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.     

The effects of prenatal protein-energy malnutrition on ossification of fetal rat bones: a biochemical study

In fetal rats whose dams were fed a low-protein diet, 35S sulfate uptake into the growth plate of the long bone and rib was higher than in the control group. The elution pattern of guanidine-HCl extract in gel chromatography revealed that the malnourished group had more high molecular weight proteoglycans in the dissociative condition and a larger aggregated portion in the associative condition than did the control group; however, the same chondroitin-sulfate chain size existed. Calcium content did not differ in both groups. Aggregated proteoglycan or a high molecular weight proteoglycan that existed in the malnourished group probably played an inhibitory role in calcification. Prenatal protein-energy malnutrition may delay the change of proteoglycan character, which could affect mineralization of fetal bones.     

Effect of magnetic field on pineal gland volume and pinealocyte size in the rat

Abstract: Light microscopic observations on the superficial pineal gland of Wistar-King rats were made to examine whether or not pineal volume and pinealocyte size, expressed as nuclear density, at daytime or nighttime are affected by long-term exposure to 50 Hz rotating magnetic field (MF) at 5.0 μT. Determinations of pineal volume and pinealocyte size were repeated twice (April and October) during the year. Size of pinealocytes in MF-exposed and sham-exposed rats exhibited, in addition to the difference between peripheral and central regions, regional differences in a proximodistal direction; pinealocytes in the distal and middle-peripheral regions were usually larger than those in the proximal and middle-central regions at daytime or nighttime. In October, distal and proximal pinealocytes showed significant day-night changes in size in sham-exposed rats, but not in MF-exposed animals. The situations in the two groups were almost reversed in April. Significant day-night differences were scarcely found in pinealocyte size in the middle region in the two groups. Throughout the study, pineal volume and pinealocyte size in each region were generally the same between MF-exposed and sham-exposed rats at daytime or nighttime. The results suggest that pinealocytes in the distal and proximal regions, but not those in the middle region, are affected by MF-exposure; day-night differences in sizes of distal and proximal pinealocytes appear in April and disappear in October under the influence of MF. MF may exert an effect on mechanisms controlling day-night rhythms of pinealocyte size in the rat.     

Aggressive resection for advanced pancreatic carcinoma

An aggressive pancreatectomy was performed on a 53 year old Japanese man with advanced cancer of the pancreas. The tumor originated from the body of the pancreas and invaded the stomach, duodenum, left kidney, transverse colon and common hepatic artery. An unexpected cancer was also found in the head of the pancreas during the operation. Therefore, total pancreatectomy, total gastrectomy, left adrenonephrectomy, resection of the left transverse colon and dissection of the regional lymph nodes were performed. Resection of the common hepatic artery was also performed, followed by an end-to-end anastomosis between the common hepatic artery and celiac trunk. The postoperative course was uneventful and the patient was doing well until nine months after the operation when multiple metastatic lesions were noted in the liver. He died 391 days after the operation from hepatic failure.     

Overexpression of suppressor of cytokine signalling-5 augments eosinophilic airway inflammation in mice

BACKGROUND: Enhanced expression of the suppressor of cytokine signalling (SOCS)-5 might be of therapeutic benefit for T-helper type 2 (Th2) dominant diseases, as its expression is reported to result in a reduction of Th2 differentiation in vitro due to the inhibition of IL-4 signalling. OBJECTIVE: To investigate the regulatory role of SOCS-5 in vivo, we explored the phenotype of an experimental asthma model developed in SOCS-5 transgenic (Tg) mice. METHODS: The SOCS-5 Tg mice or wild-type (WT) mice were sensitized and repeatedly challenged with ovalbumin (OVA). We examined bronchoalveolar lavage fluid (BALF), lung specimens, and airway hyperresponsiveness (AHR) to methacholine. RESULTS: The production of IFN-gamma by CD4(+) T cells from unprimed SOCS-5 Tg mice was significantly increased in comparison with unprimed wild-type mice, indicating that SOCS-5 Tg mice have a Th1-polarizing condition under natural conditions. However, in an asthma model, significantly more eosinophils in the airways and higher levels of IL-5 and IL-13 in BALF were observed in the SOCS-5 Tg than the wild-type mice. AHR in the asthma model of SOCS-5 Tg was also more enhanced than that of wild-type mice. OVA-stimulated CD4(+) T cells from the primed SOCS-5 Tg mice produced significantly more IL-5 and IL-13 than CD4(+) T cells from wild-type mice. CONCLUSION: Our results demonstrate that the overexpression of SOCS-5 does not inhibit Th2 response, but rather augments the phenotype of the asthma model in vivo. This finding throws into question the therapeutic utility of using enhancement of SOCS-5 expression for Th2-dominant disease.     

Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; renoprotective effects of an ultrahigh dose of olmesartan.

Recent studies have suggested that aldosterone plays a role in the pathogenesis of renal injury. In this study, we investigated whether local angiotensin II (Ang II) activity contributes to the progression of renal injury in aldosterone/salt-induced hypertensive rats. Uninephrectomized rats were treated with 1% NaCl in a drinking solution and one of the following combinations for 6 weeks: vehicle (2% ethanol, s.c.; n=9), aldosterone (0.75 mug/h, s.c.; n=8), aldosterone+Ang II type 1 receptor blocker olmesartan (10 mg/kg/day, p.o.; n=8), or aldosterone+olmesartan (100 mg/kg/day, p.o.; n=9). Aldosterone/salt-treated hypertensive rats exhibited severe proteinuria and renal injury characterized by glomerular sclerosis and tubulointerstitial fibrosis. Aldosterone/salt-induced renal injury was associated with augmented expression of angiotensin converting enzyme and Ang II levels in the renal cortex and medullary tissues. Renal cortical and medullary mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) as well as the collagen contents were increased in aldosterone/salt-treated hypertensive rats. Treatment with olmesartan (10 or 100 mg/kg/day) had no effect on blood pressure but attenuated proteinuria in a dose-dependent manner. Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant. On the other hand, an ultrahigh dose of olmesartan (100 mg/kg/day) significantly decreased these values and ameliorated renal injury. These data suggest that augmented local Ang II activity contributes, at least partially, to the progression of aldosterone/salt-dependent renal injury.     

Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting.

OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.     

Hyperaemia prior to acute cerebral swelling in severe head injuries: The role of transcranial doppler monitoring

Summary Acute cerebrovascular congestion after a closed head injury is significantly related to intracranial hypertension. As an indirect method of cerebral blood flow measurement, transcranial doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral haemodynamics, including hyperaemic conditions.TCD examinations was serially performed in 35 patients with severe head injury with intact cerebral circulation; i.e. the mean flow velocity (MFV) patterns of the middle cerebral artery (MCA) did not show signs of cerebral circulatory arrest such as systolic spike, to and fro, or no flow. The results showed that the MFV of the MCAs and ipsilateral extracranial internal carotid arteries (ICAs) in 9 of these patients increased sharply and pulsatility index (PI) decreased during 48–96 hours after the injury. This was soon followed by patterns of high intracranial resistance, consistent with elevated intracranial pressure (ICP) in monitored patients and acute brain swelling on repeated computed tomographic (CT) scans. The correlation between increased MFVs, decreased PIs, and cerebral haemodynamic changes leading to acute brain swelling is discussed.The number of patients who ended with severe disability, vegetative state, or death was 66% in this group of 9 patients, compared to only 34% for the 35 patients overall with severe head injury. Though the morbidity and mortality rates largely depend on the primary injury, the presence of acute cerebral swelling aggravate the grave course in these patients. And the ability of TCD to monitor the hyperaemic state prior to oedema should lead us to adjust the therapy in order to minimize the secondary insult related to intracranial hypertension.     

Purification of 45 KDa estramustine binding protein (EMBP) and preparation of its antibody

The purification of 45 KDa EMBP and the production of monospecific anti-serum is described. 45 KDa EMBP was purified by relatively simple methods using ion exchange HPLC (TSK-GEL DEAE-5PW column) and size exclusion HPLC (TSK-GEL G3000SW column). The results clearly demonstrated the speed and simplicity of the method using these columns, compared to previously-described methods for purification of 45 KDa EMBP.     

Clinical Evaluation of a New Type of Centrifugal Pump

Abstract: The major problems with existing centrifugal pumps are leakage, mechanical trauma, and thrombus formation. In consideration of these problems, a new compact centrifugal pump system was developed. The purpose of this study was to evaluate the new centrifugal pump system clinically. Ten patients underwent open heart surgery with a centrifugal pump or a roller pump. During surgery, hemodynamic and hematological data were obtained. A pulsatile assist device in the pump circuit was used in patients with severe heart disease. There was neither operative death nor hospital mortality, and there was no difference with regard to hemodynamic data between the two groups. The centrifugal pump group, however, had significantly lower hemolysis, especially during prolonged cardiopulmonary bypass. This centrifugal pump could also create sufficient pulsatile flow with a pulsatile assist device. Postoperative macroscopic and microscopic findings demonstrated the smooth surface of the pump without thrombus formation. This centrifugal pump system might be useful for prolonged cardiopulmonary bypass.