Age-related dynamics of the genetic marker distribution in an irradiated population. Haptoglobin genetic system

The age dynamics of haptoglobin (Hp) type and allele distribution was studied in 985 workers aged 35-79 years who worked in the atomic industry. These workers were exposed to chronic radiation in a wide range of doses 17-40 years ago. Along with the chi 2 test, the relative and attributive risks of elimination of Hp types and alleles were determined to obtain the qualitative characteristics of age alterations. The substantial changes in distribution of Hp types and alleles were revealed in individuals older than 60 years. These changes depended on doses of external and internal irradiation. For instance, in individuals of this age group, who received the total dose of gamma-radiation (less than 100 cGy) and or that of plutonium-239 incorporation (less than 1.48 kBq), a decrease in Hp 2-2 and Hp2 and an increase in Hp 1-1 and Hp1 was observed. However, among the individuals of similar age (older than 62 years), who received a higher total dose of external and/or internal radiation, the different Hp type distribution showed a decrease in Hp 2-1 and an increase in Hp 1-1. In the latter case, the changes with age were dose-dependent. In individuals over 60 years of age with essential hypertension or diabetes mellitus and those who had a myocardial infarction, a decrease in Hp 2-2 and Hp2 and an increase in Hp 1-1 and Hp1 were found. This explains the changes with age in individuals irradiated at lower doses. The peculiar changes with age in individuals irradiated at higher doses are possibly due to the difference in morbidity and mortality from malignancy in various Hp type carriers.     

Haptoglobin phenotypes and gene frequencies in unipolar major depression

OBJECTIVE: Studies from the authors' laboratory have shown that major depression is accompanied by significantly increased plasma concentrations of positive acute-phase proteins such as haptoglobin. Haptoglobin is characterized by a molecular variation with three known phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2). This study investigated haptoglobin plasma levels and phenotype and gene frequencies in unipolar major depression. METHOD: Haptoglobin plasma levels of 22 healthy volunteers, 32 patients with minor depression, and 72 patients with major depression were determined by means of a laser nephelometric method. Haptoglobin phenotyping of these 126 subjects and 200 healthy blood donors was also carried out. RESULTS: The patients with major depression exhibited significantly higher haptoglobin plasma levels than the healthy comparison subjects and the patients with minor depression. Subjects with the haptoglobin phenotype Hp 2-2 had significantly lower haptoglobin levels than the phenotype Hp 1-1 and Hp 2-1 carriers. The frequencies of haptoglobin phenotypes Hp 2-1 (61.1%) and Hp 2-2 (20.8%) in the patients with major depression were significantly higher and lower, respectively, than the frequencies in the normal population (i.e., the blood donors: 48.0% and 37.0%, respectively). The frequency of the Hp-1 gene was significantly greater in the patients with major depression (48.6%) than in the normal population (39.0%). CONCLUSIONS: Major depression is characterized by a hyperhaptoglobinemia that is largely independent of haptoglobin phenotypes. This altered distribution of haptoglobin phenotypes and genes suggests that genetic variation on chromosome 16 may be associated with that illness.     

Comparison of three formulations of alpha-chloralose for immobilization of Canada geese

Haptoglobin is a hemoglobin-binding antioxidant showing a genetic polymorphism with three types: Hp 1-1, Hp 2-1, and Hp 2-2. The Hp 2-2 type has been associated with an increased risk of atherosclerosis. We investigated vitamin C metabolism in vivo and in vitro according to haptoglobin type in a study group of 135 healthy volunteers. Serum vitamin C concentrations were associated with haptoglobin type, showing lowest values in serum from Hp 2-2 subjects (P < 0.01). Renal threshold for L-ascorbic acid was within the normal range and metabolization to oxalate was not different among haptoglobin-type groups. Serum concentrations of other endogenous antioxidants (uric acid, bilirubin, albumin, ceruloplasmin, and total antioxidative status) were not different among haptoglobin-type groups. In vitro experiments showed a lower stability of L-ascorbic acid in blood from subjects with the Hp 2-2 type (P < 0.01). L-Ascorbic acid depletion in vitro was inversely related to haptoglobin concentration (r = -0.738). The results of this study indicate a higher rate of L-ascorbic acid oxidation in Hp 2-2 carriers because they have less protection against hemoglobin-iron driven peroxidation.     

Determination of the subunit composition of haptoglobin 2-1 polymers using quantitative densitometry of polyacrylamide gels

Human haptoglobin (Hp), a hemoglobin-binding glycoprotein containing two types of polypeptide chains, alpha and beta, in equimolar amounts linked by disulfide bonds, exists in three major phenotypes determined by the properties of the alpha chain: Hp 1-1 (alpha1), Hp 2-2 (alpha2), and Hp 2-1 (alpha1 and alpha2). Hp 2-2 and Hp 2-1 form a series of alpha-disulfide-linked polymers. The subunit composition of the Hp 2-1 series was studied by isolation of single Hp 2-1 polymers by polyacrylamide gel electrophoresis. After reductive disulfide cleavage and alkylation the relative content of alpha2 and alpha1 polypeptide chains was determined by quantitative densitometry of acid/urea polyacrylamide gels stained with Coomassie brilliant blue R250. The molar ratios alpha2/alpha1 for the Hp 2-1 polymers. P1 through P5 (in order of decreasing electrophoretic mobility), were found to be: P1, 0.0 (alpha1 only); P2, 0.48; P3, 0.97; P4, 1.6; P5, 2.0. Since one alphabeta-Hb half-molecule is known to bind to each Hp beta chain, the beta polypeptide chain content of each of the Hp 2-1 polymers could be estimated by by counting the number of Coomassie blue bands formed after electrophoresis of isolated Hp 2-1 polymers fractionally saturated with cyanmethemoglobin (Hb). The number of beta chains present in Hp 2-1 polymers P1 through P4 was determined to be: P1, 2; P2, 3; P3, 4 and P4, 5. Molecular weights of the Hp 2-1 polymers were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresus using as standards the almost homologous Hp 2-2 polymer series whose molecular weights are known from ultracentrifugation studies. Molecular weights for the first five Hp 2-1 polymers were estimated to be 107,000; 162,000; 217,000, 274,000; and 331,000, respectively. These data are consistent with the previously proposed model for the subunit composition of the Hp 2-1 polymer series when P1 = (alpha1 beta)2 and the subsequent polymers in order are represented as (alpha1 beta)2(alpha2 beta)n where n = 1,2,3,4...     

Arthroscopic resection of the acromioclavicular joint. Indications--surgical technique--outcome

The haptoglobin (Hp) 2-1 and 2-2 phenotypes have been shown to agglutinate Streptococcus pyogenes carrying the membrane antigen T4. In this study, the growth rate of two strains of Streptococcus pyogenes (T1 and T4) in human serum was compared among haptoglobin phenotypes in vitro. During incubation for 16 hours in serum of different haptoglobin types, only Hp 2-1 and Hp 2-2 sera showed an inhibitory effect on growth, Hp 2-2 being 1.85 times more potent than Hp 2-1. Growth of Streptococcus pyogenes T4 negatively correlated with the serum concentration of Hp 2-1 (r = -0.908) and Hp 2-2 (r = -0.953). Haptoglobin-depleted serum had no inhibitory effect on bacterial growth. Addition of haemoglobin and ferric citrate to the serum accelerated the growth of Streptococcus pyogenes T4 (P <0.05) but not in Hp 2-2 serum. Haptoglobin types 2-1 and 2-2 can be regarded as inhibitors of Streptococcus pyogenes growth in vitro. These data point towards a potential protective role of Hp 2-2 in Streptococcus pyogenes infection in vivo, independently of iron uptake.     

Relationship of tuberculosis course in adolescents with acute phase blood proteins and genetic types of haptoglobin

The phenotype of haptoglobin (Hp) was determined and Hp and alpha 1-antitrypsin (alpha 1-AT) were many times measured in the sera of 131 adolescents with first identified tuberculosis. The phenotype of Hp was found to produce no effects on tuberculosis morbidity among adolescents, but Hp2-2 carriers fall ill more frequently if they have a baseline gastrointestinal abnormality. In tuberculosis patients with Hp2-2, resolution of infiltrative changes in the lung tissue occurs less rapidly than in those with other Hp variants. Great increases in the serum levels of alpha 1-AT, which reflects the severity of tissue damages, suggest a less favourable prognosis. By the end of sixth-month continuous combined drug therapy, an inflammatory reaction diminishes and the synthesis of acute phase reactants (APR) becomes normal in patients without baseline lung tissue decay. In the presence of the latter, the intensity of inflammation considerably decreases in the first 3 months of combined drug therapy, then becomes steady-state at a definite level, which is potentiated by continuous invasion of proteolytic enzymes. APR monitoring more accurately assesses the time course of therapy-induced changes in the process.     

CCR5 chemokine receptor genotype frequencies among Puerto Rican HIV-1-seropositive individuals

Some individuals remain uninfected by human immunodeficiency virus type 1 (HIV-1), despite multiple sexual contacts with subjects with confirmed HIV-1 infection. Several studies have confirmed that individuals who are homozygous for a 32 base pair (bp) deletion mutation in the chemokine receptor gene CCR5, designated as delta 32/ delta 32, are protected against HIV-1 infection. Heterozygotes of the same chemokine receptor deletion mutation are, however, not protected from acquiring HIV-1 infection but seemingly have slower progression to acquired immunodeficiency syndromes (AIDS). Genotype frequencies of the delta 32 CCR5 mutation vary markedly among different ethnic groups; heterozygosity is found in approximately 15% of Caucasians, about 5-7% of Hispanics and African Americans and 1% or less of Asians. The ethnic background of Puerto Ricans is highly complex and usually includes admixture of Caucasian, Caribbean Indian and African traits to a varying extent. This study was conducted to examine the frequencies of the delta 32 CCR5 mutation among Puerto Ricans who are infected with HIV-1. Samples were received from different geographical regions of the island. Of 377 samples tested, 94.2% were wild type (non-deletion mutant) homozygotes, 5.8% were delta 32 CCR5 heterozygotes, and none were delta 32 CCR5 homozygotes. The incidence of CCR5 delta 32/w heterozygous mutation among Puerto Ricans seems to be somewhat lower than what was reported with US Hispanics. Some age and gender associated bias of the mutation frequency were observed with the study population, the reason for which is unclear at present.     

Cystic renal cell carcinoma: pathological features, survival and implications for treatment

Some epidemiological data point to an association between infection from Helicobacter pylori (Hp) and gastric cancer, although several unresolved issues still cast doubts on the real weight of this association. These issues are as follows: the male-to-female ratio of gastric cancer ranges from 4:1 to 1.5:1 in all studies, whereas the prevalence of Hp infection is the same in both sexes; the prevalence of Hp infection is as high as 90% in several developing countries where the frequency of gastric cancer is very low; the acquisition of the infection at a young age, considered very important with regard to the risk for cancer, varies from 4.2% to 83% in several countries in which the mortality for stomach cancer is approximately 10 in 100,000; and the incidence of cancer in patients with a duodenal ulcer is half that of the general population, but Hp infects up to 100% of these patients. In the sequence of events that leads to gastric cancer, Hp appears to play a role only in the very initial steps, as a causative agent of chronic inflammation. The further events that cause gastric atrophy, intestinal metaplasia, dysplasia, and cancer are multifactorial, involving environmental agents and the host response. It is therefore inappropriate to consider Hp a direct carcinogen for humans. This also applies to specific strains of the bacterium such as the cagA gene. In fact, Hp infection is widespread in humans, and only a small minority will ever be affected by peptic ulcer and cancer.     

Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer

Helicobacter pylori (Hp) infection almost invariably results in chronic antral gastritis, but only a proportion of patients develop peptic ulcer. Some Hp strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may also depend on the type of the host immune response. In this study, the antigen specificity and the cytokine profile of 53 Hp-specific CD4+ T cell clones derived from the antral mucosa of five patients with Hp-induced uncomplicated chronic gastritis (CG) were assessed and compared with those of 34 Hp-specific CD4+ T cell clones derived from six Hp-infected patients with chronic gastritis and peptic ulcer (CG-PU). The majority (28/34; 82%) of gastric Hp-specific T cell clones from CG-PU patients expressed the Th1 profile and 17 (all Th1) of the 34 clones were specific for cytotoxin-associated protein (CagA). In contrast, 34 (64%) of the 53 Hp-specific gastric T cell clones derived from CG patients were able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a polarized Th1 profile. The majority (85%) of Hp-specific clones from CG patients recognized Hp antigens other than CagA, since 13/53 (25%) were specific for urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp antigens. Results provide evidence that the type of T helper cell response against Hp may vary according to the antigen involved and suggest that a polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a local Th0 response, including interleukin-4 production, may represent an individual host factor which contributes to lower the degree of gastric inflammation and prevent ulcer complication.     

Drug-induced lupus erythematosus

alpha 1-Antitrypsin (AT) is the principal serum inhibitor of proteolytic enzymes such as neutrophil elastase. AT can exist as over 90 different genetically determined variants known as the Pi system; the three most important variants are type M (90% of population) and types S and Z, two of the commoner abnormal variants. Homozygotes of type Z have a severe reduction in the serum AT concentration and may develop pulmonary emphysema or hepatic cirrhosis. Heterozygotes of type SZ have a less severe reduction in serum AT concentration and the association with clinical disease is less clear. The S and Z variants are found mainly among those of European stock. The gene frequency for Pi type Z is highest on the north-western seaboard of the continent and the mutation seems likely to have arisen in southern Scandinavia. The distribution of type S is quite different; the gene frequency is highest in the Iberian peninsula and the mutation is likely to have arisen in that region. A population survey for determining the number of type Z homozygotes in a given community is important for planning purposes now that AT replacement therapy is potentially available.     

Allelic diversity at the merozoite surface protein-1 (MSP-1) locus in natural Plasmodium falciparum populations: a brief overview

The merozoite surface protein-1 (MSP-1) locus of Plasmodium falciparum codes for a major asexual blood-stage antigen currently proposed as a major malaria vaccine candidate. The protein, however, shows extensive polymorphism, which may compromise its use in sub-unit vaccines. Here we compare the patterns of allelic diversity at the MSP-1 locus in wild isolates from three epidemiologically distinct malaria-endemic areas: the hypoendemic southwestern Brazilian Amazon (n = 54), the mesoendemic southern Vietnam (n = 238) and the holoendemic northern Tanzania (n = 79). Fragments of the variable blocks 2, 4a, 4b and 6 or 10 of this single-copy gene were amplified by the polymerase chain reaction, and 24 MSP-1 gene types were defined as unique combinations of allelic types in each variable block. Ten different MSP-1 types were identified in Brazil, 23 in Vietnam and 13 in Tanzania. The proportion of genetically mixed infections (isolates with parasites carrying more than one MSP-1 version) ranged from 39% in Brazil to 44% in Vietnam and 60% in Tanzania. The vast majority (90%) of the typed parasite populations from Brazil and Tanzania belonged to the same seven most frequent MSP-1 gene types. In contrast, these seven gene types corresponded to only 61% of the typed parasite populations from Vietnam. Non-random associations were found between allelic types in blocks 4a and 6 among Vietnamese isolates, the same pattern being observed in independent studies performed in 1994, 1995 and 1996. These results suggest that MSP-1 is under selective pressure in the local parasite population. Nevertheless, the finding that similar MSP-1 type frequencies were found in 1994 and 1996 argues against the prominence of short-term frequency-dependent immune selection of MSP-1 polymorphisms. Non-random associations between MSP-1 allelic types, however, were not detected among isolates from Brazil and Tanzania. A preliminary analysis of the distribution of MSP-1 gene types per host among isolates from Tanzania, but not among those from Brazil and Vietnam, shows significant deviation from that expected under the null hypothesis of independent distribution of parasites carrying different gene types in the human hosts. Some epidemiological consequences of these findings are discussed.     

Characterization of BRO enzymes and beta-lactamase transfer of Moraxella (Branhamella) catarrhalis isolated in Japan

Of the 68 strains of beta-lactamase-producing Moraxella (Branhamella) catarrhalis isolated in Japan that were studied, 62 (91%) produced the BRO-1-type beta-lactamase and 6 (9%) produced the BRO-2 type. There were no strains containing the BRO-3-type beta-lactamase. We compared the susceptibility of BRO-1- and BRO-2-producing strains to various oral beta-lactam antibiotics. We found that the BRO-1-producing strains were less susceptible than the BRO-2-producing strains. Although the BRO-1 and BRO-2 types showed a similar hydrolysis pattern, the specific activity of BRO-1 was 3-fold that of BRO-2. We examined the transfer of the BRO-1 and BRO-2 genes to non-beta-lactamase-producing M. catarrhalis No. 4020 and found that of the 13 donor strains producing BRO-1, 11 (85%) were able to transfer the gene for BRO-1 production by conjugation. Of the 6 donor strains producing BRO-2, 2 (33%) were able to transfer the gene for BRO-2 production by conjugation. For 3 of the 13 (23%) BRO-1-producing strains and 1 of the 6 (17%) BRO-2-producing strains, about 13 Mdalton of plasmids were detected. These plasmid-containing strains were used as donors, and in beta-lactamase-producing transconjugants the same size of plasmids was detected. However, when the total DNA is extracted from strains with the ability to transfer by conjugation, the transformation of the beta-lactamase-producing gene can occur regardless of the presence or absence of plasmids. Furthermore, even if purified plasmids are transformed, beta-lactamase-producing transformants are not obtained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Light microscopic detection of sugar residues in rabbit embryo teeth with lectin-horseradish peroxidase conjugates

Tapeworms obtained 13 months after the administration to rats of cysticercoids Hymenolepis diminuta - WMS il1 measured in 3-6-specimen populations an average of 677.9 mm in length while in 23-26-specimen populations an average of 356.9 mm in length. Strobilas of an exclusively unilateral (right-sided) position of genital pores (PGP) appeared in 76.3%-79.8% of tapeworms of the investigated groups. In such tapeworms belonging to 23-26-specimen populations the frequency of occurrence of typical proglottids containing 1 testis on the poral side and 2 testes on the aporal side (1p2a) and type 0p3a proglottids averaging 86.5% and 6.8%, respectively, declines in comparison to the average frequency of occurrence of proglottids of this type in 3-6-specimen populations amounting to 87.8% and 8.8%, respectively. The frequency of occurrence of four-testes (1p3a) proglottids averaged 5.5% in tapeworms from the 23-26-specimen populations and was 4.0% higher than the 1.5% average in tapeworms from the 3-6-specimen populations, in spite of the fact that in a population with a higher number of specimens proglottids are smaller and, therefore, have less room for an additional number of these organs. In tapeworms with variable PGP type 2p1a proglottids constituted the most frequent deviation in each of investigated group of different infection intensity. Their average frequency of occurrence rose from 0.4%-0.5% in tapeworms with unilateral PGP to an average of 5.5%-5.9% in tapeworms with variable PGP. Close positive correlation was found in tapeworms with variable PGP between the frequency of occurrence of such changes and the frequency occurrence of type 2p1a proglottids in every of investigated group (P < 0.01, r = from +0.887, to +0.918).     

Surveillance of fumonisins in UK maize-based foods and other cereals

We analyzed the tyrosinase (TYR) gene of 12 Korean patients with various types of oculocutaneous albinism (OCA). We identified five different mutations in the TYR gene in 4 patients with severe OCA and in 2 patients with mild OCA, but found no mutations in the 6 patients with mild OCA phenotypes. Among the 5 mutations, a frameshift mutation, P310insC, was detected most frequently (allele frequency = 0.5), and the other mutations were found less frequently, two of which, L288delT and IVS2-7t-->a,-10(-)-11deltt, are novel. This study may provide valuable information for the molecular diagnosis of and accurate genetic counseling for OCA1 in Koreans and perhaps other Asian groups.     

Carbohydrate-deficient glycoprotein syndrome type I: determination of the oligosaccharide structure of newly synthesized glycoproteins by analysis of calnexin binding

Familial predisposition to basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are apparent in the autosomal dominant syndromes naevoid basal cell carcinoma syndrome (NBCCS) and multiple self-healing squamous epitheliomata (MSSE) respectively. The gene responsible for NBCCS has been proposed to be a tumour-suppressor gene and is mapped to the same 2 Mb interval on 9q22.3 as the MSSE gene ESS1. In an attempt to further map the NBCCS gene, we have examined loss of heterozygosity (LOH) in 16 sporadic BCCs and two familial BCCs using microsatellite markers located within the candidate gene region. The overall frequency of LOH observed was 67% in the BCCs and partial or interstitial deletions were found in eight tumours, with the highest LOH frequency at markers D9S280, D9S287 and D9S180. To determine if the same genomic region also shows frequent LOH in tumours with a squamous phenotype, we have examined 11 SCCs, four actinic keratoses and 13 cases of Bowen's disease for LOH at 9q22.3. An overall LOH frequency of 50% was observed at D9S180, and occurred in all types of squamous tumours. In contrast, a much lower LOH frequency of only 6% was found at the D9S287 locus. Our observation of different patterns of LOH at 9q22.3 in sporadic BCCs and SCCs implies that more than one tumour-suppressor gene might be located in this genomic region.     

Evidence for non-transferrin-mediated uptake and release of iron and manganese in glial cell cultures from hypotransferrinemic mice

Transferrin (Tf) is accepted as the iron mobilization protein, but its role in transport of other metals is controversial. In this study, we used mixed glial cultures from hypotransferrinemic (Hp) mice to determine the dependence of these cells on transferrin for iron and manganese delivery and release. Hp mice have a splicing defect in the transferrin (Tf) gene, resulting in < 1% of the normal plasma levels of Tf. Cellular iron and manganese uptake increases over 24 hr in cultures of normal and Hp glial cells in the presence of standard concentrations of Tf in the media; although total 59iron uptake in the Hp mouse cultures was 2X greater than normal, 54Mn uptake was similar between the two groups. The absence of Tf in the media resulted in a significant increase in 59iron uptake in both normal and Hp glial but did not affect Mn uptake. Elevated Tf (10X normal) in the media reduced both 59iron and 54Mn uptake. Efflux of 59Iron and 54Mn occurred in normal and Hp cultures, indicating the existence of a dynamic exchange of metals, and that intracellular Tf is not necessary for metal release. However, in the absence of Tf in the media, significantly more iron was retained in the cells than if Tf were present in both normal and Hp glial cultures. 54Mn release was minimally affected by extracellular Tf. The data demonstrate that Tf is not required for iron and Mn uptake into glial cells. These data further demonstrate a dynamic metal exchange system for glial cells which is not dependent on intracellular Tf.     

Pantoprazole-based dual and triple therapy for the eradication of Helicobacter pylori infection: a randomized controlled trial

BACKGROUND/AIMS: The eradication of Helicobacter pylori (Hp) infection in duodenal ulcer and dyspepsia has been achieved using various therapy regimens. The efficacy of protein pump inhibitor pantoprazole as part of these regimens has not been widely studied. METHODOLOGY: During a prospective randomized trial, 250 Hp positive patients with either duodenal ulcer, erosive bulbitis, or gastritis and dyspepsia were treated using 14 days of therapy 1) pantoprazole 40 mg daily and clarithromycin 500 mg b.i.d. (PC), 2) pantoprazole 40 mg daily and clarithromycin 500 mg b.i.d. plus amoxicillin 1 g b.i.d. (PCA), or 3) bismuth subcitrate 120 mg t.i.d., roxithromycin 150 mg b.i.d., metronidazole 250 mg b.i.d. plus ranitidin 300 mg (BRMR). Hp status was assessed on 3 tests at the inclusion (2-specimen rapid urease test, 2-specimen histology, serology) and 2 tests (2-specimen rapid urease test, 2-specimen histology) 4 weeks after the end of the treatment. RESULTS: The entry criteria was fulfilled in 250 patients, of whom 13 missed the control endoscopy. The treatment had to be discontinued for adverse effects in 8 (10%) BRMR patients, and 1 (1%) PCA patients. Compliance was 100% in the PC group. All ulcers were healed at the end of the study with one exception in the BRMR group. The best eradication rate of Hp was shown by the PCA group with 94.8% (n = 73/77) followed by the PC group with 82.5% (n = 66/80) and finally the BRMR with 67.6% (n = 48/71)-PCA:BRMR - p < 0.001; PC:BRMR-p < 0.001; PCA:PC-p < 0.05. CONCLUSION: This study showed that triple therapy using PPI pantoprazole combined with antibiotics clarithromycin and amoxicillin was very effective in the eradication of Hp and treatment of duodenal ulcer with rare side effects. The dual pantoprazole and clarithromycin therapy had the highest rate of patient compliance, but is less effective than triple therapy. The combination of ranitidin with bismuth based triple therapy had the highest number of adverse events and the lowest rate of Hp eradication and therefore, should not be recommended.     

Haptoglobin is a Sertoli cell product in the rat seminiferous epithelium: its purification and regulation

Using multiple HPLC steps, a protein of 67 kDa (estimated by gel permeation HPLC) was purified from Sertoli cell-enriched culture medium that consisted of two dissimilar subunits of 9 (alpha chain) and 24 (beta chain) kDa on SDS-polyacrylamide under reducing conditions. Direct protein sequence analysis of the 9-kDa subunit revealed a sequence of NH2-VELGNDATDIEXD, which is identical to the alpha subunit of the rat haptoglobin (Hp). Hp is a 67-kDa tetrameric serum acute-phase protein consisting of two alpha and two beta subunits (alpha2beta2) of 8.5 kDa and 24.5 kDa, respectively. Using a 351-bp cDNA coding for Hp for northerns and two Hp primers for RT-PCR, we have demonstrated the expression of Hp in Sertoli and Leydig cells, germ cells, and the testis, but not in the epididymis. In contrast to the hepatic haptoglobin, an acute-phase protein whose steady-state mRNA level increased by as much as fivefold during induced inflammation, the testicular homolog reduced by fourfold within 24 hours following induced inflammation, suggesting that this gene is regulated differently in the testis and in the liver. Moreover, the testicular steady-state Hp mRNA level increased steadily after birth during maturation, suggesting its involvement in spermatogenesis. Using primary Sertoli cell cultures in vitro, it was found that the Sertoli cell Hp expression was not regulated by either FSH, testosterone, estradiol, dexamethasone, interleukin-1beta (IL-1beta), IL-6, interferon-gamma (INF-gamma), transforming growth factor-beta (TGF-beta), lymphocyte inhibitory factor (LIF), or germ-cell-conditioned medium (GCCM). Since transferrin secreted by Sertoli cells is an important molecule in maintaining the crucial iron level necessary for spermatogenesis, the identification of haptoglobin as a Sertoli and germ cell product adds a new member to the growing family of metal transporters in the testis that are likely to play an important role in iron metabolism in the testis.