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R M Friedman

Publications and source records attributed to R M Friedman.

At least 55 records · Page 3Linked to original sources
PubMed1993

Structure of the mouse lysyl oxidase gene.

Lysyl oxidase, an extracellular enzyme involved in the maturation of collagen and elastin, also appears to function as a phenotypic suppressor of transformation by the ras gene product, p21. Genomic clones of the mouse lysyl oxidase gene have been isolated, analyzed, and sequenced. Lysyl oxidase appears to be a single-copy gene, organized into seven exons and six introns, and spans approximately 14 kb of the mouse genome. The gene encodes two messages, sized at about 4.8 and 3.8 kb, that differ in the length of the untranslated sequence at the 3' end of the gene. All of the 3' untranslated sequence and the polyadenylation signals are contained in exon VII; there is no evidence of alternate splicing. Primer extension and ribonuclease protection experiments revealed two sites of transcription initiation in a region with sequence motifs characteristic of a promoter, which was upstream and adjacent to the 5' untranslated sequence found in the cDNA.

3T3 Cells↗
PubMed1993

Parallels between properties of high-threshold mechanoreceptors of the goat oral mucosa and human pain report.

In the following experiments, we examined parallels between properties of A-delta high-threshold mechanoreceptors (HTMs; mechanonociceptors, MN, and intense pressure receptors, IPR) innervating the goat mucosa and human mucosal pain report. As suggested in previous studies, activation thresholds of afferents which are generally considered to be mechanical nociceptors are far below mechanical pain thresholds. It was determined that classification of nociceptors by frequency thresholds, i.e., the pressure at which HTMs maintained a minimum frequency (97 g/mm2 and 117 g/mm2 for IPRs and MNs respectively) brings afferent reactivity into alignment with perceptual events. The range of reactivity of the nociceptor pool paralleled pain report from "faint-weak" (142 g/mm2) to "strong-intense" (277 g/mm2). It is suggested that coding of intense mechanical pain from compressive forces is likely to arise from both individual afferents, whose reactivity spanned the range, and from recruitment of afferent populations with progressively higher thresholds.

Afferent Pathways↗
PubMed1993

Valve of Guerin as a cause of dysuria and hematuria in young boys: presentation and difficulties in diagnosis.

A valve of Guerin, or lacuna magna, is a common anatomical finding in young boys. It occasionally causes dysuria and/or bloody urethral discharge or spotting due to its location distal to the external urethral sphincter. We report on 10 patients who underwent transmeatal marsupialization of a valve of Guerin between 1984 and 1991, and review the embryology and clinical presentation. Despite evidence suggesting that a valve of Guerin is a frequent, normal anatomical variant, the incidence of clinical detection is extremely low. While many patients with this condition remain totally asymptomatic, a valve of Guerin should be suspected in boys presenting with bleeding distal to the urethral sphincter with or without voiding symptoms. In most cases physical examination is normal. A carefully performed voiding cystourethrogram visualizing the distal urethra, coupled with endoscopic examination and gentle probing of the fossa navicularis, optimizes the likelihood of correct diagnosis. Treatment is indicated solely to ameliorate symptoms, which are probably caused by distention of the lacuna magna during voiding. Transmeatal incision and marsupialization of the valve leaflet into the urethral lumen usually effectively relieve dysuria and stop the bleeding.

Adolescent↗
PubMed1993

An experimental model of neonatal testicular torsion: evidence against an exclusively extravaginal etiology.

The present study was designed to determine whether extravaginal torsion of the spermatic cord (EVT) can be distinguished from intravaginal torsion (IVT) on the basis of gross and histologic examination of the testis. It is traditionally believed that EVT, postulated to occur only in neonates, can be grossly distinguished from IVT, which occurs in older patients, on the basis of adherence between testis and tunica vaginalis. Such adherence is felt to be present in EVT but not IVT. This concept that the two types of torsion can be distinguished in the operating room has important clinical ramifications. In cases of EVT, contralateral orchidopexy theoretically need not be performed, since adhesions develop between tunica vaginalis and dartos by a few weeks of age. This is in contrast to IVT, in which contralateral orchidopexy is necessary due to the bilateral nature of the bell clapper deformity. Using a rat model, we first demonstrated that IVT could produce adherence of the tunica vaginalis to testis. Then, eight rats were operated on, producing right IVT and left EVT. Animals were then sacrificed at intervals of up to one month. Gross and histologic examination showed involvement of the tunica vaginalis in an ischemic and inflammatory response in a majority of testes, regardless of the type of torsion. Attempts to distinguish EVT from IVT on the basis of grossly evident adhesions between tunica vaginalis and testis are of questionable validity. Early contralateral orchidopexy is therefore recommended in all cases of neonatal torsion.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗