Release of cholecystokinin from rat cerebral cortex in vivo: role of GABA and glutamate receptor systems

Using cortical cups in chloralose-urethanized rats, the in vivo release of cholecystokinin-like immunoreactivity (CCK-LI) from cerebral cortex was examined. Resting levels of cholecystokinin-like immunoreactivity ranged from 20 to 30 pg/20 min sample. The addition of potassium (40 mM) in excess, resulted in a highly significant elevation in the levels of CCK-LI in the cortical superfusate. Deletion of calcium and the substitution of cobalt (10 mM), resulted in a significant reduction in both resting release and the release otherwise evoked by the addition of potassium. Focal electrical stimulation of the cortex (20 Hz), resulted in a significant (1.9 +/- 0.2-fold, n = 8) increase in the levels of CCK-LI. The addition of glutamate (10(-6)-10(-4) M) of kainic acid (10(-8)-10(-6) M), also resulted in significant elevations in the levels of CCK-LI. The co-administration of a putative glutamate receptor antagonist, kynurenic acid (10(-4) M) resulted in a significant reduction in the levels of release otherwise evoked by the addition of glutamate, but not by electrical stimulation. The addition of GABA (10(-5)-10(-3) M) resulted in a dose-dependent decrease in the resting release of CCK-LI, and the release evoked by glutamate. Picrotoxin (10(-6)-10(-4) M), resulted in a highly significant increase in the levels of CCK-LI in the cortical effluent. These results are consistent with a tonic GABAergic inhibition of CCK-releasing neurons. The treatment of the animal with diazepam (30 mg/kg, i.p.) also resulted in a significant reduction in resting release and the release otherwise evoked by focal cortical stimulation.     

Analysis of the circumstances at the end of life in children with cancer: Symptoms, suffering and acceptance

BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer.     

A case of autoimmune hepatitis needed to be differentiated from EBV hepatitis, in that the histology of liver biopsy specimen was useful for diagnosis]

A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted to our hospital because of cholestasis and elevation of liver enzymes for 2 months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA, hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth muscle antibody. The histology of her liver biopsy specimen revealed interface hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis. She was treated firstly with methylprednisolone pulses, then will prednisolone p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced because of her abnormal immune pathology. All abnormal laboratory parameters improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC became negative after 4 months. The histology of liver biopsy specimen was useful for the diagnosis of AIH in such a difficult case needed to be differentiated from EBV hepatitis.     

99mTc(V)-DMSA and99mTc-MDP uptake and no67Ga-citrate uptake in a case of primary pulmonary leiomyosarcoma

Tumor scintigraphy with 67Ga-citrate, 99mTc(V)-DMSA and 99mTc-MDP were performed on a patient with rare primary pulmonary leiomyosarcoma. While 67Ga-citrate accumulation to the tumor was not recognized, 99mTc(V)-DMSA and 99mTc-MDP scintigraphy showed relatively intense localization of the tracers in the lesion, and were very useful in suggesting the characteristics of the tumor.     

The diagnosis and treatment of esophageal perforations resulting from nonmalignant causes

Esophageal perforations are extremely difficult to diagnose and treat. We report herein our results of a review of 26 patients with esophageal perforation which were spontaneous in 11, iatrogenic in 11, and caused by a foreign body in 4. Surgical treatment was performed in 7 of the patients with spontaneous rupture, but the remaining 19 patients were treated conservatively. The abnormality was found by plain radiography (X-ray) in 22 (85%) of the 26 patients, and by computed tomography (CT) in all 13 patients who underwent this procedure. The detection rates by esophagography and esophagoscopy were 100%, or all of 25 patients examined, and 60%, or 9 of 15 patients examined, respectively. Of 12 patients with underlying diseases, 4 (33%) died after the perforation, whereas only 1 (7%) of 14 patients without any underlying disease died. Postoperative empyema developed in all of 3 patients treated by intraoperative unfixed intrathoracic drainage (UID), but in none of the 4 treated by fixed intrathoracic drainage (FID). Conservative treatment achieved satisfactory results for spontaneous esophageal ruptures confined to the mediastinum, and for iatrogenic perforations and esophageal perforations caused by foreign bodies, provided there was no serious underlying disease such as advanced cirrhosis. Moreover, intraoperative FID proved useful in helping to prevent postoperative empyema.     

Low-pressure Pneumoperitoneum for Laparoscopic Surgery Using a Disposable,Flexible Abdominal Wall Retractor

Abstract: Since April 1991, we have studied 160 patients who had had a successful laparoscopic cholecystectomy. Nine patients who presented with chronic cholecystitis with severe local adhesion and who were also considered to require a longer operative time were selected as suitable candidates for this procedure. They were successfully treated under a zero- to four-mmHg low-pressured pneumoperitoneum procedure combined with total abdominal wall lifting using a disposable, flexible vinyl tube retractor. This method enabled exactly the same clear laparoscopic vision as is possible in the routinely-used high-pressure pneumoperitoneum even in the marginal portions of the abdominal cavity. Moreover, it facilitated early reinsufflation after the cauterization-produced smoke was exhausted, which minimized the operative time and reduced the surgeon's anxiety concerning the maintenance of a sufficiently airtight condition. We believe that this low-pressure pneumopeqitoneum procedure also benefits the poor-risk patient who has restricted cardiopulmonary function, especially during advanced laparoscopic surgery which requires a longer operative and anesthetic time.     

Production of IL-6 by T cells from the femoral head of patients with rapidly destructive coxopathy (RDC)

RDC is a syndrome with unknown etiology that causes rapid destruction of a hip joint. We have investigated the production of osteoclast-activating cytokines (IL-6, IL-1α and tumour necrosis factor-alpha (TNF-α)), interferon-gamma (IFN-γ) and IL-8 by T cells in the affected joint. The level of IL-6 produced by the T cell lines (TCL) established from the femoral head was significantly higher than that from patients' or healthy donors' peripheral blood mononuclear cells (PBMC). IL-6 production by the TCL from synovial membrane or from patients' PBMC was also significantly higher than that from healthy donors' PBMC. IL-1α production by the TCL from the femoral head was significantly higher than any of the other groups when all the TCL were used for the analysis. TNF-α production was highest in the TCL from patients' PBMC. The levels of IFN-γ or IL-8 were not significantly different among these four groups. The plasma levels of all these cytokines except for IFN-γ, that was rather lower, in RDC patients were not significantly different from those in osteoarthrosis or trauma patients, or healthy donors. These results suggest that T cells at the affected femoral head, and also synovial membrane to some extent, are involved in bone resorption through the production of IL-6 and probably IL-1α in patients with RDC.     

Immunohistochemical detection of hepatocellular carcinoma in the setting of ongoing necrosis after radiofrequency ablation.

After radiofrequency ablation (RFA), hepatocellular carcinoma undergoes complete necrosis and an ongoing necrosis that is irreversible and characterized histologically by disrupted cell outlines, homogenous cytoplasmic eosinophilia, and preserved nuclear staining, with the cells appearing quite distinct from viable cancer cells. Antibody to detect single-stranded DNA (ssDNA) specifically labeled nuclei in the setting of ongoing necrosis, but not viable tumor cells, whereas human mitochondrial antibody labeled the cytoplasm of viable cells but not cells of ongoing necrosis. The results demonstrate that RFA causes denaturation of both DNA and proteins and that the immunohistochemistry of ssDNA and mitochondrial protein is useful in detection of ongoing necrosis after RFA and provides pathological information on the validity of this procedure.     

The absence of DNA polymerase kappa does not affect somatic hypermutation of the mouse immunoglobulin heavy chain gene

During the immune response to T cell-dependent antigen, somatic hypermutation (SHM) is introduced into immunoglobulin (Ig) genes. The variable region is the target for SHM and it is here that DNA lesions are introduced and mutations are generated. It has been suggested that error-prone DNA polymerase(s) may play an important role in this mutagenesis phase. Recently, DNA polymerase kappa (Polkappa), which belongs to the Y-family of DNA polymerases, was identified. Since a hot spot of SHMs (RGYW motif) is also a hot spot of mutations by human Polkappa, this enzyme was suggested to be an SHM instigator. In order to address the question whether Polkappa is involved in SHM, we immunized Polkappa-deficient mice and analyzed the SHM of the Ig heavy chain gene. We found that the SHM frequency and spectrum were indistinguishable between the Polkappa knockout mice and control mice. These results suggested that Polkappa is not essential for this process.     

Synthesis and ion-coupling reactions of telechelic polystyrene having cyclic onium salt groups

A series of mono- and bifunctional polystyrenes ( 1 c and 1 ′ c ) having 1-methylpyrrolidinium salt end groups were prepared through sequential derivatization, i.e., tosylation and quaternization reactions, of prepolymers having 3-hydroxypropyl groups ( 1 a and 1 ′ a ) produced by end-capping reactions of the relevant living polymers. The 1-methylpyrrolidinium salt end group was found to undergo a selective ring-opening reaction at 100°C by nucleophilic attack of a benzoate counter anion introduced by ion-exchange reaction. The ion-coupling reaction of 1 c and 1 ′ c with poly(styrene-co-acrylate salt) was found to take place upon coprecipitation of an equimolar mixture into methanol to afford ionically linked pseudo-graft and network products, respectively. The subsequent heat treatment, converting the ionic bond into a covalent one, results in branched and crosslinked polystyrene with predetermined structural parameters.