Stability of insulin mixtures in disposable plastic insulin syringes

The miscibility of short and long acting porcine, human and bovine insulins has been investigated using HPLC. Soluble insulin is rapidly lost from solution when mixed with both isophane and zinc insulin, although the mechanism may be different in these two cases. The time for up to 50% or more to be lost is often less than 2 min. The percentage lost is dependent upon the ratio of the mixture and the type and origin of the insulin. In the case of soluble: zinc mixtures it is greatest for porcine and least for bovine, in the case of soluble: isophane mixtures it was least for human and greatest for bovine. The greater the original amount of soluble insulin present the less the loss. The results help explain recent clinical reports that mixtures of soluble and zinc insulins fail to achieve satisfactory control of post-prandial blood sugar levels.     

Nontraumatic intracerebral hemorrhage in young adults

We reviewed our experience with 72 patients, aged 15 to 45 years, who were hospitalized for nontraumatic intracerebral hemorrhages (ICHs) between 1978 and 1985. Evaluation included arteriography in 61 patients. Computed tomography demonstrated 41 lobar, 11 putaminal, four thalamic, four pontine, four intraventricular, two caudate, two midbrain, two cerebellar, one globus pallidum, and one corpus callosum hemorrhage. Forty-three patients, with either progressive neurologic deterioration, arteriovenous malformations (AVMs), or saccular aneurysms underwent surgery. The overall in-hospital survival, including those patients treated medically, was 87.5%. A presumed cause for the ICH was found in 55 (76.4%) patients. The main causes were ruptured arteriovenous malformations (21), hypertension (11), ruptured saccular aneurysms (seven), and sympathomimetic drug abuse (five). Surgical explorations demonstrated a necrotizing angiitis in one patient and arteriovenous malformations in two patients who had negative arteriograms. Young patients with nontraumatic ICHs represent a heterogeneous group. A cause can be established in most patients. Arteriovenous malformations account for less than one third of the hemorrhages in young adults, and other causes should be sought.     

Induction of oral cavity tumors in F344 rats by tobacco-specific nitrosamines and snuff

The tumorigenic activities toward the oral cavity of snuff, its extracts, and two of its major nitrosamines, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were evaluated in male F344 rats. In one protocol, groups of 21-30 rats were treated beginning at age 10 weeks by chronic application to the oral cavity for 131 weeks of either H2O, an H2O extract of snuff, an H2O extract of snuff enriched with ten times its indigenous concentration of NNN and NNK, or with NNN and NNK in H2O. The incidence of oral cavity tumors in the rats treated with NNN and NNK was 8 of 30, compared to 0 of 30 in controls (P less than 0.05). These results demonstrate that NNN and NNK can induce tumors locally in the oral cavity of F344 rats. Oral cavity tumors were also observed in 3 of 30 rats treated with snuff extract enriched with NNN and NNK, but not in the rats treated with snuff extract alone. In a second protocol, a test canal was surgically created in the lower lip of groups of 21-32 rats, and either snuff, H2O-extracted snuff, or snuff enriched with its own H2O extract was inserted in the test canal 5 times weekly for 116 weeks. A group of 10 control rats had surgery only. Among the 32 rats treated with snuff, 3 had oral cavity tumors; one was a squamous cell carcinoma originating in the test canal and invading the gingiva, one was a papilloma of the test canal, and one was a papilloma of the hard palate. Oral cavity tumors were also observed in 2 of 21 rats treated with H2O-extracted snuff and 1 of 32 rats treated with snuff enriched with its H2O extract. Oral tumors were not observed in control rats. The results of this study indicate that snuff and individual nitrosamines present in snuff can induce oral cavity tumors in F344 rats and support the epidemiological observations which indicate that snuff dipping causes oral cancer in man.     

The Development and Teaching of the Ethical Principles and Guidelines for Family Scientists*

This article describes the development of the Ethical Principles and Guidelines for Family Scientists that the National Council on Family Relations Board of Directors unanimously approved. Furthermore, it discusses the importance of ethics education for family professionals and provides suggestions for educators. Finally, the ethical principles and guidelines are delineated. We argue that the development of a scholarship on ethics education is important for current and future family scientists.     

Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II

Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate ("thromboplastin") or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible.     

On the measurement of susceptibility in epidemiologic studies

Although relative effects of risk factors (relative risks) are commonly used in epidemiologic studies of disease, these measures do not provide estimates of the proportion of persons who are "susceptible" to the risk factor. Susceptibility may be defined under a simple sufficient cause model as the underlying factor (or set of factors) sufficient to make a person contract a disease following exposure. The authors derive simple estimates of the proportion of susceptibles in a population based on relative risk, and disease and exposure frequencies. The proportion of susceptibles increases with increasing disease frequency and relative risk but declines at high exposure frequency. For many chronic diseases with a lifetime risk in the range of 1-10 per cent, rare exposures suggest the presence of a large proportion of susceptibles, whereas common exposures suggest fewer susceptibles in the population. The estimation of the proportion of susceptibles is important in the search for genetic and environmental factors that interact with measured risk factors in etiologic studies of disease.     

Evidence for a neural basis of age-related visual field loss in normal observers

Many studies have reported a decrease in visual field sensitivity as a function of increasing age in normal individuals. This age-related sensitivity loss has mainly been attributed to reductions in pupil size and transmission losses of the ocular media (particularly the lens), although neural losses in the retina, optic nerve and visual cortex have also been suggested. We evaluated the role of preretinal factors on normal visual field changes associated with aging. The central visual field of both eyes of 62 normal subjects (ages 20 to 72) were evaluated with Program 30-2 of a modified Humphrey Field Analyzer. Three test procedures were employed: (1) a standard visual field evaluation; (2) a yellow target on a yellow background condition (530 nm cutoff filter) to minimize the influence of lens transmission losses with age; and (3) a large target/high background luminance "yellow on yellow" test condition (530 nm cutoff filter, 635 asb background, Size V target) to minimize both pupil size and lens effects on central visual field sensitivity. In addition, relative lens absorption estimates were obtained for each subject. All three test conditions revealed a loss in visual field sensitivity with increasing age (approximately 0.8 dB per decade) but no meaningful differences were found among the three test procedures. Relative lens density increased with age but was not related to visual field sensitivity for any of the three test conditions. These data suggest that normal age-related visual field sensitivity changes are primarily due to neural losses rather than preretinal factors.     

LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus

Cellular attachment factors like the C-type lectins DC-SIGN and DC-SIGNR (collectively referred to as DC-SIGN/R) can augment viral infection and might promote viral dissemination in and between hosts. The lectin LSECtin is encoded in the same chromosomal locus as DC-SIGN/R and is coexpressed with DC-SIGNR on sinusoidal endothelial cells in liver and lymphnodes. Here, we show that LSECtin enhances infection driven by filovirus glycoproteins (GP) and the S protein of SARS coronavirus, but does not interact with human immunodeficiency virus type-1 and hepatitis C virus envelope proteins. Ligand binding to LSECtin was inhibited by EGTA but not by mannan, suggesting that LSECtin unlike DC-SIGN/R does not recognize high-mannose glycans on viral GPs. Finally, we demonstrate that LSECtin is N-linked glycosylated and that glycosylation is required for cell surface expression. In summary, we identified LSECtin as an attachment factor that in conjunction with DC-SIGNR might concentrate viral pathogens in liver and lymph nodes.