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Biomedical subjects

G Holtz

Publications and source records attributed to G Holtz.

At least 19 recordsLinked to original sources
PubMed1997

Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice.

Missense mutations in the beta-amyloid precursor protein gene (APP) co-segregate with a small subset of autosomal dominant familial Alzheimer's disease (FAD) cases wherein deposition of the 39-43 amino acid beta-amyloid (A beta) peptide and neurodegeneration are principal neuropathological hallmarks. To accurately examine the effect of missense mutations on APP metabolism and A beta production in vivo, we have introduced yeast artificial chromosomes (YACs) containing the entire approximately 400 kbp human APP gene encoding APP harboring either the asparagine for lysine and leucine for methionine FAD substitution at codons 670 and 671 (APP(K670N/M671L)), the isoleucine for valine FAD substitution at codon 717 (APP(V7171)) or a combination of both substitutions into transgenic mice. We demonstrate that, relative to YAC transgenic mice expressing wild-type APP, high levels of A beta peptides are detected in the brains of YAC transgenic mice expressing human APP(K670N/M671L) that is associated with a concomitant diminution in the levels of apha-secretase-generated soluble APP derivatives. Moreover, the levels of longer A beta peptides (species terminating at amino acids 42/43) are elevated in YAC transgenic mice expressing human APP(V7171). These mice should prove valuable for detailed analysis of the in vivo effects of the APP FAD mutations in a variety of tissues and throughout aging and for testing therapeutic agents that specifically alter APP metabolism and A beta production.

Alzheimer Disease↗
PubMed1994

Transvaginal embryo transfer during the zygote intrafallopian tube transfer procedure.

OBJECTIVE: Our purpose was to evaluate a tactile non-ultrasonographically directed approach to transvaginal tubal cannulation and embryo transfer during the zygote intrafallopian tube transfer procedure. STUDY DESIGN: We studied the application of the tactile approach to transvaginal tubal cannulation and embryo transfer in 68 consecutive zygote intrafallopian tube transfer cycles. RESULTS: The tactile approach to transvaginal tubal cannulation and subsequent embryo transfer was successful in 93% of couples. Pregnancy occurred in 16 of the 63 (25%) women undergoing a successful transvaginal embryo transfer. CONCLUSION: The tactile approach to transvaginal tubal cannulation was found to be easily learned and provided a safe and convenient method of tubal embryo transfer. This low-cost approach, which has application to transfer of both embryos and gametes, deserves further study.

Catheterization↗
PubMed1987

Isthmic ectopic pregnancy and salpingitis isthmica nodosa.

Two hundred eighty-five charts were reviewed from patients who underwent surgery for ectopic pregnancy. Excluded were patients with previous tubal reparative surgery, linear salpingotomy, or failed sterilization. The incidence of isthmic ectopic pregnancy in the remaining 255 cases was 15.3%. The association of salpingitis isthmica nodosa (SIN) and isthmic ectopic pregnancy was determined by review of resected tubal segments. SIN was noted in 17 of 37 cases (45.9%) of isthmic ectopic pregnancy. SIN places the patient at risk for recurrent ectopic pregnancy or infertility. Recommended conservative management of isthmic ectopic pregnancy is segmental resection with postoperative emphasis on documentation of SIN when present. Postoperative hysterosalpingography is recommended with an abnormal contralateral tube or when SIN is noted in the resected tubal segment. Management options after an isthmic ectopic pregnancy when future fertility is desired are presented.

Fallopian Tubes↗
PubMed1987

Laparoscopy in the massively obese female.

Fifteen women weighing more than 250 pounds (113.6 kg) underwent laparoscopy. The open technique was used in two patients electively because of repeated pelvic laparotomies through periumbilical incisions. Of the remainder, four had used the closed technique and in nine it was necessary to adopt an open technique. Use of the latter effectively "lengthened" the instruments. Visualization was excellent in all but one subject, and the only complication was a single case of wound cellulitis.

Female↗
PubMed1987

Interleukin-1: a possible role in the infertility associated with endometriosis.

Increased numbers of activated macrophages are associated with mild endometriosis. Interleukin-1 (IL-1) is a protein produced by macrophages and is believed to be a primary mediator of host responses. IL-1 induces prostaglandin and fibrinogen synthesis and stimulates fibroblast proliferation. This study was undertaken to evaluate the role of IL-1 in the infertility associated with mild endometriosis. Peritoneal fluid (PF) was obtained at laparoscopy from 11 patients with minimal or mild endometriosis and from 7 women undergoing tubal ligation. Peritoneal macrophages were isolated and cultured for 24 hours. Peritoneal and macrophage culture fluids were studied for IL-1 activity, which was measured with the EL-4 assay. IL-1 activity was present in the PF of 10 of the 11 patients with endometriosis and 11 of the 11 macrophage culture fluids and was absent in the PF and macrophage culture fluid of the tubal ligation patients. The effect of recombinant alpha-IL-1 on the in vitro growth of 2-cell mouse embryos was also studied. IL-1 in concentrations similar to those present in the PF (greater than 1 U/ml) was toxic to mouse embryo development. We conclude that the IL-1 may play a role in the infertility associated with endometriosis.

Animals↗
PubMed1986

Adhesion prevention in the rabbit with sodium carboxymethylcellulose solutions.

With the use of a rabbit surgical model, the ability of 1%, 2%, and 3% solutions of sodium carboxymethylcellulose to reduce postoperative uterine adhesions was determined. At all concentrations sodium carboxymethylcellulose was more effective than either 32% dextran 70 or heparinized lactated Ringer's solution. Neither the dextran nor Ringer's solution had a significant (p less than or equal to 0.05) effect. The beneficial effects of sodium carboxymethylcellulose were closely dose-dependent (correlation coefficient 0.97). Sodium carboxymethylcellulose is highly effective in reducing postoperative adhesions in laboratory animals, and additional studies are warranted to further define its efficacy and safety.

Animals↗
PubMed1985

Luteinized unruptured follicle syndrome in mild endometriosis. Assessment with biochemical parameters.

Failure to extrude an ovum, with subsequent luteinization of the unruptured follicle (LUF), has been proposed as a cause of infertility in women with mild endometriosis. To assess the incidence of this process we performed laparoscopies in the early luteal phase on 16 women with mild endometriosis and 8 control subjects. Peritoneal fluid was aspirated and a plasma sample obtained concurrently. Estradiol (E2) and progesterone (P) concentrations were determined. A review of the literature suggested that the following hormonal criteria correlated with follicular rupture: fluid E2 greater than or equal to 500 pg/ml, E2 fluid/plasma ratio greater than or equal to 3.1, fluid P greater than or equal to 3,000 ng/dl and P fluid/plasma ratio greater than or equal to 5:1. All control subjects met at least one E2 and one P criterion: 75% met all. In contrast, less than one-third with mild endometriosis met all, and three (19%) met none. Five met only E2 criteria. These findings suggest that LUF occurs occasionally in association with mild endometriosis. Additionally, ovarian steroidogenesis, particularly P secretion, was impaired frequently in the absence of LUF in women with endometriosis.

Ascitic Fluid↗
PubMed1984

Control of basal-level codon misreading in Escherichia coli.

Basal-level misreading of asparagine codons was examined in a number of Escherichia coli strains. Lysine substitutions were measured by quantitating the amount of charge heterogeneity in MS2 coat protein. In most strains the heterogeneity was consistent with misreading of AAU codons at a frequency of 3-6 X 10(-3). Strains with streptomycin resistance mutations (rpsL) have reduced levels of misreading. There is no significant difference in the frequency of basal-level errors in stringent (relA+) and relaxed (relA) strains, even during starvation for amino acids unrelated to the substitution being studied.

Amino Acids↗
PubMed1983

Update on ectopic pregnancy.

Ectopic pregnancy is the leading cause of maternal death in the first trimester. Its incidence is increasing, probably owing to the increasing incidence of pelvic inflammatory disease. Although up to 15% of patients have been reported to present in shock, a large number seek care earlier because of pelvic pain and irregular menses. With strong clinical suspicion and the use of culdocentesis, assays of the beta subunit of human chorionic gonadotropin in the blood and ultrasonography, the diagnosis can be made before rupture occurs. Although the woman's subsequent fertility has traditionally been poor, some improvement has been achieved with the use of conservative surgical techniques. Early diagnosis facilitates this approach.

Chorionic Gonadotropin↗
PubMed1983

Codon usage and mistranslation. In vivo basal level misreading of the MS2 coat protein message.

The coat protein of the small RNA virus MS2 shows charge heterogeneity in vivo. In most strains there is a basic satellite of the native protein. We have shown that this basic satellite is greatly diminished or absent in strains with the streptomycin-resistant allele, rpsL, a mutation which leads to increased translational accuracy. Further, the satellite is present in cells where the coat protein is encoded by duplex DNA. Tryptic digests of the satellite show that it contains new lysine-containing peptides which appear to be the same as those found in derivatives of coat protein which have a lysine for asparagine substitution. Sequencing of the NH2-terminal 19 amino acids of the satellite protein shows that the asparagine codon AAU at amino acid 12 is misread approximately 8 times more frequently than the AAC at amino acid 3. We conclude that the satellite species is the result of basal level lysine for asparagine substitution. These substitutions are most likely caused by preferential misreading of AAU codons at a frequency of approximately 5 X 10(-3), 10-fold higher than the average error frequency.

Amino Acid Sequence↗