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Biomedical subjects

M Hamilton

Publications and source records attributed to M Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed1989

Normal hematopoietic progenitor cells and malignant lymphohematopoietic cells show different susceptibility to direct cell-mediated MHC-non-restricted lysis by T cell receptor-/CD3-, T cell receptor gamma delta+/CD3+ and T cell receptor-alpha beta+/CD3+ lymphocytes.

To evaluate the capability of NK cells and cytotoxic T lymphocytes to interact with normal hematopoietic progenitor cells (HPC), as compared to neoplastic lymphohematopoietic cells, we investigated inhibition of colony growth of these cell populations in semi-solid culture systems, after incubation with cloned cytotoxic effector cells. Three different types of cloned effector cells were investigated: TCR-/CD3- NK cells, TCR-gamma delta+/CD3+ cells, and TCR-alpha beta+/CD3+ cytotoxic T lymphocytes. Effector cells showed differential levels of tumor cell colony inhibition, but no MHC-non-restricted lysis of normal HPC was observed. Pre-stimulation of normal HPC by culturing on established stromal layers had no effect. Cell-mediated lysis of HPC only occurred by Ag-specific MHC-restricted lysis by CTL, or by antibody-dependent cellular cytotoxicity. In cell mixing experiments, irradiated tumor cells, but not normal bone marrow cells inhibited tumor cell lysis. Furthermore, cloned effector lymphocytes were able to specifically eliminate malignant cells from tumor contaminated bone marrow without damaging normal HPC. When fresh leukemic cells were used as targets, growth of acute myeloblastic leukemia colonies was inhibited after incubation with several cytotoxic effector clones, whereas chronic myeloid leukemia precursor cells showed limited sensitivity to MHC-non-restricted cytolysis. These results indicate that MHC-non-restricted cytolysis by NK cells is selectively directed against neoplastic cells and not against normal HPC.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1989

Multiple idiopathic external root resorption.

An unusual case of multiple idiopathic root resorption involving all of the maxillary and mandibular incisor, canine, and premolar teeth is presented. A review of the literature reveals that this case is unusual in that, although other cases of multiple idiopathic root resorption have been described, the site of the resorption has been at the cervical margin in most reports, not at the apices as in this case. In other reports in which the resorption did affect the apices, the resorption usually affected only one, two, or three teeth. The pattern of resorption in this case, affecting only teeth with deciduous precursors, appears to be unique.

Adolescent↗
PubMed1989

Placental transfer and fetal distribution of fluoxetine in the rat.

Previously conducted reproduction and teratology studies in rats (unpublished observations) exposed to fluoxetine have revealed no compound-related adverse effects on fertility and no teratogenic effects. In order to confirm embryonic/fetal exposure to fluoxetine and/or metabolites, dissection and whole-body autoradiographic techniques were utilized to determine the placental transfer and fetal distribution in 12- and 18-day-pregnant Wistar rats 1, 4, 8, and 24 hr following a single oral 12.5 mg/kg dose of [14C]fluoxetine. On gestation Days 12 (organogenesis) and 18 (postorganogenesis), peak concentrations of radiocarbon occurred 4-8 hr after dose administration in the placenta, embryo/fetus, amniotic fluid, and maternal kidney, brain, and lung, and declined slightly at 24 hr postdose. Maternal lung contained the highest tissue concentration of radiocarbon at all time points. Placenta and maternal brain, kidney, and liver contained moderate levels of radioactivity, while embryonic/fetal tissue, amniotic fluid, and maternal plasma contained low levels of radioactivity. Mean fetal concentrations of radiocarbon at 4, 8, and 24 hr on gestation Day 18 were higher than mean embryonic concentrations on Day 12 of gestation. Analytical characterization of radioactivity indicated that combined fluoxetine and norfluoxetine concentrations accounted for 63-80% of the total radiocarbon concentrations in embryonic/fetal tissue. Results indicated that embryonic/fetal and maternal tissue levels of fluoxetine were greatest at early time points and declined with time, while norfluoxetine tissue levels were highest at the 24-hr time point. Whole-body autoradiographic techniques demonstrated that radioactivity associated with [14C]fluoxetine and/or its metabolites traversed the placenta and distributed throughout the 18-day fetus 4 hr following dose administration. Visual and quantitative evaluations of the autoradiograms indicated that the highest fetal concentrations of radiocarbon were associated with brain and thymus. Results from these studies indicate that fluoxetine and norfluoxetine traverse the placenta and distribute within the embryo/fetus during the periods of organogenesis and postorganogenesis and confirm embryonic/fetal exposure of parent and metabolite in previous negative rat teratology and reproductive studies.

Animals↗
PubMed1989

Frequency of symptoms in melancholia (depressive illness)

Symptoms of depression were quantitatively recorded using a rating scale, for 239 men and 260 women. The frequency of the various symptoms were similar for the sexes, with a high frequency for anxiety, both psychic and somatic. The results show that the symptoms of depressive patients differ from those found in the classic descriptions.

Affect↗
PubMed1989

Clinical pharmacology of a novel diarylsulfonylurea anticancer agent.

LY186641 (diarylsulfonylurea, [DSU]) is a novel anticancer agent because of its unique diarylsulfonylurea chemical structure, broad-spectrum antisolid-tumor activity in preclinical models, presumed novel mechanism of action and preclinical toxicities of methemoglobinemia (Met Hgb) and decreased red blood cell (RBC) survival. In this study, the in vitro drug sensitivity of human tumors as well as clinical pharmacology and toxicology of DSU in patients with cancer were examined. DSU was administered orally, daily for 7 days with a 3-week treatment cycle. Dose-limiting toxicities were Met Hgb and RBC hemolysis. The maximum-tolerated dose was found to be 1,200 mg/m2/d for 7 days. In pharmacokinetic studies, DSU was found to have a prolonged serum half-life (approximately 30 hours) and a large area under the plasma disappearance curve (8,883.3 micrograms.hr/mL at 1,200 mg/m2/d). A partial remission was observed in one patient with refractory ovarian cancer. In conclusion, DSU can be safely administered to cancer patients and does display antitumor activity. Potential means of obviating the toxicities of this compound are discussed.

Adult↗
PubMed1989

Pancreatic amylase measured in serum by use of a monoclonal antibody immunochemically immobilized to a solid phase.

We studied a method for measuring the pancreatic isoenzyme of amylase (EC 3.2.1.1) by use of a mouse monoclonal antibody against human salivary-type amylase (Clin Chem 1985;31:1283) coupled indirectly to particles of polyvinylidene fluoride via polyclonal goat anti-mouse immunoglobulin. These particles, in 200 microL of a suspension, could remove salivary amylase (activity 2200 U/L) from an equal volume of serum in 5 min. Measurement of amylase activity in the supernatant fluids from treated sera thus provided an assay of pancreatic amylase. Precision studies at three activity concentrations yielded within-run CVs of 1.6% to 1.7% (n = 25) and total CVs of 2.2% to 5.1% (20 days). Salivary amylase added to each of 10 sera was completely (99.8%, SD 1.6%) removed. The new method (y) showed the following regression statistics when compared with an electrophoretic method (x): slope = 0.989 (SD 0.019), intercept = -0.220% (SD 1.48%), SEE 4.0%, n = 51. Similar respective regression values were found for urine samples: slope = 0.934 (SD 0.053), intercept = 2.3 U/L (SD 3.2), SEE 8.4 U/L, n = 26. The following respective values were found when the new method (y) was compared with the previously described immunoprecipitation assay (x): slope = 1.02 (SD 0.02), intercept = 2.2% (SD 1.4%), SEE 3.3%, n = 23 sera. Reference intervals for pancreatic amylase activity in serum were established for three different substrates: maltotetraose, maltopentaose, and p-nitrophenylheptaoside.

Acute Disease↗
PubMed1987

Evolution of a highly successful in vitro fertilization-embryo transfer program.

During the first 2 1/2 years of operation of the University of California at Los Angeles in vitro fertilization-embryo transfer program, 47 clinical pregnancies were achieved in 154 laparoscopies for oocyte aspiration (31%). Two of these pregnancies were achieved through transfer of cryopreserved embryos when ongoing pregnancy did not result from embryo transfer in the stimulated cycle. An increase in clinical implantation was noted with a reduction of transfer volume and proportion of air, with 34% of laparoscopies being followed by clinical pregnancy over the last 18 months. No difference in the rate of clinical pregnancy was noted relative to uterine depth or position. The high rate of multiple implantation (47%) suggested a high level of embryo quality. The success rate was attributed to a strong ovarian, human menopausal gonadotropin stimulation, accurate timing of human chorionic gonadotropin, a high oocyte retrieval rate, meticulous laboratory technique, atraumatic, high-fundal transfer of embryos, and initiation of embryo cryopreservation.

Embryo Transfer↗
PubMed1985

Differential effects of pimozide on response-rate and choice accuracy in a self-stimulation paradigm in mice.

Intracranial self-stimulation (ICSS) from the dopamine (DA) A9 cell grouping was evaluated in mice following pimozide administration in both a one hole head dipping task and a two hole discrimination paradigm. While pimozide reliably decreased response rates, choice accuracy in the discrimination paradigm was unaffected by the drug treatment. The data were taken to suggest that neuroleptics influence response rate owing to motoric disturbances, without influencing the effectiveness of cues that previously had been associated with primary reinforcement.

Animals↗
PubMed1979

A comparative trial of the decanoates of flupenthixol and fluphenazine.

A double-blind trial was carried out comparing the effects of decanoates of flupenthixol and fluphenazine on the symptoms, ward behaviour and functional capacity in occupational therapy in 51 chronic schizophrenic patients. The patients were carefully selected on the basis of rigid criteria for diagnoses. To exclude nonresponders to neuroleptics the patients were first taken off neuroleptic drugs and only those who appeared to show deterioration were included in the trial. The dosage of drugs was varied according to clinical indications. The length of the trial was initially 4 months and 31 patients were followed for an additional 4 months. To ensure reliability multiple assessments were made at the start and the end of the trial. Most of the statistical tests showed no differences between the treatments, but some of those relating to affective symptoms showed an advantage for flupenthixol as compared with fluphenazine. There were no differences in the incidence of extra-pyramidal side-effects which required treatment in only 32% of the patients on each drug.

Adult↗
PubMed1979

Post-ECT cognitive defect and elevation of blood pressure.

There is evidence that ECT causes a breakdown of the blood-brain barrier through the rise of blood pressure it induced. Using the Benton test of cognitive function the day before and three hours after ECT treatment in 27 depressed patients, impairment of function was highly correlated with the maximum rise of systolic BP during the treatment.

Adult↗
PubMed1979

[Rating of antidepressant activity (author's transl)].

In this brief review. I have mentioned recent developments and the possibility of new ones. I have referred to technical problems in the organisation of trials, the selection of patients, methods of assessment and their statistical anlaysis, the specific problems of side-effects of drugs and, finally, the social aspects of depressive illness.

Antidepressive Agents↗