Regional chromosome mapping of the human skin type I procollagen gene using adenovirus 12-fragmentation of human-mouse somatic cell hybrids

Prevous work, using human-mouse somatic cell hybrids, has localized the structural gene for human skin type I procollagen (COL 1) to chromosome 17. One of these hybrids contained only the long arm of human chromosome 17, translocated onto a mouse chromosome, as human chromosomal material. This hybrid was treated with adenovirus 12, and various clones were picked which contained different-sized fragments of human chromosome 17 that were still translocated onto a mouse chromosome. Measurements of these fragments, combined with assays for human COL 1 production and galactose kinase (GAK) activity (also localized on the long arm of human chromosome 17), has allowed us to regionally map the structural gene for human COL 1 to an area just distal to the thymidine kinase (TK) and GAK genes within bands q21 and q22 on human chromosome 17.     

Hepatoma Nucleic Acid-Histamine Interactions

The effect of histamine on exponentially growing, ascites form, Taper hepatoma cells (TLT) has been characterized by study of diamine-nucleic acid interactions. Thermal denaturation studies demonstrate that the midpoint of the melting profiles of unfractionated TLT ribosomal RNA and sheared native TLT DNA are increased 13°C and 18°C respectively when they are denatured in physiological concentrations of histamine. Similar shifts in melting profiles were observed in studies with the diamine, putrescine, and the intercalating dye ethidium bromide. The role of histamine-nucleic acid stabilization in the control of hepatoma cell differentiation is discussed.     

Long term effects of prenatal cocaine exposure on bone in rats

Prenatal exposure to cocaine has been shown to produce a variety of effects on skeletal development and mineralization in humans, mice, and rats. The effects of cocaine on bone cell function and mineral metabolism pre- and postnatally are poorly understood. The present study examined the long term effects of prenatal cocaine exposure on femoral growth and mineralization in male rats. Pregnant rats were given 80 or 100 mg cocaine hydrochloride/kg during days 7-20 of gestation. At birth, body weights of pups born to these females were significantly decreased compared to normal and pair-fed controls. At the termination of the study (32 weeks), body weights of offspring from C100-treated females were still lower than normal. Long term effects of prenatal exposure to cocaine on femoral growth were most pronounced in offspring of C80-treated females. Femur dry weight, ash weight, organic matrix weight and density were significantly reduced in these animals compared to normal or pair-fed controls. The apparent osteopenic effects of prenatal exposure to cocaine suggests some long term postnatal impact on bone cell or mineral metabolism. Previous studies of cocaine use during pregnancy in humans and animals have focused primarily on physical and behavioral defects in offspring. The present findings indicate that prenatal exposure to cocaine may also have long term consequences to the skeleton.     

Synthesis and DNA binding properties of tryptophan linked monocationic netropsin analogues

One tryptophan (Trp-Net) and two tryptophan (Trp-Trp-Net) residues have been linked to the amino terminus of a minor groove binding Netropsin analogue. DNA metling measurements indicate that Trp-Trp-Net binds significantly stronger than Trp-Net to double helical DNA. Both compounds induce helix extension as measured by changes in DNA viscosity indicating the possibility of intercalation of the tryptophan indole ring.     

The distribution of synaptonemal complex material in metaphase I bivalents of Locusta and Chloealtis (Orthoptera: Acrididae)

At metaphase I synaptonemal complex (SC) material is located in a continuous but irregularly shaped bundle between sister chromatids. Only at the site of a chiasma is it present between homologous chromosomes. When the chromosomes pull apart at anaphase I the SC material becomes rearranged into poly-SCs which dissociate from the chromosomes. The observations agree with previous reports that modified SCs may function in meiotic chromosome disjunction.     

Proposed follow up programme after curative resection for lower third oesophageal cancer

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy.     

Strategies to Improve Survival from Surgery for Heart Valve Implantation in Sheep

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by difficulties in restarting the heart, causing significant on-table mortality. Therefore, optimal cardioprotective management during heart valve implantation in sheep is essential. However, little is known about successful cardioprotective management techniques in sheep. This article reports our experience in the cardioprotective management of 20 female sheep that underwent surgical aortic valve replacement with a stented tissue-engineered heart valve prosthesis. During this series of experiments, we modified our cardioprotection protocol to improve survival. We emphasize the importance of total body hypothermia and external cooling of the heart. Furthermore, we recommend repeated cardioplegia administration at 20 min intervals during surgery, with the final dosage of cardioplegia given immediately before the de-clamping of the aorta. To reduce the number of defibrillator shocks during a state of ventricular fibrillation (VF), we have learned to restart the heart by reclamping the aorta, administering cardioplegia until cardiac arrest, and de-clamping the aorta thereafter. Despite these encouraging results, more research is needed to finalize a protocol for this procedure.

Sheep are a commonly used and well-validated model for cardiovascular research, particularly for heart valve research, as blood pressure, heart rate, cardiac output, and intracardiac pressures are similar between sheep and humans. Sheep are particularly useful for heart valve research because observable changes in implanted heart valve bioprostheses that would take several years to develop in humans are apparent after only a few months in sheep.^3,11 This feature allows the ovine model to provide relevant and important information about heart valve prostheses in a relatively short time span. The first preclinical step in developing novel heart valves is to test the valve in the pulmonary position in sheep. This surgical technique is relatively easy, as the procedure can be performed on a beating heart in a low-pressure circulation. However, aortic valve surgery is the most frequently performed valvular surgical intervention in human patients.¹² Thus, an important next step is to prove the clinical applicability of a new valve by testing the valve in-vivo in the aortic position in an animal model. In contrast to pulmonary valve replacement, aortic valve replacement must be performed on an arrested heart, which makes the surgical procedure significantly more complex. The sheep is a difficult model for aortic valve replacements due to its narrow annulus, short distance between the annulus and coronary ostia, a short ascending aorta, and difficulty in de-airing of the heart prior to suturing the aortotomy.¹⁹ Consequently, high on-table mortality rates, ranging from 9% to 33%, have been reported.^1,18,21,24 Furthermore, the incidence of mortality during the first 30 d after surgery, directly related to the surgical procedure, is often high, ranging from 17% to 50%.^1,2,16,18,21 Therefore, optimizing cardioprotective strategies during surgery would improve postoperative survival. However, little is known about protective strategies in sheep. In the current series of experiments, we implanted stented, tissue engineered, aortic heart valve prostheses in 20 adult domestic sheep and developed cardioprotective techniques to increase survival rates. In this observational study, we share our experience and insights regarding cardioprotective management to potentially improve the outcome of future surgeries that require an arrested heart in sheep.     

Regional assignment of the mouse alpha A2-crystallin gene (Crya-1) to chromosome 17A3----B by in situ hybridization

Previously, we assigned the alpha A2-crystallin (Crya-1) structural gene to mouse chromosome 17 via Southern blot hybridization analysis of mouse x Chinese hamster somatic cell hybrids. Using in situ hybridization, we have now localized this gene to 17A3----B, a subchromosomal region containing several genes whose linkage relationships have been shown to be conserved on human chromosome 6. In man, however, the homologous gene (CRYA1) is located on human chromosome 21, indicating that internal rearrangements can occur within highly conserved chromosomal regions during the divergence of man and mouse.