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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
PubMed1995

Comparison of otoplasty techniques in the rabbit model.

The relative merit of cartilage scoring versus suturing in otoplasty remains a subject of debate among leading plastic surgeons. We compared a variety of otoplasty techniques in 42 rabbit ears using anterior or posterior scoring, horizontal or vertical mattress sutures, and combinations of scoring and suturing. The ears were splinted with a right-angle fold for 10 postoperative days, and the animals were killed after 8 weeks. Suturing techniques, alone or in combination with scoring, maintained an angulation significantly closer to the desired 90 degrees than anterior or posterior cartilage scoring (p < 0.05). The greatest accuracy and consistency were seen with horizontal mattress suturing, which provided an average angle (+/- SD) of 86 +/- 8.5 degrees. Histological analysis demonstrated a significant increase in cartilage hyperplasia with suturing alone, whereas the other techniques achieved only mild to moderate increases. Our findings support the usage of horizontal mattress sutures to create the antihelical fold in otoplasty.

Animals↗
PubMed1995

Iloprost enhances survival of axial-pattern skin flaps in an ischemia-reperfusion model.

Iloprost, a stable prostacyclin analogue, significantly enhances the survival of an axial-pattern groin flap in rats after ischemia-reperfusion. Treated flaps showed viability over 90 percent of their area 7 days after an 8-hour ischemic episode, whereas the saline-treated controls were viable over only 20 percent of their area (p = 0.002). This effect was seen at a low (10 ng/kg) dosage, and no apparent side effects were noted.

Animals↗
PubMed1995

Nasal tip blood supply: an anatomic study validating the safety of the transcolumellar incision in rhinoplasty.

The nasal tip blood supply was studied through anatomic dissections and microangiography in 31 fresh cadaver specimens. The lateral nasal artery was present in all specimens, bilaterally in 30 (97 percent) and unilaterally in one (3 percent) and was located in the subdermal plexus 2 to 3 mm superior to the alar groove. The columellar branch of the superior labial artery was visualized bilaterally in 3 specimens (9 percent) and unilaterally in 21 (68 percent), and was absent in 7 (23 percent). Transcolumellar (external rhinoplasty) incisions were performed in 11 of these cadavers prior to dye injection. A consistent crossover flow (100 percent) was seen from the lateral nasal artery arcades to the distal aspect of the transected columellar branches. We conclude that nasal tip blood supply is derived primarily from the lateral nasal arteries, with a variable contribution from the columellar arteries. Collateral flow to the nasal tip may be provided by branches of the ophthalmic artery. The external rhinoplasty transcolumellar incision does not compromise nasal tip blood supply unless extensive tip defatting or extended alar base resections (above the alar groove) are performed.

Angiography↗
PubMed1995

A critical band filter in touch.

Separate mechanoreceptor systems in humans were isolated by varying the spectra of vibrotactile stimuli. First, the function relating threshold to frequency of a sinusoid was obtained on the fingertip for each of four subjects, and it was found to comprise two limbs: a Pacinian and a non-Pacinian limb. The peak sensitivity within the Pacinian limb (mediated by Pacinian corpuscles) was around 250 Hz and spanned the region from 65 to 400 Hz. The non-Pacinian limb showed no detectable change in sensitivity in the region between 10 and 65 Hz. These two limbs were then treated as psychophysical channels in experiments in which narrow band noise and individual sinusoids were used to excite one or both channels. In the second and third experiments, the noise stimuli varied in bandwidth from 8 to 70 Hz and varied in center frequency from 25 to 218 Hz. Masking functions were obtained for ON-frequency conditions (the sinusoidal test and noise masker occupied the same frequency region) and for OFF-frequency conditions (the test and masker occupied different frequency regions). The ON-frequency experiments were used to estimate the signal-to-noise ratio (S/N) of the Pacinian channel at threshold. The OFF-frequency masking experiments were used to infer the shape of the Pacinian channel at frequencies below 65 Hz, where thresholds for Pacinian activation were above detection threshold. The results of these three experiments predicted the findings of a fourth masking experiment with a parameter free model that treated the Pacinian channel as a filter that integrates stimulus power. The results show that the Pacinian channel is analogous to a critical band in the auditory system.

Acoustic Stimulation↗
PubMed1994

Fertility after cryptorchidism: a comparative analysis of early orchidopexy with and without concomitant hormonal therapy in the young male rat.

Infertility is common in patients with a history of bilateral cryptorchidism, even after successful prepubertal orchidopexy. Recent data suggest that this defect may be partially due to the existence of hormonal abnormalities in some forms of cryptorchidism. To analyze any potential benefit of hormonal therapy, we have evaluated the immediate and long-term effects of chronic hormonal therapy administered following surgical correction of cryptorchidism. First, using young male rats, we examined the effects of chronic human chorionic gonadotropin (HCG) and a luteinizing hormone-releasing hormone agonist (LHRH-A), alone or combined, on acute pituitary-gonadal axis responsiveness to LHRH administration. High doses of HCG and/or LHRH-A induced deleterious effects on the pituitary-testicular axis in terms of suppression of response to LHRH. Therefore, treatment with a low dose of HCG (50 U/kg/day) for 14 days was used, since it produced a significant increase in intratesticular testosterone (ITT). Second, we tested this hormonal regimen in a cryptorchid rat model. Bilateral cryptorchidism was produced by gubernaculum resection at 14 days of age. Early orchidopexy was performed at age 30 days, and HCG therapy was given from 31 to 44 days of age. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels were determined before and immediately after hormonal therapy, and at sacrifice. Animals were sacrificed at 61 days of age for determination of serum and testicular hormone levels, accessory sex organ weights and testis histology. Five or six animals from each group were retained for breeding studies at the age of 90 days. Hormonal alterations noted immediately following treatment of cryptorchid animals with HCG are not lasting. The data reveal that the fertility defect in bilateral cryptorchidism is partially prevented by early orchidopexy and that adjunctive hormonal therapy is probably of little additional benefit.

Analysis of Variance↗
PubMed1994

Defective transport of herpes simplex virus glycoprotein in interferon-treated cells: role of intracellular pH.

We have investigated the mechanism(s) of interferon (IFN)-induced inhibition of assembly steps of herpes simplex virus (HSV-1) in mouse LB cells. Data showed that physiological doses of mouse IFN-beta (10-100 IU/ml) significantly inhibited the infectivity (5- to 100-fold) of HSV-1; however, viral protein synthesis was marginally inhibited (2- to 5-fold). Immunofluorescence studies showed that most of the HSV-1gD glycoprotein accumulated intracellularly in IFN-treated LB and LMtk- cells transfected with gD cDNA, as compared to untreated controls, where most of the gD was localized on the plasma membrane. Double-immunofluorescence studies demonstrated that rhodamine-labeled wheat germ agglutinin (WGA) was co-localized with gD protein, suggesting the block was in the transport from the trans-Golgi to the plasma membrane. IFN treatment of LB and LMtk- cells raised the intracellular pH as measured by DAMP distribution and SNARF-1 using laser spectroscopy; this could play an important role in the inhibition of transport of HSV-1gD.

Animals↗
PubMed1993

A novel human cDNA with a predicted protein similar to lysyl oxidase maps to chromosome 15q24-q25.

A novel human cDNA with a predicted protein homologous to the carboxyl end of lysyl oxidase, an extracellular enzyme involved in the maturation of collagen and elastin, has been isolated. The homology to lysyl oxidase begins exactly at the position of the exon 1/exon 2 boundary in the mouse gene (Contente, S., Csiszar, K., Kenyon, K., and Friedman, R. M. (1993) Genomics 16, 395-400). This lysyl oxidase-like gene, which appears to be no larger than 22.1 kilobases, codes for a single polyadenylated RNA species of 2.48 kilobases and has been mapped to chromosome 15q24-q25.

Amino Acid Sequence↗
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↗
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↗