Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies.

Discordant assessment of lupus activity between patients and their physicians: the Singapore experience.

Patients with systemic lupus erythematosus often assess their disease activity differently from their physicians. We studied the factors associated with this discordance. The data provided by 534 systemic lupus erythematosus patients were analyzed. We compared the physician and patient assessments of lupus activity on a visual-assessment scale from the same visit. We collected clinical data and scores from MOS 36-Item Short-Form Health Survey, Systemic Lupus Erythematosus Quality-of-Life Questionnaire, Rheumatology Attitudes Index, Systemic Lupus Erythematosus Disease Activity Index, and revised Systemic Lupus Activity Measure. Patients tended to score their disease activity higher than do their physicians, when these factors were present: poorer general health assessment, presence of thrombocytopenia, hypertension and urinary sediments, and difficulty in carrying groceries. Physicians tended to score the disease activity higher than do the patients in these circumstances proteinuria, hemolysis, use of azathioprine or cyclophosphamide, tiredness, photosensitivity, higher revised Systemic Lupus Activity Measure score, casturia, and patient report of being more easily ill than are other patients. There was only moderate correlation between the discordance in the baseline and the subsequent visits. The physician assessment of disease activity at baseline correlated better with an objective measure of disease activity (revised Systemic Lupus Activity Measure) in the subsequent visit than the patient assessment. In conclusion, discordance in the perception of disease activity between patients and physicians may be amenable to intervention.

Enhanced expression of interferon-inducible protein-10 correlates with disease activity and clinical manifestations in systemic lupus erythematosus.

Our objective was to investigate the serum levels of interferon-inducible protein-10 (IP-10) in systemic lupus erythematosus (SLE) and their correlation with disease activity and organ manifestations. Serum IP-10 levels were assessed in 464 SLE patients and 50 healthy donors. Disease activity was assessed by the revised SLE Activity Measure, and the concomitant active organ manifestations, anti-ds DNA antibody titres, complement levels and erythrocyte sedimentation rates recorded. Peripheral blood mononuclear cell (PBMC) synthesis of IP-10 in SLE patients and controls was determined by in vitro cultures stimulated with mitogen or lipopolysaccharide. Elevated serum IP-10 levels were observed in SLE patients, which were significantly higher in the presence of active haematological and mucocutaneous manifestations. SLE PBMCs exhibited enhanced spontaneous IP-10 production in vitro. Serial IP-10 levels correlated with longitudinal change in SLE activity, even at low levels where anti-dsDNA antibody and complement levels remain unchanged. These data demonstrate that IP-10 levels are increased in SLE and serum IP-10 may represent a more sensitive marker for monitoring disease activity than standard serological tests.

Computer-assisted mapping of immunoreactive mammalian gonadotropin-releasing hormone in adult human basal forebrain and amygdala.

Immunocytochemistry performed on 80-microns unembedded tissue sections was used to study the localization of GnRH-containing neurons and fibers in the basal forebrain and amygdala of six adult (four male, two female) human brains. Sections from one of the female brains were subjected to computer-assisted microscopic mapping to generate a three-dimensional analysis of immunoreactive structures. In all six brains examined, cell bodies were concentrated in the preoptic area and basal hypothalamus, but were also evident in the septal region, anterior olfactory area, and cortical and medial amygdaloid nuclei. GnRH-containing fibers were observed within the hypothalamus (predominantly infundibular region and preoptic area), septum, stria terminalis, ventral pallidum, dorsomedial thalamus, olfactory stria, and anterior olfactory area. Many fibers could also be seen coursing along the base of the brain between the hypothalamus and cortical and medial amygdaloid nuclei. The localization of GnRH-containing cells and fibers in several of these areas represents new observations in the human brain and suggests a role for the amygdaloid complex in the regulation of gonadotropin secretion. The comprehensive view provided by these data may be useful in the clinical application of novel transplantation strategies.

Effect of anti-insulin serum on the hepatic lipid metabolism of BHE rats.

The effects of daily injections of anti-insulin serum (AIS) on the hepatic synthesis of lipids was studied in young male BHE rats after 3 weeks of feeding either a 45% carbohydrate 40% protein diet, a 65% sucrose diet, or a 65% protein diet. One-half of the animals in each diet group received injections daily with AIS, and the remaining animals in each group received injections with isotonic saline solution. After 3 weeks the animals were killed, and levels of serum insulin cholesterol, and triglycerides were determined as were the levels of liver lipid, cholesterol, fatty acid synthetase, and the conversion of acetate 14C to cholesterol 14C. AIS treatment lowered serum insulin levels, serum triglyceride levels, caloric intake, weight gain, liver weight, acetate 14C incorporation into cholesterol 14C, and the percentage of liver lipid that was cholesterol. Diet affected serum and liver lipid levels, fatty acid synthetase activity, and the incorporation of acetate 14C into cholesterol 14C. The results of this study show that the lipogenic characteristic of the BHE rat is diet dependent, but that this characteristic can be modified to a limited extent by AIS treatment. Further, the results also suggest that the hyperlipemic characteristic of these rats may be independent of the hyperinsulinemic characteristic.

Clinical signs found in association with nutritional deficiencies as related to race, sex, and age for adults.

Clinical signs of various nutritional deficiencies for 429 adults were compared by race, age, and sex. The nutrients studied were vitamin A, riboflavin, vitamin C, vitamin D, and calcium. The prevalence of clinical signs of deficiency for all nutrients was much higher in blacks than in whites. Clinical lesions due to multiple nutrient deficiencies showed the same racial difference. Men had a higher prevalence of clinical signs for all nutrient deficiencies, except for vitamin A, that did the young. The racial and age differences in the nutritional status may be explained by the difference of educational and income levels. In comparison to the results reported from the Health and Nutrition Examination Survey (HANES), 1971 to 1974, the white subjects in this study had slightly higher prevalences of clinical signs than did those in HANES. Also, the prevalence of these clinical signs is much higher in the black subjects of the present study than in those of HANES.

Comparison of selected blood components by race, sex, and age.

The effects of race, age, and sex on selected blood components for 429 black and white adults over 34 year in southwest Mississippi were studied. Fasting blood was collected early in the morning. Whole blood was used for the determination of hematocrit and hemoglobin. The sera were used for the analysis of iron, glucose, triglycerides, cholesterol, vitamin C, alkaline phosphatase, and protein and its fractions such as albumin, alpha-, beta-, and gamma-globulins. The data of whites versus blacks, males versus females, and those under versus over 60 years were compared. A significant racial difference was observed for all selected blood components except alpha-1-globulin, cholesterol, and alkaline phosphatase. Albumin, alpha-2-globulin, hemoglobin, hematocrit, serum iron, triglycerides, and vitamin C were significantly higher in whites than in blacks and total protein, beta-1- and gamma-globulins and glucose were significantly higher in blacks than in whites. Males had higher levels of alpha-1- and gamma-globulins, hemoglobin, and hematocrit, and females had higher levels of cholesterol and alkaline phosphatase. Those 60 years and over had higher gamma-globulin and alkaline phosphatase, while adults under 60 years had higher hematocrit. Although results of this study showed significant differences between the races for certain blood parameters and suggest that these differences should be considered in determining guidelines for nutritional evaluation and criteria of diagnosing diseases, further studies are needed to determine the contributions of environment, economic status, and nutritional status to these differences.

Use of xanthan gum in dietary management of diabetes mellitus.

Xanthan gum (12 g/day) was fed in muffins during either the first or second half of a 12-wk period of muffin feeding, to free-living subjects. Nine subjects were diabetic, having moderately elevated serum glucose but managing without insulin or hypoglycemic drugs, and four were nondiabetic controls. Before the study and at the end of the xanthan and xanthan-free periods, bloods were taken before and 2 h after an oral glucose load. The feeding of xanthan gum lowered fasting and postload serum glucose and reduced fasting levels of total plasma cholesterol in diabetic subjects. Xanthan gum also tended to lower fasting and postload levels of gastrin and gastric inhibitory polypeptide (GIP) and fasting levels of total and VLDL triglyceride and cholesterol in VLDL and LDL fractions. Subjects reported a sense of fullness after consuming xanthan muffins but no severe digestive symptoms.

Computer-aided mapping of specific neuronal populations in the human brain.

Antibody-staining methods and computer-aided microscopic systems have been used to generate high-resolution panoramic maps of specific neuronal populations in the human brain (4,6,11). This report focuses on the problems inherent in attempting high-resolution mapping of large brain sections, and describes how they are solved by computer-aided mapping. Further applications of computers to the study of brain structure are considered.

Functionally and anatomically distinct populations of vasopressinergic magnocellular neurons in the female golden hamster.

The present study was done to determine whether the vasopressinergic neurons in the hypothalamus controlling flank marking behavior are distinct from the magnocellular neurons comprising the hypothalamo-neurohypophysial system. Animals were either hypophysectomized or injected with a suicide transport lectin, volkensin, into the neurohypophysis. Both procedures resulted in a pronounced loss of vasopressin-immunoreactive perikarya throughout the hypothalamus concomitant with increases in water intake and urine output and decreases in circulating levels of vasopressin. The loss of the hypothalamo-neurohypophysial system was most pronounced in volkensin-treated animals that presented with frank diabetes insipidus and exceedingly low levels of plasma vasopressin. However, the vasopressinergic fibers and magnocellular neurons in and around the anterior hypothalamus implicated in the control of flank marking survived the volkensin treatment. Volkensin-treated animals exhibited levels of flank marking typical of untreated animals. These data suggest the presence of anatomically and functionally distinct populations of vasopressinergic magnocellular neurons in the hypothalamus of the golden hamster.

Computer-Aided Mapping of Vasopressin Neurons in the Hypothalamus of the Male Golden Hamster: Evidence of Magnocellular Neurons that do not Project to the Neurohypophysis.

Abstract Vasopressin-sensitive neurons in the region of the anterior hypothalamus are necessary for the mediation of flank marking behavior in the Golden hamster. The precise nature of the vasopressinergic innervation to the anterior hypothalamus is unknown. In this study we seek to examine the potential sources of this innervation by mapping and counting the vasopressin-immunoreactive neurons that contribute to the hypothalamo-neurohypophysial system, and those that do not. Vasopressin-immunoreactive neurons in the hypothalamus were visualized by immunocytochemistry. Sections were mapped with a computer-aided microscope system, and labeled neurons counted. Two-dimensional maps were stacked into a three-dimensional wireframe model which could be manipulated for further examination. The average number of vasopressin neurons was 3,135, with over 60% of all perikarya localized to the lateral supraoptic nucleus. In a double-labeling study, neurons contributing to the hypothalamo-neurohypophysial system were retrogradely labeled by the injection of horseradish peroxidase into the neurohypophysis. The enzyme reaction product was visualized by treatment with tetramethylbenzidine followed by nickel-conjugated diaminobenzidine. Sections were subsequently stained for vasopressin by immunocytochemistry. Single- and double-stained neurons from serial sections were mapped and counted. Wireframe and contoured three-dimensional representations were generated. The average number of neurons projecting to the neurohypophysis was 5,619. However, an average of 981 neurons was immunoreactive to vasopressin but devoid of horseradish peroxidase. The greatest number of these non-projecting perikarya were found in and around the anterior hypothalamus, localized primarily in the lateral and medial aspect of the supraoptic nuclei, the ventral area of the paraventricular nucleus, and the nucleus circularis. By comparing the number of non-projecting neurons found by double-staining to the total cell count of the entire vasopressin system, it was estimated that approximately 30% of all vasopressin neurons in and around the anterior hypothalamus did not project to the neurohypophysis. Based on the distribution and localization of the non-projecting perikarya, it is speculated that these neurons may provide neurotransmitter for vasopressin-dependent flank marking in the male Golden hamster.

Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat.

Ascending projections from the caudal (general-visceroceptive) part of the nucleus of the solitary tract (NTS) were studied experimentally in the rat by the aid of the anterograde autoradiographic and the retrograde horseradish peroxidase (HRP) tracer techniques. Microelectrophoretic deposits of tritiated proline and leucine which involved the caudal part of the NTS, the dorsal motor nucleus of the vagus (dmX), and portions of the hypoglossal nucleus, nucleus intercalatus and/or nucleus gracilis were found to label ascending fibers that, besides going to numerous brain stem territories that included prominently the parabrachial area, could also be traced to serveral forebrain structures, namely, the bed nucleus of the stria terminalis (BST), the paraventricular (PA), dorsomedial (HDM) and arcuate (ARC) nuclei of the hypothalamus, the central nucleus of the amygdaloid complex (AC), the medial preoptic area (PM) and the periventricular nucleus of the thalamus (TPV). Smaller isotope injections almost completely confined to the NTS and dmX resulted in lighter labeling of a similar set of parabrachial and forebrain projections, whereas in another case, in which the deposit was almost exclusively limited to the nucleus gracilis, no label was seen in the aforementioned structures. In another series of experiments, aimed at further localizing the neurons of origin of the prosencephalic projections under consideration, small microelectrophoretic HRP injections confined almost totally to BST, PA, HDM, AC, PM or TPV, as well as both small and large injections involving ARC, resulted in labeled neurons situated in the dorsal medullary region, mainly in the medial portion of the NTS at the level of and caudal to the area postrema. Taken together, these observations indicate for the first time the existence of relatively direct conduction lines by which interoceptive information might be conveyed to limbic forebrain structures; some of the possible physiological correlates of these anatomical findings are discussed.

Sexual differences in the magnocellular vasopressinergic system in golden hamsters.

Golden hamsters, as compared to rats, lack several parvicellular vasopressinergic cell groups, particularly sexually dimorphic populations. We decided to test the possibility that magnocellular vasopressinergic neurons are subjected to sexual differences in hamsters, as they are known to display vasopressin (AVP)-dependent sexually dimorphic behaviors. The distribution of magnocellular vasopressinergic neurons was mapped and compared between males and females. Approximately 50% more vasopressin-immunoreactive (AVP-ir) neurons were counted in males within the medial and lateral divisions of the supraoptic nucleus. Furthermore, levels of AVP extracted from the hypothalamus and the pituitary gland were three to four times higher in males than in females. Finally, hypothalamic extracts from a male and a female hypothalamus were fractionated by HPLC and assayed for AVP immunoreactivity. Immunoreactivity from each extract had the same retention time as synthetic AVP standards; and the levels were twice as high in the male. These results support the existence of sexual differences in the magnocellular vasopressinergic system in golden hamsters. These differences appear to be related to previously reported sexual differences in AVP secretion from the neurohypophysis.

Architecture of the suprachiasmatic nuclei in BALB/c and C57BL/6 inbred mouse strains.

Quantitative values representing the length, girth, volume, shape, and cell counts of the suprachiasmatic nuclei (SCN) were measured in BALB/cByJ and C57BL/6J inbred mouse strains, which exhibit a large interstrain difference in the free-running period of their circadian locomotor rhythms. There were no differences in the gross architectural features of the SCN in these two strains.

Food resources of low-income households in Southwest Mississippi.

Demographic data and food resources were studied for 1,400 households in seven counties in Southwest Mississippi. The results were compared for industrialized and non-industrialized counties and the urban areas. Household incomes and the educational levels of household heads were far below the national level. Hunger is still prevalent among those with the lowest incomes and the least education. Since most of the household heads with lower incomes either were unemployed or had unskilled jobs, the government was their main food resource. Welfare accounted for 25% and Food Stamps for 30%. The next important source was the school. Such critical conditions as lower income, limited education, unemployment, hunger, and need for government assistance were more prevalent in non-industrialized counties than in industrialized counties and the urban areas. The government assistance programs for food are necessary to prevent hunger, to maintain nutritional adequacy, and, consequently, to reduce medical bills. This is especially true for the poverty-level families, who need the federal food programs for daily survival.

Selected anthropometric measurements for a low-income, black population in Mississippi.

The anthropometric battery for the present study included measurement of height, weight, triceps and subscapular skinfolds, blood pressure, and pulse for a low-income, black population. All measurements were affected by age and sex. They generally increased with age. Blood pressures and skinfold thickness were greater in female subjects and in the old than in male subjects or in the young. Male subjects were always taller than female subjects at a comparable age. Women weighed more than men in the 30 to 60 age group. Hypertension and obesity were more prevalent among women and the old. The total anthropometric measurements of height, weight, and subscapular skinfold (but not of triceps skinfold) of children in this study were generally greater than those of children in other studies. This study shows that genetic and endocrine mechanisms may override environmental factors for selected anthropometric data.

Comparison of dietary energy intakes and sources by race, sex, and age for adults in Mississippi.

Energy intake and sources and alcohol and caffeine consumption of 384 Mississippians older than 34 were studied by 24-hour recall. The data were compared by race, sex, and age. Whites consumed more energy and had more adequate energy intake than blacks. Energy intake was more adequate in women than in men. The mean protein intake for all groups, except black men, was in excess of the Recommended Dietary Allowance (RDA). Protein represented 12% of the calories consumed daily by whites and 14% by blacks. Both figures are slightly more than the RDA for this age group. Whites consumed 66 gm fat and blacks 56 gm, representing 33% of total energy for whites and 38% for blacks. The mean cholesterol consumption was 339 mg for blacks and 310 mg for whites. Men consumed slightly more cholesterol than women. Whites consumed 334 gm total carbohydrates and blacks 202 gm. Starch and sugar provided 59% of total energy for whites and 52% for blacks. Whites drank 4 times more alcohol than blacks, with alcohol representing 3% of energy for whites and 1% for blacks. Whites consumed 2.5 times more caffeine than blacks. Young individuals consumed more caffeine than older ones. This study clearly shows a significant racial difference in energy content and sources in the diet of adults in Mississippi.

Frequency of selection of food groups by low-income families in southwestern Mississippi.

Food resources and frequency of food use of 1,000 households in Claiborne County in southwestern Mississippi were studied and related to income and educational level of the family heads. Income and educational levels of the family heads were much lower than the national average. The data on food frequency use indicated that the meal patterns of these households could not provide sufficient nutrients for individual family members. Income and educational levels of the family heads correlated highly with food frequency scores. The households with higher incomes and more education had better food consumption patterns than those with lower incomes and less education. However, income had more effect on low nutrient intake than education.

Nutrient intake of low-income, black families in southwestern Mississippi.

A dietary intake study for 250 low-income households in Claiborne County in southwestern Mississippi was conducted from June through August 1974. Data were obtained during daily home visits for seven days by trained college students. The adequacy of nutrient intake for individuals was evaluated by comparing the data with the 1974 Recommended Dietary Allowances by age and sex. The data was also compared with those of the Ten-State Nutrition Survey and HANES. Mean intakes of protein, vitamin A, thiamin, riboflavin, and ascorbic acid for all subjects were above the RDAS; those of energy, calcium, iron, and preformed niacin were below the allowances. Whereas calcium was the nutrient least adequately consumed by all persons, protein was most adequately consumed. Sixty per cent of children had calcium intakes below two-thirds of the allowance. By sex, 66.7 per cent of all males and 73.3 per cent of all females had calcium intakes below two-thirds of the standard. None of children received less than two-thirds of the allowance for protein. Nutrient intake was low for a substantial number of the subjects. Adolescents, ages eleven to eighteen years, of both sexes had the poorest diets for all nutrients. Regarding the sex difference, females had better nutrient intakes than did males for all nutrients except calcium and iron.

Effects of fructose feeding on blood parameters and blood pressure in impaired glucose-tolerant subjects.

The effects of fructose and glucose on selected blood parameters and blood pressure after 4 weeks of oral ingestion were investigated in nine impaired glucose-tolerant subjects (IGTS) and nine normal glucose-tolerant subjects (NGTS). The criteria for IGTS were (1) 1- or 2-hour postprandial glucose levels between 160 and 200 mg/dL (8.8 to 11.1 mmol/L); (2) compliance with the diet; and (3) no cardiac or renal complication. The mean increment in the area under the plasma glucose and insulin curves after a glucose load was significantly greater following glucose than following fructose ingestion in both IGTS and NGTS (p less than .05). Glycosylated hemoglobin was greater after glucose than after fructose ingestion in IGTS and NGTS (71 gm/L vs. 61 gm/L in IGTS; 61 gm/L vs. 59 gm/L in NGTS). Serum triglyceride level in IGTS fed glucose was 173 mg/dL (1.90 mmol/L), whereas in those fed fructose, it was 154 mg/dL (1.69 mmol/L). Serum cholesterol was also greater after glucose than after fructose ingestion in all subjects. However, the differences were not statistically significant. Urate, pyruvate, and lactate levels were significantly greater in IGTS fed glucose than in IGTS fed fructose. Systolic and diastolic pressures were lower in IGTS fed fructose than in IGTS fed glucose. The present study shows that a 4-week oral ingestion of moderate amounts of fructose appears to have more benefits than an equivalent glucose ingestion in both IGTS and NGTS. However, greater benefits were found in IGTS than in NGTS.