Mössbauer spectroscopy: recent developments.

In this review I have emphasized two basic points. First, Mössbauer spectroscopy has been widely used as a tool for basic research in solid-state physics, chemical structure, and magnetism. Second, the technique has been applied to many analytical and materials science problems where the nature of the sample prevents the use of more traditional approaches. Mössbauer spectroscopy research on frozen solutions, colloids, interface chemistry, and crystallographic transformations can be expected to increase rapidly in the next few years.

Hydrogen storage materials: properties and possibilities.

The physics, chemistry, and possible applications of the storage of hydrogen in intermetallic reservoirs are discussed. Storage in the form of intermetallic hydrides can be safe and, where hydrogen has some special value as a fuel, economical. New pumps and refrigerators based on the heat of sorption of the hydrogen into the intermetallic are approaching commercial viability.

The urokinase receptor is expressed in invasive breast cancer but not in normal breast tissue.

We have studied expression of the urokinase receptor (u-PAR) in paraffin-embedded breast tissues at various stages of malignant progression. Forty-nine of 59 invasive cancers studied showed varying degrees of reactivity with our polyclonal antibody. The staining pattern was variable from case to case, although strong surface staining of tumor-associated macrophages was evident in most of these sections. In several cases, blood vessels in selected tumor areas were stained, as confirmed by treatment of adjacent sections with an anti-factor VIII antibody. These could represent regions of recent angiogenesis. Staining of tumor cells was observed in 21 of 59 cases and was extensive in 5 cases but confined to a small percentage of cells in the remaining 16 samples. In contrast with the cancer sections, all normal breast tissue (12 cases) was negative, as well as all fibroadenomas (4 cases), papillomas (5 cases), and hyperplasia with atypia (2 cases) studied. Seven carcinomas in situ examined were also negative for u-PAR, with the exception of few macrophages in two cases, suggesting that u-PAR expression may be associated with invasive tumor. The presence of u-PAR in human breast cancer and its absence from nonmalignant breast tissue supports the idea that plasminogen activation plays an important role in the process of cancer invasion. Expression of u-PAR on macrophages, endothelial cells, and cancer cells suggests the existence of complex paracrine interactions between tumor cells and stroma.

Thrombopoietin mobilizes CD34+ cell subsets into peripheral blood and expands multilineage progenitors in bone marrow of cancer patients with normal hematopoiesis.

Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, also mediates biologic effects in vitro on hematopoietic cells more primitive than those committed to the megakaryocyte (MK) lineage. To assess the spectrum of hematopoietic effects of recombinant human (rh)TPO in vivo, we evaluated its proliferative effect on bone marrow (BM) progenitor cells, its maturation effect on BM MKs, and its mobilizing effect on peripheral blood (PB) progenitor cells during a phase I clinical laboratory investigation in which rhTPO was administered to cancer patients with normal hematopoiesis. Twelve patients received a single dose of rhTPO (0.3, 0.6, 1.2, or 2.4 microg/kg of body weight) prior to chemotherapy. BM and PB samples from these patients were analyzed 1 to 2 days before (baseline) and 7 days after rhTPO administration. At higher doses (1.2-2.4 microg/kg), rhTPO produced increased concentrations of primitive CD34+Thy-1+Lin-cells (mean 2.1-fold), CD34+mpl+ cells (mean 5.2-fold), CD34+CD41+CD14- promegakaryoblasts (mean 2.9-fold), and myeloerythroid colony-forming cells (mean threefold) in BM. No significant increases in the frequency of BM colony-forming unit (CFU)-MK were observed. Elevated numbers of both immature (2N-8N) and more mature (64N and 128N) CD41+ MKs were detected in BM, with modal ploidy remaining at 16N. Higher doses of rhTPO (1.2-2.4 microg/kg) also induced increased concentrations of CD34+ cell subsets in PB, including both primitive CD34+Thy-1+Lin- (mean 8.8-fold) and MK lineage-committed CD34+CD41+CD14- cells (mean 14.6-fold) as well as various myeloerythroid colony-forming cells (mean 3.6- to 5.5-fold). These results demonstrate that rhTPO given as a single dose not only promotes proliferation and maturation of cells of the MK lineage, but also expands the pool of BM primitive hematopoietic cells. In addition, rhTPO induces mobilization of hematopoietic progenitors into peripheral circulation. The extent to which such multilineage effects on human progenitor cells will contribute to clinical efficacy remains to be determined.

Knowledge about AIDS and high-risk behavior among intravenous drug users in New York City.

Two hundred and sixty-one intravenous (IV) drug users, distributed between a methadone maintenance program and a large detention facility in New York City, were interviewed about knowledge of AIDS, needle use practices, and risk-reduction efforts. Ninety-seven per cent of subjects recognized needle-sharing as an AIDS risk factor; subjects showed less awareness about the effectiveness of certain risk-reduction techniques and tended to over-estimate the risk of casual contact. Of those still sharing needles at the time of first becoming aware of AIDS, 63% reported having subsequently either stopped needle-sharing or ceased IV drug use entirely. Logistic regression analysis indicated that continued needle-sharing behavior was associated with the detention facility site and lower scores on an AIDS knowledge questionnaire; reduced needle-sharing was more evident among methadone program patients and among subjects with greater knowledge about AIDS. The most common reasons for continued needle-sharing among those who continued to share needles despite knowledge of risk were: 'need to inject drugs, with no clean needle available' and 'only share with close friend or relative', offered by 46 and 45% of subjects, respectively. Results suggest that certain subgroups of IV drug users have adopted risk-reduction measures in response to AIDS. Expanded educational programs, increased drug treatment capacity, and additional strategies addressing drug users' access to sterile injection equipment and the social context of needle-sharing may be necessary to curb the further spread of AIDS among IV drug users.

Characterization of a human Kaposi's sarcoma cell line that induces angiogenic tumors in animals.

OBJECTIVE: To characterize a Kaposi's sarcoma (KS) cell line established from a tumor biopsy from the oral mucosa of an iatrogenically immunosuppressed HIV-negative man. METHODS: Cells were placed in culture and evaluated by a variety of biologic, serologic, karyotypic, and immunologic procedures. Electron microscopic examination was performed. The ability to produce tumors in nude mice was evaluated, and the nature of the cells within the tumor determined. Assays for urokinase plasminogen activator type (uPA), plasminogen activator inhibitor-1 (PAI-1) and the urokinase receptor (uPAR) were conducted. RESULTS: The SLK cell line has an endothelial cell morphology with very little anaplasia. The karyotype indicates diploid phenotype of human origin. Immunohistochemical and electron microscopic examinations confirmed the endothelial nature of this cell line. No viruses were detected. The tumors induced in nude mice showed hypervascularization, with characteristics of KS. The cell line produces uPA and PAI-1, and also expresses uPAR. CONCLUSIONS: The SLK cell line is of endothelial cell origin and the first human cell line to induce KS-like tumors in recipient animals. The expression of urokinase and its receptor suggests a paracrine and autocrine interaction that may be important for the growth of the tumor. The SLK line should be valuable for studies of KS pathogenesis and therapeutic approaches to this malignancy.

Thy-1+ epidermal cells are not demonstrable in rat and human skin.

Recent studies have revealed the presence of a population of Thy-1+ epidermal cells in murine epidermis. These experiments were designed to determine whether analogous Thy-1+ cell populations occur in rat and human epidermis. Thy-1+ cells could not be demonstrated in epidermal sheets derived from rat and human skin or in epidermal cell lines, KB and A431. To date, Thy-1+ epidermal cells have been observed only in murine epithelia. The cellular equivalent of the murine Thy-1+ cell in other species remains elusive.

Direct effects of minoxidil on epidermal cells in culture.

Minoxidil, a potent antihypertensive agent, induces generalized hypertrichosis when administered systemically, or localized hair regrowth when applied topically to sites of severe alopecia areata. The pharmacologic mechanisms by which minoxidil stimulates hair growth are unknown. This study was designed to examine whether minoxidil has direct effects on neonatal murine epidermal cells in culture. In the presence of minoxidil, cultures showed a marked dose-dependent second peak of DNA synthesis 8-10 days after culture initiation. In addition, two morphologically distinct cell types appeared. Indirect immunofluorescence staining with keratin-specific antibody revealed cytoplasmic keratin fibers, suggesting the epidermal origin of these cells. Our experiments demonstrate that minoxidil can affect epidermal cells in culture by altering their growth pattern and phenotypic appearance.

Ostensible versus actual reasons for seeking pediatric attention: another look at the parental ticket of admission.

The presentation of parental anxiety that appears excessive in view of the nature of the child's "chief complaint" is a frequent occurrence in pediatric practice. This study reviews 370 sick-patient visits in one pediatric office during a three-month period. Additional questioning in the area of parental anxieties concerning these symptoms revealed that in 125 instances (33.8%), the parent was entertaining unverbalized fears that something much more serious was wrong with the child than could be anticipated from the ostensible reason for seeking assistance. An analysis of the "actual reason for coming" reveals that the child's presenting complaint has become associated for the parent with (1) family history of serious life-threatening illness; (2) fears of loss and separation; (3) death; (4) the fears of another family member who is pressing for "answers" about the problem; (5) fears of loss of vital functions and a variety of other thought processes that have somehow become linked to the child's symptom. Techniques for recognizing and ameliorating this parenting difficulty are discussed.

Thrombin increases expression of urokinase receptor by activation of the thrombin receptor.

PURPOSE: To investigate the effect of thrombin on the urokinase plasminogen activator receptor (u-PAR) in retinal pigment epithelial (RPE) cells. METHODS: The authors analyzed u-PAR mRNA by Northern blot hybridization. Retinal pigment epithelial cell surface u-PAR was assayed by measuring the amount of functional urokinase plasminogen activator (u-PA) bound to cells at saturation. Retinal pigment epithelial cells were derived from fetal retinal tissue and established in primary cell culture. RESULTS: Thrombin increased u-PAR mRNA 4-fold in RPE cells examined by Northern blot hybridization, whereas the amount of thrombin receptor mRNA was unchanged. Thrombin stimulated u-PA binding to RPE cells 2.5- to 5-fold in a time- and dose-dependent manner. Hirudin, a thrombin antagonist, completely blocked the effects of thrombin on u-PAR expression in RPE cells. Phosphatidylinositol phospholipase C treatment of RPE cells resulted in the abolition of thrombin-induced u-PA binding. Recombinant soluble u-PAR competitively inhibited two-chain u-PA binding to the surface of thrombin-treated RPE cells. A thrombin receptor agonist peptide (SFLLRNPNDKYEPF) also induced a 2.5-fold increase in binding of u-PA to the surface of RPE cells. CONCLUSION: Thrombin increases u-PAR expression by RPE cells by a mechanism involving activation of the seven transmembrane thrombin receptor.

Neuroimmune modulation: signal transduction and catecholamines.

In recent years, much interest has centered on the commonalities and bi-directional interactions between the nervous system and the immune system. This review focuses on mechanisms through which, catecholamines, a class of neuro-endocrine molecules, modulate immune functions. Catecholamines can be immune suppressive and inhibit lymphocyte activation of both T and B cells as well as the generation of immune-mediated anti-tumor responses. Some of these catecholamine-regulated activities appear to be modulated through the second messenger, cyclic AMP, whereas others appear to be catecholamine-dependent but cyclic AMP independent. Further delineation of the interacting ligand-receptor complexes, populations of responding cells and signal transduction mechanisms leading to the activation of specifically involved genes and gene products, will lead to enhanced understanding of the integratory functions of the nervous system in immune responses, the biology of stress, the role of stress-associated molecular mechanisms in perturbations of physiological homeostasis and the development of a new biological psychiatry with accompanying rational therapeutic modalities.

Failure of the urinalysis and quantitative urine culture in diagnosing symptomatic urinary tract infections in patients with long-term urinary catheters.

Since urine culture and urinalysis are both of uncertain reliability in diagnosing symptomatic urinary tract infections in patients with chronic urinary catheters, we performed sequential quantitative cultures and urinalyses on 177 urine specimens from 14 patients with long-term urinary catheters during a 12-month period. We found high concentrations of greater than or equal to 2 species of aerobic bacteria or fungi in most specimens examined. Pyuria was common even during asymptomatic periods; hematuria was less common. During symptomatic urinary tract infections, neither urinalyses nor quantitative urine cultures exhibited changes specific for such infections. Thus neither urinalysis nor urine culture appears to be a reliable test for symptomatic urinary tract infections in patients with chronic urinary catheters.

In vivo immunomodulation by peripheral adrenergic and cholinergic agonists/antagonists in rat and mouse models.

Our work is devoted to defining relationships between the immune system and the adrenergic and cholinergic systems in vivo. In the rat model, we have shown that the cells of different immune compartments express the genes of a defined set of adrenergic/cholinergic receptors, and it was shown that lymphocytes are a site of non-neuronal production of norepinephrine and acetylcholine. Furthermore, using implantable slow-release tablets containing adrenergic or cholinergic agonists/antagonists, distinct and partly opposite effects were observed on peripheral immune functions. Concerning sympathetic immunoregulation, our data--in contrast to those of other studies--suggest that an enhanced adrenergic tonus leads to immunosuppression primarily via alpha 2-receptor-mediated mechanisms. Beta-blockade strongly enhances this effect, most likely by inhibition of pineal melatonin synthesis. In recent experiments on the kinetics it was found that the continuous alpha-adrenergic treatment entails a strong suppression of cellular responsiveness during the first few hours, which is increasingly followed by a general loss of lymphocytes in blood and lymphoid organs most likely due to enhanced apoptosis. More recently, we have extended our studies to the mouse model. First data obtained with RNAse protection assays suggest a biphasic effect on the gene expression of several cytokines in spleen cells due to adrenergic in vivo treatment.

Child and adolescent psychiatry: mid-course corrections.

The President of the American Academy of Child and Adolescent Psychiatry examines and assesses past Academy plans for its scientific development, educational program, service delivery, advocacy, and recruitment initiatives. The influence of governmental programs, reimbursement trends (managed care), and over-sight and review mechanisms are described. The Academy's future medical agenda, public policy efforts, and research priorities are noted.

Research careers in child psychiatry: an update on five NIMH workshops.

To foster research in child psychiatry, the National Institute of Mental Health and the American Academy of Child and Adolescent Psychiatry sponsored three workshops in 1981-82 and two others in 1984. Overall, 60 trainees and several senior researchers participated. A 30-month follow-up of the careers of 34 residents who participated in the first three workshops and a description of the workshops were published earlier. This report summarizes the nature and degree of postworkshop activities of 23 additional child psychiatrists involved in the 1984 workshops, along with the needs, problems, and sources of help that they recognized as important. Promising is the fact that the vast majority were involved in research and research training and employed in academic settings.

Alopecia areata treated with topical minoxidil.

A 1% minoxidil topical solution was used to treat 48 patients with alopecia areata, ie, 24 patients with patchy disease and 24 patients with alopecia totalis or alopecia universalis. Twenty-five patients had terminal hair regrowth; in 11 of the 25 patients, it was cosmetically acceptable. No clinical features of the disease seemed to indicate the likelihood of hair regrowth. Hair regrowth began approximately two months after the initiation of treatment and was not uniformly well maintained after the treatment was terminated. One patient had an allergic contact dermatitis reaction to the minoxidil solution; no systemic side effects were seen. No notable systemic absorption was found in 18 adult patients. Effects on cutaneous blood flow or the immune system or some direct effect on hair follicles are possible mechanisms by which minoxidil therapy might stimulate hair growth.

Association of gingival crevicular fluid aspartate aminotransferase levels with histopathology during ligature-induced periodontitis in the beagle dog.

Previous investigations have shown a clear association between the presence of the enzyme aspartate aminotransferase (AST) in gingival crevicular fluid (GCF) and clinical evidence of periodontal disease in humans, as well as in the beagle dog model. This paper describes a 26-week study that uses the beagle dog model of ligature-induced periodontitis in which GCF-AST (corrected for collection time) was correlated with microscopic evidence of tissue destruction in the periodontium at the sites of fluid collection. GCF and clinical data were collected at baseline, at optimal gingival health, during gingivitis, and after ligation. A cross-mouth design was implemented so that six premolar teeth in each dog were ligated for periods up to five weeks. Formalin-fixed tissues from the sites of GCF collection were prepared for light microscopy and evaluated for the presence of epithelial ulceration, bone resorption, and inflammatory cell infiltration. The relationship between GCF-AST levels and microscopic findings was analyzed by calculation of sensitivity and specificity and by plots of Receiver Operating Characteristics. These data revealed a correlation between elevated enzyme concentration and microscopic evidence of disease activity. Taken together with human studies, these results provide support for the use of AST as a marker of periodontal disease progression.

Aging and memory for words and action events: effects of item repetition and list length.

We were concerned with the effects of item repetition, list length, and class of item on free recall in elderly as compared with young adults. In Experiment 1, samples of young and elderly adults recalled a list of 27 words and a list of 27 action events (minitasks performed by the subjects). Some items were presented once and some twice. Although the younger subjects showed better recall on both types of lists, the older sample benefited from item repetition as much as did the younger sample. This finding was replicated in Experiment 2. A second finding in Experiment 2 was a significant aging effect in the recall of long but not of short lists of both words and action events. The absence of an Age X Repetition Effect interaction was ascribed to the strength nature of the repetition manipulation. The age effects in the recall of the long lists were attributed to possible deficits in retrieval proficiency.