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Biomedical subjects

Jennifer Jacobs

Publications and source records attributed to Jennifer Jacobs.

7 recordsLinked to original sources

A genetic screen identifies genes essential for development of myelinated axons in zebrafish.

The myelin sheath insulates axons in the vertebrate nervous system, allowing rapid propagation of action potentials via saltatory conduction. Specialized glial cells, termed Schwann cells in the PNS and oligodendrocytes in the CNS, wrap axons to form myelin, a compacted, multilayered sheath comprising specific proteins and lipids. Disruption of myelinated axons causes human diseases, including multiple sclerosis and Charcot-Marie-Tooth peripheral neuropathies. Despite the progress in identifying human disease genes and other mutations disrupting glial development and myelination, many important unanswered questions remain about the mechanisms that coordinate the development of myelinated axons. To address these questions, we began a genetic dissection of myelination in zebrafish. Here we report a genetic screen that identified 13 mutations, which define 10 genes, disrupting the development of myelinated axons. We present the initial characterization of seven of these mutations, defining six different genes, along with additional characterization of mutations that we have described previously. The different mutations affect the PNS, the CNS, or both, and phenotypic analyses indicate that the genes affect a wide range of steps in glial development, from fate specification through terminal differentiation. The analysis of these mutations will advance our understanding of myelination, and the mutants will serve as models of human diseases of myelin.

Animals↗

Homeopathic combination remedy in the treatment of acute childhood diarrhea in Honduras.

BACKGROUND: Despite the widespread availability of oral rehydration therapy, diarrheal illness remains a major cause of morbidity and mortality around the world. Previous studies have shown individualized homeopathic therapy to be effective in treating childhood diarrhea, but this approach requires specialized training. OBJECTIVE: A homeopathic combination medicine, if effective, could be used by health personnel on a widespread basis. METHODS: A double-blind randomized controlled trial was conducted in Honduras to evaluate the effectiveness of a homeopathic combination therapy to treat acute diarrhea in children. A total of 292 children with acute diarrhea was recruited; 145 were randomized to the experimental group and 147 to the placebo group. Tablets containing a combined preparation of the five most common single homeopathic remedies used to treat diarrhea or placebo were administered by a parent after each unformed stool. Children were followed up daily for 7 days or until symptoms resolved, whichever occurred first. Time until resolution of symptoms, daily rate of unformed stools, and total number of unformed stools were compared between the two groups. RESULTS: There was no significant difference in the likelihood of resolution of diarrheal symptoms between the treatment and placebo groups (hazard ratio = 1.02, 95% confidence interval: 0.79-1.32), with a median time until resolution of 3 days for both groups. Children in the treatment group had an average of 2.6 unformed stools per day compared to 2.8 among those in the placebo group; this difference was not significant (p = 0.43). The median number of unformed stools was 7 among children in the treatment group and 8 among those in the placebo group (p = 0.41). DISCUSSION: The homeopathic combination therapy tested in this study did not significantly reduce the duration or severity of acute diarrhea in Honduran children. Further study is needed to develop affordable and effective methods of using homeopathy to reduce the global burden of childhood diarrhea.

Acute Disease↗

An unusual abdominal tumor--leiomyosarcoma of the mesentery: a case report.

We report the case of an 82-year-old woman who presented with an ill-defined mass and tenderness in the right lower quadrant of the abdomen. On computerized tomography scan, she had an irregular large bosselated mass of the mesentery located medial to the cecum and associated with multiple loops of small intestine. Preoperative differential diagnoses included leiomyosarcoma, lymphoma and gastrointestinal stromal tumor. The mesenteric mass was resected and identified as a leiomyosarcoma. This patient's tumor is typical of a mesenteric leiomyosarcoma and recurred with hepatic metastases two years after its initial removal. Such tumors usually do not become symptomatic until late in the course of disease, often after distant metastases have occurred. Mesenteric leiomyosarcomas are rare and have a reported incidence of 1: 350,000.

Aged, 80 and over↗

erbb3 and erbb2 are essential for schwann cell migration and myelination in zebrafish.

BACKGROUND: Myelin is critical for efficient axonal conduction in the vertebrate nervous system. Neuregulin (Nrg) ligands and their ErbB receptors are required for the development of Schwann cells, the glial cells that form myelin in the peripheral nervous system. Previous studies have not determined whether Nrg-ErbB signaling is essential in vivo for Schwann cell fate specification, proliferation, survival, migration, or the onset of myelination. RESULTS: In genetic screens for mutants with disruptions in myelinated nerves, we identified mutations in erbb3 and erbb2, which together encode a heteromeric tyrosine kinase receptor for Neuregulin ligands. Phenotypic analysis shows that both genes are essential for development of Schwann cells. BrdU-incorporation studies and time-lapse analysis reveal that Schwann cell proliferation and migration, but not survival, are disrupted in erbb3 mutants. We show that Schwann cells can migrate in the absence of DNA replication. This uncoupling of proliferation and migration indicates that erbb gene function is required independently for these two processes. Pharmacological inhibition of ErbB signaling at different stages reveals a continuing requirement for ErbB function during migration and also provides evidence that ErbB signaling is required after migration for proliferation and the terminal differentiation of myelinating Schwann cells. CONCLUSIONS: These results provide in vivo evidence that Neuregulin-ErbB signaling is essential for directed Schwann cell migration and demonstrate that this pathway is also required for the onset of myelination in postmigratory Schwann cells.

Animals↗

Homeopathy for menopausal symptoms in breast cancer survivors: a preliminary randomized controlled trial.

OBJECTIVES: To carry out a preliminary trial evaluating the effectiveness of two types of homeopathy for the treatment of menopausal symptoms in breast cancer survivors. DESIGN: Randomized, double-blinded, placebo-controlled. SETTINGS/LOCATION: Private medical clinic, Seattle, WA. SUBJECTS: Women with a history of breast cancer who had completed all surgery, chemotherapy, and radiation treatment and who had an average of at least three hot flashes per day for the previous month. INTERVENTIONS: Subjects were randomized to receive either an individualized homeopathic single remedy, a homeopathic combination medicine, or placebo. Patients were seen by homeopathic providers every 2 months for 1 year. OUTCOME MEASURES: Hot flash frequency and severity, Kupperman Menopausal Index (KMI), Short Form 36 (SF-36). RESULTS: There was no significant difference found in the primary outcome measure, the hot flash severity score, although there was a positive trend in the single remedy group during the first 3 months of the study (p = 0.1). A statistically significant improvement in general health score in both homeopathy groups (p < 0.05) on the SF-36 after 1 year was found. Evidence of a homeopathic "drug proving" in the subjects receiving the homeopathic combination medicine who were not taking tamoxifen also was found. CONCLUSIONS: Small sample size precludes definitive answers, but results from this preliminary trial suggest that homeopathy may be of value in the treatment of menopausal symptoms and improving quality of life, especially in those women not on tamoxifen. Larger studies should be carried out that also include healthy women who want to avoid hormone replacement therapy.

Adult↗

Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized-controlled trial.

OBJECTIVES: The aim of this study was to carry out a preliminary trial evaluating the effectiveness of homeopathy in the treatment of attention-deficit/hyperactivity disorder (ADHD). DESIGN: This work was a randomized, double-blind, placebo-controlled trial. SETTINGS/LOCATION: This study was conducted in a private homeopathic clinic in the Seattle metropolitan area. SUBJECTS: Subjects included children 6-12 years of age meeting Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria for ADHD. INTERVENTIONS: Forty-three subjects were randomized to receive a homeopathic consultation and either an individualized homeopathic remedy or placebo. Patients were seen by homeopathic physicians every 6 weeks for 18 weeks. OUTCOME MEASURES: Outcome measures included the Conner's Global Index-Parent, Conner's Global Index- Teacher, Conner's Parent Rating Scale-Brief, Continuous Performance Test, and the Clinical Global Impression Scale. RESULTS: There were no statistically significant differences between homeopathic remedy and placebo groups on the primary or secondary outcome variables. However, there were statistically and clinically significant improvements in both groups on many of the outcome measures. CONCLUSIONS: This pilot study provides no evidence to support a therapeutic effect of individually selected homeopathic remedies in children with ADHD. A therapeutic effect of the homeopathic encounter is suggested and warrants further evaluation. Future studies should be carried out over a longer period of time and should include a control group that does not receive the homeopathic consultation. Comparison to conventional stimulant medication for ADHD also should be considered.

Adolescent↗

Homeopathy for childhood diarrhea: combined results and metaanalysis from three randomized, controlled clinical trials.

BACKGROUND: Previous studies have shown a positive treatment effect of individualized homeopathic treatment for acute childhood diarrhea, but sample sizes were small and results were just at or near the level of statistical significance. Because all three studies followed the same basic study design, the combined data from these three studies were analyzed to obtain greater statistical power. METHODS: Three double blind clinical trials of diarrhea in 242 children ages 6 months to 5 years were analyzed as 1 group. Children were randomized to receive either an individualized homeopathic medicine or placebo to be taken as a single dose after each unformed stool for 5 days. Parents recorded daily stools on diary cards, and health workers made home visits daily to monitor children. The duration of diarrhea was defined as the time until there were less than 3 unformed stools per day for 2 consecutive days. A metaanalysis of the effect-size difference of the three studies was also conducted. RESULTS: Combined analysis shows a duration of diarrhea of 3.3 days in the homeopathy group compared with 4.1 in the placebo group (P = 0.008). The metaanalysis shows a consistent effect-size difference of approximately 0.66 day (P = 0.008). CONCLUSIONS: The results from these studies confirm that individualized homeopathic treatment decreases the duration of acute childhood diarrhea and suggest that larger sample sizes be used in future homeopathic research to ensure adequate statistical power. Homeopathy should be considered for use as an adjunct to oral rehydration for this illness.

Child, Preschool↗