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Biomedical subjects

M A Berman

Publications and source records attributed to M A Berman.

At least 19 recordsLinked to original sources

Mechanism of a lymphocyte abnormality associated with HLA-B8/DR3: role of interleukin-1.

Lymphocytes from normal individuals with the histocompatibility antigens HLA-B8 and DR3 have impaired proliferative responses when stimulated with suboptimal concentrations of mitogens. We have previously shown that an important factor in the impaired response is a failure to produce normal quantities of interleukin-2 (IL-2). To examine the mechanism of decreased responsiveness further, we measured interleukin-1 (IL-1) production of low responder subjects compared with controls. The peripheral blood mononuclear cells of five low responder individuals with HLA-B8/DR3 stimulated with 0.05 micrograms/ml of phytohaemagglutinin (PHA) accumulated only 0.036 U/ml of IL-1 compared with 0.32 U/ml for normal responders. There was a highly significant correlation between the PHA-stimulated IL-1 concentration at 12 h and the subsequent IL-2 concentration at 48 h(r = 0.89, P less than 0.0001) suggesting a role of decreased IL-1 production in the impaired response. A study of unfractionated or column-fractionated culture supernatants revealed no evidence that the decreased IL-1 activity in the supernatants of low responder subjects was related to increased IL-1 inhibitor concentrations. These results suggest that impaired IL-2 production and lymphocyte proliferation in healthy subjects with HLA-B8/DR3 may be mediated at least in part by decreased IL-1 production, and implicates a defect of a very early event in lymphocyte activation.

Adult

Interleukin-1 and a 7-kDa T-cell inhibitory monokine reflect disease activity in infection with HIV-1.

Previous studies demonstrated that cultured peripheral blood mononuclear cells (PBMC) from patients with AIDS produce high levels of interleukin 1 (IL-1) and a 7-kDa T-cell inhibitory monokine (TCIM). To determine if the increase in the production of these cytokines corresponded with disease activity, we studied the production of IL-1 and TCIM by PBMC from patients with different stages of human immunodeficiency virus (HIV) infection. Eight patients with asymptomatic seropositive infection, three patients with AIDS-related complex (ARC), three patients with persistent generalized lymphadenopathy (PGL), and six patients meeting the full criteria for diagnosis of AIDS were studied. Patients with AIDS produced increased amounts of TCIM (4.1 times control values, p less than 0.003) and IL-1 (2.0 times control values, p less than 0.05). In contrast, asymptomatic seropositive patients produced less TCIM (0.36 times control values, p less than 0.004) and IL-1 (0.61 times control values, p less than 0.05). Different trends in the levels of these factors produced by patients with ARC and PGL were noted, although results were not statistically significant in general. Patients with ARC tended to produce less IL-1 (0.42 times control values, p less than 0.05), whereas patients with PGL tended to produce increased amounts of IL-1 (1.7 times control values, NS). ARC patients produced a wide range of TCIM values (0.05-2.8 times control values, NS), and patients with PGL tended to produce increased TCIM values, (4.0 times control values, p less than 0.02). No correlations between the levels of IL-1 or TCIM and T-cell subpopulation numbers (CD4 or CD8) or CD4/CD8 ratios were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

Modulation of IL-1 alpha, IL-1 beta, and 25K Mr non-IL-1 activity released by human mononuclear cells.

To determine if the release of IL-1 alpha and IL-1 beta by cultured PBMC could be independently modulated by different exogenous stimuli, we examined the effect of LPS, IFN gamma, latex beads, and indomethacin on the release of IL-1 alpha and IL-1 beta. PBMC culture supernatants were fractionated by Sephacryl-S-200 column chromatography or HPLC (TSK G3000SW), and each fraction was tested for thymocyte mitogenic activity in the presence or absence of preincubation with anti-IL-1 alpha or anti IL-1 beta monoclonal antibody (mAb) and for the presence of IL-1 alpha or IL-1 beta protein by ELISA. In all experiments, thymocyte mitogenic activity not neutralizable by anti-IL-1 alpha or anti-IL-1 beta mAb was detected in the 25K Mr range, which ranged from 12 to 50% of the total thymocyte mitogenic activity released, depending on the stimuli. Cultured PBMC from 95% of individuals release thymocyte mitogenic activity in the absence of exogenous stimuli, which was increased 1.3-to 7-fold by lopopolysaccharide (LPS) (25-50 micrograms/ml). All of this increased activity was due to increased release of IL-1 beta and non-IL-1 thymocyte mitogenic activity, with no change in the total amount of IL-1 alpha released. Indomethacin (0.1 microgram/ml) induced release of increased thymocyte mitogenic activity of 1.3- to 1.4-fold over unstimulated cultures. All of this increased activity was due to increased release of IL-1 alpha and non-IL-1 activity with a concomitant decrease in IL-1 beta release. Interferon gamma (40-100 U/ml) increased the amount of IL-1 alpha and decreased IL-1 beta and non-IL-1 activity released, resulting in no overall change in the total amount of thymocyte mitogenic activity. Molecular weight fractionation of the PBMC culture supernatants revealed that thymocyte mitogenic activity eluting in the 25K Mr range was not due to IL-1 alpha or IL-1 beta. With certain culture conditions, thymocyte mitogenic activity was detected in the 30-40K Mr range. PBMC cultured with LPS and latex beads in the absence of serum released 30-40K Mr IL-1 alpha, as well as 17K Mr IL-1 alpha and 17K Mr IL-1 beta. PBMC cultured in 2% fetal calf serum (FCS) alone from some donors released only 30-40K Mr thymocyte mitogenic activity. Both IL-1 alpha and IL-1 beta protein was detected by ELISA in this Mr range but only the IL-1 alpha was bioactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured

Fibrolamellar carcinoma of the liver: an immunohistochemical study of nineteen cases and a review of the literature.

Hepatocellular carcinoma (HCC) is a rapidly fatal neoplasm of high worldwide prevalence. Fibromellar carcinoma (FLC), a variant of HCC, lacks the dismal prognosis of "ordinary" HCC (O-HCC) and is characterized by a diagnostic histologic appearance. The current study analyzes the clinical characteristics, immunohistochemistry, and treatment of nineteen cases of FLC. These data, together with a detailed review of the literature, further characterize this unique variant. FLC affects younger patients and lacks the male predominance of O-HCC. Also, FLC lacks specific association with cirrhosis, hepatitis B virus infection, use of oral contraceptives, and alcohol abuse, all of which are implicated in other hepatic tumors. This, along with differences in serum tumor marker prevalence (AFP, B12 binding protein) suggests that its pathogenesis differs from that of O-HCC. Despite these differences, FLC shares a common differentiation with O-HCC. The increased amounts in FLC of stainable alpha-1-antitrypsin, fibrinogen, and C-reactive protein, all of which are acute phase reactants and normal hepatocyte products, implies better differentiation of FLC cells. Finally, the better prognosis of FLC is supported by this study, since only two of the 19 patients died because of tumor. This contrasts with the reported survival of patients with O-HCC, usually measured in weeks. Hepatic transplantation may hold promise for future patients with "surgically unresectable" FLC as procedure-related complications are overcome.

Adult

Cervical aortic arch with retroesophageal aortic obstruction: report of a case with successful surgical intervention.

The clinical, roentgenographic, hemodynamic, and angiographic features of a patient with a right cervical aortic arch and retroesophageal aortic obstruction associated with a ventricular septal defect are presented. Surgical relief of the aortic obstruction was successfully achieved by placement of a bypass graft between the left common carotid artery and the descending thoracic aorta.

Aorta, Thoracic

d-Transposition of the great arteries and atresia of the mitral and pulmonary valves: association with a normal anatomic left ventricle.

The clinical, angiographic, and pathologic features are presented for a case of d-transposition of the great arteries with atresia of the mitral and pulmonary valves and two well-developed ventricles. The morphologic left ventricle appeared to be functioning as a systemic ventricular aneurysm, and this may have led to the patient's death. A possible explanation for this anomaly is given.

Female

B-lymphocytes activation by the Fc region of IgG.

Strong stimulation of DNA synthesis (up to 150-fold) and blast transformation can be induced in mouse spleen cells by Fc fragments of human IgG. The mitogenic response is optimal on day 5 of culture and is dependent on the concentration of Fc fragments with a sedimentation rate of 3-5S. Intact IgG is also stimulatory, but only when modified by heat aggregation, and produces only a 10-fold increase in [3H]thymidine uptake. The stimulation by aggregated IgG is dependent on the Fc portion, since aggregated (or soluble) Fab or F(ab')2 fragments are inactive. The results show that the response is T-cell independent and that it is a function of nylon wool adherent, surface Ig-positive, Fc receptor-bearing B lymphocytes. Fc fragments do not induce plaque-forming cells to human IgG in normal mouse spleen cell cultures, but rather trigger polyclonal antibody synthesis (anti-goat erythrocytes, anti-2,4,6-trinitrophenyl). It is postulated that the Fc region of antibodies plays a role in the regulation of the humoral immune response by triggering clonal expansion of B lymphocytes.

Animals

The hemodialysis-induced reaction in patients with leukemia.

The white blood cell count response was documented in various patients following transfusions of 500 ml of autologous or unrelated donor blood that had been subjected to 10 minutes of dialysis with 15 minutes of stagnation. Patients studied included 1 patient with acute nonlymphocytic (ANLL) and 2 patients with chronic lymphocytic leukemia (CLL). The control group consisted of 4 patients with renal failure. The ANLL patient showed a normal two-phase reaction after administration of donor's blood. It is possible that even under conditions of severe disturbance of hemopoiesis the general dependence on normal humoral regulation remains. The CLL patients showed a marked drop in circulating WBC in the first descending phase of the hemodialysis-induced reaction (HDIR). All blood cell types including lymphocytes and blast cells took part in this decrease of blood count; this suggests a cell-nonspecific effect. It is presumed that leukocytes that leave the circulation do not return into the blood and the procedure may be considered as a form of leukophoresis in vivo, with possible therapeutic value.

Aged

One hundred consecutive coarctation resections followed from one to thirteen years.

The technique of operative repair for coarctation of the aorta is now well standardized and the immediate surgical mortality has been lowered to less than 5% in most large series. Long term follow up, however, is only recently being reported. This paper describes the current status of 100 consecutive patients who underwent elective resection from 1--13 yr ago. There was only one operative death. In contrast with other reports, residual systemic hypertension is rare in the 97 survivors. These observations confirm that coarctation of the aorta can be repaired surgically with an acceptable operative mortality; the outlook of the survivors appears excellent.

Adolescent

Diagnosis of cor triatriatum by echocardiography.

The echocardiographic findings in a case of cor triatriatum are described. The diagnosis was suggested by a normal anterior mitral valve echo and a dense band of echoes posterior to the aortic root and within the body of the left atrium; it was documented at cardiac catheterization and proved surgically. Echocardiography is an important diagnostic aid in assessing pulmonary venous obstruction in children.

Echocardiography

Late development of severe pulmonary venous obstruction following the Mustard operation.

While four patients with d-transposition of the great arteries who had a Mustard operation before 2 years of age developed severe pulmonary venous obstruction 2, 3 1/2, 3 9/12, and 5 years following their operation, initial postoperative catheterization (less than 1 year) revealed only minimal pulmonary artery wedge and right ventricular end-diastolic pressure differences, with normal peak systolic pulmonary artery pressures. Serial clinical examination, including height and weight percentiles, chest X-rays, electrocardiograms, and the presence of a continuous murmur in one patient suggested development of pulmonary venous obstruction. Repeat catheterizations demonstrated pulmonary artery pressures greater than or equal to systemic and pulmonary artery wedge minus right ventricular end-diastolic differences greater than 13. Successful relief of the pulmonary venous obstruction included insertion of a Dacron patch to enlarge the pulmonary venous atrium, incision of the obstructing orifice, and repair of associated intra-atrial defects. Operation and postoperative course have been unremarkable. It is concluded that pulmonary venous obstruction can be both an early and progressively late sequela of the Mustard operation. Serial examinations with a high index of suspicion should allow repeated catheterizations to document the occurrence. Operative revision of the obstruction appears to be effective with minimal risk.

Body Height

Echocardiographic assessment of the severity of aortic stenosis in children and adolescents.

The magnitude of ventricular hypertrophy in response to afterloading is determined by wall stress, with wall thickness increasing in proportion to ventricular load until systolic wall stress is normalized. With use of echocardiographic measurements of left ventricular end-systolic wall thickness (Ws) and cavity transverse dimension (Ds), the pressure constant k was calculated in 16 patients without left heart obstruction according to the formula k = P-Ds/Ws. The mean value for k was 225 +/- 6.7 (standard deviation) mm Hg. From this value, left ventricular pressure was estimated in 13 patients with aortic stenosis aged 4 to 17 years using the formula P = k-Ws/Ds. No subject had evidence of cardiac failure. Peak systolic aortic pressure difference (delta P) was calculated by subtracting cuff-measured brachial arterial peak systolic pressure from the estimated left ventricular pressure. Excellent correlation was obtained between the estimated delta P and that found at cardiac catheterization (r = 0.89). In two patients, echocardiographic data predicted significant obstruction in the presence of normal electrocardiographic, vectorcardiographic and vector lead tracings. Echocardiography offers a noninvasive method for estimating the severity of aortic stenosis, in the absence of myocardial failure; it appears to be more sensitive than other currently employed techniques.

Adolescent

Markedly improved pulmonary function after open heart surgery in infancy utilizing surface cooling, profound hypothermia, and circulatory arrest.

The use of surface-induced profound hypothermia with limited cardiopulmonary bypass and circulatory arrest markedly diminished the need for mechanical ventilation for patients undergoing cardiac surgery. Eleven of twenty-two patients were extubated in the operating room and five more patients within 70 minutes postoperatively. Five patients required mechanical ventilation. Four of the five were extubated within 24 hours (mean, 19.05 hours); only one patient required mechanical ventilation greater than 24 hours. This experience would indicate that as the age of surgery is decreased, in conjunction with improved technics of cardiac surgery and anesthesia, the need for mechanical ventilation should be diminished.

Anesthesia, Inhalation