Biomedical subjects

Y Xu

Publications and source records attributed to Y Xu.

At least 901 records · Page 50Linked to original sources

PubMed1996

Effects of polyethyleneglycol chain length and phospholipid acyl chain composition on the interaction of polyethyleneglycol-phospholipid conjugates with phospholipid: implications in liposomal drug delivery.

PURPOSE: The purpose of this study was to investigate polyethyleneglycol(PEG)-phosphatidylethanolamine(PE) conjugate interaction with phospholipid bilayers, in an attempt to explain the dependence of liposome circulation time on formulation. METHODS: Differential scanning calorimetry, electron microscopy, dynamic light scattering and NMR were the major methods used in the study. RESULTS: Mixtures of PEG-phospholipid conjugates and phosphatidylcholine existed in three different physical states: a lamellar phase with components exhibiting some miscibility, a lamellar phase with components phase separated, and mixed micelles. Beyond 7 mol-percent of PEG(1,000-3,000)-dipalmitoyl phosphatidylethanolamine (DPPE), and 11 mol% PEG(5,000)-DPPE in dipalmitoyl phosphatidylcholine (DPPC), a strong tendency towards mixed micelle formation was observed. All concentrations of PEG(12,000)-DPPE and PEG(5,000)-DPPE beyond 8 mol% formed phase separated lamellae with phosphatidylcholine. Decreasing the acyl chain length from C(16:0) to C(14:0) caused a decrease in tendency towards micelle formation and phase separation. These tendencies increased upon increasing acyl chain length to C(18:0). Phase separation was at least partly due to PEG chain-chain interaction. This was supported by an increased fraction of PEG chains exhibiting a fast NMR transverse relaxation in DPPC/PEG(5,000)-DPPE mixtures as compared to that in distearoyl phosphatidylcholine (DSPC)/PEG(5,000)-dioleoyl-PE (DOPE). CONCLUSIONS: These phenomena are discussed in relation to both bilayer and steric stabilization of liposomes, and the lack of prolonged circulation with certain formulations is discussed.

Calorimetry, Differential Scanning↗

PubMed1996

Different expression of the plasminogen activation system in renal thrombotic microangiopathy and the normal human kidney.

Renal thrombotic microangiopathy is characterized by glomerular and vascular thrombosis. The persistancy of fibrin deposits may result from imbalance between plasminogen activation and inhibition. In the present study, we used immunohistochemistry and in situ hybridization techniques to determine the localization of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators, type 1 plasminogen activator inhibitor (PAI-1) and membrane receptor for u-PA (uPA-R) antigen and their sites of synthesis in renal thrombotic microangiopathy (N = 10) as compared to acute tubular necrosis (N = 5) and normal human kidneys (N = 7). We found an induction of PAI-1 and uPA-R expression in glomeruli and in arterial walls in renal thrombotic microangiopathy. In addition, the induction of uPA-R expression was also found in some tubular epithelial cells. In most case, local synthesis of PAI-1 and uPA-R was confirmed by in situ hybridization with the corresponding cDNA probes. In contrast, using similar techniques PAI-1 and uPA-R antigens and messenger RNAs could not be detected in normal kidneys. In both renal thrombotic microangiopathy and normal kidneys, t-PA mRNA was detected in large amounts in all glomeruli and in vascular endothelial cells, but t-PA antigen was only detected in a limited number of glomerular and arterial endothelial cells, whereas it was strongly expressed by all venous endothelial cells. Although u-PA antigen was found in almost all tubular sections, u-PA mRNA was only found in tubular epithelial cells in the deep cortex and the outer medulla. Our results indicate that there is an up-regulation of PAI-1 and u-PA-R expression in the glomeruli and in the arterial walls of thrombotic microangiopathy. The local release of PAI-1 could play a role in the persistancy of fibrin deposition and the further development of fibrotic lesions. Whether uPA-R plays a pathogenic role in the development of glomerular and vascular lesions, or is involved in the repair process of these lesion, remains to be elucidated.

Adult↗

PubMed1996

Regulation of monocyte chemoattractant protein 1 by cytokines and oxygen free radicals in rat hepatic fat-storing cells.

BACKGROUND & AIMS: Monocyte chemoattractant protein 1 (MCP-1) is a potent monocyte/macrophage chemoattractant expressed by fat-storing cells (FSCs) in rat models of liver injury. This study investigated the mechanism of this activation of hepatic MCP-1 expression. METHODS: The regulation of MCP-1 messenger RNA (mRNA) expression and protein synthesis was examined in FSC lines derived from CCl4-induced cirrhotic rat liver (cirrhotic FSCs) and normal rat liver (normal FSCs). RESULTS: Northern blot hybridization analysis revealed low levels of MCP-1 mRNA in cultured cirrhotic FSCs that increased markedly after treatment with tumor necrosis factor alpha, interleukin 1 alpha, or transforming growth factor beta 1. All three cytokines increased the synthesis and secretion of MCP-1 protein. Oxygen free radical production also increased MCP-1 mRNA levels. These increases in MCP-1 mRNA were blocked by dexamethasone. In normal FSCs, levels of MCP-1 mRNA and secreted protein were increased in response to cytokines or oxygen free radical production, but the magnitude and duration of this increase was less than in cirrhotic FSCs. CONCLUSIONS: In liver injury, monocyte/macrophage recruitment and activation from FSC production of MCP-1 may be stimulated by cytokines and oxygen free radicals. During chronic liver injury leading to cirrhosis, FSCs may become hypersensitive to these stimuli, further fueling the inflammatory response.

Animals↗

PubMed1996

An iterative algorithm for correcting sequencing errors in DNA coding regions.

Insertion and deletion (indel) sequencing errors in DNA coding regions disrupt DNA-to-protein translation frames, and hence make most frame-sensitive coding recognition approaches fail. This paper extends the authors' previous work on indel detection and "correction" algorithms, and presents a more effective algorithm for localizing indels that appear in DNA coding regions and "correcting" the located indels by inserting or deleting DNA bases. The algorithm localizes indels by discovering changes of the preferred translation frames within presumed coding regions, and then "corrects" them to restore a consistent translation frame within each coding region. An iterative strategy is exploited to repeatedly localize and "correct" indels until no more indels can be found. Test results have shown that this improved algorithm can detect and "correct" more indels while not worsening the rate of introduction of false indels when compared to the authors' previous work.

Algorithms↗

PubMed1996

A polynomial-time algorithm for a class of protein threading problems.

This paper presents an algorithm for constructing an optimal alignment between a three-dimensional protein structure template and an amino acid sequence. A protein structure template is given as a sequence of amino acid residue positions in three-dimensional space, along with an array of physical properties attached to each position; these residue positions are sequentially grouped into a series of core secondary structures (central helices and beta sheets). In addition to match scores and gap penalties, as in a traditional sequence-sequence alignment problem, the quality of a structure-sequence alignment is also determined by interaction preferences among amino acids aligned with structure positions that are spatially close (we call these 'long-range interactions'). Although it is known that constructing such a structure-sequence alignment in the most general form is NP-hard, our algorithm runs in polynomial time when restricted to structures with a 'modest' number of long-range amino acid interactions. In the current work, long-range interactions are limited to interactions between amino acids from different core secondary structures. Dividing the series of core secondary structures into two subseries creates a cut set of long-range interactions. If we use N, M and C to represent the size of an amino acid sequence, the size of a structure template, and the maximum cut size of long-range interactions, respectively, the algorithm finds an optimal structure-sequence alignment in O(21C NM) time, a polynomial function of N and M when C = O(log(N + M)). When running on structure-sequence alignment problems without long-range intersections, i.e. C = 0, the algorithm achieves the same asymptotic computational complexity of the Smith-Waterman sequence-sequence alignment algorithm.

Algorithms↗

PubMed1996

Occupation and risk for the occurrence of low-back pain (LBP) in Danish employees.

Using data from a nation-wide cross-sectional survey in 1990 a study examining the risk for occurrence of LBP in various specific occupations was made among 5,185 Danish employees aged 19-59 years old. After adjusting for the confounding effects of age and gender we found significantly increased risks of LBP in three out of nine major occupational categories. They were 'health care and social work' (OR = 1.52, 95% Cl = 1.28-1.80), 'mining, quarrying and construction work' (OR = 1.97, 95% Cl = 1.41-2.74) and 'manufacturing and machine operation work' (OR = 1.21, 95% Cl = 1.05-1.40). Among 39 second-level occupational categories the highest risks were observed among persons employed in 'building construction work' (OR = 1.97, 95% Cl = 1.41-2.74), 'social work, child day care work and psychological work' (OR = 1.64, 95% Cl = 1.32-2.05). Skilled and unskilled manual workers had an increased risk of LBP.

Adult↗

PubMed1996

Improved survival in rats administered NG-nitro L-arginine methyl ester due to converting enzyme inhibition.

Blockade of the renin-angiotensin system (RAS) prevents the increase in blood pressure (BP) induced by chronic administration of NG-nitro L-arginine methyl ester (L-NAME) in rats. In the present study, we showed how a converting enzyme inhibitor can prevent the end-stage tissue damage due to chronic nitric oxide (NO) synthase blockade and thus improve the survival rate. Three experiments were performed. In the first, rats (n = 10) were given L-NAME (50 mg/kg) and 10 other rats were given L-NAME plus quinapril (10 mg/kg) starting 1 month after L-NAME administration. Ten untreated rats were used as controls. Rats were killed after 2 months, and the RAS, renal function, and renal morphology were analyzed. In the second experiment, a similar protocol was used, and function and morphological damage in renal slices and cervical medullary tissue were assessed after 4 months of L-NAME and 3 months of quinapril + L-NAME. In the third experiment, a similar protocol was used, but to establish survival curves, the animals were not killed. L-NAME significantly increased BP without causing any significnat changes in plasma renin activity (PRA) at 2 months. The aortic wall cyclic GMP content was significantly decreased, and the angiotensin-converting enzyme (ACE) activity was increased by L-NAME. Quinapril significantly reversed the high BP induced by L-NAME without changing the decrease in the aortic wall cyclic GMP. Two-month L-NAME treatment decreased renal function and damaged renal tissue. Quinapril prevented both proteinuria and morphological damage. Four-month L-NAME treatment induced renal end-stage damage and infarctions of the cervical medulla. Quinapril prevented this end-stage damage in the kidney and cervical medulla. Quinapril therefore prevented the increased mortality due to L-NAME. Hence, inhibition of ACE, despite its lack of effect on arterial wall cyclic GMP, does reverse the hypertension and prevent end-stage vascular damage induced by chronic L-NAME in target organs.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Viral etiology of acute childhood encephalitis in Beijing diagnosed by analysis of single samples.

OBJECTIVE: To understand the viral etiology of acute childhood encephalitis in Beijing. METHODS: Ninety-seven Chinese children (between 7 months and 13 years of age) with acute encephalitis were retrospectively investigated. They were treated in Beijing Children's Hospital between June, 1991, and October, 1994. Different serologic methods (immunofluorescence assay, enzyme-linked immunosorbent assay, solid phase reverse immunosorbent test) were used for detection of IgM antibody to enteroviruses, herpesviruses, mumps, measles, rubella and Japanese encephalitis virus. The viral DNA of six herpesviruses was detected by polymerase chain reaction. RESULTS: Viral etiology was identified in 35 of 97 (36.0%) cases. The most frequently identified pathogens were enteroviruses (15; 15.4%), followed by mumps (7; 7.2%), rubella (6; 6.1%), Japanese encephalitis virus (5; 5.1%), human herpesvirus 6 (2; 2.0%), herpes simplex virus (2; 2.0%) and Epstein-Barr virus (1; 1.0%). IgM antibody in cerebrospinal fluid was detected for enterovirus, mumps and rubella viruses. CONCLUSIONS: Enteroviruses were the most frequent viral pathogens of acute childhood encephalitis in Beijing. Detection of IgM in cerebrospinal fluid may be useful for diagnosis in certain cases of viral encephalitis.

Acute Disease↗

PubMed1996

Differential expression of soybean cysteine proteinase inhibitor genes during development and in response to wounding and methyl jasmonate.

Three cysteine proteinase inhibitor cDNA clones (pL1, pR1, and pN2) have been isolated from a soybean (Glycine max L. Merr.) embryo library. The proteins encoded by the clones are between 60 and 70% identical and contain the consensus QxVxG motif and W residue in the appropriate spatial context for interaction with the cysteine proteinase papain. L1, R1, and N2 mRNAs were differentially expressed in different organs of plants (juvenile and mature) and seedlings, although N2 mRNA was constitutive only in flowers. R1 and N2 transcripts were induced by wounding or methyl jasmonate (M-JA) treatment in local and systemic leaves coincident with increased papain inhibitory activity, indicating a role for R1 and N2 in plant defense. The L1 transcript was constitutively expressed in leaves and was induced slightly by M-JA treatment in roots. Unlike the chymotrypsin/trypsin proteinase inhibitor II gene (H. Peña-Cortés, J. Fisahn, L. Willmitzer [1995] Proc Natl Acad Sci USA 92: 4106-4113), expression of the soybean genes was only marginally induced by abscisic acid and only in certain tissues. Norbornadiene, a competitive inhibitor of ethylene binding, abolished the wounding or M-JA induction of R1 and N2 mRNAs but not the accumulation of the wound-inducible vspA transcript. Presumably, ethylene binding to its receptor is involved in the wound inducibility of R1 and N2 but not vspA mRNAs. Bacterial recombinant L1 and R1 proteins, expressed as glutathione S-transferase fusion proteins, exhibited substantial inhibitory activities against vicilin peptidohydrolase, the major thiol endopeptidase in mung bean seedlings. Recombinant R1 protein had much greater cysteine proteinase inhibitor activity than recombinant L1 protein, consistent with the wound inducibility of the R1 gene and its presumed role in plant defense.

Acetates↗

PubMed1996

Effect of low-dose gamma radiation of HIV replication in human peripheral blood mononuclear cells.

Recent studies have demonstrated that UV light and x-irradiation enhance human immunodeficiency virus (HIV) gene expression. There are few published data on related effects of gamma-radiation. This may be of clinical relevance, as radiotherapy has been used extensively for the treatment of acquired immunodeficiency syndrome associated conditions. With this in mind, we have studied the effects of gamma-radiation on HIV replication in mononuclear cells (MC). These cells were obtained from five seronegative healthy donors, exposed to 0-200 cGy gamma-radiation, stimulated with phytohemagglutinin-P (PHA-P) for 24 h, infected with a laboratory strain of HIV (HTLV-IIIB, multiplicity of infection = 0.001), then carried in culture for 14 days. Overall, when considering p24 antigen levels on days 7 and 11 in cultures established from cells exposed to 50 cGy, the maximal levels were significantly higher than those measured in the parallel control cultures taken as a whole (P < 0.05), with viral replication enhanced as much as 1000-fold in one case. No significant cytotoxicity was observed following exposure to doses up to 50 cGy. The mechanism of the observed effect remains unknown but may relate to direct gene activation and/or free radical generation, leading to such activation. To date, there is no evidence that viral stimulation occurs following therapeutic radiation in a clinical setting.

Dose-Response Relationship, Radiation↗

PubMed1996

Pertussis toxin-catalyzed ADP-ribosylation of Gi-2 and Gi-3 in CHO cells is modulated by inhibitors of intracellular trafficking.

In previous studies, an in vitro ADP-ribosylation assay was developed to quantitatively evaluate the in vivo ADP-ribosylation of eukaryotic target proteins in intact Chinese hamster ovary (CHO) cells by pertussis toxin (PT). Immunoblot analysis identified the two PT-sensitive target proteins in CHO cells as Gi-2 and Gi-3. In this in vitro ADP-ribosylation assay, the ability of PT and ADP-ribosylate Gi-2 and Gi-3 intact CHO cells was not inhibited by cytochalasin D but was inhibited by chloroquine, monensin, and nocodazole. These data implicated the involvement of a cytochalasin D-independent endocytic mechanism, a pH-sensitive step, and microtubules in the ADP-ribosylation of Gi-2 and Gi-3 by PT in intact CHO cells. Preincubation of CHO cells with cycloheximide, at concentrations that reduced protein synthesis by > 95%, did not inhibit the ability of PT to ADP-ribosylate Gi-2 and Gi-3. Control experiments showed that these agents did not affect either the ability of PT to directly ADP-ribosylate the heterotrimeric G protein, Gt, or the binding of PT to CHO cells, except that monensin slightly inhibited the binding of PT to CHO cells. These results are consistent with a model in which PT is internalized by receptor-mediated endocytosis, probably via a cytochalasin D-independent pathway, which involves intracellular trafficking through late endosomes and the Golgi apparatus. An alternative model predicts the presence of a eukaryotic factor that traffics within cells via this pathway and is required by PT to ADP-ribosylate Gi proteins.

Adenosine Diphosphate Ribose↗

PubMed1996

Correlation of plasmids with infectivity of Borrelia burgdorferi sensu stricto type strain B31.

The correlation of plasmid profiles with infectivity was investigated by using five clones of Borrelia burgdorferi sensu stricto strain B31 (ATCC 35210). Plasmid profiles were determined by pulsed-field and two-dimensional gel electrophoresis. The 50% infectious dose (ID50) in hamsters was determined. The ID50 of the clone that possessed a full complement of eight linear and three circular plasmids was 10(3) cells. The loss of the 27.5- and 40-kb linear plasmids did not decrease the infectivity of these cells. Rather, the loss of the 27.5-kb linear plasmid was associated with a more disseminated infection. A moderate decrease of the ID50 from 10(3) to 10(5) cells correlated with the loss of the 9.0-kb circular plasmid and the 27.5-kb linear plasmid. A major loss of infectivity (ID50 > 10(3) cells) occurred with cells that lost the 24.7- and 27.5-kb linear plasmids and the 9.0-kb circular plasmid. A 3.0-kb HindIII fragment of the 24.7-kb linear plasmid was used as a probe to determine the presence of the homologous sequences in the three genospecies of Lyme disease spirochetes. An analysis of 21 infectious strains of B. burgdorferi sensu stricto, B. garinii, and B. afzelii revealed a consistent association of infectivity with strains possessing a linear plasmid (size range, 24 to 36 kb) that hybridized with the HindIII fragment. Western immunoblotting with hamster antisera against infectious B31 clone C-3 revealed two proteins with molecular masses of 28 and 43 kDa that were absent in the noninfectious B31 clone C-1. Additionally, a 14-kDa protein was absent in C-1 but present in infectious clone C-9 as shown by two-dimensional polyacrylamide gel electrophoresis.

Animals↗

PubMed1996

Identification of sigma S-regulated genes in Salmonella typhimurium: complementary regulatory interactions between sigma S and cyclic AMP receptor protein.

sigma S (RpoS)-regulated lacZ transcriptional fusions in Salmonella typhimurium were identified from a MudJ transposon library by placing the rpoS gene under the control of the araBAD promoter and detecting lacZ expression in the presence or absence of arabinose supplementation. Western blot (immunoblot) analysis of bacteria carrying PBAD::rpoS demonstrated arabinose-dependent rpoS expression during all phases of growth. sigma S-dependent gene expression of individual gene fusions was confirmed by P22-mediated transduction of the MudJ insertions into wild-type or rpoS backgrounds. Analysis of six insertions revealed the known sigma S-regulated gene otsA, as well as five novel loci. Each of these genes is maximally expressed in stationary phase, and all but one show evidence of cyclic AMP receptor protein-dependent repression during logarithmic growth which is relieved in stationary phase. For these genes, as well as for the sigma S-regulated spvB plasmid virulence gene, a combination of rpoS overexpression and crp inactivation can result in high-level expression during logarithmic growth. The approach used to identify sigma S-regulated genes in this study provides a general method for the identification of genes controlled by trans-acting regulatory factors.

Amino Acid Sequence↗

PubMed1996

Topological characterization of the essential Escherichia coli cell division protein FtsN.

Genetic and biochemical approaches were used to analyze a topological model for FtsN, a 36-kDa protein with a putative transmembrane segment near the N terminus, and to ascertain the requirements of the putative cytoplasmic and membrane-spanning domains for the function of this protein. Analysis of FtsN-PhoA fusions revealed that the putative transmembrane segment of FtsN could act as a translocation signal. Protease accessibility studies of FtsN in spheroblasts and inverted membrane vesicles confirmed that FtsN had a simple bitopic topology with a short cytoplasmic amino terminus, a single membrane-spanning domain, and a large periplasmic carboxy terminus. To ascertain the functional requirements of the N-terminal segments of FtsN, various constructs were made. Deletion of the N-terminal cytoplasmic and membrane-spanning domains led to intracellular localization of the carboxy domain, instability,and loss of function. Replacement of the N-terminal cytoplasmic and membrane-spanning domains with a membrane-spanning domain from MalG restored subcellular localization and function. These N-terminal domains of FtsN could also be replaced by the cleavable MalE signal sequence with restoration of subcellular localization and function. It is concluded that the N-terminal, cytoplasmic, and transmembrane domains of FtsN are not required for function of the carboxy domain other than to transport it to the periplasm. FtsQ and FtsI were also analyzed.

ATP-Binding Cassette Transporters↗

PubMed1996

Translocation between chromosomes 6 and 15 (45,XX,t(6;15)(q25;q11.2)) with further evidence for lack of imprinting of the insulin-like growth factor II/mannose-6-phosphate receptor in humans.

We report a 24 year old female with growth retardation, microcephaly, and congenital abnormalities who has an unbalanced de novo translocation between chromosomes 16 and 6: 45,XX,t(6;15)(q25;q11.2). FISH analysis confirmed that the deletion on chromosome 15 is proximal to the Prader-Willi locus. Several genes have been assigned to the 6q25-qter region including the insulin-like growth factor II/mannose-6-phosphate (IGF-II/M6P) receptor. DNA analysis from our patient documented the loss of one IGF2R gene copy. These data confirm the localisation of the IGF2R receptor to distal 6q25. We also showed reduced expression of the soluble and membrane bound IGF-II receptor, a gene dosage effect incompatible with imprinting. The IGF2R gene has been shown to be imprinted in the mouse but not in humans. Our data provide further evidence for lack of imprinting of this gene in humans.

Adult↗

PubMed1996

Induction of hepatoma cell apoptosis by c-myc requires zinc and occurs in the absence of DNA fragmentation.

Since c-myc expression is increased during apoptosis in toxin-induced liver injury in vivo, the role of c-myc in liver cell apoptosis was investigated. The human hepatoma cell line HuH-7, which constitutively expresses c-myc, was stably transfected with sense and antisense c-myc expression vectors under the control of the zinc-inducible metallothionein promoter. None of the three cell types (wild-type, sense c-myc, or antisense c-myc) underwent apoptosis when cultured in serum-free medium (SFM). With the addition of SFM plus 37.5 microM zinc, wild-type and sense c-myc-expressing cells underwent rapid cell death, whereas antisense c-myc-expressing cells exhibited increased survival. This cell death had the light, fluorescent, and electron microscopic appearance of apoptosis, but did not result in DNA fragmentation. This apoptosis could be terminated by the addition of medium containing 2% fetal calf serum or the overexpression of bcl-2 but not by supplementation with specific growth factors. Altering c-myc expression did not affect cellular metallothionein mRNA levels or the rate of cell death from copper or cadmium. The requirement for zinc and absence of DNA fragmentation in c-myc-induced hepatoma cell apoptosis under serum-free conditions provides further evidence of the complex regulation of apoptosis in different cell types.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1996

Paracrine stimulation of cell growth by cholecystokinin/gastrin through cholecystokinin-B receptor on GH3 cells in vitro.

Cholecystokinin (CCK) is detected in pituitary tumors but its role remains unknown. On the hypothesis that CCK may facilitate the cell growth in pituitary tumors, we have examined the effect of CCK on cell growth using a rat pituitary tumor cell line, GH3, cultured in a serum-free, chemically defined medium. Addition of sulfated CCK-(26-33) (CCK-8) in two different concentrations (0.5 approximately 1 nM) caused a significant increase in the number of GH3 cells. The antagonist (1 microM) for CCK-B receptor, but not CCK-A receptor, significantly inhibited the number of GH3 cells. Northern blot analysis revealed a significant expression of CCK-B receptor mRNA in GH3 cells, but not in normal rat pituitary glands. In addition, immunoreactive CCK/gastrin was detected by RIA in the GH3 cell extracts as well as the serum-free culture medium. In GH3 cell extracts, both CCK-8 and gastrin like peptides were identified by gel chromatography. These findings provided the first evidence for an autocrine/paracrine role of CCK and gastrin on stimulation of GH3 cell growth through the CCK-B receptor.

Animals↗

PubMed1996

The inhibition of vitamin K3 on rabbit fibroblast proliferation in vitro.

Vitamin K3 that is commonly used to treat hemorrhagic diseases can inhibit human lymphatic neoplasms in vitro. This study was undertaken to investigate the effects of vitamin K3 on rabbit conjunctival fibroblast proliferation in cell culture. Vitamin K3 was added to cultured rabbit conjunctival fibroblasts. Remarkable inhibition was observed at a concentration of 4 mg/l. Because of its lower toxicity, vitamin K3 may prove to be of significant value in the treatment of intraocular proliferative disorders.

Animals↗