Phase II Study of Orally and Rectally Administered Tegafur in Liver Metastases from Gastric Carcinoma

Twenty-four eligible and evaluable patients with measurableliver metastases from gastric cancer were treated with oralor rectal Tegafur. Objective responses were seen in 8 of thepatients (33.3%), lasting between 1.5 and 15 months. The mediansurvival period was 10 months for the responders and 2.6 monthsfor non-responders. No complete response was observed. The survivalof responders was significantly longer than that of non-responders(p<0.01). Toxicity was mild and consisted principally ofgastrointestinal and hematological side effects. No centralnervous system toxicity was seen.     

Serratia marcescens lung abscess in a child with autoimmune neutropenia

Though Serratia marcescens is widely known to be the cause of serious infections in immuno-compromised hosts, a lung abscess caused by S. marcescens is very rare. A 5 year old boy who had previously been diagnosed with autoimmune neutropenia was admitted because of fever and cough. In spite of treatment with some antibiotics, he developed a lung abscess. Aspiration of the pleural fluid revealed that S. marcescens was the pathogen of the disease. In the present case, there were feasible risk factors for the development of Serratia lung abscess namely neutropenia, chronic gingivitis at the time, and treatment with cyclosporin A. There are no reported cases of autoimmune neutropenia which developed into a S. marcescens lung abscess in the literature as far as we can determine.     

Aluminum alters cell viability and axonal transport system in Alzheimer's disease pathogenic mutation-bearing cells

Background: We previously reported that pulse exposure of cultured rat neurons to aluminum‐maltol resulted in an abnormal distribution of both neurofilament‐L (NF‐L) and fast axonal transported proteins. It was also found that the presenilin 1 (PS1) missense mutation and aluminum affected early neuronal development of the mouse brain. It has been reported that the presenilin (PS) mutation alters neurite outgrowth, and the axonal transport of the amyloid precursor protein (APP)/PS complex is mediated by kinesin. The present study hypothesizes that aluminum might modulate axonal transport and neurite outgrowth in APP/PS mutant‐bearing cells. Methods: We treated SH‐SY5Y cells and HEK293 cells bearing FAD mutations with aluminum‐maltol (Al‐mal) (0, 250 µm , 500 µm , 1 mm , 2 mm ) for 1 h, followed by propidium iodide (PI) and Calcein‐AM staining, live and dead assay, double staining of NF‐L/synaptophysin or APP/JNK interacting protein‐1 (JIP‐1) 3 days after treatment. Results: Apoptosis was induced Al‐mal treatment in a dose‐dependent manner in all cell lines. In SH‐SY5Y cells bearing PS1 mutations, there were no differences in the rate of cell viability, except for morphological changes observed by Calcein‐AM staining. The distribution of NF‐L and synaptophysin was modified by PS1 mutations and aluminum, suggesting that the PS mutation induces neuronal dysfunction by disturbance of the axonal transport system. The APP mutation‐bearing cell lines showed significant induction of apoptosis compared to that of wild‐type cells. Oxidative stress might thus influence cell viability in APP mutation‐bearing cells. Enhancement of JIP‐1 staining may reflect a disturbance of the intracellular axonal transport system, as well as compensation due to apoptotic changes. Conclusion: The present results, when taken together, show that aluminum alters cell viability and the axonal transport system in FAD pathogenic mutation‐bearing cells.     

Increased IL-6 and IL-8 in bronchoalveolar lavage fluids (BALF) from patients with sarcoidosis: correlation with the clinical parameters

A variety of cytokines have been implicated in the pathogenesis of pulmonary sarcoidosis, but the exact roles of IL-6 and IL-8 are not yet clear. We studied these cytokine levels in BALF from patients with pulmonary sarcoidosis, idiopathic pulmonary fibrosis (IPF), systemic screlosis (SSc) with interstitial lung disease and control subjects. IL-6 and IL-8 levels were significantly elevated in sarcoidosis, IPF and SSc with interstitial lung disease compared with control subjects. Subjects with sarcoidosis had significantly increased levels of both cytokines compared with controls when the cytokine values were corrected by the total albumin content and the two cytokine levels correlated with each other (r=0.876). BALF IL-6 levels correlated with percent lymphocytes and percent CD3⁺ cells. Moreover, when sarcoidosis patients were divided into three groups, those who needed steroid therapy or had progressive disease showed increased cytokine levels in BALF over stable or improved patients. These observations suggest that locally derived IL-6 and IL-8 were increased in sarcoidosis and correlated with activity of this granulomatous lung disease.     

Well-developed infant with hypoxic-ischemic encephalopathy associated with EEG burst suppression and subcortical leukohypodensity on CT scan

In the prediction of neurological sequelae after hypoxic-ischemic encephalopathy (HIE) in the newborn, the electroencephalogram (EEG) burst suppression pattern (BS) and subcortical leukomalacia can mean grave neurodevelopmental problems will develop. This study presents an infant with HIE associated with BS and subcortical leukohypodensity (SLH) on computed tomography scan. At first her neurodevelopmental outcome was considered poor, but unexpectedly she showed good development in 32 months follow-up. The findings of BS and SLH do not always result in a poor neurodevelopmental outcome, if the subsequent clinical state and EEG return to normal at an early stage.     

Sulphate conjugation enhances reversible binding of drug to human serum albumin

Abstract— Reversible binding of model compounds, their conjugated metabolites (sulphates and glucuronides), and also derivatives of the compounds, to human serum albumin (HSA) has been examined using an ultrafiltration method. p-Nitrophenol (P-NP), α-naphthol (α-NA) and β-naphthol (β-NA) were used as model compounds. Reversible binding of 500 μm p-NP sulphate to 4% HSA (96·6 ± 0·35%, mean ± s.d. n = 3) was significantly higher (P < 0·001), whereas reversible binding of p-NP glucuronide to 4% HSA (33·3 ± 9·82%) was much lower (P < 0·001) than that of 500 μm p-NP (90·9 ± 0·60%). Reversible binding of 500 μm p-NP glucopyranoside to 4% HSA (25·8 ±2·82%) was comparable with that of the glucuronide, with which it is structurally similar. In contrast, reversible binding of 500 μm p-NP phosphate, an anionic compound like p-NP sulphate, to 4% HSA (61·4 ± 5·28%) was significantly lower than that of p-NP (P < 0·001). Similar results were observed in reversible binding of sulphates of α-NA and β-NA. Significant differences of dissociation constants for HSA binding were observed between the parent compound (α- or β-NA) and its sulphate conjugate (P < 0·005 for α-NA and α-NA sulphate, P < 0·001 for β-NA and β-NA sulphate), but the number of binding sites was the same. These results indicated that sulphate conjugation enhances reversible binding of a parent compound to HSA by increasing the binding affinity of the parent compound to HSA. This enhancement appeared to be advantageous for preventing random distribution of this metabolite to organs in the body.     

Multiple Forms of Catalase From Normal Human Liver, Hepatomas and Tumor-Bearing Livers

Multiple forms of catalase from normal human liver, hepatomas,fetal liver and tumor-bearing livers were examined by the methodof DEAE-cellulose column chromatography. In normal adult humanliver, three peaks were found by addition of 0.05 M, 0.1 M and0.2 M NaCl in 0.01 M phosphate buffer (pH 7.4), and no catalaseactivity was detected in the unadsorbed fraction. On the otherhand, in human hepatomas, fetal liver and tumor-bearing livers,an existence of the unadsorbed catalase fraction was ascertained.It is suggested that the presence of the unadsorbed catalaseon DEAE-cellulose may be ascribed to the dedifferentiated natureof liver tissues. Furthermore, no difference in molecular sizebetween the unadsorbed catalase and the adsorbed one was confirmedby gel filtration on Sephadex G-200. ^*This study was presented at the 9th Annual Meeting of the JapaneseHepatological Society, Tokyo, July, 1973, and 32nd Annual Meetingof the Japanese Cancer Association, Tokyo, October, 1973.     

Radiographic and Endoscopic Features of Colonic Ulcers in Systemic Lupus Erythematosus

The radiographic and endoscopic features of the colonic ulcers during the course of a case of systemic lupus erythematosus are illustrated. Barium enema revealed the "collar button" type of penetrating ulcers in the left half of the colon and endoscopy demonstrated multiple round- or oval-shaped discrete ulcers, so-called "punched-out" ulcers with pale mucosa. These findings are compared with those of the reported cases of systemic lupus erythematosus and ulcerative colitis. Steroid and 6-mercaptopurine therapy was effective in this case.     

Dissociative identity disorder and childhood trauma in Japan

A series of 15 cases of dissociative identity disorder (DID) was reviewed using an 85-item checklist. The cases resembled those seen in North America, particularly with respect to clinical symptoms, alter personalities and history of childhood trauma. The authors suggest that DID may be as common in Japan as in North America.