Intraspecific variation in morphology of spiny pollen grains along an altitudinal gradient in an insect-pollinated shrub.

Intraspecific variations in pollen morphological traits are poorly studied. Interspecific variations are often associated with pollination systems and pollinator types. Altitudinal environmental changes, which can influence local pollinator assemblages, provide opportunities to explore differentiation in pollen traits of a single species over short distances. The aim of this study is to examine intraspecific variations in pollen traits of an insect-pollinated shrub, Weigela hortensis (Caprifoliaceae), along an altitudinal gradient. Pollen spine phenotypes (length, number and density), pollen diameter, lipid mass (pollenkitt) around pollen grains, pollen production per flower and pollinator assemblages were compared at four sites at different altitudes. Spine length and the spine length/diameter ratio of pollen grains were greater at higher altitudes but not correlated with flower or plant size. Spine number and density increased as flower size increased, and pollen lipid mass decreased as plant size increased. Bees were the predominant pollinators at low-altitude sites whereas flies, specifically Oligoneura spp. (Acroceridae), increased in relative abundance with increasing altitude. The results of this study suggest that the increase in spine length with altitude was the result of selection favouring longer spines at higher-altitude sites and/or shorter spines at lower-altitude sites. The altitudinal variation in selection pressure on spine length could reflect changes in local pollinator assemblages with altitude.

Dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features.

A 35-year-old Japanese man was admitted to the National Cancer Center, Tokyo, Japan, in December 2000, with a 2-month history of pain around the left thigh. Radiographs showed a poorly demarcated osteolytic lesion with focal mineralisation and endosteal scalloping in the left proximal femur. Biopsy showed a proliferation of highly anaplastic cells without any cartilaginous component. A wide excision of the left proximal femur with a replacement by endoprosthesis was carried out in February 2001 after treatment with methotrexate and 20 Gy radiation therapy. Pathological examination of the surgical specimen showed a focus of low-grade chondrosarcoma and the coexistence of telangiectatic osteosarcoma-like features. The patient was diagnosed with dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features. Lung metastasis appeared in July 2001 despite an adjuvant chemotherapy including methotrexate, cis-platinum and doxorubicin. The latest follow-up study in June 2004 showed multiple lung metastases. Establishing a definitive diagnosis of dedifferentiated chondrosarcoma may be difficult with limited small biopsy specimens. Dedifferentiated chondrosarcoma should be included in the differential diagnosis of osteolytic tumours with focal calcification and endosteal scalloping even if an extraosseous tumour component is not identified.

Acyclovir improves recovery rate of facial nerve palsy in Ramsay Hunt syndrome.

OBJECTIVE: Although the antiviral agent, acyclovir, is currently employed for the treatment in Ramsay Hunt syndrome, the benefit of acyclovir on facial nerve is still unknown and remains controversial. This study was designed to evaluate the effect of acyclovir in facial nerve recovery in Ramsay Hunt syndrome. METHODS: To evaluate drug effect on facial nerve function, evaluation of the facial voluntary movement and nerve excitability testing were performed. We have used an infusion therapy of acyclovir in combination with a high dose of steroid (AS), which was started within 7 days of onset of facial nerve palsy in 91 patients with Ramsay Hunt syndrome. The results were compared with those of 47 patients whose therapy was steroid alone started within 7 days of onset. RESULTS: Out of 91 patients treated with AS, nerve exitability was good in 68 (75%), while it was poor in 17 and absent in six. Of 47 patients treated with steroid alone, nerve exitability was good in 25 (53%), while it was poor in 11 and absent in 11. There was statistically significant difference between AS and steroid therapy in the posttreatment degree of nerve function. Complete recovery to grade I in facial voluntary movement was attained in 82 of 91 patients (90%) in the AS therapy, while out of 47 patients treated with steroid alone complete recovery to grade I was attained in only 30 (64%). A statistically significant difference in the recovery rate of facial nerve function was induced between AS and steroid therapy. CONCLUSION: The AS therapy was proved to keep good degree of nerve function indicated with nerve excitability testing and improve recovery rate of facial nerve in Ramsay Hunt syndrome. Based on this study, we now believe that the AS therapy is an advisable treatment modality to improve the recovery rate of facial nerve function in Ramsay Hunt syndrome.

Development of growth hormone and adrenocorticotropic hormone deficiencies in patients with prenatal or perinatal-onset hypothalamic hypopituitarism having invisible or thin pituitary stalk on magnetic resonance imaging.

A gradual loss of anterior pituitary hormones is suspected in patients treated with irradiation due to brain tumors. Development of growth hormone deficiency (GHD) with age has been documented in patients with idiopathic GHD. A gradual loss of adrenocorticotropic hormone (ACTH) secretion has been also shown in a patient with severe GHD and an invisible pituitary stalk on magnetic resonance imaging (MRI). The purpose of this longitudinal and cross-sectional study was to evaluate the gradual loss of growth hormone (GH) and ACTH in a homogeneous group of patients with hypopituitarism. Twenty-eight patients (23 males, 5 females) from four hospitals were diagnosed as having prenatal or perinatal-onset hypothalamic hypopituitarism. They had an abnormal pituitary stalk on MRI (invisible in 18 patients, thin in 10 patients) without any other organic disease of the brain. Each patient had GHD upon initial evaluation. Height (n=20) was analyzed as standard deviation score (SDS). Longitudinal (n=8) and cross-sectional (n=28) GH secretion capacity was evaluated by GH peaks, in response to insulin tolerance test (ITT) and growth hormone releasing factor test (GRF test). Longitudinal (n=10) and cross-sectional (n=28) ACTH secretion capacity was evaluated by cortisol peaks in response to ITT. Height SDS decreased each year in all the untreated patients after birth. GH peaks decreased gradually with age. Longitudinal data showed decreased GH peaks with age in seven out of eight patients using ITT and in all four patients using GRF tests. Cortisol peaks also decreased gradually together with signs and symptoms for adrenal deficiency such as general fatigue. Cortisol peaks of less than 414 nmol/L (15 microg/dl) in response to ITT were seen in 24% of the tests before age 10 and 56% before age 25. In conclusion, GHD and ACTH deficiency developed gradually in patients with prenatal or perinatal-onset hypothalamic hypopituitarism who had invisible or thin pituitary stalks examined by MRI.

Cardiac functional and structural alterations induced by endotoxin in rats: importance of platelet-activating factor.

OBJECTIVE: In this study, we evaluated the time course of the alterations in left ventricular (LV) dimensions, LV wall thickness, and LV systolic function in rats with endotoxemia by using echocardiography as well as myocardial histopathologic assessments. Our second goal was to examine whether pretreatment with a platelet-activating factor (PAF) antagonist would ameliorate the lipopolysaccharide (LPS)-induced cardiovascular collapse during the early phase. DESIGN: A prospective, controlled, in vivo animal laboratory study. SETTING: Research laboratory at a university. SUBJECTS: Male, Wistar rats (8-9 wks old; n = 83). INTERVENTIONS: In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein also was catheterized for the administration of drugs. LPS (2 mg/kg) derived from Klebsiella pneumoniae or physiologic saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with an 8- to 13-MHz transducer. MEASUREMENTS AND MAIN RESULTS: LPS administration immediately induced progressive hypotension. The maximal hypotensive response was observed at 10 mins after LPS infusion with mean arterial pressure decreasing from 119 +/- 2 to 56 +/- 3 mm Hg (p < .001). LV end-diastolic internal dimensions decreased from 6.4 +/- 0.1 to 3.1 +/- 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced compared with control rats. LV end-systolic dimensions also decreased dramatically from 3.5 +/- 0.2 to 0.5 +/- 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45 +/- 1% to 84 +/- 2% (p < .001) at 30 mins after LPS and remained elevated compared with control rats. LV wall thickness increased strikingly from 15 mins until 2 hrs after LPS infusion. Pathologic studies demonstrated marked congestion of capillaries and mild edema in the LV myocardium. The hematocrit increased after the administration of LPS. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma concentrations of epinephrine and norepinephrine. There was no elevation of concentrations of nitrite and nitrate. Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated LV functional and structural changes. TCV-309 administration reduced the LPS-induced adrenergic activation and hemoconcentration. CONCLUSIONS: The hypotension that occurred during the initial phase of LPS-induced shock was accompanied by LV functional and structural alterations. The marked increase in LV wall thickness can be ascribed to the congestion of capillaries and edema in the LV myocardium. Pretreatment with a PAF antagonist reduced LPS-induced alterations. PAF may play a pivotal role during the initial phase of LPS-induced cardiovascular responses.

Effect of long-term, low-dose acyclovir suppressive therapy on susceptibility to acyclovir and frequency of acyclovir resistance of herpes simplex virus type 2.

We have examined the susceptibility to acyclovir and frequency of acyclovir-resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive therapy (200 mg/day) for 1-9 years and 15 patients naive to acyclovir. Suppressive therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of acyclovir, were subjected to the acyclovir susceptibility test, and 155 clones isolated in the presence of acyclovir were analysed for the mechanisms of resistance to acyclovir. There were no significant differences in the susceptibility to acyclovir, the frequency of acyclovir-resistant virus and the ratio of thymidine kinase-deficient viruses in acyclovir-resistant viruses between the two groups. The frequency of acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with genital herpes with or without acyclovir-suppressive therapy. Thus, the low dose of acyclovir suppressive therapy did not affect the susceptibility to acyclovir or increase the frequency of acyclovir-resistant viruses in the genital lesions.

Hepatocyte growth factor attenuates collagen accumulation in a murine model of pulmonary fibrosis.

We investigated the in vivo effects of recombinant human hepatocyte growth factor (HGF) on epithelial cell proliferation in normal mouse lung and on the repair process that follows bleomycin-induced lung injury. Intratracheal administration of 100 micrograms of rhHGF to C57BL/6 mice led to proliferation of bronchial and alveolar epithelial cells as indicated by an increased number of cells staining for proliferating cell nuclear antigen (PCNA). The effect of HGF on the lung repair process was examined by administration of 100 micrograms of rhHGF on Day 3 and Day 6 after intratracheal injection of bleomycin to mice. We found that HGF significantly attenuated collagen accumulation induced by bleomycin as determined by quantitation of hydroxyproline content and by scoring of the extent of fibrosis. To explore the potential mechanisms involved in the beneficial effects of HGF, we performed in vitro studies with A549 pulmonary epithelial cells and found that HGF enhanced cell surface plasmin generation, expression of u-PA activity, and cell migration. In summary, HGF has potent in vivo and in vitro effects on epithelial cells, which suggests it may have a role in the therapy of pulmonary fibrosis.

Chlorella accelerates dioxin excretion in rats.

We investigated the effects of Chlorella on fecal excretion of polychlorinated dibenzo-p-dioxin (PCDD) congeners and polychlorinated dibenzofuran (PCDF) congeners in Wistar rats administered the rice oil that caused Yusho disease, as a substitute for purified dioxin. The rats were fed 4 g of a control diet or a 10% Chlorella diet containing 0.2 mL of the rice oil once during the 5-d experimental period. The amounts of PCDD and PCDF congeners excreted in feces from d 1 to 5 in the group fed 10% Chlorella were 0.2-11.3 and 0.3-12.8 times greater (P < 0.05), respectively, than those of the control group. We then investigated the fecal excretion of PCDD and PCDF congeners from d 8 to 35 in rats administered 0.5 mL of the rice oil. Rats consumed the basal diet for 1 wk. After 1 wk, they consumed either the basal diet or the 10% Chorella diet. The fecal excretions of PCDD and PCDF congeners in the group fed 10% Chlorella were 0.3-3.4 and 0.5-2.5 times greater (most, P < 0.05), respectively, than those of the control group. Thus, the fecal excretions of PCDD and PCDF congeners were greater in rats fed Chlorella. These findings suggest that the administration of Chlorella may be useful in preventing gastrointestinal absorption and for promoting the excretion of dioxin already absorbed into tissues. Moreover, these findings suggest that Chlorella might be useful in the treatment of humans exposed to dioxin.

26-cholesterol hydroxylase in rat corpora lutea: A negative regulator of progesterone secretion.

From a subtracted cDNA library of rat luteal tissue, where cDNA fragments in functional luteal tissue were subtracted from those in regressing luteal tissue, a cDNA clone corresponding to 26-cholesterol hydroxylase (P450(C26)) was obtained. It is known that P450(C26) catalyzes the conversion of cholesterol to 26-hydroxycholesterol, which blocks cholesterol utilization in the cell, and that 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catalyzes the conversion of progesterone to an inactive steroid, 20alpha-dihydroprogesterone (20alpha-OHP). Thus, using pseudopregnant rats as a model, physiological cooperation of P450(C26) and 20alpha-HSD in the reduction of progesterone release toward the end of the luteal phase was evaluated. Levels of P450(C26) and 20alpha-HSD mRNA were examined in corpora lutea from pseudopregnant rats by Northern blot or reverse transcription-polymerase chain reaction or both. P450(C26) mRNA was ubiquitously expressed in corpora lutea, and its expression increased toward the end of pseudopregnancy, while 20alpha-HSD was expressed in all corpora lutea on Day 16 (Day 0 = the day of after cervical stimulation) but not detected before Day 10. An inhibitor of 20alpha-HSD, STZ26 (D-homo-16-oxa-4-androstene-3,16alpha-dione), was administered at various doses to rats from Day 12 to 20, effectively suppressing the elevation of 20alpha-OHP in a dose-dependent manner but not the depletion of progesterone completely. The expression of P450(C26) mRNA was increased as STZ26 dose increased, which negatively correlated with the progesterone levels. These results strongly suggest that P450(C26) cooperated with 20alpha-HSD in the reduction of progesterone release from the rat luteal tissue at the end of the functional luteal phase.

The importance of the plasma amino acid molar ratio in patients with biliary atresia.

BACKGROUND: Plasma amino acid patterns and the therapeutic benefits of amino acid supplements are not examined well in postoperative patients with biliary atresia (BA). This study aimed to investigate profiles of the amino acid molar ratio, the Fischer molar ratio (FR, valine + leucine + isoleucine/phenylalanine + tyrosine), and relationships with other nutritional parameters and to assess the efficacy of enteral nutrient preparations for hepatic failure in patients with BA. METHODS: In study 1 profiles of FR were analyzed in 24 patients with BA (aged 3 to 12 years) in the postoperative period and compared with liver function tests and anthropometric measures. In study 2 10 patients with BA with a FR < 2.0 were begun on a dietary regimen consisting of an ordinary diet supplemented with a branched-chain amino acid-enriched elemental diet. RESULTS: Study 1: In jaundiced patients with total bilirubin levels > 2.0 mg/dL the FR remained below 2.0 throughout the period of observation, in contrast with nonjaundiced patients. The FR was closely related to the levels of serum albumin and plasma rapid turnover proteins and anthropometric measures as well as biochemical data reflecting intrinsic liver function. Study 2: A significant increase in rapid turnover proteins and improvement of general status were noted concurrently with an increase of the FR. CONCLUSIONS: The FR indicates a combination of nutritional status and intrinsic liver function in post-operative BA patients. The FR is a useful parameter in conducting nutritive therapy with a branched-chain amino acid-enriched elemental diet in those patients.

The cDNA sequences of equine antioxidative enzyme genes Cu/Zn-SOD and Mn-SOD, and these expressions in equine tissues.

The entire cDNA sequences were determined by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) techniques for equine copper/zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) through the use of total RNA extracted from the testis of an adult Thoroughbred. The results revealed a protein coding region for equine Cu/Zn-SOD with bases totaling 465 bp, accompanied by an estimated 154 residues of amino acids. As for equine Mn-SOD, its coding region contained a total of 669 bp and an estimated 222 residues of amino acids. Further, the expression of Cu/Zn-SOD and Mn-SOD genes were confirmed in the equine tissues by RT-PCR and in situ hybridization.

Colonoscopic diagnosis of lymphoid hyperplasia causing recurrent intussusception: report of a case.

This paper describes a 6-year-old boy with recurrent ileocecal intussusception due to lymphoid hyperplasia in the terminal ileum, which was diagnosed preoperatively by colonoscopy. At the age of 3 years, he developed diarrhea and a tender abdominal mass. He was diagnosed as having intussusception by ultrasound and was treated by hydrostatic barium enema. After resolution, he had three recurrent episodes of intussusception. A contrast barium enema revealed a small mass in the ileocecal region. Colonoscopy showed several exaggerated folds of the terminal ileum and a biopsy showed lymphoid hyperplasia. Because the repeated intussusception seemed to have been caused by the lymphoid hyperplasia in the terminal ileum, he underwent an ileocecal resection without any subsequent recurrence. Based on the above findings, we conclude that a colonoscopy may thus be useful both for diagnosing lymphoid hyperplasia in the terminal ileum as a cause of recurrent intussusception and for deciding how to manage it.

Long-term effect of alpha-glucosidase inhibitor on late dumping syndrome.

Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an excessive insulin secretion after a sharp rise in plasma glucose. Several treatments, including operation, dietary fibre and somatostatin, have been attempted to relieve dumping symptoms. These treatments take effect through modulation of plasma insulin and glucose levels, but their efficacy is still under consideration. Alpha-glucosidase inhibitor attenuates the postprandial increase of plasma glucose levels and is widely used for treatment of non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of alpha-glucosidase inhibitor on late dumping syndrome has been reported by some studies with test meals. The purpose of this study was to evaluate a long-term effect of alpha-glucosidase inhibitor treatment with ordinary meals in late dumping patients with NIDDM because administration of alpha-glucosidase inhibitor is only ethically allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were orally administered alpha-glucosidase inhibitor, acarbose (50 or 100 mg), three times a day before each meal for 1 month. Diurnal changes of plasma glucose, insulin and pancreatic glucagon levels were compared before and after the alpha-glucosidase inhibitor treatment. All patients had late dumping-related symptoms, such as weakness, palpitation and dizziness before the induction of alpha-glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma glucose levels from hyperglycaemia at the same time as dumping symptoms. These late dumping-related symptoms disappeared and a rapid change of plasma glucose and insulin levels were attenuated after the alpha-glucosidase inhibitor treatment. These data suggest a long-term therapeutic efficacy of alpha-glucosidase inhibitor for late dumping patients.

Continuous infusion of beta-amyloid protein into the rat cerebral ventricle induces learning impairment and neuronal and morphological degeneration.

To investigate the toxicity of beta-amyloid protein, a component of the senile plaques in Alzheimer's disease, it was infused into the cerebral ventricle of rats for 14 days by a mini-osmotic pump. Performances in the water maze and passive avoidance tasks in beta-amyloid protein-treated rats were impaired. Choline acetyltransferase activity significantly decreased in the hippocampus both immediately and 2 weeks after the cessation of the infusion. However, the learning impairment was recoverable 2 weeks after cessation of the infusion. Both immediately and 2 weeks after the cessation of the infusion, glial fibrillary acidic protein immunoreactivity increased. Furthermore, beta-amyloid protein altered the staining in the nuclei of hippocampal cells for only 2 weeks after the cessation. These results suggest that beta-amyloid protein produces some damage in the central nervous system in vivo.

[Selenium methylation and toxicity mechanism of selenocystine].

Selenium is an essential trace element and a toxicant for animals. Selenocystine, a selenium-containing amino acid, is one of the chemical forms in which selenium exists in food. This review summarized recent studies on the toxicity mechanism of selenocystine in experimental animals. Hepatotoxicity is caused by repeated oral administration of selenocystine. Selenocystine is metabolized by reduced glutathione and/or glutathione reductase to hydrogen selenide via selenocysteine-glutathione selenenyl sulfide. The hydrogen selenide is a key intermediate in the selenium methylation metabolism of inorganic and organic selenium compounds. Accumulation of the hydrogen selenide resulting from inhibition of the selenium methylation metabolism, detoxification metabolic pathway of selenium, is found in animals following repeated administration of a toxic dose of selenocystine. The excess of the hydrogen selenide produced by inhibition of the selenium methylation metabolism contributes to the hepatotoxicity caused by selenocystine.

The use of a hypoxic cell radiosensitizer AK-2123 gave no improvement in thermoradiotherapy combined with hydralazine.

An electron-affinic compound, AK-2123, and the anti-hypertensive agent, hydralazine, were combined with radiation and hyperthermia for treatment of murine SCC-VII tumours. Hydralazine markedly decreased tumour perfusion while AK-2123 had no influence on it. Hydralazine enhanced the tumouricidal effects of hyperthermia alone and in combination with radiation. AK-2123 provided a radiosensitization which was significant only in tumours irradiated without supplementary hyperthermia. The greatest tumour response was achieved when thermoradiotherapy was combined with hydralazine alone; the additional use of AK-2123 with this treatment combination did not further increase the effect. It is concluded that hydralazine plus heat virtually eliminated a hypoxia-related radioresistance in tumours, thus removing the requirement for AK-2123 administration.

Prophylactic treatment of cytomegalovirus infection with traditional herbs.

Hot water extracts of four traditional herbs, Geum japonicum, Syzygium aromaticum, Terminalia chebula and Rhus javanica, which have been shown to have anti-herpes simplex virus (HSV) activity in vivo, were examined for anti-cytomegalovirus (CMV) activity in vitro and in vivo in this study. They inhibited replication of human CMV and murine CMV (MCMV) in vitro. These anti-CMV activities in vivo were examined in an MCMV infection model using immunosuppressed mice. Mice were subcutaneously treated with various doses of cyclosporine, and immunosuppression and MCMV infection were monitored by suppression of antibody production and virus yield in the lung, respectively. Each herbal extract was orally administered to mice treated with 50 mg/kg of cyclosporine from a day before intraperitoneal infection, and the efficacy of herbs was evaluated by the reduction in the virus yield in the lung. Among them Geum japonicum, Syzygium aromaticum, and Terminalia chebula significantly suppressed MCMV yields in lungs of treated mice compared with water treatment. Efficacy of oral treatment with 750 mg/kg per day of Geum japonicum extract was similar to that of the intraperitoneal administration of 2 mg/kg per day of ganciclovir in increasing the body weight of infected mice and reducing the virus yield in the lungs. These herbs may be beneficial for the prophylaxis of CMV diseases in immunocompromised patients.

[Pneumonia due to the Chinese medicine pien tze huang].

A 47-year-old woman who had been treated for chronic hepatitis was admitted to our hospital because of a productive cough that developed after she took Pien Tze Huang. A chest X-ray film revealed a reticular shadow in both lower lung fields and pulmonary-function tests showed a restrictive pattern. Pien Tze Huang was discontinued and the patients condition was observed. No other treatment was given, and the patient's symptoms, laboratory data, chest roentgenographic findings, and pulmonary function gradually improved. The result of a leukocyte migration inhibition test was positive for Pien Tze Huang, and the final diagnosis was drug-induced pneumonia due to Pien Tze Huang. We know of no previous report of Pien Tze Huang-induced pneumonia.

Protective effect of an acidic glycoprotein obtained from culture of Chlorella vulgaris against myelosuppression by 5-fluorouracil.

An acidic glycoprotein prepared from a culture of Chlorella vulgaris (CVS) was examined for its protective effect on 5-fluorouracil(5FU)-induced myelosuppression and indigenous infection in mice. Subcutaneous administration of CVS greatly reduced the mortality of non-tumor-bearing mice given a high dose of 5FU, and could increase the LD50 value of 5FU for these mice. After 5FU treatment, indigenous infection developed probably as a result of the impairment of the host defense system. CVS reduced the incidence of indigenous infections and this effect was attributable to the acceleration of recovery from 5FU-induced myelosuppression. Early recovery of hematopoietic stem cells, or cells responding to interleukin-3 or granulocyte/macrophage-colony-stimulating factor, was especially observed in the bone marrow of CVS-treated mice on days 4-9 after the injection of 5FU. When tumor-bearing mice were given CVS during treatment with 5FU, CVS prolonged the survival of mice without affecting the antitumor activity of 5FU. In addition, CVS was itself shown to exert an antitumor effect. These results suggested that CVS may be beneficial for the alleviation of side-effects in cancer chemotherapy without affecting the antitumor activity of the chemotherapeutic agent.