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J Silverstein

Publications and source records attributed to J Silverstein.

At least 19 recordsLinked to original sources
PubMed2001

Cerulenin mimics effects of leptin on metabolic rate, food intake, and body weight independent of the melanocortin system, but unlike leptin, cerulenin fails to block neuroendocrine effects of fasting.

Cerulenin and a related compound, C75, have recently been reported to reduce food intake and body weight independent of leptin through a mechanism hypothesized, like leptin, to involve hypothalamic nutrition-sensitive neurons. To assess whether these inhibitors act through mechanisms similar to mechanisms engaged by leptin, ob/ob and Ay (agouti) mice, as well as fed and fasted wild-type mice, were treated with cerulenin. Like leptin, cerulenin reduced body weight and food intake and increased metabolic rate in ob/ob mice, and cerulenin produced the same effects in wild-type mice, whereas lithium chloride, at doses that produce conditioned taste aversion, reduced metabolic rate. However, in contrast to leptin, cerulenin did not prevent effects of fasting on plasma corticosterone or hypothalamic levels of neuropeptide Y, agouti-related peptide, pro-opiomelanocortin, or cocaine- and amphetamine-related peptide mRNA. Also, in contrast to leptin, cerulenin was highly effective to reduce body weight in Ay mice, in which obesity is caused by blockade of the melanocortin receptor. These data demonstrate that cerulenin produces metabolic effects similar to effects of leptin, but through mechanisms that are independent of, or down-stream from, both leptin and melanocortin receptors.

Animals↗
PubMed2000

Physicians' experiences with patients who transgress boundaries.

BACKGROUND: Boundary violations have been discussed in the literature, but most studies report on physician transgressions of boundaries or sexual transgressions by patients. We studied the incidence of all types of boundary transgressions by patients and physicians' responses to these transgressions. METHODS: We surveyed 1,000 members of the Society of General Internal Medicine (SGIM) for the number of patient transgressions of boundaries which had occurred in the previous year. Categories were created by the investigators based on the literature. Physicians picked the most important transgression, and then were asked about their response to the transgression and its effect on the patient-physician relationship. Attitudinal questions addressed the likelihood of discharging patients who transgressed boundaries. The impact of demographic variables on the incidence of transgressions was analyzed using analysis of variance. RESULTS: Three hundred thirty (37.5%) randomly selected SGIM members responded to the survey. Almost three quarters of the respondents had patients who used their first name, while 43% encountered verbal abuse, 39% had patients who asked personal questions, 31% had patients who were overly affectionate, and 27% encountered patients who attempted to socialize. All other transgressions, including physical abuse and attempts at sexual contact, were uncommon. Only gender affected the incidence of transgressions; female physicians encountered more personal questions (P = .001), inappropriate affection (P < .005), and sexually explicit language (P < .05) than male physicians and responded more negatively to boundary transgressions. Respondents dealt with transgressions by discussion with the patient or colleagues or by ignoring the incident, but such transgressions generally had a negative impact on the relationship. Most physicians would discharge patients who engaged in physical abuse or attempts at sexual contact, but were more tolerant of verbal abuse and overly affectionate patients. CONCLUSIONS: Boundary transgressions by patients is common, but usually involves more minor infractions. Female physicians are more likely to encounter certain types of transgressions. The incidence and outcomes of such transgressions are important in assisting physicians to deal effectively with this issue.

Adult↗
PubMed2000

Development and application of small-subunit rRNA probes for assessment of selected Thiobacillus species and members of the genus Acidiphilium.

Culture-dependent studies have implicated sulfur-oxidizing bacteria as the causative agents of acid mine drainage and concrete corrosion in sewers. Thiobacillus species are considered the major representatives of the acid-producing bacteria in these environments. Small-subunit rRNA genes from all of the Thiobacillus and Acidiphilium species catalogued by the Ribosomal Database Project were identified and used to design oligonucleotide DNA probes. Two oligonucleotide probes were synthesized to complement variable regions of 16S rRNA in the following acidophilic bacteria: Thiobacillus ferrooxidans and T. thiooxidans (probe Thio820) and members of the genus Acidiphilium (probe Acdp821). Using (32)P radiolabels, probe specificity was characterized by hybridization dissociation temperature (T(d)) with membrane-immobilized RNA extracted from a suite of 21 strains representing three groups of bacteria. Fluorochrome-conjugated probes were evaluated for use with fluorescent in situ hybridization (FISH) at the experimentally determined T(d)s. FISH was used to identify and enumerate bacteria in laboratory reactors and environmental samples. Probing of laboratory reactors inoculated with a mixed culture of acidophilic bacteria validated the ability of the oligonucleotide probes to track specific cell numbers with time. Additionally, probing of sediments from an active acid mine drainage site in Colorado demonstrated the ability to identify numbers of active bacteria in natural environments that contain high concentrations of metals, associated precipitates, and other mineral debris.

Acetobacteraceae↗
PubMed2000

Blood glucose monitoring skills in children with Type I diabetes.

While blood glucose monitoring has become increasingly important in diabetes care, studies have yet to address the accuracy of youngsters' performance of blood glucose testing with current reflectance meters. The present study examined testing skills and predictors of accurate testing skills in a sample of 7-14-year-old children attending a summer camp for youth with diabetes (n=266). A 15-item behavior observational skill test was used to assess accuracy of blood glucose monitoring skills with reflectance meters. Accurate performance of individual skills ranged between 14.6% and 99.6% for the sample. However, a number of children made critical errors (errors that were likely to lead to inaccurate blood glucose testing results). When duration of diabetes and metabolic control were controlled, female gender, older age, experience with a particular meter, and absence of hypoglycemia at the time of testing were positively associated with accurate skill performance. Findings suggest that younger children, children using a new blood glucose testing meter, and children suspected of having hypoglycemia should be supervised and observed when testing. Although all young children should be supervised when blood glucose testing, boys may need closer supervision until an older age than girls. This study underscores the need for health care providers to periodically observe children's blood glucose monitoring techniques to assure accurate testing habits and to correct problematic testing behaviors.

Adolescent↗
PubMed2000

Adrenalectomy reverses obese phenotype and restores hypothalamic melanocortin tone in leptin-deficient ob/ob mice.

In genetically obese leptin-deficient ob/ob mice, adrenalectomy reverses or attenuates the obese phenotype. Relative to lean controls, ob/ob mice also exhibit decreased hypothalamic proopiomelanocortin (POMC) mRNA and increased hypothalamic agouti-related peptide (AGRP) mRNA and neuropeptide Y (NPY) mRNA. It has been hypothesized that this profile of hypothalamic gene expression contributes to the obese phenotype caused by leptin deficiency. To assess if reversal of obese phenotype by adrenalectomy entails normalization of hypothalamic gene expression, male wild-type and ob/ob mice were adrenalectomized (with saline supplementation) or sham adrenalectomized at 2 months of age. Mice were sacrificed 2 weeks after adrenalectomy, during which time food intake and body weight were monitored daily. After sacrifice, hypothalamic gene expression was assessed by Northern blot analysis as well as in situ hybridization. In wild-type mice, adrenalectomy significantly decreased AGRP mRNA but did not significantly influence POMC or NPY mRNA. In ob/ob mice, adrenalectomy reduced the levels of plasma glucose, serum insulin and corticosterone, and food intake toward or below wild-type levels, and it restored hypothalamic POMC and AGRP mRNA but not NPY mRNA to wild-type levels. These studies suggest that adrenalectomy reverses or attenuates the obese phenotype in ob/ob mice, in part by restoring hypothalamic melanocortin tone toward wild-type levels. These studies also demonstrate that factors other than leptin may play a major role in regulating hypothalamic melanocortin function.

Adrenalectomy↗
PubMed1999

Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2beta predict immune-mediated (Type 1) diabetes in relatives.

We report here our prospective study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2beta autoantibodies (ICA, IAA, GAD65A, IA-2A and IA-2betaA), on the first available serum samples. The latter three autoantibodies were however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year risk=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year risk=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2beta A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant beta-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing.

Adolescent↗
PubMed1999

Fasting regulates hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocortin in diabetic mice independent of changes in leptin or insulin.

Fasting increases hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AGRP) messenger RNA (mRNA) and reduces hypothalamic POMC mRNA, and is also characterized by a reduction in plasma leptin, insulin, and glucose, each of which has been implicated in the regulation of hypothalamic gene expression. To further evaluate the roles of leptin, insulin, and glucose in mediating effects of fasting, we examined hypothalamic gene expression in nondiabetic and streptozotocin (STZ)-induced diabetic mice both under ad lib fed and 48-h fasted conditions. In both diabetic and nondiabetic mice, fasting stimulated hypothalamic NPY and AGRP mRNA and inhibited hypothalamic POMC mRNA and adipose leptin mRNA. However, in diabetic mice fasting had no effect on plasma leptin and insulin while decreasing plasma glucose, whereas in nondiabetic mice fasting decreased plasma leptin, insulin, and glucose. Furthermore, in nondiabetic fasted mice, NPY and AGRP mRNA were higher, and POMC mRNA and plasma glucose were lower, than in diabetic ad lib fed mice, even though insulin and leptin were similar in these two groups. These data are consistent with the hypothesis that although leptin and insulin regulate hypothalamic gene expression, glucose or other factors may have independent effects on hypothalamic and adipose gene expression under conditions of low insulin and leptin.

Adipose Tissue↗
PubMed1999

Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia.

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization of cartilage and bone matrix. We investigated two independently generated TNSALP gene knock-out mouse strains as potential models for hypophosphatasia. Homozygous mice (-/-) had < 1% of wild-type plasma TNSALP activity; heterozygotes had the predicted mean of approximately 50%. Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate are putative natural substrates for TNSALP and all were increased endogenously in the knock-out mice. Skeletal disease first appeared radiographically at approximately 10 days of age and featured worsening rachitic changes, osteopenia, and fracture. Histologic studies revealed developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones. Progressive osteoidosis from defective skeletal matrix mineralization was noted but not associated with features of secondary hyperparathyroidism. Plasma and urine calcium and phosphate levels were unremarkable. Our findings demonstrate that TNSALP knock-out mice are a good model for the infantile form of hypophosphatasia and provide compelling evidence for an important role for TNSALP in postnatal development and mineralization of the murine skeleton.

Age Factors↗
PubMed1998

Web-based segmentation and display of three-dimensional radiologic image data.

In many clinical circumstances, viewing sequential radiological image data as three-dimensional models is proving beneficial. However, designing customized computer-generated radiological models is beyond the scope of most physicians, due to specialized hardware and software requirements. We have created a simple method for Internet users to remotely construct and locally display three-dimensional radiological models using only a standard web browser. Rapid model construction is achieved by distributing the hardware intensive steps to a remote server. Once created, the model is automatically displayed on the requesting browser and is accessible to multiple geographically distributed users. Implementation of our server software on large scale systems could be of great service to the worldwide medical community.

Algorithms↗
PubMed1997

Effect of microgravity on Escherichia coli and MS-2 bacteriophage disinfection by iodinated resins.

Experiments on chemical disinfection by iodinated resins were conducted on STS 50 (USML-1), which flew a 13 day mission during 1992. Fluid processing apparatus containing microorganisms and iodinated resins was assembled in either Manhattan, Kansas, or Boulder, Colorado, and loaded on-board the Space Shuttle for the mission. Pentaiodide resin was more effective than the triiodide resin against Escherichia coli. Both resins were more effective bactericides at unit gravity than microgravity because of cosedimentation of bacteria and iodinated resin beads. In bacteriophage experiments, the triiodide resin reduced the viable titer of MS-2 by nine logs. The few viable phage surviving chemical disinfection were associated with precipitant formation in the fluid processing apparatus.

Anion Exchange Resins↗
PubMed1997

Incidence of percutaneous injuries at a dental school: a 4-year retrospective study.

BACKGROUND: Infection control training for predoctoral dental students, dental hygiene students, and dental assistant students has assumed an important role in the educational process at our institution. As part of an ongoing review of the curriculum at our school, we conducted a retrospective analysis of reported percutaneous injuries during the years 1991 through 1994 to determine whether the increase in infection control training introduced at the school in 1990 has had an effect on our rate of percutaneous injuries. METHODS: The population examined in this retrospective study consisted of predoctoral and postdoctoral dental students, dental hygiene students, dental assistant students, and staff. The data for this retrospective study were obtained from annual reports of occupational exposures incurred by students and staff. These annual reports were generated by compiling and summarizing all percutaneous injury incident reports that were prepared for that year. RESULTS: Our results indicate, that except for an increase in 1992, the total number and incidence of reported percutaneous injuries decreased from 1991 to 1994. Statistically significant decreases were seen in the total number of reported percutaneous injuries for all students, staff, and all groups combined. On the basis of data available for 1993 and 1994, the incidence of reported percutaneous injuries per 1000 procedures was fairly constant over these 2 years. Distribution of percutaneous injuries by source varied during the 4-year period. CONCLUSIONS: As part of the outcomes assessment program at our institution, we conducted a retrospective study of reported percutaneous injuries from 1991 to 1994. This study demonstrated that, although the total number of injuries decreased significantly, the rates within certain individual groups remained unchanged. On the basis of this observation, increased emphasis in the prevention of percutaneous injuries through additional training is indicated for these groups.

Curriculum↗
PubMed1996

Although DR3-DQB1*0201 may be associated with multiple component diseases of the autoimmune polyglandular syndromes, the human leukocyte antigen DR4-DQB1*0302 haplotype is implicated only in beta-cell autoimmunity.

Human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed using a PCR-based sequence-specific priming technique in 16 patients with autoimmune polyglandular syndrome type I (APS-I), 31 patients with APS-II, and 110 patients with component diseases of APS-II, including 9 patients with isolated Addison's disease, 43 patients with Hashimoto's thyroiditis, 22 patients with Graves' disease, and 36 patients with vitiligo. No significant associations was observed between HLA and APS-I patients in our data set, nor was sharing of HLA haplotypes by sibling pairs affected by APS I significantly different from the random expectation. Thus, HLA-DRB1 and -DQB1 genes are probably not involved in APS-I. To delineate the associations between HLA-DRB1, DQB1, and APS-II, we analyzed APS-II patients with or without beta-cell autoimmunity [i.e. insulin-dependent diabetes (IDD) and/or islet cell or glutamic acid decarboxylase autoantibodies]. Our results suggest that the association between DR4-DQB1*0302 and APS-II was entirely due to the presence of pancreatic beta-cell autoimmunity, since this haplotype was otherwise not significantly associated with APS-II or with any other of its component diseases. In contrast, the DR3-DQB1*0201 haplotype was associated not only with IDD, but also with APS-II in the absence of pancreatic beta-cell autoimmunity, as were several its component diseases, including isolated Addison's disease, Graves' disease, and Hashimoto's thyroiditis. Interestingly, the frequency of DQB1*0602, a dominantly protective allele against IDD, was not significantly decreased in the APS-II patients with IDD or beta-cell autoimmunity, albeit the patient numbers were small. This phenomenon may suggest that the development of autoimmunity to nonpancreatic endocrine glands may predispose autoimmunity to the pancreatic beta-cells and involve genes other than those of the MHC.

Adolescent↗
PubMed1995

Association of anophthalmia and esophageal atresia.

We report on a boy and a girl with bilateral anophthalmia and proximal esophageal atresia. In addition to vestigial optic nerves and chiasma, MRI studies showed other central nervous system abnormalities; one had ectopic tissue in the hypothalamic region, and the other hand generalized ventriculomegaly associated with atrophy. Two other cases, both males, have been reported with anophthalmia and esophageal atresia as their only malformations. These 4 cases are reviewed in light of recent advances in the understanding of ocular embryogenesis and of the midbrain as a development field. Concurrence of these defects appears to be non-random.

Anophthalmos↗
PubMed1995

A 15-year review of esophagectomy for carcinoma of the esophagus and cardia.

OBJECTIVE: To evaluate the effect of surgical approach and adjuvant therapy on patients with carcinoma of the esophagus and/or cardia. DESIGN: Retrospective analysis of 157 consecutive patients who underwent esophagectomy. SETTING: A private university medical center and its affiliated community hospital. PATIENTS: One hundred twenty men and 37 women (mean age, 61.7 years) with carcinoma of the esophagus and/or cardia that was surgically treated between 1978 and 1993. INTERVENTIONS: Three approaches were used for resection: Transhiatal esophagectomy (THE) (n = 67), transthoracic esophagectomy (TTE) (n = 71), and abdominal-only esophagectomy (AOE) (n = 19). Sixty-five patients received adjuvant radiotherapy and chemotherapy. MAIN OUTCOME MEASURES: Surgical mortality, morbidity, and survival and the effect of adjuvant therapy. RESULTS: The overall surgical mortality rate was 7.6%: 12.7% with the TTE, 4.5% with the THE, and 0% with the AOE approach. A significantly increased incidence of adult respiratory distress syndrome (P < .001) and empyema (P < .001) was seen with the TTE approach. The average intraoperative blood loss (P = .08) and the median intensive care unit stay (P = .26) and hospital stay (P = .40) were decreased with the THE and AOE approaches when compared with the TTE approach without significance. The overall median survival time was 17 months, with a 5-year survival rate of 21%. There was no significant difference in survival by pathologic stage between approaches. The addition of adjuvant therapy did not affect the overall median survival time or the 5-year survival rate. Node-positive patients did benefit from adjuvant radiotherapy and chemotherapy, with increased median survival times from 7 to 15 months and a 5-year survival rate from 0% to 15% (P = .01). CONCLUSIONS: The THE and AOE approaches have fewer early complications than does TTE. Both THE and TTE have equal long-term survival rates. Adjuvant therapy provides increased survival to node-positive patients with carcinoma of the esophagus and/or cardia.

Adult↗
PubMed1994

Islet cell antibodies predict insulin-dependent diabetes in United States school age children as powerfully as in unaffected relatives.

Islet cell antibodies (ICA) in the sera of nondiabetic relatives of patients with insulin-dependent diabetes (IDD) are predictive of the disease, a finding that permits the design of intervention strategies to prevent it. However, 85% or more of patients with new onset IDD have no affected relative. We therefore screened 9,696 schoolchildren between the ages of 5 and 18 yr (mean age 10.7 yr) in Pasco County, Florida for ICA in three surveys during 1984/5, 1987/8, and 1990/1 and have followed them prospectively. Approximately 4,000 of these children have been followed for nearly 8 yr. ICA titers > or = 10 Juvenile Diabetes Foundation units on replicate tests were detected in 57 of the children (0.59%). 10 children have developed diabetes so far, and all had ICA detected beforehand. The likelihood of developing IDD among the ICA-positive children was compared with 2,959 age-matched nondiabetic first degree relatives of IDD probands who were screened for ICA by our laboratory during the same time period and also followed prospectively. Of 103 (3.5%) ICA-positive relatives, 31 have developed IDD. Life table analysis reveals no statistically significant differences in the probability of developing IDD between the ICA-positive schoolchildren and ICA-positive first degree relatives (P = 0.3). The estimated risk of developing IDD by 7 yr in the ICA-positive schoolchildren was 45% (95% confidence interval 15-74%) compared with 43% (confidence interval 22-63%) in the relatives. We conclude that ICA appear to be as predictive of IDD in low-risk schoolchildren as they are in high-risk relatives. These data suggest that it is feasible to predict IDD by screening a general population of schoolchildren for ICA and that those found to be positive could be considered, in addition to relatives, for intervention protocols to prevent the disease.

Adolescent↗
PubMed1993

A comparison of growth rates of acoustic neuromas: nonsurgical patients vs. subtotal resection.

A conservative approach to the management of acoustic neuromas in elderly patients has been used since 1971. Elderly patients without symptoms of brain stem compression are initially treated by observation and yearly radiographic imaging. A translabyrinthine radical-subtotal resection is performed if brain stem compression is present or if tumor is growing rapidly. Twenty-three patients, ages 65 to 86 years, had initial nonsurgical management of their tumors. Growth rates could be determined for 16 patients. Thirteen patients not requiring surgery had an average tumor growth rate of 0.6 mm/yr. Three patients with an average growth rate of 6.8 mm/yr eventually required surgery. No patient whose tumor was < 15 mm at initial evaluation has experienced brain stem symptoms or demonstrated rapid tumor growth. Twenty-four patients ages 65 to 86 years underwent planned subtotal tumor excision. Eighteen patients followed postoperatively for more than 1 year demonstrated an average rate of regrowth of tumor of 0.7 mm/yr.

Aged↗