Presence of a metallothionein-like protein in the bovine pineal gland

Summary The high concentration of zinc in the bovine pineal gland prompted us to investigate the existence of a zinc-binding protein in this organ. In this study, we report that the subcellular distribution of zinc in the bovine pineal gland is nonuniform, with the crude nuclear, mitochondrial, microsomal, and supernatant fractions having 0.264±0.038, 0.160±0.019, 0.130±0.016, and 0.287±0.010 g zinc/mg protein, respectively. Furthermore, gel filtration studies using Sephadex G-75 and a 105,000 g supernatant fraction revealed two zinc binding protein peaks that bind 1.7 and 3.7 g Zn⁺⁺/mg protein, respectively. Furthermore, purification of the protein peak with an elution volume (ve/vo) of 2.06 on anion exchange chromatography (DEAE-A 25) yielded a single protein peak which binds 10 g zinc/mg protein. The comparative high performance liquid Chromatographic (HPLC) profiles of the zinc-induced hepatic metallothionein isoform I (retention time=17.39 min) and of the bovine pineal metallothionein-like protein isoform I (retention time=17.49 min) are similar. Since zinc is a potent inhibitor of sulfhydryl-containing enzymes and receptor sites, we investigated the effects of zinc and found that it inhibited the binding of [³H]glutamate (IC 50=80 M) and of [³H]spiroperidol (IC 50=0.6 mM) to the pineal membranes. The results of these studies are interpreted to indicate that the bovine pineal gland possesses an active and dynamic zinc homeostatic mechanism, whose precise function(s) remain(s) to be delineated.     

The ultrastructure of the avian Golgi tendon organ

The ultrastructure of the avian Golgi tendon organ (GTO) is described and compared with those of mammals using transverse sections through the myo-tendinous junctions of wing muscles of adult mallard ducks. The capsule, which is continuous with the perineural epithelial sheath of the Ib afferent nerve fiber, consists of four to seven flattened cellular lamellae. Two to four muscle fibers attach to large collagen bundles which enter the GTO through a tight collar at the proximal end of the fusiform capsule. These collagen bundles divide into many smaller bundles, which run longitudinally through the lumen in compartments formed by septal cells. The septal cells contain many prominent lipid accumulations. The Ib axon divides several times, and the unmyelinated branch axons weave between the small collagen bundles. Schwann cell processes or basement membrane usually intervene between the axons and collagen bundles. The small collagen bundles regroup into larger bundles, which pass through tight capsular collars and merge with the main muscle tendon. The size of the duck GTOs was measured and found to be smaller than the GTOs of man, cat or rat.     

Cancer by negative heterosis: breast and ovarian cancer excess in hybrids of inbred ethnic groups

Breast and ovarian cancer rates in Pakistan are significantly higher than in neighboring countries. The cancer rate discrepancies cannot be explained with discrepancies of their risk factors. We propose that observed cancer excess in Pakistan is due to cancer development by negative heterosis. Heterosis occurs when a hybrid has a phenotypic characteristic significantly different from that in either parent (hybrid vigor). At a molecular level, heterosis occurs in a heterozygote when one of the two alleles is inactivated. Gene inactivation occurs by methylation of cytosine in a promoter region of a gene. Initiation of allele inactivation is linked to the factors like stress, gender, diet, or another gene. In heterozygote, inactivation of one of the two tumor-suppressor alleles leads to monoallelic expression. This increases cancer risk in the same way the risk is increased in individual who inherit a single mutated tumor-suppressor gene (hereditary cancer syndrome). In both, cancer by heterosis and inherited cancer syndrome, cancer develops after inactivation of a second allele (second hit hypothesis). In a population, conditions that favor development of cancer by heterosis are those that favor mating of a large number of different homozygotes because they produce a large number of different heterozygotes. Among a large number of heterozygotes, there is an increased chance that some of hybrids will develop cancer by heterosis. In Pakistan, conditions were favorable for cancer development by heterosis because country has a high number of different ethnic groups and brotherhoods all of which have a higher rate of homozygosity due to a high frequency of consanguineous marriages, and marriages between members of different groups occurred because of intense population mixing. Result was birth of a large number of inter-ethnic/brotherhood hybrids (heterozygotes), some of which have developed cancer by heterosis.     

Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.     

Progression and regression of cervical lesions: Review of smears from women followed without initial biopsy or treatment

Cervical smears were reviewed from patients in whom a cytological abnormality was followed, after an interval without interference, either by regression to `negative' or else by progression to invasive carcinoma. Twenty-eight cases were from a previously analysed series with positive smears and an interval of at least two years before investigation, resulting from refusal or failure to trace. Slides were also reviewed from 25 cases in which `positive' smears had regressed to negative without escaping from surveillance, and from 10 patients subsequently developing invasive carcinoma whose previous slides, taken several years earlier, showed abnormalities on review. None of these 63 patients had any biopsy or other surgical procedure to the cervix between the initial smear and the outcome.

Slides showing `superficial cell dyskaryosis' and/or well-differentiated `parabasal cell dyskaryosis' were found only among the groups with subsequent regression. Those showing dissociated poorly differentiated dyskaryotic parabasal cells regressed to negative in two cases and progressed to invasion in nine. This suggests that many examples of spontaneous regression correspond to mild dysplasias which are not precancerous, and overdiagnosis must often have resulted in unnecessary surgical procedures in the past.

`Regressing' and `progressing' groups both included cases in which the spatula had removed coherent pieces of undifferentiated epithelium. These are difficult to interpret cytologically. In nine of them (including four which regressed) the cytological picture was that of carcinoma in situ. The remainder (14 cases) were probably examples of reserve cell hyperplasia, and it is noteworthy that, of the 21 cases subsequently progressing to invasive carcinoma, five were preceded by appearances of this type. It is concluded that cell aggregates suggesting an unusual degree of reserve cell hyperplasia are a danger signal and require careful surveillance.

     

Developmental alterations in 5'-nucleotidase kinetics and lipid composition of rat heart sarcolemma

The objective of these studies was to examine the mechanism by which the specific activity of heart sarcolemma 5'-nucleotidase decreases as function of age. We examined the kinetic properties and the lipid composition of the sarcolemma from animals with different ages. The age groups used were 1 month, 6-8 months and 13-15 months. It was found that the Km of this enzyme increases as the animal develops from 1 month to 6-15 months. The opposite was true with 5'-nucleotidase Vmax. There was no significant difference between the middle age and the older age groups in those parameters. The results of these experiments suggest that the increase in Km in sarcolemma 5'-nucleotidase could be due to the reduction of the sarcolemmal polyunsaturated fatty acid concentration, the only lipid alteration observed.     

HLA polymorphisms in Nigerians

The HLA class I and class II phenotypes of a panel of 114 unrelated Nigerians have been determined. The panel was tested for all the known class I antigens and comparisons of the HLA-A and -B frequencies with those of other African Negroid populations revealed some differences. Only limited comparisons could be made for the HLA-DR and -D frequencies as these are not available for any well-defined African Negroid population. The data concerning the class II antigens of this panel are the most interesting. Half of the DRw11-positive panel members are DQw3 negative and DQw1 positive. In addition, there is dissociation of some HLA-D and -DR specificities, a number of panel members are positive for an HLA-D specificity and are negative for the corresponding HLA-DR specificity. Our results show the value of population studies in the investigation of the relationship between the different HLA class II antigens.