Sole Target Research Articles

The Paradoxical Nature of DNA Damage and Cell Death Induced by 125 I Decay

Chinese hamster ovary cells were synchronized at the G1/S-phase boundary of the cell cycle and pulse-labeled for 10 min with 125I-iododeoxyuridine 30 min after entering the S phase. Cell samples were harvested for freezing and 125I-decay accumulation at intervals ranging from 15 to 480 min after termination of labeling. The survival data showed a marked shift from cell killing characteristic of low-LET radiation to that more characteristic of killing by high-LET radiation with increasing intervals between DNA pulse-labeling and decay accumulation. Cells harvested and frozen within 1 h after pulse-labeling yielded a low-LET radiation survival response with a pronounced shoulder and a large D0 of up to 0.9 Gy. With longer chase periods the shoulder and the D0 decreased progressively, and cells harvested 5 h after pulse-labeling or later exhibited a high-LET survival response (D0: 0.13 Gy). Two interpretations for these findings are discussed. (1) If DNA is the sole target for radiation death, the results indicate that DNA maturation increases radiation damage to DNA or reduces damage repair. (2) If radiation cell death involves damage to higher-order structures in the cell nucleus, the findings suggest that newly replicated DNA is not attached to these structures during the initial low-LET period, but 125I starts to induce high-LET radiation effects as labeled DNA segments become associated with the target structure(s). On balance, or data favor the latter interpretation.

The Role of Medicaid and Other Government Programs in Providing Medical Care for Children and Pregnant Women

This article provides an overview of the major federal and state health care programs serving children and pregnant women, including Medicaid, the Maternal and Child Health Block Grant Program, the Community and Migrant Health Center Program, and the Special Supplemental Food Program for Women, Infants, and Children. A detailed description of key amendments to the federal Medicaid statute which substantially expanded the number of pregnant women and children eligible for benefits is presented along with a discussion of the creative reforms of eligibility and service delivery systems some states implemented to expand utilization of prenatal care. Early evaluation results indicate that these perinatal reforms appear to be having a positive impact on both infants and pregnant women. An assessment of the possible impact of recent Medicaid expansions on children’s access to medical care reveals that progress has been slow. States have not yet undertaken substantial initiatives to improve the accessibility and efficacy of child health programs. The author concludes, however, that creative efforts by a growing number of states give reason to be cautiously optimistic about the prospect of progress in the future. T he latter half of the 1980s witnessed dramatic expansion in the roles that state and federal governments play in providing and financing perinatal and well-child care in America. Sweeping initiatives were begun that have the potential to commit vastly larger sums of public monies to the support of maternal and child health. Expanding the delivery of prenatal care became a cause that attracted support across the political spectrum, on the grounds that expanded coverage was both a humane course to take and an efficient investment in our nation’s future. Yet the manner in which change was achieved—by expanding eligibility for pregnant women and young children under the Medicaid program—has raised a number of questions regarding the appropriate and potential roles of government in serving these populations. Questions that have arisen include the following: n Is an insurance program like Medicaid the best vehicle to improve the health status of mothers and children? n Can a program that has such a strong historical link to the public welfare system escape that system’s stigma and be fully embraced as a positive public health care program by mothers and families? n Can families’ access to care be improved if the vehicle chosen to accomplish this goal is a financing program that is held in such negative regard by much of the private physician community? n Would government funds be better spent by increasing support for programs other than Medicaid that directly provide, rather than just finance, prenatal and well-child care? n Would real access be achieved more expeditiously by targeting dollars to expand the capacity of such public providers as state and local health department clinics and community and migrant health centers? This article describes the rapid evolution of this country’s publicly subsidized systems of health care for pregnant women and children which has taken place during the past 5 years. First, an overview of the various major federal and state programs is provided. Second, a detailed description of the key amendments in the federal Medicaid statute that enabled its expansion is presented along with a discussion of the flexibility utilized by states to implement creative reforms of eligibility and service delivery systems. Also included are early evaluation results which indicate the positive impact that perinatal reforms appear to be having on both the insurance and health status of mothers and infants. Finally, an assessment of the possible impact of recent Medicaid expansions on children’s access to medical care is presented. An Overview of Government Programs Serving Pregnant Women and Children Many government programs serve disadvantaged pregnant mothers and their children. Some hold these populations as their sole target, while others serve a much broader population. Some programs are designed to finance care by reimbursing providers for rendering care, while other programs subsidize the direct provision of services. Some programs are fully administered by federal agencies and operate under federal rules, while others share responsibility for management and rule making between federal and state levels of government. Appearing below are brief 136 THE FUTURE OF CHILDREN – WINTER 1992 descriptions of these programs—their objectives, organization, administration, and financing.

Activation of nerve growth factor synthesis in primary glial cells by phorbol 12-myristate 13-acetate: role of protein kinase C

Phorbol 12-myristate 13-acetate (PMA) induces a dramatic production of nerve growth factor (NGF) in primary cultures of newborn mouse astrocytes maintained in a serum-free medium. This stimulation is dose-dependent and a maximal effect on the levels of cell-secreted factor was observed at a concentration of 10 nM. At this concentration, the promoting effect of PMA appears much more important than that elicited by 10% fetal calf serum (FCS) under the same culture conditions. PMA acts primarily on the accumulation of NGF mRNA, which was detected by northern blot analysis after 6 h of treatment. This accumulation may be totally or partially prevented when PMA-treated glial cells are concommittantly exposed to the protein kinase inhibitors H-7, H-9, and to a lesser degree, HA-1004. The known specificity of these inhibitors agrees with the possibility that protein kinase C (PKC), which constitutes so far the sole known target of PMA, represents a key element involved in the stimulation of NGF gene. The role of PKC is further supported by the observation that α phorbol didecanoate, which has no activity on PKC, is depleted of effect on the synthesis of NGF. Likewise, 1, 2-dioctanoylglycerol (1, 2-DOG) has a weak, but significant promoting action on the production of NGF, unlike the 1, 3-isomer which is not active on PKC. Finally, a treatment of 15 min with 100 nM PMA is sufficient to stimulate the cells, suggesting that the activation phase of PKC, rather than its down regulation, constitutes an important trigger leading to an increased expression of the NGF gene. The effect of PMA and FCS can be reverted, at least in part, by dexamethasone, which depresses the levels of cell-secreted NGF and lowers the pool of NGF transcripts. It is suggested that a balance between activators of PKC and glucocorticoids might control in vivo the expression of NGF synthesis by astrocytes of the central nervous system.

Synapse formation on trochlear motor neurons under conditions of increased and decreased cell death during development

There is a normally occurring death of about half of the trochlear motor neurons during development. Early removal of the target muscle results in death of almost all neurons whereas neuromuscular blockade prevents neuron death. The present investigation was undertaken to determine whether the number of central afferent synapses on motor neurons is altered under conditions which either accentuate cell loss or rescue neurons. The sole peripheral target of innervation of the trochlear motor neurons, the superior oblique muscle, was extirpated in duck embryos before the motor axon out-growth begins. The neuromuscular blockade was achieved by application of paralyzing dosages of alpha bungarotoxin on to the vascularized chorioallantoic membrane. This treatment began prior to the onset of cell death and embryos were treated daily throughout the period of cell death. Brains were processed for electron microscopy and quantitative observations were made on synapses at the onset, during the period of, and at the end of cell death. It was found that there was no significant difference in the number of synapses on neurons following target removal, following neuromuscular blockade, and those developing normally. This observation indicates that the number of central afferent synapses on cell soma is not altered under conditions which either decrease or increase neuron survival. These results suggest that the synapse number per se may not be directly involved in the process of naturally occurring cell death. The results also suggest that the number of synapses on trochlear motor neurons is independent of interactions with the target.

Over- vs. Undercontrolled Hostility: Application of the Construct to the Classification of Maritally Violent Men

The purpose of the present investigation was to evaluate the applicability of Megargee's (1967) distinction between over- and undercontrolled hostility to maritally aggressive men. Subjects were 41 men who were referred for treatment for physical marital violence. Data were derived from a written battery of self-report measures. Overcontrolled hostile men showed patterns of abuse in which violent episodes were more severe but less frequent and in which the wife was the sole target of the aggressive behavior. Undercontrolled hostile husbands were more generally aggressive and more frequently aggressive. Additionally, undercontrolled husbands were more likely than overcontrolled husbands to have witnessed violence in their families of origin and to have had rejecting mothers. Implications for the assessment and treatment of marital violence are discussed.

Classification of the temporal discharge patterns of single auditory neurons in the dorsal medullary nucleus of the northern leopard frog

1. The dorsal medullary nucleus (DMN) of frogs is the presumed homolog of the mammalian cochlear nucleus (CN). Like the CN, the DMN is the sole target of centrally projecting primary auditory-nerve fibers and the first central auditory-processing center. To study the transformation of acoustic information in the DMN, we have utilized relatively simple stimuli--tone bursts--to detail the temporal discharge patterns of DMN neurons that can be compared with those shown by auditory-nerve fibers. 2. Based on the shape of poststimulus time (PSTH) and interspike interval (ISIH) histograms, we observed six distinctive discharge patterns to tone bursts presented at the best excitatory frequency (BEF), 10 dB above threshold. Four of these (primary-like type 1-4) resembled discharge patterns seen at the level of the auditory nerve, whereas two (phasic and phasic burst) were only observed in the DMN. 3. At stimulus levels of 20-30 dB above BEF threshold several phasic neurons became tonic responders, whereas several primary-like type-2 cells gave "pauser" discharges. The response patterns of the remaining cells were intensity independent. 4. We further showed that many of the single-unit discharge patterns were related to other neuronal response properties; specifically, spontaneous firing rate, intensity-rate functions, threshold, latency, BEF, and sharpness of tuning (Q10). 5. The implications of our findings are discussed with respect to 1) the transformation of acoustic information as it is passed from the auditory nerve to the DMN, and 2) the functional organization of the DMN.

Acetohydroxy Acid Synthase Activity in Chlorella emersonii under Auto- and Heterotrophic Growth Conditions

Acetohydroxyacid synthase (AHAS) activity was studied in the green unicellular alga Chlorella emersonii. This activity and its regulation was compared in the algae grown autotrophically and heterotrophically on glucose in the dark. No evidence for the existence of more than one enzyme was found. The activity in crude extracts from either heterotrophically or autotrophically grown cells showed a K(m) for pyruvate of 9 millimolar, a 22-fold preference for 2-ketobutyrate over pyruvate as the second substrate, 50% inhibition by 0.5 millimolar valine, and 50% inhibition by 0.3 micromolar sulfometuron methyl (SMM). Spontaneous mutants of the alga resistant to SMM were isolated, which appeared to be single gene mutants containing SMM-resistant AHAS activity. Hence, AHAS appears to be the sole direct target site of SMM in C. emersonii. The fact that the mutants had equivalent SMM resistance under auto- and heterotrophic conditions further supports the conclusion that the same enzyme functions under both physiological regimes. The addition of valine and isoleucine leads to partial relief of SMM inhibition of biomass increase, but not of SMM inhibition of cell division.

Correspondence

CORRESPONDENCE In John G. Gammie's favourable review of my dissertation Studies in the Language of Qoheleth, With Special Emphasis on the Verbal System (HS 30 [1989]:148-152), he suggests some points of criticism to which I would like to make a few comments. As point one he proposes that in discussing the conjunctive wSC forms (verb form of the suffix conjugation preceded by the conjunction waw and constituting a syntactic unity together with the preceding verb form) I should have considered the possible use of waw as a subordinating conjunction (in case of Qoh 5:5, "so that ..."). My answer is that this possibility is in no way excluded in the discussion. The term conjunctive verb form exclusively refers to the syntactic function of the verb that, being preceded by the conjunction waw, forms a syntactical complex with the preceding (usually PC) verb form (cf. my book, p. 30). Of course the conjunctive form of such a complex may (and quite often actually does) express subordination. The reason why I chose the New International Version to translate Qoh 5:5 ("and destroy the work of your hands") was that it retained the syntax of the Hebrew text. But it should be observed that even in the English the formal co-ordination actually expresses subordination (formally, co-ordination is expressed, intended, however, is the meaning of subordination: "so that he destroys"): "Why should God be angry at what you say and destroy the work of your hand?" (NIV Qoh 5:5). As to the suggestion that I should have singled out for analysis idiomatic usages of the verb in my treatment of the current verbs, 1 admit this neglect should at least have been commented in a footnote. The reason for the omission was that the predicament of a verb being part of an idiomatic phrase in this case does not affect the aspectual value of the verb forms treated-and this was the sole target of my investigation--even if the meaning in other respects was changed by this fact. Point three of Gammie's criticism I simply do not understand. Like myself he recognizes the remarkable similarity between the predominant use of the SC in both the Manual of Discipline from Qumran and in Qoheleth, but he suggests that I do not spell out an answer to this for fear that it would undermine some of my findings. Why should I? And what is the answer that Gammie expects from me (he thinks 1 have already in my dissertation provided the elements of an answer)? I regret that Gammie was not more outspoken in this respect. Hebrew Studies 31 (1990) 276 Correspondence Lastly, I would like to thank the reviewer for his valuable observation that the Samaritan Pentateuch regularly favours the use of the definite article, a fact that reminds one of the usage in Qoheleth and may be another indication of the influence of a northern Hebrew dialect in the language of the book. Bolsaksson Uppsala University 751 20 Uppsala. Sweden I would like to respond to Mayer Gruber's review of my monograph, Isaiah 1-4 and the Post-Exilic Understanding of the Isaianic Tradition (BZAW 171, Berlin & New York: de Gruyter, 1988), which appeared in HS 30 (1989):194-196. Clearly, Gruber does not agree with my work and, of course, this is his prerogative. But the grounds on which his disagreement is based require comment inasmuch as they are not entirely appropriate to the nature of the thesis of my book and the arguments put forward to support it. Gruber maintains that my central thesis is "that the book of Isaiah is to be seen at one and the same time as a compilation of prophetic oracles spanning several centuries and as a theological unity." This is true in the most general sense, but it does not account for several important aspects of my work. Most important is the redactional reinterpretation of earlier prophetic material in the later fifth century context of the final form of the book of Isaiah. Isaiah ben Amoz, for example, addresses the situation of Israel and Iudah in relation to the emergence of Assyrian power in the region in...

Identification of gonadotropin releasing hormone (GnRH) neurons projecting to the median eminence from third ventricular preoptic area grafts in hypogonadal mice

Functional gonadotropin releasing hormone (GnRH) neurosecretory activity can be restored in genetically hypogonadal ( hpg) adult mice with grafts of GnRH-containing fetal or neonatal septal-preoptic area (S/POA) tissue. Neurons implanted into the third ventricle of the host brain survive and send out axons which innervate one of the normal targets of these neurons, the median eminence (ME). Fibers terminate near primary portal vessels where GnRH is available for release into the vasculature, and this axonal outgrowth is essential for the stimulation of gonadotropin secretion, gonadal and accessory sex structure growth, gametogenesis, and fertility. Although it is known that GnRH axons reach their target, it is not known if all such neurons in a graft contribute to the projection. Taking advantage of the fact that axons in the ME, the sole host target, are outside the blood-brain barrier (BBB), long-term grafted animals were injected intraperitoneally with a retrograde tracer, Fluorogold (FG). Normal male mice were injected for comparison. Animals were sacrificed 5 days after injection and brain sections in the area of the graft were stained immunocytochemically for GnRH. In the normal male mice, two-thirds of the GnRH neurons were double-labeled with FG. In grafted individuals which slowed increased gonadal growth, the percentage of labeled cell ranged ffrom 17 to 75%. The results indicate that despite tissue injury, ectopic location, and a vastly reduced population, transplanted fetal GnRH neurons recapitulate a pattern seen in normal intact mice where some but not all neurons were capable of capturing a peripherally delivered tracer.

DNA topoisomerase-targeting antitumor drugs can be studied in yeast.

The antitumor drugs camptothecin and an anilinoacridine, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (mAMSA), which act on DNA topoisomerase I and II, respectively, are shown to inhibit the growth of Saccharomyces cerevisiae mutants selected for their permeability to other inhibitors. In addition to growth inhibition, these drugs induce high levels of homologous recombination and induce the expression of a DNA damage-inducible gene DIN3. Cytotoxicity of the drugs is more pronounced in strains that also carry a rad52 mutation. An analog of mAMSA), which is ineffective as an inhibitor of DNA topoisomerase II in mammalian cells, is also ineffective in eliciting physiological responses in these yeast strains. The physiological effects of camptothecin, but not those of mAMSA, disappear if the TOP1 gene encoding DNA topoisomerase I is disrupted. This shows that DNA topoisomerase I is the sole target of camptothecin cytotoxicity and illustrates that a nonessential enzyme can nevertheless be the target for a cytotoxic drug.

Honorary Member Address: Weed Science in Germany

Plants are components of ecosystems (Figure 1). The primary or sole target of an agro-ecosystem is still production. Production systems are centered around two points: the ecosystem and the socio-economic system (Figure 2). Weeds, except parasitic weeds, are primary producers and compete with the crop plants. They may have beneficial effects besides their detrimental ones. Weeds are, therefore, plants which are more harmful than beneficial.

Luteinizing hormone-releasing hormone in the vomeronasal system and terminal nerve of the hamster.

The vomeronasal system of mammals is a specialized chemosensory pathway that parallels the main olfactory system but is anatomically distinct from its peripheral aspect through its projections into the central nervous system.'.' Recent evidence suggests a predominant role for the vomeronasal system in conveying the influence of odor stimuli upon neuroendocrine and on a variety of motivated behaviors, including sex,6 aggression,' and maternal behavior.' This functional role probably reflects the relatively direct projections of this chemosensory system to areas of the ventral forebrain important in the control of neuroendocrine and behavioral events. The sole central target of the vomeronasal organ is the accessory olfactory bulb (AOB), neurons which in turn project to several nuclei of the medial amygdala.'.' In particular, the medial nucleus of the amygdala (M), has projections to the preoptic area and hypothalamus, and has been strongly implicated in mediating the influence of odor cues upon the neuroendocrine system and behavior.'.'' Axons containing immunoreactive luteinizing hormone-releasing hormone (LHRH) are found throughout the vomeronasal system in the rat and Sparse LHRH fibers are seen within the neuroepithelium of the vomeronasal organ itself.'*. LHRH fibers and cells, defined as a subset of the terminal are present in close proximity to the vomeronasal nerve in the nasal cavity. Centrally, a dense plexus of LHRH fibers innervates the glomerular layer of the AOB, the site of the first synapse in this sensory system. Occasionally, isolated LHRH perikarya are found within the AOB as well. Further caudally, LHRH fibers are seen adjacent to the optic tract within the superficial plexiform layer of M, that layer which receives

Nuclear events during early chondrogenesis: Phosphorylation of the precartilage 35.5-kDa domain-specific chromatin protein and its regulation by cyclic AMP

During chondrogenesis in vivo and in vitro, a family of nonhistone proteins ( M r 35,500), designated PCP 35.5, is lost from the nuclei of precartilage mesenchyme cells. A basic subcomponent of this family, designated PCP 35.5 b, is phosphorylated during the first few hours of chondrogenesis in vitro by a phosphorylating system whose activity is enhanced 12- to 15-fold by exposure of differentiating precartilage cells to dibutyryl cyclic AMP. This phosphorylating system is present in isolated precartilage cell nuclei, where it retains its dependence on cyclic AMP and its specificity for PCP 35.5 b. Assays for nuclear cyclic AMP inhibitable protein phosphatase activity capable of dephosphorylating PCP 35.5 b were negative, indicating that the system responsible for phosphorylating this protein is a cyclic AMP-dependent protein kinase. Chromatin fractionation studies indicate that PCP 35.5 b is localized at sites previously shown to be closely associated with DNase I-sensitive domains of precartilage cell chromatin. These studies define PCP 35.5 b as a strategically located component of precartilage cell chromatin which is the major or sole chromatin target of cyclic AMP-dependent phosphorylation during chondrogenesis. This chromatin modification occurs prior to overt cartilage differentiation and may therefore play a regulatory role in the acquisition of the cartilage cell phenotype.

A new bacterial dehydrogenase oxidizing the lignin model compound guaiacylglycerol β- O-4-guaiacyl ether

A lignin model compound, named in short guaiagylglycerol beta-guaiacyl ether (GGE), contains the beta-0-4 ether linkage that is common in the chemical structure of lignin. A Pseudomonas sp. (GU5) had been isolated as an organism able to grow with GGE as the sole source of carbon and energy. When grown on vanillate, the bacteria contained a NAD+ -dependent dehydrogenase converting GGE to a 355 nm absorbing product. The enzyme, named GGE-dehydrogenase, was purified about 160-fold using gel permeation, ion exchange on DEAE-Sephadex, and dye-ligand affinity chromatography. The new protein was about 52 kDa in apparent size with but one polypeptide chain after denaturation and reduction. According to several criteria, the product of GGE oxidation (Km = 12 microM) was identified as the corresponding conjugated ketone at the alpha-carbon of the C3 side-chain. The secondary alcohol function in GGE was apparently the sole target of the enzyme action. However the conversion of GGE into ketone catalyzed by the enzyme was only partial, and did not exceed 50%, probably because only one of the alpha-enantiomers was susceptible to enzyme attack. In contrast the ketone, either made by organic synthesis or by enzymic oxidation of GGE, could be totally reduced back to GGE (Km = 13 microM at pH 8.4, 8 microM at neutral pH), with NADH as the reductant, as confirmed by UV absorption and NMR spectra. Other model compounds with no primary alcoholic function, ether linkage or phenolic group were also substrates for the enzyme, confirming the specificity of GGE-dehydrogenase for the alpha-carbon position. Conjugation of the alpha-ketone with an adjacent phenolic nucleus interfered strongly with equilibrium constants and redox potentials of the system according to pH, and the enzyme displayed widely different optima with pH over 9 when oxidizing GGE, below 7 when reducing the ketone. Equilibrium studies showed that the ketone/GGE potential was -0.37 volt at pH 8.7, -0.23 volt at pH 7 (30 degrees C). The significance of this new dehydrogenase and its properties are discussed, especially in the general concern of lignin biodegradation.

Experimenting with the Family in the Newborn Period

Families randomly assigned to 1 of 4 treatment groups that varied across 2 orthogonal dimensions were compared at 1, 3, and 9 months to examine the effects of a neonatal intervention. In half of the families mothers and fathers were the target of intervention, and in the remaining half of the families mother was the sole target of intervention. The intervention itself consisted of passive or active exposure to the Brazelton Neonatal Behavior Assessment; half of the parents in each target-of-intervention group (mother only, mother and father) actively elicited responses from their newborn under the direction of a facilitator (active exposure) and the other half of the parents listened to a detailed verbal description of their infant's performance on the exam. Assessments of mother-infant interaction in the dyad and mother-infant, father-infant, and husband-wife interaction in the triad revealed no effects of the experimental intervention across groups. Discussion emphasizes the need to be cautious about the effectiveness of minor interventions and the need to be critical about past reports of success.

“Therapy is Not Going to Help”: Brief Family Treatment of a Character Disorder

Neither individual psychotherapy nor family therapy can claim much success in the treatment of psychopathic character disorders. MRI's interactional brief therapy, with its focus on problem resolution rather than pathology, offers a different way of viewing such conditions. Since people other than the identified patient are the complainants, the identified patient does not have to be the sole target of the therapist's influence and success of treatment is not dependent on the identified patient's sincere desire to change. To illustrate this point, the case of a man seen at the MRI Brief Therapy Center who had defrauded two banks as well as members of his family is described.

Transneuronal degeneration of beta retinal ganglion cells in the cat.

Transneuronal retrograde degeneration of retinal ganglion cells was investigated following neonatal visual cortex ablation in the cat. After a survival time of at least 18 months, retinal ganglion cells projecting to the thalamus were labelled by retrograde transport of horseradish peroxidase. Filled ganglion cells were classified into alpha, beta and gamma types on the basis of dendritic morphology. In normal cats, alpha cells made up 8-10% of the total population in the sample area, beta cells made up 64-67% and gamma cells made up 23-27%. In retinae of visual cortex-ablated cats, normal numbers of alpha and gamma cells were present, but the beta cell population was depleted by 90% of normal. Thalamic projections of surviving retinal ganglion cells were investigated by anterograde transport of tritiated proline injected into the eye. In these animals, ablation of visual cortex resulted in almost complete degeneration of laminae A and A1 of the dorsal lateral geniculate nucleus. In the radioautographic material, projections from the retina to the degenerated parts of laminae A and A1 were barely detectable. Survival of some ganglion cell populations and death of others after neonatal visual cortex ablation may be explained in terms of the pattern of projections of the different cell types. We conclude that the majority of beta cells degenerate following visual cortex ablation because of removal of cells in the dorsal lateral geniculate nucleus which form their sole or principal target. Alpha and gamma cells and 10% of beta-cells survive because of extensive collateral projections to targets other than cells of the laminae A and A1 of dorsal lateral geniculate nucleus.

Induction of androgen receptor formation by epithelium-mesenchyme interaction in embryonic mouse mammary gland.

The role of tissue interaction in the development of hormone responsiveness was studied in the embryonic mammary gland of the mouse, which becomes sensitive to testosterone on day 14. Previously, the mesenchyme had been identified as the sole target tissue for the hormone, although it was also demonstrated that its response to testosterone required the presence of mammary epithelium. Using autoradiography, we now show that [3H]testosterone or [3H]5 alpha-dihydrotestosterone is bound only by those mesenchymal cells closest to the epithelial mammary bud. When mammary epithelia were experimentally associated with mesenchyme of the mammary region and cultured together for 3 days in vitro, they also became surrounded by several layers of [3H]testosterone-binding mesenchymal cells. Correspondingly, this tissue association was accompanied by a substantial increase of androgen-binding sites in the explants. No hormone-building mesenchymal cells were seen in combinations with epidermis or pancreas epithelium; only salivary epithelium showed a weak positive effect. From these results we conclude that mammary epithelium induces the formation of androgen receptors in adjacent mesenchyme and thereby controls the development of androgen responsiveness in this tissue.

In vivo uptake of 125 I-Relaxin in the guinea pig.

Relaxin uptake in the guinea pig showed a time-dependent concentration in the uterine cervix and symphysis pubis. Binding in target tissues was displaceable by a concurrently adminis- tered excess of unlabeled hormone. Exogenous estrogen priming in the virgin female and retired breeder was unnecessary to demonstrate displaceable binding and concentration in the uterine cer- vix, while priming decreased displaceable binding in the uterine horns compared with similar un- primed animals. No displaceable binding or concentration was found in other tissues, including connective tissues. Thus, the uterus and symphysis pubis appear to be the principal if not the sole target tissues for relaxin.

Cell mediated lympholysis in man: an attempt to type with cytotoxic lymphocytes.

From approximately 3,000 CML combinations, originally established in order to evaluate the qualitative and quantitative influence of the serologically defined HLA-A, B, and C antigens on cellular, complement independent cytolysis, 12 combinations were selected yielding reproducible positive cytolysis on allogenic target cells, although no HLA-antigenic sharing could be demonstrated between stimulator and target lymphocytes. These 12 CytoToxic Lymphocytes (CTL's) have been tested in parallell as "CML typing combinations" against lymphocytes from a random population sample of 100 unrelated Danes. Based on a pairwise analysis 11 of these CTL's could be classified into two groups of significantly correlated CTL's. These two groups do not define monospecific traits of allelic genetic origin as judged by a mutually positive correlation and a poor fit to Hardy-Weinberg equilibrium. The traits defined by these groups may be either partially identical or governed by closely linked loci. The same groups were identified and the same conclusions reached after exclusion of those individuals in the population sample where HLA-A, B, C, or D antigens may be targets for destruction. Thus, this study gives direct evidence that known HLA antigens are not sole target determinants in CML or that cytotoxic lymphocytes recognize HLA molecules in a different way than lymphocytotoxic antibodies. The studies underline the immunogenetic complexity of CML although this reaction is most probably governed by genes in the HLA region. It is suggested that cytotoxic lymphocytes may recognize "backbone structures" of the HLA molecules.