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Biomedical subjects

R Hart

Publications and source records attributed to R Hart.

At least 109 records · Page 6Linked to original sources
PubMed1990

Soluble interleukin-2 receptor and soluble CD8 in liver cirrhosis and obstructive jaundice.

Activated lymphocytes secrete soluble interleukin-2 receptor (sIL-2R); CD8-positive lymphocytes secrete soluble CD8 (sCD8). Liver dysfunction in cirrhosis and obstructive jaundice is known to result in depressed cellular immunity. To evaluate whether this is due to real inactivation of the immune system, we measured sIL-2R and sCD8 in the serum of 46 patients with liver cirrhosis, 25 patients with obstructive jaundice, 32 patients with alcoholic liver disease without evidence of cirrhosis, 23 healthy persons and 43 patients with unrelated disease. sIL-2R in patients with cirrhosis (mean +/- s.e.m. 1499 +/- 140 U/ml) and obstructive jaundice (1517 +/- 204) was significantly increased compared with healthy subjects (363 +/- 29) and patients with unrelated diseases (685 +/- 92); sCD8 was significantly increased in patients with cirrhosis (737 +/- 63) but not in patients with obstructive jaundice (419 +/- 32) compared with healthy subjects (322 +/- 23) and patients with unrelated diseases (375 +/- 22). No difference was found between patients with cirrhosis due to alcohol abuse (n = 15) and chronic hepatitis B (n = 6). The Child-Pugh score had no significant influence on the sIL-2R or sCD8 value. In obstructive jaundice, sIL-2R correlated with alkaline phosphatase as marker of cholestasis (r = 0.43). These data show that in spite of the apparent depressed cellular immune defense both in liver cirrhosis and obstructive jaundice there is a general activation of the immune system but the CD8+ cell compartment is only activated in liver cirrhosis. The great changes of sIL-2R and sCD8 in liver dysfunction are important for the interpretation of studies using these serum proteins as markers for immune activation.

Adult↗
PubMed1990

Stimulation of the immune response in outpatients with hepatocellular carcinomas by low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (Echinacin) and thymostimulin.

Outpatients with inoperable far advanced hepato-cellular carcinomas (n = 5) were treated with LDCY--300 mg/m2 i.v. every 28 days-, echinacin--60 mg/m2 i.m.--and thymostimulin--30 mg/m2 i.m., day 3-10 after LDCY, then twice a week. Therapy was well tolerated by all patients. Their Karnofsky' index increased for 10% in the mean. A stable disease for more than 8 weeks was documented by abdominal ultrasonography in one patient. Serum levels of Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) did not increase in 2 patients. Median survival time was 2.5 months. One patient is still alive after 8 months. Absolute numbers of CD8+ cells significantly (p less than 0.02) decreased for 7% 1 day after LDCY, whereas CD4+ cells increased (p less than 0.02) from day 1-7. Numbers of natural killer (NK-) cells increased for 17% (p less than 0.05), their activity for 90% (p less than 0.05). Activities of peripheral polymorphs (p less than 0.05) increased for 27% and of Lymphokine Activated Killer (LAK-) cells for 180% (p less than 0.05).

Adjuvants, Immunologic↗
PubMed1989

Interleukin 4 inhibits the interleukin 2-induced production of its functional antagonist, interferon gamma.

Interferon gamma (IFN gamma) inhibits many effects of interleukin (IL)-4. Its production largely parallels cell proliferation but is regulated independently. As IL-4 inhibits several IL-2-induced effects including proliferation of human peripheral blood mononuclear cells, we investigated its influence on the IL-2-induced IFN gamma production. We found that both absolute IFN gamma production and IFN gamma production per proliferation unit (1000 cpm) in response to IL-2 were inhibited by IL-4. IL-2-induced interferon production was inhibited by IL-4 in both sheep red blood cell rosetting and non-rosetting cells. In bidirectional mixed lymphocyte culture, IL-4 alone enhanced proliferation but suppressed IFN gamma production. As 48% of IFN gamma-producing cells are known to show T cell phenotype, the nearly total inhibition of IFN gamma production is evidence for suppression of T cell response to IL-2. Additionally, we found that the inhibition of IL-2-induced proliferation by IL-4 was significantly more pronounced at low cell densities. Basal proliferation was only inhibited in serum-containing media. These data stress the importance of other lymphokines or accessory cells in the regulation of early lymphocyte activation.

Cells, Cultured↗
PubMed1989

Complications and protocol considerations in carbon monoxide-poisoned patients who require hyperbaric oxygen therapy: report from a ten-year experience.

We conducted a study to determine the type, incidence, and timing of complications that occur in patients who have a carbon monoxide (CO) exposure serious enough to require hyperbaric oxygen therapy (HBOT). Complication data were retrospectively collected from a ten-year period for 297 consecutive CO-poisoned emergency department patients who received HBOT. HBOT was indicated for 41% of the patients because of an elevated carboxyhemoglobin (COHb) level alone. Central nervous system dysfunction, including loss of consciousness, and/or cardiovascular dysfunction, was the criteria for HBOT in 59% of patients, regardless of their COHb level. The mean peak COHb level was 38 mg%, with 88% of patients having a peak COHb level greater than 25 mg%. The mortality rate was 6% in this case series. Cardiac arrest occurred in 8% of patients; all experienced their first arrest prior to HBOT. The 3% of patients who sustained an isolated respiratory arrest and those who had a myocardial infarction did so prior to HBOT. Several complications, however, occurred for the first time or as a recurrent event during HBOT. These included emesis (6%), seizures (5%), agitation requiring restraints or sedation (2%), cardiac dysrhythmias or arrests (2%), and arterial hypotension (2%). No patient's level of consciousness deteriorated subsequent to the initial resuscitation except for those who later had a generalized seizure. The most significant complication attributable to HBOT was tension pneumothorax, noted in three patients (1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Monoxide Poisoning↗
PubMed1988

Leucovorin and 5-fluorouracil as a treatment for disseminated cancer of the pancreas and unknown primary tumors.

Chemotherapy with leucovorin (100 to 200 mg) and 5-fluorouracil (30 mg/kg) every 2 wk produced four (three complete) objective responses among a group of eight patients with early metastatic pancreatic primary and unknown cancers. Complete remissions were associated with exceptionally long durations of survival, one in a patient failing prior combination chemotherapy. This treatment warrants testing because of its ease, scientific rationale, and the large population of patients with early metastatic pancreatic cancer for whom there is no accepted treatment. Early metastatic disease is defined as small metastatic lesions not immediately life threatening found in a physiologically intact patient. Controlled trials, demonstrating benefit associated with other 5-fluorouracil-containing regimens for patients with nonmetastatic stages of pancreatic cancer, provide a rationale for extending testing of leucovorin and 5-fluorouracil to other early stages of pancreatic cancer.

Adult↗
PubMed1988

[Vasoactive intestinal polypeptide influences human immunoglobulin secretion].

Blood lymphocytes from eight subjects were cultured for seven days and stimulated with Pokeweed mitogen. At the same time, vasoactive intestinal polypeptide (VIP) was added in rising concentrations (10(-12) M to 10(-6) M). Immunoglobulin concentrations were measured by ELISA in the remaining cultures. Mitogen-stimulated peripheral mononuclear cells were stimulated dose-dependent by VIP to a further significant rise of IgM secretion in six of the eight subjects. VIP had no influence in this respect on mononuclear cells that had not been prestimulated. This was, therefore, the first demonstration that VIP, in concentrations that occur in intestinal mucosa in certain circumstances, influences human immunoglobulin synthesis in vitro. These findings may provide a building stone towards a better understanding of local immunoregulatory events in the intestinal mucosa.

Cells, Cultured↗
PubMed1988

Substance P modulates lymphokine activities in supernatants of cultured human duodenal biopsies.

A duodenal biopsy culture technique was used to investigate the effect of substance P on lymphokine secretion by the human gut associated lymphoid tissue. Duodenal biopsies of 7 healthy volunteers were cultured in 1 ml medium each with Pokeweed mitogen (1 microgram/ml) for 4 days at 37 degrees C. Substance P (SP) was added in concentrations ranging from 10(-12) M to 10(-6) M. Media were changed every day. Interleukin (IL)-1 beta, IL-2 and IL-2-receptor activities were determined by means of specific ELISAs. Values were referred to 5 mg biopsy weight and expressed as per cent change of basal Pokeweed mitogen-pulsed supernatant activities. 10(-8) M and 10(-6) M SP led to a decrease of IL-1 beta activity (78 +/- 13.9% and 62.8 +/- 17.1%, respectively, alpha = 0.01 each). In contrast, 10(-8) and 10(-10) M SP showed an increase in IL-2 activity up to 182.9 +/- 94.5% and 295.6 +/- 144.7%, respectively. 10(-6) M and 10(-8) M SP enhanced IL-2 receptor activities by 81.5 +/- 70% and 40.9 +/- 11.8%, respectively (alpha = 0.05). The present data demonstrate for the first time distinct SP-mediated effects on lymphokine activities in supernatants of cultured human duodenal biopsies.

Adjuvants, Immunologic↗
PubMed1987

Substance P enhances interferon-gamma production by human peripheral blood mononuclear cells.

Substance P (SP), a neuropeptide widely distributed in the organism, has been shown to stimulate lymphocyte proliferation and immunoglobulin synthesis. However, the effect of SP on specific lymphokines is unknown. Therefore we investigated the influence of SP on mitogen-induced interferon-gamma (IFN-gamma) production in vitro. Peripheral blood mononuclear cells (PBMC) of healthy donors were isolated by density gradient centrifugation and cultured in supplemented RPMI 1640 medium with phytohemagglutinin (PHA) or pokeweed mitogen (PWM), 0.125 and 0.25 mg/liter each, and varying concentrations of SP (10(-12) to 10(-6) M). After 24 and 48 h, IFN-gamma was measured in the supernatant using radioimmunoassay. Results were expressed as percent change of controls. SP alone had no relevant IFN-gamma inducing properties. It enhanced the IFN-gamma production of PWM-stimulated cells significantly up to 18%. The maximal effect was observed at 10(-8) M. PHA-stimulated cells also increased their IFN-gamma production after addition of SP. However, due to great interindividual variations this effect did not attain statistical significance. Stimulation of IFN-gamma production by SP might be of physiological importance, since the effect was seen at concentrations comparable to those found in the body. Our data lend further support to the immunoregulatory functions of SP.

Cells, Cultured↗
PubMed1986

Eosinophilic infiltration with flame figures. A distinctive tissue reaction seen in Wells' syndrome and other diseases.

We report five cases, all male, of diverse clinical findings of scattered erythematous, violaceous, or centrally blue plaques. Eight biopsies from the five patients showed nodular or diffuse dermal and subcutaneous infiltration, predominantly of eosinophils and histiocytes, with "flame figures" composed of granules of eosinophils that surround collagen bundles, whose staining quality is thereby altered. Two patients were children, the younger only 18 months old. Three patients initially presented clinical evidence of insect bites, and in one of these the biopsy showed cutaneous pseudolymphoma underlying dermal changes of eosinophilic cellulitis. Eosinophilic infiltration with flame figures is a distinctive reaction to various stimuli. It may be seen in a wide variety of clinical conditions and is not confined solely to patients with Wells' syndrome, which may be an acceptable term for clinically typical cases. Eosinophilic infiltration with flame figures is preferred descriptively to identify the microscopic changes in Wells' syndrome and in other cases like that of our patient with pseudolymphoma, in which the cutaneous reaction may be secondary to some other disease.

Adult↗
PubMed1986

The use of clonidine in the treatment of neuroleptic-induced tardive dyskinesia.

A double-blind crossover comparison of clonidine and placebo was conducted in seven subjects afflicted with neuroleptic-induced tardive dyskinesia (TD). Subjects received either clonidine, 0.4 mg/day, or placebo for a period of 8 weeks and were then crossed over to the opposing treatment modality. The effects of clonidine on TD symptomatology could not be distinguished from those of placebo (p greater than 0.05). However, comparison of prestudy ratings of TD severity to poststudy ratings revealed a significant reduction in TD symptoms (p less than 0.01). Close analysis of the data indicates that clonidine's effect on TD may have carried over into the placebo phase of the study, masking any true differences between clonidine and placebo treatment. Other factors which may have contributed to the lack of significant findings are discussed.

Adult↗
PubMed1984

Characterization of lens proteins. IV. Analysis of soluble high molecular weight protein aggregates in human lenses.

Soluble proteins of individual human normal and nuclear cataractous lenses of 60-70-year-old subjects were collected for this investigation. The average wet weights of both the normal and nuclear cataractous lenses were found to be essentially identical, approximately 230 mg. When the lens proteins, either cortical or nuclear, were subjected to fractionation by Sephadex G-200 sf chromatography, six fractions (F-I to F-VI) were obtained and their respective molecular weights approximated. F-I, which contains alpha-crystallin and high molecular weight aggregates, was subsequently fractionated through a series of Bio-gel A chromatographic columns. The quantities of the proteins and the molecular weights of each fraction were obtained. All the proteins fractionated were subjected to SDS gel electrophoresis by which the molecular weights of the subunits were obtained. The distribution and molecular weights of proteins smaller than 0.2 X 10(6) showed certain changes, more noticeable in the nucleus than in the cortex, between the normal lens and nuclear cataractous lens. For the high-molecular-weight protein aggregates, the major fraction in the lens cortex was found to be in the 5-1.5 X 10(6) range, representing 10 and 12% of the total protein in the normal and cataractous lenses, respectively. The major fraction in the nucleus was found to be greater than 150 X 10(6), representing 11 and 19% for the normal and cataractous lenses respectively. The above data are presented for the first time to show the differences in distribution of the high-molecular-weight proteins in the cortical and nuclear regions, and their respective changes in cataractogenesis. Based upon these data, we are able to calculate the average molecular weights of (1) the soluble cortical and nuclear proteins and (2) the total soluble protein, in the normal and cataractous human lenses.

Aged↗