Measles, mumps, and rubella vaccination.
Explore the source record for details and available documents.
Drug Combinations↗
Biomedical subjects
A Hill
Publications and source records attributed to A Hill.
Earliest Homo.
The origin of our own genus, Homo, has been tentatively correlated with worldwide climatic cooling documented at about 2.4 Myr (million years). It has also been conjectured that members of Homo made the first stone tools, currently dated at 2.6-2.4 Myr. But fossil specimens clearly attributable to Homo before about 1.9 Myr have been lacking. In 1967 a fossil hominoid temporal bone (KNM-BC1) from the Chemeron Formation of Kenya was described as family Hominidae gen. et sp. indet. Although a surface find, its provenance within site JM85 (BPRP site K002) was established and a stratigraphic section provided indicating the specimen's position. This evidence has been affirmed but the exact age of the fossil was never determined, and the absence of suitable comparative hominid material has precluded a more definitive taxonomic assignment. Here we present 40Ar/39Ar age determinations on material from the hominid site indicating an age of 2.4 Myr. In addition, comparative studies allow us to assign KNM-BC1 to the genus Homo, making it the earliest securely known fossil of our own genus found so far.
Animals↗
Genetic modulation of antigen presentation by HLA-B27 molecules.
In studies of antigenic peptide presentation, we have found a healthy volunteer whose lymphoblastoid cells were unable to present three different virus-derived epitopes to cytotoxic T lymphocytes (CTL) despite expressing the correct restricting HLA-B27 molecules on the cell surface. B cell lines were established from other members of the donor's family, including individuals suffering from ankylosing spondylitis and related diseases, and were tested for their ability to function as target cells in the same assay. None of the eight B cell lines that expressed HLA-B27 presented a known peptide epitope to CTL. However, cells from a family member that expressed HLA-B8 could present an epitope peptide restricted by that molecule. The B27 molecule in this family proved to be the B2702 subtype on isoelectric focusing gels, appearing in exactly the same position as B2702 from other cell lines that did present the peptide. To exclude mutations resulting in noncharged amino acid substitutions, cDNA coding for B2702 was cloned from the proband's cell line and sequenced. No coding changes were found. The cloned cDNA was transfected into HLA-A- and B-negative HMy/C1R cells, and the B2702 molecules generated in this environment rendered these cells, after incubation with peptide, susceptible to lysis by peptide-specific CTL. These data are compatible with the presence of a factor(s), possibly HLA linked, interfering with antigen presentation by otherwise normal B2702 molecules in this family.
Antigen-Presenting Cells↗
Effect of interferon-gamma on complement gene expression in different cell types.
We have studied the expression of the complement components C2, C3, factor B, C1 inhibitor (C1-inh), C4-binding protein (C4-bp) and factor H in human peripheral blood monocytes, skin fibroblasts, umbilical vein endothelial cells (HUVEC) and the human hepatoma cell line G2 (Hep G2) in the absence and the presence of interferon-gamma (IFN-gamma). E.l.i.s.a. performed on culture fluids, run-on transcription assays, Northern blot and double-dilution dot-blot techniques confirmed that monocytes expressed all six components, whereas fibroblasts, HUVEC and HepG2 each expressed five of the six components. Fibroblasts and HUVEC did not synthesize C4-bp, and Hep G2 did not produce factor H. In addition to these differences, the synthesis rates of C3, C1-inh and factor H were not the same in all cell types. However, the synthesis rates of C2 and factor B were similar in all four cell types. The half-lives of the mRNAs were shorter in monocytes than in other cell types. Monocyte factor H mRNA had a half-life of 12 min in monocytes, compared with over 3 h in fibroblasts and HUVEC. The instability of factor H mRNA in monocytes may contribute to their low factor H secretion rate. IFN-gamma produced dose-dependent stimulation of C2, factor B, C1-inh, C4-bp and factor H synthesis by all cell types expressing these proteins, but decreased C3 synthesis in all four cell types. Cell-specific differences in the response to IFN-gamma were observed. The increased rates of transcription of the C1-inh and factor H genes in HUVEC were greater than in other cell types, while the increased rate of transcription of the C2, factor B and C1-inh genes in Hep G2 cells was less than in other cell types. IFN-gamma did not affect the stability of C3, factor H or C4 bp mRNAs, but increased the stability of factor B and C1-inh mRNAs and decreased the stability of C2 mRNA. Although these changes occurred in all four cell types studied, the half-life of C1-inh mRNA in monocytes was increased almost 4-fold, whereas the increases in the other cell types were less than 30%. These data show that the constitutive synthesis rates of complement components may vary in the different cell types. They also show that the degree of change in synthesis rates in response to IFN-gamma in each of the cell types often varies due to differences in transcriptional response, sometimes in association with changes in mRNA stability.
Carrier Proteins↗
The persistent vegetative state in children: report of the Child Neurology Society Ethics Committee.
Increasing concern about children in a persistent vegetative state (PVS) prompted a survey of members of the Child Neurology Society regarding aspects of the diagnosis and management of this disorder. Major findings of those responding to this survey (26% response rate) were as follows: (1) 93% believed that a diagnosis of PVS can be made in children, but only 16% believed that this applied to infants younger than 2 months and 70% in the 2-month to 2-year group; (2) a period of 3 to 6 months was believed to be the minimum observation period required before a diagnosis of PVS could be made; (3) 86% believed that the age of the patient would affect the duration of time needed to make the diagnosis of PVS; (4) 78% thought a diagnosis of PVS could be made in children with severe congenital brain malformations; (5) 75% believed that neurodiagnostic studies would be of value and supportive of the clinical diagnosis of PVS; (6) members' opinions as to the average life expectancy (in years) for the following age groups after the patients were considered vegetative were: newborn to 2 months, 4.1; 2 months to 2 years, 5.5; 2 to 7 years, 7.3; and more than 7 years, 7.4; (7) 20% believed that infants and children in a PVS experience pain and suffering; and (8) 75% "never" withhold fluid and nutrition from infants and children in a PVS and 28% "always" give medication for pain and suffering.(ABSTRACT TRUNCATED AT 250 WORDS)
Advisory Committees↗
Laparoscopy in the diagnosis and treatment of acute small bowel obstruction.
The surgical correction of acute small bowel obstruction is conventionally performed through a vertical laparotomy incision. The increasing use of the laparoscope for elective general surgery has led to an increase in its use for the diagnosis and treatment of acute abdominal conditions. The authors report five cases of acute small bowel obstruction treated with the aid of the laparoscope. All five patients were able to leave the hospital in the early postoperative period and remain symptom free. Laparoscopy is a useful technique in the management of selected cases of small bowel obstruction.
Acute Disease↗
Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin.
OBJECTIVE: To evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma. DESIGN: A retrospective case notes review. SETTING: The departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK. PATIENTS: All patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. INTERVENTIONS: Treatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5-5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. OUTCOME MEASURES: Response, toxicity and survival. RESULTS: Overall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 10(6) (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9. months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. CONCLUSIONS: Treatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.
Acquired Immunodeficiency Syndrome↗
Magnetic resonance imaging in pseudotumor cerebri.
The pathophysiology of pseudotumor cerebri is unclear, but may relate to an abnormality in water transport in the brain. The authors performed MR imaging in seven children with pseudotumor cerebri; the signal intensity in the white matter was normal in all patients. These data suggest that periventricular brain water content is not increased markedly in children with pseudotumor cerebri. The authors speculate that this may relate to the establishment of an equilibrium between increased resistance to cerebrospinal fluid outflow and increased brain stiffness, occurring as a consequence of increased cerebral blood-volume and/or interstitial pressure.
Adolescent↗
Analysis of four diverse population groups indicates that a subset of cystic fibrosis mutations occur in common among Caucasians.
To determine the nature and frequency of non-delta F508 cystic fibrosis (CF) mutations among diverse populations, we have sequenced exons 9-12 and 19-23 of the CF transmembrane conductance regulator (CFTR) gene from 128 CF chromosomes (39 U.S. Caucasian, 27 African-American, 42 Northern Irish, and 20 Israeli chromosomes). These regions were chosen because they encode the two putative ATP-binding folds of CFTR, domains which appear to have functional significance. In addition, CFTR exons 1 and 2 were analyzed in the American patients. Mutations were found on 49 of the 128 CF chromosomes. Nineteen different mutations were observed; six were novel, while the remaining 13 had been reported previously by our group or by other investigators. Six of nine different mutations found in African-American patients were unique to that population. However, the vast majority of the mutations found in U.S. Caucasians (eight of nine), Northern Irish (four of five), and Israelis (three of three) also occurred in other Caucasian groups. The preponderance of previously reported mutations in these three groups suggested that a subset of the non-delta F508 mutations occur in common among Caucasians. A survey of mutation frequencies in other Caucasian groups confirmed this observation. Unfortunately, this subset accounts for less than half of non-delta F508 CF mutations in most groups. These data suggest that screening for delta F508 and this select group of mutations will efficiently and economically maximize the number of CF mutations identified in Caucasian groups. However, it will be difficult to detect more than 90% of mutant CFTR alleles except in ethnically and geographically discrete populations where CF is the result of founder effect.
Amino Acid Sequence↗
Automated purification of canine islets.
Explore the source record for details and available documents.
1-Methyl-3-isobutylxanthine↗
MHC loss in colorectal tumours: evidence for immunoselection?
The reason for MHC loss in colorectal tumours remains uncertain. Strong evidence that the downregulation is due to immunoselective pressure would be provided by the finding of deletions or mutations directly involving MHC heavy chain or beta 2m genes. However, although in contrast to studies on cell lines (Brodsky et al, 1979a; Travers et al, 1986; D'Urso et al, 1991), our findings are in agreement with other evidence (Doyle et al, 1985; Blanchet et al, 1990; Henseling et al, 1990) that the most common mechanism of downregulation is regulatory, mostly at a transcriptional level. Does this imply that MHC loss in tumours can be incidental? The answer to this question will depend on the nature of the initial lesion identified. The existence of cis-acting regulatory mechanisms and dominant negative trans-acting mechanisms suggests that a single mutational event could result in transcriptional changes affecting a number of genes. Thus, selective pressure could result in tumour variants whose loss of MHC is due to transcriptional regulatory changes. As these mechanisms are unravelled, it may be possible to draw conclusions about the aetiology of MHC loss in colorectal tumours. Meanwhile, in the absence of demonstrated CTL to colorectal tumours, the case for immunoselective pressure remains unproven.
Animals↗
Dynamic cardiomyoplasty for hemodynamic support during acute pulmonary hypertension. An experimental study.
The efficacy of dynamic cardiomyoplasty for hemodynamic support during acute pulmonary hypertension was studied. Five dogs underwent a right latissimus dorsi cardiomyoplasty. Each dog was later studied in a short-term experiment. A graded acute pulmonary hypertension was induced by infusion of glass microspheres into the pulmonary artery. This resulted in decrease in pulmonary artery flow, systemic pressure, and systemic flow. The cardiomyoplasty was then stimulated with a new R wave synchronous rate-responsive pulse-train stimulator (Prometheus system). This pacemaker delivers a pulse train with the duration of stimulation determined as a proportion of the RR interval. At an optimal level of hemodynamic impairment, the dynamic cardiomyoplasty was able to immediately improve pulmonary artery flow 26.4% +/- 5.84% (standard error of the mean) (p less than 0.005, paired t test), mean systemic arterial pressure 11.6% +/- 3.7% (p less than 0.05), and thoracic aortic flow 15.7% +/- 6.3% (p less than 0.05). The degree of improvement in hemodynamic variables could be correlated with the magnitude of hemodynamic impairment present (e.g., r = 0.78; p less than 0.005 for pulmonary blood flow). We conclude that a significant beneficial effect of dynamic cardiomyoplasty on hemodynamics in short-term canine pulmonary hypertension is demonstrated in this study. Thus cardiomyoplasty may be useful in patients with right heart failure associated with increased pulmonary vascular resistance.
Acute Disease↗
Changing disease patterns in AIDS.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Preliminary analysis of murine cytotoxic T cell responses to the proteins of the flavivirus Kunjin using vaccinia virus expression.
A series of recombinant vaccinia viruses expressing various parts of the entire Kunjin virus (KUN) coding region was used to analyse the cytotoxic T (Tc) cell responses to KUN. CBA/H mice inoculated with KUN or West Nile virus were shown to develop responses to KUN or various vaccinia virus expression constructs in either primary cytotoxic assays, or after secondary stimulation of the Tc cells in vitro with KUN antigens. Tc cells from CBA mice showed the strongest response to target cells infected with recombinant vaccinia viruses expressing parts of the KUN NS3 and NS4A proteins, and only a weak response to the other structural or non-structural proteins. Further analysis of deleted versions of the NS3-NS4A region showed that the main epitope recognized was derived from a sequence of 99 amino acids spanning parts of NS3 and NS4A. No other major epitopes were detected by Tc cells from CBA mice in the remaining 3333 amino acids of the KUN polypeptide.
Animals↗
Serum sodium concentration and intraventricular hemorrhage in premature infants.
Recent data suggest that early loss of brain tissue water content, ie, decreased extravascular cerebral tissue pressure, may play a role in the pathogenesis of germinal matrix/intraventricular hemorrhage in the premature newborn. This study examines the relationship between the concentration of serum sodium and germinal matrix/intraventricular hemorrhage in 299 premature infants with birth weights of less than 1500 g during the first 4 days of life. Intraventricular hemorrhage developed in 34 (32%) of the 106 infants with maximum serum sodium levels of 145 mmol/L or less and in 54 (28%) of 193 infants whose highest serum sodium levels were greater than 145 mmol/L (chi 2 = 0.37). These data suggest that concentrations of serum sodium greater than 145 mmol/L are not associated with an increased risk of germinal matrix/intraventricular hemorrhage in the premature newborn. Consequently, more liberal administration of fluids to maintain extravascular cerebral tissue pressure is unlikely to reduce the incidence of germinal matrix hemorrhage/intraventricular hemorrhage.
Birth Weight↗
The effect of electrode position on flash visual evoked potentials in the newborn.
We examined how changes in electrode position affected the visual evoked potential in 74 high-risk newborns using a multiple electrode technique. The variation in the visual evoked potential across the occiput was documented. Visual evoked potentials that were visible at one occipital electrode position were absent at a different electrode position in 21 of 87 recordings (24%). Changes of greater than 20 msec between electrodes in latency of waves P1 or N2 occurred in 34% and 29% of recordings, respectively. The amplitude of response varied by a factor of 2.36 between mid occipital and lateral occipital electrodes. The results demonstrated that large changes in morphologic characteristics, latency, and amplitude in the visual evoked potential of the newborn result from small changes in the position of recording electrodes. These findings underscored the importance of electrode position and accurate electrode placement. Our observations also indicated that recordings from a single electrode are inadequate in providing an accurate representation of the neonatal visual evoked potential.
Evoked Potentials, Visual↗
Implantable rate-responsive counterpulsation assist system.
To apply the potential energy source available from skeletal muscle in cardiac assistance, we developed an implantable counterpulsation assist system. This study reports the results using this implantable counterpulsation assist system in an acute in vivo animal model. Twelve dogs had a dual-chambered, extraaortic counter-pulsation pump anastomosed in parallel to the thoracic aorta. The left latissimus dorsi muscle was used to power the pump. A newly developed implantable stimulator was used to make the muscle contract in synchrony with the diastolic phase. The unique feature of this stimulator is its ability to adjust timing of muscle contraction according to changing heart rates. The stimulator is also able to detect arrhythmias, and as a safety measure, shuts down until a normal rhythm is resumed. During counterpulsation assist with the implantable counterpulsation assist system, diastolic pressure increased an average of 34 mm Hg from baseline, equivalent to a 69% augmentation. Systolic peak pressure decreased an average of 10 mm Hg, equivalent to an 11% unloading. With induced heart rate changes, the implantable counterpulsation assist system readjusted its timing, maintaining optimal counterpulsation without systolic interference. Induced ventricular tachycardia resulted in immediate shutdown of the stimulator until resumption of a normal rhythm. The feasibility of using an intraaortic balloon pump console as back-up was also demonstrated. Excellent counterpulsation was obtained with either muscle power or balloon pump console. We conclude that the implantable counterpulsation assist system can provide effective counterpulsation assist and has the potential for continuous cardiac support.
Animals↗
Possible relationship between chromosome alterations and in vitro cellular radiosensitivity of human malignant melanoma.
In the present study, in vitro radiation survival analysis was performed on 8 human malignant melanoma cell lines with defined karyotypes. Exponentially growing cells were irradiated to doses of 0 to 8 Gy and examined for soft agar clonogenicity. Two groups emerged from this analysis: 4 cell lines with a small shoulder (extrapolation number, n less than 2) and 4 cell lines with a large shoulder (n greater than 2). Of possible significance, 4/4 cell lines with extrapolation numbers greater than 2 demonstrated clonal structural abnormalities of chromosome 7. In contrast, 3/4 cell lines with extrapolation numbers less than 2 had no structural abnormalities of chromosome 7. These very preliminary results suggest that structural alterations of chromosome 7 may be associated with melanoma tumors with high extrapolation numbers.
Cell Line↗