Portal vein thrombosis treated using danaparoid sodium and antithrombin III.

A 45-year-old man under treatment for liver cirrhosis (LC) due to chronic hepatitis C and hemophilia A was seen in our emergency room because of a 10-kg weight gain in the previous week due to ascites. Portal vein thrombosis (PVT) was detected with computer tomography (CT) and ultrasonographic (US). Danaparoid sodium (DS) and antithrombin III (AT III) were administrated and doppler US images showed improvement of portal venous blood flow. DS or AT III may be safe and alternative therapies for PVT.

Mn-SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and gamma-rays regulating expression of the BCL-2 family proteins, COX-2 and p21.

ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and gamma-rays, but the details have not been clarified. We examined the effect of transfection of Mn-SOD antisense on apoptosis by 5-FU, PLM, CDDP and gamma-rays using nu/nu mice. After inoculation of Mn-SOD antisense-transfected SCC cells into the subcutis of each mouse's back, they slowly multiplied to form tumors sized 1,460 +/- 70 mm(3) at day 60, while control vector-transfected SCC cells rapidly multiplied, with a mean tumor size of 2,330 +/- 220 mm(3). Inversely, mice in the Mn-SOD antisense group survived longer (mean survival duration 94.4 +/- 12.7 days) compared to those in the empty vector group (67.3 +/- 6.8 days). After treatment with 5-FU (5 microg/day), PLM (50 microg/day), CDDP (10 microg/day) and gamma-rays (2 Gy/day), mean survival times were largely prolonged, to 126.3 +/- 22.7, 123.0 +/- 22.1, 136.3 +/- 24.0 and 143.0 +/- 20.8 days, respectively, while mean survival times in the empty vector group were 91.7 +/- 14.8, 85.7 +/- 13.3, 97.5 +/- 16.0 and 100.7 +/- 17.1 days, respectively. Immunohistologically, tumors in the Mn-SOD antisense group revealed additional nick end-labeled cells compared to those in the empty vector group. In comparison, strong expression of Bax, Bak and p21(waf1/cip1) and suppressed expression of Bcl-2, Bcl-X(L) and COX-2 were observed in the Mn-SOD antisense group and the expression pattern of these proteins was the inverse in the empty vector group. The increased expression of these proapoptotic proteins appeared to be p53-independent because p53 protein expression was not increased in the antisense group. These immunohistologic results were supported by Western blotting of each protein. In conclusion, Mn-SOD antisense transfection is advantageous for apoptosis induction of SCC cells by anticancer drugs and gamma-rays through induction of proapoptotic Bcl-2 family proteins and suppression of antiapoptotic protein expression.

Unusual primary lung neoplasms.

Bronchial carcinoids and hamartomas are, respectively, the most common malignant and benign unusual primary lung neoplasms. These tumors are often asymptomatic but can cause central airway obstruction. Helical computed tomographic and radionuclide scintigraphic advances in their detection and evolution, together with newer interventional bronchoscopy techniques such as neodymium:yttrium-aluminum-garnet laser phototherapy and cryotherapy, represent important improvements in the diagnosis and management of patients with such tumors.

Regulation of aquaporin-4 expression in astrocytes.

Aquaporin-4 (AQP4), a mercury-insensitive water channel protein, is abundant in the central nervous system and is localized in astrocytes and ependymal cells. AQP4 is speculated to maintain the homeostasis of intracellular and extracellular water in the brain, but little is known about the mechanism of induction of its expression. To investigate the expressional regulation of AQP4, we analyzed changes in its expression during chemically induced differentiation of embryonal carcinoma cells (P19) to neuronal and astrocytic cells, and during the cell cycle of glioma cells. After exposure to retinoic acid for 4 days AQP4 mRNA expression started at the initiation of astrocytic differentiation of P19 cells at 6 days, and increased markedly by 21 days. AQP4 expression was parallel to that of GFAP, a marker intermediate filament of astrocytes. In glioma cell lines, AQP4 mRNA was not detected in the growing phase, but was induced when the cell cycle was arrested at G0/G1 by transient expression of p21. Although quiescent astrocytes in the G0/G1-phase cultured under the serum-free condition exhibited a high expression of AQP4, serum supplement moved them to the S-phase and markedly decreased the AQP expression. These results suggest that AQP4 expression may be induced not only at the initiation of astrocytic differentiation of neural stem cells, but also at the G0/G1-phase during the cell cycle of astrocytes.

[Usefulness of ramosetron hydrochloride on nausea and vomiting in CMF or CEF therapy for breast cancer].

The inhibitory effect of ramosetron hydrochloride (Ram), a 5-HT3 receptor antagonist, on nausea and vomiting occurring in CMF or CEF therapy as a pre- or postoperative adjuvant chemotherapy or chemotherapy for recurrent cancer was evaluated in 34 patients with breast cancer. On days 1 and 8, the patients received Ram (0.3 mg) concomitantly with these agents intravenously and were observed for nausea and vomiting to evaluate the inhibitory effect. Food intake was observed at the same time. On day 1, there was moderate to severe nausea in one patient and vomiting in two patients, while results for 32 of 34 patients (94.1%) were classified as "excellent". On day 8, no moderate or severe nausea was seen, but vomiting occurred in one patient; the results of 33 patients (97.1%) were classified as "excellent". Even when considering only 12 patients who had experienced nausea or vomiting on chemotherapy, 11 showed an "excellent" response on day 1. Moreover, no patient received any additional dose of an anti-emetic drug within 24 hours of Ram administration. Food intake decreased to less than 50% of the baseline in three patients on day 1 and four patients on day 8. Administration of Ram to breast cancer patients on CMF or CEF therapy is thus concluded to be useful in the inhibition of nausea and vomiting.

Fine structure of rat liver, adrenal, testis and seminal vesicle in experimental emaciation.

Experimentally emaciated male rats were produced by a bilateral electrical destruction of a part of hypothalamus. In a typical case, when the animals were fixed by perfusion, dissected, and organs weighted, the body weight became 1/2 of the control in 10 weeks. The weight of the viscera (including the subserous fat) was more decreased in comparison with the controls than the weight of the body wall (including extremities and the subcutaneous fat). The weight of the liver became 1/3, the adrenal 1/4, the testis 1/6 and the seminal vesicle 1/19 of the control. Light and electron microscopic examinations showed atrophy and fatty degeneration in the liver, atrophy of the zona reticularis in the adrenal, failure of spermatogenesis, especially at its spermiogenetic stage, in the testis, and an apoptosis in glandular epithelial cells of the seminal vesicle. Two weeks after partial hypothalamus destruction, the weight of the body wall was more decreased in comparison with the controls than the weight of the viscera. Possible pathophysiological mechanisms are discussed. An experimental model of electron microscopical research of apoptosis are presented.

[A case of cutaneous pseudallescheriosis resembling sporotrichosis].

An 83-year-old man with aplastic anemia and steroid induced diabetes mellitus developed multiple nodules with pus on the back of his right hand and forearm. He had been treated with a daily dose of 30mg prednisolone for 2 months. These lesions had appeared a month before his visit. The histopathological findings revealed dermal abscesses containing hyphal structures, lymphocytes, histiocytes and giant cells. Grocott-Methenamine stain demonstrated abundant fungal elements. In culture, colonies grow rapidly and produce a white, cottony mycelium which later becomes gray in color. Microscopically, ovoid and pyriform conidia are produced at the ends of long slender conidiophores. On PCA agar, synnemata with small conidal heads developed at 37 degrees C but cleistothecia did not appear. The patient did not respond to itraconazole therapy, however, with hyperthermic treatment, the eruptions gradually healed. Based on these findings, this fungal infection was diagnosed as pseudallescheriosis.

The expression of urokinase type plasminogen activator is a novel prognostic factor in dukes B and C colorectal cancer.

Urokinase type plasminogen activator (u-PA) secreted by cancer cells is considered to play a key role in promoting invasion and metastasis of cancer cells. This study was designed to evaluate the expression and prognostic value of u-PA in Dukes B and C colorectal cancer. u-PA expression was investigated in 57 Dukes B or C colorectal cancers using a monoclonal antibody against u-PA. u-PA expression was mainly observed on the cytoplasm of cancer cells, and was associated with relapse, especially hematogenous metastasis (p=0.025, the chi2 test). Patients with high u-PA expression had a lower rate of DFS (9/22 events) compared to those with low u-PA expression (6/35 events) (p=0.061, log-rank test). This study demonstrated that u-PA expression might be a novel prognostic factor in Dukes B and C colorectal cancer.

Effects of preparations of Chinese medicinal prescriptions on digestive enzymes in vitro and in vivo.

The effects of preparations of Chinese medicinal prescriptions on the activities of digestive enzymes were investigated. The starch dextrinizing activity of pancreatin was inhibited by Keishi-bukuryo-gan, Sho-seiryu-to, Hachimi-jio-gan, Unsei-in and Keishi-ka-shakuyaku-to to below 40% of the control activity. Hachimi-jio-gan and Sho-seiryu-to, in particular, lowered the activity to 4% and 24% of the control activity, respectively. The protein digestive activity of pancreatin was lowered by Keishi-bukuryo-gan, Oren-gedoku-to, Ryutan-shakan-to, Tokaku-joki-to, Yokuinin-to and Hange-shashin-to, to 56 to 70% of the control activity. To investigate the effects of the preparations of Chinese medicinal prescriptions on digestive enzymes in vivo, 600 mg (185 kBq) of 125I-egg white albumin were administered orally to rats 30 min before the administration of 100 mg of Tokaku-joki-to or Oren-gedoku-to. The radioactivity which transferred to the blood was less in the animals pre-fed these prescriptions than in the control animals, indicating that the digestion of egg white albumin was delayed in the presence of the prescriptions.

Polysaccharide of Astragali radix enhances IgM antibody production in aged mice.

The effect of Astragali Radix (AR) on IgM antibody production in mice of various ages (10 weeks, 36 weeks and 60 weeks) was examined. The antibody production levels in the 36- and 60-week-old mice were significantly decreased to about 70 and 60% of that in the 10-week-old mice. The enhancement effect of a crude polysaccharide AR fraction on the antibody production was nil in the 10-week-old mice, but significant enhancement effects were observed in the 36- and 60-week-old mice, compared to the age-matched control. Two polysaccharides active in the enhancement of the IgM antibody production in the aged mice were isolated from the high molecular weight fraction of AR by cetavlon precipitation, ion-exchange and gel permeation chromatography. The molecular masses of these polysaccharides were calculated by HPLC in salt solution. Only one major peak was observed for each, and their molecular masses were estimated to be 1.2 x 10(4) and 2.2 x 10(4). The major components of these polysaccharides were neutral carbohydrates (89.3 and 95.5%), followed by uronic acid and protein; glucose was the predominant sugar component.

Protective effect of astragali radix by oral administration against Japanese encephalitis virus infection in mice.

We investigated the protective effect of Astragali Radix (AR) by oral administration against Japanese encephalitis virus (JEV) infection in mice, the pharmacological effects of AR extracts (AE) in different origin, and the chemical composition of the AEs. A protective effect was demonstrated in all four AEs used, however, the effective grade for each one was different. In the control group, an increase of hemagglutination inhibition (HI) antibody titer was observed in all mice surviving 25 d after JEV inoculation. However, the increase of HI antibody titer was not observed in some animals administered an AE. In the control group, the rate of HI antibody positive mice was 90% 3 d after JEV inoculation, while the four groups which received the AE had a 30-60% positive rate. In mice which received the AE, the peritoneal exudate cell (PEC) numbers increased significantly compared to the control group. The predominant cell population of PECs in mice receiving the AE was macrophages, and in the PEC, the active oxygen (AO) production was high. From these results, we propose that the protective effect of AE by oral administration is based on a non-specific mechanism during the early stage of infection, before shifting to antibody production, and that macrophages play an important role in this resistance to JEV infection, e.g., by inducing the production of AO. In the chemical composition of each AE, carbohydrate was the major component.

Protective effect of Astragali Radix by intraperitoneal injection against Japanese encephalitis virus infection in mice.

We examined the protective effect of Astragali Radix extracts (AE) by intraperitoneal injection against Japanese encephalitis virus (JEV) infection in mice. A protective effect was observed by all four samples of AE used. However, the degree of effectiveness for each AE was different. The observed survival rates of the groups injected with sample A (from Shanhsi, Japanese name Sansei-syo) and sample D (from Hokkaido) extracts were higher than 80% at 21 d after JEV inoculation. The groups injected with sample B (from Hopei, Japanese name Kahoku-syo) and sample C (from Hsiahsi, Japanese name Sensei-syo) extracts had a 60% survival rate. The increase in hemagglutination inhibition antibody titer was negligible in mice that survived 21 d after JEV inoculation. The antiviral effect of AE was examined by plaque assay in vitro, but no antiviral effect was shown. In mice injected with AE, the peritoneal exudate cell (PEC) numbers increased significantly, compared to the control. In these PEC, active oxygen production was also high. Also the group as a whole displayed a high survival rate against JEV infection, these were so strong. From these results, we propose that the protective effect of AE is dependent on a non-specific mechanism during the early stage of infection, before it shifts to antibody production, and that PEC plays an important role.

[Chemical evaluation and consideration on the traditional drug "ULUUS" (2)].

Traditional patent medicine named "ULUUS" has been regarded to be the first Dutch precipitation with a western name in Japan. It was found that this drug consists of Rhubarb mainly, and it contained high amounts of effective compounds as for the traditional sample that has been stored for more than 100 years. In fact, a dose of this medicine was supposed to cause a laxative effect.

[Chemical evaluation and consideration on the traditional drug "ULUUS" (1)].

Traditional medicine named "ULUUS" is regarded to be the first Dutch precipation with a western name in Japan. It was found that this drug consists of Rhubarb (originated from Rheum sp.). Although it is still uncertain whether it was made only of Rhubarb by being kneaded hard into the monotonous square form, we could not find out any other ingredients except Rhubarb, on the bases of our chemical analysis.

PUVA irradiation restores altered binding patterns of lectins in psoriatic epidermis.

We examined a series of biopsy specimens obtained from lesional skin in five psoriatic patients receiving topical PUVA treatment to see the effect of PUVA on epidermal cell membrane glycoconjugates by fluorescent staining techniques using lectins as surface markers. In psoriatic epidermis, Ulex europaeus agglutinin and Concanavalin A depicted only cytoplasmic patterns and did not show the plasma membrane fluorescence that was normally seen in nonpsoriatic skin. Following PUVA treatment, these altered staining patterns gradually normalized, with the appearance of the plasma membrane fluorescence. Restoration of the membrane staining tended to precede improvement in clinical and histologic features of psoriasis, suggesting that normalization of the altered profiles of membrane glycoconjugates is one of the beneficial effects of PUVA irradiation on psoriatic epidermis.