Effects of hypothermal and circulatory arrest on the auditory brainstem response during operation in children

Twenty-two children were monitored by the auditory brainstem response (ABR) during the open chest and/or open heart surgery for cardiac anomalies under the extracorporeal circulation (ECC) with moderate to deep hypothermia. These patients were divided into two groups, namely, the ECC only group (group A: 9 cases) and the total circulatory arrest (TCA) group (group B: 13 cases). The mean age of group A was 36 months and group B was 6.1 months. In group A, moderate hypothermia was conducted with the rectal temperature ranging from 25 degrees C to 30 degrees C, and in group B profound hypothermia was conducted lowering the temperature to 18 degrees C. The ABR recorded at the following points, namely; before inducing anesthesia, before lowering the body temperatures, during the cooling process, at the time of TCA, and during the rewarming process. Accompanying the decrease in body temperature the peak latency of waves I, III and V were markedly prolonged. When the rectal temperature fell to 23 degrees C, the peak latency of each wave was prolonged to about 150% of their precooling values at 36 degrees C. When it fell to 22 degrees C, the ABR disappeared entirely in 16 of 22 cases, and in remaining 6 cases, only I wave was detected. During rewarming, in both the A and B groups, at 24 degrees C, the wave of ABR started to reappear beginning with I waves, and on reaching 26 degrees C, I, III and V waves from became detectable. The peak latency of all waves at rectal temperature of 33 degrees C recovered to almost the same values as these at 36 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable,epigenetic gene silencing: a mammalian cell culture model of gene variegation

Heterochromatin protein 1 (HP1) is a key component of constitutive heterochromatin in Drosophila and is required for stable epigenetic gene silencing classically observed as position effect variegation. Less is known of the family of mammalian HP1 proteins, which may be euchromatic, targeted to expressed loci by repressor-corepressor complexes, and retained there by Lys 9-methylated histone H3 (H3-MeK9). To characterize the physical properties of euchromatic loci bound by HP1, we developed a strategy for regulated recruitment of HP1 to an expressed transgene in mammalian cells by using a synthetic, hormone-regulated KRAB repression domain. We show that its obligate corepressor, KAP1, can coordinate all the machinery required for stable gene silencing. In the presence of hormone, the transgene is rapidly silenced, spatially recruited to HP1-rich nuclear regions, assumes a compact chromatin structure, and is physically associated with KAP1, HP1, and the H3 Lys 9-specific methyltransferase, SETDB1, over a highly localized region centered around the promoter. Remarkably, silencing established by a short pulse of hormone is stably maintained for >50 population doublings in the absence of hormone in clonal-cell populations, and the silent transgenes in these clones show promoter hypermethylation. Thus, like variegation in Drosophila, recruitment of mammalian HP1 to a euchromatic promoter can establish a silenced state that is epigenetically heritable.     

Neutralizing antibody responses to human herpesviruses 6 and 7 do not cross-react with each other, and maternal neutralizing antibodies contribute to sequential infection with these viruses in childhood

Seroprevalence of human herpesvirus 6 (HHV-6) and HHV-7 infections is very high throughout the world, and almost all people are exposed first to HHV-6 and second to HHV-7 in their childhood. However, it is not clear whether the neutralizing (NT) antibody response between each virus is cross-reactive or not. To elucidate the NT antibody response between each virus, 55 serum samples from an adult group (subjects 22 to 88 years old) and 60 serum samples from a young group (subjects 2 to 18 years old) were examined by a dot blot method for detecting viral late antigen. Thirty-nine serum samples obtained from cord bloods and a few serum samples obtained from pediatric patients with exanthem subitum were also examined to assess the maternal transferred NT antibodies against each virus. The NT antibody titers against HHV-7 in the adult group remained high throughout all the individuals, and none were negative. Those against HHV-6 were high values in the young group but low values, including negative values (three samples), in the adult group. These results suggested that the NT antibody response to either HHV-6 or HHV-7 in each individual was specific to each virus and did not cross-react with each other. In the adult group, the NT antibody response to HHV-6 decreased, while that to HHV-7 remained high throughout all the individuals. Maternal transferred NT antibody titers against HHV-7 were higher and remained longer after birth than those of HHV-6, and these findings were in accord with the clinical observation that HHV-6 infection usually occurs earlier than HHV-7 infection.     

Intraosseous epithelioid malignant peripheral nerve sheath tumor of the phalanx. Case report

We report the first case of intraosseous epithelioid malignant peripheral nerve sheath tumor (MPNST) occurring in the phalanx. The patient was a 50-year-old Japanese man with an intramedullary lytic lesion of the proximal phalanx. Microscopically, the tumor was composed of epithelioid cells or polygonal cells, forming large cell nests with central necrosis. Most tumor cells were diffusely and strongly immunopositive for S-100 protein and vimentin, and negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, alpha-smooth muscle actin, and HMB-45. Laminin-positive material was discontinuously demonstrated between the individual tumor cells. Electron microscopy showed prominent external lamina. Our case indicated that laminin is useful for differentiating epithelioid MPNST from metastatic carcinoma and malignant melanoma.     

Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, a cancer-associated retinopathy antigen, possibly related with a better prognosis in a paraneoplastic syndrome

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome, and the recoverin-specific autoantibody is suggested to contribute to the pathogenesis of retinopathy, including apoptosis of retinal cells. Because it is known that CAR(+) cancer patients have a preferable prognosis, we hypothesized that aberrantly expressed recoverin in cancer cells can become a target of cytotoxic T lymphocytes (CTL). Here we tested nine recoverin-derived HLA-A24-binding peptides for their capacity to elicit antitumor CTL. We observed recoverin-specific CTL responses in two HLA-A24(+) CAR(+) cancer patients. In addition, the CTL responses were obtained from three of ten CAR(-) cancer patients and two of six healthy individuals. The CTL precursor frequency of CAR(+) cancer patients and that of CAR(-) cancer patients was higher than that of healthy individuals. Of nine recoverin peptides, R49 (QFQSIYAKF), R49.2 (QFQSIYAKFF), and R64 (AYAQHVFRSF) were discovered to induce the peptide-specific CTL. Taken together, our present data suggest that peripheral activation of recoverin-specific antitumor CTL is likely to contribute to the preferable prognosis of CAR(+) cancer patients. Moreover, in cases other than CAR(+) cancer patients, recoverin may offer the opportunity to design epitope-based immunotherapeutic approaches for treating HLA-A24(+) cancer patients with a recoverin-expressing tumor.     

A Pilon Fracture With Fibular Head Dislocation Treated With the Use of 3D Preoperative Planning: A Case Report and Literature Review

Pilon fractures with intact fibula have been associated with low-energy trauma. However, the compression force onto the ankle joint can damage the tibiofibular linkage as in a Maisonneuve fracture. Herein, we describe a case of a patient who had a pilon fracture (AO type 43 C3.2) without a fibular fracture. Three-dimensional preoperative simulation by reduction with the surface registration technique was performed as the fibular length was intact and there was no reference for the tibial length. The preoperative simulation revealed superior fibular head dislocation and shortening of the distal tibia. After emergency external fixation on the day of arrival, a 2-staged surgery was performed. During the first operation, the fibular head was reduced and the tibial posterolateral fragment was fixed to restore the tibia length. During the second operation, medial and anterolateral fragments were fixed in order to reduce joint surface of the distal tibia. In general, proximal fibular head fractures are easily overlooked. In the case of pilon fractures with severe length shortening of the tibia without a fibular fracture, a proximal tibiofibular injury should be suspected.     

Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells.

The aim of antitumor immunotherapy is to induce CTL responses against autologous tumors. Previous work has shown that fusion of human dendritic cells and autologous tumor cells induce CTL responses against autologous tumor cells in vitro. However, in the clinical setting of patients with colorectal carcinoma, a major difficulty is the preparation of sufficient amounts of autologous tumor cells. In the present study, autologous dendritic cells from patients with colorectal carcinoma were fused to allogeneic colorectal tumor cell line, COLM-6 (HLA-A2(-)/HLA-24(-)), carcinoembryonic antigen (CEA)(+), and MUC1(+) as an alternative strategy to deliver shared colorectal carcinoma antigens to dendritic cells. Stimulation of autologous T cells by the fusion cells generated with autologous dendritic cells (HLA-A2(+) and/or HLA-A24(+)) and allogeneic COLM-6 resulted in MHC class I- and MHC class II-restricted proliferation of CD4(+) and CD8(+) T cells, high levels of IFN-gamma production in both CD4(+) and CD8(+) T cells, and the simultaneous induction of CEA- and MUC1-specific CTL responses restricted by HLA-A2 and/or HLA-A24. Finally, CTL induced by dendritic cell/allogeneic COLM-6 fusion cells were able to kill autologous colorectal carcinoma by HLA-A2- and/or HLA-A24-restricted mechanisms. The demonstration of CTL activity against shared tumor-associated antigens using an allogeneic tumor cell line, COLM-6, provides that the presence of alloantigens does not prevent the development of CTL with activity against autologous colorectal carcinoma cells. The fusion of allogeneic colorectal carcinoma cell line and autologous dendritic cells could have potential applicability to the field of antitumor immunotherapy through the cross-priming against shared tumor antigens and provides a platform for adoptive immunotherapy.     

Importance of thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase expression at the invasive front of T3 rectal cancer as prognostic factors

BACKGROUND/AIMS: We evaluated a relationship between postoperative recurrence and thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) expression at the invasive front of T3 rectal cancer. METHODOLOGY: This study was conducted on 61 patients with T3 rectal cancer who underwent surgically curative resection between 1998 and 2002. Paraffin-embedded sections of these patients were immunostained for TP, DPD and TS. Relationship between expression level of the three factors and postoperative recurrence were evaluated. RESULTS: There was no relationship between expression of DPD or TS in the tumor cells and recurrences. Although no relationship was present between expression of TP in the stromal cells around the invasive front of the tumor and postoperative recurrences, there was a strong correlation between expression of TP in the invasive front of the tumor and postoperative recurrence. Moreover, by multivariate logistic regression analysis, TP expression in the tumor cells was the only independent contributory factor for postoperative recurrences (p = 0.021) with an odds ratio of 8.27. CONCLUSIONS: TP expression at the invasive front of the tumor may be an important prognostic factor for T3 rectal cancer, and patients with such a condition may benefit from intensive chemotherapy.     

Selenium deficiency in a patient with Crohn's disease receiving long-term total parenteral nutrition

We report a case of selenium deficiency in a patient with Crohn's disease on long-term total parenteral nutrition (TPN). She manifested lassitude of the legs, discoloration of the nail beds, and macrocytosis. Since her plasma selenium level was found to be below the measurable level, we diagnosed this case as selenium deficiency. After intravenous administration of sodium selenite, her symptoms were reversed. Careful attention should be paid to selenium deficiency when a patient receives long-term TPN; supplementary administration of selenium via TPN may be required because selenium is often not routinely added to TPN formulations.