Genetic and environmental determinants for lipoprotein concentrations in blood

Path and segregation analyses have been performed on cholesterol and triglyceride contents of serum as well as on very low, low and high density lipoproteins in 78 Swedish nuclear families. The effect of environmental variables like alcohol and smoking on the concentrations of the different lipoproteins has been studied. Genetic heritability was 0.16-0.68 for the cholesterol fractions and 0-0.56 for the triglyceride fractions. No major gene was evident for any of the variables studied.     

Chromosomal polymorphisms of 1, 9, 16, and Y in 4 major ethnic groups: a large prenatal study

Using trypsin Giemsa banding (GTG), major polymorphisms of the constitutive heterochromatin regions of chromosome 1, 9, 16, and Y were recorded in a New York City population. Polymorphisms were recorded from amniotic fluid specimens received from 6,250 patients from 4 major population groups, ie, White (European)-2,334 cases, American Black-1,795 cases, Hispanic descent-1,737 cases, and Asian (Oriental and Indian)-384 cases. The major chromosomal polymorphisms were classified as follows: obvious pericentric inversion of the constitutive heterochromatin of the long arm of the chromosome (inv qh); significantly enlarged heterochromatic region of the long arm (qh + is greater than, or equal to, twice the size of the short arm of chromosome 16 [16p]); very small or deficient heterochromatic region in the long arm (qh-); large Y (Yq + greater than size of chromosome 18), small Y (Yq- less than size of a G-group chromosome), and pericentric inversion of Y. Our prenatal study confirmed that the incidence of specific chromosomal variants is different in each population group. The most striking examples of this are the pericentric inversion of chromosome 9 and the different polymorphisms of the Y chromosome. The incidence of inv (9) is highest in the Black population (3.57%); slightly above average in Hispanics (2.42%); and relatively low in Whites (0.73%) and Asians (0.26%). The Y appears to be more variable in Asian (3.37%) and Hispanic (1.82%) than in White or Black groups. The 9qh+ is seen more frequently than 1qh+, or 16qh+. Inv (1), 9qh-, and 16qh- are rare. There were no cases of either 1qh- or inv (16).(ABSTRACT TRUNCATED AT 250 WORDS)     

Virilism as a late manifestation in the Bardet-Biedl syndrome

The second case of virilism as a late manifestation of Bardet-Biedl syndrome (BBS) is described, with endocrine and histological evaluation. Both cases manifested ovulatory cycles and developed virilism in adulthood. Elevated plasma testosterone and 17-OH-progesterone were not suppressed by dexamethasone but were suppressed by medroxyprogesterone acetate. Peripheral and ovarian venous blood obtained at the time of surgery demonstrated a marked gradient for testosterone in both ovaries and for progesterone in the ovary bearing the corpus luteum. Histological evaluation of the ovaries demonstrated bilateral ovarian stromal hyperplasia with focal hyperthecosis. Bilateral ovariectomy resulted in complete correction of the endocrine abnormality, although the established hirsutism remains a mark of previous androgen excess.     

Localization and axonal transport of immunoreactive cholinergic organelles in rat motor neurons—An immunofluorescent study

Antisera produced in rabbits against pure fractions of cholinergic vesicles from Narcine brasiliensis were used to study cholinergic organelles in rat motor neurons. The indirect immunofluorescence method was used on perfusion-fixed material. The rats were surgically sympathectomized to remove sympathetic adrenergic and cholinergic nerves from the sciatic nerve. In the intact animal immunoreactive material, likely to represent cholinergic vesicles, was observed in motor endplates, identified by labelling with rhodamine-conjugated α-bungarotoxin or with subsequent acetylcholinesterase staining. The motor perikarya contained very little immunoreactive material. Non-terminal axons were virtually devoid of immunofluorescence in the intact animal. After crushing the sciatic nerve, immunoreactive material (likely to represent axonal cholinergic organelles) accumulated rapidly on both sides of the crush, indicating a rapid bidirectional transport. The transport was sensitive to local application of mitotic inhibitors.The axons which accumulated immunoreactive organelles were motor axons, as demonstrated by various procedures: (1) Cutting of ventral roots prevented accumulation of immunoreactive material in the nerve. (2) Deafferentation did not notably influence accumulations of immunoreactive material. (3) Ligated axons with immunoreactive material were acetylcholinesterase positive when identification was made on the same section; the intra-axonal distribution of immunoreactive material and acetylcholinesterase was not identical, however, and the Narcine antisera did not cross-react with bovine acetylcholinesterase in a solid phase immunoassay. (4) Most axons in ventral roots, but not in dorsal roots, accumulated strongly fluorescent immunoreactive material, while axons in dorsal roots contained weakly fluorescent material. On the other hand, substance P-like immune reactivity was present in many dorsal root axons, but only very rarely in ventral roots.It is suggested that the antisera against Narcine cholinergic vesicles can be used as a marker for cholinergic organelles in the motor neuron, and may be an important tool for studying the axonal cholinergic vesicles. It cannot, however, be used to identify cholinergic structures in unknown locations because it recognizes common antigenic determinants in transmitter organelles of other nerves e.g. adrenergic nerves. The axonal cholinergic organelles may carry important molecules, other than acetylcholine to the nerve endings.     

Nonspecific cytotoxic cells in fish ( ) IV. Target cell binding and recycling capacity

The morphology of nonspecific cytotoxic cells (NCC) was identified. NCC were purified by target cell conjugate formation and density gradient separation. NCC are monocyte-like. They have reniform nuclei and a low nucleus/cytoplasm ratio. Cytoplasmic granules were not seen after giemsa staining. Scanning electron microscopy demonstrated moderate surface villi and target cell attachment occurred via long membraneous filament-like surface projections extending to the target cell membranes. Transmission electron microscopy of effector: target cell conjugates revealed membrane contact areas without fusion or fragmentation. The nucleus of the NCC had accentuated peripheral chromation and a prominent Golgi apparatus; the cytoplasm contained osmiophilic granules.Michaelis-Menten and Lineweaver-Burk transformation of target cell binding revealed a Vmax of 11–15,000 and a Km of 40,000. The percentage of NCC bound to target cells was 16–18%. Results of these studies were combined with the conjugate experiment to obtain an estimated percentage of active NCC (5–7%). A maximum recycling capacity of .16–.30 indicated that once attachment by NCC to the target cell occurred (and a lethal signal delivered by an effector cell), either the NCC did not recycle or a long lag period was required to restore its cytotoxic capability.     

An unusual expression of a squamous cell marker, small proline-rich protein gene, in tracheobronchial epithelium: differential regulation and gene mapping.

An unusual expression of a putative squamous cell marker, small proline-rich protein (spr1), in mucociliary epithelial cells of conducting airways was demonstrated in a serum-free culture system. A cDNA clone was isolated from the cDNA library of monkey tracheobronchial epithelial (TBE) cells by differential hybridization. This cDNA clone, MT5, exhibited 98% homology to a DNA sequence obtained from human keratinocytes treated with either UV light or phorbol esters (T. Kartasova et al., 1988, Mol. Cell. Biol. 8:2195-2230). The predicted peptide of MT5 is unusual for its high content of proline (29%), glutamine (18%), and cysteine (9%) and its repeated PKVPEPC units. The level of spr1 mRNA in cultured cells was inhibited more than 90% by vitamin A. In contrast, phorbol 12-myristate 13-acetate (PMA) stimulated the level of spr1 mRNA by 3- to 8-fold. This differential regulation coincided with the effects of these chemicals on the cornification of cultured TBE cells. Using MT5 as a probe, we have localized the tracheal spr1 gene on the human chromosome 1 by a Southern blot analysis using a panel of human-rodent somatic cell hybrid DNAs. The gene was further sublocalized to bands q22-23 by in situ hybridization.     

Higher levels of plasma estradiol and testosterone in healthy elderly men compared with age-matched women may protect aspects of explicit memory

OBJECTIVE: To assess longitudinally the relationships between plasma levels of estradiol (E2) and free testosterone (T) and cognitive functioning in elderly men, women who use estrogen, and women who do not use estrogen. DESIGN: At two test times 18 months apart (time 1 and time 2), men (time 1, n = 31; time 2, n = 23), women who were using estrogen (time 1, n = 14; time 2, n = 10), and women who were not using estrogen (time 1, n = 41; time 2, n = 27), whose average age was 72.1 and 73.4 years at time 1 and time 2, respectively, were administered a battery of neuropsychological tests that measured verbal memory, visual memory, concentration and attention, language fluency, and semantic memory. Plasma levels of E2 and free T were assessed by radioimmunoassay. RESULTS: The men had higher free T levels than both groups of women at both test times. Although women who were using estrogen had higher E2 levels than those of the men and of the women who were not using estrogen, the men's E2 levels were also significantly higher than those of the women who were not using estrogen. Moreover, the women who were using estrogen and the men had higher Forward Digit Span scores compared with the women who were not using estrogen at both test times, and women who were using estrogen had higher Backward Digit Span scores than those who were not using estrogen. Both groups of women performed better than the men on the Category Retrieval Test (verbal fluency). The performance of women who were using estrogen on the Delayed Selective Reminding Test (long-term rote memory) improved over time compared with that of the men and of the women who were not using estrogen. CONCLUSIONS: These findings raise the possibility that higher E2 levels in elderly men and in women who use estrogen may protect against some declines in explicit memory with normal aging.     

Activation and Sorting of Human White Blood Cells

We demonstrate a novel activation behavior of human leucocyte adhesion under physiological flow conditions in a microfabricated silicon array of channels with length scales similar to those of human capillaries. Vital nuclei stains and cell specific, flourochrome labeled antibodies reveal that the equilibrium distribution of stuck cells in the arrays displays a strong dependence on cell type and nuclear morphology, and there is eventual separation of the two cell types in the array. The distortion of the cells is the same as they experience in vivo and the response of the granulocytes is consistent with a model describing adhesion as a function of the distortion of the cell by its environment; in other words, activated adhesion. We propose that this complex non-random behavior is due to a deformation activated change in the cells relevant to observed in vivo behavior.     

Identification of loci determining susceptibility to the lethal effects of amyloid precursor protein transgene overexpression

Phenotypes produced by expression of human amyloid precursor protein (APP) transgenes vary depending on the genetic background of the mouse. FVB/N mice overexpressing human APP695 develop a central nervous system disorder and die prematurely, precluding development of Abeta peptide amyloid plaques. 129S6 mice are resistant to the lethal effects of APP overexpression, allowing sufficient levels of Abeta expression for the development of amyloid plaques and age-dependent memory deficits. To identify the genes that determine susceptibility or resistance to APP we analyzed crosses involving FVB/NCr and 129S6.Tg2576 mice that overexpress 'Swedish' mutant (K670N, M671L) APP695. APP transgene-positive FVB129S6F1 (F1) mice are resistant to the lethal effects of APP overexpression, so FVBxF1 backcross and F2 intercross offspring were produced. Analysis of age of death as a quantitative trait revealed significant linkage to loci on proximal chromosome 14 and on chromosome 9; 129S6 alleles protect against the lethal effects of APP. Within the chromosome 14 interval are segments homologous to regions on human chromosome 10 that have been linked to late onset Alzheimer's disease or to levels of Abeta peptide in plasma. However, analysis of plasma Abeta peptide concentrations at 6 weeks in backcross offspring produced no significant linkage. Similarly, elevation of human Abeta peptide concentrations by expression of mutant presenilin transgenes did not increase the proportion of mice dying prematurely, suggesting that early death reflects effects of APP or fragments other than Abeta.