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Biomedical subjects

S A Wolfe

Publications and source records attributed to S A Wolfe.

At least 55 records · Page 3Linked to original sources

Haloperidol and spiperone potentiate murine splenic B cell proliferation.

The neuroleptics haloperidol and spiperone potentiated anti-mu induced murine B-lymphocyte proliferation in vitro and lowered the threshold of anti-mu antibody needed to trigger proliferation. Because haloperidol and spiperone are best known for actions at D2, 5HT2, alpha 1 and sigma (sigma) receptors, a series of agonists and antagonists of these receptors were tested. Dopamine and norepinephrine inhibited, and serotonin (5HT) enhanced B-cell proliferation. Spiperone opposed the suppression of proliferation by dopamine and norepinephrine. However, antagonists of D1, D2, D3, D5, 5HT2, 5HT1A, and alpha 1 receptors did not mimic the effect of haloperidol and spiperone. Furthermore, a series of sigma agonists failed to affect B-cell proliferation. Therefore it is likely that the effects of haloperidol and spiperone are not due to actions at known dopamine, 5HT, alpha 1, or sigma receptors. These findings indicate neuroleptics act not only in the CNS, but also directly on B-lymphocytes of the immune system. The pharmacological site of this action is not clear at this time.

Adjuvants, Immunologic↗

Initial characterization and autoradiographic localization of a novel sigma/opioid binding site in immune tissues.

High concentrations of novel, haloperidol- and DTG-inaccessible (+)-[3H]-3-PPP binding sites were found in human peripheral blood leukocytes rat spleen and splenocytes, but not in rat brain. Splenic sites were localized in a course punctate pattern in the marginal zones and red pulp. The pharmacology of the splenic sites was: (-)-SKF 10,047 > or = naltrexone = (-)-pentazocine > (+)-pentazocine = (-)-3-PPP = (+)-SKF 10,047 > or = (+)-3-PPP > or = dextrorphan > dextromethorphan > PCP > clorgyline. DTG, haloperidol, TCP, (-)-deprenyl and SKF 525-A did not complete. Binding activity was destroyed by heating and phospholipase C, but not by proteases or glycosidases. These sites may be involved in immunomodulation by opiate and sigma receptor agonists.

Animals↗

The use of the labiocolumellar crease incision in rhinoplasty.

Aurel Rethi, in 1934, first described the transverse upper columellar incision for open rhinoplasty for resection of a portion of columella in cases of overly projecting nasal tip. The mid columellar incision has come to be known as the "Rethi" incision. Numerous variations of this approach have been popularized through the years. Recently, a great debate has raged over the criteria to be used in selecting patients for rhinoplasty. In this paper, we review 100 consecutive rhinoplasties and discuss our technique of labiocolumellar crease incision for open approach, and relate the criteria that we utilize to select patients for open rhinoplasty. There were 37 male and 63 female patients. Of these, 32 primary, 45 secondary, 18 cleft, and 5 reconstructive rhinoplasties were performed. Twenty-eight percent of primary, 62% of secondary, 78% of cleft, and 80% of reconstructive rhinoplasties were performed using the open approach via the labiocolumellar crease incision. There were no cases of circulatory compromise of the columella. The presence of a scar along the columella base (as with the C-flap in cleft patients) should be an indication for open rhinoplasty. Several myths about the labiocolumellar crease incision are dispelled. Adhering to principles of aesthetic subunits should guide the surgeon to place scars in a less noticeable position.

Adult↗

Cranial plate and screw fixation in infancy: an assessment of risk.

Sixty-seven surgeons, members of the International Craniofacial Surgery Society, responded to a questionnaire focused on assessing the incidence and risk of cranial plate and screw translocation intracranially in infants undergoing cranial surgery. Despite screws, plates, and wires being evident intracranially in individual cases, no apparent increase in seizure frequency or susceptibility to head trauma was noted in this preliminary study.

Bone Plates↗

The temporalis muscle flap revisited on its centennial: advantages, newer uses, and disadvantages.

Analysis of a series of 85 temporalis muscle flaps performed in 81 patients is presented. The flaps were used in a wide range of locations ranging from intracranial to mandible and for a large variety of diagnostic categories. A detailed examination of the indications and use of the muscle for cranial base and palatal defects is provided. The amount of muscle used varied considerably from 10 to 90 percent. Complications associated with the use of the temporal muscle included a 2.4 percent total flap failure rate and a 9.4 percent minor complication rate. When greater than half the muscle was used, temporal hollowing, the principal donor defect, was imperceptible (39 percent) or mild (46 percent) in a majority of patients and severe in only a few (16 percent). Recommendations for prevention and treatment of this contour deformity are discussed in depth.

Adolescent↗

Assessing substance abuse treatment needs among the homeless: a telephone-based interactive voice response system.

OBJECTIVES: We report on a pilot project that used a telephone-based interactive voice response system accessed by cellular phones at diverse sites, to interview homeless persons on their need for alcohol and other drug treatment. METHODS: Using this technique we surveyed 207 homeless adults at eight shelters in Cleveland, Ohio. RESULTS: The cellular approach was comparable to human-administered interviews in reliability and validity and yielded higher self-reported levels of drug use. CONCLUSIONS: Cellular telephones and interactive voice response interviewing systems can be useful tools in assessing for the health-service needs of difficult-to-reach populations.

Adult↗

Expression of the testis-specific histone H1t gene: evidence for involvement of multiple cis-acting promoter elements.

The histone H1t gene is expressed exclusively in testis primary spermatocytes. Previous studies indicate that accumulation of H1t mRNA occurs only in primary spermatocytes in normal rats and in transgenic mice bearing the rat H1t transgene. In this study, DNA sequences of human, monkey, mouse, and rat H1t genes were compared and found to be almost identical in the proximal promoter region extending from the H1/AC box through the TATAA box. In addition to conserved elements common to replication-dependent H1 promoters, the H1t promoter contains a unique TE element, and sequences within this element may contribute to enhanced expression of the gene in primary spermatocytes. Two imperfect inverted repeat sequences designated TE1 and TE2, that are located within the larger TE element, overlap a central GC-rich region and bind specifically to nuclear proteins derived from primary spermatocytes. Protein interactions characterized by methylation interference and UV cross-linking experiments indicate that a complex of proteins with a molecular mass of approximately 180 kDa binds TE1. The GC-rich region in H1t and in some replication dependent histone H1 promoters contains an Sp1 consensus sequence. Although the H1t/TE element that contains the GC-rich region binds nuclear proteins, it does not appear to bind Sp1 obtained from cell populations enriched in primary spermatocytes as determined by electrophoretic mobility supershift assays using polyclonal anti-Sp1 antibodies.

Animals↗

Testis-specific expression of the rat histone Hlt gene in transgenic mice.

The testis-specific histone Hlt gene is transcribed only in testis. The appearance of testis-specific nuclear proteins that bind to a unique promoter sequence element designated Hlt/TE located between the H1/AC box and the H1/CCAAT box correlates with the onset of transcription of the Hlt gene during the meiotic cell cycle. In order to determine whether sequences flanking the rat Hlt gene are sufficient to confer tissue-specific expression in vivo, a 6859 bp EcoRI restriction fragment of genomic DNA containing the rat histone Hlt gene has been microinjected into mouse embryos. S1 nuclease protection analysis has shown that the descendants of the resulting transgenic mice express the rat gene in the proper tissue and at the proper meiotic cell cycle stage. Furthermore, when populations of mouse testis cells were prepared by centrifugal elutriation, only the fraction enriched in pachytene primary spermatocytes had a significant steady-state level of rat Hlt mRNA. Although the copy-number of the transgene was variable in these animals, rat Hlt mRNA levels in high copy-number animals never exceeded 2.6 times the level in normal rat testes. The appearance of appropriate meiotic cell cycle-specific transcription indicates the importance of the conserved promoter sequence elements between the two species.

Animals↗

Sigma-1 receptors modulate functional activity of rat splenocytes.

Neuroleptics, opiates, and cocaine are commonly prescribed for or abused by humans. Although primarily used for their actions at other receptors in brain, these compounds also act at sigma receptors. We have previously identified sigma-1 receptors on human peripheral blood leukocytes and rat spleen, and in the present study we demonstrate a correlation between the pharmacology of these receptors and the ability of drugs to suppress concanavalin A-induced splenocyte proliferation. These results support the hypothesis that sigma-1 receptors regulate functional activities of immune cells, and suggest that sigma agonists may cause changes in immune competence in vivo.

Animals↗

Biochemical folate, B12, and iron status of a group of pregnant adolescents accessed through the public health system in southern Ontario.

PURPOSE: This study was designed to estimate the prevalence of biochemical iron, folate, and vitamin B12 depletion among a group of Canadian pregnant adolescents accessed through the Public Health system. Further, the impact of prenatal supplement use, chronologic age, gynecologic age, living arrangement, main source of income, postpartum custody plan, time of entry into prenatal care, and cigarette smoking on laboratory indices of the three nutrients were determined. METHODS: Fifty-eight adolescents (14.5-19.0 years) were interviewed and blood samples were collected at 36 +/- 2 wk gestation. RESULTS: Thirteen (22%) of the pregnant adolescents had anemia (hemoglobin < 110 g/L) and forty-five (78%) had depleted iron stores (plasma ferritin < 26.6 pmol/L or 12.0 micrograms/L). Twenty-five subjects had plasma B12 values in the sub-optimal range (< 148 pmol/L). Five of the 16 adolescents who infrequently or never consumed a folate-containing supplement had suboptimal erythrocyte folate values. Twenty-four percent of the subjects had hypersegmented neutrophils and of these, all and 71% of subjects had plasma ferritin and B12 concentrations in the suboptimal range, respectively. Self-reported folic acid and B12 supplement intakes were correlated with the corresponding blood values for these nutrients. In contrast, supplement iron use was only weakly, or not at all associated with biochemical indices of iron status. CONCLUSIONS: Data from the present study indicate that plasma B12 and ferritin levels are low in a group of pregnant adolescents. These low values appear to be associated with a high prevalence of hypersegmented neutrophils. Prenatal supplement use appears to reduce the risk of low folate and B12 blood values but not biochemical iron status.

Adolescent↗

Modifying the helical structure of DNA by design: recruitment of an architecture-specific protein to an enforced DNA bend.

BACKGROUND: Proteins can force DNA to adopt distorted helical structures that are rarely if ever observed in naked DNA. The ability to synthesize DNA that contains defined helical aberrations would offer a new avenue for exploring the structural and energetic plasticity of DNA. Here we report a strategy for the enforcement of non-canonical helical structures through disulfide cross-linking; this approach is exemplified by the design and synthesis of an oligonucleotide containing a pronounced bend. RESULTS: A localized bend was site-specifically introduced into DNA by the formation of a disulfide cross-link between the 5' adenines of a 5'-AATT-3' region in complementary strands of DNA. The DNA bend was characterized by high-resolution NMR structure determination of a cross-linked dodecamer and electrophoretic mobility assays on phased multimers, which together indicate that the cross-linked tetranucleotide induces a helical bend of approximately 30 degrees and a modest degree of unwinding. The enforced bend was found to stimulate dramatically the binding of an architecture-specific protein, HMG-D, to the DNA. DNase I foot-printing analysis revealed that the protein is recruited to the section of DNA that is bent. CONCLUSIONS: The present study reports a novel approach for the investigation of non-canonical DNA structures and their recognition by architecture-specific proteins. The mode of DNA bending induced by disulfide cross-linking resembles that observed in structures of protein-DNA complexes. The results reveal common elements in the DNA-binding mode employed by sequence-specific and architecture-specific HMG proteins.

Cross-Linking Reagents↗

Vertical orbital dystopia: definition, classification and treatment.

Correction of vertical orbital dystopia is an important component part of providing facial symmetry in a number of conditions of varied etiology having facial imbalance and asymmetry. The most important step is the initial one of making a proper diagnosis, since some conditions represent globe dystopia rather than true orbital dystopia, and can be treated by extracranial procedures. However, if an intracranial procedure is felt indicated, it adds to the safety rather than the complexity of the procedure, and one should not hesitate advocating this to the patient.

Adolescent↗

Complications associated with the harvesting of cranial bone grafts.

This study was undertaken to determine the incidence of serious neurologic injury associated with the harvesting of cranial bone grafts. A personal series of 1000 consecutive bone-grant harvestings (cranial, iliac, costal, tibial, and mandibular) was examined in detail for complications. Then a survey of members of the International Society of Craniofacial Surgeons was performed, and data were compiled on complications of bone-graft harvestings performed by the respondents. Data also were compiled on neurologic complications related to cranial bone-graft harvestings performed by other surgeons which the respondents were aware of through direct personal knowledge, medicolegal review, the medical literature, or other channels. No neurologic complications were associated with any of the 586 cranial bone grafts taken in the authors' series. The survey respondents reported that they had performed 12,672 cranial bone-graft harvestings. Temporary neurologic complications were associated with graft harvesting in 3 cases (0.02 percent). The respondents also identified 8 other neurologic complications (4 permanent and 4 temporary) associated with cranial bone-graft harvestings performed by other surgeons. Five cases were performed by surgeons having little or no experience in harvesting cranial bone grafts, and three were performed by surgeons having only limited training. It appears that cranial bone grafts can be harvested with an extremely low incidence of serious complications by surgeons who have had proper training. Techniques are suggested for safe harvesting of cranial bone grafts, as well as for detecting and managing complications when they arise.

Bone Transplantation↗

Primate testicular histone H1t genes are highly conserved and the human H1t gene is located on chromosome 6.

The testis-specific histone H1t gene is known to be transcribed only in pachytene primary spermatocytes during spermatogenesis. Previous studies of the rat histone H1t gene revealed a unique promoter sequence element between the H1/GC box and the H1/CCAAT box. Proteins in crude nuclear extracts of rat testis bind specifically to this sequence element and a temporal correlation exists between the appearance of these DNA binding proteins and the onset of transcription. These discoveries led to a search for histone H1t genes in other mammalian species. The human and monkey histone H1t genes were amplified from genomic DNA using the polymerase chain reaction (PCR). The amplified genes were cloned and the genomic derived inserts were sequenced using linear PCR. Both proximal promoters contained the highly conserved H1/AC box, H1/CCAAT box, and H1/TATA box found in nongerminal H1 genes. Both promoters also contained the H1/GC box and the H1t/CCTAGG sequence element between the H1/GC box and H1/CCAAT box previously seen only in the H1t promoter. Specific amplification of the human H1t gene using template DNA samples from a NIGMS human/rodent somatic cell hybrid mapping panel has shown that the human histone H1t gene is located on chromosome 6.

Amino Acid Sequence↗

Zinc status of a group of pregnant adolescents at 36 weeks gestation living in southern Ontario.

OBJECTIVE: Pregnant adolescents have very high zinc (Zn) requirements to support the developing fetus and to maintain skeletal maturation after menarche. METHODS: Sixty-six adolescents aged 17.1 +/- 0.15 years (mean +/- SEM; range 14.5-19.0 years) were recruited from three regions of Southern Ontario at 35.9 +/- 0.15 weeks gestation. Data on sociodemographic status, health, infant birth weight and birth length, smoking, alcohol consumption, and prenatal supplement use were collected. Fasting venipuncture blood was analyzed for Zn (via AAS) and alkaline phosphatase in plasma; scalp hair was analyzed for Zn by instrumental neutron activation. RESULTS: Mean (95% CI) values were: plasma Zn 10.7 (10.0-11.5) mumol/L; plasma alkaline phosphatase 46.6 (43.7-49.5) U/L; hair Zn 2.64 (2.52-2.77) mumol/g. None of the plasma and hair Zn values were indicative of suboptimal Zn status. Mean plasma Zn concentrations of subjects (n = 19) consuming a supplement with Zn sulfate were higher than those of subjects consuming a supplement with Zn oxide (n = 18) (12.2 vs 9.7 mumol/L; p < 0.02) and unsupplemented subjects (n = 11) (9.4 mumol/L). Plasma Zn concentrations correlated negatively with reported birth lengths (mean +/- SEM = 51.6 +/- 0.31 cm) while accounting for chronological age (r = 0.42; p < 0.01), but not with reported birth weights (mean +/- SEM = 3.439 +/- 0.107 kg). CONCLUSIONS: Results emphasize that the form of Zn must be taken into account when considering the impact of prenatal supplements containing Zn on plasma Zn concentrations. Suboptimal Zn status was not prevalent in these pregnant adolescents.

Adolescent↗

Lengthening the nose: a lesson from craniofacial surgery applied to posttraumatic and congenital deformities.

Various methods of nasal lengthening presented in the literature are discussed, including extensive skin undermining, provision of extra skin by forehead flaps, bone grafts, cartilage grafts to the nasal tip, extensive dissection of nasal lining, and buccal flaps to provide additional nasal lining. This paper describes a method that entails a nasofrontal osteotomy and mobilization of previous fractures in posttraumatic foreshortened noses and a perinasal osteotomy (Le Fort II minus Le Fort I) in congenitally short noses such as seen in Binder's syndrome. Nine posttraumatic and two congenital short noses have been treated in this manner without complication. The procedure draws on experience in craniofacial surgery, where there is a nasofrontal osteotomy and division of lining in extracranial Le Fort II and III osteotomies with insertion of an interpositional bone graft. This method is recommended for markedly foreshortened noses of either traumatic or congenital origin.

Adolescent↗

Histone H1t: a tissue-specific model used to study transcriptional control and nuclear function during cellular differentiation.

One of the most prominent and best studied family of genes is the histone gene family. In recent years, histone gene regulation during the cell cycle of somatic cells has been studied extensively. This paper is intended to highlight and emphasize recent data concerning the tissue-specific expression of histone H1t using spermatogenesis as a model system. In this article we describe a unique DNA element within the proximal promoter of the histone H1t gene. This element has been shown to bind exclusively to nuclear proteins from pachytene spermatocytes and early spermatids. Thus, there is a strong temporal correlation between the appearance of the testis-specific DNA-binding protein and the onset of transcription of the testis-specific histone H1t gene.

Animals↗