Breaking free from thermodynamic constraints: thermal acclimation and metabolic compensation in a freshwater zooplankton species.

Respiration rates of ectothermic organisms are affected by environmental temperatures, and sustainable metabolism at high temperatures sometimes limits heat tolerance. Organisms are hypothesized to exhibit acclimatory metabolic compensation effects, decelerating their metabolic processes below Arrhenius expectations based on temperature alone. We tested the hypothesis that either heritable or plastic heat tolerance differences can be explained by metabolic compensation in the eurythermal freshwater zooplankton crustacean Daphnia magna We measured respiration rates in a ramp-up experiment over a range of assay temperatures (5-37°C) in eight genotypes of D. magna representing a range of previously reported acute heat tolerances and, at a narrower range of temperatures (10-35°C), in D. magna with different acclimation history (either 10 or 25°C). We discovered no difference in temperature-specific respiration rates between heat-tolerant and heat-sensitive genotypes. In contrast, we observed acclimation-specific compensatory differences in respiration rates at both extremes of the temperature range studied. Notably, there was a deceleration of oxygen consumption at higher temperature in 25°C-acclimated D. magna relative to their 10°C-acclimated counterparts, observed in active animals, a pattern corroborated by similar changes in filtering rate and, partly, by changes in mitochondrial membrane potential. A recovery experiment indicated that the reduction of respiration was not caused by irreversible damage during exposure to a sublethal temperature. Response time necessary to acquire the respiratory adjustment to high temperature was lower than for low temperature, indicating that metabolic compensation at lower temperatures requires slower, possibly structural changes.

Event excess in the MiniBooNE search for ¯νµâ†’¯νe oscillations.

The MiniBooNE experiment at Fermilab reports results from a search for ¯ν_{µ}→¯ν_{e} oscillations, using a data sample corresponding to 5.66×10²° protons on target. An excess of 20.9±14.0 events is observed in the energy range 475

A single ThinPrep slide may not be representative in all head and neck fine needle aspirate specimens.

OBJECTIVES: Ideally, head and neck aspiration should be performed by trained aspirators within the setting of a one-stop clinic, where smeared material is available for immediate assessment. However, this may not always be possible for practical reasons and the use of liquid-based techniques in head and neck cytology is increasing. Although liquid-based cytology has been extensively validated for use in gynaecological cytology, no studies have investigated whether or not a single ThinPrep slide is representative for head and neck aspirate specimens. We performed a prospective audit of head and neck fine needle aspiration specimens processed by the ThinPrep method to investigate whether a single ThinPrep slide was representative. METHODS: A prospective audit of 115 consecutive head and neck aspirates was carried out. A single ThinPrep slide was prepared and a diagnosis recorded. The remainder of the specimen was then spun down and prepared as a cell block. The ThinPrep and cell block diagnoses were compared. RESULTS: In 36 cases (31%), the cell block provided additional information that contributed to the diagnosis. In 14 (12%), the cell block was regarded as essential to the diagnosis. CONCLUSIONS: A single ThinPrep slide may not provide representative diagnostic material in all head and neck aspirates. This should be taken into consideration when contemplating the use of liquid-based methods for non-gynaecological cytology.

Human papilloma virus in squamous carcinoma of the head and neck: a study of cases in south east Scotland.

Several studies have found human papillomavirus virus (HPV) in tissue from head and neck squamous cell carcinomas (HNSCCs), although the number of positive cases varies greatly from study to study. The extent and molecular epidemiology of HPV in HNSCC were assessed within cases drawn from southeast Scotland by performing broad-spectrum, real-time HPV polymerase chain reaction (PCR) on DNA extracted from 100 cases of HNSCC in formalin-fixed, paraffin wax-embedded material. All HPV-positive specimens were genotyped and sampled by laser capture microdissection. Pure samples of tumour, and, where possible, dysplastic and normal epithelium were then submitted for further HPV PCR and genotyping to investigate the sensitivity of the technique in small tissue samples. 10 of 100 cases tested positive for HPV, with 8 of these being derived from Waldeyer's ring. HPV DNA was found in adjacent epithelium in two of four cases where this was available. These findings confirm that HPV is likely to be involved in a subset of HNSCC in this population and that successful amplification of HPV nucleic acid is possible even using small amounts of paraffin wax-embedded tissue.

Factors influencing the viscous properties of chicken tracheal mucins.

1. Reduced viscosities, in water, of different types of mucin, such as fibrillar, gelatinous and soluble phase, separated from chicken tracheal secretions were measured. 2. H-bond breaking agents caused a significant decrease in the reduced viscosity of these mucins, but thiol-reagents alone did not have any effect. 3. Papain and Pronase did not cause any decrease in the reduced viscosity of these mucins. Neuraminidase decreased the reduced viscosity of soluble phase mucin by 50% by removing about 30% of its N-acetylneuraminic acid but had no effect on fibrillar and gelatinous mucins. Sulphatase neither removed any sulphate ester groups nor decreased the reduced viscosity. Due to some nonspecific intermolecular interaction, mixtures of mucins and enzymes or ovalbumin exhibited elevated reduced viscosities. 4. Ionic strength of the solutions appeared to decrease the reduced viscosity of these mucins. Increasing concentrations of Ca2+ in solutions of ionic strength of approx. 0.1 caused significant decrease in the reduced viscosity, but had no such effect in solutions of ionic strength of more than 0.1. 5. N-Acetylneuraminic acid and sulphate ester residues were 46.6 +/- 0.2, 43.4 +/- 0.6, 27.9 +/- 3.3 mg/g and 66.0 +/- 2.0, 34.2 +/- 3.3, 2.5 +/- 0.8 mg/g for fibrillar, gelatinous and soluble phase mucins, respectively. There appeared to be a good correlation between viscosity and N-acetylneuraminic acid contents among mucins of low reduced viscosities and between viscosity and sulphate ester residues among mucins of high reduced viscosities.

HLA genotypic study of insulin-dependent diabetes the excess of DR3/DR4 heterozygotes allows rejection of the recessive hypothesis.

The genetics of insulin-dependent diabetes mellitus (IDDM) is currently an area of controversy, with some investigators proposing heterogeneity within the HLA region and even the existence of non-HLA-linked susceptibility genes, and others maintaining that a simple autosomal recessive gene linked to HLA with reduced penetrance is an adequate explanation. To resolve this latter question, we report here a simple method of testing whether a single HLA-linked susceptibility gene is inherited in a recessive fashion when it is associated with two different HLA alleles, as is the case for IDDM. It is shown that if the number of DR3/DR4 heterozygotes in a diabetic population exceeds the combined sum of DR3/3 and DR4/4 homozygotes in that same diabetic population, then a recessive mode of inheritance can be rejected. The advantages of the method are that it does not depend on ratios, as do relative risk calculations, nor does it depend on control data, but is based only on studies of the diabetics themselves. With data on 193 genotyped IDDM patients, we can clearly reject the recessive mode of inheritance, since the number of heterozygotes is 68 compared with a maximum of 22 homozygotes (P less than 10(-4)). Eight other published studies are in concordance with these results. Therefore, a nonparametric test, independent of the significance of any individual study, rejects equality of heterozygotes and homozygotes (P less than 0.002) and rejects the simple recessive mode of inheritance as a direct consequence. We conclude that more complex modes of inheritance of HLA-linked IDDM susceptibility, such as two different diabetogenic alleles or multiple loci, must be entertained. DIABETES 32:169-174, February 1983.

Metabolic and underlying causes of diabetes mellitus.

It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements. Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines.

The gene for Bazex-Dupré-Christol syndrome maps to chromosome Xq.

Bazex-Dupré-Christol syndrome is an inherited condition with skin cancer predisposition characterized by follicular atrophoderma, hypotrichosis, and early onset of multiple basal cell carcinomas. Previous reports suggested an X-linked mode of inheritance. We therefore performed linkage analysis with microsatellite markers of the X chromosome in three families. We obtained evidence for X-linkage and regional assignment to Xq24-q27 of this syndrome (maximal lod score = 5.26 with a recombination fraction of 0% at the DXS1192 locus). This represents a first step towards the identification of a gene involved in hair follicle development and skin tumor formation.

Biodistribution and dosimetry of indium-111-polyclonal IgG in normal subjects.

UNLABELLED: Indium-111-polyclonal IgG is a new imaging agent of infection and inflammation that has been developed as a possible replacement for radiolabeled leukocytes. We undertook a study to determine the safety, biodistribution and dosimetry of the agent in normal subjects. METHODS: Twelve normal male volunteers with an average age of 34 yr (range 21-55 yr) were studied. Each was injected with 1.22-1.47 mCi 111In-labeled polyclonal IgG; digital whole-body images, in addition to blood, urine and fecal samples, were obtained immediately after injection and at 6, 24, 48, 72, 96 and 120 hr. Whole-body counts, as well as individual organ data obtained by outlining regions of interest, were measured. Blood, urine and fecal counting were done in a well counter and compared to known standards; dosimetry calculations were performed with the MIRD technique. RESULTS: The mean whole-blood activity had a two-phase disappearance curve: the T1/2I was 11.4 hr (61.1%) and the T1/2II was 112.5 hr (38%). Twelve percent of the dose was excreted in the urine and 1.14% in the feces. Skeletal muscle had the highest percentage of uptake, followed by the bone marrow, liver and lungs; the spleen showed less than 1% uptake. Activity in the lungs varied with time, falling by 37% after 18 hr and by 68% after 72 hr. Dosimetry calculations indicated that the highest absorbed dose was to the liver (1.42 rad/mCi) followed by the testes (1.23 rad/mCi) and red marrow (0.976 rad/mCi). The total-body dose was 0.467 rad/mCi, with an effective dose equivalent of 790.84 mrem. CONCLUSION: The biodistribution of 111In IgG is similar to that of 99mTc-HMPAO-labeled leukocytes. Activity in the liver, kidneys and GI tract may make evaluation of infection in these regions difficult. The dosimetry data indicate that adequate doses can be administered for clinical imaging without exposing the patient to excessive radiation.

The efficacy of indium-111-polyclonal IgG for the detection of infection and inflammation.

UNLABELLED: The purpose of this study was to determine the efficacy of 111In-polyclonal immunoglobulin (IgG) for the diagnosis of infection or inflammation. METHODS: Fifty-three patients with suspected infection were prospectively studied. Each underwent an 111In-polyclonal IgG study; biopsy, surgery, additional nuclear medicine scans and radiographic studies were used to confirm the IgG scan results. RESULTS: The polyclonal IgG scan had a sensitivity of 97.9% and a specificity of 94% for infection or inflammation. When only infection or severe inflammation such as bowel infarction was considered, the sensitivity remained the same but the specificity fell to 83%. Chronic infections were detected equally as well as acute infections. Antibiotics, steroids, anti-inflammatory agents, diabetes and diminished renal function did not affect scan sensitivity. There were no adverse reactions to the radiopharmaceutical. Three patients underwent extended imaging. Their scans stayed positive for an average of 8 days. Three patients treated for infection had their scans turn negative on repeat study, confirming the efficacy of their antibiotic therapy. CONCLUSION: Indium-111-polyclonal IgG is an effective imaging agent of infection and/or inflammation that is useful in a variety of infections and in severe inflammatory diseases. The ease of preparation and safety make it an attractive alternative to labeled leukocytes.

The search for heterogeneity in insulin-dependent diabetes mellitus: evidence for familial and nonfamilial forms.

Using five different published sets of data, we looked at the distribution of HLA-DR genotypes among diabetic probands. It was possible to reject dominant inheritance at the HLA-associated locus, but some of the data were compatible with recessive inheritance while some were not. An attempt to reconcile the conflicting data by proposing a three-allele model apparently failed. It proved possible to resolve some of the conflicting data by proposing that simplex families represent primarily a recessive form of insulin dependent diabetes mellitus (IDDM) while multiplex families represent primarily two other subforms: one showing three-allele inheritance and one not. We also propose that the HLA locus involved in IDDM mediates the effect of an environmental agent on a second disease locus.

Dubowitz syndrome in a boy without developmental delay: further evidence for phenotypic variability.

Dubowitz syndrome is an autosomal recessive condition characterized by pre- and postnatal growth retardation, eczema, telecanthus, epicanthal folds, blepharophimosis, ptosis, and broadening of the bridge and tip of the nose. The initial patients described had varying degrees of mental retardation and there is little information about long-term developmental outcome. We present a boy with Dubowitz syndrome who does not have developmental delays, providing additional evidence that the phenotype includes normal neurodevelopmental status.

Marker chromosomes: cytogenetic characterization and implications for prenatal diagnosis.

Satellited marker chromosomes were identified in four individuals from unrelated families; one was first encountered in cultured amniotic fluid cells obtained for prenatal diagnostic studies. We present cytogenetic characterization of these marker chromosomes and clinical findings in the individuals carrying them. Identification of a marker chromosome in amniotic fluid cell cultures presents problems in genetic counseling, as it is often difficult to determine the clinical significance of such a finding. Chromosome-banding techniques now allow the precise identification of satellited marker chromosomes originating from chromosome 15. Presence of a supernumerary bisatellited der(15) marker chromosome containing the proximal long arm of 15 has been associated with mental and developmental retardation. Application of chromosome-banding techniques was useful in characterization of the marker chromosomes and providing prenatal genetic counseling.

Ring chromosome 4 mosaicism coincidence of oligomeganephronia and signs of Seckel syndrome.

We present a patient with features suggestive of Seckel syndrome who was found to be mosaic for ring 4 chromosome. Seckel syndrome is a rare entity characterized by marked growth retardation, microcephaly, facies characterized by receding forehead and chin, large beaked nose, and severe retardation, usually thought to be inherited as an autosomal recessive condition. In addition, our patient had oligomeganephronia, a rare and usually sporadic renal malformation, previously reported in two other patients with abnormalities of chromosome 4. Besides pointing out the overlap between the Seckel phenotype and Wolf-Hirschhorn syndrome, our patient illustrates the need to consider cytogenetic studies in patients with the Seckel phenotype, so that accurate diagnoses can be given to families. Also, the case suggests that there may be a locus for oligomeganephronia distal to the Wolf-Hirschhorn critical region on 4p.

Spondylometepiphyseal dysplasia, Strudwick type.

The clinical and radiographic observations in eight patients, radiographs on an additional six patients, and morphologic observations on chondro-osseous tissue from two of these 14 patients form the basis for delineating an entity distinct from the heterogeneous group of skeletal dysplasia involving spine and tubular bones, the spondyloepiphyseal, and spondylometaphyseal dysplasias. Disproportionately short limbs and delayed epiphyseal maturation are present at birth, and the entity is radiographically indistinguishable from spondyloepiphyseal dysplasia (SED) congenita during infancy. The metaphyseal change that allows identification of the entity described here develops during early childhood, and radiographically is seen as "dappling," ie, the mottled appearance of alternating zones of osteosclerosis and osteopenia. Severe scoliosis and cord compression may be important clinical problems related to the spine changes in adulthood. We have identified one family with two affected sibs and normal parents, suggesting autosomal recessive inheritance and distinguishing the entity from SED congenita that has autosomal dominant inheritance.

Best practice in thyroid pathology.

Thyroid pathology is a specialist area but is often encountered by the general pathologist in a variety of forms including cytology, frozen sections, and resection specimens. In the thyroid gland, as for other endocrine organs, many aspects of diagnosis are unique to this area of histopathology; thus, the aims of this paper are to set out best practice guidelines which, although not entirely comprehensive, will be of practical use.

A search for heterogeneity in insulin dependent diabetes mellitus (IDDM): HLA and autoimmune studies in simplex, multiplex and multigenerational families.

HLA antigens (A, B, C and DR loci), serum islet cell antibodies, thyrogastric antibodies, and insulin antibodies were studied in 77 families (25 simplex, 42 multiplex, and 10 multigenerational). In order to test for intrafamilial constancy and intergroup variation, we compared simplex with multiplex families, HLA identical and non identical siblings within families, as well as groups of families characterized by different DR alleles (DR3, DR4, and DR3/DR4) for various immunologic and clinical characteristics. These comparisons did not reveal all the distinct subgroups suggested by different cross-sectional population studies, but did provide evidence for a compound form having an aggregation of different high risk alleles. This study suggests that in many cases (and possibly especially in families with multiple affected individuals), there are several different genetic influences leading to IDDM.

Hereditary considerations in common disorders.

We have reviewed the approach of the modern clinical geneticist to the genetics of common diseases. The importance of considering genetic heterogeneity within these groups of disorders has been emphasized. The physician should recognize our present inability to deliver exact recurrence risks for most families with these common disorders. As our knowledge improves, we must constantly update our counseling. Until then, in most cases, we can only utilize the empirical risk data presently available and provide an idea of the magnitude of risk, which in many of these disorders appears low. However, continued utilization of imprecise risk data must not impede recognition of potential and demonstrated heterogeneity within these disorders, or retard the development of new and improved risk data based on knowledge of the heterogeneity within common diseases.

Ether-linked glycerolipids in human brain tumors.

In this investigation, the lipid composition of a number of human brain tumors was determined and compared to that of normal adult brain. Glioblastomas (11 samples), astrocytomas (4 samples), an acoustic neurinoma, an oligodendroglioma, and a meningioma were analyzed. All of the tumors had substantial levels (0.8-3.4% of total phospholipids) of choline plasmalogen which was present in only trace amounts in normal brain. With the exceptions of the acoustic neurinoma and the meningioma, the concentration of alkylacylglycerophosphorylcholine was also higher in the tumors than in normal brain. Neutral lipids of brain tumors also contained high concentrations of both alkyl (1.6-4.8% of total neutral gsults from this investigation indicate that increases in ether-linked glycerolipids may be characteristic of human brain tumors.

The synthesis of(14)C- and (3)H-labeled glycerol ethers.

The racemic(14)C-and(3)H-labeled alpha and beta derivatives of octadecyl glycerol ether (batyl alcohol) and of hexadecyl glycerol ether (chimyl alcohol) of high specific activity were synthesized by treating the appropriate alkyl halides with a large excess of the potassium salts of isopropylidene or benzylidene glycerol. By use of the trifluoroacetic anhydride esterification procedure, the labeled diesters of alpha and beta octadecyl and hexadecyl glycerol ethers were prepared. The labeled monoesters of beta octadecyl and of beta hexadecyl glycerol ethers were isolated from the reaction mixtures by silicic acid column chromatography.