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J I Allen

Publications and source records attributed to J I Allen.

17 recordsLinked to original sources
PubMed1991

Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients.

Although altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease, the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown. We, therefore, sought to correlate circulating concentrations of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients. We used an enzyme-linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin-1 and a bioassay to measure serum interleukin-6 in three groups of alcoholic men as follows: (a) actively drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking alcoholic men with stable cirrhosis and (c) patients with acute alcoholic hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease. Tumor necrosis factor-alpha and interleukin-1 alpha concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis, whereas interleukin-6 normalized in parallel with clinical recovery. Concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations. We could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia. Percentages of peripheral blood monocytes that reacted with monoclonal antibodies to CD25 (interleukin-2 receptor) and human lymphocyte antigen-DR were similar for alcoholic patients and controls. These data suggest that tumor necrosis factor-alpha and interleukin-1 alpha are related to some of the metabolic consequences of both acute and chronic alcohol-induced liver disease, whereas interleukin-6 is related to abnormalities seen in acute liver injury.

Adult↗
PubMed1990

Interaction between endogenous opioids and IL-2 on PHA-stimulated human lymphocytes.

Endogenous opioids exert a variety of extra central nervous system (CNS) functions, including modulation of some human lymphocyte functions. The latter opioid activity may result in elevation of human natural killer (NK) function (i.e. by beta-endorphin), which is reversed by an opioid antagonist, Naloxone. Since recent evidence has suggested both structural and functional similarities between lymphokines known to elevate human NK function (interferon and interleukin-2) and endogenous opioids, we investigated if Naloxone could modulate lymphokine-enhanced human NK activity. Naloxone blunted, in a dose-dependent fashion, the NK-enhancing activity of peripheral blood lymphocytes or large granular lymphocytes by recombinant interferon-alpha (IFN-alpha) or interleukin-2 (IL-2). Naloxone decreased the uptake of radiolabelled IL-2 receptors. beta-endorphin also decreased the binding of radiolabelled IL-2 or IL-2 receptor-positive human lymphocytes. Finally, labelled Naloxone was inhibited from binding to phytohaemagglutinin (PHA)-stimulated lymphocytes by either beta-endorphin or IL-2. These findings strongly suggest that human lymphocyte receptors for opioid, IFN or IL-2 molecules, once occupied, have distinct influences on the alternate receptor. In addition, these data further strengthen the potential role of CNS-mediated influences on the human immune system.

Binding, Competitive↗
PubMed1989

Peritoneovenous shunting as compared with medical treatment in patients with alcoholic cirrhosis and massive ascites. Veterans Administration Cooperative Study on Treatment of Alcoholic Cirrhosis with Ascites.

The optimal management of severe ascites in patients with alcoholic cirrhosis has not been defined. in a 5 1/2-year study, we randomly assigned 299 men with alcoholic cirrhosis, who had persistent or recurrent severe ascites despite a standard medical regimen, to receive either intensive medical treatment or peritoneovenous (LeVeen) shunting. We identified three risk groups: Group 1 had normal or mildly abnormal results on liver-function tests, Group 2 had more severe liver dysfunction or previous complications, and Group 3 had severe prerenal azotemia without kidney disease. For the patients who received the medical treatment and those who received the surgical treatment combined, the median survival times were 1093 days in Group 1, 222 days in Group 2, and 37 days in Group 3 (P less than or equal to 0.01) for all comparisons). For all the groups combined, the median time to the resolution of ascites was 5.4 weeks for medical patients and 3.0 weeks for surgical patients (P less than 0.01). Within each risk group, mortality during the initial hospitalization and median long-term survival were similar among patients receiving either treatment. However, the median time to the recurrence of ascites in Group 1 was 4 months in medical patients, as compared with 18 months in surgical patients (P = 0.01); in Group 2 it was 3 months in medical patients as compared with 12 months in surgical patients (P = 0.04). The median duration of hospitalization was longer in medical patients than in surgical patients (6.1 vs. 2.4 weeks in Group 1 [P less than 0.001] and 5.0 vs. 3.1 weeks in Group 2 [P less than 0.01]). Group 3 was too small to permit a meaningful comparison. During the initial hospitalization, the incidence of infections, gastrointestinal bleeding, and encephalopathy was similar among the medical and surgical patients. We conclude that peritoneovenous shunting alleviated disabling ascites more rapidly than medical management. However, survival was closely related to the severity of the illness at the time of randomization and was not altered by shunting.

Ascites↗
PubMed1989

Accumulation of colony-stimulating factor 1 in amniotic fluid during human pregnancy.

Colony-stimulating factor 1 is a hematopoietic growth factor that increases 1000-fold in the uteri of pregnant mice, and its receptor is abundantly expressed in the human placenta. The concentration of colony-stimulating factor 1 in amniotic fluid at 33 to 40 weeks (9.0 +/- 1.1 ng/ml) was twofold higher than that at 16 to 18 weeks gestation (4.1 +/- 0.5 ng/ml), whereas maternal serum colony-stimulating factor 1 levels did not rise significantly. Colony-stimulating factor 1 was detected in endometrial extracts from pregnant women and levels were higher than those in extracts from nonpregnant women.

Amniotic Fluid↗
PubMed1989

Detection of endogenous macrophage colony-stimulating factor (M-CSF) in human blood.

We have detected endogenous human macrophage colony-stimulating factor (M-CSF) in blood of normal individuals, using a novel RIA that accurately measures M-CSF concentrations as low as 60 U/ml (1.2 ng/ml) in the presence of serum proteins. The RIA uses an antibody to highly purified recombinant human M-CSF and is calibrated to a mouse bone marrow colony-forming assay. Ten samples of normal human blood plasma contained an average 118 +/- 9 U/ml of M-CSF, and similar concentrations were detected in serum prepared from the same individuals. RIA-positive samples contained biologically active M-CSF, as determined in a colony assay performed on mouse bone marrow cells. The M-CSF biological activity was removed by specific immune precipitation and inhibited by addition of M-CSF antibody. Physical characterization of plasma M-CSF was done by immunoblotting after partial purification on controlled pore glass and immunoaffinity chromatography. The major reduced protein species of plasma M-CSF had an apparent molecular weight of about 24 kd, and minor species of 30, 45, and 60-70 kd were also present. The RIA results on ten normal individuals suggest that endogenous circulating M-CSF is present at a low but detectable concentration. This RIA can be used to measure M-CSF in clinical samples that contain serum proteins and other growth factors that may interfere with accurate bioassay determinations.

Colony-Forming Units Assay↗
PubMed1988

Opiate antagonist nalmefene inhibits ethanol-induced flushing in Asians: a preliminary study.

Ethanol-induced flushing (EIF) occurs in up to 80% of Asians and is characterized by facial flushing, tachycardia, and increased cardiac output. Since endogenous opiates and prostaglandins may be mediators of flushing syndromes, we attempted to block EIF in four Asian flushers with single doses of either the opiate antagonist nalmefene, or the prostaglandin synthesis inhibitor indomethacin. Nonflushers (2 Caucasian, 2 Asian) and four Asian flushers were given on separate days water, ethanol (0.4 g/kg p.o.), ethanol plus nalmefene (2 mg i.v.), or ethanol plus indomethacin (50 mg p.o.). Ethanol concentrations of flushers and nonflushers were similar. Mean (+/- SEM) plasma acetaldehyde concentrations of flushers (28.2 +/- 11.8 microM) were significantly greater than nonflushers (1.4 +/- 0.5 microM) following ethanol ingestion (p less than 0.001). Ethanol alone always induced a significant rise in facial skin temperature [mean area under the curve (AUC) = 5142 +/- 648 % delta T x min, p less than 0.01] and of pulse (mean AUC = 1622 +/- 120 bpm x min, p less than 0.001) in flushers compared to water ingestion. A single dose of nalmefene (2 mg i.v.) but not indomethacin (50 mg p.o.), reduced the mean (+/- SEM) ethanol-induced rise in facial skin temperature of flushers by 58 +/- 14% (p less than 0.05) without changing plasma acetaldehyde concentrations. These data are preliminary evidence that the opiate antagonist, nalmefene, blocks some of the vascular manifestations of EIF without altering the elevated plasma concentrations of acetaldehyde.

Acetaldehyde↗
PubMed1987

Pseudomonas infection of the biliary system resulting from use of a contaminated endoscope.

Pseudomonas aeruginosa was present in bile cultures from 10 patients who had undergone previous endoscopic retrograde cholangiopancreatography in 1984. After environmental cultures and review of instrument disinfection, we traced the infections to a single endoscope contaminated with P. aeruginosa, serotype 10. Although the instrument had been cleaned repeatedly with an automatic endoscope cleaning machine, P. aeruginosa survived on residual moisture left in the channels of the endoscope. Contamination ended only after we began to manually suction alcohol through the endoscope before air drying. In 5 of 10 patients, P. aeruginosa caused clinical infections including gangrenous cholecystitis, abscesses, and death. We could identify no factor that distinguished symptomatic from asymptomatic patients. In asymptomatic patients, P. aeruginosa was recovered from gallbladder bile up to 2 mo after endoscopic retrograde cholangiopancreatography. As this P. aeruginosa epidemic was discovered retrospectively because we monitor bile cultures, we advocate this practice as part of endoscopic retrograde cholangiopancreatography procedures.

Bile↗
PubMed1987

Cimetidine modulates natural killer cell function of patients with chronic lymphocytic leukemia.

Peripheral blood natural killer (NK) activity in patients with B-cell chronic lymphocytic leukemia (B-CLL) is frequently low or absent. Because cimetidine (a histamine-2 antagonist) has been shown to alter human lymphocyte function in vitro, we decided to study cimetidine's effect on peripheral blood NK activity of patients with B-CLL and controls. We administered cimetidine orally (1.2 gm per day) to seven patients with B-CLL and 12 controls for up to 28 days. Peripheral blood NK activity of patients with B-CLL rose from a pretreatment level of 0.7 +/- 0.5 (mean +/- SEM) lytic units/10(6) cells (LU) to 8.7 +/- 2.4 LU (P less than 0.05) at day 28. Peripheral blood NK activity of controls decreased after 14 days of cimetidine treatment but returned to pretreatment levels by day 28. When peripheral blood cells from controls were exposed to cimetidine during in vitro incubation (10 micrograms/ml), mean NK activity was increased at 48 hours (54% +/- 22% increase over controls, n = 5, P less than 0.05). Single cell cytotoxicity assays revealed increased killing of target cells (but not effector-target conjugation) with cimetidine-exposed effector cells. These data suggest that cimetidine may be useful to augment peripheral blood NK activity for patients with B-CLL.

B-Lymphocytes↗
PubMed1986

The monoclonal antibody CJA3 down-regulates the susceptibility of human tumor cell lines to natural cell-mediated cytotoxicity.

While developing monoclonal antibodies (MoAb) to colorectal carcinoma (CRC) cells, we noted that one MoAb, termed CJA3, down-regulated natural cell-mediated cytotoxicity (NCMC) against CRC cell lines SW480 and SW620. The MoAb CJA3 was developed by immunizing a BALB/c mouse with fresh human colorectal adenocarcinoma cells. The antigen recognized by the MoAb CJA3 was expressed on several solid tumor cell lines and on one of the six lymphoreticular cell lines tested, but was not detected on normal peripheral blood lymphocytes (PBL). SDS-PAGE analysis of the antigen immunoprecipitated by the MoAb CJA3 from the CRC cell lines SW480 and SW620 and from the melanoma cell line MALME-3M revealed a component with a m.w. of 150,000. Preincubation of CRC cell lines SW480 and SW620 with the MoAb CJA3 for 16 hr reduced their susceptibility to NCMC by about 50%. Kinetic experiments showed that prolongation of the incubation of target cells with the MoAb CJA3 resulted in a time-dependent increase in the amount of MoAb bound. Maximum binding of the MoAb CJA3 was reached after 4 hr of incubation. The increase in antigen expression chronologically paralleled the decrease in NCMC target cell sensitivity, suggesting that the membrane alterations induced by the MoAb CJA3 were important for NCMC against these two cell lines.

Antibodies, Monoclonal↗
PubMed1986

Role of zinc supplementation in type II diabetes mellitus.

Zinc is required for normal immune function and taste acuity and enhances the in vitro effectiveness of insulin. Impaired immune function and taste have been reported in diabetic subjects, and decreased serum zinc levels and hyperzincuria occur in some diabetic subjects and animals. Subjects with type II diabetes were examined to determine whether the similar effects of zinc depletion and diabetes are causally related. Low serum zinc levels were found in 16 of 180 subjects (9 percent). There was no correlation between serum zinc and glycosylated hemoglobin levels. Natural killer cell activity did not differ between diabetic subjects (n = 28) and control subjects (n = 38) and did not correlate with serum zinc levels. T lymphocyte response to phytohemagglutinin was lower in diabetic subjects than in control subjects (70 +/- 10 versus 103 +/- 7 X 10(3) counts per minute) but was not lowest in those with the lowest zinc levels. Taste thresholds for hydrochloric acid, sucrose, sodium chloride, and urea were elevated in diabetic subjects (n = 28) versus control subjects (n = 10), but thresholds did not correlate with glycosylated hemoglobin or serum zinc levels. Zinc supplementation in nine diabetic subjects had no effect on the glycosylated hemoglobin level, natural killer cell activity, or taste thresholds, but it did increase mitogen activity in those with the lowest initial phytohemagglutinin responses. It is concluded that zinc deficiency occurs in a subset of subjects with type II diabetes but is not related to diabetes control and does not explain decreased taste acuity. Zinc deficiency may play a role in abnormal immune function in type II diabetes mellitus.

Adult↗
PubMed1986

Pills in the colon.

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Administration, Oral↗
PubMed1986

Naltrexone hydrochloride (Trexan): a review of serum transaminase elevations at high dosage.

In summary, evidence is presented associating typically asymptomatic and reversible elevations of serum transaminase values with high daily dosages of naltrexone. Statistical significance was found only between placebo and the 300 mg dosage. Subjects aged 40 years and over were significantly more likely to develop this finding than younger subjects. All subjects with significant elevations of transaminase values in these studies took daily naltrexone dosages higher than recommended for opioid addiction. The daily dosage of naltrexone recommended for opioid addiction did not cause abnormalities of serum transaminase values in these studies.

Adult↗
PubMed1985

Simultaneous presentation of relapsing Hodgkin's disease and treatment-related non-Hodgkin's lymphoma.

A 55-year-old white man was diagnosed in 1975 with Hodgkin's disease stage IIA, mixed cellularity. He was treated with 4,500 rads to an inverted-Y field followed by six cycles of MOPP and remained in complete remission. In 1983 a right axillary lymph node biopsy showed recurrent Hodgkin's disease, mixed cellularity. While receiving his initial chemotherapy he developed persistent epigastric distress. Endoscopic gastric biopsy demonstrated a diffuse large-cell non-Hodgkin's lymphoma. Surface marker studies confirmed the separate identity of these two malignant lymphoproliferative processes. This represents the first reported simultaneous occurrence of relapsing Hodgkin's disease with treatment-related non-Hodgkin's lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Association between urinary zinc excretion and lymphocyte dysfunction in patients with lung cancer.

Patients with bronchogenic carcinoma often have low serum zinc concentrations and sometimes have markedly elevated renal zinc losses. Since normal zinc metabolism is critical for the proper function of T lymphocytes and natural killer cells, the effect of zinc status on T cell phytohemagglutinin response and peripheral blood lymphocyte natural killer cell activity was studied in patients with lung cancer. Mean (+/- SEM) serum zinc concentration in 75 patients with cancer was 67.4 +/- 2.2 micrograms/dl versus 96.0 +/- 8.0 micrograms/dl for normal subjects. Patients with low serum zinc levels (less than 70 micrograms/dl) had significantly higher urine zinc excretion than patients with normal serum zinc levels (1,385 +/- 240 micrograms per 24 hours versus 392 +/- 107 micrograms per 24 hours) (p less than 0.001). This pattern of zinc concentrations (i.e., low serum zinc in combination with high urine zinc) is typical of patients with mild zinc deficiency, and suggests that a mild chronic zinc deficiency state was present in some of these patients. When lymphocyte data were analyzed according to serum zinc concentrations and urinary zinc excretion, low serum zinc concentration and high urine zinc excretion both correlated with depressed T cell phytohemagglutinin response (p less than 0.005 and p less than 0.001, respectively). For instance, mean maximal phytohemagglutinin response in patients with urinary zinc excretion of more than 700 micrograms per 24 hours was 22,132 +/- 3,201 cpm (n = 14) compared with 68,130 +/- 6,850 cpm for patients with normal zinc excretion (n = 7). Peripheral blood lymphocyte natural killer cell activity did not correlate with either serum or urine zinc values. Oral zinc sulfate (220 mg, three times daily for six weeks) was then administered to patients with hyperzincuria (mean = 992 micrograms per 24 hours). Zinc-supplemented patients had normalization of T cell phytohemagglutinin response after zinc therapy, whereas control patients demonstrated continued T cell dysfunction. Natural killer cell activity did not change in either group during the study period. These data suggest that a mild subclinical zinc deficiency state may exist in some patients with lung cancer and may be an important cause of abnormal T cell function. Furthermore, zinc supplementation may be useful to improve lymphocyte function in selected patients. Whether zinc supplementation would alter the course of the disease or the patient's prognosis is presently unknown.

Adenocarcinoma↗