PubMed Health⌕ Search

Biomedical subjects

C A Toth

Publications and source records attributed to C A Toth.

At least 55 records · Page 3Linked to original sources
PubMed1995

Visible retinal lesions from ultrashort laser pulses in the primate eye.

PURPOSE: To evaluate the effects of ultrashort laser pulses of visible wavelengths on the retinas of rhesus monkey eyes and to perform threshold measurements for minimum visible lesions (MVLs) at pulsewidths from nanoseconds to femtoseconds. METHODS: Single laser pulses at visible wavelengths were placed within the macular area of live rhesus monkey eyes at varying pulse energies at five pulsewidths (4 ns, 60 ps, 3 ps, 600 fs, and 90 fs). The number of visible lesions was determined after 1 hour and 24 hours postexposure, and a probit analysis was performed for the dosage, causing 50% probability for damage (ED50) as well as the 95% fiducial intervals for ED50. Fluorescein angiography (FA) was performed, and hemorrhagic lesions were recorded as they became visible. RESULTS: The ED50 threshold doses at the 1-hour reading, calculated from the measured data, decreased from 1.5 microJ at 4 ns to 0.60 microJ at 600 fs, but it increased to 1.18 microJ at 90 fs. At the 24-hour reading, the ED50 calculated doses decreased from 0.90 microJ at 4 ns down to 0.26 microJ at 600 fs, but it increased to 0.43 microJ at 90 fs. Fluorescein angiography visible lesion ED50 values were all higher than MVL values, showing that FA was not as sensitive in determining damage levels. CONCLUSIONS: Laser pulses for pulsewidths between 4 ns and 90 fs are capable of producing visible lesions in monkey eyes with energies less than 1 microJ. Fluorescein angiography is not as sensitive in determining threshold levels as visually observing the retina through a fundus camera.

Animals↗
PubMed1994

Kupffer cell/tumor cell interactions and hepatic metastasis in colorectal cancer.

The degree of interaction with Kupffer cells of two moderately well differentiated cell lines, CX-1 and CCl-188 of high metastatic potential (61%) were compared to two poorly differentiated cell lines, MIP-101 and Clone A of low metastatic potential (6%) in the intrasplenic injection model for liver metastasis. MIP-101 and Clone A bound significantly better to mouse Kupffer cells in vitro than either CX-1 or CCL-188. We also identified specific cell surface proteins mediating attachment of colorectal carcinoma cells to murine Kupffer cells. Kupffer cells were radiolabelled and their surface proteins incubated with MIP-101 and CX-1. Two radiolabelled proteins from murine Kupffer cells of 14 and 34 kDa were identified consistently binding to the tumor cells. Binding of both proteins was inhibited by asialofetuin but not by fetuin. This suggests that the major binding proteins between Kupffer cells and colorectal cancer cells are galactose binding lectins.

Animals↗
PubMed1993

Carcinoembryonic antigen: enhancement of liver colonisation through retention of human colorectal carcinoma cells.

Carcinoembryonic antigen (CEA) is an oncofetal antigen whose function in the progression of colorectal carcinoma remains unclear although recent studies suggest it participates in homotypic cellular adhesion. We have previously shown that 40 micrograms of CEA injected intravenously into athymic nude mice enhances experimental metastasis in liver and lung by two human colorectal carcinoma cell lines that are injected intrasplenically 30 min later. The metastatic potential of another three moderately to highly metastatic colorectal carcinoma cell lines and of one weakly metastatic line has now been analysed in this model. CEA pretreatment only enhanced colony formation by cell lines that were weakly metastatic in untreated nude mice; it did not affect experimental metastasis by highly metastatic lines. CEA pretreatment enhanced the retention of 125I Idudr-labelled weakly metastatic tumour cells within the liver and lungs 4 h after intrasplenic injection but not the retention of highly metastatic tumour cells or inert latex beads. A significant correlation existed between the formation of experimental metastases and the early retention of tumour cells within the liver after intrasplenic injection. Aggregation did not appear to be important for retention in liver because CEA did not aggregate colorectal carcinoma cells in vitro. Also CEA did not alter natural host effector cell function in a cytolysis assay in vitro. We suggest that CEA facilitates liver colonisation by three of eight human colorectal carcinomas in athymic nude mice by increasing the hepatic retention of tumour cells. The potential mechanisms by which CEA may increase the retention of tumour cells in the liver are discussed.

Animals↗
PubMed1993

Role of the complement system in antigen-induced bronchoconstriction and changes in blood pressure in the guinea pig.

Systemic anaphylaxis involves life-threatening bronchoconstriction and a serious hypotensive response often complicated by cardiac arrhythmias. The purpose of the present study was to determine whether complement system activation is essential to the bronchoconstriction and the changes in blood pressure seen in guinea pig models of anaphylaxis. The soluble complement receptor 1 (sCR1; BRL 55730) was used to inhibit activation of the classical and alternative pathways of complement in the guinea pig, and to determine whether this inhibition prevents bronchoconstriction and changes in blood pressure induced by i.v. antigen injection in guinea pigs that are either passively or actively sensitized to the antigen ovalbumin. sCR1 at 15 mg/kg did not affect significantly either the antigen-induced bronchoconstriction or the changes in blood pressure in a guinea pig passively sensitized with immunoglobulin G antibody to ovalbumin. However, it shortened the duration of the antigen-induced increase in blood pressure and inhibited the antigen-induced decrease in circulating platelets in an actively sensitized guinea pig. Continued studies using a cumulative dose of sCR1 of 105 mg/kg administered over a 24-hr period demonstrated that sCR1 attenuated the bronchoconstrictor response and the decrease in circulating platelets and prevented the hypotension induced by antigen in an actively sensitized guinea pig. At a cumulative dose of 105 mg/kg, sCR1 did not inhibit the bronchoconstrictor or blood pressure response to either histamine or bradykinin, indicating that its attenuation of cardiovascular and respiratory reactivity is specific for complement-related processes. The anaphylactic response was accompanied by complement activation as evidenced by cleavage of the C3 molecule. In the presence of sCR1, no C3 cleavage products were detectable in the plasma. Our studies demonstrate that complement activation is an essential step in the antigen-induced bronchoconstriction and the changes in blood pressure in an actively sensitized guinea pig model of anaphylaxis. Continued studies of the differing mechanisms and mediators of anaphylaxis are of importance, and the complement system clearly warrants consideration as a source of those mediators.

Animals↗
PubMed1992

A peptide sequence on carcinoembryonic antigen binds to a 80kD protein on Kupffer cells.

Clearance of carcinoembryonic antigen (CEA) from the circulation is by binding to Kupffer cells in the liver. We have shown that CEA binding to Kupffer cells occurs via a peptide sequence YPELPK representing amino acids 107-112 of the CEA sequence. This peptide sequence is located in the region between the N-terminal and the first immunoglobulin like loop domain. Using native CEA and peptides containing this sequence complexed with a heterobifunctional crosslinking agent and ligand blotting with biotinylated CEA and NCA we have shown binding to an 80kD protein on the Kupffer cell surface. This binding protein may be important in the development of hepatic metastases.

Amino Acid Sequence↗
PubMed1992

Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases.

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.

Animals↗
PubMed1992

Ultramicrosurgical removal of subretinal hemorrhage in cats.

Subretinal hemorrhages are associated with progressive degeneration of the outer retina and a corresponding poor visual prognosis. Mixed results have been reported in previous attempts to remove such subretinal hemorrhages. We developed an ultramicrosurgical system that used the control of a stereotactic micromanipulator to direct a micropipette tip through a small retinotomy into the subretinal space in three cat eyes. Low-dose recombinant tissue plasminogen activator was then introduced into the subretinal space around the subretinal hemorrhage via a controlled microinfusion system. The recombinant tissue plasminogen activator solution facilitated clot lysis and subsequent removal through the micropipette. Light- and electron-microscopic analysis of histopathologic specimens disclosed good preservation of retinal architecture in the three cat eyes in which experimental subretinal hemorrhages were removed. This was in contrast to the retinal degeneration observed in similar but untreated experimental subretinal hemorrhages.

Animals↗
PubMed1992

Treatment of retinopathy of prematurity with argon laser photocoagulation.

Fifteen eyes of nine infants were treated for retinopathy of prematurity by confluent photocoagulation of the avascular retina using an argon laser indirect ophthalmoscope. All treated eyes presented at or beyond threshold of stage 3 retinopathy of prematurity with "plus" disease. Three treated eyes had retinopathy of prematurity in zone I. Early complete regression of extraretinal proliferation was seen in 13 eyes. At 6 month's [corrected] minimum follow-up, 11 (73%) of the treated eyes demonstrated a favorable outcome, while four eyes (27%) progressed to an unfavorable outcome. No intraocular hemorrhages occurred during any laser treatment.

Cryosurgery↗
PubMed1992

Carcinoembryonic antigen binding proteins on elicited peritoneal macrophages.

Carcinoembryonic antigen (CEA), a member of the immunoglobulin supergene family, is recognized by a specific 80-kd receptor on Kupffer cells and alveolar macrophages. Peritoneal macrophages were harvested from male Sprague-Dawley rats 72 h after intraperitoneal injection with thioglycolate broth and from unstimulated animals. The elicited peritoneal macrophages had a much greater capacity to endocytosed CEA than the cells isolated from unstimulated animals. They took up CEA in a concentration- and time-dependent manner. Cellular uptake was temperature and colchicine sensitive indicating internalization of CEA. The process was saturable and could be specifically inhibited by CEA and nonspecific crossreacting antigen (NCA), a member of the CEA supergene family. Two binding proteins of approximately 35 and 80 kd were isolated from the surface of the peritoneal macrophages by affinity chromatography on a CEA-Sepharose column. Using CEA coupled to sulfo-succininidyl-2-[p-azidosalicyl amide]-1,3'-dithiopropionate (SASD), a photoactivatable crosslinker, two binding proteins of 55 and 80 kd were identified on the surface of live peritoneal macrophages. The specificity of CEA endocytosis and binding proteins exhibited by the elicited peritoneal cells are similar to that previously reported for Kupffer cells and alveolar macrophages.

Animals↗
PubMed1992

Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production.

The relationship between cellular differentiation and carcinoembryonic antigen (CEA) production by human colorectal tumor cells and their ability to form hepatic metastases was studied. Eight human colon cancer cell lines were injected into athymic mice using different routes of administration to characterize their metastatic potential. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver after intrasplenic injection. After intraperitoneal implantation the same cell lines were highly tumorigenic, and subsequently metastatic to the liver. In contrast, the four moderate to well-differentiated cell lines that produced moderate to high levels of CEA were highly metastatic to the liver following intrasplenic injection. After intraperitoneal implantation they were less tumorigenic, and metastatic to the liver. We conclude that in this system poorly differentiated non or low CEA producing colorectal cell lines have a lower metastatic capacity compared to the well-differentiated high CEA producing colorectal cell lines. These data correlate directly with the pattern of metastatic spread and clinical course observed in patients with these tumors, suggesting that degree of differentiation and level of CEA production may play a role in development of site-specific metastases.

Animals↗
PubMed1992

Antifibrotic and uveitogenic properties of gamma interferon in the rabbit eye.

The feasibility of gamma (gamma)-interferon injection for the treatment of ocular fibrotic conditions was studied in rabbits using recombinant rabbit gamma-interferon and the cell-injection model of tractional detachment. A toxicity study revealed that intravitreal injection of greater than 10(4) units gamma-interferon consistently produced panuveitis. For tractional detachment, 250,000 rabbit dermal fibroblasts were injected intravitreally into 20 eyes; 1 day later, 5 of these eyes received intravitreal injections of 10(4) units gamma-interferon, another 5 were given 10(6) units, and the remaining 10 received balanced salt solution. Slit-lamp examination and fundus photography were performed at regular intervals for 21 days and were graded by a masked observer. The eyes were then enucleated and processed for histology. Doses of 10(4) units gamma-interferon significantly reduced the severity of detachments, but injections of 10(6) units induced panuveitis.

Animals↗
PubMed1992

Type I interferon resistance in a colorectal cancer cell line is associated with a more aggressive phenotype in vivo.

A type I interferon resistant variant (beta-MIP101) of the poorly differentiated human colon cancer cell MIP101 has a more aggressive phenotype in vivo in the nude mouse. Subcutaneous tumours grew at twice the rate of MIP101, but with similar morphology. beta-MIP101 also produced liver metastases at a higher frequency. beta-MIP101 tumours were diploid while MIP101 tumours were aneuploid. Both cell lines had doubling times of approximately 25 h in vitro.

Animals↗
PubMed1992

An experimental model of ectropion uveae and iris neovascularization in the cat.

Neovascularization of the iris (NVI) is one of the most frequently studied intraocular vascular proliferations in animal models. Ectropion uveae has not been a consistent finding in these studies. In this study, a surgical model of ectropion uveae and iris neovascularization was developed that involved lensectomy, vitrectomy, bipolar cautery and transection of all three principal branch veins in the cat eye. Twelve of 14 eyes that received this procedure developed postoperative retinal detachments with a clinical picture of hemorrhagic retinopathy. These eyes progressed to a clinical picture of NVI within 1-7 wk. Eight eyes developed ectropion uveae for as much as 300 degrees. At the light microscopic level, a fibrovascular membrane was apparent on the anterior iris stroma in 9 of 14 eyes and further involved the angle in six eyes.

Animals↗
PubMed1991

Fibrin directs early retinal damage after experimental subretinal hemorrhage.

Subretinal blood within the macula may cause visual loss in a number of macular diseases. The clinical and histopathologic effects of experimental subretinal hemorrhage were evaluated in the cat. Subretinal hemorrhages were produced by creating a focal neurosensory retinal detachment with micropipette techniques, then inserting a needle tip transsclerally to allow choroidal blood to fill the bleb. Experimental lesions were examined clinically and with light and electron microscopy during a 14-day postoperative period. Initial observations included clot organization with retraction of fibrin strands. In six of nine clots more than 1 hour old, fibrin was associated with tearing of sheets of photoreceptor inner and outer segments. Later degeneration progressed to involve all retinal layers overlying the densest areas of fibrin in the clots. Hemorrhages into subretinal blebs containing tissue plasminogen activator did not form fibrin strands or cause photoreceptor tearing. These findings highlight the potential for improved retinal survival if organized subretinal clot can be eliminated soon after formation.

Animals↗