Effects of recombinant human erythropoietin therapy on blood coagulation and fibrinolysis system.

This study was designed to examine the effects of recombinant human erythropoietin (rHuEPO) therapy on blood coagulation and fibrinolysis in patients scheduled for elective heart surgery and undergoing preoperative autologous blood donation. Twenty-seven patients were studied, of whom 16 patients received rHuEPO (group E) and 11 patients no rHuEPO therapy (group N). The patients in group E were given 6000 units of rHuEPO intravenously every other day, three times a week, beginning from two weeks prior to the operation. In both groups, 400 ml of blood was collected preoperatively for predeposit once a week for two weeks, and the self-donated blood was returned to the patient intra- and postoperatively. Blood samples were drawn at the beginning of the study, immediately before the operation and two weeks after the operation. They were analyzed to assess blood coagulation, fibrinolysis, platelet function and vascular endothelial cell function, in order to examine the effects of the administration of rHuEPO. No significant difference was observed between the two groups in the degree of changes in these parameters following the operation. As enhancement of blood coagulability and fibrinolytic activity was evident postoperatively in both groups, changes in these parameters during the preoperative autologous blood donation period were also assessed excluding the postoperative data. Again, there was no significant intergroup difference in any of the markers evaluated. It was concluded that the administration of rHuEPO during preoperative autologous blood donation is unlikely to affect coagulation and fibrinolysis.

Expression of metallothionein in colorectal cancers and synchronous liver metastases.

The aim of this study is to clarify whether the expression of metallothionein (MT) is related with the malignant potential in primary colorectal cancer and/or synchronous liver metastasis. Immunohistochemical staining for MT was performed on the specimens of adenocarcinoma of the colon and rectum and its liver metastases in 34 patients treated with curative surgery, respectively. Expression of MT was compared with clinicopathological variables and patient survival. In patients with primary colorectal cancer, positive expression was found in 7 of 34 (20.6%) patients, but MT was not detected in any of the cases of liver metastases (0%; p = 0.0111). In the primary tumor, positive MT expression was significantly associated with a higher degree of lymph node involvement (mean +/- SD: 48.4 +/- 33.8 vs. 18.6 +/- 24.4% in MT-positive and MT-negative tumors, respectively; p = 0.0122). The survival rate in the patients with MT-negative tumors was significantly better than that in those with MT-positive tumors as primary sites (p = 0.0198). MT expression in colorectal cancer may be a potential marker affecting lymph node metastases and may be a predictor of a poor prognosis, particularly in patients with synchronous liver metastases.

Preoperative diagnosis of ileal lipoma by endoscopic ultrasonography probe.

The occurrence of tumor in the small intestine is relatively rare. It has been demonstrated that lipoma of the ileum is a cause of intussusception. We report a 59-year-old man admitted to our hospital for lower abdominal pain. Diagnosis of intussusception was made by abdominal x-ray and ultrasonography. Enema contrast studies revealed ileocolic intussusception. Colonoscopy revealed a tumor with an submucosal tumor (SMT)-like head and coil-spring appearance in the ascending colon. Endoscopic ultrasonography (EUS) revealed a hyperechoic submucosal lesion with features compatible with lipoma. Subsequently, this was confirmed histopathologically after resection. To our knowledge, this is the first report of preoperative diagnosis of ileal lipoma by EUS.

Expression and characterization of Xenopus type I collagen alpha 1 (COL1A1) during embryonic development.

A cDNA encoding Xenopus type I collagen alpha 1 (Xenopus COL1A1) has been isolated from an ovary cDNA library. The COL1A1 cDNA is approximately 5.7 kb pairs and encodes 1447 amino acids. The putative COL1A1 polypeptide shares high identities of amino acid sequence with other vertebrate COL1A1 proteins. The level of Xenopus COL1A1 transcripts was increased markedly in the posterior region of the embryo at the tail-bud stage, then gradually spread to the anterior region. Histological observations of the tail-bud embryos showed that COL1A1 was mainly expressed in the inner layer of the posterior dorsal epidermis exposed to the somite mesoderm, except for in the dorsal fin. Less intense signals were also detected in the outer layer of the dorsal epidermis and dermatome. The expression of COL1A1 was increased in posteriorized embryos resulting from treatment with retinoic acid but decreased in hyper-dorsalized embryos resulting from lithium chloride treatment. These results suggest that COL1A1 is a major component of the dorsal dermis exposed to the somite in Xenopus embryos, but its expression is not related to the temporal sequence of somite segregation.

Concurrent expressions of metallothionein, glutathione S-transferase-pi, and P-glycoprotein in colorectal cancers.

PURPOSE: Because the status of the inherent drug-resistance of colorectal cancers remains obscure, human colorectal cancers with no neoadjuvant therapy were retrospectively investigated regarding the expression of three drug-resistant proteins: metallothionein, glutathione S-transferase-pi, and P-glycoprotein. METHODS: Paraffin-embedded tissues of 130 colorectal cancers (Dukes A, 20; B, 49; C, 41; D, 20) obtained by surgical resections from 1982 to 1989 were used. The three proteins were immunostained by the streptavidin-biotin complex method. The immunostaining was judged to be positive if more than 5 percent of cells showed positive staining by use of cell analysis system. The data were compared with clinicopathologic features (Dukes A-D) and patients' prognosis (Dukes AC). RESULTS: Metallothionein, glutathione S-transferase-pi, and P-glycoprotein were positively expressed in 91 (70 percent), 30 (23 percent), and 98 (75 percent), respectively. A total of 120 (86 percent) expressed at least one drug-resistant protein. No intergroup differences were observed between positive and negative expressions of the proteins and their clinicopathologic features except tumor location. Rectal cancers positively expressed P-glycoprotein and three proteins more frequently. Twenty-six (20 percent), 65 (50 percent), and 21 (16 percent) cancers positively expressed one, two, and three proteins, respectively. The disease-free survival rates of patients with Dukes A through C cancer with positive staining for one, two, and three proteins were 100, 94, and 83 percent (at 1 year); 100, 72, and 51 percent (at 3 years); and 94, 66, and 38 percent (at 5 years), respectively (Kaplan-Meier with log-rank test; P = 0.016). In the multivariate Cox analysis, age, Dukes stage, tumor size, and glutathione S-transferase-pi were independent prognostic factors. CONCLUSIONS: The patients with concurrent expression of drug-resistant proteins in their cancers had worse prognoses. Examining drug-resistant proteins in colorectal cancers may be useful in selecting adjuvant chemotherapy and in predicting prognosis more accurately.

Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/ tropical spastic paraparesis.

We report here the results of therapeutic trials in 200 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) conducted in our department between 1986 and 1993. Motor disability grades were improved by more than one grade in 69.5% (91/131) of patients by oral administration of prednisolone, 50% (3/6) by eperisone hydrochloride only, 43.8% (7/16) by blood purification (lymphocytapheresis and plasmapheresis), 40.0% (2/5) by intrathecal injection of hydrocortisone, 30.0% (3/10) by intravenous injection of high-dose methylprednisolone, 23.3% (10/43) by interferon-alpha (intramuscular injection and inhalation), 22.2% (2/9) by azathioprine, 20.0% (4/20) by high-dose vitamin C, 16.0% (4/25) by erythromycin, 12.5% (3/24) by salazosulfapyridine, 11.8% (2/17) by mizoribine, 7.1% (1/14) by fosfomycin, and 6.3% (1/16) by thyrotropin releasing hormone. No critical side effects of these therapies were seen with the exceptions of one patient with adult respiratory distress syndrome due to cytomegalovirus infection and one patient with drug-induced hepatitis/hepatic failure. Selection of these treatments for patients with HAM/ TSP must be considered on the basis of age, sex, disease severity and complications to reduce adverse events and to improve quality of life. Although the results were a synopsis of different treatments given to 200 patients with HAM/ TSP as an open trial, we consider this the first report of a large-scale therapeutic trial in patients with HAM/TSP. The results of this study indicate that immunomodulatory therapies have some beneficial effects in HAM/TSP, and the functions of these agents are related to the pathophysiology of this disease.

Role of preoperative transcatheter arterial oily chemoembolization for resectable hepatocellular carcinoma.

To clarify the effect of preoperative transcatheter arterial oily chemoembolization (TAOE) for resectable hepatocellular carcinoma (HCC) on long-term survival after curative resection, we retrospectively evaluated 60 patients with and 68 patients without preoperative TAOE. Although there was no substantial difference in the clinical backgrounds between the two groups, the 5-year survival rate was lower for the patients with preoperative TAOE than for those without TAOE: 24% versus 63%, respectively (p < 0.05). A worse survival rate was particularly observed for the cirrhotic patients with TAOE than for those without TAOE: 35% and 72% at 4 years, respectively (p < 0.01). As the cause of death, liver failure and gastrointestinal bleeding were more frequent in the patients with TAOE (13.3% versus 1.5%;p < 0.05). Although the TAOE seemed to retard intrahepatic recurrence during the first 1.5 years after operation (1.7% versus 10.3%;p < 0.05), the overall cancer death rate was similar between the two groups (18.3% versus 11.8%). Therefore we suggest that preoperative TAOE must not be performed for resectable HCC as a routine procedure, particularly in patients with cirrhosis. A prospective randomized trial is warranted to elucidate the merits and demerits of preoperative TAOE for surgically resectable HCC.

Primary jejunal adenocarcinoma masquerading as a primary ovarian malignancy.

Primary adenocarcinoma of the jejunum which accounts for only approximately 3% of all gastrointestinal tract malignancies, is distinctly unusual. Ovarian metastasis from a jejunal cancer is extremely rare. It has significant therapeutic and prognostic implications to differentiate primary ovarian carcinoma from metastatic disease to the ovary. A 49-year-old Japanese woman presented with intermittent nausea, vomiting, and palpable abdominal mass. Pelvic examination and imaging studies revealed a huge ovarian tumor, suspicious for malignancy. Upper GI series and barium enema were unremarkable. Exploratory laparotomy was done for presumed primary ovarian malignancy. Mucinous adenocarcinoma of the right ovary, measuring 25 x 18 x 12 cm, without other intraabdominal dissemination was found. Exploration of the upper abdomen revealed an annular constriction of the jejunum 30 cm distal to the ligament of Treitz. Partial jejunectomy with end-to-end anastomosis was done. Metastatic ovarian cancer from the primary jejunal adenocarcinoma was confirmed microscopically. Although small bowel malignancy is uncommon, small bowel follow-through examination or enteroclysis may be indicated in patients with positive stool for occult blood who have no abnormality in the upper gastrointestinal series and barium enema. In addition to the imaging studies, thorough exploration of the entire abdominal cavity is necessary at ceiliotomy in patients with ovarian malignancy to distinguish primary ovarian cancer from metastatic disease to the ovary.

[New oral contrast material for gastrointestinal MR examination--green tea mixed with sodium alginate].

We found incidentally the stomach filled with the material of high signal intensity on T1 weighted images. The material was a mixture of green tea and sodium alginate (drug for peptic ulcer). We proved that T1 and T2 were significantly shortened by the mixture in the experimental study. This was successfully used for the patients.

Effect of arginine on gramicidin S biosynthesis by Bacillus brevis.

Effects of arginine on gramicidin S (GS) biosynthesis were investigated by growing Bacillus brevis ATCC 9999 in a synthetic medium consisting of 10 g fructose, 0.15 g l-proline, 1.3 g l-histidine, 1.3 g l-glutamine, 0.5 g L-methionine, 1 g L-phenylalanine and six mineral salts per liter. Supplement of 3 g/liter L-arginine to the medium, especially at the logarithmic phase of growth, enhanced the cell growth and GS production. Twice supplement of 3 g/liter arginine at the beginning and middle logarithmic phase of growth gave much more GS production than any once supplement, but the soluble GS synthetase extractable by lysozyme digestion was remarkably decreased. However, the decrease of enzyme by arginine seemed to be merely an apparent phenomenon, because GS-synthesizing ability of the cell was strongly enhanced by arginine and the enzyme which was not extracted by lysozyme digestion could efficiently be solubilized by ultrasonic homogenization. In the soluble fraction of cells grown in an arginine-added synthetic medium, no arginine was detected, but a large amount of ornithine was accumulated. When L-ornithine, instead of L-arginine, was added to the synthetic medium, cell growth and GS production was stimulated with increase of its concentration without decrease in the soluble enzyme activity.

NAD glycohydrolase activity in the liver of rats fed on excess leucine diet and low or high protein diet.

In rats fed for 2 weeks on a 10% casein diet supplemented with 5% leucine, the hepatic NAD content was lowered when comparing with the control rats pair-fed on the 10% casein diet. The hepatic NAD glycohydrolase [EC 3.2.2.5] activity increased by 25% in the leucine-supplemented diet-fed rats and by 40% in the nicotinic acid-free diet-fed rats. The hepatic NAD glycohydrolase activity in the rats fed on the nonprotein diet freely for 1 week was elevated by 60% compared to the rats fed on the 18% casein diet. The hepatic NAD content in the former animals was significantly lower than that in the latter. The 70% casein diet caused changes in neither hepatic NAD content nor NAD glycohydrolase activity. These results indicated an inverse relationship between hepatic NAD content and NAD glycohydrolase activity.