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PubMed1972

Lymphocyte transformation in immunoproliferative disorders.

Lymphocyte transformation with phytohaemagglutinin (PHA) was studied in 30 patients with immunoproliferative disorders (lymphoproliferative and plasma cell disorders).Lymphocyte transformation at 3 days was reduced in the lymphoproliferative disorders (chronic lymphocytic leukaemia (CLL), well-differentiated (lymphocytic) follicular lymphoma (FLL) and Waldenström's macroglobulinaemia (WM)), and normal in the plasma cell disorders (myelomatosis, primary systemic amyloidosis, α-chain disease and benign monoclonal gammopathy) and in idiopathic cold haemagglutinin disease. A case of plasma-cell leukaemia with increased numbers of abnormal cells in the circulation also showed reduced transformation. It is suggested that the presence in the circulation of abnormal lymphocytes (or plasma cells) accounts for the results in CLL and FLL, WM and plasma-cell leukaemia. In WM a correlation was found between the activity of the disease (expressed by the levels of IgM paraprotein) and the degree of blast transformation.The long-term (28 days) in vitro survival of lymphocytes using subconcentrations of PHA was also studied in 7 patients. The cell populations (PHA-non-responsive) of CLL and FLL, but not of WM, had a good in vitro survival, resembling in this respect the normal PHA-responsive population of lymphocytes, but they remained PHA-non-responsive after 4 weeks' culture. It is speculated that in CLL the long survival in vitro of the PHA-non-responsive (leukaemic) population corresponds to their long life-span in vivo.

Amyloidosis↗
PubMed1999

Inverse association between IgG-anti-kappa and antierythrocyte autoantibodies in patients with cold agglutination.

It has been known for a long time that IgG-anti-F(ab')(2) antibodies (Abs) are able to suppress the B-cell response. We showed that natural IgG-anti-F(ab')(2) autoantibodies appear in the serum of patients with cold agglutination. If the anti-F(ab')2 Ab suppresses cold agglutinin (CA)-producing B cells, one would expect an inverse correlation between the titers of these two Abs. Our study confirmed this correlation. Subsequent experiments showed that some anti-F(ab')(2) Abs bind to the hinge region of IgG. It was difficult to explain how this Ab suppresses CA-producing B cells, which are of IgM isotype. Here we show that patients with cold agglutination have an IgG-anti-kappa light chain autoantibody in their serum. This is another member of the anti-F(ab')(2) Ab group. Because the vast majority of CAs are IgM-kappa Abs, the anti-kappa Ab might suppress CA-producing B cells. If this is the case, there should be an inverse association between the titer of anti-kappa Ab and CA. In a group of 302 patients, we found that high titers of the anti-kappa Ab correlate with low titers of CA and vice versa (P =.009). Interestingly, this association is found only in patients whose disease is caused by noninfectious agents, including mainly B-cell proliferations (P =.0058). Our data show that the inverse correlation is not confined to a particular CA autoantibody specificity. The results are discussed in the light of recent findings showing that anti-IgM Abs may either inactivate or kill tumoral B cells by apoptosis.

Anemia, Hemolytic, Autoimmune↗
PubMed2000

Photoreactivation does not alter ras and p53 mutation spectra in ultraviolet radiation-induced corneal sarcomas of Monodelphis domestica.

When chronically exposed to ultraviolet radiation (UV), opossums of the species Monodelphis domestica develop corneal sarcomas at high frequency. Post-UV exposure to photoreactivating light enhances repair of UV-induced pyrimidine dimers and suppresses, but does not abrogate, corneal tumor development. We compared mutation spectra in ras and p53 genes in 32 eye tumors from Monodelphis exposed to UV alone and in 25 tumors from Monodelphis exposed to UV followed by photoreactivation in order to identify the particular types of mutation suppressed by enhanced repair of pyrimidine dimers. Mutations were detected by polymerase chain reaction amplification followed by direct sequencing or by "cold" single-strand conformational polymorphism analysis. The overall frequency of mutations was low, and there was no statistically significant difference between the two groups of tumors in the frequency or type of mutation. All mutations occurred at dipyrimidine sites, and most were C to T or CC to TT mutations, the hallmark UV-induced mutations. Hotspots of p53 mutation identified in a previous study of invasive tumors were absent, and mutations identified in the present study included synonymous mutations not previously detected. The difference in stage of the tumors examined is believed to account for these differences. The preponderance of signature UV mutations in p53 and ras genes confirm that UV is the proximate carcinogen for these tumors. The low incidence of mutations suggest that neither ras activation nor p53 inactivation is essential for tumor formation. Mutations attributable specifically to pyrimidine dimer formation could not be identified.

Animals↗
PubMed1998

Two types of mRNA encoding myosin regulatory light chain in carp fast skeletal muscle differ in their 3' non-coding regions and expression patterns following temperature acclimation.

cDNA clones encoding the myosin regulatory light chain (RLC) were isolated from a cDNA library prepared from fast skeletal muscle of the carp Cyprinus carpio L. Two types of cDNA clone encoding carp RLC were found with identical deduced amino acid sequences. The two mRNAs differed in the number of polyadenylation signals prior to the poly(A) tail in the 3' non-coding region. The two mRNA species, with approximate sizes of 1.4 and 0.8 kilobases, were also observed in northern blot analysis. Carp were acclimated for a minimum of 5 weeks to either 10 degreesC or 30 degreesC (14 h:10 h light:dark photoperiod). The total levels of mRNA transcripts coding for the RLC and myosin heavy chain were, respectively, 3.3 and 3.9 times higher in cold- than in warm-acclimated fish. Differences in the levels of RLC in mRNA transcripts were largely due to the concentration of the 1.4 kilobase mRNA species.

Journal Article↗
PubMed1978

On the rate-limiting step in the transfer of long-chain acyl groups across the inner membrane of brown adipose tissue mitochondria.

Brown adipose tissue mitochondria predominantly oxidize fatty acids in order to generate heat for non-shivering thermogenesis, and have an unusually high capacity for net transfer of long-chain fatty acyl groups from the outer to the inner (matrix) compartment. The activities of the "outer" and "inner" carnitine long-chain acyltransferases have been estimated in isolated mitochondria of cold-acclimated guinea pits by the continuous spectrophotometric recording of the redox level of flavoproteins in the acyl-CoA dehydrogenase pathway. This redox level is determined by the intramitochondrial content of acyl-CoA under the selected experimental conditions. The apparent initial rate of the "inner" acyltransferase (palmitoyl-L-carnitine added) is three order of magnitudes higher than the "outer" acyltransferase (palmitoyl-CoA added), and this difference is not influenced by the substrate concentration, pH and reaction temperature. Thus, the "outer" acyltransferase reaction is rate limiting in the transfer of long-chain acyl groups across the inner membrane of these mitochondria and catalyzes a non-equilibrium reaction in the intact organelle. Estimates of the absolute rate of the "outer" long-chain acyltransferase indicate that it exceeds that of rat liver mitochondria by a factor of 20.

Acclimatization↗
PubMed1992

Characterization of the cDNA of a broadly reactive neutralizing human anti-gp120 monoclonal antibody.

The F105 mAb, identified in an HIV-1-infected individual, binds to a discontinuous epitope on the HIV-1 gp120 envelope glycoprotein, blocks the binding of gp120 to the CD4 viral receptor, and neutralizes a broad range of HIV-1 isolates. This study reports the primary nucleotide and deduced amino acid sequences of the rearranged heavy and light chains of the mAb F105. This IgG1k mAb uses a VH gene member of the VH4 gene family (V71-4) and is productively rearranged with a D-D fusion product of the dlr4 and da4 germline DH genes and the JH5 gene. This rearranged heavy chain gene expresses the VH4-HV2a idiotope, which is seen in human monoclonal IgM cold agglutinins. The F105 Vk appears to be derived from the Humvk325 germline gene and is rearranged with a Jk2 gene. For both chains, the mutational pattern in the rearranged VH and VL genes is indicative of an antigen-driven process. These studies show that production of a broadly neutralizing anti-HIV-1 antibody that recognizes determinants within the CD4 recognition site of the envelope glycoprotein is achieved by rearrangement of the V71-4 and Humvk325 germline variable region genes along with selected individual point mutations in the rearranged genes.

Amino Acid Sequence↗
PubMed2006

Kinetics and energetics of ligand binding determined by microcalorimetry: insights into active site mobility in a psychrophilic alpha-amylase.

A new microcalorimetric method for recording the kinetic parameters k(cat), K(m) and K(i) of alpha-amylases using polysaccharides and oligosaccharides as substrates is described. This method is based on the heat released by glycosidic bond hydrolysis. The method has been developed to study the active site properties of the cold-active alpha-amylase produced by an Antarctic psychrophilic bacterium in comparison with its closest structural homolog from pig pancreas. It is shown that the psychrophilic alpha-amylase is more active on large macromolecular substrates and that the higher rate constants k(cat) are gained at the expense of a lower affinity for the substrate. The active site is able to accommodate larger inhibitory complexes, resulting in a mixed-type inhibition of starch hydrolysis by maltose. A method for recording the binding enthalpies by isothermal titration calorimetry in a low-affinity system has been developed, allowing analysis of the energetics of weak ligand binding using the allosteric activator chloride. It is shown that the low affinity of the psychrophilic alpha-amylase for chloride is entropically driven. The high enthalpic and entropic contributions of activator binding suggest large structural fluctuations between the free and the bound states of the cold-active enzyme. The kinetic and thermodynamic data for the psychrophilic alpha-amylase indicate that the strictly conserved side-chains involved in substrate binding and catalysis possess an improved mobility, responsible for activity in the cold, and resulting from the disappearance of stabilizing interactions far from the active site.

Animals↗
PubMed2005

Tissue carnitine homeostasis in very-long-chain acyl-CoA dehydrogenase-deficient mice.

Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD) is the most common long-chain fatty acid oxidation defect and presents with heterogeneous clinical manifestations. Accumulation of long-chain acylcarnitines and deficiency of free carnitine have often been proposed to play an important role in disease pathogenesis. The VLCAD-deficient mouse exhibits similar clinical and biochemical phenotypes to those observed in humans and, therefore, represents an excellent model to study VLCAD deficiency. We measured carnitine and acylcarnitine profiles in liver, skeletal muscle (SkM), bile, and blood from VLCAD knock-out mice and controls under nonstressed and various stress conditions. Carnitine and acylcarnitines were extracted from body fluids with methanol and from tissues with acetonitrile, respectively, and were analyzed as their butyl esters using electrospray ionization tandem mass spectrometry. Fasting combined with a cold challenge for 8 h significantly induced liver long-chain acylcarnitine and free carnitine production. Acylcarnitines in SkM predominantly accumulated during exercise with a concomitant decrease of free carnitine. Changes in blood free carnitine did not correlate with carnitine homeostasis in liver and SkM. Our results demonstrate different tissue-specific long-chain acylcarnitine profiles in response to various stressors, which may be of importance with respect to the heterogeneous clinical manifestations of VLCAD deficiency in humans. Furthermore, we conclude that carnitine biosynthesis in the liver seems sufficiently active to maintain liver carnitine levels during increased demand. Our data suggest that carnitine supplementation in long-chain beta-oxidation defects may not be required, and blood carnitine concentrations do not reflect tissue carnitine homeostasis.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2000

Vibration-induced multifocal neuropathy in forestry workers: electrophysiological findings in relation to vibration exposure and finger circulation.

OBJECTIVES: To investigate neural conduction in the upper limbs of symptomatic forestry workers with and without exposure to hand-transmitted vibration. A further aim was to assess the possible relationships between vibration exposure, nerve conduction and finger circulation in the forestry workers who used chain saws. METHODS: A detailed neurophysiological investigation was performed on the upper extremities of 20 chain saw workers, 20 forestry operators with heavy manual work but without vibration exposure, and 20 healthy male controls. All subjects were screened to exclude polyneuropathy. Measurements of sensory and motor nerve conduction (velocity and amplitude) were obtained bilaterally from the median, ulnar and radial nerves. To assess peripheral vascular function, the forestry workers underwent a cold test with plethysmographic measurement of finger systolic blood pressure (FSBP). In the chain saw operators, vibration exposure was evaluated according to the International Standard ISO 5349. Indices of daily vibration exposure and lifetime cumulative vibration dose were estimated for each chain saw operator. RESULTS: Sensory nerve conduction in several segments of the median and radial nerves was significantly reduced in the chain saw operators compared with that in the workers doing heavy manual work and the controls. The neurophysiological pattern more frequently observed in the chain saw operators was a multifocal nerve conduction impairment to several neural segments with predominant involvement of sensory rather than motor fibres. Sensory nerve conduction velocities in the hands of the chain saw operators were inversely related to both daily and lifetime cumulative vibration exposures. In the vibration-exposed forestry workers, neither were sensori-motor complaints associated with vascular symptoms (finger whiteness) nor were electrophysiological data related to cold-induced changes in FSBP. CONCLUSIONS: Exposure to hand-transmitted vibration, in addition to ergonomic stress factors, can contribute to peripheral nerve disorders occurring in forestry workers who operate chain saws. The findings of this study suggest the existence of an exposure-effect relationship for vibration-induced neuropathy. Different underlying mechanisms are likely to be involved in the pathogenesis of the neurological and vascular components of the hand-arm vibration syndrome.

Adult↗
PubMed1996

Experimental rhinovirus infection in volunteers.

Experimental viral disease studies in volunteers have clarified many aspects of the pathogenesis of human viral disease. Recently, interest has focused on rhinovirus-associated asthma exacerbations, and new volunteer studies have suggested that airway responsiveness (AR) is enhanced during a cold. For scientific, ethical and safety reasons, it is important to use validated methods for the preparation of a virus inoculum and that the particular virological characteristics and host responses should not be altered. We have prepared a new human rhinovirus (HRV) inoculum using recent guidelines and assessed whether disease characteristics (for example, severity of colds or changes in AR) were retained. Studies were conducted in 25 clinically healthy volunteers using a validated HRV inoculum in the first 17 and a new inoculum in the subsequent eight subjects. Severity of cold symptoms, nasal wash albumin levels and airway responsiveness were measured, and the new inoculum was prepared from nasal washes obtained during the cold. The new inoculum was tested using standard virological and serological techniques, as well as a polymerase chain reaction for Mycoplasma pneumoniae. No contaminating viruses or organisms were detected and the methods suggested were workable. Good clinical colds developed in 20 of the 25 subjects and median symptom scores were similar in the validated and new inoculum groups (18 and 17.5, respectively; p=0.19). All subjects shed virus, and there were no differences noted in viral culture scores, nasal wash albumin and rates of seroconversion in the two groups. Although airway responsiveness increased in both groups (p=0.02 and p=0.05), the degree of change was similar. We have performed experimental rhinovirus infection studies and demonstrated similar clinical disease in two inoculum groups. Amplified airway responsiveness was induced; continuing studies will define the mechanisms and suggest modes of treatment.

Adult↗
PubMed1996

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

IgM paraproteins associated with autoimmune peripheral neuropathy and anti-Pr cold agglutinins react with sialic acid epitopes present on disialylated gangliosides including GD1b, GT1b, GQ1b, and GD3. A causal relationship between the paraprotein and the neuropathy has never been proven experimentally. From peripheral blood B cells of an affected patient, we have cloned a human hybridoma secreting an antidisialosyl IgM mAb, termed Ha1, that shows identical structural and functional characteristics to its serum counterpart. Variable region analysis shows Ha1 is encoded by the same VH1 family heavy chain gene, V1-18, as the only other known anti-Pr antibody sequence and is somatically mutated, suggesting that it [correction of is] arose in vivo in response to antigenic stimulation. In the rodent peripheral nervous system, Ha1 immunolocalizes to dorsal root ganglia, motor nerve terminals, muscle spindles, myelinated axons, and nodes of Ranvier. After intraperitoneal injection of affinity-purified antibody into mice for 10 d, electrophysiological recordings from the phrenic nerve-hemidiaphragm preparation demonstrated impairment of nerve excitability and a reduction in quantal release of neurotransmitter. These data unequivocally establish that an antidisialosyl antibody can exert pathophysiological effects on the peripheral nervous system and strongly support the view that the antibody contributes to the associated human disease.

Amino Acid Sequence↗
PubMed2006

Identification of cold acclimation-responsive Rhododendron genes for lipid metabolism, membrane transport and lignin biosynthesis: importance of moderately abundant ESTs in genomic studies.

We have previously analysed expressed sequence tags (ESTs) from non-acclimated (NA) and cold-acclimated (CA) Rhododendron leaves, and identified highly abundant complementary DNAs (cDNAs) possibly involved in cold acclimation. A potentially significant, but relatively unexplored, application of these EST data sets is the study of moderately abundant cDNAs, such as those picked only 1-3 times from each Rhododendron EST library containing approximately 430 ESTs. Using statistical tests and Northern blots, we established that the probability of differential expression of moderately abundant cDNAs based on the EST data is, indeed, a reasonably accurate predictor of their 'true' upregulation or downregulation as 11 out of 13 cDNAs (85%) studied fit this criterion. The analyses also revealed four aspects of cold acclimation in Rhododendron leaf tissues. Firstly, the concomitant upregulation of long-chain acyl-coenzyme A (acyl-CoA) synthetase, CTP:cholinephosphate cytidylyltransferase and delta-12 fatty acid desaturase in CA leaf tissues suggests that phospholipid biosynthesis and desaturation are important components of cold hardening in Rhododendron. Secondly, upregulation of plastidic nicotinamide adenine dinucleotide phosphatemalic enzyme (NADP-ME) in CA tissues suggests that malate is an important source of acetyl-CoA used for fatty acid biosynthesis during cold acclimation. Thirdly, down-regulation of plasma membrane intrinsic protein (PIP)2-1 aquaporin and upregulation of gated outward rectifying K+ channel (GORK) in CA tissues may be associated with the protection of overwintering leaves from freeze-induced cellular dehydration. Fourthly, upregulation of coumarate 3-hydroxylase may be associated with cell wall thickening in CA tissues. Physiological implications of these results, which reveal potentially novel regulations of cold acclimation in overwintering woody evergreens, are discussed. This work highlights the importance of also investigating low/moderately abundant ESTs (in addition to highly abundant ones) in genomic studies, in that it offers an effective strategy for identifying stress-related genes, especially when large-scale cDNA sequencing/microarray studies are not possible.

Acclimatization↗
PubMed1978

Effect of growth temperature on membrane fatty acid composition and susceptibility to cold shock of Bacillus amyloliquefaciens.

We investigated the fatty acid composition of the membrane of Bacillus amyloliquefaciens grown at different temperatures. A decrease in growth temperature was accompanied by an increase in the ratio of branched- to straight-chain fatty acids and a marked increase in the level of unsaturation of branched-chain fatty acids. When cells of this organism grown at 30 degrees C were cold shocked, viability and ability to secrete extracellular protease were lost. Growth of this organism at lower temperatures or addition of Tween 80 to cells caused the critical temperature zone for cold shocking to be lowered significantly. These results suggest a direct correlation between membrane fluidity and the susceptibility to cold shock.

Bacillus↗
PubMed2000

Dietary n-3 long-chain polyunsaturated fatty acid deprivation, tissue lipid composition, ex vivo prostaglandin production, and stress tolerance in juvenile Dover sole (Solea solea L.).

Larval Dover sole fed an Artemia diet supplemented with n-3 long-chain (C20 + C22) polyunsaturated fatty acids (PUFA) are known to be more resistant to low-temperature injury. Here we explore the relationship between tissue fatty acid composition and tolerance of stressful environmental conditions over the larval and early juvenile periods. Artemia nauplii supplemented with n-3 long-chain PUFA-deficient and PUFA-enriched oil emulsions were fed to two groups of larvae. Whole body tissue samples from the resulting PUFA-deficient and -enriched juveniles possessed 12.1 and 21.9% n-3 long-chain PUFA, respectively. These differences were at the expense of C18 PUFA, while proportions of saturated fatty acids, monounsaturated fatty acids, and total PUFA were unaffected. Brain and eye tissues from the PUFA-deficient fish contained lower levels of 22:6n-3, known to be important for optimal nervous system function, incorporating instead a range of fatty acids of lower unsaturation. PUFA-deprived juveniles showed substantially greater mortality when exposed to a combination of low temperature and low salinity, as well as to high temperature and to hypoxia. After adaptation to the different diets, both dietary groups were fed a common formulated feed high in n-3 long-chain PUFA. Tissue PUFA in both groups progressively increased to the same high value, with a consequent loss of the differences in cold-susceptibility. These correlated changes support a link between dietary manipulation of n-3 long-chain PUFA and development of a stress-sensitive phenotype. PUFA deprivation had no detectable effect upon static hydrocarbon order of purified brain membranes (as assessed by fluorescence polarization) but was associated with an increase in the whole-body content of prostaglandins. We conclude that susceptibility to environmental stress is responsive to dietary n-3 long-chain PUFA manipulation, possibly due to altered tissue development or the overproduction of eicosanoids.

Aging↗
PubMed2006

Isolation and characterization of a myo-inositol-1-phosphate synthase gene from yellow passion fruit (Passiflora edulis f. flavicarpa) expressed during seed development and environmental stress.

BACKGROUND AND AIMS: Myo-inositol-1l-phosphate synthase (MIPS) catalyses the conversion of d-glucose 6-phosphate to 1-l-myo-inositol-1-phosphate, the first and rate-limiting step in the biosynthesis of all inositol-containing compounds. Inositol phospholipids play a vital role in membrane trafficking and signalling pathways, auxin storage and transport, phytic acid biosynthesis, cell wall biosynthesis and production of stress-related molecules. In the present study, an MIPS cDNA from developing Passiflora edulis f. flavicarpa seeds was characterized and an investigation made into its spatial and differential expression, as well as changes in its transcription during exposure of growing plants to cold and heat stresses. METHODS: The MIPS-encoding gene was isolated by polymerase chain reaction (PCR) methods, and transcript levels were examined using semi-quantitative reverse transcription-PCR (RT-PCR) during seed development and in response to heat and cold stress. In addition, the copy number of the cloned PeMIPS1 gene in the genome of Passiflora edulis, P. eichleriana, P. caerulea, P. nitida and P. coccinea was determined by Southern blot analyses. KEY RESULTS: A full-length cDNA clone of the PeMIPS1 from P. edulis was isolated and characterized. Southern blot analyses indicated that the genomic DNA might have diverse sequences of MIPS-encoding genes and one copy of the cloned PeMIPS1 gene in the genomes of P. edulis, P. eichleriana, P. caerulea, P. nitida and P. coccinea. RT-PCR expression analyses revealed the presence of PeMIPS1 transcripts in ovules, pollen grains and leaves, and during the seed developmental stages, where it peaked at 9 d after pollination. The PeMIPS1 gene is differentially regulated under cold and heat stress, presenting a light-responsive transcription. CONCLUSIONS: Experimental data suggest that PeMIPS1 transcription plays an important role in the establishment of developmental programmes and during the response of plants to environmental changes. The PeMIPS1 is differentially transcribed during cold and heat stress, presenting a light response pattern, suggesting that it is important for environmental stress response.

Cloning, Molecular↗
PubMed1988

Time course of thermal adaptation in plasma membranes of trout kidney. II. Molecular species composition.

The molecular species composition of phosphatidylcholine (PC) was determined in plasma membranes of kidney for rainbow trout, Salmo gairdneri, undergoing thermal acclimation between 5 and 20 degrees C. Species of PC from 5 degrees C-acclimated trout were characterized by significantly higher values of unsaturation ratio (8.78 vs. 3.15), unsaturation index (2.32 vs. 1.84), and average chain length (34.18 vs. 33.12 carbons) than those of 20 degrees C-acclimated trout, primarily because of elevated proportions of 16:0/20:4 (8.67 vs. 4.42%) and 16:0/22:6 (15.61 vs. 7.18%) and reduced levels of 14:0/16:0 (3.34 vs. 12.41%). Proportions of saturated and monoenoic species responded most rapidly (within 16-48 h) to temperature change, whereas species containing long-chain, polyunsaturated fatty acids increased only after 10-21 days of cold acclimation. The combined results of the present and preceding paper [Hazel and Landrey, Am. J. Physiol. 255 (Regulatory Integrative Comp. Physiol. 24): R352-R357, 1988] indicate that the metabolic adaptation responsible for the thermal compensation of membrane structure differ in response times, which range from rapid adjustments in both headgroup and molecular species composition to considerably slower changes in the proportions of species containing long-chain polyunsaturated fatty acids. Furthermore, the restructuring of phospholipid molecular species composition modifies membrane structure in different ways at different times during the acclimation response.

Acclimatization↗
PubMed1993

A comparative analysis of nasal secretions from subjects with and without acute rhinitis and its application to forensic medicine.

Proteins in nasal secretions obtained from healthy subjects and subjects with acute rhinitis were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The bands of 79 kilodalton (kD), 67 kD, 58 kD, 52 kD, 43 kD, 38 kD, 28 kD, 26 kD and below 26 kD were the proteins shared by most specimens. The state of the common cold was identified by determining the ratios of these proteins to the total proteins. 58 kD protein (IgA alpha-chain), contained mainly in glandular secretions, was found in abundance on average. However, the ratio of 67 kD protein (albumin) filtrated from the vascular system varied considerably. The highest ratio of 67 kD protein (albumin) was found in the nasal secretions obtained only from subjects with rhinitis. In nasal secretions from healthy subjects, the highest ratios of the major proteins were those of 58 kD protein (IgA alpha-chain) or proteins below 26 kD. These observations may be useful in discriminating rhinitis subjects with a common cold from healthy subjects in the forensic medical analysis of nasal smears.

Acute Disease↗
PubMed1989

Cold agglutination.

Autoantibodies against red cells optimally reacting at 0 degree C, ie, CA, are normally found with low titers in the serum of human adults. High-titer CA may be induced by certain infectious agents, including M pneumoniae, EBV, CMV, and rubella virus, or may develop on the basis of chronic (malignant) B cell lymphoproliferation. The main clinical manifestation of cold agglutination is AIHA. Antigens and antibodies of cold agglutination are the best characterized reaction partners of a human autoimmune process. CA may recognize I and i antigens, which are lipid- and protein-linked branched and linear N-acetyl-lactosamine chains, respectively. They are precursors of the ABH blood group antigens and are converted into H by fucosylation. An alternative substitution by sialylation creates Gd, Fl, and probably Vo/Li antigens. CA with anti-Pr and anti-Sa specificities recognize 0-glycans with immunodominant sialyl groups on glycophorins. Several Pr subspecificities can be identified by chemically modified sialyl groups on glycophorins. Because CA in chronic lymphoproliferation are monoclonal antibodies, structure-specificity-interrelations of the antibodies could be identified by primary structure analyses of the N-terminal variable regions of H and L chains and by studies on CA idiotypes. Interrelations between distinct CA specificities and particular infectious agents could explain cold agglutination as a response to receptors for the agents or to the binding sites of antibodies against the agents. Interrelations also existing between certain CA isotypes (Ig classes and L chain types) and CA specificities could be a basis for the elucidation of the enigmatic etiology of chronic (malignant) monoclonal cold agglutination.

Agglutination↗