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Biomedical subjects

M Stanley

Publications and source records attributed to M Stanley.

At least 19 recordsLinked to original sources
PubMed1992

Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients.

Serious suicidal behavior, affective disorders, and a variety of other psychopathologic behaviors and syndromes have been found to correlate with measures of the serotonin system. Clinical studies have employed a range of serotonin indexes, including the cerebrospinal fluid level of 5-hydroxyindoleacetic acid, the prolactin response to serotonin agonists, such as fenfluramine hydrochloride, and platelet serotonin-related proteins or serotonin content. Many of these indexes are correlated with suicidal behavior, but the interrelationship of these biologic measures has been uncertain. We studied the relationship of a series of serotonin indexes in patients in whom these measures were correlated with suicidal behavior. A positive correlation was found between cerebrospinal fluid 5-hydroxyindoleacetic acid and the maximal prolactin response to fenfluramine but not with platelet serotonin2 receptor indexes. The fenfluramine-stimulated maximal prolactin response correlated with platelet serotonin2 receptor number, particularly in older patients. We conclude that cerebrospinal fluid 5-hydroxyindoleacetic acid measurements cannot be replaced but can be complemented by less invasive procedures, such as a fenfluramine challenge test or platelet serotonin2 measures, in the study of the relationship of the serotonin system to psychiatric disorders.

Adult↗
PubMed1992

In vivo measure of average bacterial cell size from a polarized light scattering function.

A particular combination of elements of the Mueller matrix for scattering of polarized light given by (S34 + S14)/(S11 + S13) identical to (S34/S11)++ is measured vs angle at a wavelength of 633 nm for randomly oriented suspensions of several species of bacteria in different stages of growth. (This combination of elements is dominated in the present measurements by the behavior of the normalized S34 matrix element, as is indicated by the notation defined on the right side of the equation.) The resulting graph in each case shows an oscillating function of angle. This function is compressed toward smaller angles when the bacteria are in the exponential phase of growth in comparison with results for a suspension of the same bacteria in the stationary (starving-smaller cells) phase of growth. Microscopic measurements were made to determine, for each case, the average dimensions of the bacterial population. Graphs were then plotted of the peak positions from the Mueller matrix function plots vs either cell length or cell diameter. The function was shown to be strongly correlated with cell diameter under the conditions of this experiment and poorly correlated with cell length. The measurements were shown to have a sensitivity to changes in average diameter of about 20 nm.

Bacillus megaterium↗
PubMed1992

Increased CSF HVA response to arecoline challenge in Alzheimer's disease.

The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p < .01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease.

Aged↗
PubMed1992

Effects of fenfluramine on plasma homovanillic acid in healthy subjects.

The specificity of fenfluramine as a pharmacological probe of the serotonin system has been questioned, since animal studies with high dose l-fenfluramine show increases in striatal levels of the dopamine metabolite homovanillic acid. To test the specificity of fenfluramine in humans with clinical doses, we compared plasma homovanillic acid (pHVA) concentration in healthy volunteers after administration of fenfluramine (60 mg) and placebo. There were no significant effects on pHVA, which supports previous findings that at doses used in pharmacological challenge paradigms, the effect of fenfluramine on the dopamine system is insufficient to alter measures of its change.

Dopamine↗
PubMed1992

Regional studies of serotonin and dopamine metabolism and quantification of serotonin uptake sites in human cerebral cortex.

An increasing number of studies have indicated that neuronal metabolism of serotonin (5-HT) and other monoamines may be altered in patients with affective disorders and in completed suicides. However, studies have yielded discordant results. The purpose of this study was to determine the regional variation of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), (5-HT) and 5-HT uptake sites within the human cerebral cortex. Our sample consisted of 19 patients who died suddenly and accidently. Cortical concentrations of 5-HIAA, HVA and 5-HT were measured in six regions using an HPLC. 5-HT uptake sites in cortex were examined using [3H]-Paroxetine. 5-HT values within each brain were fairly constant in cortical regions studied except for the posterior parietal areas. By contrast, 5-HIAA values showed a trend towards a rostro-caudal increase, with peak values seen at sections corresponding to the post-central gyrus and the occipital pole. Using the ratio of 5-HIAA/5-HT as a crude index of 5-HT turnover, there was a progressive rostro-caudal increase of values which achieved statistical significance: the posterior superior parietal area and the occipital pole displayed a greater ratio than the other four cortical regions. HVA values were highest in the pre-central region and decreased both rostrally and caudally. 5-HIAA and HVA values were correlated positively in 5 of 6 cortical areas, while 5-HIAA and 5-HT were correlated in areas 4 and 5. Results obtaining using [3H]-Paroxetine suggest that 5-HT uptake sites in the human cortex are distributed rather uniformally and are not correlated with 5-HT levels.

Adolescent↗
PubMed1992

Reliability of polymerase chain reaction in the detection of human immunodeficiency virus infection in children.

During a 3-year period we followed 128 human immunodeficiency virus (HIV) antibody-positive children ages 6 days to 11 years clinically and with an HIV diagnostic panel consisting of antibody (by enzyme-linked immunosorbent assay and confirmed by indirect fluorescence assay or Western blot), p24 antigen detection, HIV isolation from peripheral blood culture and molecular detection of HIV nucleic acids by polymerase chain reaction (PCR). The PCR procedure included 30 cycles of amplification using two separate gag primer pairs (SK38/39 and SK101/145), followed by detection with probes to areas amplified (SK19 and SK102). Results of PCR were available within 48 hours and were sensitive (97%) and specific (100%). PCR should be obtained on all children exposed perinatally, and aggressive management should be undertaken for those found to be positive.

AIDS Serodiagnosis↗
PubMed1992

Epidermal keratinocyte self-renewal is dependent upon dermal integrity.

The epidermis is a major site of self-renewal in which there is constant replacement by cell division in the basal layers of cells lost by desquamation in the superficial layers. Such a tissue is therefore likely to contain stem cells and in this study we have examined the role of the dermis in the maintenance of epidermal self-renewal. We have developed a mouse model to address the question of whether the maintenance of epidermal self-renewal is dependent, as in the hemopoietic system, upon a heterologous cell type. Intact epidermis separated from dermis at the dermo-epidermal junction or epidermis derived from disaggregated epidermal cells, can reconstitute a stratified squamous epithelium when grafted onto the lumbo-dermal fascia of the mouse or onto an experimentally induced granulation tissue bed. However, we have shown that, after grafting, the clonogenic capacity of the keratinocytes declines sharply and the colonies that are produced are incapable of self-renewal in vitro. Although initially hyperplastic, these epidermal grafts assume an atrophic appearance after 40-70 d and this may be related to the loss of self-renewal observed in vitro. With both experimental murine grafts and clinical grafts the failure of keratinocytes to self-renew can be alleviated, partially, by the presence of the dermis in full-thickness or split-thickness grafts, which implies that the dermis has a functional role in epidermal stem cell maintenance. The relevance of these observations to the clinical experience with cultured autologous keratinocyte sheets as wound dressings to patients is discussed.

Animals↗
PubMed1992

Inhibition of increases in ornithine decarboxylase and putrescine has no effect on rat liver regeneration.

Polyamines are considered critical for cell proliferation. During liver regeneration in the rat, ornithine decarboxylase (ODC) mRNA and enzyme activity and polyamines (primarily putrescine and spermidine) are known to increase substantially. We examined the effect of inhibition of polyamine synthesis with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of the ODC enzyme, on regenerating liver weight and total DNA, RNA, and protein, [3H]thymidine and [14C]leucine incorporation, number of mitotic figures, and putrescine, spermidine, and spermine contents. Rats received DFMO beginning 4 days before or immediately after two-thirds partial hepatectomy. In control rats, ODC activity, putrescine, and spermidine increased significantly during regeneration, whereas spermine was unchanged. In rats receiving DFMO, ODC and putrescine changed minimally but spermidine increased as usual. Spermine levels were modestly higher in rats receiving DFMO beginning 4 days before partial hepatectomy. However, despite ODC inhibition and substantially lower levels of putrescine, the course of liver regeneration in rats treated with DFMO was not affected. Total liver mass, DNA, RNA, and protein increased over 5 days equally in rats receiving DFMO and control rats. In addition, there were no differences in [3H]thymidine incorporation into DNA, [14C]leucine incorporation into protein or mitotic indexes between DFMO-treated and control rats at 24 and 48 h after partial hepatectomy. These results suggest that the well-known increases in ODC activity and polyamines that occur during regeneration are not required for liver to undergo its proliferative response to partial hepatectomy.

Animals↗
PubMed1992

Self-mutilation in personality disorders: psychological and biological correlates.

OBJECTIVE: The goal of this study was to determine whether self-mutilators with personality disorders differ from nonmutilators with personality disorders in impulsivity, aggression, and other psychopathology and whether serotonergic dysfunction contributes to self-mutilation. METHOD: Twenty-six self-mutilators with personality disorders were matched to 26 control subjects with personality disorders for gender, age, education, axis I diagnosis of affective disorder, and axis II diagnosis of personality disorder. Numerous indexes of psychopathology as well as CSF 5-hydroxyindoleacetic acid (5-HIAA) levels and platelet imipramine binding sites (Bmax) and affinity (Kd) were determined. RESULTS: Self-mutilators had significantly more severe character pathology, had greater lifetime aggression, and were more antisocial than the control subjects. The self-mutilators scored higher on the Hamilton Rating Scale for Depression but not on the Beck Depression Inventory or the Beck Hopelessness Scale. The two groups did not differ on the Buss-Durkee Hostility and Guilt Inventory or on the Sensation Seeking Scale. The degree of self-mutilation was significantly correlated with impulsivity, chronic anger, and somatic anxiety. Both self-mutilation and impulsivity showed significant negative correlations with Bmax, although the two groups did not differ in CSF 5-HIAA levels or in platelet imipramine binding. CONCLUSIONS: The results demonstrate the contribution of severe character pathology, aggression, impulsivity, anxiety, and anger to self-mutilation and provide preliminary support for the hypothesis of underlying serotonergic dysfunction facilitating self-mutilation.

Humans↗
PubMed1992

Elderly patients in critical care: an overview.

Elderly patients who enter the critical care setting have special nursing care needs based on the physiologic changes of aging. An overview of the changes of aging associated with the immunologic, cardiovascular, integumentary, musculoskeletal, and renal systems provides the basis for care planning to meet the needs of older adults in the intensive care unit.

Aged↗
PubMed1992

Rating the severity of trichotillomania: methods and problems.

The capacity to measure the severity of trichotillomania is necessary for studies of the efficacy of treatment interventions. To date, researchers have used diverse methods, including: the adaptation of instruments designed for other purposes, counting episodes of hair pulling, counting hairs that have been pulled out, and both physician- and self-administered scales of severity or improvement. In this paper, the authors review the methods that have been employed, discuss problems in the measurement of trichotillomania, explore the potential for objective measures of hair loss and introduce a new instrument, the Psychiatric Institute Trichotillomania Scale.

Hair↗
PubMed1992

Lack of immortalizing activity of a human papillomavirus type 16 variant DNA with a mutation in the E2 gene isolated from normal human cervical keratinocytes.

The oncogenic potential of a human papillomavirus type 16 (HPV16) variant cloned from normal human cervical keratinocytes has been tested in vitro using primary rodent epithelial cells and human cervical keratinocytes. The HPV16 variant was able to extend the lifespan of, but failed to immortalize, human keratinocytes. It could however cooperate with an activated ras oncogene to transform primary rodent cells. Radioimmunoprecipitation assays of the rodent cells showed that they expressed the E7 protein. DNA sequence analysis of the URR/E6/E7 and E5 regions of the HPV16 showed them to be fully functional, but a deletion in the viral E2 open reading frame was detected. This truncated E2 only weakly stimulated transcription of the viral regulatory region. Complementation assays using the HPV16 variant and a full-length E2 enabled the cloned variant to immortalize human cervical keratinocytes with wild-type efficiency. These results suggest that other viral gene products in addition to E6/E7 may play an important role in the in vitro immortalization of cervical keratinocytes in HPV16 and the development of cervical cancer.

Amino Acid Sequence↗
PubMed1992

Clinical characteristics of trichotillomania and its response to fluoxetine.

BACKGROUND: In general, effective treatments for trichotillomania have been elusive. Although behavioral therapies and hypnosis have provided benefits to some, adult patients with chronic hair pulling have often proved refractory to treatment. Medication has generally been unhelpful until the recent introduction of serotonin reuptake inhibitors for the treatment of this condition. Furthermore, there has been little systematic study of the clinical characteristics of these patients. METHOD: Twenty individuals with trichotillomania were interviewed and were characterized on the basis of hair-pulling patterns, comorbidity, obsessionality, and the presence of symptoms of depression and anxiety. Twelve patients participated in an open 16-week trial of fluoxetine (up to 80 mg/day). RESULTS: Compared with baseline scores derived from a scale of trichotillomania severity, severity scores at endpoint decreased (improved) by 34% (p less than .025). Among the 8 responders, the mean decrease in severity scores was 60%. Fifty-five percent (11 of 20) had current or past additional DSM-III-R Axis I diagnoses (disorders of mood, anxiety, and psychoactive substance use). CONCLUSION: We conclude that in an open 16-week trial, patients treated with fluoxetine improved significantly. Data are presented on comorbid conditions, depressive symptoms, and anxiety. Baseline behavioral assessments of patients with trichotillomania suggest that substantial differences exist between this syndrome and obsessive compulsive disorder.

Adult↗
PubMed1992

Antidepressants and suicide risk: issues of chemical and behavioral toxicity.

Recent reports have described several patients who experienced suicidal preoccupation while being treated with antidepressant drugs. This phenomenon has been interpreted as antidepressant-induced suicidal behavior. The association of antidepressant medication with suicide was noted early in their clinical use. Antidepressants have been a common cause of suicide when taken in overdose. Epidemiologic studies have reported that antidepressants differ from one another in the frequency with which they are associated with suicide by overdose. This differential association of antidepressants with suicide might support the possibility that certain agents may induce suicidal behavior. However, it seems that the frequency with which an antidepressant is related to suicide by overdose is correlated with each compound's inherent toxicity. Reported cases of emergence of suicidal preoccupation during fluoxetine treatment have raised the possibility that serotonergic drugs may induce this destructive behavior. Although this hypothesis rests on only a few reported cases, large-scale clinical trials of serotonin uptake inhibitors such as fluoxetine, paroxetine, and sertraline do not support it. Thus, the decreased toxicity of newer antidepressants such as fluoxetine and other selective serotonergic drugs makes them an attractive choice for treatment of depressed patients who are at risk for suicide.

Animals↗
PubMed1991

Human papillomavirus 16 E7 protein is associated with the nuclear matrix.

The cellular localization of the human papillomavirus (HPV)-16 E7 gene product in the cell lines CaSki and SiHa has been determined by both biochemical and immunocytochemical methods. These measurements show E7 to be localized in the cell nucleus, specifically with the nonchromatin nuclear structure or nuclear matrix. This localization of E7 required an unambiguous fractionation of the nuclear constituents. This was achieved by using a gentle sequential fractionation procedure to prepare the scaffold consisting of the nuclear matrix and intermediate filaments (NM-IF). Chromatin was cleaved with nuclease and the resulting nucleosomes eluted with 0.25 M ammonium sulfate. Immunostaining of cells after this extraction procedure with monoclonal antibodies (mAbs) to E7 revealed a fine grained, punctate nuclear fluorescence in CaSki and SiHa, which was absent in normal cervical keratinocytes and the HPV-negative cell line C33.1. Western blots of cell fractions with these mAbs showed that E7 was localized in the NM-IF fraction in SiHa and CaSki but was not detected in HPV-negative cells. A second protein of slightly higher mobility is identified by these antisera in HPV-16-containing cells. The data suggest that the previous inability to directly visualize E7 by immunocytology is due to the masking of epitopes by cellular components and not to low levels of protein.

Blotting, Western↗
PubMed1991

Tritiated imipramine binding. A peripheral marker for serotonin in Parkinson's disease.

Tritiated imipramine binding in platelets has been used to evaluate serotonin activity in depression in previous studies. This article examined this marker as a possible measure of central nervous system serotonergic activity for depression in patients with Parkinson's disease (PD). The number of binding sites was significantly lower in depressed patients with PD than in a healthy control group. Patients with PD who were not depressed had lower values than the comparison group, but this difference was not significant. We also found a significant correlation between the receptor site values in platelets and cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (r = .59), but this was independent of a diagnosis of depression. Receptor site values were examined to identify appropriate cutoff scores to predict depression in the group of patients with PD. A maximum sensitivity of 50% was achieved with a specificity of 64%. Our results strongly support a generalized alteration in serotonin metabolism in depressed patients with PD, but tritiated imipramine binding in platelets is not a useful diagnostic tool for depression.

Aged↗