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Biomedical subjects

J Lieberman

Publications and source records attributed to J Lieberman.

At least 19 recordsLinked to original sources

Cytotoxic T lymphocytes from HIV-1 seropositive individuals recognize immunodominant epitopes in Gp160 and reverse transcriptase.

The CTL response to HIV-1 is more vigorous than for any known human pathogen and may be a significant factor in preventing the progression to symptomatic disease. T cell lines, generated by non-specific stimulation with PHA and IL-2, may be reproducibly used to identify HIV-1 isolate-invariant epitopes recognized by the CTL of infected individuals. The CTL response in each of 12 infected individuals to envelope and reverse transcriptase (RT) is dominated by the recognition of one or two viral isolate-invariant epitopes. Seven subjects respond to a single gp160 epitope; three subjects recognize 2 gp160 epitopes. There is a significant increase in recognition of epitopes in the C terminal 104 amino acids of gp41 (p less than 0.002); in fact 40% of the subjects that respond to gp160 recognize the C terminal 20-mer. The CTL-mediated lysis of gp160-expressing targets is MHC restricted, but not all individuals that share the same serologically defined class I-restricting element respond to the same epitope. Recognition of the terminal 20mer is restricted by both A30 and B8. The response to RT in six subjects is distributed over the RT protein. The six subjects recognize four separate regions defined by truncated RT-vaccinia recombinants, but none of the subjects' CTL demonstrate significant recognition of the RT epitope identified in H-2k mice and some humans.

Amino Acid Sequence

A comparison of clinical examination, history, and magnetic resonance imaging for identifying orthodontic patients with temporomandibular joint disorders.

The temporomandibular joint (TMJ) status of 51 juvenile orthodontic patients was assessed with magnetic resonance imaging (MRI), clinical examination, and questionnaire data. The results of this study demonstrated that the prevalence of anterior displacement of the meniscus was 11.8% (6 of 51) as assessed by MRI. Clicking or pain in the TMJ area was found in 9.8% (5 of 51) of the subjects by clinical exam, and 19.8% (10 of 51) of the subjects had a history of pain or clicking of the TMJ. Three subjects had a positive MRI and a negative history and clinical examination. However, all subjects with positive MRI findings had a history of other risk factors known to be associated with TMJ internal derangement (TMJ-ID). Therefore practitioners should use a history form and a clinical examination technique that includes a broad range of signs and symptoms of temporomandibular disorders (TMD) to identify patients who may have abnormal condyle disk relationships and be at risk for TMD. Clicking and pain in the TMJ helped identify only one half of the patients with abnormal condyle-disk relationships in this study population. Future cephalometric studies will monitor the effects of abnormal condyle disk relationships on facial growth during orthodontic treatment.

Adolescent

Increased prevalence of the cavum septum pellucidum in magnetic resonance scans and post-mortem brains of schizophrenic patients.

A cavum septum pellucidum (CSP) has been regarded as an incidental finding of little clinical importance. However, an association between this developmental anomaly and a diagnosis of psychosis has previously been reported. We determined the prevalence of the CSP in parallel studies of brain scans obtained with magnetic resonance (MR) imaging and in the post-mortem brains of schizophrenic patients compared with normal controls. We found a significantly increased prevalence of the CSP in both the MR scans and post-mortem brains of schizophrenic patients compared with controls. In the MR study, 17 of 81 (21%) schizophrenic patients but only 1 of 46 (2%) control subjects had a CSP. In the post-mortem study, 17 of 28 (61%) schizophrenic patients and 12 of 39 (31%) normal controls had a CSP. The increased prevalence of a CSP in schizophrenic patients further indicates that anomalous development of the limbic system is an important aspect of this disorder.

Adult

Inflammatory abdominal aortic aneurysm and the associated T-cell reaction: a case study.

The immune response associated with an inflammatory abdominal aortic aneurysm was studied by determining the phenotypes of lymphocytes in the peripheral blood, the aortic aneurysm wall, and the perianeurysmal tissue. Increased numbers of activated T cells were found in all three areas. After aneurysm repair, peripheral blood analysis demonstrated normalization of the T-cell subsets. These data suggest that inflammatory abdominal aortic aneurysm is associated with a measurable immune response in peripheral blood with elevation of the same subset of inflammatory cells (CD4) as detected in abdominal aortic aneurysm tissue, and the immune response regresses after aneurysm repair.

Aged

Emergency thoracotomy: survival correlates with physiologic status.

Emergency thoracotomy is a standard procedure in the management of cardiac arrest in patients sustaining severe trauma. We examined the records of 463 moribund trauma patients treated at our institution from 1980 to 1990 to refine indications for emergency thoracotomy. Patients underwent thoracotomy either in the emergency department (ED) (n = 424) or in the operating room (OR) (n = 39) as a component of continuing resuscitation after hospital arrival. The survival rate was 13% (61 of 463) overall, 2% (3 of 193) for blunt, 22% (58 of 269) for all penetrating, 8% (10 of 131) for gunshot, 34% (48 of 141) for stab-wound patients, and 54% (21 of 39) for patients who underwent emergency thoracotomy in the OR. Survival correlated with the physiologic status of patients both on initial evaluation in the field by paramedics and on arrival at the ED. Patients with penetrating trauma and in profound shock (BP less than 60 mm Hg) or mild shock (BP 60-90 mm Hg) with subsequent cardiac arrest had survival rates of 64% (27 of 42) and 56% (30 of 54), respectively. None of the patients with absent signs of life, defined as full cardiopulmonary arrest with absent reflexes (n = 215), on initial assessment by paramedics in the field, survived. We conclude that (1) no emergency thoracotomy should be performed if no signs of life are present on the initial prehospital field assessment; (2) emergency thoracotomy is an indicated procedure in most patients sustaining penetrating trauma; (3) blunt traumatic cardiac arrest is a relative contraindication to emergency thoracotomy.

Adult

Qualitative assessment of brain morphology in acute and chronic schizophrenia.

OBJECTIVE: Neuroimaging studies of brain morphology in schizophrenia have used predominantly morphometric techniques to assess brain scans. However, as currently implemented, such methods are not particularly helpful in the routine assessment of individual patients. The purpose of this study was to evaluate brain morphology seen with magnetic resonance imaging (MRI) by qualitative assessment, the most frequently used method in clinical practice for evaluating brain scans. METHOD: First-episode (N = 62) and chronic, multi-episode (N = 24) schizophrenic patients and healthy comparison subjects (N = 42) underwent MRI of the whole head in a sequence that provided 63 contiguous brain slice images. Each subject received a rating of normal, questionably abnormal, or definitely abnormal for four brain regions (lateral ventricles, third ventricle, medial temporal lobe structures, and frontal/parietal cortex) and a global rating. RESULTS: The schizophrenic patients had significantly higher global rates of abnormal morphology (first-episode group, 31%; chronic group, 42%) than the normal subjects (5%). The highest regional rates of abnormalities were seen in the lateral ventricles and the lowest in the frontal/parietal cortex. Although the chronic patients had generally higher abnormal rates than the first-episode patients, these differences were not statistically significant. The qualitative ratings of brain morphology were significantly correlated with quantitative assessments performed in separate studies. CONCLUSIONS: Despite its limits in sensitivity (and until quantitative morphometric techniques are made practical and more widely available), qualitative evaluation of MRI scans can be a useful technique in research and clinical evaluation of patients with schizophrenia.

Adolescent

Major histocompatibility complex associations with clozapine-induced agranulocytosis. The USA experience.

In order to determine associations between the major histocompatibility complex (MHC) and the development of clozapine-induced agranulocytosis, HLA typing was performed in a group of 42 clozapine-treated patients, of whom 11 had developed this adverse reaction. Among the patients with agranulocytosis, 7 (63%) were of Ashkenazi Jewish background and 4 (37%) were non-Jewish. An association between the HLA-B38, -DR4, -DQw3 haplotype and clozapine-induced agranulocytosis was found in all Jewish cases (7/7; 100%); in contrast only 4 of 21 (19%) Jewish control (nonagranulocytic) patients carried this haplotype. Among non-Jewish patients the HLA-DR2, -DQw1 haplotype was present in 4 of 4 (100%) patients with clozapine-induced agranulocytosis and in only 3 of 10 (30%) ethnically matched control patients. Our results indicate that gene products within the MHC could be involved in clozapine-mediated haematological toxicity.

Agranulocytosis

Mood responses of remitted schizophrenics to methylphenidate infusion.

To investigate the mood response of schizophrenic subjects to psychostimulant challenge, 29 neuroleptic-treated subjects (22 with schizophrenia and 7 with schizoaffective disorder) in clinical remission received two infusions, one with methylphenidate 0.5 mg/kg and the other with normal saline, under double-blind conditions. Twenty-five of these subjects were withdrawn from neuroleptics and given a second set of double-blind infusions. Infusion mood responses were classified as euphoric, neutral, mixed or dysphoric. Subjects were also rated as either psychotic symptom activators to the infusion or no change in psychotic symptoms. Overall response by mood category was as follows: 35.2% euphoric, 50% neutral, 5.6% mixed and 9.3% dysphoric. Mood responses were not correlated with sex, methylphenidate plasma levels or diagnostic distinctions between schizophrenia and schizoaffective disorder. Although they occurred infrequently, dysphoric and mixed mood responses were associated with high rates of psychotic activation. Comparing subjects on and off neuroleptics, subjects on neuroleptics had more euphoric responses than the same subjects off neuroleptics. This increased number of euphoric responses in subjects taking neuroleptics compared to off neuroleptics suggests that neuroleptic treatment status may be an important factor in assessing psychostimulant use in schizophrenia patients.

Adolescent

Measurement standards for the prevertebral region in the lateral soft-tissue radiograph of the neck.

One hundred thirty-one lateral soft-tissue radiographs of the neck, taken over a 6-month period, were reviewed. Eighty-six radiographs were normal. The mean prevertebral soft-tissue thickness in the posterior-anterior dimension for each normal radiograph was measured. The mean thickness in the retropharyngeal region ranged from 6.2 mm in the infant to 3.7 mm in the adult, while the mean thickness in the retrotracheal region ranged from 9.2 mm in the preschool group to 12.1 mm in the adult.

Abscess

A CF-lectin factor in amniotic fluid from pregnancies at risk for cystic fibrosis.

A method was developed for the assay of the CF-lectin factor in amniotic fluid using samples from fetuses identified by other means as having or not having cystic fibrosis (CF). The method involves protein removal from the amniotic fluid by filtration through Centricon-10 Amicon filters, admixture of filtrate with normal serum as a source of IgM, and incubation in 5% Dextran-Sulfate with mouse red blood cells to detect specific hemagglutination. Blind samples submitted from four different laboratories were used to evaluate the ability of the assay to differentiate CF fetuses from fetuses without CF. Storage of samples from one laboratory had been quite prolonged and was associated with poor correlations. Freezing and thawing of samples were shown to deactivate the CF-lectin factor. In three of the four studies, CF lectin was detected in 77% of pregnancies identified as CF at birth, prenatally through microvillar enzyme assay or through DNA analysis of terminated pregnancies. Eighty-three percent of samples identified as normal were confirmed as such by a lack of CF-lectin activity. These data suggest that CF fetuses produce, and are exposed to, the CF-lectin factor at least as early as the second trimester of gestation.

Amniotic Fluid

Alpha-1 antitrypsin deficiency in a patient with widespread prurigo nodularis.

Skin lesions associated with alpha 1-antitrypsin deficiency are becoming better defined and understood. Deficiency in this major antiproteinase, which neutralizes multiple proteolytic enzymes ranging from collagenases and elastases to trypsin and chymotrypsin, thus results in significant tissue autodigestion. This anti-proteinase is secreted by activated lymphocytes and macrophages, suggesting the existence of homeostasis which titrates the release of proteolytic enzymes by these cells, and the adequate neutralization of these proteases in order to prevent excessive tissue autodigestion each time these inflammatory cells are activated. We report a patient with alpha 1-antitrypsin deficiency who, following insect bites and cellulitis developed widespread itching and scratching, leading to widespread lesions of prurigo nodularis. The colonization of his multiple skin lesions with Staphylococcus aureus and the release of potent T cell mitogens, such as Protein A and enterotoxin A from the bacterial cell membrane may have resulted in the release of additional proteolytic enzymes by the activated lymphocytes and macrophages, without the concomitant secretion of alpha 1-antitrypsin with subsequent aggravation of his pruritus. These concepts are supported by electron microscopic evidence of excessive tissue autodigestion, and by immunocytochemical data identifying the presence of T helper and T cytotoxic/suppressor lymphocytes as well as macrophages within the upper dermis.

Humans

Intermediate alpha 1-antitrypsin deficiency with apical lung bullae and spontaneous pneumothorax. Presence of a Z variant in an American black.

A 43-year-old black man had an 18-year history of apical lung cystic-bullous disease. Following two episodes of spontaneous pneumothorax and two instances of thoracotomy for bullectomy and pleural abrasion, he was found to have an intermediate AAT deficiency with an MZ phenotype. It is believed that this is the first case of localized bullous lung disease to be reported in association with any degree of AAT deficiency. There is evidence that the cystic lesions progressed to form upper lobe bullae. It is postulated that the AAT deficiency may have played a role in this progression, as did the patient's cigarette smoking. Following two instances of surgery, CT scans of the lungs, compliance studies and complete pulmonary function tests show no further evidence of lung bullae or emphysema. The rarity of the Z variant of AAT in blacks is discussed.

Adult

Age-related decrease in serum angiotensin converting enzyme activity: the role of thyroidal status and food intake.

The serum ACE activity was determined in male Fischer 344 rats at 2, 6, 13, and 25 months of age to determine whether serum angiotensin converting enzyme (ACE) activity is a potential biomarker of tissue hypothyroidism in aged rats. Since rodent serum contains an ACE activity inhibitor, the measurements were done in both undiluted and 1:8 diluted sera. The highest serum inhibitor activity was found in the 2-month-old animals. The serum ACE activity measured in the diluted serum of the aged rats (77.6 +/- 2.9 units/ml) was significantly reduced compared to 2-month-old (178.2 +/- 6.4 units/ml), 6-month-old (101.5 +/- 6.1 units/ml) and 13-month-old rats (84.9 +/- 8.6 units/ml); (p less than 0.001). Hyperthyroidism induced by injecting L-triiodothyronine (T3) 15 micrograms/100 gm body weight intraperitoneally for 10 days increased the serum ACE activity in the older rats, but reduced the levels in 2-month-old rats. There was no significant change in 6-month-old rats. The levels of serum ACE activity in hypothyroid 6-month-old rats (95.5 +/- 3.5 units/ml) and in 2-month-old-rats (94.2 +/- 4.0 units/ml) were similar to the level seen in hypothyroid old rats (88.9 +/- 5.8 units/ml). Pair feeding of young rats (8 months old) with old did not alter the baseline ACE level (117.4 +/- 3.7 units/ml) or the T3 stimulated (105.2 +/- 10.2 units/ml) serum ACE activity. It is concluded that the reduced serum ACE activity in aged rats cannot be accounted for by the reduced caloric intake or reduced serum thyroid hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Assay of a urinary CF-lectin factor as a second diagnostic test for cystic fibrosis.

Analysis of urine samples for a lectin-like factor in patients with a diagnosis of cystic fibrosis (CF) revealed that the low molecular weight (MW) factor is present in urine only from such patients and not from heterozygous carriers of the CF gene or from normal controls. The urine fraction containing the factor must be separated from whole urine by a gel filtration column (TSK-20) for the activity to appear. The assay requires addition of an aliquot of normal serum to provide the necessary IgM to which the CF-factor binds, resulting in the lectin-like activity that causes agglutination of mouse erythrocytes. All 22 CF patients tested, who were not receiving intravenous (IV) antibiotics had positive CF-lectin urinary activity, whereas five others receiving IV aminoglycosides were negative. Four patients with a clinical diagnosis of CF, but with normal sweat tests (35-54 mEq/L), all had positive urinary CF-lectin tests. A blind study in which urine samples were shipped from Miami, FL to Sepulveda, CA was completely successful in correctly identifying 11 samples from CF patients as compared with ten from non-CF patients. It was concluded that an assay for urinary CF-lectin factor is specific and reliable for confirming a diagnosis of CF when the sweat test is indeterminate, and when patients have not received recent IV aminoglycosides.

Adolescent