Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Functional differentiation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed2001

Luteinizing hormone-dependent activity and luteinizing hormone-independent differentiation of rat fetal Leydig cells.

Addition of 5x10(-2) U/ml recombinant luteinizing hormone (LH) to testes from fetuses at 16.5 day post conception (dpc) cultured for 5 days increased the number of Leydig cells by 34% and the acute LH-stimulated testosterone production by 600%. To determine whether these positive effects of LH in vitro are physiologically relevant in vivo, fetuses were decapitated on days 16.5 pc (before the onset of LH expression in the hypophysis) or 18.5 pc (before the surge of LH in the fetal plasma) and removed at 21.5 dpc. The number of fetal Leydig cells per testis and the acute LH-stimulated testosterone production by the testes ex vivo were unaltered by decapitation. Since, in all groups, the number of Leydig cells doubled between 16.5 and 18.5 dpc and between 18.5 and 21.5 dpc, these results suggest that neither the appearance of new fully differentiated fetal Leydig cells nor the maintenance of differentiated functions in existing fetal Leydig cells depend on LH during late fetal life, although this hormone is present in the plasma. Decapitation reduced the testosterone concentrations in the plasma (-56%) and in the testis in vivo (-67%) and the basal testosterone secretion of the testis ex vivo (-70%). This suggests that LH is required to maintain the physiological activity of the Leydig cell during late fetal life. However, the decrease of the in vivo testosterone production after decapitation was not sufficient to impair the growth of the Wolffian ducts and the lengthening of the anogenital distance. In conclusion, during late fetal life in the rat, Leydig cells are LH-independent for their functional differentiation and LH-dependent for their activity.

Animals↗
PubMed2006

A Rasch model analysis of DSM-IV Alcohol abuse and dependence items in the National Epidemiological Survey on Alcohol and Related Conditions.

BACKGROUND: Questions persist about the diagnoses of alcohol abuse and alcohol dependence as defined by Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV). These questions center around the performance of individual alcohol use disorder (AUD) criteria and the nature of items used to assess them. In this study, we conduct in-depth analyses of interview items used to assess alcohol abuse and dependence. METHOD: We conducted Rasch model analyses of responses to 33 items assessing alcohol abuse and dependence criteria in the National Epidemiological Survey on Alcohol and Related Conditions, a nationally representative sample of 34,550 participants. We also examined whether items performed differentially by gender, race/ethnicity, age, education, and time frame of assessment (i.e., past year vs lifetime). RESULTS: A single latent dimension explained the vast majority of shared variance among the items. Abuse symptoms were not of consistently lower severity than dependence symptoms, and some were consistently prone to differential functioning across subgroups. Items related to tolerance also functioned differentially across subgroups especially in the comparison of past-year symptoms between young adults (ages 18-24) and older adults. Items differed widely in their empirically estimated severity, even when they were intended to assess the same DSM-IV criterion. CONCLUSIONS: The use of Rasch model analyses demonstrated the essential unidimensionality of AUD criteria and the lack of hierarchical ordering between abuse and dependence criteria, as well as potential sources of bias in the abuse diagnosis and the tolerance criterion. Results highlight that the prevalence and even the meaning of AUD criteria can differ substantially depending on the wording of items used to assess them. Implications for assessment of specific DSM criteria and for development of DSM-V are discussed.

Alcoholism↗
PubMed1987

1,25-Dihydroxycholecalciferol receptor regulation in hormonally induced differentiation of mouse mammary gland in culture.

Mammary explants from pregnant mouse cultured in the presence of insulin, cortisol, and PRL express their differentiated function by producing milk proteins such as casein. Sucrose density gradient analysis of high salt extract of cultured explants showed the presence of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3 specific binding activity sedimenting at 3.3 S. Specific 1,25-(OH)2D3 binding activity in mammary explants varied as a function of the hormonal milieu in culture. The highest activity was found in explants cultured in the presence of insulin, cortisol, and PRL, whereas only a marginal activity was present in explants cultured with insulin. The comparison of 1,25-(OH)2D3 binding activity in explants cultured with insulin and with the three hormone combination by Scatchard plot analysis indicated that the synergistic actions of insulin, cortisol, and PRL increased the number of 1,25-(OH)2D3 specific binding proteins as much as 6-fold; however, the affinity constant of the binding protein was relatively constant in the two systems. Time course studies showed that the increase in 1,25-(OH)2D3 binding activity was detectable as early as 12 h after the addition of cortisol and PRL to insulin-primed explants. The increase was inhibited by the presence of actinomycin D and cycloheximide, suggesting that the hormonal stimulation of 1,25-(OH)2D3 binding activity involves both transcriptional and translational process. These results indicate that insulin, cortisol, and PRL stimulate the specific 1,25-(OH)2D3 binding activity during the induction of mammary functional differentiation when milk protein synthesis takes place.

Animals↗
PubMed1996

Establishment of Schwann cell lines from normal adult and embryonic rat dorsal root ganglia.

Schwann cells, an important component of the peripheral nervous system, interact with neurons to mutually support growth and replication in the embryo and survival and differentiated function in the adult. The ability of adult Schwann cells to re-enter the cell cycle after nerve injury is crucial to their role in nerve repair. This ability suggests that it should be possible to obtain non-transformed, cell lines which maintain the characteristics of proliferating adult Schwann cells in vivo, as well as obtaining Schwann cells from rapidly dividing embryonic tissues. One approach to obtaining normal functionally differentiated cell lines has been to start primary cultures in serum-free medium containing growth factors and attachment proteins specifically selected to favor the replication of the cell type of interest. By culturing dispersed dorsal root ganglia on laminin, in serum-free medium with hormones and growth factors, we repeatedly generate homogenous Schwann cell cultures which yield normal Schwann cell lines from the dorsal root ganglia (DRG) of both embryonic and adult rats. These cells maintain the phenotype of Schwann cells as determined by morphology and staining for GFAP, S100, p75 NGF receptor, laminin, and MAG production in co-culture with DRG neurons.

Animals↗
PubMed2000

The long-term followup of newborns with severe unilateral hydronephrosis initially treated nonoperatively.

PURPOSE: During the last decade it has become apparent that prenatally detected, unilateral severe hydronephrosis does not necessarily represent obstruction and may spontaneously improve or resolve postnatally. To define its natural history better we performed a long-term (mean 78 months) followup study of infants with hydronephrosis. MATERIALS AND METHODS: A total of 104 newborns with antenatally diagnosed, primary, unilateral severe hydronephrosis were followed nonoperatively unless evidence of renal deterioration occurred for which pyeloplasty was performed. RESULTS: All 23 infants (22%) who required pyeloplasty were younger than 18 months and had progressive hydronephrosis and/or reduction in differential renal function. Differential function exceeded predeterioration levels in all kidneys postoperatively. Of those cases followed nonoperatively hydronephrosis resolved in 69% and improved in 31%. Mean time to maximum improvement of hydronephrosis was 2.5 years. In 76% of those cases followed nonoperatively initial differential function was greater than 40% and final function averaged 49%. In the remaining 24% of cases differential function was less than 40% (mean 23%), and in an average of 18 months differential function increased to a mean of 47%. Initial half-time in nonoperative cases was greater than 30 minutes in 37%, 20 to 30 in 21% and less than 20 in 42%. Final half-time was greater than 30 minutes in 16%, 20 to 30 in 17% and less than 20 in 67%. Half-time was greater than 30 minutes in 87% of the patients and 20 to 30 in 4% before, and greater than 30 in 10%, 20 to 30 in 27% and less than 20 in 63% after pyeloplasty. CONCLUSIONS: Unilateral newborn hydronephrosis appears to be relatively benign and in most instances dilatation and renal function improve with time. However, close followup is necessary to identify the subgroup of less than 25% of infants with obstruction because prompt pyeloplasty will prevent permanent loss of renal function. Standard tests for assessing obstruction in older patients appear to be invalid in infants because prolonged half-time and/or high grade hydronephrosis is neither an indicator of obstruction or surgery. Nonoperative treatment with close followup especially during the first 2 years is safe and recommended for these children.

Disease Progression↗
PubMed1989

Transforming growth factor-beta 1 selectively inhibits IL-3-dependent mast cell proliferation without affecting mast cell function or differentiation.

Transforming growth factor-beta 1 (TGF-beta 1) is an important regulator of cell growth, differentiation, and function. We show that TGF-beta 1 selectively inhibits IL-3-dependent mouse bone marrow derived mast cell (MBMMC) proliferation without affecting MBMMC function or differentiation. TGF-beta 1 significantly decreased [3H]thymidine uptake by IL-3-dependent MBMMC in a dose-dependent manner with 50% inhibition of proliferation occurring with a TGF-beta 1 concentration of 0.1 ng/ml. A brief (i.e., 30 min) incubation of MBMMC with TGF-beta 1 is sufficient to inhibit IL-3-induced proliferation of MBMMC (cultured in the absence of TGF-beta 1) for 24 to 48 h. The inhibitory effect of TGF-beta 1 on the IL-3-dependent proliferation of MBMMC is not cytotoxic as evident from the absence of MBMMC trypan blue staining, the retained functional characteristics of the MBMMC cultured in TGF-beta 1, and the reversibility of the TGF-beta 1 induced inhibition of IL-3 dependent MBMMC proliferation. MBMMC grown in TGF-beta 1 acutely (24 to 48 h) or chronically (7 to 14 days) do not exhibit functional differences in performed or newly generated mediator secretion (Ag/IgE or calcium ionophore A23187 induced MBMMC beta-hexosaminidase or leukotriene C4 release) from MBMMC grown in the absence of TGF-beta 1. In addition, MBMMC cultured for 2 wk in TGF-beta 1 do not show evidence of differentiation as assessed by cellular histamine content or Alcian blue/safranin staining. Thus, TGF-beta 1 is an important negative regulator of IL-3-dependent mast cell proliferation in vitro, selectively inhibiting IL-3-dependent MBMMC proliferation without affecting MBMMC function or differentiation.

Animals↗
PubMed2005

Inhibition of sarco(endo)plasmic reticulum Ca2+-ATPase differentially regulates contractile function in cardiac myocytes from normotensive and spontaneously hypertensive rats: role of Ca2+ regulatory proteins.

Hypertension leads to impaired contractile function. This study examined the impact of inhibition of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by thapsigargin or cyclopiazonic acid (CPA) on cardiac contractile function in ventricular myocytes from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Mechanical properties were examined including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), and maximal velocity of shortening/relengthening (+/-dL/dt). Intracellular Ca2+ transients were evaluated as fura-2 fluorescent intensity (FFI), excitation-induced change in FFI (DeltaFFI = peak-basal), and fluorescence decay rate (tau). Expression of Ca2+ regulatory proteins SERCA2a, Na+-Ca2+ exchanger (NCX), and phospholamban (PLB) were assessed by reverse transcriptase polymerase chain reaction and Western blot. SHR rats exhibited elevated blood pressure. SHR myocytes displayed decreased PS +/- dL/dt, peak FFI, and DeltaFFI; shortened TPS; prolonged tau with normal TR90; and basal FFI compared with WKY myocytes. Inhibition of SERCA with thapsigargin (5 microM) or CPA (10 microM) significantly depressed PS +/- dL/dt, baseline FFI, and DeltaFFI, and prolonged TPS, TR90, and tau in WKY myocytes. However, SHR myocytes were relatively insensitive to thapsigargin or CPA with only TPS and TR90 prolonged. Both mRNA and protein expressions of NCX and PLB were significantly enhanced, whereas SERCA2a protein abundance was reduced in SHR rats compared with the WKY group. Our data suggest that inhibition of SERCA function differentially affected cardiac contractile function in ventricular myocytes from normotensive and hypertensive rats possibly through reduced SERCA2a, elevated PLB, and NCX expression under hypertension.

Animals↗
PubMed1995

Contradictory supranormal nuclear renographic differential renal function: fact or artifact?

We previously reported contradictory supranormal nuclear renographic differential renal function in cases of unilateral hydroureteronephrosis, in which the kidneys with hydroureteronephrosis paradoxically had a greater differential function than the contralateral normal mate, based on diethylenetriaminepentaacetic acid (DTPA) nuclear renography. To evaluate whether DTPA supranormal differential function represented true hyperfunction, patients with DTPA supranormal differential function were evaluated with dimercaptosuccinic acid (DMSA) nuclear renography and the results were compared. A total of 16 patients with unilateral hydronephrosis was identified to have DTPA differential function of 53% or more. They were younger than age 1 year and had never undergone any urological surgery. In all 16 patients the DMSA differential function (mean 51.1%, range 42 to 57%) was lower than their own corresponding DTPA differential function (mean 58.3%, range 53 to 66%, p < 0.0001). In addition, the DMSA differential function was not significantly different from the intuitively anticipated mean of 50% (p = 0.48). The DTPA supranormal differential function identified in our patients was not corroborated by the DMSA differential function. With recent evidence that DMSA differential function may be a better predictor of outcome following relief of unilateral ureteral obstruction consideration should be given to using DMSA as a potentially more relevant method for differential function measurement in the setting of unilateral hydronephrosis. Conversely, until the potential deficiencies of DTPA are fully understood caution should be exercised in the interpretation of DTPA differential function in the setting of hydronephrosis.

Artifacts↗
PubMed2006

A 37-item shoulder functional status item pool had negligible differential item functioning.

OBJECTIVE: Measures of shoulder function may differ by dominance of affected shoulder, surgical history, gender, or race. We present a technique for determining whether observed differences in function between groups are due to biased test items or real differences in function. STUDY DESIGN AND SETTING: Four hundred patients who were receiving rehabilitation for a variety of shoulder impairments completed a survey of shoulder function. Thirty-seven items measuring shoulder function were analyzed for differential item functioning (DIF) related to demographic characteristics using an ordinal logistic regression (OLR) and item response theory (IRT) approach. When DIF was identified in an item, we modified the IRT analysis to calibrate item parameters separately in appropriate demographic groups. We compared adjusted and unadjusted patient ability measures in each demographic group. RESULTS: Several items were found to have a modest amount of DIF related to the different demographic characteristics, especially gender; however, adjusting measures for DIF had little impact on overall measures of shoulder function and made almost no difference in average shoulder function across demographic groups. CONCLUSION: In this pool of shoulder function items, adjustment for DIF made almost no difference in measures of function across demographic groups.

Activities of Daily Living↗
PubMed2006

Integration of CD28 and CTLA-4 function results in differential responses of T cells to CD80 and CD86.

CD80 and CD86 have the capacity to either stimulate or inhibit T cell responses through their receptors CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Blockade of CD80 and CD86 in autoimmune disease settings has revealed distinct outcomes, yet the differential functions of CD80 and CD86 are still unclear. We have studied the ability of individual ligands to stimulate primary responses in human CD4(+) T cells. Our data reveal both quantitative and qualitative differences between the ligands. Both CD80 and CD86 demonstrated the capacity to costimulate T cell proliferation. However, CD80 committed a greater number of T cells to divide with faster kinetics, consistent with it being a superior ligand for CD28. Once cell division had been initiated, all T cells undergoing cell division expressed CTLA-4, irrespective of whether CD80 or CD86 costimulation was used. However, only in the presence of CD80 was evidence of CTLA-4 engagement and inhibitory function observed. Finally, differences between CD80 and CD86 costimulation extended to the T cell phenotype, in particular the levels of CD40 ligand expression.

Animals↗
PubMed2006

Rapid detection of differential item functioning in assessments of health-related quality of life: The Functional Assessment of Cancer Therapy.

REASON FOR STUDY: Differential item functioning (DIF) occurs when a test item functions differently in different groups when controlling for the level of the underlying construct measured by the test. DIF assessment is a first step in the evaluation of test bias. We sought to demonstrate a rapid hybrid approach to DIF detection by determining the presence and scale-level impact of DIF related to eight covariates in four domains measured by the Functional Assessment of Cancer Therapy (FACT). MAJOR FINDINGS: The number of items found with DIF in each domain depended on the criterion chosen to define the presence of DIF. With a few exceptions, scale-level differential functioning was similar regardless of the criteria chosen. For physical well-being, there was relevant scale-level differential functioning related only to race. For social and family well-being, there was relevant scale-level differential functioning related to each of the covariates. For emotional well-being, there was relevant scale-level differential functioning related to ethnicity, language, and race. For functional well-being, there was relevant scale-level differential functioning related to ethnicity, race, education, and self- vs. interviewer-administration. PRINCIPAL CONCLUSIONS: Our rapid hybrid approach to DIF detection may be broadly applicable in other studies of health-related quality of life.

Adolescent↗
PubMed1995

Outcome analysis of pediatric pyeloplasty as a function of patient age, presentation and differential renal function.

PURPOSE: We retrospectively reviewed a consecutive series of patients who underwent pyeloplasty. In all cases preoperative and postoperative isotope renal scans were performed to assess the surgical outcome with particular emphasis on the change in renal function postoperatively. MATERIALS AND METHODS: The clinical records of 108 consecutive children with ureteropelvic junction obstruction were reviewed. Individual renal function was evaluated and obstruction was confirmed by diuretic assisted 99mtechnetium diethylenetriaminepentaacetic acid or mercaptoacetyltriglycine renography. A total of 100 pyeloplasties in 98 children between 5 days and 16 years old was included. Results were analyzed by groups according to patient age and symptoms at presentation. RESULTS: Drainage half-times improved in 98% of patients and only 1 required reoperation. Improved renal function greater than 5% was noted in about a third of each age group. Function remained stable in 68% of the kidneys and decreased in only 1. Of the improved kidneys 77% had impaired function preoperatively (40% or less of the total contribution). Those presenting with a renal mass had the greatest improvement in function. There was no statistically significant difference in improvement in renal function by age group or patient presentation. Regression analysis revealed that preoperative differential renal function was the only statistically significant predictor of improvement in renal function after pyeloplasty. CONCLUSIONS: Pyeloplasty in children is safe and renal functional improvement can be expected in the majority of kidneys with impaired function at presentation. However, there was no indication that early pyeloplasty in infants is more likely to result in improved function than in older children.

Adolescent↗
PubMed1990

The class II major histocompatibility complex antigen deficiency syndrome: consequences of absent class II major histocompatibility antigens for lymphocyte differentiation and function.

The class II major histocompatibility complex antigen deficiency syndrome is a rare immunodeficiency disease associated with defective expression of the class II antigens encoded for by the major histocompatibility complex. Clinically, this syndrome is manifest as a combined immunodeficiency presenting early in life, and affected individuals are susceptible to a variety of severe and/or opportunistic infections. Chronic, severe diarrhea and malabsorption are also characteristically found, and death is common within the first few years of life. Although the precise molecular lesions responsible for the failure of membrane antigen expression in this syndrome have not yet been identified, the pathogenetic mechanisms involve regulatory defects in the transcription of structural genes encoding for class II antigens. The absence of class II MHC antigens results in profound abnormalities in lymphocyte function and differentiation. Of central importance is the defective MHC-restricted interactions between CD4+ "helper" T lymphocytes and the various types of antigen-presenting cells found in the skin and elsewhere. The absence of class II MHC antigens also appears to alter the ability of affected B cells to be activated by a variety of membrane-mediated stimuli, and it profoundly disrupts both the intrathymic development and post-thymic differentiation of immunoregulatory T cells. This "experiment of nature" thus demonstrates the critical role of class II MHC antigens in the proper development and function of the immune system.

Animals↗
PubMed2006

[Proteomics of breast cancer: From differential to functional analysis].

From differential analysis to identify biomarkers, to functional analysis for finding new therapeutic targets, proteomics bring new comprehensive information for a better understanding of the molecular basis of oncology and new perspectives for the clinic. However the major limitation of proteomic investigations, more generally of post-genomic approaches, remains the molecular and cellular complexity of the mammary gland that is still a major challenge.

Biomarkers, Tumor↗
PubMed2002

Tyrosines 559 and 807 in the cytoplasmic tail of the macrophage colony-stimulating factor receptor play distinct roles in osteoclast differentiation and function.

Osteoclast (OC) differentiation requires that precursors, such as macrophage colony-stimulating factor (M-CSF)-dependent bone marrow macrophages, receive signals transduced by receptor activator of nuclear factor kappaB (RANK) and c-Fms, receptors for RANK ligand (RANKL) and M-CSF, respectively. Activated c-Fms autophosphorylates cytoplasmic tail tyrosine residues, which, by recruiting adaptor molecules, initiate specific signaling pathways. To identify which tyrosine residues are involved in c-Fms signaling in primary cells, we retrovirally transduced M-CSF-dependent bone marrow macrophages with a chimera comprising the external domain of the erythropoietin (Epo) receptor linked to the transmembrane and cytoplasmic domains of c-Fms. Transduced cells differentiate into bone-resorbing osteoclasts when treated with RANKL and either M-CSF or Epo, confirming that both endogenous and chimeric receptors transmit osteoclastogenic signals. Cells expressing chimeric receptors with Y(697)F, Y(706)F, Y(721)F, and Y(921)F single point mutations generate normal numbers of bone-resorbing OCs, with normal bone-resorbing activity when treated with RANKL and Epo. In contrast, those expressing Y(559)F generate fewer OCs, whereas theY807F mutant is incapable of osteoclastogenesis. Finally, although mature OCs expressing Y(559)F exhibit impaired bone resorption, those bearing Y807F do not. Thus, we have identified specific tyrosine residues in the cytoplasmic tail of c-Fms that are critical for transmitting M-CSF-initiated signals individually required for OC formation or function, respectively.

Animals↗
PubMed1999

Differential modulation by copper and zinc of P2X2 and P2X4 receptor function.

Differential Modulation by Copper and Zinc of P2X2 and P2X4 Receptor Function. The modulation by Cu2+ and Zn2+ of P2X2 and P2X4 receptors expressed in Xenopus oocytes was studied with the two-electrode, voltage-clamp technique. In oocytes expressing P2X2 receptors, both Cu2+ and Zn2+, in the concentration range 1-130 microM, reversibly potentiated current activated by submaximal concentrations of ATP. The Cu2+ and Zn2+ concentrations that produced 50% of maximal potentiation (EC50) of current activated by 50 microM ATP were 16.3 +/- 0.9 (SE) microM and 19.6 +/- 1.5 microM, respectively. Cu2+ and Zn2+ potentiation of ATP-activated current was independent of membrane potential between -80 and +20 mV and did not involve a shift in the reversal potential of the current. Like Zn2+, Cu2+ increased the apparent affinity of the receptor for ATP, as evidenced by a parallel shift of the ATP concentration-response curve to the left. However, Cu2+ did not enhance ATP-activated current in the presence of a maximally effective concentration of Zn2+, suggesting a common site or mechanism of action of Cu2+ and Zn2+ on P2X2 receptors. For the P2X4 receptor, Zn2+, from 0.5 to 20 microM enhanced current activated by 5 microM ATP with an EC50 value of 2.4 +/- 0.2 microM. Zn2+ shifted the ATP concentration-response curve to the left in a parallel manner, and potentiation by Zn2+ was voltage independent. By contrast, Cu2+ in a similar concentration range did not affect ATP-activated current in oocytes expressing P2X4 receptors, and Cu2+ did not alter the potentiation of ATP-activated current produced by Zn2+. The results suggest that Cu2+ and Zn2+ differentially modulate the function of P2X2 and P2X4 receptors, perhaps because of differences in a shared site of action on both subunits or the absence of a site for Cu2+ action on the P2X4 receptor.

Adenosine Triphosphate↗
PubMed1994

A new functional classification of stomach cancer and its pathobiological and clinical significance.

The functional differentiations of stomach cancer specimens from 121 patients were investigated by enzyme-, mucin-, affinity- and immunohistochemical methods, and the stomach cancers were divided into five functionally differentiated types: 1) Absorptive Function Differentiation Type (AFDT), 19.8%; 2) Mucin Secreting Function Differentiation Type (MSFDT), 24.0%; 3) Absorptive and Mucin-Producing Function Differentiation Type (AMPFDT), 47.1%; 4) Special Function Differentiation Type (SFDT), 0.8%; and 5) Non-Function Differentiation Type (NFDT), 8.3%. The results indicate that stomach cancer tissues of the same histological type often display differing functional differentiation, and these functionally differentiated types have different invasive and metastatic characteristics. In addition, the functionally differentiated types have particular organic affinities of metastasis and different clinical prognoses. This study suggests that this new functional classification may supplement histological classification. The mechanisms of liver and ovary metastases of stomach cancer are also discussed.

Adenocarcinoma↗