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Biomedical subjects

K Farmer

Publications and source records attributed to K Farmer.

At least 19 recordsLinked to original sources
PubMed1999

A prospective study of long-term health outcomes among Oklahoma City bombing survivors.

A follow-up study was conducted to identify long-term physical and emotional outcomes among Oklahoma City bombing survivors. Baseline data were gathered by the Oklahoma State Department of Health in 1995. Follow-up data were gathered by telephone interviews of survivors from 1-1/2 to 3 years after the bombing. The frequency of medical diagnoses, symptoms, medical cost, physical and social life changes, and services utilized since the bombing were assessed. A total of 494 persons were interviewed, 92 percent had been physically injured in the bombing. Seventy-nine percent of persons interviewed rated their general health status as "good," "very good," or "excellent." Overall, one-fourth to one-third of survivors reported being newly diagnosed with audiologic changes, anxiety, and depression since the bombing. One-third of persons reported preexisting medical conditions that had worsened since the bombing including depression (26%) and asthma/bronchitis (22%). The most frequently reported posttraumatic stress disorder symptoms were "being jumpy or easily startled" and "recurring distressful thoughts of the bombing." The most frequently utilized medical services were psychological counseling (63%) and audiology services (48%). Total costs were estimated of $ 5.7 million. Overall, persons who had been hospitalized with bombing injuries reported higher rates of diagnoses, symptoms, and services utilization. These findings suggest that a large proportion of survivors of a terrorist bombing, especially those seriously injured, will experience long-term physical and/or emotional outcomes and increased need for treatment for bombing-related medical conditions. All survivors should be carefully assessed over time for auditory damage, depression, anxiety, and posttraumatic stress disorder.

Adolescent↗
PubMed1997

Measles control.

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Humans↗
PubMed1996

Monoclonal antimyogenin antibodies define epitopes outside the bHLH domain where binding interferes with protein-protein and protein-DNA interactions.

We have developed a panel of monoclonal antibodies against rat myogenin, a skeletal muscle regulatory protein of the bHLH family. Some of these monoclonals have been widely used by others, and details of their production are presented. Mapping the epitopes by immunoprecipitation of myogenin deletion mutants demonstrates that this panel recognizes epitopes spanning the entire molecule outside the HLH region. Four antibodies against epitopes outside the bHLH region interfere with the binding of myogenin/E-protein heterodimers to DNA sequences containing the myogenin heterodimer consensus recognition site. Three of these epitopes are partially masked in the heterodimers; antibody binding to these epitopes reduces the interactions between myogenin and E12. This suggests that surfaces outside the HLH dimerization domain may contribute to the stability of myogenin/E12 complexes. The binding of one antibody to its epitope did not appear to affect the myogenin/E12 interaction but nonetheless interfered with the binding of the complex to DNA, suggesting that this epitope lies near to a surface occupied by DNA.

Animals↗
PubMed1994

Myogenic cell lines derived from transgenic mice carrying a thermolabile T antigen: a model system for the derivation of tissue-specific and mutation-specific cell lines.

Skeletal myoblasts cloned from limb muscles of H-2Kb-tsA58 transgenic mice remained proliferative through at least 80 generations under conditions permissive for expression and function of the tsA58 gene product. When switched to nonpermissive conditions or implanted into muscles of nude mdx mice they underwent differentiation but, in one clonal cell line, a small proportion appeared to become quiescent muscle precursors in vivo. H-2Kb-tsA58 X mdx/mdx F1 male mice yielded dystrophin-deficient myoblasts. By such simple genetic crosses, H-2Kb-tsA58 transgenic mice provide a valuable tool for the rapid isolation of cell lines, myogenic or otherwise, bearing mutations of interest.

Animals↗
PubMed1993

Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma: I. Clinical and vascular studies.

A trial of FAA and rIL-2 has been performed both to study the clinical efficacy of this combination and to determine whether they cause haemorrhagic necrosis by acting upon tumour vasculature. FAA and rIL-2 were given to 23 patients with progressing metastatic melanoma. FAA 4.8 gm m-2 was given as a 1 h infusion without urine alkalinisation on days 1, 8 and 15. rIL-2 (6-18 x 10(6) IU/m2/day) was given as a continuous infusion days 8-12 and 15-19 (nine patients) or days 8-12 only (14 patients). Treatment was repeated after 2 weeks unless there was disease progression. Of the 21 assessable patients there have been one complete (skin and liver) and two partial responses (skin and liver, skin and nodes) lasting 20 + 17 + and 15 months, overall response rate 14%. Unexpectedly severe hypotension after the third FAA, when given 2-4 days after RIL-2, was the major toxicity (8/15 grade 3 or 4). No alteration in coagulation parameters were seen during therapy of the first ten patients. No increase in tumour necrosis was seen in any of the 15 biopsies taken from ten patients after therapy. This suggests that FAA does not have similar vascular effects in human as it does in murine tumours.

Adult↗
PubMed1993

Proliferation and differentiation of human fetal myoblasts is regulated by PDGF-BB.

A myoblast clone, G6, was obtained from thigh muscle of an 11 week old human fetus, and used to examine the effect of platelet-derived growth factor (PDGF) on cell multiplication and differentiation. G6 myoblasts showed extensive fusion, and expressed creatine phosphokinase activity and muscle specific gene mRNA (myosin heavy chain, alpha-actin) when switched to a differentiation medium. The cells expressed PDGF beta-receptor mRNA, and bound 125I-PDGF-BB specifically. Expression of PDGF beta-receptors declined during in vitro differentiation. Relative levels of transcripts for the myogenic regulatory factors Myf4 (myogenin), Myf5, and Myf6 (MRF4) increased during the differentiation process, whereas Myf3 (MyoD1) was preferentially expressed in undifferentiated myoblasts. Treatment of the myoblasts with PDGF-BB increased DNA synthesis and cell density. Myogenic differentiation, analyzed as number of nuclei present in myotubes and expression of creatine phosphokinase and myosin heavy chain, was partly inhibited by the presence of PDGF-BB in the differentiation medium. PDGF-BB may, therefore, have the potential of regulating human muscle development and muscle regeneration.

Becaplermin↗
PubMed1992

Alternative multimeric structures affect myogenin DNA binding activity.

The native molecular weight of the basic helix-loop-helix (bHLH) proteins myogenin, MyoD, and E12 was calculated from their mobilities on sucrose gradients and molecular sieve chromatography. The muscle bHLH proteins associate to form a variety of higher order complexes, most of which are larger than dimers. Homodimers bind to DNA sequences such as the MEF-1 site in the creatine kinase enhancer whereas homotetramers and larger forms do not recognize this DNA sequence. The ubiquitous bHLH protein E12 forms monomers or homodimers with little evidence for higher order complexes. Mixtures of myogenin and E12 show some heterodimeric structures, but most of the myogenin remains in large complexes. This result using purified proteins is also obtained in nuclear extracts from differentiated myotubes, in which most of the myogenin is present in large complexes that do not bind to the creatine kinase enhancer. A fusion protein containing only the myogenin HLH region forms large homomeric complexes. A model is presented in which each helix associates with a different subunit to form chains or ring structures to explain these observations. The partition of myogenin in nuclear extracts into dimers that recognize known DNA sequences and higher order complexes that do not raises important new issues concerning the regulation of skeletal muscle bHLH protein activity during myogenesis.

Animals↗
PubMed1992

Preliminary studies on the interaction of TNF alpha and IFN gamma with alpha 2-macroglobulin.

The binding of 125I-labelled recombinant human TNF alpha and IFN gamma to isolated human blood alpha 2-macroglobulin has been investigated using molecular sieving procedures and non-denaturing PA gel electrophoresis in combination with autoradiography. These studies revealed that both cytokines readily bind to the electrophoretically fast form of alpha 2M generated by methylamine or protease treatment of this protein. PAGE/SDS gel investigations indicated that TNF alpha bound non-covalently while the IFN gamma interaction was covalent in nature. Preliminary competition studies also indicate that cold TNF alpha and IL-2 are more effective than cold IFN gamma at inhibiting the binding of labelled IFN gamma to alpha 2M. Bioassays revealed that "native" alpha 2M or its derivatives at 2 mg/ml concentration did not impair the antiproliferative effects of TNF alpha and IFN gamma on susceptible bladder tumour cell lines. Furthermore they did not interfere in the induction of Class II antigen expression by IFN gamma on inducible cell lines or in a 2-site ELISA assay for TNF.

Antigens, Neoplasm↗
PubMed1992

MyoD, myogenin independent differentiation of primordial myoblasts in mouse somites.

The accumulation of two myogenic regulatory proteins, MyoD and myogenin, was investigated by double-immunocytochemistry and correlated with myosin heavy chain expression in different classes of myoblasts in culture and during early myogenesis in vivo. During in vitro differentiation of fetal myoblasts, MyoD-positive cells were detected first, followed by the appearance of cells positive for both MyoD and myogenin and finally by the appearance of differentiated myocytes and myotubes expressing myosin heavy chain (MHC). A similar pattern of expression was observed in cultures of embryonic and satellite cells. In contrast, most myogenic cells isolated from newly formed somites, expressed MHC in the absence of detectable levels of myogenin or MyoD. In vivo, the appearance of both myogenin and MyoD proteins was only detected at 10.5 d postcoitum (d.p.c.), when terminally differentiated muscle cells could already be identified in the myotome. Parasagittal sections of the caudal myotomes of 10.5-d-old embryos showed that expression of contractile proteins preceded the expression of myogenin or MyoD and, when coexpressed, MHC and myogenin did not co-localize within all the cells of the myotome. In the limb bud, however, many myogenin (or MyoD) positive/MHC negative cells could be observed in the proximal region at day 11. During further embryonic development the expression of these proteins remained constant in all the muscle anlagens examined, decreasing to a low level during the late fetal period. Western and Northern analysis confirmed that the myogenin protein could only be detected after 10.5 d.p.c. while the corresponding message was clearly present at 9.5 d.p.c., strongly suggesting a posttranscriptional regulation of myogenin during this stage of embryonic development. These data show that the first myogenic cells which appear in the mouse myotome, and can be cultured from it, accumulate muscle structural proteins in their cytoplasm without expressing detectable levels of myogenin protein (although the message is clearly accumulated). Neither MyoD message or protein are detectable in these cells, which may represent a distinct myogenic population whose role in development remains to be established.

Animals↗
PubMed1992

Multimeric structures influence the binding activity of bHLH muscle regulatory factors.

Sucrose gradients and molecular sieve chromatography were used to determine the native molecular weight of the basic HLH proteins myogenin, MyoD and E12. The muscle bHLH proteins not only formed dimers but also associated in a variety of higher order complexes. Although homodimers bind to DNA sequences such as the MEF-1 site in the creatine kinase enhancer, homotetramers and larger forms do not recognize this DNA sequence. Little evidence for complexes larger than dimers was found for the ubiquitous bHLH protein E12. Most of the myogenin remains in large complexes when myogenin and E12 are mixed. The same result was obtained in nuclear extracts from differentiated myotubes, in which most of the myogenin was found to be present in large complexes that do not bind to the creatine kinase enhancer. A fusion protein that contains only the myogenin HLH region fused to glutathione-S-transferase also forms large homomeric complexes. A model to explain these results is that each helix of the HLH motif can associate with a different subunit to form chains or ring structures. The presence of myogenin in nuclear extracts as both dimers that recognize known DNA sequences as well as higher order complexes that do not raises significant issues concerning the regulation of skeletal muscle bHLH protein activity during myogenesis.

Animals↗
PubMed1989

Morbidity from acquired cytomegalovirus infection in a neonatal intensive care unit.

In a prospective study of transfused neonates, 32 of 262 infants were viruric at greater than 20 days of life. Of 212 neonates whose early status was known, postnatally acquired infection was proven in 21, two of whom were seronegative at birth and were thought to have transfusion-acquired cytomegalovirus (CMV). Maternal transmission of CMV is important in this population as there was 91% seropositivity for CMV at birth among the 21 babies who acquired CMV compared with 55% positivity among 150 babies who did not shed CMV (P less than 0.01). Significantly increased morbidity (increased length of stay in hospital, increased use of antibiotics, and longer duration of antibiotic administration) was found in babies with acquired CMV compared with matched controls who did not become viruric. Significant morbidity and mortality was not restricted to the two seronegative babies with transfusion-acquired CMV. The cost of providing CMV antibody negative blood for this neonatal unit would be less than the cost of providing the extended hospital care needed by the two babies with transfusion-acquired CMV found during this 3 year study.

Cytomegalovirus↗
PubMed1987

A combination of hepatitis B vaccine and immunoglobulin does not protect all infants born to hepatitis B e antigen positive mothers.

In 42 infants of hepatitis B e antigen positive carrier mothers a randomised study of a low dose (5 micrograms) hepatitis B vaccine regimen starting within 24 hours of birth with or without hepatitis B immunoglobulin (0.25 ml/kg) showed that in the vaccine group 72% were antibody positive at the age of one year and in the vaccine plus immunoglobulin group 81%. In the vaccine group four of 18 infants were not protected and in those infants receiving vaccine plus immunoglobulin three of 21 were HBsAg carriers by 12 months of age. Hepatitis B vaccine either with or without concomitant HBIg did not protect all babies born of HBeAg positive mothers, from developing the HBsAg carrier status. Thus for full protection of all infants a more vigorous immunisation programme will be necessary.

Carrier State↗
PubMed1985

Passive immunoprophylaxis of hepatitis B virus infections in newborn infants.

Newborn infants of mothers who were chronic carriers of hepatitis Bs antigen (HBsAg) were randomly allocated to be treated or not treated with hyperimmune hepatitis B immunoglobulin (HBIg) at birth and six weeks and were then followed up to one year with sequential blood tests. Ninety percent of all untreated infants born of mothers positive for both HBsAg and hepatitis Be antigen became chronic carriers of HBsAg at one year. In contrast only 9% of infants treated with HBIg became HBsAg positive. Mothers who were HBsAg positive but hepatitis Be antigen negative only uncommonly infected their infants, with 6% being HBsAg positive at one year. Nearly all infections were in Pacific Islanders, Maoris or Asians. It is recommended that antenatal testing of these groups most at risk for hepatitis B virus spread, be initiated, followed by passive immunoprophylaxis with HBIg of infants born of HBsAg, HBeAg positive mothers.

Carrier State↗
PubMed1984

High admission rate of infants and young children with whooping cough: clinical aspects and preventive implications.

Eighty-five children hospitalized with clinical whooping cough over an 8 month period were studied. Of the 53 cultured for Bordetella pertussis, 29 (55%) were culture positive. There was a preponderance of young infants who required a long hospitalization (35% were less than 3 months of age). Many of these children had apnoeic attacks requiring active intervention. Pulmonary atelectasis-consolidation was found in 46% in spite of negative viral and bacterial studies. Over-crowding and poor socioeconomic status was noted frequently in those hospitalized. This group makes the least use of child health services, and has the lowest rate of immunizations.

Age Factors↗
PubMed1984

A case of agammaglobulinaemia complicated by meningoencephalitis due to Echo virus 27.

A boy with agammaglobulinaemia diagnosed and treated from the age of 3 years 2 months developed encephalitis at 4 years 3 months. The illness showed a remitting but deteriorating course until death aged 6 years 5 months. Echo virus type 27 was isolated from the cerebrospinal fluid during the terminal illness. The virus was not isolated from five earlier cerebrospinal fluid samples nor was virus detected in a temporal lobe biopsy.

Agammaglobulinemia↗