD age of 77.5 +/- 8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic-subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (3H-QNB), an antagonist for muscarinic acetylcholine receptor, to the rat synaptic membrane, was 18.1 +/- 7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7 +/- 3.8%). However, that in the VD group (8.4 +/- 6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on 3H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r = 0.480, p less than 0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT.