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Biomedical subjects

M Stanley

Publications and source records attributed to M Stanley.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in the pediatric opsoclonus-myoclonus syndrome.

To study the purported role of central monoamine disturbances in the pathophysiology of the opsoclonus-myoclonus syndrome, the serotonin metabolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid were measured in cerebrospinal fluid samples from 27 affected children and 47 age- and gender-matched control subjects by high-pressure liquid chromatography with electrochemical detection. 5-Hydroxyindoleacetic acid and homovanillic acid concentrations in the cerebrospinal fluid were approximately 30 to 40% lower in opsoclonus-myoclonus patients compared to control subjects, and the normal inverse correlation between age and monoamine metabolite concentrations in the cerebrospinal fluid of control subjects was not found in opsoclonus-myoclonus patients. Patients with the lowest values were less than 4 years old, and a subgroup had extremely low levels, but differences in older children were not significant. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid were more positively correlated in control subjects than in opsoclonus-myoclonus patients. None of the patients exhibited high levels of monoamine metabolites. Homovanillic acid levels were slightly lower in the cerebrospinal fluid of patients receiving corticotropin or steroids at the time of lumbar puncture. Clinical variables that could be excluded were paraneoplastic etiology, anesthetic for lumbar puncture, syndrome duration, age at onset, gender, response to steroids, length of time until initiation of corticotropin or steroids, presence of seizures, opsoclonus, and functional impairment. These data suggest a disturbance and possible altered ontogeny of serotonin or dopamine neurotransmission in a subpopulation of children with opsoclonus-myoclonus with low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1995

Analysis of human papillomavirus type 16 E5 oncogene expression in vitro and from bicistronic messenger RNAs.

During a human papillomavirus infection (HPV), a set of spliced messenger RNAs (mRNA) are produced from the coding strand of the 8-kilobase virus DNA genome. These mRNAs have been isolated from cervical intraepithelial neoplasia biopsies, tumor biopsies and HPV type 16 (HPV-16)-containing cell lines, and subsequent analyses have shown that the different mRNAs are obtained by often complex splicing events. In the present study we have investigated the coding capacity of the HPV-16 E5 open reading frame (ORF) in an in vitro translation system and by the expression of a HPV-16 E5-CAT fusion gene from bicistronic messenger RNAs derived from polycistronic mRNAs which have previously been identified by others. Our results show that the HPV-16 E5 protein synthesis can only be initiated from the authentic ATG codon in the presence of E2 ORF translation. The E5 gene is found to be expressed only from a bicistronic mRNA with an E2 ORF upstream of the E5 gene indicating that the E5 protein is synthesized coordinated with the E2 protein. The supposition that the E5 protein is synthesized early in infection is discussed.

3T3 Cells↗
PubMed1995

Seasonal rhythm of platelet [3H]imipramine binding in adolescents who attempted suicide.

OBJECTIVE: This study was designed to determine the seasonality of serotonin functions among adolescents who attempt suicide. METHOD: Platelet [3H]imipramine binding was assessed over a period of 18 months in 98 adolescents who attempted suicide and a comparison group of 23 never-suicidal youths with conduct disorder. RESULTS: [3H]Imipramine (Bmax) was uncorrelated with age, but showed considerable seasonal variability over time in those who had attempted suicide. CONCLUSIONS: [3H]Imipramine binding density in adolescents who attempted suicide exhibited significant seasonality, reaching a nadir in late winter/early spring.

Adolescent↗
PubMed1994

A designed peptide ligase for total synthesis of ribonuclease A with unnatural catalytic residues.

An engineered variant of subtilisin BPN', termed subtiligase, which efficiently ligates esterified peptides in aqueous solution, was used for the complete synthesis of ribonuclease (RNase) A that contains unnatural catalytic residues. Fully active RNase A (124 residues long) was produced in milligram quantities by stepwise ligation of six esterified peptide fragments (each 12 to 30 residues long) at yields averaging 70 percent per ligation. Variants of RNase A were produced in which the catalytic histidines at positions 12 and 119 were substituted with the unnatural amino acid 4-fluorohistidine, which has a pKa of 3.5 compared to 6.8 for histidine. Large changes in the profile of the pH as it affects rate occurred for the single and double mutants with surprisingly little change in the kcat for either the RNA cleavage or hydrolysis steps. The data indicate that these imidazoles function as general acids and bases, but that the proton transfer steps are not rate-limiting when the imidazoles are present in their correct protonation states. These studies indicate the potential of subtiligase for the blockwise synthesis of large proteins.

Amino Acid Sequence↗
PubMed1994

Negative and depressive symptoms in suicidal schizophrenics.

The aim of this study was to determine the value of positive, negative and depressive symptoms, and of the dexamethasone suppression test (DST), in differentiating schizophrenics with and without a history of suicide. Fifty-seven hospitalized patients with schizophrenia were assessed at the end of a neuroleptic free interval with the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HRSD), and with a dexamethasone challenge. Suicide attempters were significantly more likely to meet criteria for major depression than nonattempters. Scores on the HRSD differentiated the two groups whereas the sums of positive and negative symptom items from the BPRS did not. DST a.m. and p.m. cortisol values differentiated suicide attempters from nonattempters and HRSD scores correlated significantly with cortisol levels. This study confirms the importance of depressive symptoms in schizophrenic patients with a history of suicide. Assessment of the hypothalamic-pituitary-adrenal axis in schizophrenia may also provide useful information.

Adult↗
PubMed1994

HPV and p53 in cervical cancer.

OBJECTIVE: To determine the prevalence of HPV 16 and 18 E6 by DNA detection and p53 abnormal protein expression in cervical cancers in Hong Kong. MATERIALS AND METHODS: Seventy-three squamous cell cervical cancer biopsy were analysed. Detection of HPV DNA was carried out by the polymerase chain reaction and Southern blotting (PCR/SB) technique using primers to the HPV16 & 18 E6 region and consensus primers to the L1 region. Abnormal expression of the p53 protein was detected by immunohistochemical staining (IHS) using the antibody CM1 on frozen sections of 55 cervical cancer samples. Forty-six samples were analysed for both the presence of HPV DNA and abnormal expression of p53. RESULTS: 67.2% of the 64 samples showed the presence of HPV 16 E6 DNA and 39.1% showed the presence of HPV 18 E6 DNA. 32.8% showed the presence of both HPV 16 and 18 E6 DNA. No HPV DNA was shown in 10.9% of samples. Only 3.6% (2) of 55 samples showed positive IHS with CM1. One occurred in a HPV negative sample and the other in a HPV positive sample. CONCLUSION: A high prevalence of HPV DNA was detected in cervical cancer in Hong Kong using the PCR/SB technique. However, abnormal expression of p53 was uncommon amongst patients with or without HPV 16 or 18 infection.

Base Sequence↗
PubMed1994

Stereotactic resection of brain metastases in eloquent brain.

We have treated 14-patients with metastatic tumors located in eloquent cortical areas by a stereotactic-guided keyhole craniotomy and total microsurgical excision utilizing the Pelorus stereotactic device. Patients ranged in ages from 26 to 82 years with a median age of 59 years. There were 9 women and 5 men. Ten patients presented with hemiparesis and 4 with aphasia. Primary tumor location was lung in 7, colon in 2, melanoma in 2, and breast, renal, and bone in 1 case each. Gross total resection was accomplished in all cases, with postoperative imaging confirmation of complete removal. Single metastatic tumors were removed in 12 cases, and multiple lesions in 2 cases. Twelve patients had postoperative whole brain irradiation (30 Gy/10 fractions); 2 patients had previously received whole brain irradiation, yet demonstrated tumor growth. Complete resolution of neurologic deficits was accomplished in 8 patients, 3 had improved and 2 were unchanged. One patient had resolution of preoperative deficit but developed hemiparesis secondary to a hemorrhagic infarction contralateral to the operative site. Nonneurologic morbidity includes deep venous thrombosis in 3 patients, and pneumonia in 1. Thirty-day perioperative mortality is zero, and to date no patient had died of intracranial disease. We believe that with the assistance of stereotactic localization, metastases in vital regions of the cortex can be removed with very low neurologic morbidity, and with a high proportion of patients having improvement in their level of neurologic function. The morbidity in this series compares favorably with that of stereotactic radiation series reported in the literature with local disease control and resolution of neurologic deficits that equals or exceeds stereotactic radiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The host response to lesions induced by human papillomavirus.

Human papillomaviruses (HPVs) are strictly intraepithelial pathogens: in the natural productive infection they induce benign epithelial proliferations of mucocutaneous surfaces, some of which may progress to malignancy. Benign HPV-induced lesions are chronic persistent growths; high levels of viral antigen are expressed in the apparent absence of a host immune response suggesting that these viruses have evolved efficient mechanisms of immune evasion. Cell-mediated responses are central in the pathogenesis of HPV and regression of both cutaneous and genital warts histologically resembles a delayed-type hypersensitivity response (DTH). The antigen(s) in the wart against which this response is initiated are not known but in an experimental murine model DTH responses to the E6 and E7 proteins of HPV-16 can be elicited when viral antigen is presented via the epithelial route. Priming with low levels of viral antigen in this model induces non-responsiveness and the loss of DTH. In HPV-associated cancers the E6/E7 genes are expressed and an antibody response to the proteins is found in at least 50% of cases indicating that these oncoproteins are potential targets for immunotherapy.

Animals↗
PubMed1993

Differential visualization of dopamine D2 and D3 receptors in rat brain.

The mRNA for the dopamine D3 receptor is confined to limbic regions and the D3 receptor may be a target for antipsychotic medications. We used quinpirole and domperidone to try to visualize D3 and dopamine D2 receptors selectively in rat brain, using in vitro autoradiography and digital subtraction. We used 125I-sulpiride, a ligand with high affinity for the D2 receptor in brain and for the D3 and D2 receptors in transfected cells. Our data indicate that the D2 receptor is present in much greater density than the D3 receptor in rat brain, even in limbic regions.

Animals↗
PubMed1993

A comparison of the response of near-fatal acute hemorrhage models with and without a vascular injury to rapid volume expansion.

Recent studies in which animals were bled from a vascular injury rather than an intravascular catheter demonstrate increased blood loss and mortality with rapid volume expansion. The purpose of this study was to better define the importance of incorporating a vascular injury in animal models of acute hemorrhage. We directly compared the response to resuscitation from hemorrhage of comparable severity in animals with and without a vascular injury. Thirty-four immature swine (14.6 to 23.2 kg) were instrumented and subjected to severe blood loss (40 to 46 mL/kg). Groups I and II were hemorrhaged from a femoral artery catheter only. Groups III and IV were initially bled in the same manner; however, when the mean arterial pressure (MAP) decreased to 30 mm Hg, a 4-mm tear was created in the infrarenal aorta, allowing free intraperitoneal hemorrhage. In all groups, the catheter hemorrhage was discontinued once the pulse pressure reached 5 mm Hg. Groups II and IV were resuscitated with normal saline (NS) infused at a rate of 6 mL/kg/min followed by shed blood at a rate of 2 mL/kg/min. The resuscitation fluids were infused as needed to maintain a MAP of 80 mm Hg. Groups I and III served as controls and were not resuscitated. All animals were observed for 60 minutes or until death. The data were compared using repeated measures analysis of variance with a post hoc Tukey Kramer and the Fisher's exact test. Mortality was 100%, 0%, 88%, and 78% for groups I, II, III, and IV, respectively (P < .05 for group II vs groups I, III, and IV).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
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↗