Allogeneic cell stimulation enhances cytomegalovirus replication in the early period of primary infection in an experimental rat model.

BACKGROUND: Cytomegalovirus (CMV) diseases commonly occur in allograft recipients in the early post-transplant period. However, factors responsible for the high incidence of CMV diseases during this period are not yet fully defined. METHODS: Wistar-Furth (WF; RT-1(u)) rats were inoculated with 10(4) plaque-forming units (PFU) of rat CMV (RCMV) intraperitoneally, and then transplanted with allogeneic lungs from Dark Agouti (DA; RT-1avl) rats or stimulated with 10(7) mitomycin C-treated spleen cells from DA rats by daily sub-cutaneous injections for 2 weeks. No immunosuppressive agent was used. Naive WF rats and WF rats grafted with syngeneic lungs or cells were used as controls. The level of RCMV replication in rats was assessed by infectious virus titers in tissues. RESULTS: The virus titers in salivary glands of allogeneic and syngeneic lung graft recipients were significantly higher than in naive WF rats. The level of RCMV replication in rats stimulated with allogeneic spleen cells was significantly higher than in the syngeneic recipient rats: virus titers in the salivary gland of allogeneic and syngeneic recipients reached 4.61 +/- 0.33 and 4.00 +/- 0.37 log(10) PFU/g tissue, respectively, at 14 days post-infection (p = 0.015). The augmented viral replication in allogeneic recipients was confirmed by an increase in the number of RCMV antigen-positive macrophages present in tissue sections of the salivary gland. CONCLUSIONS: Acute lung allograft rejection and allogeneic spleen cell stimulation enhance CMV replication in the salivary gland of rats. Various responses to allogeneic antigens occurring in the process of acute allograft rejection could be risk factors for post-transplant CMV replication and infection.     

A Synergistic Effect Between PG490-88 and Tacrolimus Prolongs Renal Allograft Survival in Monkeys

This study was undertaken to determine if PG490-88 and tacrolimus (Tac) act synergistically to prevent renal allograft rejection in monkeys and to explore possible mechanisms of synergy between these agents. MHC-mismatched renal allografts were transplanted into cynomolgus monkeys after bilateral nephrectomy. Recipients were divided into the following groups: (i) no treatment; (ii) PG490-88 (0.03 mg/kg); (iii) Tac (1 mg/kg); (iv) PG490-88 (0.01 mg/kg) + Tac (1 mg/kg) and (v) PG490-88 (0.03 mg/kg) + Tac (1 mg/kg). Through synergy PG490-88 and Tac inhibited anti-CD3/PMA-induced T-cell proliferation and IFN-gamma expression in vitro. Tac monotherapy only marginally prolonged survival (27 +/- 3.2 days), while the combination of PG490-88 and Tac significantly prolonged graft survival to a median of 99 days (PG490-88 at 0.03 mg) and 38.5 days (PG490-88 at 0.01 mg/kg). Prolonged survival correlated with inhibited IgM production as well as reduced T-cell infiltration, IL-2 protein expression and NF-AT/NF-kappaB activity. We conclude that PG490-88 and a subtherapeutic dose of Tac significantly prolong renal allograft survival in monkeys through the synergistic inhibition of T-cell activation and a decrease in IFN-gamma production and NF-AT/NF-kappaB activity.     

Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW/Jms

Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct.     

Validity of a newly developed ultraminiature cordless EMG measurement system.

To verify validity of a newly developed ultraminiature EMG measurement system (BMS), the ability of BMS to record masseteric EMG was compared with that of a conventional polygraph system (PG) in the daytime. Effective distance between the transmitter unit and receiver unit of BMS was also examined. Subjects were 12 healthy volunteers. During tapping, maximum clenching, and gum chewing of all subjects, distinct bursts were observed in EMG recorded by BMS as well as PG. RMS values of maximum clenching measured by BMS and PG showed a linear and significant correlation, and there was no significant difference between the data of BMS and PG. When distance between the transmitter unit and receiver unit of BMS was 100 cm or less, no artifact signal was observed. Having obtained these findings suggesting ability for precise measurement in the daytime, we are planning to use BMS in home sleep studies in the next step.     

A case of aberrant left pulmonary basal aneurysm arising from the descending aorta]

A 65-year-old man was referred to our hospital because of fever and abnormal shadow in the left lung. An aortogram revealed a large artery arising from the descending aorta supplying the left basal segment and, which then flowed into the pulmonary vein. This artery had an aneurysm and 30 mm in diameter. Bronchography showed compression of the left basal branch. A clinical diagnosis of an aberrant left pulmonary basal aneurysm arising from descending aorta was made, and left lower lobectomy was performed, because of the danger apprehension of the aneurysmal rupture. The procedure was successful. There are only 15 case reports of a systemic artery supplying the lung with normal bronchial branch in Japan. Differences of this anomaly from pulmonary sequestration were discussed.     

Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.