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Biomedical subjects

J Hamilton

Publications and source records attributed to J Hamilton.

At least 73 records · Page 4Linked to original sources

BDNF and NT4/5 promote survival and neurite outgrowth of pontocerebellar mossy fiber neurons.

The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), and NT4/5 are all found in the developing cerebellum. Granule cells, the major target neurons of mossy fibers, express BDNF during mossy fiber synaptogenesis. To determine whether neurotrophins contribute to the development of cerebellar afferent axons, we characterized the effects of neurotrophins on the growth of mossy fiber neurons from mice and rats in vitro. For a mossy fiber source, we used the basilar pontine nuclei (BPN), the major source of cerebellar mossy fibers in mammals. BDNF and NT4/5 increased BPN neuron survival, neurite outgrowth, growth cone size, and elongation rate, while neither NT3 nor NGF increased survival or outgrowth. In addition, BDNF and NT4/5 reduced the size of neurite bundles. Consistent with these effects, in situ hybridization on cultured basilar pontine neurons revealed the presence of mRNA encoding the TrkB receptor which binds both BDNF and NT4/5 with high affinity. We detected little or no message encoding the TrkC receptor which preferentially binds NT3. BDNF and NT4/5 also increased TrkB mRNA levels in BPN neurons. In addition to previously established functions as an autocrine/paracrine trophic factor for granule cells, the present results indicate that cerebellar BDNF may also act as a target-derived trophic factor for basilar pontine mossy fibers.

Afferent Pathways↗

Microdentistry: the new standard of care? Part 3. Is air abrasion safe?

Practicing microdentistry is not for the weak-spined dentist. It takes guts to face the possible challenges and resistance described in this report. Those who truly believe microdentistry will become the standard of care remain its best advocates. They are better equipped to manage any resistance encountered from peers, boards, insurance companies and patients. But to avoid legal and board troubles, always obtain informed consent from patients of indications, costs, risks of providing and not providing treatment, and alternative treatments and their costs. The debate over whether microdentistry will become the standard of care, replacing traditional restorative dentistry, continues. Most of those who hold onto the tried and true methods of traditional diagnosis and treatment are probably trying to err on the side of caution. Most of those who embrace microdentistry are not unscrupulous opportunists but are probably trying to provide the care that represents the highest quality in their opinion. Best case scenario, traditionalists and microdentists can coexist and dialogue peacefully within their communities and through their dental organizations to navigate the future of optimal treatment. Worst case scenario, attorneys and insurance companies will profit more than ever while the division in dentistry over microdentistry widens. The shakeout will prove interesting.

Air Abrasion, Dental↗

The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein.

Previously, we showed that the addition of human erythrocyte glycosphingolipids (GSLs) to nonhuman CD4(+) or GSL-depleted human CD4(+) cells rendered those cells susceptible to HIV-1 envelope glycoprotein-mediated cell fusion. Individual components in the GSL mixture were isolated by fractionation on a silica-gel column and incorporated into the membranes of CD4(+) cells. GSL-supplemented target cells were then examined for their ability to fuse with TF228 cells expressing HIV-1LAI envelope glycoprotein. We found that one GSL fraction, fraction 3, exhibited the highest recovery of fusion after incorporation into CD4(+) nonhuman and GSL-depleted HeLa-CD4 cells and that fraction 3 contained a single GSL fraction. Fraction 3 was characterized by MS, NMR spectroscopy, enzymatic analysis, and immunostaining with an antiglobotriaosylceramide (Gb3) antibody and was found to be Gal(alpha1-->4)Gal(beta1-->4)Glc-Cer (Gb3). The addition of fraction 3 or Gb3 to GSL-depleted HeLa-CD4 cells recovered fusion, but the addition of galactosylceramide, glucosylceramide, the monosialoganglioside, GM3, lactosylceramide, globoside, the disialoganglioside, GD3, or alpha-galactosidase A-digested fraction 3 had no effect. Our findings show that the neutral GSL, Gb3, is required for CD4/CXCR4-dependent HIV-1 fusion.

Acetylation↗

Familial growth hormone deficiency associated with MRI abnormalities.

Idiopathic growth hormone deficiency is, in most cases, a sporadic condition. In a number of these patients magnetic resonance imaging (MRI) demonstrates a small anterior pituitary, small or absent pituitary stalk, and ectopically located posterior pituitary. These findings have been attributed to a developmental defect, trauma, or ischemia at birth. We report on a case of familial isolated growth hormone deficiency with mother and son demonstrating the MRI findings described above. The son also had a Chiari type I malformation and medial deviation of the carotid arteries secondary to a narrow skull base. Testing failed to identify a mutation in either the Pit-1 gene or GH gene cluster. This case appears to be an autosomal dominant defect in early development, lending support to the hypothesis that dysgenesis, rather than birth trauma, may cause a small anterior pituitary and ectopic posterior pituitary.

Child↗

Isoenzymes of pyruvate dehydrogenase phosphatase. DNA-derived amino acid sequences, expression, and regulation.

Pyruvate dehydrogenase phosphatase (PDP) is one of the few mammalian phosphatases residing within the mitochondrial matrix space. It is responsible for dephosphorylation and reactivation of the pyruvate dehydrogenase complex (PDC) and, by this means, is intimately involved in the regulation of utilization of carbohydrate fuels in mammals. PDP is a dimeric enzyme consisting of catalytic and regulatory subunits. The catalytic subunit of PDP is a Mg2+-dependent enzyme homologous to the cytosolic phosphatases of the 2C family. In the present study, we isolated two cDNAs encoding for mitochondrial phosphatases. The first cDNA is highly homologous to the previously identified cDNA encoding for the catalytic subunit of PDP (PDP1). The second cDNA encodes a previously unknown catalytic subunit of PDP (PDP2). The new phosphatase, expressed as the recombinant protein in Escherichia coli, shows strict substrate specificity toward PDC and does not use phosphorylated branched chain alpha-ketoacid dehydrogenase as substrate. Like PDP1, PDP2 is a Mg2+-dependent enzyme, but its sensitivity to Mg2+ ions is almost 10-fold lower than that of PDP1. In contrast to PDP1, PDP2 is not regulated by Ca2+ ions. Instead, it is sensitive to the biological polyamine spermine, which, in turn, has no effect on the enzymatic activity of PDP1. Western blot analysis of PDP extracted from mitochondria isolated from liver and skeletal muscle revealed that PDP1 is predominantly expressed in mitochondria from skeletal muscle, whereas PDP2 is much more abundant in the liver rather than muscle mitochondria. Both isoenzymes are expressed in mitochondria from 3T3-L1 adipocytes, but the level of expression of PDP2 is considerably higher. These observations are consistent with previous findings on the enzymatic parameters of PDP in adipose tissue. Thus, our results provide the first evidence that there are at least two isoenzymes of PDP in mammals that are different with respect to tissue distribution and kinetic parameters and, therefore, are likely to be different functionally.

3T3 Cells↗

Quebec's ice storm '98: "all cards wild, all rules broken" in Quebec's shell-shocked hospitals.

The remarkable ice storm that brought life to a standstill in most of Eastern Ontario and Quebec in January had a huge impact on medical services. Hospitals that lost power found themselves serving as shelters not only for patients but also for staff members and nearby residents. Doctors' offices were forced to close and a large number of operations were cancelled. The 2 articles that follow detail the huge impact the "ice storm of the century" had on health care.

Disaster Planning↗

Foot TcPO2 response to lumbar sympathectomy in patients with focal ischemic necrosis.

We prospectively evaluated all patients with superficial foot necrosis of 1-3 cm and transcutaneous oxygen tension (TcPO2) values of <30 mmHg who received a sympathectomy as the primary treatment of their vascular occlusive disease. Preoperatively, and every 2-3 days in the postoperative period, measurement of TcPO2 of the forefoot was performed. Clinical success was defined as healing of the necrosis or healing of a toe amputation and avoidance of a major below-knee/above-knee amputation for 1 year. Ten patients were available for long-term evaluation. During the first 4-5 days, all patients increased their foot TcPO2 and the mean increase (23 mmHg) was significant (p = 0.04). Clinical improvement was marked by an average increase of 29 mmHg by postoperative day 10. In contrast, patients with clinical failure had only an average increase of 5 mmHg in TcPO2 by the same postoperative interval. Preoperative increase in TcPO2 by at least 20 mmHg in response to dependency predicted a favorable response to sympathectomy. In addition, sustained postoperative increases in tissue oxygen levels by postoperative day 10 also favored wound healing.

Adult↗

The development of a culture-based substance abuse treatment program in the Kuskokwim Delta, Alaska.

This paper describes the development of a substance abuse program for three remote Western Alaska villages with strong traditional cultures. Although the impact of substance abuse is known to be substantial in the Kuskokwim Delta, intervention and treatment services have not been universally accepted by the traditional Yup'ik and Cup'ik communities. The reason may be that services do not accommodate the cultural values of the people they are intended to serve. The Chemical Misuse Treatment and Recovery Services (CMTRS) program was designed to address this issue. The paper will describe the demographics and cultural characteristics of the people of the three villages participating in the program, describe how traditional Yup'ik and Cup'ik values were incorporated into the program, and discuss some of the early data on the acceptance and use of the program services.

Alaska↗

Methodological issues in evaluating a culture-based substance abuse treatment program in the Kuskokwim Delta, Alaska.

This paper presents a rationale for using videotape records in evaluation research. Although videotaping is commonly used in ethnographic and sociometric analysis, the evaluation literature does not show the application of these recording techniques to program evaluations. The authors outline a model for exploring the effectiveness of video in qualitative program evaluation.

Alaska↗

MR imaging in idiopathic growth hormone deficiency.

BACKGROUND AND PURPOSE: MR imaging findings of one or more of the following has been suggested to be a sensitive and specific indicator of hypopituitarism: small anterior pituitary gland, attenuated or absent pituitary stalk, and ectopic posterior pituitary. We hypothesized that these MR findings would be common in our group of patients with idiopathic isolated growth hormone deficiency (GHD) or multiple pituitary hormone deficiencies (MPHD) and would be a good indicator of the severity of the hypopituitarism. METHODS: MR images were obtained for 35 patients with idiopathic GHD (20 with isolated GHD and 15 with MPHD; age range, 2 to 17 years) and analyzed to define one or more of the following triad of abnormalities: 1) small/absent anterior pituitary, 2) truncated/absent pituitary stalk, and 3) ectopic posterior pituitary, as well as for any other associated anomalies. The findings were correlated with the clinical and biochemical presentation. RESULTS: Pituitary abnormalities were common in both groups (80% with isolated GHD, 93% with MPHD). We found a high frequency of midline CNS malformations, including optic nerve hypoplasia (9%), Chiari type I malformations (20%), and medial deviation of the carotid arteries (37%). Breech delivery, neonatal hypoglycemia, jaundice, micropenis, or single central incisor occurred equally with both isolated GHD and MPHD. In patients whose peak growth hormone level was less than 3 microg/L (n = 19), 90% had the MR triad, compared with 390% of those with growth hormone levels 3 microg/L or greater or less than 8 microg/L (n = 13) (P <.01). Almost all (92%) of those with ectopic posterior pituitary had anterior pituitary heights less than -2 SD for age. CONCLUSION: MR abnormalities were common in children with both isolated GHD and MPHD and were closely associated with peak growth hormone levels less than 3 microg/L. The presence of other CNS and clinical findings (eg, single central incisor and micropenis) supports the theory of an embryologic defect as the cause of the pituitary abnormalities.

Adolescent↗