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PubMed1989

Methods of simultaneous treatment of the mandible defects and the adjacent soft tissues.

Original methods of removing combined defects of the mandibular body and the adjacent soft tissues are described: osteoplasty by local tissues and nonfree osteoplasty. A compression-distraction apparatus of the authors' own construction is used. During the re-arrangement of the bone fragments and the osteotomized portions of the mandible, simultaneous repair of the defect of the bony tissue and the soft tissues takes place without using free bone transplants and soft-tissue flaps. Duration of treatment varies between 2 1/2 and 5 months depending on the size of the defect. A total of 12 persons with traumatic defects of the lower jaw from 2 to 8 cm in length and of the adjacent soft tissues were treated by these methods. Good functional and cosmetic results were obtained.

Adult↗
PubMed1986

Tissue of origin of elevated alpha-fetoprotein in ataxia-telangiectasia.

Although only a single gene exists for alpha-fetoprotein (AFP), differential glycosylation generates several different forms and these are associated with different tissues of origin, namely, liver, gastrointestinal tract, and yolk sac. This microheterogeneity of serum AFP was studied in seven patients with ataxia-telangiectasia (AT) in order to determine the tissue of origin of their elevated AFP levels. Concanavalin A (Con A), Lens culinaris agglutinin A (LCA-A), and erythroagglutinating phytohemagglutinin (E-PHA) affinity electrophoresis and antibody-affinity blotting were used to fractionate AFP. It was found that serum AFP in AT patients was composed mainly of Con-A band 2 (AFP-C2), LCA-A band 1 (AFP-L1), and E-PHA band 2 (AFP-P2). This profile of AFP species in AT patients is similar to those seen in neonates and patients with chronic hepatitis, but clearly different from AFP originating in hepatocellular carcinoma, gastric carcinoma, and yolk sac tumour cells. These data are compatible with a hepatic origin for the elevated AFP in AT patients. Since no evidence exists for ongoing liver damage in these patients, we suggest that the AFP gene in the AT liver may be under aberrant transcriptional control, perhaps secondary to a defect of DNA regulatory proteins which are necessary for hepatic maturation.

Ataxia Telangiectasia↗
PubMed1999

Equilibrium binding characteristics of [3H]thiomuscimol.

The equilibrium binding characteristics of the tritiated GABAA agonist, 5-aminomethyl-3-isothiazolol (thiomuscimol) are described. Using the filtration technique to separate bound- from free-ligand, [3H]thiomuscimol was shown to bind to the GABA(A) receptor site(s) in a saturable manner with a Kd value of 28+/-6.0 nM and a Bmax value of 50+/-4.0 fmol/mg original tissue. In parallel binding experiments, the Kd and Bmax values for [3H]muscimol were determined to be 5.4+/-2.8 nM and 82+/-11 fmol/mg original tissue, respectively. In binding assays using the centrifugation technique, Kd and Bmax values for [3H]thiomuscimol were found to be 116+/-22 nM and 154 13 fmol/mg original tissue, respectively, whereas a Kd value of 16+/-1.8 nM and a Bmax value of 155+/-8.0 fmol/mg original tissue were determined for [3H]muscimol. In comparative inhibition studies using the GABA(A) antagonist SR 95531 and a series of specific GABAA agonists, the binding sites for [3H]thiomuscimol and [3H]muscimol were shown to exhibit similar pharmacological profiles. Autoradiographic studies disclosed similar regional distribution of [3H]thiomuscimol and [3H]muscimol binding sites in rat brain. Highest densities of binding sites were detected in cortex, hippocampus, and cerebellum, whereas low densities were measured in the midbrain structures of rat cortex. In conclusion, the equilibrium GABA(A) receptor binding characteristics of [3H]thiomuscimol are very similar to those of [3H]muscimol.

Animals↗
PubMed2001

Synthesis and characterization of a quinolinonic compound activating ATP-sensitive K(+) channels in endocrine and smooth muscle tissues.

Original quinolinone derivatives structurally related to diazoxide were synthesized and their effects on insulin secretion from rat pancreatic islets and the contractile activity of rat aortic rings determined. A concentration-dependent decrease of insulin release was induced by 6-chloro-2-methylquinolin-4(1H)-one (HEI 713). The average IC(50) values were 16.9+/-0.8 microM for HEI 713 and 18.4+/-2.2 microM for diazoxide. HEI 713 increased the rate of (86)Rb outflow from perifused pancreatic islets. This effect persisted in the absence of external Ca(2+) but was inhibited by glibenclamide, a K(ATP) channel blocker. Inside-out patch-clamp experiments revealed that HEI 713 increased K(ATP) channel openings. HEI 713 decreased (45)Ca outflow, insulin output and cytosolic free Ca(2+) concentration in pancreatic islets and islet cells incubated in the presence of 16.7 or 20 mM glucose and extracellular Ca(2+). The drug did not affect the K(+)(50 mM)-induced increase in (45)Ca outflow. In aortic rings, the vasorelaxant effects of HEI 713, less potent than diazoxide, were sensitive to glibenclamide and to the extracellular K(+) concentration. The drug elicited a glibenclamide-sensitive increase in (86)Rb outflow from perifused rat aortic rings. Our data describe an original compound which inhibits insulin release with a similar potency to diazoxide but which has fewer vasorelaxant effects. Our results suggest that, in both aortic rings and islet tissue, the biological effects of HEI 713 mainly result from activation of K(ATP) channels ultimately leading to a decrease in Ca(2+) inflow.

Adenosine Triphosphate↗
PubMed2001

Different representations of inescapable noxious stimuli in the periaqueductal gray and upper cervical spinal cord of freely moving rats.

Previous work suggested that pain of distinct tissue origins was differentially represented in the midbrain periaqueductal gray (PAG). That is, persistent pain of deep origin (muscle, joint viscera) "activated" ventrolateral PAG neurons and triggered quiescence, hyporeactivity and vasodepression (i.e. passive emotional coping); whereas intermittent cutaneous pain "activated" lateral PAG neurons and triggered fight-flight (i.e. active emotional coping). Cutaneous noxious stimuli, if inescapable however, trigger a passive emotional coping reaction similar to that evoked by pain of deep origin. This raised the question--is it the behavioural significance (escapability versus inescapability) or the tissue origin (cutaneous versus deep) of the pain, that is represented in the PAG? In this study we used immediate-early-gene (c-Fos) expression to examine PAG and spinal activation patterns following "inescapable" (persistent) pain of cutaneous versus deep origin. It was found that selective activation of the ventrolateral PAG and passive emotional coping were evoked by an inescapable cutaneous noxious stimulus (i.e. clip of the neck), as well as by a deep noxious stimulus (i.e. neck muscle pain). In the upper cervical spinal cord, however, these noxious manipulations evoked distinct patterns of Fos expression which reflected the different patterns of primary afferent termination arising from skin versus muscle. The results suggest that whereas pain representation in the spinal cord accurately reflects tissue origin, pain representation in the PAG better reflects behavioural significance.

Animals↗
PubMed2026

Cancer of unknown primary: the evolution of tissue of origin identification in the artificial intelligence era.

Cancer of Unknown Primary (CUP) presents substantial diagnostic and therapeutic challenges owing to its heterogeneous nature and the absence of an identifiable primary tumor site. This review provides a structured search of the pathogenesis, epidemiological characteristics, and limitations of traditional diagnostic and therapeutic approaches for CUP, with an emphasis on the evolution of Tissue of Origin (TOO) identification techniques. Recent advances in precision medicine have accelerated the development of machine learning-based TOO identification tools, representing a paradigm shift in CUP diagnostics. Deep learning (DL) algorithms that integrate multi-omics data (such as genomics and transcriptomics) with clinical features have markedly enhanced the accuracy of tracing tumor origin, and artificial intelligence (AI) driven TOO models are increasingly being incorporated into clinical practice, offering new insights for pathological diagnosis, treatment selection, and prognostic evaluation. Nevertheless, several challenges remain, including issues of data standardization, model generalizability, and interpretability. Ethical considerations related to data privacy, algorithmic fairness, and clinical implementation also warrant careful attention. Future research should focus on establishing standardized multi-center databases, developing more interpretable AI models, and fostering multidisciplinary collaborative strategies for CUP management. Through continued refinement of technical solutions and regulatory guidelines, TOO identification is anticipated to progress from research to routine clinical application, ultimately supporting precise and personalized care for patients with CUP.

Artificial intelligence↗
PubMed1994

Cultured neurons from mouse brain reproduce the muscarinic receptor profile of their tissue of origin.

These studies investigate the regional variations in the muscarinic acetylcholine receptor (mAChR) profiles in neuron populations of the CNS using primary neuron cultures derived from three areas of the mouse brain--the cerebral hemispheres, the mesencephalon and the medulla-pons--that have distinct mAChR systems. We first assessed the extent to which neurons reproduced their in vivo properties in culture by monitoring the binding capacity, the pharmacological profiles and the levels of mAChR transcripts in neuron cultures and their tissues of origin. We showed that the primary neuron cultures accumulated mAChRs with initial rates similar to those in vivo, had pharmacological profiles very close to those of their area of origin, and accumulated m1, m2, m3, m4 and m5 receptor transcripts according to patterns resembling those in the tissues. We conclude that most of the characteristics of the mAChRs in a given area are proper to the neuron population of that area, that the pattern is established early in ontogenesis, and that it is reproduced in vitro. We also show that the stimulation of phosphoinositide turnover is mediated by mAChRs with distinct pharmacological profiles in neuron cultures from the three brain areas.

Amino Acid Sequence↗
PubMed1991

Simple technique for culture of highly differentiated cells from dog tracheal epithelium.

Cultures of dog tracheal epithelium have proved very useful in studies of ion transport. Their short-circuit current (Isc), however, is usually much less than the original tissue. We have tested a variety of conditions in an attempt to produce large numbers of cells with electrical properties comparable with the original tissue. Of several growth supports, human placental collagen (HPC) gave the best results. When plated at 2.5 x 10(5) cells/cm2 onto HPC, cells grown in serum-free, growth factor-supplemented medium (GF medium) showed increases in cells per unit area, thickness of cell sheet, numbers of domes, numbers of apical microvilli, and degree of basolateral membrane interdigitation compared with cells grown in medium containing 5% fetal calf serum (FCS medium). Transepithelial resistance (Rte) and the increases in Isc and intracellular Ca in response to isoproterenol were also increased. However, baseline Isc and adenosine 3',5'-cyclic monophosphate levels were not changed. The improved electrical properties were maintained for up to 4 mo. GF medium combined with an air interface produced further increases in Rte, Isc, and changes in Isc in response to amiloride and isoproterenol. Ultrastructural features such as the presence of cilia, greater thickness of the cell sheet, and increased amplification of apical and basolateral membranes also indicated improved differentiation. Our results show that GF medium and an air interface can be combined with a simple growth support and a relatively low-plating density to allow the easy production of greater than 500 cm2 of cultured cells from a single trachea, with a level of differentiation similar to that of the original tissue.

Animals↗
PubMed1994

Equilibrium constants for the binding of fatty acids with fatty acid-binding proteins from adipocyte, intestine, heart, and liver measured with the fluorescent probe ADIFAB.

Affinities of long chain fatty acids (FA) for fatty acid-binding proteins (FABPs) have been measured by monitoring the concentrations of the unbound or free fatty acids (FFA) in equilibrium with the FABPs using the fluorescent probe ADIFAB. This probe allows the measurement of the concentration of FFA in equilibrium with FABPs, without physical separation of any of the reactants. Equilibrium characteristics were measured at 37 degrees C for palmitate, stearate, oleate, linoleate, linolenate, and arachidonate binding to six FABPs from intestine, heart, adipose, and liver from different species. Equilibrium constants for each FA were found to be extremely sensitive to the tissue origin of the FABP but largely independent of species differences. The measured values of the dissociation constants (Kd) ranged from about 2 to 1000 nM, depending upon the tissue origin of the FABP and the FA. Binding constants for some FABPs varied considerably with different FA, as much as 80-fold in the case of the intestinal FABP. In contrast, Kd values for adipocyte FABPs exhibited less than 4-fold variation with FA type and are generally larger (lower affinities) than for the other FABPs. For all FABPs, Kd values for fatty acids with the same chain length were considerably lower for saturated as compared to polyunsaturated FA. This characteristic likely reflects the lower aqueous solubilities of the saturated fatty acids. In contrast to the other FABPs, rat liver FABP was found to have two FA-binding sites/monomer. Each of these two sites had similar high affinities for the saturated FA, while for the unsaturated FA the two sites exhibited affinities that differ by more than 7-fold. This study disagrees with earlier investigations in finding that equilibrium binding of FA to FABPs is a sensitive function of FA type and FABP tissue origin and that FA-FABP dissociation constants are submicromolar. These results provide a framework with which to understand better the biological function of FABPs and the FA-FABP interaction.

Adipocytes↗
PubMed1981

The particular traits of carcinogenesis induced in Wistar rats by aflatoxin B1. III. Porphyrins and the activity of gamma-glutamyltranspeptidase in primary hepatomas and in their tissue of origin.

Inbred Wistar rats were fed aflatoxin B1 (AFB1) during a period of 15 weeks. Some of the rats were sacrificed successively at different time intervals, and the remaining animals died a natural death. Beginning with the day of AFB1 treatment termination multifocal hepatomas appeared on the 265th day in males and on the 296th day in females. The progress of AFB1 carcinogenesis was accompanied by an ever increasing disorder of porphyrin metabolism. The content of the porphyrin fractions in primary hepatomas was greater than in the tissue of origin. Serum and hepatic GGTP activity increased with the advancement of hepatocarcinogenesis and paralleled the increase of tumor weight. The GGTP activity in hepatoma reached values exceeding those in their host liver.

Aflatoxin B1↗
PubMed2002

New human microvascular endothelial cell lines with specific adhesion molecules phenotypes.

Vascular endothelial cells recognize blood-borne circulating cells and allow them to extravasate in a tissue-specific manner. Because this property determines the selectivity of lymphocyte homing, it is fundamental in physiological as well as pathological processes (inflammation, autoimmune diseases, metastasis). As a tool to assess the molecular basis of endothelium selectivity, microvascular endothelial cell lines of distinct tissue origin were established. Endothelial cells, isolated from lymphoid tissues (lymph nodes and appendix) and from nonlymphoid immune sites--intestine, lung, and skin--were immortalized in vitro. Their general endothelial characteristics, such as the presence of von Willebrand factor (wWf), angiotensin-converting enzyme (ACE), VE-cadherin, and the intracellular E-selectin, were preserved. This article shows that these cell lines display phenotypic characteristics related to their tissue origin. Hence, endothelial cells from lymph nodes expressed peripheral lymph node addressins (PNAds). Endothelial cells from nonlymphoid tissues were ICAM-1 (intercellular adhesion molecule-1) and CD49e positive, whereas P-selectin was not equally distributed among the cell lines. Endothelial cells from mucosal sites reacted with antibody against human MAdCAM-1 (mucosal addressin cell adhesion molecule). In the adhesion test, lymphoid and myeloid cells adhere to endothelial cell lines in a distinct manner. These lines could be useful to study molecular mechanisms involved in tissue-specific cell-cell interaction.

Animals↗
PubMed1999

Female urethral adenocarcinoma: immunohistochemical evidence of more than 1 tissue of origin.

PURPOSE: Urethral adenocarcinoma is a rare malignancy whose origin remains controversial. The monoclonal antibody mAbDas1 (formerly 7E12H12) was developed against a unique colonic epithelial epitope and is reactive in areas of intestinal metaplasia. Recently the antibody was shown to react in cystitis glandularis as well as adenocarcinoma of the bladder, suggesting that cystitis glandularis may be the precursor of bladder adenocarcinoma. We examined urethral adenocarcinomas and benign urethral specimens using mAbDas1 to determine whether it could provide insight into their histogenesis. MATERIALS AND METHODS: Archival tissue from 12 cases of primary female urethral adenocarcinoma and urethral specimens of inflamed urethral mucosa, urethritis glandularis and transitional cell carcinoma was studied. Immunohistochemical analysis of formalin fixed, paraffin embedded archival tissue was done using the monoclonal antibody mAbDas1. Tumors were also evaluated with a prostate specific antigen (PSA) polyclonal antibody as previous studies have noted PSA reactivity in these tumors. RESULTS: Of the 12 cases 9 were columnar/mucinous adenocarcinoma, 2 clear cell adenocarcinoma and 1 a cribriform pattern resembling adenocarcinoma of the prostate. All columnar/mucinous adenocarcinomas reacted positively (6 strongly and 3 focally) with the mAbDas1 antibody but did not react with the PSA antibody. The tumor with a cribriform pattern reacted strongly with PSA but did not react with mAbDas1. The 2 clear cell adenocarcinomas did not react with either antibody. The benign urethral specimens demonstrated strong reactivity to the mAbDas1 antibody in areas of urethritis glandularis but normal and inflamed urethral mucosa and transitional cell carcinoma did not react. CONCLUSIONS: Primary adenocarcinoma of the female urethra arises from more than 1 tissue of origin. Columnar/mucinous adenocarcinomas of the female urethra and urethritis glandularis demonstrate consistent reactivity with the mAbDas1 antibody, suggesting that these tumors arise from glandular metaplasia analogous to the potential histogenesis previously demonstrated in the bladder. PSA reactivity occurred in 1 tumor with a cribriform pattern and likely represents origin from Skene's glands. Clear cell adenocarcinomas did not react with either antibody, suggesting a third possible pathway in the development of this rare subset of adenocarcinomas.

Adenocarcinoma↗
PubMed1995

Female urethral adenocarcinoma: evidence for more than one tissue of origin?

Adenocarcinoma of the female urethra accounts for 10% of all urethral cancers. Controversy continues to exist over the origin of primary urethral adenocarcinomas. The periurethral (Skene's) glands appear to be the homologues of the male prostate as defined by authors evaluating cadaver-derived periurethral glands pathologically and immunohistochemically (prostate-specific antigen (PSA)). It is traditionally assumed that the origin of female urethral adenocarcinoma is the Skene's gland. However, no one has evaluated a series of primary urethral adenocarcinomas in an effort to scrutinize this assumption. We, therefore, evaluated 13 primary adenocarcinomas of the female urethra comparing histologic and immunohistochemical characteristics. Tumors were classified into two major histologic groups: columnar/mucinous (11) and clear cell (2). Excluding one case, the columnar/mucinous tumors resembled either endometrial or colonic adenocarcinoma. The exception was a case bearing a striking resemblance to prostatic adenocarcinoma. Immunohistochemical results revealed positive PSA staining for this tumor alone. The patient's preoperative serum PSA was elevated, but rapidly declined postoperatively. Based on immunohistochemical findings and the presence of distinct histologic subtypes (columnar/mucinous, clear cell), it appears that female urethral adenocarcinoma has more than one tissue of origin with a minority arising from the Skene's glands.

Adenocarcinoma, Clear Cell↗
PubMed2006

A quantitative reverse transcriptase-polymerase chain reaction assay to identify metastatic carcinoma tissue of origin.

Identifying the primary site in patients with metastatic carcinoma of unknown primary origin can enable more specific therapeutic regimens and may prolong survival. Twenty-three putative tissue-specific markers for lung, colon, pancreatic, breast, prostate, and ovarian carcinomas were nominated by querying a gene expression profile database and by performing a literature search. Ten of these marker candidates were then selected based on validation by reverse transcriptase-polymerase chain reaction (RT-PCR) on 205 formalin-fixed, paraffin-embedded metastatic carcinoma specimens originating from these six and from other cancer types. Next, we optimized the RNA isolation and quantitative RT-PCR methods for these 10 markers and applied the quantitative RT-PCR assay to a set of 260 metastatic tumors. We then built a gene-based algorithm that predicted the tissue of origin of metastatic carcinomas with an overall leave-one-out cross-validation accuracy of 78%. Lastly, our assay demonstrated an accuracy of 76% when tested on an independent set of 48 metastatic samples, 37 of which were either a known primary or initially presented as carcinoma of unknown primary but were subsequently resolved.

Algorithms↗
PubMed1994

Muscarinic receptor profiles of mouse brain astrocytes in culture vary with their tissue of origin but differ from those of neurons.

The two main cell populations in brain tissues are neurons and astrocytes. Cultures of both bear muscarinic acetylcholine receptors (mAChRs). Available data indicate that astrocyte mACRs are heterogeneous, but the particular subtypes on these cells are not known, nor is there any information as to whether there is a regional variation in the mAChR profile of astrocytes. This paper describes the mAChR profiles of cultured astrocytes derived from the cerebral hemispheres, mesencephalon and medulla-pons, and is a continuation of our study on cultures of neurons from these same tissues. Pharmacological studies showed that astrocytes accumulated small amounts of mAChRs with distinct pharmacological profiles which, for a given area, differed from those of neurons in culture. Northern blot analyses showed transcripts for m1 and m3 mAChRs only. Their concentrations differed from one cell population to another. Astrocyte cultures from the mesencephalon contained m1 mRNA amounts close to those in the tissue. Thus, at least part of the mAChR profile in vitro might be a true reflection of the cell's properties in vivo. Functional studies showed that mAChRs mediate the stimulation of phosphoinositide turnover in all three astrocyte cultures, that the amplitude of this response varies greatly with the origin of the cell, and that two pharmacological subclasses, M1 and M1-2-, are involved in these responses, but to different extents. Thus the CNS contains discrete astrocyte populations which in culture differ in their mAChR profiles at the molecular, the pharmacological and the functional levels.

Animals↗
PubMedDate not supplied

[Origin of tissue basophils and basophilic granulocytes of the blood].

The paper deals with analysis of modern literature on origin of basophils and basophilic blood granulocytes. Data of radioimmunologic, electron-microscopic, cytochemical and morphological studies make it possible to conclude that these cells are of bonemarrow origin.

Animals↗
PubMed1999

Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineage.

The cardiac pacemaking and conduction system sets and maintains the rhythmic pumping action of the heart. Previously, we have shown that peripheral cells of the conduction network in chick (periarterial Purkinje fibers) are selected within a cardiomyogenic lineage and that this recruitment occurs as a result of paracrine cues from coronary arteries. At present, the cellular derivation of other elements of this specialized system (e.g. the nodes and bundles of the central conduction system) are controversial, with some proposing that the evidence supports a neurogenic and others a myogenic origin for these tissues. While such ontological questions remain, it is unlikely that progress can be made on the molecular mechanisms governing patterning and induction of the central conduction system. Here, we have undertaken lineage-tracing strategies based on the distinct properties of replication-incompetent adenoviral and retroviral lacZ-expressing constructs. Using these complementary approaches, it is shown that cells constituting both peripheral and central conduction tissues originate from cardiomyogenic progenitors present in the looped, tubular heart with no detectable contribution by migratory neuroectoderm-derived populations. Moreover, clonal analyses of retrovirally infected cells incorporated within any part of the conduction system suggest that such cells share closer lineage relationships with nearby contractive myocytes than with other, more distal elements of the conduction system. Differentiation birthdating by label dilution using [(3)H]thymidine also demonstrates the occurrence of ongoing myocyte conscription to conductive specialization and provides a time course for this active and localized selection process in different parts of the system. Together, these data suggest that the cardiac conduction system does not develop by outgrowth from a prespecified pool of 'primary' myogenic progenitors. Rather, its assembly and elaboration occur via processes that include progressive and localized recruitment of multipotent cardiomyogenic cells to the developing network of specialized cardiac tissues.

Adenoviridae↗
PubMed1994

DNA interstrand crosslinking agents and human ocular fibroblasts: differential sensitivity to mitomycin-C and cis-diaminedichloroplatinum(II).

Although clinical application of mitomycin-C (MMC) as an adjunct to glaucoma filtration and pterygium ablation surgeries is based on its inhibitory effect on the local fibroblast proliferation, the extent to which fibroblasts of Tenon's capsule and adjacent tissues (ocular fibroblasts) are susceptible to MMC still remains to be investigated. In this context, we substantially compared the sensitivity of ocular fibroblasts to MMC with normal fibroblasts of other tissue origins and with Fanconi's anemia (FA) fibroblasts known to be supersensitive to MMC due to presumable genetic susceptibility. Since MMC kills cells mainly by forming DNA interstrand crosslinks, cis-diaminedichloroplatinum (CDDP), another crosslinking agent, was also used to evaluate the cytotoxic effect of crosslinks on ocular and other fibroblasts. Following the treatment with various concentrations of MMC or CDDP for 1 hr, fibroblasts were incubated for 14 days until colonies developed. Based on the colony number reflecting the cell number which survived, the regression lines of survival rates were plotted in a semilogarithmic fashion. D0 and D10, doses which reduced survival rate to 37% and 10%, respectively, were interpolated and compared among the three cell groups. Ocular fibroblasts were about 2.5 times more sensitive than other normal fibroblasts, but 4-5 times more resistant than FA fibroblasts, to MCC, since the mean D0 of ocular, other normal, and FA fibroblasts was 0.063, 0.171 and 0.015 micrograms ml-1, respectively, and the mean D10 of these was 0.154, 0.401 and 0.029 micrograms ml-1, respectively. On the other hand, ocular fibroblasts exhibited an isosensitivity to CDDP compared with other normal fibroblasts. FA fibroblasts showed a supersensitivity to CDDP as well. DNA synthesis assay analysed by immunocytochemistry using bromodeoxyuridine (BrdU) and anti-BrdU antibody showed a similar hypersensitivity to MMC but a normosensitivity to CDDP of ocular fibroblasts. These results may indicate that intracellular activation of MMC to the reactive reduced form progresses more effectively in ocular fibroblasts than in fibroblasts originating in other tissues. The hypersensitivity to MMC of ocular fibroblasts is not attributed to genetic susceptibility because of the normosensitivity to CDDP. CDDP may be a promising agent as an alternative to MMC in the ophthalmic fields.

Cell Division↗