Surfactant: clinical applications.

Pulmonary surfactant is an important chemical component of the lung. It decreases surface tension in the alveolar cells to help stabilize the alveoli, and it may help prevent pulmonary edema. Currently, naturally and synthetically derived surfactants are being used to treat neonatal respiratory distress syndrome, a leading cause of death in premature infants. Surfactant is recommended for prophylactic therapy in infants weighing less than 1,350 g (3 lb) and in infants weighing more than 1,350 g who show signs of pulmonary immaturity and for rescue therapy in infants with respiratory distress syndrome. Surfactant is administered by endotracheal tube, and the recommended dose is 5 mg per kg. Three doses, given 12 hours apart, is the recommended regimen for prophylactic therapy. Rescue therapy consists of one dose of surfactant given at the onset of respiratory distress and another dose given 12 hours later.     

Molecular biology and clinical diabetology

Recent advancement of molecular biology highlighted three areas of basic research which may be important for clinical diabetology. One is the understanding of mechanisms of differentiation in pancreatic beta-cells and adipocytes. The second is the development of methods of tissue-specific knock-out mouse. This approach revealed that muscle may not be important for insulin-dependent glucose disposal in vivo. The third is the advancement of genetics which enabled to clone a major susceptibililly gene for type 2 diabetes mellitus (NIDDM1). These progress may bring new therapies for clinical diabetology.     

Serotonin and migraine: biology and clinical implications

Migraine is the most frequent neurological disorder in the adult population worldwide, affecting up to 12% of the general population and more frequent in women ( approximately 25%). It has a high impact on our society due to its disabling nature and, therein, reduced quality of life and increased absenteeism from work. Headache is the primary clinical manifestation and it has been associated with 'a hereditary or predisposed sensitivity of neurovascular reactions to certain stimuli or to cyclic changes in the central nervous system' (1). Amongst the many neurotransmitters in the brain, the serotonergic (serotonin, 5-HT) system from the brainstem raphe nucleus has been most convincingly implicated in migraine pathophysiology. The documented changes in 5-HT metabolism and in the processing of central 5-HT-mediated responses during and in between migraine attacks have led to the suggestion that migraine is a consequence of a central neurochemical imbalance that involves a low serotonergic disposition. Although the exact cascade of events that link abnormal serotonergic neurotransmission to the manifestation of head pain and the accompanying symptoms has yet to be fully understood, recent evidence suggests that a low 5-HT state facilitates activation of the trigeminovascular nociceptive pathway, as induced by cortical spreading depression. In this short review, we present and discuss the original and most recent findings that support a role for altered serotonergic neurotransmission in the manifestation of migraine headache.     

Dopamine and migraine: biology and clinical implications

In the last 30 years dopamine has been considered as playing a role in the pathogenesis of migraine. The literature indicates that migraineurs are hypersensitive to dopamine agonists with respect to some of the premonitory symptoms of migraine such as nausea and yawning. There are various non-specific dopamine D(2) receptor antagonists that show good clinical efficacy in migraine, and also a number of polymorphisms of dopaminergic genes related to migraine. Animal studies have also shown that dopamine receptors are present in the trigeminovascular system, the area believed to be involved in headache pain, and neuronal firing here is reduced by dopamine agonists. There appears to be little effect of dopamine on peripheral trigeminal afferents. We assess some of the limitations of the clinical studies with regard to the therapeutics, and those found in the studies that discovered differences in genetic polymorphisms in migraine, and consider the implications of this on a dopaminergic hypothesis of migraine.     

Bone biology and the clinical implications for osteoporosis

Bone biology is a complex and vastly growing area of study. It brings together the traditional fields of anatomy, physiology, and biomechanics with the increasingly complex fields of developmental biology and molecular genetics. For clinicians who treat bone disorders such as osteoporosis, developing a working knowledge of this topic is essential. This article discusses bone from a structural, anatomical, and functional perspective. It reviews skeletogenesis as a developmental process and from a regulatory perspective and presents biomechanical principles and theories. Osteoporosis is reviewed, including recent literature related to the role of exercise in prevention and treatment of this disease.     

The biology and clinical applications of dendritic cells

Dendritic cells (DC) have an essential role in the induction of immune responses to antigen by naive T cells. As 'professional' antigen-presenting cells they are specialized to take up, process and present soluble antigens in complexes with either class I or class II MHC molecules. They are present in only trace numbers in most tissues and in a relatively immature state but, in the presence of inflammatory signals, they rapidly take up foreign antigens and undergo maturation into potent antigen-presenting cells that migrate to secondary lymphoid tissue where they initiate an immune response. It is now possible to expand populations of DC in vitro both from primitive haemopoietic progenitors as well as from more mature peripheral blood mononuclear cells. This has shed light on many developmental aspects of DC biology and furthered our knowledge of the mechanisms of antigen processing and presentation. It is clear that there is more than one pathway of DC differentiation and that some DC may actually induce immunological unresponsiveness — a possible mechanism for tolerance to self-antigens. For clinicians the most exciting prospect is of their use as cellular adjuvants to generate beneficial responses to antigens of low immunogenicity such as tumour antigens. This review outlines aspects of human DC development and the way in which a greater understanding of their biology may lead to promising clinical applications.     

Surfactant replacement in reperfusion injury after clinical lung transplantation

Background: Reperfusion injury remains a significant risk factor in the immediate postoperative course after lung transplantation. We report on our initial clinical experience of surfactant replacement in reperfusion injury after clinical lung transplantation. Methods and results: In 31 consecutive patients, lung (8 single lung, 16 bilateral lung) or heart-lung (7) transplantation was performed. In 6 patients, severe reperfusion injury developed and was treated with continuously nebulized surfactant. Compliance of the allograft increased 40 ± 25 % within 3 h following treatment with surfactant. Alveolar arterial oxygen gradient decreased by 23 ± 11 % after 3 h and by 35 ± 20 % after 6 h. Normal graft function was reestablished within 1–3 days after transplantation. All treated recipients were extubated until the 6th postoperative day. The 30-day mortality for the 31 recipients was 3.3 %, the 1-year survival 84 %. Conclusions: Surfactant replacement may become a clinical method for treatment of reperfusion injury after lung transplantation. Final revision received: 14 April 1999 Accepted: 23 April 1999     

Invasion and metastasis: biology and clinical potential.

Metastatic dissemination of tumor is the primary cause of death for most cancer patients. The expanding field of study of the metastatic cascade has been the source of novel approaches to the diagnosis and treatment of cancer. The metastatic process involves angiogenesis, tumor cell adhesion to vascular basement membrane, local proteolysis to create an opening in the basement membrane, migration through that rent and into the secondary site, and finally, successful proliferation. Important components of the metastatic cascade such as basement membrane structures, adhesion molecules and their receptors, proteolytic enzymes, migration-inducing factors, and growth factors have been demonstrated to have reproducible patterns in malignant and metastatic tissues. These patterns have led to clinical correlations demonstrating their utility in the identification and follow-up of malignant and metastatic disease. In addition, several promising new anti-cancer drugs such as inhibitors of angiogenesis, protease-inhibitors, and blockers of signal transduction have been identified and are awaiting introduction into the clinical arena.     

The calcitonin gene peptides: biology and clinical relevance

The calcitonin/CGRP multigene complex encodes a family of peptides: calcitonin, its C-terminal flanking peptide, katacalcin, and a third novel peptide, calcitonin gene-related peptide (CGRP). The 32-amino acid peptide calcitonin inhibits the osteoclast, thereby conserving skeletal mass during periods of potential calcium lack, such as pregnancy, growth, and lactation. This hormonal role is emphasized by observations that lower circulating calcitonin levels are associated with bone loss and that calcitonin replacement prevents further bone loss. Structurally, CGRP resembles calcitonin and has been implicated in neuromodulation and in the physiological regulation of blood flow. Here we review the molecular genetics, structure, and function of the calcitonin-gene peptides as analyzed in the laboratory and focus on more recent clinical studies relating to disorders and therapeutics.     

Challenges in application of Raman spectroscopy to biology and materials

Raman spectroscopy has become an essential tool for chemists, physicists, biologists and materials scientists. In this article, we present the challenges in unravelling the molecule-specific Raman spectral signatures of different biomolecules like proteins, nucleic acids, lipids and carbohydrates based on the review of our work and the current trends in these areas. We also show how Raman spectroscopy can be used to probe the secondary and tertiary structural changes occurring during thermal denaturation of protein and lysozyme as well as more complex biological systems like bacteria. Complex biological systems like tissues, cells, blood serum etc. are also made up of such biomolecules. Using mice liver and blood serum, it is shown that different tissues yield their unique signature Raman spectra, owing to a difference in the relative composition of the biomolecules. Additionally, recent progress in Raman spectroscopy for diagnosing a multitude of diseases ranging from cancer to infection is also presented. The second part of this article focuses on applications of Raman spectroscopy to materials. As a first example, Raman spectroscopy of a melt cast explosives formulation was carried out to monitor the changes in the peaks which indicates the potential of this technique for remote process monitoring. The second example presents various modern methods of Raman spectroscopy such as spatially offset Raman spectroscopy (SORS), reflection, transmission and universal multiple angle Raman spectroscopy (UMARS) to study layered materials. Studies on chemicals/layered materials hidden in non-metallic containers using the above variants are presented. Using suitable examples, it is shown how a specific excitation or collection geometry can yield different information about the location of materials. Additionally, it is shown that UMARS imaging can also be used as an effective tool to obtain layer specific information of materials located at depths beyond a few centimeters.

This paper reviews various facets of Raman spectroscopy. This encompasses biomolecule fingerprinting and conformational analysis, discrimination of healthy vs. diseased states, depth-specific information of materials and 3D Raman imaging.     

分子生物学新技术与新方法的临床应用

20世纪90年代起，分子生物学进入临床检测。短短的几年中，以聚合酶链反应(PCR)为核心的分子生物学技术深入到临床多个领域。在临床检验中，我国分子生物学在遗传病诊断及产前筛查、肿瘤诊断与疗效预后判断、微生物耐药机理的研究等方面取得较突出的成绩。