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PubMed1991

Effect of age on gastric acid secretion and serum gastrin concentrations in healthy men and women.

The effects of age on basal, meal-stimulated, and human gastrin-17-stimulated gastric acid secretion rates and serum pepsinogen concentrations were evaluated in 41 healthy men and women. Older subjects (ages 44-71 years; mean, 57 years) had higher mean basal, meal-stimulated, and gastrin-17-stimulated acid secretory rates and basal serum pepsinogen I and II concentrations than younger subjects (ages 23-42 years; mean, 33 years). Age-related differences in acid secretion were especially prominent in men, and age-related differences in serum pepsinogen I and II concentrations were more prominent in women. Higher gastric acid secretion rates in older subjects could not be explained by body size (height, weight, body surface area, or fat-free body mass) or by the higher incidence of infection with Helicobacter pylori. Using a multivariate linear regression model, age had an independent positive effect on acid secretion, and H. pylori infection had an independent negative effect. It was concluded that aging is associated with an increase in gastric acid secretion in humans, especially in men, while infection with H. pylori is associated with lower acid secretion rates.

Adult↗
PubMed1982

The effect of prostaglandin E2 on duodenal ulcer healing.

Oral prostaglandin E2 (PGE2) has specific protective effects so called cytoprotection on the gastrointestinal mucosa that are independent of the acid secretion. This has recently been documented in man. A clinical study was performed to test whether this mucosal reinforcing property also could be used to accelerate duodenal ulcer healing. Twenty-eight patients with endoscopically confirmed duodenal ulcers were randomized to treatment with PGE2 0.5 mg three times daily and 1 mg at night or to placebo under double-blind conditions during a four week period. To reduce antacid consumption a fluid placebo antacid was given regularly. An active antacid could be used for pain relief. Healing rate was assessed with repeated endoscopies after 2 and 4 weeks. The treatment groups were comparable with respect to age, duration of ulcer history and present ulcer symptoms, smoking habits, family history, gastric acid secretory rate and number of patients with blood group 0. There was a slight difference in sex distribution. 2 mg PGE2 did not reduce pentagastrin-stimulated acid secretion in five of the patients. After the treatment significantly more in the PGE2-group (12/14, 86%) had healed than in the placebo-group (6/14, 43% P less than 0.05). There was no difference in pain relief between PGE2 and placebo-treated. The antacid consumption was very low in both PGE2 and placebo-treated. No significant side effects or changes in laboratory test-results were recorded. It is suggested that the cytoprotective effect of PGE2 can be used to accelerate healing of duodenal ulcer.

Administration, Oral↗
PubMed1984

Role of LH pulse amplitude in controlling rat ovarian oestradiol-17 beta secretion in vitro.

Ovaries from di-oestrous rats were removed and placed in perifusion culture: 4-6 ovaries were cultured for 3 h with (1) no gonadotrophin; (2) tonic FSH (200 ng/ml); (3) tonic LH (30 ng/ml); (4) tonic FSH and tonic LH; (5) tonic FSH and hourly pulses of 40 ng LH/ml; or (6) tonic FSH and hourly pulses of 50 ng LH/ml. The total amount of LH administered was 3060 ng LH, regardless of mode of delivery. Perifusate was collected every 10 min and assayed for oestradiol-17 beta by RIA. The total amount of oestradiol-17 beta secreted was not altered by any treatment except when LH was administered in hourly pulses with an amplitude of 50 ng/ml; the total amount of oestradiol-17 beta secreted in 3 h was increased by 300% (P less than 0.05). Without gonadotrophic stimulation, oestradiol-17 beta was secreted at a constant rate (4.48 +/- 0.21 pg/mg 10 min-1). Tonic gonadotrophin stimulation did not alter this pattern. However, pulses of 50 ng LH/ml but not 40 ng LH/ml resulted in periodic increases in oestradiol-17 beta secretory rates. Thus, oestradiol-17 beta secretion is stimulated by LH pulses with the degree of stimulation dependent, in part, on the amplitude and/or the rate of change of the LH pulse.

Animals↗
PubMed1995

Alterations in the patterns of insulin secretion before and after diagnosis of IDDM.

OBJECTIVE: To study the natural history of beta-cell dysfunction in an individual who developed insulin-dependent diabetes mellitus (IDDM) over a 13-month period while under observation. RESEARCH DESIGN AND METHODS: Insulin secretion rates (ISR) in response to intravenous glucose and mixed meals were estimated by deconvolution of C-peptide levels. RESULTS: When fasting glucose and glycosylated hemoglobin concentrations were still within the normal range, insulin secretory responses to intravenous glucose infusion were reduced, but 80- to 100-min secretory oscillations could still be detected. Sequential glucose infusion studies over a 3-month period demonstrated a progressive reduction in insulin secretion. The tight temporal coupling between ultradian oscillations in ISR and glucose observed in nondiabetic subjects was lost. In response to mixed meals, the oscillatory pattern of secretion was preserved, but the magnitude of the secretory responses was reduced. CONCLUSIONS: Our results indicate that despite the lower absolute secretory rates, ultradian ISR oscillations persist in the period before and immediately after the onset of IDDM in this subject, but they are less tightly coupled to glucose than in nondiabetic subjects.

Adult↗
PubMed1997

Growth hormone secretion in night workers.

We previously reported that, in night workers, cortisol and TSH rhythms, known to have a high endogenous component, adapted only partially to the nocturnal schedule. The aim of the present study was to investigate the degree of adaptation of the growth hormone (GH) rhythm, considered to be mainly sleep-dependent, but for which a weak circadian drive has also been suggested. Eleven night workers were studied during their usual sleep-wake cycle, and two groups of 11 normally day-active subjects, sleeping once during the night and once after an 8-h sleep delay, were used as control groups. GH secretory rates were calculated by deconvolution of the plasma concentrations analyzed at 10-min intervals. The total amount of GH secreted during the 24 h did not differ between the three groups and the main secretory episode occurred, in most cases, during the first half of the sleep period. In night sleepers and night workers the enhanced amount of GH secreted at that time was followed by a significantly lower amount secreted during the second part of the sleep period (p < 0.001 and p < 0.05, respectively). For night sleepers, an enhanced GH pulse frequency was found at the beginning of sleep, whereas for night workers and day sleepers the pulses were distributed more randomly throughout the nychthemeron. After an abrupt sleep shift, all the subjects displayed a GH pulse at the usual time of early sleep, but such a pulse was present in only 8 of 11 night workers. Thus the amount of GH secreted between 23:00 h and 03:00 h in day sleepers did not differ significantly from that observed in night sleepers, whereas it differed for night workers. These results confirm the considerable influence of sleep in driving the GH rhythm and the existence of a circadian influence revealed by an acute shift in the sleep period. They also provide evidence of an incomplete adjustment of GH rhythms in night workers.

Adult↗
PubMed1996

Method to measure apolipoprotein B-48 and B-100 secretion rates in an individual mouse: evidence for a very rapid turnover of VLDL and preferential removal of B-48- relative to B-100-containing lipoproteins.

We have developed a procedure to measure the rates of apolipoprotein (apoB) and triglyceride secretion from the liver of an individual mouse. Using the well-characterized method of Triton WR-1339 injection to block peripheral removal of newly secreted VLDL, the rate of triglyceride accumulation is monitored and at the end of the experimental period, blood is extracted for quantitative VLDL preparation. ApoB species in isolated VLDL are analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the mass of the apoB-48 and apoB-100 species are estimated by Coomassie staining and laser densitometric scanning, using known quantities of LDL-apoB-100 as standards. This methodology was applied to measure the rate of apoB secretion in male and female FVB/N mice and we found that the molar ratio of newly secreted ApoB-48 to B-100 is 4.6 in the male, and 3.8 in the female. Measurements of the steady state apoB levels indicate that liver-derived apoB-48 is cleared from the circulation 7.1 times faster than B-100 in the male and 4.7 times faster in the female mouse. VLDL apoB-48 fractional turnover is approximately 1800 pools per day in both the male and female mouse (1814 +/- 139 vs. 1831 +/- 365 respectively, P = 0.92). ApoB-100 fractional turnover rates are much slower and show a statistically significant difference between males and females (255 +/- 19 pools per day vs. 386 +/- 65 pools per day, respectively, P = 0.006). This procedure provides for quantification of secretory rates of these apo proteins in vivo, and may be useful for studying the effects of genetic manipulation on the simultaneous secretion of apoB-48- and apoB-100-containing VLDL, afforded by the panoply of transgenic mouse models now available for study, as well as for effects of diet and drug therapy.

Animals↗
PubMed1977

Effect of atropine and proximal gastric vagotomy on the acid response to fundic distension in man.

In four healthy subjects and in 12 patients with duodenal ulcer (DU), graded balloon distension of the gastric fundus and body caused increments in acid output related to the distension volumes. The mean peak distension response amounted to about 50% of the mean peak acid output (PAOpg) evoked by intravenous infusion of pentagastrin in a dose of 300 microng/h, eliciting maximum observed secretory response. During distension with the largest balloon volume, 1-0 mg atropine injected intravenously significantly depressed the acid secretory rate, the median inhibition amounting to about 80%. In two patients with DU, 2-5 mg atropine completely abolished acid secretion during fundic distension. In nine subjects with DU, complete proximal gastric vagotomy profoundly depressed the secretory responses to graded fundic distension, eliminating the acid response to the smallest balloon volume used. A slight, but significant, response to the largest distension volume persisted after complete vagotomy. Incomplete proxomal gastric vagotomy was found to reduce only moderately the distension responses in five patients, and the peak acid response to fundic distension as related to PAOpg remained unchanged. In conclusion, distension of the gastric fundus and body in man stimulates acid secretion by means of an atropine-sensitive, presumably cholinergic, reflex mechanism and the findings after vagotomy are in agreement with the concept that this reflex mechanism is conveyed by both short intramural and long vagovagal pathways.

Adult↗
PubMed1991

Dose effects of cholecystokinin and acetylcholine on phosphorus compounds and secretory responses in isolated perfused pancreas of rat.

Phosphorus nuclear magnetic resonance (31P NMR) spectroscopy was used to study energy supply for protein secretion in the isolated perfused rat pancreas. Stimulation with cholecystokinin (CCK-8) increased fluid secretion and protein output. With 10pM of CCK-8, the tissue contents of ATP, inorganic phosphate (Pi), and creatine phosphate (PCr) remained unchanged. With 100pM of CCK-8, which induced the maximum response in fluid secretion and protein output, Pi increased slightly, ATP and PCr remained almost unchanged. A high dose of CCK-8 (1 nM) suppressed the fluid and protein secretory rates, decreased ATP, and increased Pi significantly, but PCr showed a tendency of increase. Significant changes in ATP and Pi occurred on withdrawal of CCK-8 (1 nM), suggesting activation of ATP hydrolysis for recovery from secretory suppression. During stimulation with 0.1, 0.3, and 3.0 microM of acetylcholine, the similar dose-dependent response was observed in the secretion and the phosphorus metabolism. The present study demonstrated that cytosolic energy metabolism for secretory responses in the pancreas is low and the Lohmann reaction showed less contribution than in the salivary gland. The findings suggest that the energy supply for protein secretion may be cytosolic diffusion of ATP and that the Lohmann reaction system may contribute to synthesis and storing of secretory protein at resting state.

Acetylcholine↗
PubMed2001

Salivary fluid secretion in the ixodid tick Rhipicephalus appendiculatus is inhibited by Thogoto virus infection.

Adult Rhipicephatus appendiculatus ticks, infected with Thogoto (THO) virus or control, were fed on guinea pigs and removed at intervals throughout the feeding cycle. Salivary fluid secretion was measured by an in vitro technique. The salivary glands of infected, partially-fed ticks secreted fluid in vitro at about 75% the rate of controls, but the difference between infected and controls among engorged ticks was not statistically significant. Basal and DA-stimulated levels of cyclic AMP (cAMP) were determined in isolated glands and were significantly affected by THO virus infection. The differences in secretory rate among control and infected ticks could not be explained in terms of altered cAMP levels. Haemolymph volume was measured by a tracer-dilution technique using 3H-inulin. The mean haemolymph volume for both THO-infected and control groups was between 23-24% body weight throughout the feeding cycle, indicating that infection by this arbovirus did not influence salivary fluid secretion via altered haemolymph volume. The mechanism by which THO virus affects secretory activity of its tick vector remains unknown.

Animals↗
PubMed1990

Organ culture of ixodid-tick salivary glands.

This work describes an organ-culture method for isolated salivary glands of the ixodid tick Amblyomma hebraeum Koch. The support medium is a TC 199-1% agarose gel with no hormonal or undefined supplements. I used a fluid-transport assay for measuring viability of salivary glands. When cultured at 26 degrees C, female glands secreted fluid at 65% on day 2, 59% on day 4 and 42% on day 6 post-culture compared to glands tested on day 0. Fluid secretory rates in culture were higher than rates of glands from partially fed ticks (about 180-250 mg) on days 2, 4 or 6 post-removal from the host. Salivary glands from fed males cultured for 4 days lost only 5% of their fluid secretory competence, whereas glands dissected from males 4 days post-removal lost 63% of their fluid secretory competence.

Animals↗
PubMed1993

Secretion of prostanoids by platelets and monocytes in normal and hypertensive pregnancies.

OBJECTIVES: Secretory products of immune cells may induce or potentiate coagulation disturbances and vasoconstriction, both central features of pregnancy-induced hypertension. Women with chronic essential hypertension are at high risk of superimposed pregnancy-induced hypertension. The aim of our study was to compare secretory rates of prostanoids (active in coagulation and vascular reactivity) by peripheral blood monocytes and platelets from nonpregnant controls and from women in the third trimester of pregnancy, normals and those with either pregnancy-induced hypertension or uncomplicated chronic essential hypertension. STUDY DESIGN: From 100 ml blood, peripheral blood monocytes and platelets were isolated; their relative rates of in vitro production of prostacyclin, prostaglandin E2, and thromboxane were measured, and responses to stimulation by arachidonic acid or the calcium ionophore A23187 were compared among the four groups of subjects. RESULTS: Basal peripheral blood monocyte secretory levels of prostanoids were low in all groups, with responses to both stimuli. Cells from women with chronic essential hypertension had a relatively exaggerated rise in thromboxane secretion (and to a lesser extent, prostacyclin) in response to the stimuli used, with a similar but less marked trend for those with pregnancy-induced hypertension. Platelets from women with chronic essential hypertension had particularly high basal secretory levels of thromboxane, with little further response to stimulation by arachidonic acid or A23187. CONCLUSIONS: Our work demonstrates clearly for the first time that peripheral blood monocytes from pregnant women secrete low levels of vasoactive prostanoids and respond to the stimuli used in a manner similar to that of nonpregnant women, and that cells from pregnant women with hypertension have a tendency to increased reactivity that is most marked in those with chronic essential hypertension. Platelets from women with chronic essential hypertension secrete near-maximal amounts of thromboxane in the absence of exogenous stimuli, indicating a degree of prior activation.

Adult↗
PubMed1984

The mammalian gastric parietal cell in vitro.

To summarize the metabolic status of the parietal cell: There does not seem to be a close relationship between cellular ATP levels and acid secretion. Acid secretion is absolutely dependent on oxygen, and oxygen consumption will increase in direct proportion to the rate of acid secretion. However, the absolute rate of respiration is not closely related to the formation of acid in the subtissue systems. Acid formation can be driven directly by addition of ATP in permeabilized glands, even under apparent anoxic conditions. This correlates well with the presence of the gastric (H+, K+)-ATPase in the parietal cell. If ATP is the main source of energy for the acid secretion, it is quite possible that the relevant ATP pool is compartmentalized and that the content in this pool has a high turnover rate, whereas the ATP used for other cellular functions would be spared. A pure redox mechanism in the gastric mucosa is not possible. However, it remains to be shown that a redox component is not involved in the secretory process. The acid formation measured by AP accumulation in the gastric glands is not an indication of secretory rate. Thus even though ATP appears to restore acid formation in permeabilized glands, this effect has been mainly studied in nonstimulated systems. A detailed study over the energy requirement in the permeabilized resting cell remains to be done. In the mammals we only have information so far about the piglet and the rabbit in terms of substrate preference. The differences between the two could either be due to species or age difference. In both mammals and amphibia, there is no evidence to suggest that acid secretion results in an increase in oxygen consumption purely due to a state IV to III transition of mitochondrial respiration. Rather, increased Krebs-cycle activity would appear to be the major metabolic result of stimulation.

Animals↗
PubMed1987

Prostaglandin protection against ethanol-induced gastric injury: regulatory effect on the mucus glycoprotein metabolism.

Effects of ethanol and prostaglandin on the metabolic processes of gastric mucosal cells have been evaluated by studying the biosynthesis and intra- and extracellular distribution of mucus glycoprotein. The rat gastric mucosal cell suspensions were subjected to a short-term tissue culture in the presence of 0-1.5 M ethanol and 0-100 ng/ml 16,16-dimethyl prostaglandin E2 (DMPGE2), using [3H]proline and [3H]palmitic acid as markers of mucin apoprotein synthesis and modification. Ethanol at concentrations of 0.02-0.1 M stimulated the glycoprotein synthesis, but the product was 2-3 times more extensively and rapidly degraded by pepsin than the glycoprotein synthesized in the absence of ethanol. Higher concentrations of ethanol (0.1-1.5 M) caused a marked reduction in the glycoprotein synthesis and a depletion of the intracellular mucus glycoprotein stores, and at 1.5 M ethanol the synthetic processes ceased to function. When the incubated tissue cultures were challenged with DMPGE2, the highest synthetic and secretory stimulation was achieved at 10 ng/ml. The peptic susceptibility of the glycoprotein synthesized in the prostaglandin-enriched culture was somewhat lower than that of controls, and the proportion of the undegraded glycoprotein remaining after 22 h of digestion was significantly higher. Furthermore, the intracellular compartments were not depleted of mucus glycoprotein and the amount of the mucin apoprotein precursor increased to about 30%. Addition of DMPGE2 prior to ethanol treatment resulted in the stabilization of cellular processes and the cells responded as if ethanol was not present in the medium. Moreover, the intracellular stores of mucus glycoprotein were not depleted and the secretory rate was moderately elevated. The regulatory effect of DMPGE2 on the glycoprotein synthesis and distribution was significant, but diminished with increasing amounts of ethanol in the medium. The results suggest that DMPGE2 imposes a stabilizing effect on the secretory processes and controls the mucus glycoprotein synthesis, but the extent of this protective action against ethanol is limited and depends upon the concentration of ethanol penetrating the mucosal cells.

16,16-Dimethylprostaglandin E2↗
PubMed1995

Increasing gestational age and cortisol alter the ratio of ACTH precursors:ACTH secreted from the anterior pituitary of the fetal sheep.

We have used a perifusion system and slices of the anterior pituitary of the fetal sheep combined with specific immunoradiometric assays to investigate the effect of increasing gestational age and cortisol infusion on the output of ACTH(1-39) and the ACTH precursors, pro-ACTH and pro-opiomelanocortin, from the fetal sheep pituitary. Two slices from each fetal anterior pituitary at 106-113 days (n = 3), 120-136 days (n = 5) and 140-143 days (n = 5) of gestation were used. Slices from each anterior pituitary were perifused with the perifusion buffer for at least 120 min prior to the infusion of cortisol (100 nM) for 30 min or buffer alone (control). The anterior pituitary output (fmol/5 min per mg pituitary) of ACTH(1-39) and the ACTH precursors were measured using specific immunoradiometric assays. There was a significant increase in the anterior pituitary secretion rate of ACTH(1-39) between 120 and 136 days (1.04 +/- 0.23 fmol/5 min per mg) and between 140 and 143 days of gestation (3.08 +/- 0.33 fmol/5 min per mg). In contrast, there was no change in the secretory rate of the ACTH precursors between 105 and 143 days of gestation. The ratio of the anterior pituitary output of the ACTH precursors:ACTH(1-39) therefore decreased between 120 and 143 of days gestation from 19.10 +/- 2.05 to 6.36 +/- 0.58. There was no effect of cortisol infusion on the anterior pituitary secretion of either ACTH(1-39) or the ACTH precursors before 116 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1983

Effect of estradiol treatment on the secretion and structure of gastric H+ and pepsin-secreting cells in the rat.

Gastrin-stimulated secretory rate of gastric H+ and pepsin were markedly inhibited (P less than 0.001) in ovariectomized rat after 7 days of estradiol treatment (80 micrograms/kg/day) in comparison to ovariectomized untreated rat and sham control. In correlation to the secretions, the majority of parietal cells failed to show the typical ultrastructural transformation associated with active secretion. Pyknotic nuclei with dilatation of nuclear envelope and degenerative changes were observed in the parietal cells. Meanwhile, the chief cell showed inactive characteristics in that a large number of pepsinogen granules were retained in the cells. In contrast, in ovariectomized untreated rat, the rate of gastrin-stimulated H+ and pepsin secretion were not significantly different from the sham (P greater than 0.05). Consistent with secretion, after gastrin stimulation, the morphology and ultrastructure of the parietal cell and chief cell showed active secretory features in a pattern similar to changes observed in sham. The results suggest that impairment in the structure of the functional parts of secretory cells by estrogen treatment was a factor contributing to the inhibition of the gastric secretions.

Animals↗
PubMed1980

Intracellular distribution of lysosomal enzymes in the mouse pigment mutants pale ear and pallid.

The size distribution of lysosomes was determined in kidney proximal tubule cells of two mouse pigment mutants, pale ear and pallid, which have an increase in kidney lysosomal enzyme content caused by a decreased rate of secretion of lysosomal enzymes into urine. Both mutations have larger lysosomes when compared with normal mice. However, neither mutant contains the giant lysosomes (up to 11 micron diameter) common to the well-characterized beige mutant, which has a kidney secretory defect similar to the pale ear and pallid mutants. Subcellular distribution studies, performed by the osmotic shock technique, likewise suggested differences among the pigment mutants. A very high content of soluble enzyme, indicative of lysosomal fragility during homogenization, was found in extracts from the beige mutation. By comparation, the percent of soluble enzyme became progressively lower in extracts of the pallid and pale ear mutants and was lowest in extracts from normal mice. All 3 pigment mutants had normal concentrations of osmotically resistant membrane-bound lysosomal enzymes. This indicates that the excess, non-secreted, lysosomal enzyme in all three pigment mutants likely is present in classical lysosomal organelles rather than in other non-lysosomal subcellular membrane fractions. The results also illustrate that mammalian mutants which exhibit lysosomal secretory rates can have strikingly different effects on morphology of lysosomes.

Animals↗
PubMed1989

Control of insulin secretion by sulfonylureas, meglitinide and diazoxide in relation to their binding to the sulfonylurea receptor in pancreatic islets.

Sulfonylureas inhibit an ATP-dependent K+ channel in the B-cell plasma membrane and thereby initiate insulin release. Diazoxide opens this channel and inhibits insulin release. In mouse pancreatic islets, we have explored whether other targets for these drugs must be postulated to explain their hypo- or hyperglycaemic properties. At non-saturating drug concentrations the rates of increase in insulin secretion declined in the order tolbutamide = meglitinide greater than glipizide greater than glibenclamide. The same rank order was observed when comparing the rates of disappearance of insulin-releasing and K+ channel-blocking effects. The different kinetics of response depend on the lipid solubility of the drugs, which controls their penetration into the intracellular space. Allowing for the different kinetics, the same maximum secretory rates were caused by saturating concentrations of tolbutamide, meglitinide, glipizide and glibenclamide. A close correlation between insulin-releasing and K+ channel-blocking potencies of these drugs was observed. The relative potencies of tolbutamide, meglitinide, glipizide and glibenclamide corresponded well to their relative affinities for binding to islet-cell membranes, suggesting that the binding site represents the sulfonylurea receptor. The biphasic time-course of dissociation of glibenclamide binding indicates a complex receptor-drug interaction. For diazoxide there was no correlation between affinity of binding to the sulfonylurea receptor and potency of inhibition of insulin secretion. Thus, opening or closing of the ATP-dependent K+ channel by diazoxide or sulfonylureas, respectively, appears to be due to interaction with different binding sites in the B-cell plasma membrane. The free concentrations of tolbutamide, glipizide, glibenclamide and diazoxide which are effective on B-cells are in the range of therapeutic plasma concentrations of the free drugs. It is concluded that the hypo- and hyperglycaemic effects of these drugs result from changing the permeability of the ATP-dependent K+ channel in the B-cell plasma membrane.

ATP-Binding Cassette Transporters↗
PubMed1998

Salivary acidic proline-rich proteins in rheumatoid arthritis.

In an ongoing attempt to investigate qualitative salivary parameters in diseases affecting salivary glands, patients with rheumatoid arthritis (RA) were examined. Patients were selected from the Oslo RA register for the present study if they fulfilled the following criteria: age 52-74 years, disease duration 10-20 years, and disability score as assessed by the Modified Health Assessment Questionnaire < or = 2.5. From these 105 patients, two subgroups of patients were selected, one group with pronounced sicca symptoms from eyes and mouth, and one group without such symptoms. Sicca symptoms were assessed using a postal questionnaire with the questions on dry mouth and dry eyes of the European classification criteria for Sjögren's syndrome. Patients were excluded from further examinations if they used medication that could cause dryness in eyes or mouth. Thus, nine patients remained in the sicca group (having four or more sicca symptoms), and ten matched RA patients were selected for the nonsicca group. A healthy sex- and age-matched control group (n = 10) was also examined. In a preliminary report we have shown that differences in flow rates between sicca and nonsicca RA patients were limited to lower values of unstimulated whole saliva. To further evaluate salivary changes in RA, a disease frequently associated with secondary Sjögren's syndrome, we have studied qualitative salivary parameters in these patients,' including secretory rates of proline-rich proteins (PRPs), statherins, and histatins. In the present report, phenotypes of PRPs, the ratio of PRPs derived from the two loci (PRH1 and PRH2), and PRP concentration and output in parotid and submandibular saliva derived from the two loci are presented. Parotid (PS) and submandibular saliva (SS) were collected from all individuals using 2% citric acid as a saliva stimulus. PRPs in PS and SS were identified using a SMART microchromatographic system with a Mono Q column and a Tris-HCl/NaCl gradient (method adapted from ref. 5). For PRPs, the primary polypeptide products are coded for on two loci (PRH1 and PRH2), which have three and two commonly occurring gene variants, respectively. On PRH1, the proteins PIF-s, Db-s, and Pa are coded for, whereas PRP-1 and PRP-2 are coded for on the PRH2 locus. As each protein variant has a postranscriptional cleavage product, individuals will exhibit four, six, or eight PRPs in their saliva, depending on whether they are homozygous at both, one, or neither of the two loci. Accordingly, 18 possible phenotypes may exist, but as few as three phenotypes were found in 79% of the 127 healthy individuals examined by Hay et al. The SMART system allows the determination of the different acidic PRPs present in saliva. Concentrations of the various phenotypes were calculated by peak integration versus pure PRP standards. Total PRP concentration derived from each locus was calculated as the sum of the concentrations of PRP variants from that locus.

Aged↗