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Biomedical subjects

R M Friedman

Publications and source records attributed to R M Friedman.

At least 19 recordsLinked to original sources

Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific.

Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta 2-microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels of beta 2-microglobulin and neopterin significantly predicted the development of Kaposi's sarcoma. These two markers were highly correlated (r = 0.74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients.

Acquired Immunodeficiency Syndrome

Induction of IFN-alpha in peripheral blood mononuclear cells by HIV-infected monocytes. Restricted antiviral activity of the HIV-induced IFN.

PBMC cocultured with HIV-infected monocytes for 12 to 48 h released high levels of IFN activity. IFN titers were directly dependent upon time after virus infection and level of HIV replication in infected cells. IFN induction in PBMC was evident with HIV-infected monocytes and PBMC and with myeloid and lymphoblastoid cell lines with at least three different HIV strains. In HIV-infected cell line pairs in which virus infection occurs in both productive and restricted forms, IFN induction in PBMC occurred only with productive infection. IFN activity was acid stable and completely neutralized by antibodies against IFN-alpha. Induction of IFN required cell-cell contact between HIV-infected cells and PBMC, but was independent of MHC compatibility. With PBMC co-cultured with autologous HIV-infected monocytes, IFN induction was highly selective: IL-1 beta, IL-6, or TNF-alpha activity and mRNA were not detected. Cell surface determinants on HIV-infected monocytes that induced IFN in PBMC remained active after fixation in 4% paraformaldehyde. Both adherent and nonadherent PBMC produced IFN after coculture with HIV-infected monocytes. Ability to produce IFN by PBMC was not affected by depletion of T cell, NK cell, B cell, or monocyte subpopulations. The IFN activity produced by PBMC cocultured with HIV-infected cells was about 20-fold less active than equal quantities of rIFN-alpha 2b for inhibition of HIV replication in monocytes and at low concentrations enhanced virus growth. Clinical studies with HIV-infected patients and parallel findings in animal lentivirus disease suggest an adverse role for IFN in disease progression. Conditions for induction of IFN in the culture system described in this report may mimic those in the HIV-infected patient. Defining the molecular basis for IFN induction, the cells that produce IFN, and the altered biologic activity of this important cytokine may provide insight into the pathogenesis of HIV disease.

Cells, Cultured

Family functioning and psychopathology among adolescents with severe emotional disturbances.

Family psychosocial functioning and its relation to psychopathology among adolescents with severe emotional disturbances (SED) was assessed. Subjects were 353 adolescents with SED, ages 12-18, and their parents. During a semi-structured interview, adolescents were administered Family Adaptability and Cohesion Evaluation Scale (FACES-III), Diagnostic Interview Schedule for Children-Child Version (DISC-C), and the Self-Derogation Scale. Parents were administered FACES-IIII and the Child Behavior Checklist (CBCL) in a phone interview. Results indicated that on the FACES-IIII cohesion dimension, both parents and adolescents perceived their family relations as more disengaged and less connected than did normative families (p less than .001). In contrast, only parent FACES-IIII adaptability scores were significantly more extreme than a normative sample (p less than .01). Additionally, both parent and adolescent cohesion scores were significantly correlated with adolescent psychopathology measures: DISC-C conduct disorder (p less than .01), depression (p less than .05), alcohol/marijuana (p less than .01), and CBCL externalizing symptoms (p less than .01). These relationships did not deviate from linearity.

Adaptation, Psychological

Endoureteropyelotomy in adults. Review of procedure and results.

We report on 17 adult patients who underwent antegrade endoureteropyelotomy for primary (7) and secondary (10) ureteropelvic junction obstruction. Complications were limited to failure to relieve the obstruction, which occurred in 2 patients (12%) requiring a subsequent open pyeloplasty. The two failures were due to high insertion of the ureter in one, and lower renal pole vessel in the other case. A new endoureteropyelotomy stent was developed to enhance healing and patient comfort. No failures occurred due to technical difficulties.

Adolescent

Effectiveness of a handsewn nipple valve for reflux prevention in bladder reconstruction.

The intussuscepted nipple has proved to be a versatile mechanism to provide continence or prevent reflux in urological reconstructive surgery. Early in its use detussusception of the nipple was recognized as a common complication, which was usually prevented by using several rows of staples to stabilize the nipple. The use of staples has reduced the rate of reoperation for eversion or obstruction but it has led to a higher stone formation rate, ranging from 10 to 18% in recent series. Since 1983 we have used a handsewn intussuscepted ileal nipple stabilized without staples as our antireflux mechanism in bladder augmentations and continent diversions. This technique has been performed in 30 patients with an average followup of greater than 3 years. A small bladder stone developed in only 1 (3%) of the patients, who was completely dependent on intermittent catheterization, while 4 (13%) required reoperation due to eversion of the nipple. This incidence compares well with nipple reoperation rates in recent series, which range from 7 to 28%. We conclude that absorbable sutures are as effective as staples in stabilizing the antireflux nipple, and that they result in a lower incidence of subsequent stone formation.

Child

Post-transcriptional regulation by interferon-alpha of epsilon-globin production in human erythroleukemia K-562 cells.

Treatment of human K-562 erythroleukemia cells with interferon-alpha (IFN-alpha) resulted in a six-fold increase in the production of epsilon-globin, a component of embryonic hemoglobin, but in a two-fold or less augmentation of the production of other globin species. There was no comparable increase in the production of epsilon-globin mRNA following IFN treatment. We did, however, observe a shift in the cytoplasmic location of the epsilon-globin mRNA from the messenger ribonucleoprotein (mRNP) to the polysome fraction after IFN-alpha addition. No such shift was noted in the location of the mRNA for A gamma-globin, the major globin product of K-562 cells, which was always present in the polysome fraction. These results are significant with respect to the mechanisms of cellular regulation and differentiation induced by IFNs.

Antibodies, Monoclonal

Lesions of cat sacrocaudal spinal cord: a minimally disruptive model of injury.

As part of our studies of the organization of the cat sacrocaudal spinal cord (S3-Ca7), the portion of the neuraxis that innervates the tail, we have begun to evaluate the behavioral effects of hemisection or complete transection at the level of Ca1. Clinical observations that the tail strongly deviated to the side of a hemisection indicated the presence of an ipsilateral hypertonia. After complete transection of the spinal cord, the tail became ventroflexed in a midline position and exhibited spasticity, i.e., hypertonia, hyperreflexia, and clonus. Bowel and bladder functions and hindlimb gait and reflexes remained intact following either lesion. Quantitative behavioral measures corroborated our clinical observations. With the tail tethered to a force transducer, tail muscle tone was measured after the tail was passively positioned. Following a transection, resistance to dorsiflexion of the tail was greater than resistance to ventroflexion. In addition, tonic deviation of the tail was documented with videotape analysis while cats walked on a plank. Normal cats walked with the tail sharply dorsiflexed and centered. In contrast, the tail deviated ipsilaterally in cats with a hemisection, and the tail was ventroflexed in cats with a transection. These observations indicate that the sacrocaudal spinal cord provides a model with special advantages for investigation of changes in segmental motor functions following spinal cord injury. The effects of lesions on the tail are quantifiable and can resemble that spasticity observed after spinal cord injury in humans. Importantly, minimal effects on locomotive and autonomic functions were observed following hemisection or transection of the sacrocaudal spinal cord.

Animals

Substance abuse prevalence and comorbidity with other psychiatric disorders among adolescents with severe emotional disturbances.

Among 547 adolescents with serious emotional disturbances, ages 12 to 18, this study assessed (1) prevalence of DSM-III substance use disorders (i.e., alcohol and marijuana abuse/dependence), and (2) comorbidity with DSM-III Axis I disorders. Factors of age, sex, state location, and type of treatment program also were examined. Data were analyzed by logistic regression. Significant factors (p less than 0.05) associated with severe alcohol or marijuana abuse/dependency diagnosis included (1) residential mental health treatment program, 2.37 Odds Ratio (OR); (2) conduct disorder diagnosis, 2.18 OR; (3) depression diagnosis, 1.75 OR; (4) states, 1.43 OR; (5) age, 1.29 OR; and (6) a depression x facility interaction, 1.91 OR.

Adolescent

Primary amines enhance the antiviral activity of interferon against a membrane virus: role of intracellular pH.

Inhibition of vesicular stomatitis virus (VSV) replication in LB cells by interferon (IFN) resembles the action of IFN on some retroviruses, in that the incorporation of glycoprotein into virions is defective. Primary amines added between 1 and 2 h post-infection significantly enhanced (five- to 1000-fold) the antiviral activity of IFN against VSV, but no enhancement of the antiviral activity of IFN against encephalomyocarditis virus, a virus with no membrane component, by primary amines was seen. SDS-PAGE and immunofluorescence analysis of viral proteins, and Nycodenz gradient fractionation, suggested that both IFN and primary amines inhibited the transport of VSV glycoprotein (G) to the plasma membrane; instead, G accumulated in the trans-Golgi network (TGN). Using sensitive intracellular pH (pHi) indicators, we found that IFN treatment significantly raised the pHi. A further increase in pHi was seen with a combination of IFN and primary amines; the increase in pHi correlated with an enhancement of the antiviral activity of IFN by primary amines. Amiloride inhibited the IFN-induced increase in pHi and a concomitant increase in the concentration of Na+ ions; this observation suggested that IFN induced cytoplasmic alkalinization by activating an Na+/H+ antiporter system. These results indicated that the IFN-induced increase in pHi may be responsible for the accumulation of G in the TGN, thereby producing G-deficient virus particles with reduced infectivity.

Adamantane

Induction of alpha interferon by human immunodeficiency virus type 1 in human monocyte-macrophage cultures.

The induction of interferon (IFN) by human immunodeficiency virus type 1 (HIV-1) in primary, nonstimulated monocyte-macrophage cultures was studied. HIV-1 infection, as confirmed by p24 antigen levels in the cell supernatant, led to the production of alpha interferon (IFN-alpha) over 7 to 21 days following infection. In two of seven experiments, the IFN detected was acid labile. Coupled reverse transcription-polymerase chain reaction analysis confirmed the induction of IFN-alpha mRNA in cells of HIV-1-infected cultures.

Cell Adhesion

Properties of high-threshold mechanoreceptors in the oral mucosa. I. Responses to dynamic and static pressure.

1. Mechanical response properties of high-threshold mechanoreceptors (HTMs) of the goat oral mucosa were determined by single-unit recording from the palatine and alveolar nerves and from the trigeminal ganglion. The following observations were made. 2. HTMs of the oral mucosa could be separated into two subgroups on the basis of their threshold to mechanical stimulation. Intense pressure receptors (IPRs) comprised a group of A-delta afferents with thresholds of 2-16 g. Mechanonociceptors (MNs) comprised a group of relatively slowly conducting afferents (A-delta and C-fibers) with a higher threshold range (16-300 g). 3. In most instances, MNs lacked pressure-transducing capacity. Tests of reactivity to dynamically or statically applied stimuli revealed that significant functions were rarely fit between MN activity and pressure (4/20 cases). 4. IPRs differed from MNs by their pressure-transducing properties. The afferent response interval was in inverse proportion to the applied pressure. Significant pressure interval functions were fit in 16/20 cases. The relationship between pressure and response interval was best described by power functions. 5. Tests of reactivity to dynamically or statically applied stimuli revealed that IPRs preferred static pressure. Tighter fits and steeper slopes were observed in power functions fit to data generated by statically applied stimuli (mean fitted function, dynamic test: LnISI = -0.97 LnP + 3.4; mean fitted function, static test: LnISI = -1.6 LnP + 4.71). 6. Pressures-frequency thresholds (PFTs), asymptotes (PFAs), and mean response intervals (MRIs) were determined for IPRs from the static test series. The first two values are the pressures that produce the lower and upper limits of response frequency of mucosal HTMs (mean PFT, 1.48 N/mm2; mean PFA, 3.34 N/mm2). The MRI (28 ms) is simply computed from the function. When PFTs and PFAs are combined with activation threshold and power functions, they provide a relatively complete description of the range and form of reactivity of the IPR of the oral mucosa.

Animals

Properties of high-threshold mechanoreceptors in the goat oral mucosa. II. Dynamic and static reactivity in carrageenan-inflamed mucosa.

1. We have previously described two classes of high-threshold mechanoreceptors (HTMs) of the oral mucosa of the goat. Mechanonociceptors (MNs) had very high thresholds (16-300 g) and were poor transducers of pressure. Intense pressure receptors (IPRs) had thresholds from 2 to 16 g and were good transducers of pressure. After carrageenan inflammation (CI) we observed mechanical sensitization in both classes of HTMs. The characteristics were as follows. 2. Sensitization of MNs was manifested as qualitative shifts in the capacity to encode intense pressure. MNs that were unable to code intensity before CI acquired pressure coding properties after treatment with carrageenan. Qualitative shifts in coding capacity were suggested by the greater proportion of MNs coding in preinflamed (10 of 14) compared with noninflamed tissue (8 of 25 cases). Improved afferent reactivity was directly observed, in additional experiments, in which MNs were characterized in normal tissue before the injection of carrageenan into the mucosa. In five of six cases, either qualitative or quantitative improvements were observed. In control experiments, improved reactivity was observed in one of six cases. 3. Sensitization in IPRs was manifested as both qualitative and quantitative improvement in intensity coding properties. Power functions fit to individual IPRs indicated sensitization for most mucosal afferents after inflammation. Carrageenan induced decreases in the mean response interval, pressure-frequency threshold (PFT), and pressure-frequency asymptote (PFA), and decreases in variability of functions fit to units sampled from preinflamed and noninflamed tissue (n = 23). Experiments were also conducted in which units were characterized before and after carrageenan treatment. In 7 of 10 cases, injection of carrageenan into the oral mucosal led to improved dynamic and/or static reactivity. Injection of vehicle led to changes in reactivity in one of five cases. 4. Carrageenan induced decreases in activation thresholds only when afferent receptive fields fell into restricted tissue zones. Large shifts in activation thresholds were observed for five of five (3 MNs and 2 IPRs) units in the sulcal zone of the incisal papilla (IP). In contrast, activation thresholds increased or remained the same in 11 of 12 units (10 IPRs and 3 MNs) with receptive fields in the medial or ventral tissue zones. Changes in activation threshold evolved slowly after carrageenan injection and required 1-2 h to develop. Rapid changes in activation threshold were also observed in a limited number of cases (3). These threshold shifts were unrelated to carrageenan inflammation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals