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Biomedical subjects

M Stanley

Publications and source records attributed to M Stanley.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1991

Immunocytochemical characterization of large granular lymphocytes in normal cervix and HPV associated disease.

A quantitative immunocytochemical study of large granular lymphocytes (LGLs) in the normal cervix and in human papillomavirus (HPV) associated disease was performed using a panel of monoclonal antibodies which included those for LGL surface markers CD56, CD16, and CD57. Only CD56-positive cells were found within the ectocervical epithelium and these cells increased in number in cervical intraepithelial neoplasia (CIN) in comparison with normal cervix. Examination of serial sections and double labelling suggests that these cells are CD3+, CD8+, CD56+, CD16+. The observed increase in number of this subset was not associated specifically with HPV infection but was related to CIN. Lymphocytes expressing all three LGL markers were found in the stroma and CD16(+)-positive cells clustered around endocervical glands with occasional cells extending into the endocervical epithelium. These results indicate that a small subset of LGLs which express T-cell markers is increased in number in CIN. Cells expressing classical NK markers are restricted to the stroma and are not found within the ectocervical epithelium.

Adult↗
PubMed1991

Placental teratoma.

The rare teratoma of the placenta has been compared to the fetus amorphus, two distinguishing characteristics being the teratoma's lack of structural organization and lack of large vessels entering the tumor. A case of placental teratoma and theories of origin are discussed.

Adult↗
PubMed1991

Long-term human immunodeficiency virus infection in asymptomatic homosexual and bisexual men with normal CD4+ lymphocyte counts: immunologic and virologic characteristics.

From a prospective cohort study, 24 asymptomatic men were identified who had been antibody positive for human immunodeficiency virus (HIV) for at least 5 years (median = 9.1) with CD4+ lymphocyte counts greater than or equal to 400 cells/mm3. Of these "nonprogressors", 23 (96%) had evidence of HIV infection by either HIV culture or the polymerase chain reaction (PCR) for HIV DNA, although only 1 (4%) had a positive assay for HIV RNA (by PCR) and no one was positive for p24 antigen. Compared with 24 antibody-negative men and 14 men with AIDS, nonprogressors had higher CD8+ counts and lower natural killer cell activity. Nonprogressors had higher beta 2-microglobulin levels than did seronegative controls, suggesting some degree of immune system activation. Compared with men with AIDS, nonprogressors seemed to have a stronger antibody response to six different HIV-related proteins but did not differ significantly in neutralizing antibody or antibody-dependent cellular cytotoxic activity.

Adult↗
PubMed1991

Self-injurious behavior: a review of the behavior and biology of self-mutilation.

OBJECTIVE: The authors describe the clinical characteristics of self-injurious behavior, giving special emphasis to self-injurious behavior occurring among individuals with character disorders. DATA COLLECTION: They review data suggesting the involvement of serotonergic, dopaminergic, and opiate neurotransmitter systems in the expression of self-injurious behavior. FINDINGS: Self-injurious behavior occurs among mentally retarded individuals, psychotic patients, prison populations, and individuals with severe character disorders. Although theoretical psychological models of self-injurious behavior are helpful in understanding the patient's experience of self-injury, no generally useful therapeutic approach has yet evolved from these models. Data derived from animal models and treatment studies suggest the involvement of opiatergic and dopaminergic mechanisms in self-injury among the mentally retarded. Serotonergic influences on self-injurious behavior may be present in varying forms of this behavior. The scientific literature on the benefits of pharmacological agents for mentally retarded individuals is beset with a number of problems. Support is emerging, however, for the use of lithium and carbamazepine with self-injuring mentally retarded patients, and some behavioral interventions appear to be successful for mentally retarded individuals. Self-injuring patients with borderline personality disorder may benefit from milieu treatment. CONCLUSIONS: Although no form of treatment has yet been demonstrated to be of general benefit, the literature suggests that therapeutic trials with dopamine antagonists, serotonin reuptake inhibitors, and opiate antagonists may be of value.

Adolescent↗
PubMed1991

The autonomic and hemodynamic effects of oral theophylline in patients with vasodepressor syncope.

Adenosine appears to be an important mediator of hypotension and bradycardia in certain subsets of patients with vasodepressor syncope. Adenosine receptor blockage with methylxanthines may hypothetically prevent the vasodepressor spell. We studied the chronotropic, hemodynamic, and cardiac autonomic responses to head-up tilt in patients (mean age 40.7 +/- 18.1 years) with vasodepressor syncope before and after treatment with oral theophylline. At baseline, hypotension and syncope or near syncope were induced at 11.7 +/- 2.3 minutes of 60 degrees head-up tilt in all patients. Cardiac vagal and sympathetic tone showed biphasic and directionally opposite changes during tilt. Repeat tilt during oral theophylline therapy (6-12 mg/kg/day for 14 +/- 6 days) did not provoke symptomatic hypotension in 82% of patients. During 10.7 +/- 6.1 months of follow-up, seven patients had no recurrence of vasodepressor syncope and seven patients discontinued theophylline because of adverse reactions. Low-dose theophylline prevents tilt-induced vasodepressor syncope and may prevent spontaneous vasodepressor syncope in selected patients who can tolerate theophylline.

Administration, Oral↗
PubMed1991

A multicenter proficiency trial of gene amplification (PCR) for the detection of HIV-1.

The sensitivity and specificity of the polymerase chain reaction (PCR) for the detection of HIV-1 proviral DNA was determined in five laboratories with extensive experience in PCR testing. Five panels consisting of 105 HIV-1-seronegative specimens from regularly repeating blood donors with no risk factors for HIV infection and 99 HIV-1-seropositive and culture-positive specimens from a cohort of homosexual/bisexual men were sent under code to each laboratory. Amplification procedures and testing algorithms by which specimens were judged positive, negative, or indeterminate varied between laboratories. The average sensitivity for the five laboratories was 99.0%, with two laboratories achieving 100%. The average specificity was 94.7%, varying between 90.5 and 100%. The overall false-positive rate was 1.8%, the false-negative rate was 0.8%, and the indeterminate rate was 1.9%. Of 1,005 determinations made by the five laboratories, 32 (3.2%) were misclassifications. Most of the classification errors occurred in specimens from uninfected individuals and were distributed among the laboratories in such a way as to indicate laboratory error rather than the inherent reactivity of some samples. This emphasizes the need for standardization of PCR testing and caution in interpreting positive PCR reactions in HIV-1-seronegative persons.

DNA, Viral↗