Exploring common ground in the stem cell ethical debate—A perspective for scientists

The purpose of this special issue of Stem Cell Reviews is to address some of the most difficult ethical debates surrounding the derivation of pluripotent stem cell lines. The possible benefits of stem cells are widely discussed, but the scientific community is particularly aware that research in this area is still at an early, but essential, stage of development. With this research at such an early stage, it is noteworthy that the media, the public, religious leaders, politicians, policy makers, and regulators have had as much interest in stem cell research as for any other area of scientific inquiry. The central issue that has made this area so controversial has been the use of the human embryo for deriving stem cell lines.     

Testicular function after orchiopexy for unilaterally undescended testis.

Testicular function was determined in 29 men, 21 to 35 years old, who had undergone orchiopexy for unilaterally undescended testis at four to 12 years of age. Serum testosterone and dialyzable testosterone concentrations of these men were not significantly different from those of a control group of 30 normal men, and their basal serum luteinizing hormone concentrations and serum luteinizing hormone responses to synthetic gonadotropin-releasing hormone were only slightly higher than those of the normal men. The mean sperm density of the patients, however, was only one third of that of the normal men (p less than 0.001). The mean serum follicle stimulating hormone response ro gonadotropin-releasing hormone of the patients was doubled that of the normal men (p less than 0.001). The data indicate that spermatogenesis may be abnormal after orchipexy, and suggest that men with unilaterally undescended testis may have bilateral testicular abnormality.     

Development and preliminary evaluation of a slide latex agglutination assay for detection of Clostridium perfringens type A enterotoxin

A slide latex agglutination (SLA) assay was developed for rapid screening for Clostridium perfringens type A enterotoxin (CPE). SLA specifically detected CPE added to buffer or normal feces (sensitivity limit of 1 μg CPE/g feces). Using clinical fecal samples from C. perfringens food poisoning cases, a strong correlation was shown between (1) SLA results and results from other CPE assays and (2) between SLA results and illness status.     

Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency

An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4) deficiency. Activities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively. Western blot analysis demonstrated that the amount of E3 protein in fibroblasts from the patient and her father was about half of controls, while Northern blot analysis showed normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs from the patient revealed two mutations in separate alleles. One is a single base insertion of an extra adenine in the last codon of the leader peptide sequence (TAC-->TAAC) leading to a nonsense mutation which results in the premature termination of the precursor E3 polypeptide (Y35X). The other is a missense mutation due to substitution of guanine for adenine, causing an Arg-->Gly substitution at amino acid 460 of the mature protein (R460G) which triggers the loss of E3 activity probably by structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the parents demonstrated that the nonsense mutation was inherited from the father and the missense mutation was inherited from the mother.      

Morphine-induced metabolic changes in human brain. Studies with positron emission tomography and [fluorine 18]fluorodeoxyglucose

Morphine sulfate effects (30 mg, intramuscularly) on cerebral glucose utilization and subjective self-reports were examined in 12 polydrug abusers by positron emission tomography and [fluorine 18]fluorodeoxyglucose in a double-blind placebo-controlled crossover study. During testing, subjects sat with eyes covered, listening to white noise and "beep" prompts. Morphine significantly reduced glucose utilization by 10% in whole brain and by about 5% to 15% in telencephalic areas and the cerebellar cortex, assuming no contribution of hypercapnia. When the contribution of PaCO2 (45 minutes after morphine was administered) was partialled out, significant morphine-induced reductions persisted in whole brain and six cortical areas. Irrespective of morphine, left-greater-than-right asymmetry occurred in the temporal cortex, and an interaction between hemisphere and drug was noted in the postcentral gyrus. In most cases, effects on glucose utilization were not significantly related to measures of euphoria.     

Caring for adults with mental retardation: survey of family practice residency program directors

In their core curriculum guidelines, the Society of Teachers of Family Medicine has recognized the importance of training family physicians in caring for persons with mental retardation. We mailed surveys to all family practice residency directors in the United States, questioning them about experiences and methods used to teach residents about health care needs of adults with mental retardation and the importance of this education. We found that 84% of programs provide residents with one or more experiences, and 60% instruct residents in this area. Most directors ranked this education as very important or important. There was no relationship between type or age of residency program and likelihood that residents were educated about mental retardation. The importance of this education is discussed.     

Differential cellular expression of isoforms of inositol 1,4,5-triphosphate receptors in neurons and glia in brain

Inositol 1,4,5-trisphosphate receptors (IP3R) are mediators of second messenger-induced intracellular calcium release. Three isoforms are known to be expressed in brain, but their regional distributions and cellular localizations are little known. In order to better understand the roles of IP3 receptor isoforms in brain function, a first step is to define their distributions. We have used affinity-purified antibodies directed against peptides unique to each isoform to determine their sites of expression in rat brain. Type 1 IP3R (IP3R1) is dramatically enriched in Purkinje neurons in cerebellum and neurons in other regions, consistent with previous studies. By contrast, IP3R2 is only detected in glia, whereas IP3R3 is predominantly neuronal, with little detected in glia. IP3R3 is enriched in neuropil, especially in neuronal terminals (which often contain large dense core vesicles) in limbic and basal forebrain regions including olfactory tubercle, central nucleus of the amygdala, and bed nucleus of the stria terminalis. In addition, IP3R1 and IP3R3 have clearly distinct time courses of expression in developing brains. These data suggest separate roles for inositol 1,4,5-trisphosphate receptor isoforms in development, and for glial and neuronal function. The IP3R3 may be involved in regulation of neurotransmitter or neuropeptide release in terminals within specific nuclei of the basal forebrain and limbic system.