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Biomedical subjects

D Hinton

Publications and source records attributed to D Hinton.

At least 19 recordsLinked to original sources
PubMed2003

Anger-associated panic attacks in Cambodian refugees with PTSD; a multiple baseline examination of clinical data.

Despite the increasing recognition of the importance of anger as a key aspect of post-traumatic stress disorder (PTSD), the presence of anger-induced panic attacks has been understudied in traumatized groups. The present investigation determines the prevalence of anger-associated panic attacks among Cambodian refugees suffering from PTSD. Specific characteristics of these episodes that were examined included frequency, symptoms, and cognitions (in particular, fear of death from bodily dysfunction). In a survey of 100 Khmer patients suffering PTSD, 58% reported anger-associated panic attacks in the last month. These attacks occurred at a mean rate of 6.2 attacks a month and were characterized by extreme arousal and in 81% of these cases, fears of death due to bodily dysfunction during the anger-induced panic. Mechanisms for this high rate of fear of death during anger arousal are discussed with a focus on culture-specific catastrophic cognitions.

Adult↗
PubMed2001

Influence of EEG electrodes on the BOLD fMRI signal.

Measurement of the EEG during fMRI scanning can give rise to image distortions due to magnetic susceptibility, eddy currents or chemical shift artifacts caused by certain types of EEG electrodes, cream, leads, or amplifiers. Two different creams were tested using MRS and T2* measurements, and we found that the one with higher water content was superior. This study introduces an index that quantifies the influence of EEG equipment on the BOLD fMRI signal. This index can also be used more generally to measure the changes in the fMRI signal due to the presence of any type of device inside (or outside) of the field of view (e.g., with fMRI and diffuse optical tomography, infrared imaging, transcranial magnetic stimulation, ultrasound imaging, etc.). Quantitative noise measurements are hampered by the normal variability of functional activation within the same subject and by the different slice profiles obtained when inserting a subject multiple times inside a MR imaging system. Our measurements account for these problems by using a matched filtering of cortical surface maps of functional activations. The results demonstrate that the BOLD signal is not influenced by the presence of EEG electrodes when using a properly constructed MRI compatible recording cap.

Artifacts↗
PubMed2001

A unique panic-disorder presentation among Khmer refugees: the sore-neck syndrome.

This article describes a previously unreported cultural syndrome among Khmer refugees. This common presentation of distress centers on the complaint of a sore neck, the sufferer fearing that wind-and-blood pressure may burst the vessels in this area. During an acute episode, a Khmer endures many--if not all--of the following neck-and-head complaints: headache, blurry vision, a buzzing in the ear, and dizziness. While in the throes of the sore-neck attack, the patient frequently experiences palpitations as well as other symptoms of autonomic arousal, such as diaphoresis, shortness of breath, and trembling. A sufferer of sore-neck episodes often meets panic disorder criteria. In a clinic survey, thirty-five out of eighty-five patients (41%) were found to currently suffer the "sore-neck syndrome" (i.e., to have endured at least one episode in the last month), with almost all of these thirty-five patients (80%) fearing death during the acute event. The sore-neck syndrome represents a common and important way in which distress becomes embodied. The clinician must learn this body language; otherwise, the patient's communication of psychic, interpersonal, and physical pain goes unheard--and grave somatic suffering and disability unattended to--discounted as puzzling somatic complaints and unreasonable obsessionalism about blood pressure.

Adult↗
PubMed1999

Inverted immunodominance and impaired cytolytic function of CD8+ T cells during viral persistence in the central nervous system.

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) clear infectious virus; nevertheless, virus persists in the CNS as noninfectious RNA, resulting in ongoing primary demyelination. Phenotypic and functional analysis of CNS infiltrating cells during acute infection revealed a potent regional CD8+ T cell response comprising up to 50% virus-specific T cells. The high prevalence of virus-specific T cells correlated with ex vivo cytolytic activity and efficient reduction in viral titers. Progressive viral clearance coincided with the loss of cytolytic activity, but retention of IFN-gamma secretion and increased expression of the early activation marker CD69, indicating differential regulation of effector function. Although the total number of infiltrating T cells declined following clearance of infectious virus, CD8+ T cells, both specific for the dominant viral epitopes and of unknown specificity, were retained within the CNS, suggesting an ongoing T cell response during persistent CNS infection involving a virus-independent component. Reversed immunodominance within the virus-specific CD8+ T cell population further indicated epitope-specific regulation, supporting ongoing T cell activation. Even in the absence of infectious virus, the CNS thus provides an environment that maintains both unspecific and Ag-specific CD8+ T cells with restricted effector function. Chronic T cell stimulation may thus play a role in preventing viral recrudescence, while increasing the risk of pathological conditions, such as demyelination.

Acute Disease↗
PubMed1999

The effect of vomitoxin (Deoxnivalenol) on testicular morphology, testicular spermatid counts and epididymal sperm counts in IL-6KO [B6129-IL6 [TmlKopf] (IL-6 gene deficient)] and WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] mice.

The potential of vomitoxin (VT) to affect testicular morphology and testicular and epididymal sperm counts was assessed in three strains of mice: IL-6KO [B6129-IL6 (tmlKopf) (IL-6 gene deficient)], WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] and B6C3F1 mice in a 90-day feeding study. The treated mice received VT at a concentration of 10 ppm in their diet. The body weight of VT-treated animals was significantly reduced compared with control animals. Slight changes, not statistically significant, were observed in relative testis weight and testicular spermatid counts. Histological changes were not apparent in the testes of VT-treated animals. The diameter of the seminiferous tubules, the height of the seminiferous epithelium and the number of Sertoli cell nucleoli per cross-sectioned seminiferous tubule in the VT-treated groups were not significantly different from their respective untreated controls. The IL-6KO and B6C3F1 VT-treated mice had significantly reduced cauda epididymal weights compared with their respective controls. These changes were not attributed to decreased sperm counts and this finding suggests that VT may exert an adverse affect on the epididymis.

Animals↗
PubMed1999

Intracerebral Whipple's disease diagnosed by stereotactic biopsy: a case report and review of the literature.

OBJECTIVE AND IMPORTANCE: This case demonstrates the rare occurrence of intracerebral Whipple's disease in a patient lacking classic systemic manifestations of the disease. Because of the nonspecific presentation and the typically deep-seated location of cerebral lesions in these patients, definitive diagnosis is frequently problematic. We present the first reported use of stereotaxy-guided brain biopsy to confirm the diagnosis of isolated intracranial Whipple's disease. CLINICAL PRESENTATION: The patient was a 36-year-old man who presented with a 4-month history of progressive lethargy, hypersomnia, behavioral changes, and weight gain. The results of the physical examination were remarkable only for findings of hypogonadism. Subsequent laboratory evaluation confirmed the diagnosis of hypogonadotrophic hypogonadism, with low levels of testosterone, luteinizing hormone, cortisol, and prolactin. INTERVENTION: A magnetic resonance image of the brain demonstrated hyperintense lesions on T2-weighted images in the regions of the right fornix, hypothalamus, and putamen that subsequently enhanced with intravenously administered contrast medium. A biopsy was then obtained from the right putaminal lesion under stereotactic guidance. Histopathological analysis of the tissue revealed findings consistent with intracerebral Whipple's disease that were subsequently confirmed using electron microscopy. CONCLUSION: Intracerebral Whipple's disease should be included in the differential diagnosis of patients presenting with progressive dementia and cognitive decline. In these patients, lesions have typically been observed in the hypothalamus, cingulate gyrus, basal ganglia, insular cortex, and cerebellum. As evidenced by our case, stereotaxy affords clinicians the attractive option of a minimally invasive technique by which to obtain tissue from such deep-seated areas. A review of this rare neurosurgical entity is presented.

Adult↗
PubMed1998

Using a defective-interfering RNA system to express the HE protein of mouse hepatitis virus for studying viral pathogenesis.

We have developed a defective-interfering (DI) RNA of mouse hepatitis virus (MHV) as a vector for expressing a variety of cellular and viral genes including the chloramphenicol acetyltransferase (CAT), hemagglutinin' esterase (HE), and gamma interferon. Here, we used the HE-expressing DI RNA for examining the role of HE protein in viral pathogenesis. The pseudorecombinant virus containing an expressed HE protein was generated by infecting cells with MHV-A59, which does not express, HE, and transfecting the in vitro-transcribed DI RNA containing the HE gene. These pseudorecombinant viruses (DE-HE A59) were then inoculated intracerebrally into mice. Viruses recovered from cells infected with A59 and transfected with DI RNA expressing the CAT gene (DE-CAT A59) were used as a control. At various time points after inoculation, mice were observed for clinical symptoms. Tissues (brains and livers) were obtained for determining the replication of DI RNA by RT-PCR, virus replication by plaque assay, antigen expression by immunohistochemistry, and pathological changes. Results showed that all mice infected with DE-CAT A59 succumbed to infection by 9 days postinfection (d p.i). These data are identical to the pathogenesis of the parental A59 virus, demonstrating that inclusion of the DI RNA did not by itself alter pathogenesis. In contrast, only 40% of mice infected with DE-HE A59 succumbed to infection. The subgenomic mRNAs transcribed from the DI vector were detected at 1 and 2 d p.i. but not at subsequent time points, indicating that the genes in the DI vector were expressed only at an early stage of viral infection. No significant difference in virus replication in the brains was detected between these two groups of mice, suggesting that virus replication in brains was not affected by the expression of the HE. Histopathological examination showed only a small increase in the extent of inflammatory cell infiltration and reduced viral antigen in the mice infected with DE-HE A59. There was no difference in virus replication in the livers at 2 and 4 d p.i., but a 3 log10 reduction was detected in the livers of mice infected with DE-HE A59 at 6 d p.i. Histological examination showed a significant reduction in viral antigen, inflammation and necrosis in mice infected with DE-HE A59. These results indicate that the expression of HE from the DI vector altered the viral pathogenesis. This study thus demonstrates the usefulness of this system in studying the role of viral or cellular genes expressed locally at the sites of viral infection in viral pathogenesis.

Animals↗
PubMed1994

The lack of a role for p53 in astrocytomas in pediatric patients.

Mutations in the p53 gene, which codes for a cell division regulatory protein, have been identified in approximately one-third of adult astrocytomas. We evaluated 35 astrocytic tumors (17 pilocytic, 4 diffuse low grade, 12 anaplastic, and 2 glioblastoma) in pediatric patients for p53 mutations, using polymerase chain reaction-single-stranded conformation polymorphism analysis as a screening technique. Additionally, those tumors identified with homozygosity in the area of the p53 gene on chromosome 17 by Southern blotting were sequenced to look for p53 mutations. No tumors were identified with polymerase chain reaction-single-stranded conformation polymorphism analysis shifts indicative of mutations in the p53 gene. Five of 21 tumors were homozygous in the region of the p53 gene on chromosome 17; no mutations in exons 5 to 8 were found in any of these tumors. The frequency of p53 mutation in pediatric astrocytomas is significantly less than the frequency for adult tumors, regardless of tumor grade. Furthermore, the frequency of p53 mutations in high-grade astrocytomas is significantly lower in pediatric tumors than in adult tumors. These results suggest that p53 is not important in the oncogenesis of pediatric astrocytomas. Oncogenesis in pediatric astrocytomas may occur by different mechanisms than those of similar tumors in adults.

Adolescent↗
PubMed1994

Magnetic resonance imaging and quantitative analysis of intracranial cystic lesions: surgical implication.

The authors evaluated a series of proven intracranial cystic lesions prospectively. The relative signal intensities of these lesions on both T1- and T2-weighted sequences were correlated with the composition and viscosity of the cystic contents. Specimens were collected from 51 patients by cyst aspiration or at the time of surgery. Once a specimen was obtained, it was immediately sent for quantitative analysis of proteins, cholesterol, triglyceride, calcium, and blood by-products. In 30 patients, the cystic lesion was hypointense on T1 and hyperintense on T2 relative to white matter. The cystic content in this group of patients was a watery fluid that could be easily aspirated. In another 14 patients, the cystic lesion was either isointense or hyperintense on T1 and hyperintense on T2-weighted sequences. In this group of patients, the cystic contents were mild to moderately viscous and a wide bore needle or cannula was required for aspiration. In the remaining seven patients, the cystic contents were hyperintense (n = 4), isointense (n = 2), or hypointense (n = 1) on T1 but all were markedly hypointense on T2-weighted sequences. The contents of the cystic lesions in these seven patients ranged from pastelike to solid and had to be removed surgically. This study concludes that the observed T1- and T2-weighted signal intensities can predict the relative viscosity and the composition of intracranial cystic contents. This information is found to be quite useful in planning surgery and using appropriate instrumentation in the management of intracranial cystic masses.

Adolescent↗
PubMed1992

The period gene encodes a predominantly nuclear protein in adult Drosophila.

The period gene of Drosophila melanogaster (per) is important for the generation and maintenance of biological rhythms. Previous light microscopic observations indicated that per is expressed in a variety of tissues and cell types and suggested that the per protein (PER) may be present in different subcellular compartments. To understand how PER influences circadian rhythms, it is important to define its subcellular location, especially in adult flies where inducible promoter experiments suggested that it is most relevant to circadian locomotor activity rhythms. To this end, we report the results of an immunoelectron microscopic analysis of wild-type flies and per-beta-galactosidase (beta-gal) fusion gene transgenics using a polyclonal anti-PER antibody or an anti-beta-gal antibody, respectively. Most of the PER antigen and the fusion gene product were located within nuclei, suggesting that PER acts in that subcellular compartment to affect circadian rhythms. The results are discussed in terms of per's possible biochemical functions.

Animals↗
PubMed1989

Nutritional status of home hemodialysis patients.

We studied the nutritional status of 32 patients (23 men), aged 50 (SD14) yr, on home hemodialysis (HHD) for one-138 months. No formal dietary restrictions were imposed. Anthropometric measurements were made using standard techniques, diet assessed by three-day dietetic diary and interview and plasma concentrations of nutrients were measured. Mean caloric intake was 29.4 (SD 10.7) kcal/kg; 24 (75%) patients had lower energy intakes than recommended for normals. Protein, vitamin C and folate intakes were above recommended minimum safe intakes. Intakes were less than recommended for calcium in four (13%) patients, iron in one (3%) and vitamin B12 in two (6%). One-third of both sexes had body mass indices (kg/m2) less than 25th percentile for normals, but none was less than 80% of ideal bodyweight. Arm muscle circumference was less than 10th percentile for normals in six men and three women. Triceps skin fold thickness was less than 10th percentile in four men (17%) and five women (55%). No anthropometric measurements were correlated with energy, protein or fat intake. Biochemical measurements were not useful in predicting protein intake. Neither nutritional intake nor anthropometric measurements were correlated with the duration of HHD. There was little evidence of malnutrition and wasting in this group of well rehabilitated HHD patients.

Adult↗
PubMed1988

The association of infantile osteopetrosis and neuronal storage disease in two brothers.

Neurological manifestations in infantile osteopetrosis are common and varied, and not always attributable to the skeletal pathology. An unusual association of osteopetrosis with neuronal storage of ceroid lipofuscin is reported in two infant brothers born of nonconsanguinous parents. The first child became symptomatic at age 5 days with weight loss and vomiting. He had poor head control, hypertonia, and persistent fisting, and died at age 2 months. In the second infant, the diagnosis of osteopetrosis was confirmed at age 2 days. His neurological symptoms included blindness, deafness, and recurrent seizures. The infant died at 7 months of age. In both cases, autopsy confirmed the diffuse bony sclerosis with hepatosplenomegaly and extramedullary hematopoiesis. Neuropathological examination revealed cerebral atrophy with ventricular dilation, neuronal loss, and astrogliosis. The most striking finding was widespread accumulation of neuronal ceroid lipofuscin associated with formation of axonal spheroids. The optic nerves were compressed at the optic foramina and showed loss of myelinated axons and gliosis. Rapid Golgi impregnations of neurons from the calcarine cortex in the second infant were analyzed quantitatively, showing a reduction in the total dendritic length and number of branches. The primary defect in osteopetrosis is thought to be a lysosomal dysfunction involving the monocyte cell line from which osteoclasts are derived. Thus, the association in two brothers of osteopetrosis with accumulation of neuronal ceroid lipofuscin may not be fortuitous. The neuronal storage disorder in this instance probably reflects lysosomal dysfunction.

Brain↗
PubMed1986

Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain.

Frozen brain specimens from eight multiple sclerosis (MS) patients were examined for the presence of leukocytes and their cell products by using a panel of monoclonal antibodies. The results presented here demonstrated that in the MS lesion, there was a marked accumulation of HLA-Dr-positive (Ia-positive) cells. These Ia-positive cells were identified as being glial fibrillary acidic protein positive by using double staining methods. Furthermore, the cells in the MS lesion expressed the interleukin 2 (IL 2) receptor, as identified by the anti-TAC monoclonal antibody. The cells in the region of the plaque also exhibited positive staining with antibodies to IL 1, IL 2, and prostaglandin E. Neither normal brain nor brain specimens from progressive multifocal leukoencephalopathy or Alzheimer's disease showed such patterns of staining. These results suggest that stimulated cells are present in the MS brain, thus implicating an active immune mechanism in the pathogenesis of MS.

Adolescent↗