A unique sequence of the laminin alpha 3 G domain binds to heparin and promotes cell adhesion through syndecan-2 and -4.

Laminin-5, consisting of the alpha 3, beta 3, and gamma 2 chains, is localized in the skin basement membrane and supports the structural stability of the epidermo-dermal linkage and regulates various cellular functions. The alpha chains of laminins have been shown to have various biological activities. In this study, we identified a sequence of the alpha 3 chain C-terminal globular domain (LG1-LG5 modules) required for both heparin binding and cell adhesion using recombinant proteins and synthetic peptides. We found that the LG3 and LG4 modules have activity for heparin binding and that LG4 has activity for cell adhesion. Studies with synthetic peptides delineated the A3G75aR sequence (NSFMALYLSKGR, residues 1412--1423) within LG4 as a major site for both heparin and cell binding. Substitution mutations in LG4 and A3G75aR identified the Lys and Arg of the A3G75aR sequence as critical for these activities. Cell adhesion to LG4 and A3G75aR was inhibited by heparitinase I treatment of cells, suggesting that cell binding to the A3G75aR site was mediated by cell surface heparan sulfate proteoglycans. We showed by affinity chromatography that syndecan-2 from fibroblasts bound to LG4. Solid-phase assays confirmed that syndecan-2 interacted with the A3G75aR peptide sequence. Stably transfected 293T cells with expression vectors for syndecan-2 and -4, but not glypican-1, specifically adhered to LG4 and A3G75aR. These results indicate that the A3G75aR sequence within the laminin alpha 3 LG4 module is responsible for cell adhesion and suggest that syndecan-2 and -4 mediate this activity.

The role of alpha-galactosylceramide-activated Valpha14 natural killer T cells in the regulation of Th2 cell differentiation.

Valpha14 natural killer T (NKT) cells produce large amounts of both IL-4 and IFN-gamma upon stimulation with a ligand, alpha-galactosylceramide (alpha-GalCer), and play a crucial role in various immune responses, including allergic diseases. Interestingly, Valpha14 NKT cells are not essential for the induction of IgE responses but rather induce suppression of specific IgE production upon activation. The suppression in the IgE production is not detected either in Valpha14 NKT cell-deficient mice or in IFN-gamma-deficient mice. Thus, activated Valpha14 NKT cells are likely to exert a potent suppressive activity on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-gamma. In marked contrast, little regulatory effect of IL-4 produced by Valpha14 NKT cells on Th2 cell differentiation is suggested.

Encapsulated necrosis associated with Behçet's syndrome.

We reported a case of a 45-year-old woman with encapsulated necrosis associated with Behçet's syndrome. The lesions were characterized by multiple, small subcutaneous nodules on the extremities. Histologically, a nodule consisted of degenerative adipocytes encapsulated by fibrous tissue. A membranocystic lesion was also observed in the cavity of the nodule. The patient had a long-term history of Behçet's syndrome and suffered from erythematous subcutaneous nodules, resembling erythema nodosum on the extremities with a tendency to recurrence. These observations indicate that Behçet's syndrome could be implicated in the development of encapsulated necrosis as an underlying disease.

[Roles and problems of nurses taking care of terminally-ill patients at home].

Since May in 1994, we have started to take care of terminally-ill patients at home to support patients who want to die at home and their family. Many patients in the terminal stage become stable temporarily from being back home, and their family are happy to care for them. Their family tend to think that they may well escape death, so they are sometimes confused when patients become worse suddenly. The author learned something important from the visiting care system in connection with two cases. Although case 1 had a short period of time at home and case 2 died in the hospital, their families were satisfied with our system and could accept patient's death without a big problem. It was very important to educate the family about death because it is very difficult to foresee a sudden change in terminal cancer patients. From the nursing standpoint, it remains to consider how to judge the patient's conduct and when to call the doctor. Another problem is whether to inform patients of their cancer or not.

[A consideration in regard to 16 patients died at home].

We had given the service to the patients who desired home care. And now we made inquiries about 16 cases died at home. They were satisfied with our service and death at home. But in regard to the question "If you die at home, Are you satisfied?¿, half the number answered "NO". We should recognize the present condition that we can not fulfill the needs of patients and their families.

SF2446, new benzo[a]naphthacene quinone antibiotics. I. Taxonomy and fermentation of the producing strain, isolation and characterization of antibiotics.

New antibiotics SF2446A1, A2, A3, B1 and B2 have been isolated from the culture of Streptomyces sp. SF2446 and antibiotic SF2446B3 has been obtained by methanolysis of SF2446B1 or B2. SF2446A1, A2 and B1 showed strong inhibitory activities against mycoplasmas and Gram-positive bacteria. Empirical molecular formulae of antibiotics SF2446-A1, A2, A3, B1, B2 and B3 were determined to be C34H35NO15, C26H21NO11, C34H35NO14, C34H35NO14 and C26H21NO10, respectively.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-1. Toxicity of metabolites of miocamycin: acute toxicity of Mb1 in mice.

Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic isolated from a culture broth of Streptomyces mycarofaciens. MOM is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. The object of this study was to evaluate acute toxicity in male and female mice after single oral administration of Mb1, a metabolite of MOM, at a dose level of 5,000 mg/kg as the maximum physically applicable dose. Observations were kept for 1 week after administration. In conclusion, Mb1 exhibited no acute toxicity in present study. The LD0 values were estimated as more than 5,000 mg/kg.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-2. Toxicity of metabolites of miocamycin: acute toxicity of Mb1 in rats.

Acute toxicity studies on miocamycin (MOM), non-crystalline solid, and its metabolite Mb1 were performed in mice in the previous studies. In the present studies, we evaluated acute toxicity of Mb1 in male and female rats after single oral administration at the maximum physically applicable dose of 5,000 mg/kg. Observations were continued for 1 week after treatment. It is concluded that LD0 values of Mb1 were estimated more than 5,000 mg/kg.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-3. Toxicity of metabolites of miocamycin: subacute toxicity of Mb1 in rats.

Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. In the previous study, LD0 values of Mb1 were estimated more than 5,000 mg/kg in male and female rats as Mb1 did not exhibited any lethal toxicity even at the maximum physically applicable dose of 5,000 mg/kg. The object of this study was to examine subacute toxicity in male and female rats after repeated p.o. administration of Mb1 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is concluded that no manifest toxicity was observed in this subacute toxicity study on Mb1 in rats.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-4. Toxicity of metabolites of miocamycin: acute toxicity of Mb2 in mice.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites. At previous study, LD0 values of Mb1 were estimated more than 5,000 mg/kg in male and female mice. The object of this study was to evaluate acute toxicity in male and female mice after single oral administration of Mb2, a metabolite of MOM, at a dose level of 5,000 mg/kg as the maximum physically applicable dose. It is concluded that LD0 values of Mb2 were estimated more than 5,000 mg/kg.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-5. Toxicity of metabolites of miocamycin: acute toxicity of Mb2 in rats.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites. At previous study, LD0 values of Mb1 were estimated more than 5,000 mg/kg in male and female rats. The object of this study was to evaluate acute toxicity in male and female rats after single oral administration of Mb2, a metabolite of MOM. It is concluded that LD0 values of Mb2 were estimated more than 5,000 mg/kg.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-6. Toxicity of metabolites of miocamycin: subacute toxicity of Mb2 in rats.

Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. At previous study, the acute and subacute toxicity of Mb1 and acute toxicity of Mb2 were performed that those metabolites did not exhibit any lethal toxicity even at the maximum physically applicable dose. The object of this study was to examine subacute toxicity in male and female rats after repeated p.o. administration of Mb2 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is, therefore, concluded that Mb2 exerted no toxic effects in this subacute toxicity.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-7. Toxicity of metabolites of miocamycin: acute toxicity of Mb6 in mice.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites. In the present studies, we evaluated acute toxicity and estimated LD50 values of Mb6, one of the main metabolites of MOM, in male and female mice after single oral administration. Observations were continued for 1 week after treatment. The LD50 values were calculated according to Litchfield-Wilcoxon's method. It is concluded that LD50 values of Mb6 were 4,150 mg/kg (3,577.6 approximately 4,814.0 mg/kg) in male mice and 4,000 mg/kg (3,389.8 approximately 4,720.0 mg/kg) in female mice, respectively.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-8. Toxicity of metabolites of miocamycin: acute toxicity of Mb6 in rats.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. In the previous studies, we estimated LD50 values of Mb6 in male and female mice after single oral administration. The LD50 values were 4,150 mg/kg in male mice and 4,000 mg/kg in female mice, respectively. In the present studies, we evaluated acute toxicity and estimated LD50 values of Mb6 in male and female rats after single oral administration. Observations were continued for 1 week after treatment. It is concluded that LD0 values of Mb6 in male and female rats, were estimated more than 5,000 mg/kg as Mb6 did not exhibit any manifest acute toxicity even at the maximum physically applicable dose of 5,000 mg/kg.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-9. Toxicity of metabolites of miocamycin: subacute toxicity of Mb6 in rats.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. It is also known that LD50 values of Mb6 were 4,150 mg/kg in male mice and 4,000 mg/kg in female mice but LD0 values in male and female rats were estimated more than 5,000 mg/kg. The object of this study was to examine subacute toxicological effects in male and female rats after repeated oral administration of Mb6 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is concluded that no manifest toxicity was observed in this study with Mb6 in male and female rats after oral administration at dosage levels of 125, 250, 500 and 1,000 mg/kg for 5 weeks.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-10. Toxicity of metabolites of miocamycin: acute toxicity of Mb12 in mice.

We evaluated acute toxicity and estimated LD50 values of Mb12, one of the main metabolites of MOM, in male and female mice after single oral administration. Observations were continued for 1 week after treatment. The LD50 values were calculated according to Litchfield-Wilcoxon's method. It is concluded that LD50 values of Mb12 were 5,750 mg/kg (4,914.5-6,727.5 mg/kg) in male mice and 4,950 mg/kg (4,194.9-5,841.0 mg/kg) in female mice, respectively.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-11. Toxicity of metabolites of miocamycin: acute toxicity of Mb12 in rats.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. In the previous studies, LD50 values of Mb12 were 5,750 mg/kg in male mice and 4,950 mg/kg in female mice, respectively. The object of this study was to evaluate acute toxicity in male and female rats after single oral administration of Mb12. Observations were continued for 1 week after treatment. It is concluded that LD0 values of Mb12 were estimated more than 5,000 mg/kg.

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-12. Toxicity of metabolites of miocamycin: subacute toxicity of Mb12 in rats.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. In the previous study, LD0 values of Mb12 in male and female rats were estimated more than 5,000 mg/kg. The object of this study was to evaluate subacute toxicity in male and female rats after repeated oral administration of Mb12 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is concluded that no manifest toxic effects were caused by Mb12 even at the highest dosage level of 1,000 mg/kg/day for 5 weeks to male and female rats.