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Biomedical subjects

J Halpern

Publications and source records attributed to J Halpern.

At least 91 records · Page 5Linked to original sources

Human peripheral blood mononuclear cells (PBM) cultured in serum-free medium. III. Morphological study of an in vitro microcytotoxicity model.

An in vitro tumor immunity model is suggested. Interactions between lymphocytes and macrophages in serum-free medium are being studied as well as the effect induced upon these interactions by the addition of heterologous and homologous tumor cells. In our model, the tumor cells seem to be approached by the lymphocytes before any contact with the macrophages and then presented to the latter. The macrophages may then acquire an "activated" structure and display cytotoxic properties. A pattern of in vitro cellular immunity is obtained. This description may serve as a model for further study and understanding of the process of tumor immunity. It is suggested that in contrast to generally accepted models of cellular immunology, lymphocytes can interact directly with antigen complexes and present them to macrophages. The latter would in turn be activated, become cytotoxic and produce or accumulate immune globulins. These cells seem to be an in vitro analog of the recently described tumor infiltrating lymphocytes (TIL) which reside in vivo within spontaneous tumors.

Cell Communication↗

Choroidal metastases arising from carcinoma of the breast. Review and analysis of five cases.

Five cases of breast carcinoma metastasizing to the choroid were investigated and compared with the current literature. Choroidal metastases were found to bear an unfavorable prognostic factor (median survival of 11 months), and are related to heavy metastatic involvement even when the latter is not evident. Two patients responded to treatment, one to irradiation and one to systemic chemotherapy. The peak incidence is in perimenopasual women (mean age 48.2) which suggests that in this group of patients ocular examination may be advised for the routine followup.

Adenocarcinoma↗

Congenital see-saw nystagmus associated with retinitis pigmentosa.

Two sibling patients with see-saw nystagmus associated with advanced retinitis pigmentosa are presented. The see-saw nystagmus was most likely congenital but demonstrated a torsional pattern different from that previously reported for congenital see-saw nystagmus. Anatomic and etiologic factors associated with see-saw nystagmus are discussed.

Adult↗

Mechanisms of coenzyme B12-dependent rearrangements.

Coenzyme B12 serves as a cofactor in various enzymatic reactions in which a hydrogen atom is interchanged with a substituent on an adjacent carbon atom. Measurement of the dissociation energy of the coenzyme's cobalt-carbon bond and studies of the rearrangement of model free radicals related to those derived from methylmalonyl-coenzyme A suggest that these enzymatic reactions occur through homolytic dissociation of the coenzyme's cobalt-carbon bond, abstraction of a hydrogen atom from the substrate by the coenzyme-derived 5'-deoxyadenosyl radical, and rearrangement of the resulting substrate radical. The only role thus far identified for coenzyme B12 in these reactions--namely, that of a free radical precursor--reflects the weakness, and facile dissociation, of the cobalt-carbon bond.

Carbon↗

Human peripheral blood mononuclear cells (PBM's) cultured in serum free medium (II): Lymphocyte-macrophage interaction and related morphological changes.

Morphological descriptions of the attachments between lymphocytes and macrophages are made in serum free cultures. Dynamic morphological processes related to these attachments are explored in live cells using an inverted microscope and the phase technique. The May Grunwald-Giemsa stain and scanning and transmission electron microscopy are also described for the same population of cells. Immunoglobulins were detected in the cells by the immunoflourescence technique. Following lymphocyte-macrophage attachments, the macrophages shrink and round up and subsequently, their cytoplasm becomes laden with immunoglobulin. The membrance surface of interacting macrophages gradually changes from the ruffled appearance characteristic of a monocyte to a blebbed structure. The blebs seem to be related to an exocytotic process, which is most probably immunoglobulin secretion.

Cell Communication↗

Quantitation of maternal-fetal IgG transport in the chicken.

Quantitative and temporal features of maternal-fetal transport of IgG in the chicken have been determined by means of a sensitive and specific radioimmunoassay. The first step in this two-step process is the transport of maternal IgG from the hen plasma across the oolemma into the maturing oocyte in the ovarian follicle. Oocytes sequester IgG throughout most of their maturation from 10 mg pre-vitellogenic oocytes to fully mature 20 g oocytes ready to be shed into the oviduct. IgG uptake is exactly proportional to mass accumulation at every point. Thus, the concentration of IgG in the yolk is invariant throughout maturation of the oocyte (approximately 8 mg/ml) and the rate of uptake in this single specialized cell can be as great as 45 mg/day during its last 3 days of growth before ovulation. The second step, uptake of yolk IgG across the yolk sac and into the fetal circulation, is detectable at the earliest time points tested (Day 7), but accumulation into the embryonic plasma occurs at a relatively low rate (less than 100 micrograms/day) until a dramatic increase in uptake (greater than 600 micrograms/day) occurs in the last 3 days before hatching. The hatchling has 1-2 mg/ml of maternal IgG in its plasma. Increase in IgG uptake lags significantly (approximately 4 days) behind increase in mass by the developing embryo, suggesting that IgG uptake occurs predominantly in the last few days before hatching. This ensures that the hatching is endowed with those maternal IgGs which will be its planopy when it enters the hostile world.

Animals↗

Evaluation of topically applied (AET) 2-aminoethyl-iso-thiouronium for radiation protection of the skin. A preliminary study in pigs.

AET (Aminoethyl-iso-thiouronium) was applied topically on irradiated pig skin in different vehicles (emulsions and solutions) for testing a protective effect. A simple normal saline solution (200 mg/100 ml) proved to exert the best effect, both macroscopically and histologically. The solution was applied two hours and immediately before the irradiation which consisted of one 2000 rad fraction with a 20 MeV electron beam. A protective effect was noticed only in the superficial epithelial layers, the deeper radiobiological effect remained unaltered.

Animals↗

Multivariate analysis of factors associated with outcome of treatment for adults with acute myelogenous leukemia.

Utilizing multivariate logistic regression statistical analysis, the authors evaluated prognostic features associated with achievement of complete remission (CR) and remission and survival duration in acute myelogenous leukemia (AML). These clinical variables were analyzed in 77 consecutive adult patients who underwent 108 courses of remission induction therapy with daunomycin, cytosine arabinoside, and 6-thioguanine (DAT) chemotherapy for newly diagnosed and first relapse of AML. Eight patients had developed leukemia in the setting of other malignant or immunologic diseases (therapy-linked AML) and 69 patients had not (primary AML). Sixty-three percent of patients with primary AML achieved CR with median remission and survival durations of 11 and 24 months, respectively. Significant unfavorable predictive features for achievement of CR were splenomegaly, and elevated leukocyte count or serum alkaline phosphatase levels. Patients who had leukocyte counts of less than or equal to 10,000/mm3 at diagnosis or less than or equal to 40,000/mm3 at the start of therapy, and those who received greater than 120 mg/m2 of daunomycin had significantly longer remissions and survival than those who did not. Fifty-seven percent of patients in first relapse also achieved CR; however, relative to first remissions, second remission durations were significantly shorter (median, 4.6 months). Sixty-two percent of patients with therapy-linked AML achieved CR, but remission durations (median, 2.8 months) were significantly shorter than first remissions of primary AML patients. These data identify clinical features associated with increased risk of failure to achieve CR and potential for short remission duration and survival. Alternative forms of therapy should be considered for such high-risk patients.

Adolescent↗

Primary Kaposi's sarcoma of the lung in an immunocompetent 32-year-old heterosexual white man.

Primary visceral involvement by Kaposi's sarcoma in the immunocompetent adult American population is extremely rare. Six cases of primary Kaposi's sarcoma of the lung have been previously reported; all four patients in whom immune function was evaluated had abnormalities. A case of primary Kaposi's sarcoma of the lung in a young adult heterosexual man with normal immunologic function is described. The patient had no response to either weekly vinblastine or doxorubicin (Adriamycin). A subsequent solitary right occipital metastasis responded to 3500 rad of radiotherapy. The patient died 3 months after diagnosis; postmortem examination revealed only two small nodules of extrathoracic Kaposi's sarcoma, one in the liver and the other in the right posterior occipital lobe of the brain. Bacterial, mycobacterial, fungal, and viral cultures were negative.

Adult↗

Malignant fibrous histiocytoma developing in irradiated sacral chordoma.

Malignant fibrous histiocytoma (MFH), arising at the site of a sacral chordoma 8 years after massive radiotherapy, is described. Initially, the patient received 7000 rad to the sacral area and, on recurrence, 5 years later, an additional 4000 rad. Two years later, a sacral mass was noted again. Biopsy then revealed MFH; chest x-ray showed multiple lung metastases. A combination chemotherapy, consisting of cyclophosphamide, vincristine, adriamycin (doxorubicin), and DTIC, resulted in a 6 month partial response. Subsequently, the patient died because of progressive metastatic disease. At autopsy, 8 years after diagnosis, both the sacral lesion and the lung metastases proved to be MFH, and no residual chordoma was found.

Aged↗

Procarbazine, CCNU and vincristine (PCV) combination chemotherapy for brain tumors.

12 patients with brain tumors were treated with a combination of procarbazine, CCNU (bis-2-chloroethyl-3-cyclohexyl-1-nitrosourea) and vincristine. 3 of 8 patients (37.5%) with primary brain tumors responded to chemotherapy, with a mean duration of 9.3 months. The mean survival of responders was 11.7 months, versus 3.6 months for nonresponders. 4 patients with metastatic brain tumors were also treated with the same combination chemotherapy; only 1, suffering from a lymphoma of the brain, responded partially.

Adult↗

Characterization of thyroid hormone stimulation of uridine uptake by rat pituitary tumor cells.

T3 caused a dose-related increase in the rate of [3H]uridine uptake into GH4C1 rat pituitary tumor cells. T3 increased uridine uptake to 130-180% of the control value, with a half-maximal effect at approximately 1 nM. T3 exerted a half-maximal effect at 1 h and a maximal effect at 2 h. In contrast, epidermal growth factor also increased uridine uptake by 75%, with an ED50 of 0.6 ng/ml (0.1 nM), but a half-maximal response required 4 min and a maximal effect required 20 min. T3 increased the rate of uptake at all uridine concentrations from 30 nM to 130 microM. Equilibrium binding of [125I]T3 to nuclear receptors required from 15 min at 50 nM [125I]T3 to 1 h at 0.5 nM, indicating that occupancy of nuclear receptors precedes maximal stimulation of uridine uptake. T3 did not stimulate the rate of uridine uptake at 20 C, when binding to nuclear receptors does not occur. Various thyroid hormones caused an increase in uridine uptake, with the rank order of potency 3,3',5-triiodothyroacetic acid greater than T3 greater than L-T4 greater than D-T4 approximately equal to 3,3',5,5'-tetraiodothyroacetic acid; rT3 was inactive. This order parallels the affinities of these compounds for nuclear thyroid hormone receptors.

Animals↗

A call for caution in the use of aminoglutethimide: negative interactions with dexamethasone and beta blocker treatment.

Two case reports are described, both breast carcinoma patients with metastatic disease. One of the patients had a dexamethasone dependent brain metastatic condition. The second patient suffered from high blood pressure, which was controlled with beta-blocker drugs. Both patients developed severe complications when treated with aminoglutethimide as a cancer hormonal therapy. The case reports are described and possible drug interaction mechanisms are discussed.

Adrenergic beta-Antagonists↗