Acetylcholine and choline levels in rabbit fetuses exposed to anticholinergics.

It has been hypothesized that acetylcholine, choline acetylase and acetylcholinesterase may have an ontogenic and trophic influence in the embryo, and that therefore certain drugs may produce malformations via their effect on the acetylcholine and choline levels in the fetus. Thalidomide and the anticholinergics, scopolamine hydrobromide and orphenadrine hydrochloride, and doxylamine succinate, an antihistamine with secondary anticholinergic action, were administered to pregnant New Zealand White rabbit does from day 8 to day 15 of gestation. Cesarean sections were performed on gestational day 16, the fetuses removed and the acetylcholine and choline contents of the fetuses and placentas were estimated by organic extraction and derivation for injection into a GCMS. These acetylcholine and choline levels were compared with those of the fetuses and placentas of the control animals mated with the same buck on the same day as the treated animals. Thalidomide (50 mg/kg) did not affect acetylcholine or choline levels in the fetuses or the placentas obtained from the treated animal. Scopolamine (approximately 100 micrograms/kg) reduced the choline level in the placenta and fetus but not the acetylcholine levels. Orphenadrine (approximately 24 mg/kg) reduced acetylcholine and choline levels in the fetus and choline levels in the placenta. Doxylamine succinate (10 mg/kg) reduced the acetylcholine levels in the fetus and the choline levels in the placenta. The placenta is a fetal organ and the significance of acetylcholine production by the placenta is as yet unknown. The reduction in acetylcholine levels in the fetus exposed to drugs with an anticholinergic action may be of significance in the production of malformations.(ABSTRACT TRUNCATED AT 250 WORDS)

Pseudoepidemic of Legionella pneumophila serogroup 6 associated with contaminated bronchoscopes.

An investigation of a pseudoepidemic of Legionella pneumophila serogroup 6 contaminating bronchoalveolar lavage specimens traced the source to contaminated tap water used to rinse disinfected bronchoscopes. The problem recurred despite plumbing changes and the installation of filters in the endoscopy unit water system because of inadequate maintenance of the filters.

Who needs unnecessary stress? Basic steps prevent insurer audits.

To say the least, any type of audit or investigation can be very stressful on a physician's practice. And, of course, negative findings may lead to severe financial repercussions when an insurer demands refunds of overpayments, or you find yourself on the defensive in criminal or civil litigation. Although there can be no guarantees, taking the necessary steps now can prevent an audit and protect your practice if one does occur.

The use of mental status in death certification of suicide.

A 5-year study (1982-1986) illustrates the use of mental status in death certification of suicide in 182 consecutive cases from Marion County, Oregon, U.S.A. The presence of specific mental illness was documented in Part II of the filed death certificate whenever sufficient data supported such a diagnosis. This study represents, so far as we are aware, the first use of mental illness in the routine death certification of suicide. The study subjects were described in terms of sex; age group; the presence or absence of a suicide note; the anatomical cause of death (Part I of the death certificate); and the presence of mental illness, severe physical illness, or alcohol abuse (Part II of the death certificate) as contributive to the death. About half (97 of 182 = 53.30%) of the study group was diagnosed as suffering from a major affective disorder. Another portion (18 of 182 = 9.89%) was classified as schizophrenic. A subgroup of 18 men, all of whom were residents of state mental or correctional institutions at the time of death, was also briefly described.

A 28-year (1963-90) study of homicide in Marion County, Oregon.

We describe 240 consecutive homicidal deaths that occurred in Marion County, Oregon, over a 28-year period (1963-90). An epidemiological assessment of the homicides yielded the following information: More than 91% of these deaths were primary homicides. In primary homicide, 63% of the victims and 88% of the offenders were male. In secondary homicide, 76% of the victims and all of the offenders were male. A high percentage of victims (83%) and offenders (84%) in primary homicide were Caucasian, as were 100% of victims and offenders in secondary homicide. About 12% of victims and 10% of offenders in primary homicide were Hispanic. Fifty-nine percent of primary homicides were intrasexual, as compared to 87% of secondary homicides. An intraracial pattern was found in 90% of primary homicides and in 100% of secondary homicides. The most frequent means of death in both primary and secondary homicides were firearms, physical beating, and stabbing. Strangers committed 80% of secondary homicides. This was in marked contrast to the victim-offender relationship found in primary homicides, where strangers were responsible for approximately 16% of the total, acquaintances for approximately 36%, and family members for approximately 48%. The overall clearance rate (i.e., the identification and charging of a suspect for the death) was 88%.

Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity.

Four monoclonal IgG antibodies to purified, recombinant murine gamma-interferon (rIFN-gamma) have been produced by fusion of immune hamster splenocytes with HAT-sensitive murine myeloma cells. Specificity was confirmed either with an enzyme-linked immunosorbent assay (ELISA) that used immobilized rIFN-gamma or with a radioimmunoassay that employed soluble 125I-rIFN-gamma and heat-killed, fixed Staphylococcus aureus-bearing Protein A. Competition binding experiments suggested that the monoclonal antibodies (MoAb) displayed two distinct epitope specificities: one displayed by H1 and H2, and the other displayed by H21 and H22. By using murine-human recombinant IFN-gamma hybrid molecules, the H1/H2 epitope was shown to depend on the amino-terminus of IFN-gamma, whereas the H21/H22 epitope was formed by the carboxy-terminal amino acid sequence. The MoAb also reacted with natural IFN-gamma. When bound to a surface, all four MoAb, but not normal hamster IgG, removed 100% of the antiviral and MAF activities present in supernatants of cultures of the murine 24/G1 T cell hybridoma. In free solution, all four antibodies inhibited IFN-gamma dependent antiviral activity, but with different efficiencies. Soluble H21/H22 also blocked all of the 24/G1-derived activity that induces nonspecific tumoricidal activity in macrophages (MAF) while H1/H2 enhanced MAF activity. The differential inhibitory or enhancing activities of H21 or H1 reflected their ability to inhibit or enhance binding of 125I-rIFN-gamma to macrophages, respectively. Soluble H21/H22 and solid-phase H1/H2 inhibited 100% of the MAF, microbicidal, and Ia-inducing activities from lymphokine preparations produced by mitogen stimulation of normal murine splenic cells. These results help to establish definitive structure-function relationships for the IFN-gamma molecule, and indicate that IFN-gamma is the primary lymphokine responsible for inducing nonspecific tumoricidal activity and Ia antigen expression, and for enhancing microbicidal activity in macrophages.

Death by smothering and its investigation.

This case report provides details from an extensive death investigation, the results of which led to the certification of suicidal manner of death by means of smothering in a pillow, without additional assistance from other persons or mechanical devices. This was the death of a chronically mentally ill person who was under currently approved professional treatment. Major investigative aspects of this case were the death-scene observations of the body, elimination of the possibility of homicide, and the study and analysis of the subject's psychiatric illness. Reasons for the uncommonness of reported deaths in this category are discussed.

Circulating IgG-specific immune complexes as a potential tumor marker in gynecological malignancies.

A longitudinal study of circulating immune complexes (CIC) of the IgG class has been undertaken in patients presenting for operation of active malignant disease of the female reproductive tract. These values were compared with data obtained during subsequent clinical remission and prior to the clinical diagnosis of relapse. The results showed that irrespective of the site of disease (e.g., ovary, fallopian tube, cervix, endometrium, or vagina) values for CIC were elevated in most patients compared to controls. Postoperative remission status was associated with a significant decrease in values for all tumor sites. Similarly, relapse was associated with elevation of CIC levels to values similar to the preoperative concentrations. It is concluded that CIC may provide a useful biochemical marker of the progression of malignant disease.

Toxicity to fish of flame retardant fabrics immersed in their water. Part I.

A number of commercial and candidate flame retardants were studied with regard to their toxicity to fish when released from fabrics immersed in their water. Immersion of laundered or unlaundered flame retardant 100% polyester or polyester blend fabrics used in children's sleepwear in water containing goldfish resulted in release of the anticholin-esterase flame retardant TDBPP (tris (2, 3-dibromopropyl) phosphate) and death of all fish within 24 hours. TDBPP undergoes loss of HBr in water and production of a metabolite.

The value of the monoclonal antibody (cancer antigen 125) in serial monitoring of ovarian cancer: a comparison with circulating immune complexes.

The use of circulating immune complexes and a commercial monoclonal antibody to ovarian cancer (CA 125 kit) in monitoring progress in patients with ovarian cancer has been assessed. While changes in immune complexes were apparent in some patients with active progression of disease, the marked change in values and linear trend make the use of CA 125 a useful clinical marker.

cDNA sequence and tissue distribution of the mRNA for bovine and murine p11, the S100-related light chain of the protein-tyrosine kinase substrate p36 (calpactin I).

We have isolated and sequenced cDNA clones of bovine and murine p11 mRNAs. The nonpolyadenylated mRNAs are predicted to be 614 and 600 nucleotides, respectively. The p11 mRNAs both contain a 291 nucleotide open reading frame, preceded by a 5'-untranslated region of 73 nucleotides in bovine p11 mRNA and of 68 nucleotides in murine p11 mRNA. The deduced bovine p11 amino acid sequence is identical to the previously published partial bovine and complete porcine p11 protein sequence except for an additional COOH-terminal lysine residue. The bovine and murine p11 proteins are 92% homologous, whereas at the nucleotide level the conservation is 89% in the coding region and 75% in the 3'-untranslated region. Southern analysis of murine genomic DNA detected a single p11 gene, less than 10 kilobase pairs in size, containing as many as three introns. The p11 gene has been assigned to mouse chromosome 3 by analysis of interspecific hybrid cell panels and recombinant inbred mouse strains. The p11 gene is closely linked to the Xmmv-65 endogenous leukemia virus env gene and the guanylate binding protein-1 gene. Northern analyses of RNAs from mouse tissues and cell lines indicated that p11 mRNA levels vary widely. They are very low in liver, heart, and testes, moderate in brain, spleen, and thymus, and high in kidney, intestine, and lung. Analysis of the same RNA samples for p36 mRNA levels showed that expression of p11 and p36 mRNAs is not always coordinated. Brain and the mouse embryonal carcinoma cell line F9 contain moderate to high levels of p11 mRNA with very low levels of p36 mRNA. Sequence homology between p11 and the S100 proteins, and the serum-induced 2A9 gene product, as well as possible functions of p11 are discussed.

Primary structure of bovine calpactin I heavy chain (p36), a major cellular substrate for retroviral protein-tyrosine kinases: homology with the human phospholipase A2 inhibitor lipocortin.

An amplified Okayama-Berg plasmid cDNA library was constructed from total poly(A)+ RNA isolated from the Madin-Darby bovine kidney cell line MDBK. This library was screened with a partial murine calpactin I heavy chain (p36) cDNA clone, the identification of which was based on bovine p36 tryptic peptide sequences generated during the course of these studies. The largest p36 cDNA insert (p36/6 of 1.6 kilobase pairs) was fully sequenced by the dideoxy method. The DNA sequence of this insert had an open reading frame of 1014 base pairs and coded for a protein with a molecular weight of 38 481. The deduced protein sequence of 338 residues was concordant with 173 residue positions of p36 determined at the protein level. The 5'- and 3'-ends of p36/6 contained 54 and 307 base pairs of untranslated sequence, respectively. Examination of poly(A)+ RNA prepared from the Madin-Darby cell line indicated a p36 mRNA species of about 1.6 kilobases. Four regions of internal homology, each about 70 amino acid residues in length, were observed in the deduced protein sequence for p36. Thirty-three of the 70 residue positions were conserved in at least three of the four repeating units. A comparison of derived amino acid sequence for bovine p36 with that previously determined for human lipocortin [Wallner, B. P., Mattaliano, R. J., Hession, C., Cate, R. L., Tizard, R., Sinclair, L. K., Foeller, C., Chow, E. P., Browning, J. L., Ramachandran, K. L., & Pepinsky, R. B. (1986) Nature (London) 320, 77-81] revealed extensive homology (66% overall) and the presence of four repetitive regions in the lipocortin structure.(ABSTRACT TRUNCATED AT 250 WORDS)