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Biomedical subjects

E Kaplan

Publications and source records attributed to E Kaplan.

At least 91 records · Page 5Linked to original sources
PubMed1995

Does thyroidectomy, radioactive iodine therapy, or antithyroid drug treatment alter reactivity of patients' T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases?

The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves' disease (GD) before and after thyroidectomy, 19 patients with GD before and after radioactive iodine (RAI) therapy, and 9 patients maintained euthyroid on antithyroid drugs (ATD). Twenty subjects matched for age and sex without known thyroid disease served as controls. In GD patients, the responses of peripheral blood mononuclear cells (PBMC) and TSH receptor (TSHR)-specific T cell lines to recombinant human TSHR extracellular domain, thyroglobulin, and TSHR peptides were examined on the day of surgery or RAI therapy (day 0) and also 6-8 weeks and 3-6 months thereafter. Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain. Six to 8 weeks after subtotal thyroidectomy, the number of patients' PBMC responding to any peptide and the average number of recognized peptides decreased. A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery. The responses of PBMC from Graves' patients before RAI therapy were less than those in the presurgical group. Six to 8 weeks after RAI therapy, the number of patients responding to any peptide and the average number of recognized peptides increased. Three to 6 months after RAI, T cell responses to TSHR peptides were less than those 6-8 weeks after RAI therapy, but still higher than the values on day 0. Responses of PBMC from patients with GD, maintained euthyroid on ATD, were lower than those before surgery or RAI therapy. The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment. TSHR antibody and microsomal antibody levels decreased after surgery, but increased after RAI therapy. The difference in the number of recognized peptides by patients' PBMC before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery. The decreased T cell reactivity to thyroid antigens after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer T cells. The increased T cell response after RAI therapy is probably epitope specific, rather than a response to the whole TSHR molecule. Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD, and the loss of recognition of one of these epitopes may be an early sign of immune remission and a predictor of euthyroidism.

Adult↗
PubMed1994

Combined modality treatment using BID radiation for locally advanced non-small cell lung carcinoma.

BACKGROUND: From February 1988 to August 1991, 82 patients were treated on Phase II trial of split-course multimodality treatment for locally advanced, non-small cell lung cancer (NSCLC). METHODS: Treatment consisted of twice-daily radiation (150 cGy/fraction) delivered with concomitant infusional cisplatin, etoposide, and fluorouracil for 1 week every third week. Patients were classified before initial treatment as either potentially resectable (eligible for surgery [ES]) or ineligible for surgery (IES). The ES group consisted of 38 Stage IIIA and 7 Stage IIIB patients. The IES group had 5 patients staged as IIIA and 32 staged as IIIB. Most patients were staged clinically. ES patients received three cycles of treatment (39 Gy) before resection. IES patients received four cycles (60 Gy) delivered with curative intent. RESULTS: Thirty-nine of 45 ES patients underwent resection. The pathologic response rate was 27%. Three-year actuarial local control was 86% for 41 evaluable ES patients. Three-year actuarial survival for the whole ES group was 39%, with a median follow-up for living patients of 32 months. The IES group faired less well, with an 18% 3-year actuarial survival. Treatment was well tolerated with a median weight loss of one-half pound, mild or moderate pneumonitis in 5%, mild esophagitis in 15%, and severe nausea and/or vomiting in 10% of patients. Treatment-related mortality was 5%. CONCLUSIONS: Patients treated with conventional radiation alone for Stage III NSCLC are rarely cured. This well tolerated Phase II study demonstrated encouraging results for such patients. Both local control and survival appeared promising, especially in patients rendered resectable after combined-modality treatment.

Adult↗
PubMed1994

[Diagnosis and misdiagnosis in familial dysautonomia].

The method of diagnosis in 122 patients with familial dysautonomia (FD) was reviewed. In all cases the diagnosis was based on the clinical history, physical examination and results of the histamine test (concentrations of 1:1,000 and 1:10,000). In 8 patients the diagnosis was also supported by a meiotic response to pilocarpine (0.0625 mg/dl). 69 (56%) were diagnosed in the first year of life (19 of them relatives of known FD patients), 16 (13%) in the second year, 31 (25%) from 25 months to 10 years, 3 (2%) from 10.1-20 years, and 3 from 20.1-44 years. At diagnosis the mean age was 2.9 years (SD 5.84) and the median age 11 months. In 17 diagnosis was delayed by an average of 18.5 months (SD 16.9) from the time FD was initially suspected, mainly because of false interpretation of the histamine test. Early correct diagnosis is essential to prevent unnecessary morbidity and mortality from FD.

Adolescent↗
PubMed1994

Primate antibodies to components of the human immune system.

The feasibility to raise nonhuman primate antibodies against selected components of the human immune system was tested. The immunogens were whole cells (human T lymphocytes) or purified, recombinant human proteins (cytokines: TNF alpha or GM-CSF; soluble forms of cell surface antigens: sCD4 or sCD25). Significant immunizations, yielding functionally relevant antibodies, were readily achieved in rhesus monkeys, but, not surprisingly, may be less frequent in chimpanzees. The results suggest a general strategy for production of therapeutically useful MAB.

Animals↗
PubMed1993

On the molecular origin of photoreceptor noise.

Retinal photoreceptors are noisy. They generate discrete electrical events in the dark indistinguishable from those evoked by light and thereby limit visual sensitivity at low levels of illumination. The random spontaneous events are strongly temperature-dependent and have been attributed to thermal isomerizations of the vitamin A chromophore of rhodopsin, the light-sensitive molecule in photoreceptors. But thermal generation of dark events in both vertebrate and invertebrate photoreceptors requires activation energies in the range of 23 to 27 kcal mol-1, which are significantly less than the energy barrier of 45 kcal mol-1, for photoisomerization of the chromophore of native rhodopsin. We propose that photoreceptor noise results from the thermal isomerization of a relatively unstable form of rhodopsin, one in which the Schiff-base linkage between the chromophore and protein is unprotonated. This molecular mechanism is supported by both theoretical calculations of the properties of rhodopsin and experimental measurements of the properties of photoreceptor noise.

Animals↗
PubMed1993

Response variability in retinal ganglion cells of primates.

The signal encoded by a sensory neuron is usually characterized as the cell's average response to repeated presentations of a stimulus. However, each stimulus presentation elicits a slightly different response. This response variability may obscure the signal represented by neural activity, but it might also be an important aspect of a neuron's message and in some instances may even serve useful function. Here we present evidence that response variability (noise) in primate retinal ganglion cells at photopic light levels is (i) independent of the amplitude of either the stimulus or the response and is therefore additive, (ii) independent of receptive field size and retinal eccentricity, and (iii) similar for all primate ganglion cells. Our results show that the primate retina maintains a uniform noise level across the entire visual field and suggest that the noise originates within the ganglion cells themselves.

Acoustic Stimulation↗
PubMed1993

Interleukin-1 pretreatment protects against endotoxin-induced hypotension in rabbits: association with decreased tumor necrosis factor levels.

Rabbits were infused with either low-dose recombinant human interleukin (IL)-1 beta or vehicle 16 h prior to receiving lipopolysaccharide (LPS). In controls pretreated with vehicle, mean arterial pressure decreased to 68% of the baseline value by 90 min after LPS infusion and remained low for the duration of the study period. In IL-1-pretreated animals, a similar decrease in mean arterial pressure to 69% was observed at 60 min but returned to 90% of baseline after 180 min (P < .05). IL-1-pretreated animals showed no significant rise in serum tumor necrosis factor after LPS infusion compared with vehicle-treated animals (P < .05). Rabbits were pretreated as above with IL-1 and, 40 h later, plasma was transfused into a second group of rabbits just prior to LPS infusion. An infusion of post-IL-1 plasma did not reduce LPS-induced hypotension. Thus, pretreatment with IL-1 reduces the hypotension in response to LPS by a mechanism that is not plasma-mediated but that is associated with reduced serum tumor necrosis factor levels.

Animals↗
PubMed1993

Idarubicin/cytosine arabinoside and mitoxantrone/etoposide for the treatment of de novo acute myelogenous leukemia.

Since January 1989, 56 patients (31 females and 25 males) with de novo acute myelogenous leukemia have been included in the study. Their median age was 43 years (range, 15 to 60 years) with a distribution according to French-American-British morphologic subtypes as follows: six M1, 14 M2, four M3, 19 M4, nine M5, two M6, and two M7. The induction regimen (IDAC) consisted of idarubicin (12 mg/m2/d intravenously [IV] days 1 to 3) in combination with cytarabine (100 mg/m2/d continuous IV days 1 to 7). Patients achieving complete remission (CR) or partial remission received another cycle of IDAC followed by NOVE (mitoxantrone 10 mg/m2/d IV days 1 to 5 and etoposide 100 mg/m2/d IV days 1 to 5). Fifty-four patients are evaluable for response: after two cycles of IDAC, 42 patients had attained CR (78%), while 76% of these had already reached CR after the first cycle. Of the initial 11 nonresponders to IDAC, four obtained CR after NOVE. Thus, 46 of 54 patients (85%) achieved CR after sequential treatment with IDAC and NOVE. In the last 17 patients who entered CR or partial remission after the first cycle of IDAC, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 3 micrograms/kg/d) was administered for 6 days starting 3 days prior to the second cycle of IDAC. For consolidation with NOVE, rhGM-CSF was given according to the same dosage schedule. After 72 hours of rhGM-CSF treatment, the white blood cell count showed a median 3.9-fold increase, without appearance of myeloblasts in the peripheral blood. During sequential chemotherapy, no significant complications (in particular, no major cardiac toxicity) were observed. Postremission, patients were either given bone marrow transplants, received late consolidation with high-dose cytarabine/mitoxantrone, or were followed up without any further treatment. Of the 46 patients evaluable for disease-free survival, 21 patients (45%) remain in CR with a 34% probability of disease-free survival at 37 months. The response-adapted treatment with IDAC/NOVE is effective and very well tolerated. To define the therapeutic impact of rhGM-CSF, a randomized trial will be required.

Acute Disease↗
PubMed1992

Combined modality therapy for stage III non-small cell lung carcinoma: results of treatment and patterns of failure.

Patients with Stage III non-small cell lung carcinoma continue to pose a therapeutic problem with dismal cure rates. In an effort to improve on these results, 129 patients with biopsy-proven clinical Stage III non-small cell lung carcinoma from November 1982 through November 1987, were entered into two consecutive Phase II studies at Rush-Presbyterian-St. Luke's Medical Center. Treatment in the first study consisted of Cisplatin and 5-Fluorouracil infusion with concomitant split course radiation; in the second Etoposide was added. Radiation and chemotherapy were given simultaneously on days one through five of each cycle in a preoperative fashion for four cycles in patients considered eligible for surgery and in a definitive fashion for six cycles in patients considered ineligible for surgery. Radiation was given in 2 Gy fractions for a planned preoperative dose of 40 Gy and a definitive dose of 60 Gy. Surgical resection was attempted four to five weeks later in patients treated preoperatively. Thus, 83 patients were treated preoperatively and 46 definitively. Eighty-three patients (64%) had IIIA disease and IIIB disease was found in the remainder of the patients. Sixty-two patients (75%) in the eligible for surgery group had a thoracotomy after the combined treatment with a resectability rate of 97% and an operative mortality rate of 5%. There were 17 patients (27%) with no evidence of residual cancer in the resected specimen. Three-year survival for the eligible for surgery group at 40% was significantly better than 19% observed in the ineligible for surgery group (p = 0.003). Seventy-six percent of the patients with no residual cancer in the resected specimen are recurrence-free at three years compared to 34% of the patients with gross residual. A total of 81 patients have failed after their treatment; 49 (59%) in the eligible for surgery group and 32 (70%) in the ineligible for surgery group. Of all the patients who failed, local failure alone and as a component occurred in 21 (26%) and 36 (44%) patients, respectively. Failure in distant sites alone was noted in 56% of the overall failures. Severe toxicity was unusual. There were three treatment related deaths (2%). Radiation esophagitis and pneumonitis were only mild to moderate seen in less than 10% of the patients. Survival rates and patterns of failure according to the stage of the disease, histology, treatment group and pathologic response will be presented in detail.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Contrast gain control in the primate retina: P cells are not X-like, some M cells are.

Primate retinal ganglion cells that project to the magnocellular layers of the lateral geniculate nucleus (M) are much more sensitive to luminance contrast than those ganglion cells projecting to the parvocellular layers (P). We now report that increasing contrast modifies the temporal-frequency response of M cells, but not of P cells. With rising contrast, the M cells' responses to sinusoidal stimuli show an increasing attenuation at low temporal frequencies while the P cells' responses scale uniformly. The characteristic features of M-cell dynamics are well described by a model originally developed for the X and Y cells of the cat, where the hypothesized nonlinear feedback mechanism responsible for this behavior has been termed the contrast gain control (Shapley & Victor, 1978, 1981; Victor, 1987, 1988). These data provide further physiological evidence that the M-cell pathway differs from the P-cell pathway with regard to the functional elements in the retina. Furthermore, the similarity in dynamics between primate M cells and cat X and Y retinal ganglion cells suggests the possibility that P cells, being different from either group, are a primate specialization not found in the retinae of lower mammals.

Animals↗
PubMed1992

Neuropsychological and neuroanatomical dimensions of ideomotor apraxia.

Fifty-five right-handed men with left hemisphere stroke were systematically investigated for ideomotor apraxia of various body parts. Standardized aphasia and apraxia examinations in all cases, and appropriately timed CT in 28 cases, were used for analysis of psychological and anatomical properties of ideomotor apraxia. It is not possible to ignore the modality of eliciting the movement (command or imitation) and the body part being moved (buccofacial, limb or whole body) from any comprehensive theory about ideomotor apraxia. Different levels of performance are seen with different body parts to different modalities in different aphasic groups. Some subtypes of ideomotor apraxia (buccofacial) have highly specified anatomical basis. Some (limb) have apparently distributed anatomies, and others (whole body) have as yet unknown bases.

Adult↗
PubMed1992

Distribution of polysaccharide side chains of lipopolysaccharide determine resistance of Escherichia coli to the bactericidal activity of serum.

The lipopolysaccharide (LPS) of serum-sensitive strains of Escherichia coli was compared with LPS derived from serum-resistant clones. Polysaccharide O-antigen side chains (PSSC) of LPS from serum-resistant clones contained 12%-40% more of the longer carbohydrate molecules (L-PSSC) than did LPS from serum-sensitive parent strains; in contrast, 12%-27% more of the shorter PSSC (S-PSSC) were found in LPS from serum-sensitive strains. The sensitivity or resistance to the bactericidal activity of human serum correlated with the distribution and the length of PSSC fractions of LPS. This was demonstrated in a liposome model in which LPS was incorporated into simulated bacterial membranes. The incubation of serum with liposomes incorporated with various ratios of S-PSSC-to-L-PSSC concentrations resulted in liposomal lysis at S-PSSC-to-L-PSSC ratios greater than 2:1. These findings demonstrate the importance of the length of carbohydrate side chains of LPS in determining sensitivity or resistance to the bactericidal activity of human serum.

Blood Bactericidal Activity↗
PubMed1992

Randomized phase II trial of high-dose 4'-epi-doxorubicin + cyclophosphamide versus high-dose 4'-epi-doxorubicin + cisplatin in previously untreated patients with extensive small cell lung cancer.

One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospective randomized study with the aim to assess the efficacy and tolerance of high-dose epirubicin (120 mg/m2) in combination with either cyclophosphamide (800 mg/m2; arm 1) or cisplatin (60 mg/m2; arm 2). Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only. The overall response rate (CR+PR) in arm 1 and 2 were 61.4 (27/44) and 67.3% (35/52), respectively. The mean duration of remission was 4.4 months (arm 1) and 4.9 months (arm 2). The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8% of patients in arm 1 and 2, respectively. One case of cardiotoxicity resulting in the patient's death was observed in arm 1. Both combinations showed considerable antitumor activity. Toxicity was acceptable.

Adult↗