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R J Bosch

Publications and source records attributed to R J Bosch.

At least 37 records · Page 2Linked to original sources
PubMed1998

Flexible assessment of trends in age-specific HIV incidence using two-dimensional penalized likelihood.

We present a method for estimating age- and time-specific HIV incidence using back-calculations of AIDS incidence data. Two-dimensional penalized likelihood is employed, using a flexible bivariate step function model of HIV incidence, together with a quadratic roughness penalty which leads to thin-plate spline smoothing. This allows incidence estimates to vary flexibly and smoothly in both age and time. We propose generalized cross-validation as a guide for choice of an appropriate level of smoothing and describe an EM algorithm for computing the estimates. We propose the method primarily for qualitative assessment of trends in age-specific incidence over time and apply it to a small Italian data set on men who have sex with men. The analysis suggests a trend over time of increasing relative incidence among younger individuals, consistent with incidence patterns observed in other countries.

Adult↗
PubMed1998

Age-related increase in expression of TGF-beta1 in the rat kidney: relationship to morphologic changes.

In the kidney, aging is characterized by the development of structural changes, including glomerulosclerosis and interstitial fibrosis. Transforming growth factor-beta1 (TGF-beta1) is known to play a critical role in the genesis of these alterations in pathologic conditions. The present experiments were designed to test the hypothesis that TGF-beta1 may be involved in the development of age-related histopathologic changes in rat kidney, and that captopril, an angiotensin-converting enzyme inhibitor, may influence the progression of glomerular and interstitial lesions. In this study, 3-, 18-, 24-, and 30-mo-old rats were examined, and an age-related increase in urinary protein excretion was found; plasma creatinine and systolic BP did not change. Significant structural changes, including glomerular sclerosis and interstitial fibrosis, were found in the group of aged rats (24- and 30-mo-old). Immunostaining for TGF-beta in the renal cortex interstitium was increased in the group of 24-mo-old rats, with a parallel increase in TGF-beta1 mRNA expression, measured with reverse-transcription PCR. Captopril-treated animals showed a statistically significant decrease in urinary protein excretion but no significant changes in BP. Moreover, captopril reduced the extent of interstitial fibrosis, but did not affect the degree of glomerulosclerosis. A significant inhibition of TGF-beta1 mRNA expression was observed in the captopril-treated animals. These findings suggest that TGF-beta1 may act as a fibrogenic growth factor that could be responsible, at least partially, for the renal interstitial fibrosis associated with aging. Treatment with captopril might delay the progression of these lesions.

Aging↗
PubMed1998

Comparison of 4 questionnaires for assessment of fruit and vegetable intake.

OBJECTIVE: This study compared fruit and vegetable assessments derived from 4 self-administered questionnaires. METHODS: Among 102 adolescents, servings of fruits and vegetables assessed by 4 questionnaires were compared with estimates from 24-hour recalls. RESULTS: The prevalence of consuming 5 or more servings of fruits and vegetables a day was underestimated by the questionnaires. Questionnaires asking subjects to recall their diet over the previous year were more effective in ranking subjects (r's > or = .42) than those assessing previous-day diet (r's > or = .30). CONCLUSIONS: Brief assessments of fruit and vegetable intake are more useful for ranking subjects than for estimating prevalence of consumption of 5 or more servings per day.

Adolescent↗
PubMed1997

Decreasing age at infection for homosexually acquired HIV in Italy: results of a back-calculation analysis.

The age-specific incidence of homosexually acquired HIV in Italy was examined, based on 3918 AIDS cases diagnosed by the end of 1994 and reported by the end of 1995 through the national surveillance system. Using a smoothed back-calculation analysis, the estimated median age at infection decreased over time, and HIV incidence among younger age groups peaked much later than among older age groups. These results support recent findings from other developed countries, and suggest that measures for preventing homosexual transmission of HIV are best targeted at younger age groups.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Growth failure as a prognostic indicator of mortality in pediatric HIV infection.

OBJECTIVE: To study the effect of perinatally acquired human immunodeficiency virus (HIV) on somatic growth and examine the relationship of nutritional status to mortality in HIV-infected infants. METHOD: Pregnant women attending the antenatal clinic at Mulago hospital in Kampala, Uganda, were enrolled. All live-born babies born to HIV-1 seropositive (HIV+) women, and to every fourth age-matched HIV-1 seronegative (HIV-) woman, were followed for 25 months. RESULTS: The mean weight-for-age and length-for-age curves of HIV+ children were significantly lower than those of HIV- controls and seroeverters. Forty-five (54%) of the 84 HIV+ infants died before their second birthday, as compared with a 1.6% and 5.6% mortality in HIV- and seroeverters. HIV+ infants with an average weight-for-age Z-score below -1.5 in the first year of life have a nearly fivefold risk of dying before 25 months of age compared with noninfected controls. CONCLUSION: Perinatally acquired HIV infection is associated with early and progressive growth failure. The severity of growth failure is associated with an increased risk of mortality. The effect of early, aggressive nutritional intervention in delaying HIV progression and mortality should be evaluated by controlled intervention studies.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A semiparametric approach to risk assessment for quantitative outcomes.

Characterizing the dose-effect relationship and estimating acceptable exposure levels are the primary goals of quantitative risk assessment. A semiparametric approach is proposed for risk assessment with continuously measured or quantitative outcomes which has advantages over existing methods by requiring fewer assumptions. The approach is based on pairwise ranking between the response values in the control group and those in the exposed groups. The work generalizes the rank-based Wilcoxon-Mann-Whitney test, which for the two-group comparison is effectively a test of whether a response from the control group is different from (larger than) a response in an exposed group. We develop a regression framework that naturally extends this metric to model the dose effect in terms of a risk function. Parameters of the regression model can be estimated with standard software. However, inference requires an additional step to estimate the variance structure of the estimated parameters. An effective dose (ED) and associated lower confidence limit (LED) are easily calculated. The method is supported by a simulation study and is illustrated with a study on the effects of aconiazide. The method offers flexible modeling of the dose effect, and since it is rank-based, it is more resistant to outliers, nonconstant variance, and other departures from normality than previously described approaches.

Animals↗
PubMed1995

The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.

A previous study reported the increased expression of the cytokine TNF in the adipose tissue of genetically obese rodents. To examine this paradigm in humans, we studied TNF expression in lean, obese, and reduced-obese human subjects. TNF mRNA was demonstrated in human adipocytes and adipose tissue by Northern blotting and PCR. TNF protein was quantitated by Western blotting and ELISA in both adipose tissue and the medium surrounding adipose tissue. Using quantitative reverse transcriptase PCR (RT-PCR), TNF mRNA levels were examined in the adipose tissue of 39 nondiabetic subjects, spanning a broad range of body mass index (BMI). There was a significant increase in adipose TNF mRNA levels with increasing adiposity. There was a significant correlation between TNF mRNA and percent body fat (r = 0.46, P < 0.05, n = 23). TNF mRNA tended to decrease in very obese subjects, but when subjects with a BMI > 45 kg/m2 were excluded, there was a significant correlation between TNF mRNA and BMI (r = 0.37, P < 0.05, n = 32). In addition, there was a significant decrease in adipose TNF with weight loss. In 11 obese subjects who lost between 14 and 66 kg (mean 34.7 kg, or 26.6% of initial weight), TNF mRNA levels decreased to 58% of initial levels after weight loss (P < 0.005), and TNF protein decreased to 46% of initial levels (P < 0.02). TNF is known to inhibit LPL activity. When fasting adipose LPL activity was measured in these subjects, there was a significant inverse relationship between TNF expression and LPL activity (r = -0.39, P < 0.02, n = 39). With weight loss, LPL activity increased to 411% of initial levels. However, the magnitude of the increase in LPL did not correlate with the decrease in TNF. Thus, TNF is expressed in human adipocytes. TNF is elevated in most obese subjects and is decreased by weight loss. In addition, there is an inverse relationship between TNF and LPL expression. These data suggest that endogenous TNF expression in adipose tissue may help limit obesity in some subjects, perhaps by increasing insulin resistance and decreasing LPL.

Adipocytes↗
PubMed1993

Gene transfer into the mammalian kidney: first steps towards renal gene therapy.

In this review we discuss two strategies for successful retrovirally-mediated transfer (transduction) of a reporter gene (bacterial beta-galactosidase) into the mammalian kidney. Retroviruses only integrate into dividing cells, but the adult kidney has a very low cell turnover. One approach used is the rapidly-dividing metanephros, or precursor of the adult kidney, as a target for proviral integration. After infection and microtransplantation of fragments of this tissue into the renal cortex of neonatal mice, the implants grew and developed within the host kidney and reporter gene expression was located in glomerular and interstitial cells. A similar approach has been used by other investigators to grow genetically-engineered metanephros in a subcapsular location in the kidney. However, access of the gene product to the parenchyma of the kidney may be limited using this approach. A second strategy was to induce renal tubular cell replication by causing nephrotoxic damage with a folic acid injection. This created a 'biological window' in which a specific cell population, that is, tubular cells, was targeted for retroviral infection. One to four weeks later foci of tubular cells were found to express the reporter gene product. In both models, 50 to 90% of the experiments showed evidence of proviral integration as judged by the presence of a 559 base-pair DNA fragment amplified by the polymerase chain reaction. This persisted for four to seven weeks, the limit of the period of observation.

Animals↗
PubMed1992

Growth factors in the pathogenesis of renovascular complications of diabetes mellitus.

PURPOSE: We reviewed the evidence that links altered levels of circulating and intrarenal growth factors with the genesis of renal glomerular hypertrophy, microvascular disease and interstitial fibrosis as seen in diabetes mellitus. ANIMAL DATA: Insulin-like growth factor 1 (IGF-1) appears to be a hypertrophic factor in experimental renal disease, and is also known to be mitogenic for mesangial and vascular smooth muscle cells. However, an alteration in the balance of other factors, such as platelet-derived growth factor and angiotensin (Ang) II, could contribute to the growth disorder. Data from healthy animals suggest that the paracrine stimulation of interstitial fibroblasts by adjoining renal epithelial cells may contribute to the progressive interstitial fibrosis and microvascular occlusion found in diabetic nephropathy and other chronic renal diseases. HUMAN DATA: The progressive fall in the glomerular filtration rate in patients with diabetic nephropathy may be partly explained by structural damage in the glomerulus subsequent to hyperfiltration and hypertrophy. However, interstitial disease is independently correlated with serum creatinine. There is no evidence to show whether growth factors contribute to the genesis of human diabetic nephropathy, and circulatory levels of IGF-1 and Ang II are not clearly correlated with renal disease. It is possible, but not proven, that intrarenal levels of growth factors may be particularly relevant to the pathogenesis of glomerular microvascular and interstitial disease.

Angiotensin II↗
PubMed1992

Perineal pudendal neurotomy versus selective neurotomy of the S2 somatic contribution to the pudendal nerve. Effects on sacral-root-stimulated bladder and urethral responses in the dog.

In 10 dogs that underwent bilateral electrode implantation on the S2 ventral root, 5 then underwent a bilateral total perineal neurotomy of the pudendal nerve (group A) at 3 months and 5 bilateral division of the S2 somatic contribution to the pudendal nerve (group B). The effects of these 2 types of neurotomy on the bladder and urethral responses to electrostimulation were compared after another 3 months. In group A, the proximal and mid-urethral responses decreased significantly [69.1% (p = 0.004) and 79.6% (p = 0.002), respectively]. A decrease in bladder response [26% (p = 0.089)], although not significant, was also found. In group B, the decrease in the proximal urethral response was significant [67.8% (p = 0.012)]; the mid-urethral response (56.8%) was not statistically significant (p = 0.134). The bladder response decreased by 73.6% (p = 0.034). Thus, although pudendal neurotomy can be effective in reducing the outlet resistance, the pudendal nerve may have an important role in the regulation of micturition in the dog. Preoperative testing of the effect of a pudendal neurotomy by temporary nerve blocks is warranted to avoid undesirable side effects such as a decrease in bladder excitability.

Animals↗
PubMed1991

Penile detumescence: characterization of three phases.

In 22 dogs in which erection was induced by cavernous nerve stimulation, we analyzed the intracavernous pressure changes during detumescence without and with acute clamping of the aorta or electrostimulation of the lumbar sympathetic chains. Additionally, the degree of venous outflow obstruction was assessed by saline perfusion of the cavernous body during aortic occlusion. Detumescence had three distinct phases: an initial phase exhibiting a small pressure increase; a second phase showing a slow pressure decrease; and a third phase in which a fast decrease occurred. The first phase was abolished by aortic clamping, whereas the other phases were not significantly affected. Sympathetic stimulation abolished or prevented the second phase. Perfusion of the cavernous body during the second phase resulted in a pressure rise to off-scale values; however, when initiated during the terminal phase or in the nonstimulated penis, the pressure increase was slight. Our study indicates that the arterial flow rate influences the duration of the first phase of detumescence and that venous drainage is completely restored in the third phase. Furthermore, sympathetic stimulation causes an almost immediate full restoration of venous drainage, as cavernous perfusion initiated with an intracavernous pressure about twice as high as without sympathetic stimulation failed to increase pressure to off-scale values.

Animals↗
PubMed1991

Renal transplantation and red blood cell sodium transport: role of prednisone treatment.

This study assesses the role of prednisone and endogenous digoxin-like immunoreactivity (EDLI) in the increased Na+ pump activity in renal allograft patients. Red blood cell (RBC) Na+ transport activities and plasma concentrations of EDLI were measured in ten controls and ten renal allograft recipients (5 hypertensive) while undergoing treatment with cyclosporin, prednisone, and azathioprine, and also after prednisone withdrawal. As compared to controls, prednisone-treated patients showed an increased Na+ pump activity (0.323/h vs 0.571, P less than 0.05) and decreased RBC Na+ concentration (6.69 mM vs 4.99, P less than 0.05). They also showed a decrease in the activity of cotransport, countertransport, and passive Na+ efflux (0.02/h vs 0.005, P less than 0.05; 207 mumol/l vs 35, P less than 0.05; 0.02/h vs 0.005 respectively, P less than 0.05). After prednisone withdrawal, normotensive and hypertensive patients showed RBC Na+ transport system activities and RBC Na+ concentration similar to those of controls. EDLI was not detected in controls or in patients. We conclude that prednisone treatment increased the Na+ pump activity, and decreased the RBC Na+ concentration. Moreover, it induced a decrease in the activity of secondary RBC Na+ transport systems. This study provides no evidence for a modulatory role of EDLI in the RBC Na+ pump activity. Neither parameters can be presumed to be a marker of hypertension in these patients.

Adult↗
PubMed1991

Pathogenesis of benign prostatic hyperplasia.

The pathogenesis of benign prostatic hyperplasia (BPH) remains largely unresolved. Three major theories have evolved over the years, each emphasizing a possible causative mechanism. The first theory, the dihydrotestosterone hypothesis, is based on the failure of BPH to develop in men castrated prior to puberty. The second, the embryonic reawakening theory, assumes a reawakening of the embryonic induction potential of prostatic stroma. The third, or stem cell theory, postulates the development of BPH through an increase in the number of stem cells or through an abnormal increase in clonal expansion of amplifying or transit cells. These mechanisms may act in concert.

Androgens↗
PubMed1990

Synchronized electrical stimulation of the sympathetic and parasympathetic innervation of the bladder: facilitation of the initiation of micturition in the dog.

To improve the quality of bladder contractions induced by parasympathetic stimulation and to facilitate the initiation of voiding, we investigated the effect of sympathetic stimulation on the parasympathetic innervation of the bladder in 12 dogs. For the sympathetic system, the lumbar sympathetic trunks were electrically stimulated; for the parasympathetic system, either the pelvic nerve or the ventral root of S2 was stimulated. With voltages at or just above the threshold for achieving a measurable effect on bladder pressure, stimulation of the sympathetic system or the pelvic nerve alone did not lead to voiding, and sacral root stimulation alone elicited voiding in only 7.4 per cent of stimulations. However, when the same stimulus parameters were used for synchronous stimulation, the voiding process was facilitated when sympathetic stimulation was begun five to 10 seconds before parasympathetic stimulation. When the pelvic nerve was used, voiding resulted in 77.7 per cent of stimulations and the bladder was emptied by a mean of 68.7 per cent; with S2 ventral root stimulation, voiding resulted in 83.3 per cent of stimulations and the bladder was emptied by 59.7 per cent. The facilitory effect of sympathetic stimulation was not abolished when the sympathetic trunks were cut centrally to the point of stimulation, but was absent when the hypogastric nerves were transected. We feel that sympathetic stimulation modulates the parasympathetic innervation of the bladder.

Animals↗