Fcgamma receptor polymorphisms and periodontal status: a prospective follow-up study.

AIMS: The aims of this study were to assess: (i) the distribution of Fcgamma receptor polymorphisms among patients with chronic periodontitis ("cases") and control subjects with no/minimal loss of periodontal tissue support in a Caucasian population; (ii) whether these polymorphisms can serve as severity markers for periodontitis; and (iii) whether they have any bearing on the response to periodontal therapy. METHODS: The study sample consisted of 132 cases and 73 controls of comparable age and gender. Full-mouth periodontal status was assessed. Subgingival plaque (PL) samples and blood samples were obtained and analysed with respect to 19 bacterial species and homologous serum immunoglobulin G titres. Polymorphisms in the Fcgamma receptor IIa (131R/H) and IIIb (NA1/NA2) were assessed by polymerase chain reaction. Patients underwent periodontal therapy and were followed up at 4 and 30 months. RESULTS: Neither polymorphism showed a skewed distribution among cases and controls. At baseline, periodontitis patients with Fcgamma RIIa-H/H131 genotype had more PL and deeper pockets than patients in other genotype groups (p < 0.05). Both bacterial levels and antibody titres were unrelated to genotype. The longitudinal analysis failed to detect an association between genotype and response to periodontal therapy. CONCLUSIONS: The present data failed to demonstrate a clinically relevant relationship between the Fcgamma receptor IIa (131R/H) or IIIb (NA1/NA2) polymorphism and periodontal status.

A multicenter, phase II trial of weekly irinotecan (CPT-11) in patients with previously treated colorectal carcinoma.

BACKGROUND: This multicenter, Phase II trial was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma that had recurred or progressed after 5-fluorouracil (5-FU)-based chemotherapy. METHODS: CPT-11 was given as a 90-minute intravenous infusion in repeated 6-week (42-day) courses comprising weekly treatment for 4 consecutive weeks followed by a 2-week rest. Tumor measurements were obtained after every second course of therapy. Toxicity was assessed weekly using the National Cancer Institute Common Toxicity Criteria. RESULTS: A total of 166 patients were entered into the trial. The first 64 patients received a starting dose of 125 mg/m2. An additional 102 patients were enrolled at a starting dose of 100 mg/m2 to determine whether a reduction in the starting dose would result in lower toxicity without sacrificing efficacy. Objective responses to CPT-11 were observed in 18 patients (1 complete response and 17 partial responses) (response rate [RR] = 10.8%; 95% confidence interval [CI], 6.1-15.6%). An additional 67 patients (40.4%) had stable disease as their best response. At the 125 mg/m2 starting dose, the RR was 14.1% (9 of 64 patients; 95% CI, 5.5-22.6%). Among patients given a starting dose of 100 mg/m2, the RR was 8.8% (9 of 102 patients; 95% CI, 3.3-14.3%). The overall median survival was 9.9 months (range, 0.3-36.8 months). The most frequently observed Grade 3/4 toxicities were gastrointestinal events (i.e., diarrhea [27.1%], nausea [15.1%], emesis [9.6%], abdominal cramping [22.2%], and neutropenia [19.9%]). There were no significant differences in the frequencies of Grade 3/4 toxicities between the 125 mg/m2 and 100 mg/m2 starting dose levels except for Grade 3/4 emesis (21.9% vs. 2%; P < 0.001). Patients age > or = 65 years were twice as likely (38.6% vs. 18.8%; P < 0.008) to develop Grade 3/4 diarrhea compared with younger patients when all courses of therapy were evaluated. However, older age did not significantly predict for a higher incidence of first-course diarrhea (25.0% vs. 14.7%; P = 0.106). CONCLUSIONS: CPT-11 can induce tumor regression in patients with metastatic colorectal carcinoma that has progressed during or shortly after 5-FU-based chemotherapy. Gastrointestinal events and neutropenia were the most common serious toxicities. Given the trend toward a higher response rate without substantially greater toxicity, 125 mg/m2 has been selected as the preferred starting dose for further studies. Careful attention to appropriate CPT-11 dose modification and early intervention with loperamide may be especially important in elderly patients.

Procoagulant activity of reversibly acylated human factor Xa.

The plasma clotting factors used to treat hemophiliacs who have developed inhibitory antibodies have a shared history of limited clinical safety and utility. To improve on existing bypass factors, we have developed a reversibly acylated form of human plasma factor Xa capable of providing a time-dependent release of procoagulant activity. Factor Xa was treated with p-amidinophenyl p'-anisate to generate anisoyl Xa. The chemical modification of the protein involves acylation of the active site serine residue of factor Xa. Anisoyl Xa deacylated in a time, pH, and temperature-dependent manner. Active factor Xa generated on deacylation of anisoyl Xa exhibited amidolytic and prothrombinase complex activities in in vitro assays, the level being comparable to those of untreated factor Xa. When Anisoyl Xa was infused into rabbits, active factor Xa was generated on deacylation of the acylated enzyme, which shortened the activated partial thromboplastin time (APTT) in a dose-dependent manner. The duration of effect on rabbit APTT could be directly correlated to the level of human plasma factor Xa. Because anisoyl Xa bypasses the "tenase" complex that is compromised in hemophilia A and B and is unaffected by inhibitory antibodies, it has the potential to be used as an effective bypass therapy.

Effect of gamma carboxylation on prothrombinase inhibitory activity of catalytically inactive factor XA.

Recombinant catalytically inactive factor Xa (factor rXai) is capable of assembly into inactive prothrombinase complexes, thus serving as a competitive inhibitor (Ki = 0.3nM) of active factor Xa. In order to study the role of gamma carboxylation in prothrombinase complex assembly, we have prepared differentially gamma carboxylated factor rXai and have measured the activities of these proteins in prothrombinase complex inhibition and in extension of plasma clotting. A factor rXai preparation containing 8 out of a possible maximum of 11 g carboxyglutamic acid (GLA) residues was found to be as active as chemically inactivated plasma factor Xa which was fully gamma carboxylated. Loss of a single additional g carboxyglutamic acid in the recombinant protein, however lead to a marked loss in activity. Factor rXai preparation with 8 GLA residues is also detected by a monoclonal antibody specific for a GLA dependent epitope. Thus assembly of the factor Va/Xa complex on phospholipid membranes does not require the presence of all of the g carboxyglutamic acid residues present in the plasma protein.

Dose-related haemodynamic effects and pharmacokinetics of oral nicorandil in patients evaluated for chest pain.

We studied the acute haemodynamic dose response of nicorandil, a combined nitrate and potassium channel opener, in patients evaluated for chest pain. Single dose oral nicorandil (5, 10, 20, or 30 mg) or placebo was given to 42 right-heart catheterized patients using a randomized block design. Persistent, significant (P < 0.05) haemodynamic changes occurred primarily after 30 mg. Arterial systolic pressure fell significantly after all doses and remained reduced (maximum, 31 mmHg) up to 6 h after 30 mg; heart rate increased significantly up to 1 h. Individual haemodynamic sensitivity varied and three patients (1, 10 mg; 2, 30 mg) developed transient symptomatic hypotension associated with bradycardia. Pulmonary artery systolic pressure (diastolic was unchanged) declined significantly (maximum, 5 mmHg) up to 6 h after 30 mg whereas pulmonary capillary wedge (baseline normal) and mean right atrial pressures decreased transiently. Cardiac index (baseline normal) declined slightly (significantly after 30 mg); however, stroke volume index and stroke work index were significantly and persistently reduced after all doses. Total systemic vascular resistance declined slightly after 30 mg. Individual plasma nicorandil concentrations were variable and systemic bioavailability was reduced compared with values reported in healthy subjects. Nicorandil demonstrated cardiac unloading actions. Variable plasma concentrations, haemodynamic effects, and patient sensitivity warrant low initial doses with individual dose titration, especially if cardiac filling pressures are low.

Acute effects of increasing doses of nicorandil on renal function in man.

The effects of nicorandil, a nicotinamide derived vasodilator combining nitrate and potassium channel opener actions, on kidney function have not been determined. This study investigated changes in renal blood flow and glomerular filtration rate as estimated using simultaneous 131I-iodohippurate and 125I-iothalamate plasma clearances. Forty-two healthy subjects in sodium balance received placebo and 2.5 mg (n = 8), 5 mg (n = 9), 10 mg (n = 8), 20 mg (n = 8) or 30 mg (n = 9) nicorandil orally. Peak nicorandil plasma concentrations occurred in the first hour. Nicorandil produced dose related decreases in blood pressure with maximum reductions (mean +/- standard error of the mean) after 30 mg of -6 +/- 1 mmHg systolic and -8 +/- 2 mmHg diastolic. Renal blood flow averaged 655 +/- 28 ml/minute/1.73 m2 after placebo. Renal blood flow changed 10 +/- 11% after 2.5 mg, -6 +/- 8% after 5 mg, -12 +/- 11% after 10 mg, -11 +/- 5% after 20 mg, and 8 +/- 6% after 30 mg, however, these changes did not reach statistical significance. Glomerular filtration rate averaged 113 +/- 3 ml/minute/1.73 m2 and was unaltered after nicorandil. Nicorandil had no effect on filtration fraction but fractional excretion of sodium tended to decrease with dose. These dose-related effects of nicorandil are consistent with other mixed vasodilators. At therapeutic doses, renal perfusion and function are preserved despite reductions in systemic blood pressure by nicorandil.

The anion-binding exosite is critical for the high affinity binding of thrombin to the human thrombin receptor.

The thrombin receptor has been shown to be a novel member of the family of G-protein coupled receptors (Vu, T.-K. H., Hung, D.T., Wheaton, V.I., and Coughlin, S.R. (1991) Cell 64, 1057-1068). This receptor appears to be activated through a thrombin-mediated proteolytic mechanism which exposes a "tethered ligand" responsible for receptor activation. In order to investigate the initial interactions of thrombin with this receptor, we have constructed cell lines which express high levels of the human thrombin receptor and studied the binding of various forms of thrombin to the cell surface. Analysis of transfected cells with thrombin receptor monoclonal antibodies identified a particular cell line (clone #5-18) which displayed > 150,000 thrombin receptors per cell. Clone #5-18 appeared to express functional receptors since treatment with thrombin resulted in both a 15-20 fold increase of cytoplasmic phosphoinositide levels and a comparable shift in the EC50 of thrombin-mediated calcium mobilization when compared to non-transfected CHO cells. Binding of 125I-alpha-thrombin to clone #5-18 did not reach equilibrium at 37 degrees C. However, direct binding studies of 125I-alpha-, 125I-diisopropylphospho (DIP)-alpha-, and 125I-beta-thrombin to clone #5-18 demonstrated that binding at 4 degrees C was saturable and reversible for each ligand. Analysis of the binding data revealed Kd's of 0.8 nM, 0.7 nM and 9.7 nM for 125I-alpha-, 125I-DIP-alpha- and 125I-beta-thrombin respectively. Association of 125I-alpha-, DIP-alpha, and beta-thrombin could be competed by unlabelled alpha- and DIP-alpha-thrombin. Unlabelled beta-thrombin, which has a modified anion-binding exosite, was a poor competitor for 125I-alpha- and 125I-DIP-alpha-thrombin, but did compete for 125I-beta-thrombin. In addition, the hirudin54-65 peptide competed at submicromolar concentrations for the binding of alpha- and DIP-alpha-thrombin, but not for beta-thrombin. This peptide binds specifically at the anion-binding exosite of alpha-thrombin and has been shown to have a lower affinity for beta-thrombin. These results demonstrate directly a high affinity interaction between thrombin and its receptor, and suggest that an important component is the high affinity association of the thrombin receptor with the anion-binding exosite of thrombin.

Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor.

The biological effects of platelet-derived growth factor (PDGF) are mediated by cell surface alpha and beta PDGF receptors, which, as a result of ligand binding, undergo dimerization in a manner consistent with PDGF being bivalent. In order to directly demonstrate PDGF bivalency and to define the binding of PDGF AB to isolated beta receptor, we developed solid-phase binding assays using purified recombinant extracellular domain of human PDGF receptors. PDGF AA, AB, and BB were prepared from the monomeric chains expressed in Escherichia coli, and each was purified to homogeneity; PDGF AB contained < 0.5% of either homodimer. The interactions of these isoforms with immobilized PDGF receptors were examined by several approaches. Scatchard analysis revealed high affinity binding (Kd = 0.5-1.0 nM) of radiolabeled PDGF AA and AB to alpha receptor and of PDGF BB to both receptor subtypes. Contrary to previous reports, PDGF AB also bound beta receptor with high affinity (Kd = 0.9 nM). When a B-chain-specific monoclonal antibody that recognizes the putative binding domain of PDGF BB was used for ligand detection, we found that PDGF AB binding to beta receptor occurred exclusively through the B-chain subunit, whereas binding to alpha receptor occurred through either subunit. In addition, site-directed mutagenesis was used to specifically inactivate the B chain of PDGF AB, which eliminated binding to the beta receptor without affecting alpha receptor binding. These results establish that PDGF is bivalent and that monovalent ligand retains high affinity receptor binding.

Carbohydrate residues modulate the activation of coagulation factor X.

Factor X is a plasma protein involved in both the intrinsic and extrinsic pathways of blood coagulation. Post-translational modifications of the protein involve gamma-carboxylation of specific glutamic acid residues, beta-hydroxylation of one aspartic acid residue, and N- and O-linked glycosylation. Even though it is known that gamma-carboxylation is instrumental in regulating biological activity, the role of glycosylation in the function and properties of factor X has not been previously investigated. We utilized lectin binding and glycosidase treatment to investigate the functional role of carbohydrates on the activation peptide of factor X. Sambucus nigra agglutinin, a lectin that binds to sialic acid terminally linked alpha(2-6) to galactose or N-acetyl-galactosamine inhibits activation of human factor X in a dose-dependent manner. Inhibition of activation was observed for both intrinsic (factor IXa/VIIIa) and extrinsic (factor VIIa/tissue factor) pathway complexes. In accordance with this, selective removal of sialic acid residues on the activation peptide of factor X by neuraminidase also results in a drastic reduction of activation of the zymogen by these complexes. Corresponding reduction of activity in classical clotting assays (activated partial thromboplastin time and prothrombin time) also agrees with this observation. These results suggest a possible role of N-linked carbohydrates in the activation of factor X.

Continuous intravenous dosing with ciprostene using a portable pump in ambulatory patients.

Parenteral compounds present special drug delivery challenges. This open-label study evaluated a portable infusion pump as a means to deliver intravenous ciprostene, a stable prostacyclin analog. Ten patients with peripheral vascular disease and claudication received ciprostene (titrated to 120 ng/kg/min) infused over 8 hours 1 day per week for 4 consecutive weeks. Patients successfully maintained the pump strapped to the waist. The mean +/- standard deviation delivery error, with volumes of 6 to 10 mL over 8 hours, was -0.895 +/- 3.177%. Accordingly, the pump performed well with a potent drug under these clinical conditions. Headache, flushing, and infusion site irritation during infusion were the most frequent side effects. Blood pressure remained unchanged during infusion; however, heart rate increased significantly (P < .05, maximum increase was 13.9 +/- 2.1 beats per minute [mean +/- standard error of the mean]. Mean (+/- standard error of the mean) relative claudication times on treadmill remained unchanged; however, absolute claudication times increased (P < .05) from 6.6 +/- 1.8 to 10.0 +/- 2.2 minutes. Ciprostene inhibited adenosine diphosphate-induced platelet aggregation by 56.0 +/- 12.7% (mean +/- standard error of the mean). Mean template bleeding times and plasma concentrations of platelet-specific proteins (beta-thromboglobulin, platelet factor 4) did not change.

A novel monoclonal antibody dependent on domain 5 of the platelet-derived growth factor beta receptor inhibits ligand binding and receptor activation.

Platelet derived growth factor (PDGF) induces activation of the protein tyrosine kinase domain of the PDGF receptor, resulting in receptor dimerization and the initiation of mitogenesis in responsive cells. In order to identify domains of the receptor involved in these processes, a panel of monoclonal antibodies (MAbs) against the extracellular region of the human PDGF receptor was developed and screened to identify which of these specifically block PDGF binding. One of these, MAb 2A1E2, binds PDGF beta receptor with high affinity and blocks PDGF BB binding in a whole cell binding assay with an IC 50 of 0.1 nM. Inhibition of binding results in the inhibition of ligand-induced receptor phosphorylation, dimerization and mitogenesis in cells expressing the PDGF beta receptor. MAb 2A1E2 has been mapped to the fifth Ig domain of the PDGF beta receptor, implying that this domain is important for ligand binding, dimerization and/or activation. The potency of MAb 2A1E2 for inhibiting PDGF BB binding indicates that this antibody is ideally suited to identify and characterize PDGF BB-induced biological responses.

The pharmacokinetics and haemodynamic effects of continuous nicorandil infusion in healthy volunteers.

We have studied the pharmacokinetics and haemodynamic effects of nicorandil after a 12-h infusion. Nicorandil is a mixed vasodilator combining the actions of a nitrate and a potassium channel opener. Nicorandil was infused for 12 h in 21 healthy volunteers at rates of 0.05, 0.10, and 0.20 microgram.kg-1.min-1 using a placebo controlled, crossover design. Systemic blood pressure, heart rate, electrocardiographic (ECG) intervals, and cardiac output (impedance cardiography) were measured supine and standing. Dose-related, steady-state plasma nicorandil concentrations occurred within 3 to 4 h. Nicorandil's pharmacokinetics were linear with dose. Four 0.20 microgram.kg-1.min-1 nicorandil infusions were terminated early primarily because of moderate or severe headaches. There were no safety concerns (ECG intervals, laboratory assays). Blood pressure fell versus placebo only in the standing position and heart rate increased slightly (not significant). That is, standing blood pressure in the 6 to 12 h interval fell from baseline 8.0*/6.8, 1.6/5.1, and 9.8*/7.9* mmHg (systolic/diastolic, * = P < 0.05 versus placebo) at 0.05, 0.10, and 0.20 micrograms.kg-1.min-1 respectively. Cardiac output increased slightly above placebo at lower doses. Haemodynamic changes correlated poorly with plasma nicorandil concentrations. Similar total doses were less well-tolerated when extended over 12 h. We saw no evidence of pharmacodynamic tolerance to nicorandil within 12 h.

The haemodynamic effects and pharmacokinetics of intravenous nicorandil in healthy volunteers.

We have studied the effects of intravenous nicorandil, a mixed arterial and venous vasodilator, in 48 healthy volunteers. Nicorandil (20, 28, 39, 54, 74, 103, 144, or 200 micrograms.kg-1) or placebo were given over 5 min to subjects supine (16 subjects, 2 doses) or sitting (32 subjects, 1 dose) in a single-blind crossover design. Electrocardiographic intervals, blood pressure, and heart rate were measured before and for 8 h after dosing. Blood and urine safety laboratory studies were also performed before and after dosing. All intravenous infusions of nicorandil and placebo were well tolerated and there were no clinically important safety concerns. The most frequent adverse event after nicorandil was headache (24 events by 19 subjects), although its occurrence was not strictly dose related. One subject experienced transient symptomatic hypotension (144 micrograms.kg-1). Mean plasma nicorandil concentrations were dose-related and fell with a half-life of 0.7 to 1.2 h. Systemic clearance and volume of distribution tended to decrease as dose increased. Sitting subjects showed marginally lower (< 20%) systemic clearances and larger values of Cmax and AUC. Nicorandil produced dose-related reductions in blood pressure, with consistent statistically significant differences from placebo after the 144 and 200 micrograms.kg-1 doses. The falls in blood pressure were greater for diastolic pressure and in this supine position. At 200 micrograms.kg-1, the mean falls in systolic/diastolic pressures (mm Hg) during the first hour were 10.9/14.7 supine and 6.1/9.1 sitting; systolic pressure returned to baseline after 8 h and diastolic pressure after 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression, purification, and characterization of inactive human coagulation factor Xa (Asn322Ala419).

We have expressed in Chinese hamster ovary cells a catalytically inactive form of human factor Xa (factor rXai). A recombinant precursor of human factor Xa was inactivated by two point mutations in the serine protease catalytic triad, Asp322Asn and Ser419Ala. A two-step purification to homogeneity of the secreted material involved immunoaffinity followed by heparin-agarose chromatography. Two forms were identified; a fully processed dimer (70%) and a partially processed monomer (30%). Limited N-terminal amino acid sequencing of factor rXai detected the predicted residues and gamma-carboxyglutamic acid content was 90% of human plasma control. Although devoid of measurable proteolytic activity, factor rXai competitively inhibited plasma factor Xa assembly into functional prothrombinase complexes (Ki = 3 x 10(-10) M). Factor rXai also inhibited plasma clotting in a dose-dependent manner. The possible use of recombinant catalytically inactive proteins as a general approach for pharmacological regulation of human diseases is discussed.

Clinical pharmacology of nicorandil in patients with congestive heart failure.

Nicorandil is a nicotinamide derivative with a potential role in human therapeutics because of its potent vasodilating properties. The pharmacokinetics of oral nicorandil administration and the relationships between plasma nicorandil concentration and hemodynamic responses were examined in 25 patients with moderate to severe congestive heart failure. The dose range from 10 to 60 mg was studied. Elimination half-life for this dose range was substantially longer than that previously reported in normal volunteers. Total area under the curve increased in a curvilinear fashion with progressive dose increments, indicating a disproportionate increase in systemically available drug at higher doses. Hemodynamic responses generally correlated well with plasma nicorandil concentration, with rapid loss of cardiovascular activity corresponding to the efficient clearance of nicorandil.

Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans.

Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)

Design of constructs for the expression of biologically active recombinant human factors X and Xa. Kinetic analysis of the expressed proteins.

Activation of vitamin K-dependent plasma proteases occurs by specific interaction with components of the blood coagulation cascade. In this report, we describe the direct expression and enzymatic characterization of the human coagulation zymogen factor X and its activated form, factor Xa, from transformed Chinese hamster ovary fibroblast cell lines. Expression was achieved using either a full-length factor X cDNA or a unique mutant factor Xa cDNA. The functional factor Xa precursor contained a novel tripeptide bridge in place of the native 52-amino acid activation peptide. This mutation allowed for intracellular processing and secretion of the activated form of factor X. Secreted recombinant factors X (rX) and Xa (rXa) were purified by sequential anion-exchange and immunoaffinity chromatography. The enzymatic activities of factors rX and rXa were compared with those of plasma factors X and Xa in three independent assay systems. In comparison to human plasma factor X, the amidolytic, prothrombinase complex, and plasma clotting activities of factor rX were 50, 85, and 43%, respectively. The corresponding comparative activities for factor rXa were 32, 64, and 48%, respectively. The ability to directly express mutant forms of biologically active human factor X will facilitate the structure/function analysis of this important blood coagulation protein and may lead to the development of novel coagulation inhibitors.

Factory daughters, the family, and nuptiality in Java.

PIP: The commercialization of agriculture, increasing landlessness, and an expanding labor class in rural areas of Java are all the result of industrialization. This work discusses the effect of female employment on marriage patterns of women working in rural factories. The central point is that employment has not only increased the financial autonomy of these women, but also increased the level of control they have over the choice of marriage partners. The data set used for analysis consisted of the observations of all factory workers and all non-factory females age 15-24 located in an agricultural village. The observations were make over a 15 month period between 1981-83. A follow up visit was made in 1986 and the following conclusions were then made: 1) the village study gave detailed data, but the data set was not large enough, thus a follow up study that encompasses more people is called for; 2) young rural female factory workers are more likely to chose their marriage partners than those engaged in traditional village labor. Of those that married and worked in factories, their fertility rate was significantly lower, compared to non-factory workers. Factory workers also had different family structures, because they spent less time living in extended families because of a larger income for the couple. This study indicates that increased economic control results in increased life decision control. This changed the daughter's economic relationship with her family and gives her more control in marriage decisions.^ieng