Establishment of anti-Epstein–Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection

We describe an experience of a specific immune transfer treatment in a patient with chronic active EBV infection. The patient had low anti-EBV T cell-mediated cytotoxic activity in his peripheral blood mononuclear cells (PBMC), which may have been the primary cause of the disease. An EBV-specific cytotoxic T lymphocyte (CTL) line was established from PBMC obtained from the patient’s sister whose human leucocyte antigens (HLA) are identical to patient's. The patient received three courses of intravenously administered CTL at 3-week intervals. The number of the cells was increased with each course of treatment. After infusion of the T cell line, anti-EBV CTL activity was detected in the patient's PBMC. CTL activity increased markedly after the second course of immune transfer therapy. The amount of EBV DNA in the patient's plasma showed transient but repeated decreases. Serum levels of tumour necrosis factor-alpha (TNF-α), which had elevated before treatment, began to decrease after initiation of treatment. No adverse effects were directly associated with CTL infusions. Despite having previously received a pneumococcal vaccine and prophylactic antibodies, the patient died of infection caused by Streptococcus pneumoniae bacteraemia 27 days after the third infusion. Although the long-term efficacy and safety of this therapy remains to be established, our findings suggest that adoptive transfer of CTL specific for EBV obtained from an HLA-matched donor might be a promising treatment for patients with chronic active EBV infection.     

A Study on HL—A System in Japanese

Two hundred unrelated Japanese individuals were HL-A typed with UCLA Research Tray T3 (Terasaki's Tray), which contains specificities added after the Fifth International Workshop. Phenotype, gene and haplotype frequencies were calculated with standard errors and delta values. HL-A9, HL-A5 and W10 had a higher frequency and HL-A1, 3 and 8 had a lower frequency in Japanese than in Caucasians. The frequent haplotypes were HL-A9-HL-A5, HL-A9-HL-A7 and HL-A2W10. HL-A9-HL-A5 showed very positive high linkage disequilibrium parameter (delta value) and HL-A9-W10 showed negative high value. The sera designated as anti-HL-A, W5 and W15 in the T3 Tray which react identically in Caucasians showed different patterns of reaction when tested in the Japanese population. Five hundred Japanese parous women's sera were tested for cytotoxic antibodies. Some Japanese antisera showed high correlation coefficient values on HL-A2, HL-A9, HL-A10, HL-A11 and HL-A12. The women providing the anti-HL-5 complex sera and their immunizing persons were HL-A typed. These complex sera reactions were compared with the antisera in the T3 Tray. A new group of sera (SN-1), "operationally monospecific" and cross-reacting with W22, was found in the present study. Population and family studies suggested that the sera SN-1 are third in frequency within the second series (phenotypic frequency 17-22%) and show high delta values with HL-A11 in the Japanese population.     

Vitamin D-dependent rickets type I and type II

Two distinct hereditary defects, vitamin D-dependent rickets type I (VDDR I) and type II (VDDR II), have been recognized in vitamin D metabolism. VDDR I is suggested to be a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1α-hydroxylase. Muscle weakness and rickets are the prominent clinical findings. A normal physiologic dose of 1α-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ is sufficient to maintain remission of rickets in this disorder. VDDR II consists of a spectrum of intracellular vitamin D receptor (VDR) defects and is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of vitamin D analogs and calcium supplementation is usually required for the treatment; however, the response to therapy is sometimes variable.     

Alteration of the oral environment in patients undergoing esophagectomy during the perioperative period

Objective:

During the perioperative period, oral ingestion is changed considerably in esophagectomy patients. The aim of this study was to investigate oral environment modifications in patients undergoing esophageal cancer treatments due to changes in dietary intake and swallowing functions.

Material and Methods:

Thirty patients who underwent operation for removal of esophageal cancer in Tokushima University Hospital were enrolled in this study.

Results:

It was found that 1) the flow rate of resting saliva decreased significantly at postoperative period by deprived feeding for one week, although it did not recover several days after oral ingestion began, 2) the accumulation of dental plaque and the number of mutans streptococci in saliva decreased significantly after operation, while both increased relatively quick when oral ingestion began, and 3) the swallowing function decreased significantly in the postoperative period.

Conclusions:

These results suggest that dental professionals should emphasize the importance of oral health care and provide instructions on plaque control to patients during the perioperative period of esophageal cancer treatment.     

Occlusion and brain function: mastication as a prevention of cognitive dysfunction

Summary Research in animals and humans has shown that mastication maintains cognitive function in the hippocampus, a brain area important for learning and memory. Reduced mastication, an epidemiological risk factor for the development of dementia in humans, attenuates spatial memory and causes hippocampal neurons to deteriorate morphologically and functionally, especially in aged animals. Active mastication rescues the stress‐attenuated hippocampal memory process in animals and attenuates the perception of stress in humans by suppressing endocrinological and autonomic stress responses. Active mastication further improves the performance of sustained cognitive tasks by increasing the activation of the hippocampus and the prefrontal cortex, the brain regions that are essential for cognitive processing. Abnormal mastication caused by experimental occlusal disharmony in animals produces chronic stress, which in turn suppresses spatial learning ability. The negative correlation between mastication and corticosteroids has raised the hypothesis that the suppression of the hypothalamic–pituitary–adrenal (HPA) axis by masticatory stimulation contributes, in part, to preserving cognitive functions associated with mastication. In the present review, we examine research pertaining to the mastication‐induced amelioration of deficits in cognitive function, its possible relationship with the HPA axis, and the neuronal mechanisms that may be involved in this process in the hippocampus.     

Acute disseminated encephalomyelitis associated with Mycoplasma pneumoniae infection

An 8 year old girl with acute disseminated encephalomyelitis (ADEM) is described. Elevated serum antibody titers suggested recent Mycoplasma pneumoniae infection. T2-weighted image of magnetic resonance imaging (MRI) disclosed multiple lesions of high signal intensity in bilateral basal ganglia and thalami as well as in the white matter. Postcontrast T1-weighted image revealed an enhanced lesion in the deep white matter. She showed rapid clinical improvement in response to corticosteroid therapy. The lesions had disappeared completely on MRI performed 10 weeks after the onset. ADEM is believed to be a demyelinating disorder of probable autoimmune etiology. MRI findings in this case may support the hypothesis that the primary pathological event is vascular injury and demyelination occurs only as a secondary phenomenon.     

Developmental changes in electroencephalogram for term and preterm infants using an autoregressive model

The purpose of the present study was to clarify the developmental changes of electroencephalogram (EEG) background activity in term and preterm infants that take place with increasing conceptional age (CA) through an autoregressive (AR) model. Polygraphical EEG recordings were obtained from 76 healthy term and preterm infants with a CA ranging between 31 and 40 weeks. Decreases in total power and component power of δ were noted with CA during burst activity (BA) in quiet sleep (QS) and during active sleep (AS). Increases in total power and component power of δ were noted with CA during interburst interval activity (IBIA) of QS. Regression analysis (RA) of the information amount (IA) indicated a negative correlation with increasing CA in AS and in the monopolar EEG tracings Fp1, C3, O1 and O2 in BA, and a positive correlation in O1 in IBIA. Regression analysis of the IA of δ indicated a negative correlation with increasing CA in AS and in Fp1, C3, O1 and O2 in BA, and a positive correlation in O1 in IBIA. Regression analysis of the IA of δ indicated a negative correlation with increasing CA in BA and AS. These results showed that the high voltage slow wave component changed to a low voltage slow one with development in AS and that BA was longer in duration and lower in power with increasing CA, while IBIA was shorter in duration and higher in power. In conclusion, significant developmental changes occur in all derivatives of AS. Even though the EEG of BA and IBIA change separately, they are followed by EEG of QS in a continuous pattern.