Finger-Shaped GelForce: Sensor for Measuring Surface Traction Fields for Robotic Hand.

It is believed that the use of haptic sensors to measure the magnitude, direction, and distribution of a force will enable a robotic hand to perform dexterous operations. Therefore, we develop a new type of finger-shaped haptic sensor using GelForce technology. GelForce is a vision-based sensor that can be used to measure the distribution of force vectors, or surface traction fields. The simple structure of the GelForce enables us to develop a compact finger-shaped GelForce for the robotic hand. GelForce that is developed on the basis of an elastic theory can be used to calculate surface traction fields using a conversion equation. However, this conversion equation cannot be analytically solved when the elastic body of the sensor has a complicated shape such as the shape of a finger. Therefore, we propose an observational method and construct a prototype of the finger-shaped GelForce. By using this prototype, we evaluate the basic performance of the finger-shaped GelForce. Then, we conduct a field test by performing grasping operations using a robotic hand. The results of this test show that using the observational method, the finger-shaped GelForce can be successfully used in a robotic hand.

Morules in endometrial carcinoma and benign endometrial lesions differ from squamous differentiation tissue and are not infected with human papillomavirus.

BACKGROUND: Squamous differentiation/squamous metaplasia is often associated with endometrial adenocarcinoma and benign lesions, such as endometrial hyperplasia and chronic endometritis. Morules have distinct histological characteristics, and are referred to as squamous metaplasia or squamoid metaplasia. AIM: To focus on the histological characteristics of morules and clarify the difference between morules and squamous differentiation. MATERIALS/METHODS: Twenty endometrioid carcinomas with morules or squamous differentiation, five adenosquamous carcinomas, and eight non-carcinomatous endometrial lesions with morules were investigated. Numerous antibodies for epithelial membrane antigen (EMA), involucrin, cytokeratins, neuropeptides, and oncofetal antigens were used for immunohistochemistry. In situ hybridisation and polymerase chain reaction were used to detect human papillomavirus (HPV). RESULTS: The morules observed were uniform cell clusters, with no squamous differentiation. They were immunonegative for epithelial antigens including involucrin, EMA, and cytokeratins, but were positive for neurone specific enolase. A few morules were immunopositive for acetylcholine esterase, and one case was positive for somatostatin; neither oncofetal nor proliferative cell markers, including blood group A, B, and AB, or other neuropeptides were demonstrated in the morules. HPV DNA was not found in either the morules in the carcinomas or in the benign lesions. However, true squamous differentiation tissue in four endometrioid carcinomas and two adenosquamous carcinomas was HPV positive using in situ hybridisation. CONCLUSION: Morules are histologically distinct from squamous metaplasia/squamous differentiation tissue. Morules are thought to be neuroectodermal-like cell clusters, and are not infected with HPV. In contrast, some of the true squamous differentiation tissue was associated with HPV infection.

Human herpesvirus 8 (HHV8) sequence variations in HHV8 related tumours in Okinawa, a subtropical island in southern Japan.

BACKGROUND: Although rare in mainland Japan, classic Kaposi's sarcoma (KS) is frequently reported in Okinawa, a subtropical island in southern Japan. Human herpesvirus 8 (HHV8) has been identified in the tumours and geographical differences occur. AIM: To sequence HHV8 in classic and AIDS associated KS in Okinawa. MATERIALS/METHODS: Eight classic KS cases, one AIDS associated KS, five granuloma pyogenicum cases, two inflammatory pseudotumours, two Castleman's disease cases, one angiosarcoma, and one primary effusion lymphoma (PEL) were studied. As a control, HHV8 positive cultured PEL cells (TY-1) were used. The presence of HHV8 sequences was evaluated by PCR and in situ hybridisation. PCR products were sequenced. RESULTS: There were no histological differences among KS resulting from the different virus genotypes. HHV8 was detected in all cases of KS, in one PEL, and one granuloma pyogenicum. Eight classic KS cases and one granuloma pyogenicum were infected with HHV8 genotype II/C (K1 region) or subtype C (ORF26 region), which had a five amino acid deletion at K1 VR2 region. An AIDS associated KS and a PEL were infected with type I/A virus. CONCLUSION: In Okinawa, classic KS cases and one granuloma pyogenicum case were infected with HHV8 genotype II/C, also classified as subtype C. AIDS associated KS and PEL were infected with a different HHV8 (genotype I/A), similar to that found in the USA. In Okinawa, HHV8 infection is more than four times higher than in mainland Japan, resulting in many cases of KS because of HHV8 genotype II/C infection.

Squamous metaplasia induced by transfection of human papillomavirus DNA into cultured adenocarcinoma cells.

BACKGROUND/AIM: It has been reported previously in cases of adenosquamous carcinoma of the lung in Okinawa, a subtropical island 2000 km south of mainland Japan, that the squamous cell carcinoma components were positive for human papillomavirus (HPV) by non-isotopic in situ hybridisation (NISH). The adenocarcinoma cells adjacent to the squamous cell carcinoma components were enlarged and also positive for HPV. This is thought to indicate that after adenocarcinoma cells are infected with HPV, they undergo morphological changes, and that "squamous metaplasia" follows. In this present study, the effects of HPV transfection into adenocarcinoma cells were examined. The relation between the region expressing the HPV gene and squamous metaplasia was also studied. METHODS: Plasmid pBR322 containing HPV type 16 (HPV-16) was transfected into cultured colonic adenocarcinoma (DLD-1) and lung adenocarcinoma (PC-14) cells using the calcium phosphate method. Neomycin was used as a selection marker. The presence of HPV E1, E2, E4, E5, E6, E7, L1, and L2 mRNAs and also transglutaminase 1, involucrin, cyclin dependent kinases (CDKs), cyclins, caspases, apoptosis inducing factor, DNase gamma, Fas, and Fas ligand mRNAs in HPV transfected cells was investigated by means of reverse transcription polymerase chain reaction (RT-PCR). The G0-G1 cell population was analysed by flow cytometry. Morphological examination under light and electron microscopes was also carried out. RESULTS: The virus transfected cells showed squamous metaplasia when they were injected into severe combined immunodeficient mice, expressing the high molecular weight keratin (Moll's number 1 keratin) and involucrin molecules immunohistochemically, and involucrin and transglutaminase I mRNAs by RT-PCR. The squamous metaplasia was most conspicuous in the HPV transfected DLD-1 cell when compared with HPV transfected PC-14 cells. Squamous metaplasia was most clearly demonstrated in one HPV transfected DLD-1 cell clone, which expressed not only E2 but also E6-E7 fusion gene mRNA. Viral L1 mRNA expression was absent in HPV transfected cell clones, and was not related to squamous metaplasia. The growth rate of HPV transfected cells was reduced. Transfection of the virus into the cultured adenocarcinoma cells increased the G0-G1 cell population greatly, as assessed by flow cytometer analysis. Furthermore, in the virus transfected cells, apoptosis was also observed by means of the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labelling method. CONCLUSION: HPV transfection into adenocarcinoma cells induced clear squamous metaplasia. One of the HPV transfected cell clones that expressed E2 and E6-E7 fusion gene mRNA showed the squamous metaplasia particularly clearly, and apoptosis was also demonstrated.

Thermochemical pretreatment in the anaerobic digestion of waste activated sludge.

Effects of a thermochemical pretreatment on the anaerobic digestion of waste activated sludge (WAS) was investigated by semicontinuously-fed digesters operated at 37 degrees C. WAS from a return sludge line of a municipal sewage treatment plant was pretreated by autoclaving at 130 degrees C for 5 minutes after adding 0.3g NaOH/g VSS. Solids of WAS were thermochemically solubilized to one half and then 60% or more were in totality solubilized in anaerobic digesters fed with pretreated WAS at 2-8 days of hydraulic retention times (HRT), while only 16-36% were solubilized in digesters fed with raw WAS. The adverse effect of the set temperature (130 degrees C) on the biodegradability of protein was not found. As a result, removal rates of COD in digestion was increased from 38% to 57% at 8 days HRT by the pretreatment. A specific methane production rate in the pretreated process was three times as high as the normal process. The thermochemical pretreatment was found to be very effective to enhance biodegradability as well as solubilization of WAS in anaerobic digestion.

Epstein-Barr virus (EBV) subtype in EBV related oral squamous cell carcinoma in Okinawa, a subtropical island in southern Japan, compared with Kitakyushu and Kumamoto in mainland Japan.

AIM: In Okinawa, a subtropical island located between the East China Sea and Pacific Ocean, 2000 km south of mainland Japan, the incidence of oral squamous cell carcinoma is 1.5 times higher than that seen in mainland Japan, and a large number of these patients have been reported to be infected with the Epstein-Barr virus (EBV). This study aimed to gain a better understanding of the pathogenesis of this malignancy in this area by carrying out genomic analysis of EBV. METHODS: Fifty four patients with oral squamous cell carcinoma reported from 1997 to 1999 in Okinawa were compared with 21 and 20 patients from Kitakyushu and Kumamoto in Kyushu, mainland Japan, respectively. Diagnosis was confirmed by conventional histological examination of paraffin wax sections. EBV was detected by non-isotopic in situ hybridisation (NISH) and the polymerase chain reaction (PCR) (Bam HI-F, EBV nuclear antigen 2 (EBNA2), and latent membrane protein 1 (LMP-1) regions). Sequence analysis of the PCR products was also carried out. RESULTS: In Okinawa, 25 patients were found to be infected with EBV type A by analysing the 3' sequence divergence of the EBNA2 genes. Six patients were positive for EBV type B, and eight for both type A and B. Therefore, type A virus infection was demonstrated in 33 of 54 patients, and type B in 14 of 54. In total, 39 of 54 patients were infected with EBV. However, the "f" variant was shown in only one patient, who was also infected with type A virus. In contrast, 97.0% of EBV type A infected patients showed a 30 bp deletion of the LMP-1 gene, but those infected with EBV type B did not. Sequence analysis of the type A virus EBNA2 gene revealed slight variations of the sequence (mutations)-(48991)G-->T and (48998)C-->A-in 18 of 33 cases compared with the B95-8 strain, and in 14 cases, in addition to these, a further mutation of (48917)T-->C was demonstrated; in the single remaining case, only one mutation at (49137)A-->G was detected. The mutations at 48991 (G-->T), and 49137 (A-->G) are associated with amino acid changes Arg-->Met and Thr-->Ala, respectively. In contrast, no mutation was seen in the EBNA2 DNA from the 14 cases of type B virus when compared with that of the Jijoye strain. In Kitakyushu and Kumamoto, only 10 of 41 patients (six in Kitakyushu and four in Kumamoto) were infected with EBV. Among them, nine patients were infected with type A virus, and only one patient from Kitakyushu was infected with type B virus. The (48991)G-->T and (48998)C-->A mutations of the EBNA2 region were demonstrated in type A virus, but the (48917)T-->C and (49137)A-->G mutations were not when compared with the B95-8 strain. In the case of type B virus no mutation was noted. A 30 bp deletion was found in these nine cases of type A, but not in type B. The sequence analysis of EBV type A in Okinawa, Kitakyushu, and Kumamoto showed slight variations when compared with B95-8, but EBV type B LMP-1 did not when compared with the Jijoye strains. CONCLUSION: In Okinawa, EBV infection was frequently demonstrated in oral squamous cell carcinoma (p < 0.001). However, in mainland Japan there was no significant correlation between EBV and oral squamous cell carcinoma. In Okinawa, EBV type B infection is approximately 10 times more common than in the mainland. However, in these areas-Okinawa, Kitakyushu, and Kumamoto-the frequency of the "f " variant was very low, whereas a high incidence of a 30 bp deletion of LMP-1 was noted. The number of EBV (including type A and/or B) infected oral squamous cell carcinomas in Okinawa was about three times higher than that seen in the mainland, although the frequency of oral squamous carcinoma was only 1.5 times higher than that seen in the mainland. A high prevalence of type B virus infection and slight differences in the EBNA2 gene sequence in the type A virus might influence the frequency of this carcinoma in Okinawa.

Studies on anti-MRSA parenteral cephalosporins. IV. A novel water-soluble N-phosphono type prodrug for parental administration.

A systematic approach for improving the water-solubility of anti-MRSA (methicillin-resistant Staphylococcus aureus) cephalosporin derivatives is described. We first tried to improve the water-solubility of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-fluoromethoxyiminoacetamido]-3-[(E)-2-(1-methylimidazo[1,2-b]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylate (1a) by substitution of the C-3' pharmacophore. Replacement of the C-3' pharmacophore with a 1-methyl-4-pyridinio group improved the water-solubility without decreasing the anti-MRSA activity. Furthermore, we applied the N-modified prodrug strategy to the C-7 acyl group in order to enhance the water-solubility drastically. Among the compounds prepared, the N-phosphono type prodrugs 2a(1-methylimidazo[1,2-b]pyridazinium derivative) and 2b (1-methyl-4-pyridinio derivative) showed water-solubility appropriate for a product intended for intravenous injection and in vivo anti-MRSA activity comparable to that of vancomycin.

Studies on anti-MRSA parenteral cephalosporins. III. Synthesis and antibacterial activity of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido-3.

In the course of our exploration for a novel cephalosporin derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we modified the C-3 linked spacers of cephem derivatives bearing a 1-methylimidazo[1,2-b]pyridazinium-6-yl group at the C-3' position and 2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-cyclopentyloxy-iminoacetyl group at the C-7 position. The optimal spacers were the (E)-2-vinyl and (E)-2-thiovinyl groups seen in 19a and 29aa, respectively. Their anti-MRSA activity was 16 to 32 times as potent as that of cefozopran (CZOP). Focusing on the (E)-2-vinyl and (E)-2-thiovinyl spacers, we further modified the alkoxyimino groups in the C-7 acyl moiety and the 1-alkylimidazo[1,2-b]pyridazinium moieties at the C-3' position and investigated the structure-activity relationships (SAR) of the derivatives. Consequently, we selected 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-fluoromethoxyiminoacetamido]-3-[(E)-2-(1-methylimidazo[1,2-b]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylate (29ca) as a new anti-MRSA parenteral cephalosporin candidate for further biological evaluation. The selected 29ca showed anti-MRSA activity comparable to that of vancomycin (VCM) both in vitro and in vivo, high affinity (IC50)=2.7 microg/ml) for penicillin binding protein 2' (PBP2') of MRSA and potent activity against Gram-negative bacteria as well.

Utilization and acid production of beta-galactosyllactose by oral streptococci and human dental plaque.

Beta-galactosyllactose is a trisaccharide containing the beta-galactosidic linkage at the nonreducing end. The purpose of this study was to determine whether certain oral streptococci could utilize four kinds of beta-galactosyllactoses. Three of four beta-galactosyllactoses were unable to support growth of the oral streptococci and to be a substrate for producing acid from the cell suspensions and dental plaque. 4'-beta-Galactosyllactose supported growth of Streptococcus sanguis ATCC 35105, ATCC 49298, Streptococcus mitis ATCC 15914, Streptococcus oralis ATCC 35037, ATCC 10557 and Streptococcus milleri 10707 and produced acid from dental plaque. Although beta-galactosidase activities were observed in all the strains, 4'-beta-galactosyllactose could not be used as a carbon source for the growth of mutans streptococci. Enzymes metabolizing 4'-beta-galactosyllactose were induced when S. oralis ATCC 10557 was cultured in medium containing galactose. These results suggested that 4'-beta-galactosyllactose could be as cariogenic as lactose if it is consumed frequently and retained for a long period in the mouth.

Development of a stereoselective practical synthetic route to indolmycin, a candidate anti-H. pylori agent.

A stereoselective practical synthetic route to indolmycin is described. The route is composed of the regioselective coupling of indolyl magnesium halide with a trans-epoxy ester, diastereoselective oxazolone ring formation with guanidine and amine exchange reaction with methylamine. In the coupling step, use of dichloromethane as co-solvent and conversion of the resulting hydroxy ester to the hydroxy acid for purification, make this process efficient and practical. The oxazolone ring is formed in good yield without epimerization at the C5 position by treatment with guanidine and potassium tert-butoxide in tert-butanol at room temperature. In the final step, the amino group is efficiently converted to the methylamino group in aqueous methylamine solution at 5 degrees C. After examination of the route with racemates, indolmycin was synthesized stereoselectively in 22% total yield from optically active trans-epoxy ester. This route was applied to the preparation of the metabolites of indolmycin.

Two cases of supernumerary ovary: one with large fibroma with Meig's syndrome and the other with endometriosis and cystic change.

Reports of supernumerary ovaries are rare. We describe two such cases, one with fibroma and the other with endometriosis and cystic change. A large fibroma measuring 17.4 x 12.0 x 7.5 cm in size was found in the supernumerary ovary of the omentum in the first case of a 47-year-old married woman with Meig's syndrome. The second case was associated with endometriosis and cystic change, measuring 11 x 5 x 3 cm in size and located in the upper abdominal cavity. It was attached to the uterus of a 28-year-old pregnant woman who had neither fibroma nor Meig's syndrome. Histologically, corpus albicans and a few primordial germ cells were demonstrated, respectively. A fibroma showing a storiform pattern was found in the first case. The second case had endometriosis and a thin-walled cyst with bleeding and necrosis caused by torsion. Immunohistochemically, desmin, alpha-smooth muscle actin, c-kit, CA125, Na+/K+ATPase, overexpression of p53, myc and ras were all negative in the fibroma cells of the first case, and in the endometriosis and cyst wall of the second case. The fibroma cells were positive for vimentin and estrogen receptor, and the proliferating cell nuclear antigen was sporadically demonstrated in their nuclei. The mutation of the p53 gene at exons 5-8 was not detected by sequence analysis. Using RT-PCR, bax, bcl-2 and p16 were not detected either. Clinically, the two cases presented here did not show abnormal hormonal symptoms. They were diagnosed as abdominal tumors or masses. Based on these considerations, one might assume that supernumerary ovaries are probably more frequent than reported at present.

Preparation, X-ray crystal structure, and 195Pt NMR spectra of platinum(II) with dipeptides and dipeptide methyl esters.

Three dipeptide complexes of the form K[M(dipeptide)Cl] (H2dipeptide=glycylbeta-alanine, beta-alanylglycine, beta-alanylbeta-alanine) and four dipeptide methyl ester complexes of the form K[M(dipeptideOMe)Cl2] (HdipeptideOMe=glycylalpha-alanine methyl ester, alpha-alanylglycine methyl ester, dialpha-alanine methyl ester) were newly prepared. The K[Pt(glybeta-ala)Cl] complex crystallizes in the monoclinic space group C2/c with unit cell dimensions of a=25.77(1) A, b=4.09(2) A, c= 16.432(9) A, beta=103.74(4) degrees, and Z=8. The K[Pt(glyalpha-alaOMe)Cl2] complex crystallizes in the monoclinic space group P1 with unit cell dimensions of a=7.195(2) A, b=7.977(5) A, c=10.326(3) A, alpha=72.49(3) degrees, beta=103.74(4) degrees, gamma=88.27(4) degrees and Z=2. The 195Pt NMR peaks of the complexes containing the beta-alanine moiety appeared significantly more upfield than those of the complexes containing diglycine. The ratios of the species of the platinum complexes containing the dipeptide ester in neutral solution were significantly different from those in alkaline solution at 40 degrees C for a short time.

[Endoscopic evacuation of intraventricular hematoma and third ventriculostomy].

We described our experience of three cases treated with endoscopic evacuation of intraventricular hematoma and third ventriculostomy for a tight intraventricular hematoma associated with intracerebral hemorrhage. A steerable endoscope was introduced into the anterior horn of the lateral ventricle contralaterally to the intracerebral hemorrhage, through a 14 Fr. peel-away sheath. First, the hematoma in the lateral ventricle contralateral to the hemorrhage was evacuated by direct aspiration using a syringe connected to the operative channel of the endoscope, and evacuation of the hematoma was subsequently carried on the third ventricle, aqueduct and the fourth ventricle. After the evacuation of the intraventricular hematoma, third ventriculostomy was performed for acute obstructive hydrocephalus. Finally, the procedure was completed with septostomy and evacuation of the hematoma in the lateral ventricle ipsilateral to the hemorrhage. Sufficient evacuation of the hematoma was obtained in all cases and no major complications were encountered. We conclude that for patients with intraventricular hematoma associated with intracerebral hemorrhage endoscopic evacuation of intraventricular hematoma brings about sufficient removal of hematoma, reduction of hospitalization time and prevention of subsequent hydrocephalus.

Studies on anti-MRSA parenteral cephalosporins. II. Synthesis and antibacterial activity of 7beta-[2-(5-amino-1,2,4- thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido]-3-(substituted imidaz.

In an effort to discover a novel cefozopran (CZOP) derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we performed chemical modification of the alkoxyimino moiety and imidazo[1,2-b]pyridazinium group of CZOP. Among the prepared compounds, the cyclopentyloxyimino derivative 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-cyclopentyloxyiminoacetamido]-3-(3,6-diaminoimidazo[1,2-b]pyridazinium-1-yl)methyl-3-cephem-4-carboxylate (20 g) showed the most potent anti-MRSA activity, reflecting its high affinity (IC50 = 1.6 microg/ml) for penicillin binding protein 2' (PBP2'), although its anti-MRSA activity was slightly inferior to that of vancomycin (VCM). In experimental systemic infection in mice, however, 20 g showed activity comparable to that of VCM against MRSA. In addition, 20 g showed activity similar or slightly inferior to that of CZOP against Pseudomonas aeruginosa both in vitro and in vivo. Considering its favorable antibacterial activity profile, 20 g was considered to be the most promising CZOP derivative for further studies.

Sibling incest and formulation of paternity probability: case report.

Paternity determination of a fetus whose mother was admitted to an institution for the welfare and health of handicapped persons was requested of us by a doctor and lawyer of the institution. The fetus was recovered by a legal artificial abortion based on the Act on Maternity Health and Welfare (Japan) with the permission of the custodian. Commercially available MCT118, HLADQA, PM, and 9 STRs were tested for DNA samples from the fetus, the mother, her younger brother, her father, her grandfather, and 4 staff members of the institution. Only the brother was not excluded and the paternity probability was estimated at 99.857% on the basis of newly formulated expressions for multiallelic loci on the assumption of sibling incest. We concluded then that the fetus was fathered by the brother. DNA fingerprinting with multilocus and single locus minisatellite probes which were performed to confirm the paternity also support the conclusion. Bandsharing frequencies between the family members, however, did not necessarily reflect their actual kinship, which findings suggest that multilocus DNA fingerprinting requires further accumulation of data for consanguineous cases such as incest. Universal formulation for calculating paternity probability for a sibling incest case on the basis of multiallelic monolocus polymorphisms is also presented.

Growth factors: importance in wound healing and maintenance of transparency of the cornea.

The mechanism of corneal wound healing has not been clarified yet. However, evidence has accumulated that various kinds of growth factor such as epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor (TGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) play a key role in corneal wound healing. For example, these growth factors are expressed in the corneal epithelial cells, keratocytes and endothelial cells, and their receptors are expressed in the corneal cells. Furthermore, these growth factors promote the proliferation of corneal cells and induce the migration of corneal cells. In addition to the growth factors, inflammatory cytokines such as interleukin (IL)-1, IL-6 and TNF-alpha are involved in corneal wound healing. These cytokines are expressed in the normal and inflammatory cornea after infections, alkaliburn, etc. where they control the growth of corneal cells and induce the migration of corneal cells. Thus, a number of growth factors and cytokines function in the regulation of corneal cell proliferation and in the maintenance of corneal transparency.

Biodisposition characteristics of N-succinyl-chitosan and glycol-chitosan in normal and tumor-bearing mice.

Two water-soluble chitosan derivatives, N-succinyl-chitosan (Suc-chi; average MW 3x10(5)) and glycol-chitosan (Gly-chi; average MW 1.5x10(5)), were examined concerning their biodisposition characteristics in order to evaluate their possible use as water-soluble drug carriers. Their body distribution and urinary excretion were investigated by i.v. administration of FITC-labeled Suc-chi (FTC-Suc-chi) and FITC-labeled Gly-chi (FTC-Gly-chi) to normal and Sarcoma 180 solid tumor-bearing mice. In normal mice, both polymers showed good retention in blood circulation; especially, FTC-Suc-chi exhibited a long half-life of 51 h, and its distribution to other tissues was very small. FTC-Gly-chi was distributed into the kidney to a relatively high extent. In tumor-bearing mice, FTC-Suc-chi and FTC-Gly-chi were eliminated faster from the blood circulation than in normal mice, that is, with half-lives of 11 and 7 h, respectively. FTC-Suc-chi was less partitioned to the tumor tissue but accumulated more easily into it compared with FTC-Gly-chi. This suggested the enhanced permeability and retention (EPR) effect of Suc-chi and explained the previous result that a water-soluble Suc-chi-mitomycin C conjugate injected intravenously exhibited a good effect against Sarcoma 180 solid tumor. FTC-Gly-chi showed greater distribution to the kidney than in normal mice. Urinary excretion studies indicated the faster excretion of both polymers in tumor-bearing mice. The molecular weight of the products excreted into urine indicated that both polymers should be pretty resistant to the hydrolytic enzyme, lysozyme. Taking toxicities into account, Suc-chi is considered to be available as a drug carrier showing long systemic retention and tumor accumulation.

Effects of PDGF on the migration of rabbit corneal fibroblasts and epithelial cells.

PURPOSE: We investigated the effects of human platelet-derived growth factor (PDGF) isomers on the migration of rabbit corneal fibroblasts and epithelial cells in the presence or absence of fibronectin (FN). METHODS: A modified Boyden's chamber method was used to detect cell migration. Cells placed in the inner chamber were incubated with PDGF in the outer chamber at 37 degrees C at 24 h. In addition, epithelial cells were incubated in the presence or absence of FN. The migrated cells were stained and the cell number counted under a microscope. Checkerboard analysis was used to distinguish chemotaxis from chemokinesis. RESULTS: Natural PDGF and PDGF-BB enhanced the migration of corneal fibroblasts, whereas PDGF-AA did not. As for corneal epithelial cells, all the isomers of PDGF enhanced the migration, but only in the presence of FN, as in the absence of FN or at a low concentration gradient of FN, there was no enhanced cell migration. A checkerboard assay demonstrated that PDGF-BB had a chemotactic effect on the migration of corneal fibroblasts and epithelial cells, whereas PDGF-AA had a chemotactic effect on only corneal epithelial cells. CONCLUSION: These results suggest that PDGF is involved in corneal wound healing by stimulating the migration of corneal epithelial cells in the presence of FN and fibroblasts.