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Biomedical subjects

L Parker

Publications and source records attributed to L Parker.

At least 217 records · Page 12Linked to original sources

Further characterization of the in vitro assay for inhibitors of metabolic cooperation in the Chinese hamster V79 cell line.

12-O-Tetradecanoylphorbol-13-acetate (TPA) has been previously shown to inhibit metabolic cooperation in Chinese hamster V79 cells. An in vitro assay, based on this phenomenon, has been developed to study tumor promoters. Several parameters concerning the metabolic cooperation assay using V79 Chinese hamster cells were further investigated in this report. Pretreatment of the cells with TPA in situ for different periods of time did not result in any detectable change in the inhibition of metabolic cooperation. If cells were replated after TPA treatment, a different result was obtained. There was an apparent decrease in the ability of TPA to inhibit metabolic cooperation when TPA was added back to the TPA-pretreated cultures. However, when TPA was omitted from the TPA pretreated cultures after replating, the inhibition of metabolic cooperation remained high. It was also found that pretreatment of the cells with another chemical, aldrin, exhibited the same pattern as the in situ TPA pretreatment effect on inhibition of metabolic cooperation. In order to obtain a high level of inhibition of metabolic cooperation when using aldrin in this assay, it was determined that the chemical needed to be present for more than one day. Our studies also showed that a 24 h treatment with 6-thioguanine did not kill 6-thioguanine-sensitive cells quickly, nor did it prevent them from performing metabolic cooperation. The relationship of cell density and TPA concentration was also studied. It was observed that a higher cell density required higher TPA concentration to inhibit, maximally, metabolic cooperation. A 'down regulation' type effect was noted when culture was challenged with different concentrations of TPA. These results were interpreted to be consistent with the hypothesis that inhibited gap-junctional intercellular communication is one of the components of tumor promotion.

Aldrin↗

Effect of short-term bile duct ligation on peripheral blood steroids, urinary PGE2 and the rate of sodium excretion in male rabbits.

Short-term bile duct ligation in male rabbits resulted in a significant reduction in the rate of sodium excretion after saline challenge (10 ml/kg/hr for 4 hr, P less than 0.03). The reduction in the sodium excretory rate (14.3 +/- 7.8 to 6.3 +/- 5 mu-equiv/min, P less than 0.03) was associated with an increased urinary PGE2 excretion (200.9 +/- 174 to 731.8 +/- 1039.8 pg/min, P less than 0.01) without significant change in serum aldosterone and cortisol concentrations. Serum progesterone concentration increased (37.2 +/- 15.6 to 119.2 +/- 34.6 ng/dl, P less than 0.01) whereas serum 17-hydroxyprogesterone concentration declined after bile duct ligation suggesting the development of a 17-hydroxylase enzymatic block.

17-alpha-Hydroxyprogesterone↗

Orchiectomy does not selectively increase adrenal androgen concentrations.

Prostatic carcinoma is androgen dependent and, therefore, treated by orchiectomy. However, adrenal androgen secretion remains intact after orchiectomy, and several investigators even reported an increase in serum adrenal androgen concentrations after orchiectomy. Such an increase in androgen secretion theoretically could promote tumor recurrence. To investigate this question, we obtained multiple blood samples from 10 men before, within 1 week after, and up to 6 months after orchiectomy for prostatic carcinoma. Serum testosterone concentrations became unmeasurable (less than 40 ng/dl) after orchiectomy. Three of the 10 patients had transient increases of at least 50% in both serum dehydroepiandrosterone (DHA) and cortisol after orchiectomy, presumably due to surgical stress, but mean serum DHA and DHA sulfate (DHAS) did not increase in the group as a whole. Subsequently, serum DHA and DHAS concentrations were similar to preoperative values in all patients. Therefore, we find no evidence to support the hypothesis that adrenal androgen concentrations increase after orchiectomy.

Adrenal Glands↗

Lactoferrin biosynthesis during granulocytopoiesis.

We examined the synthesis of lactoferrin, an iron binding protein that, among hematopoietic cells, is restricted to secondary granules of polymorphonuclear leukocytes. Lactoferrin biosynthesis was absent from leukemic myeloblasts and promyelocytes but abundant in normal bone marrow and both the bone marrow and peripheral blood of patients with chronic myelogenous leukemia (CGL) if the samples contained substantial numbers of myelocytes and metamyelocytes. Lactoferrin was present in the steady state in normal or CGL bands and polymorphonuclear leukocytes, but no lactoferrin biosynthesis was detectable in these samples. Taken together, these results suggest that lactoferrin accumulation begins with the onset of biosynthesis at the myelocyte stage and is largely complete by the beginning of the band stage of maturation. HL-60 cells, a permanent promyelocytic leukemia cell line, synthesized no lactoferrin. Translation of messenger RNA in Xenopus laevis oocytes revealed that mRNA from patients with chronic myelogenous leukemia and abundant myelocytes and metamyelocytes directed the synthesis of readily detectable amounts of lactoferrin, whereas HL-60 cells contained no translatable lactoferrin mRNA. We thus hypothesize that lactoferrin is a useful marker of gene expression restricted to the terminal stages of granulocyte maturation. Biosynthesis of this protein appears to be mediated by appearance of translatable mRNA at the myelocyte stage, coincident with development of secondary granules. Absence of lactoferrin production by HL-60 cells is due to absence of translatable lactoferrin mRNA, either because of lineage infidelity of these transformed cells or because of arrest before the developmental stage at which secondary granules appear.

Animals↗

A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer.

The murine monoclonal antibody OC 125 reacts with an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinomas. An assay has been developed to detect CA 125 in serum. By this assay, only 1 per cent of 888 apparently healthy persons and 6 per cent of 143 patients with nonmalignant disease had serum CA 125 levels above 35 U per milliliter. In contrast, 83 of 101 patients (82 per cent) with surgically demonstrated ovarian carcinoma had elevated levels of antigen. In 38 patients with epithelial ovarian carcinoma monitored on 2 to 18 occasions during 2 to 60 months, antigen levels ranged from less than 1 to more than 8000 U per milliliter. Rising or falling levels of CA 125 correlated with progression or regression of disease in 42 of 45 instances (93 per cent). Determination of CA 125 levels may aid in monitoring the response to treatment in patients with epithelial ovarian cancer.

Adenocarcinoma↗

How useful is cerebrospinal fluid lactate estimation in differential diagnosis of meningitis?

Cerebrospinal fluid lactate (CSF) was measured by a rapid enzymatic method in 230 patients admitted with a suspected diagnosis of central nervous system infection. In all untreated cases of bacterial meningitis the levels exceeded 4.3 mmol/l and fell below 3.9 mmol/l in most patients with virus meningitis. We believe values of 3.9-4.3 mmol/l should be considered borderline as occasional CSF samples in cases of virus meningitis yield values in this range. However, distinction between untreated pyogenic meningitis and virus meningitis is rarely problematic in clinical practice, so routine use of the test as an emergency procedure offers no extra advantage. The test is unlikely to be of much help in differentiating partly treated bacterial meningitis from virus meningitis, but it is a valuable additional procedure for differentiating tuberculous meningitis from virus meningitis, highly modified bacterial meningitis and parameningeal septic states.

Brain Diseases↗

The nonmetropolitan plastic surgeon.

A questionnaire survey was conducted of 54 board-eligible or board-certified plastic surgeons practicing outside urban or suburban areas. Marketplace forces were determined to have been important in the choice of nonmetropolitan practice locations. The practitioners surveyed tended to participate in a broad spectrum of plastic surgical practice. On the whole, the surgeons reported themselves busy professionally and contented personally. A characteristic pattern of problems often accompanied the practice style.

Demography↗

Intraperitoneal immunotherapy of human ovarian carcinoma with Corynebacterium parvum.

Corynebacterium parvum has been administered i.p. to 14 patients with advanced ovarian cancer. Two patients had responded completely to cytoreductive surgery and combination chemotherapy prior to immunotherapy, and one patient with residual disease had received only a single course of C. parvum due to i.p. catheter malfunction. Among the 11 patients with residual disease evaluable for response, from three to eight i.p. treatments with C. parvum produced surgically confirmed tumor regression in five patients (45%) with three partial responses and two complete responses of 5 and 12 months duration. All responders had (a) multiple tumor nodules less than 0.5 cm at the initiation of immunotherapy, and (b) severe abdominal pain and fever after C. parvum injection. Overall, 58 courses of immunotherapy were associated with abdominal pain (91%), fever (67%), nausea (52%), vomiting (31%), and hypotension that responded promptly to i.v. infusion of fluids (10%). Use of i.p. cathethers was associated with two episodes each of infection and intraabdominal bleeding. Administration of C. parvum i.p. has augmented the ability of human peritoneal cells to lyse human ovarian carcinoma cell lines in the presence of specific rabbit heteroantiserum. C. parvum administered i.p. has inhibited the growth of human ovarian carcinoma and may prove useful for modulating the activity of human effectors for antibody-dependent cell-mediated cytotoxicity.

Adult↗

Decreased adrenal androgen sensitivity to ACTH during aging.

During the human aging process, basal plasma levels of cortisol and aldosterone demonstrate little change, while concentrations of adrenal androgens (AA) such as dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and androstenedione (A) decrease dramatically in men and women. There is no age-related change in ACTH concentrations to explain this observation. In this study, ACTH (cosyntropin, alpha1-24 corticotropin) stimulation tests were performed on elderly subjects and controls to test the hypothesis that analogous to the aging testicular. Leydig cell, AA-producing cells of the aging adrenal gland may become less sensitive to physiological levels of ACTH, but still retain their sensitivity to elevated ACTH levels. Results showed that in the elderly subjects, basal levels and ACTH-stimulatability of cortisol and aldosterone were unchanged. In agreement with earlier studies, basal levels of AA were found to be decreased in the elderly. However, ACTH stimulation demonstrated impaired reserve in DHA and A, and a total lack of stimulatability of DHAS. These findings could be explained by an age-related loss of adrenal enzymes or cell populations which produce AA, a loss or decrease in a subpopulation of ACTH receptors specific for AA production, or loss of a pituitary factor necessary for AA secretion.

Adrenal Glands↗

Psychiatric problems in third-year medical students.

Each year as many as one of four medical students experience sufficient emotional pain to seek psychiatric consultation. In many cases the precipitating stress relates to specific stresses associated with the phase of training. In the third year increased clinical responsibility may evoke feelings centered on caretaking, sexuality, and aggression that cannot be contained by an as yet fragile emerging professional identification. The authors present four case histories of third-year medical students to illustrate the complex interaction between family background, motivations to enter medicine, and the specific patient experience that resulted in sufficient distress to require psychiatric consultation.

Adjustment Disorders↗