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Biomedical subjects

C Bowers

Publications and source records attributed to C Bowers.

At least 37 records · Page 2Linked to original sources
PubMed1991

Superiority of an antagonist of the luteinizing hormone releasing hormone with emphasis on arginine in position 8, named Argtide.

In the research for more potent antagonists of the luteinizing hormone releasing hormone (LHRH), 13 new peptides with emphasis on arginine in position 8 were designed, synthesized and tested for anti-ovulatory activity (AOA). Two very potent analogs were achieved. N-Ac-D-3-Qal, D-pClPhe, D-3-Pal, Ser, cis-PzACA1a, D-PicLys, Leu, Arg, Pro, D-AlaNH2 showed 63% AOA at 0.125 microgram and 89% at 0.25 microgram, and an ED50 of 30.8 +/- 0.59 and presently may be the most promising antagonist reported. It is named Argtide. N-Ac-D-3-Qal, D-pClPhe, D-3-Pal, Ser, cis-PzACA1a, D-PicLys, Val, Arg, Pro, D-AlaNH2 showed 18% AOA at 0.125 microgram. Arg8 in antagonists may be significant for receptor binding.

Amino Acid Sequence↗
PubMed1988

Evaluation of the anaphylactoid activity of a new LHRH antagonist.

ORF 23541 [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,Ser4,Nic-Lys5,D-Nic-Lys 6, Leu7, I-Lys8, Pro9,D-Ala10NH2; "Nal-Lys antagonist"] was identified as a potent LHRH antagonist without significant anaphylactoid activity. It blocked ovulation in proestrus rats when administered subcutaneously with an ED50 of 5.8 micrograms/kg. Much higher doses of ORF 23541 than of other antagonists were required to induce a cutaneous anaphylactoid-like reaction. Intradermal administration of ORF 23541 caused an 8.75 x 8.75 mm wheal response with estimated doses of 10.9 and 13.7 micrograms in rats and guinea pigs, respectively. These doses were at least 10 times greater than that required of other LHRH antagonists for the same response. ORF 23541 also did not alter pulmonary function in guinea pigs or dogs when administered intravenously at doses up to 10 mg. These results indicate that ORF 23541 represents a new generation of LHRH antagonists with an improved safety margin.

Anaphylaxis↗
PubMed1988

Antide and related antagonists of luteinizing hormone release with long action and oral activity.

Antide is the decapeptide N-Ac-D-Nal(2),D-Phe(pCl),D-Pal(3),Ser,Lys(Nic),D-Lys(Nic),Leu,Lys(iPr),P ro,D- Ala-NH2 [Nal(2) represents 3-(2-naphthyl)alanine; Phe(p-Cl) represents 3-(4-chlorophenyl)alanine; Pal(3) represents 3-(3-pyridyl)alanine; Lys(Nic) represents N epsilon-nicotinoyllysine; Lys-(iPr) represents N epsilon-isopropyllysine], which is an antagonist of luteinizing hormone-releasing hormone (LHRH), which has high antiovulatory activity, releases negligible histamine, and is scheduled for scale-up, safety testing, and evaluation in the experimental primate and in clinical medicine. Thirty-five more peptides were synthesized, designed on antide with variations in positions 5-8. Of these, N-Ac-D-Nal(2),D-Phe(pCl),D-Pal(3),Ser,Lys(Pic),cis-D- Ala(PzAC),Leu,Lys(iPr),Pro,D-Ala-NH2 [Lys(Pic) represents N epsilon-picoloyllysine; Ala(PzAC) represents 3-(4-pyrazinylcarbonylaminocyclohexyl)alanine] was not only the most potent but also had higher antiovulatory activity than antide--i.e., 73% per 0.25 microgram and 100% per 0.5 microgram vs. 36% per 0.5 microgram and 100% per 1.0 microgram. Antide showed significant (P less than 0.001) duration of action when injected at a dose of 10 micrograms 44 hr before injection of 50 ng of the agonist [D-Qal(3)6]LHRH [Qal(3) represents 3-(3-quinolyl)alanine]. Antide showed oral antiovulatory activity at 600 micrograms (73%) and at 1200 micrograms (100%) with negligible difference between water and corn oil oral formulations.

Amino Acids↗
PubMed1986

Increased potency of antagonists of the luteinizing hormone releasing hormone which have D-3-Pal in position 6.

Ever increasing potency is an international goal for antagonists of the luteinizing hormone releasing hormone (LHRH). [N-Ac-D-2-Nal1,D-pClPhe2, D-3-Pal3,Ser4,Arg5,D-3-Pal6,Leu7,Arg8,Pro9,D- Ala10]-NH2 caused 60%/125 ng inhibition of ovulation in the rat, and appears to be the most potent antagonist yet described. Strategy of design was the replacement of D-Arg6 with D-3-Pal6 and of Tyr5 with Arg5. Replacing Arg5 with His5 reduced activity by 50% at 250 ng. Both the Arg5 and His5 analogs showed 100% inhibition of ovulation at 0.5 microgram. Of ten pairs of analogs with D-3-Pal6 and D-Arg6, 3/10 with D-3-Pal6 were more potent than those with D-Arg6. Histamine release was less for the D-3-Pal6 peptides of three pairs.

Alanine↗
PubMed1986

Maintenance of fetal human pancreatic beta cells in tissue culture.

Large quantities of viable human islet tissue (beta cells) are required for transplant and for investigations of the autoimmune basis of Type I diabetes. Fetal pancreas offers a potential advantage over other possible sources of beta cells in that it retains some capacity for growth in vitro. We have cultured a total of 45 human pancreata from fetuses of gestational ages from 18 to 23 weeks. Each pancreas was obtained within minutes after delivery and usually cultured within 30 minutes. Pancreata were dispersed and cultured for up to 32 days. Maintenance and growth of the beta cells was assessed by the content of insulin in extracts of cultured tissue. As has been reported by others, fetal human beta cells survived in vitro for over 4 weeks. In three experiments in which a direct comparison was made, collagenase digestion of the fetal pancreas resulted in a significantly greater loss of insulin content compared to minced tissue cultured without digestion. Storage of three pancreata in medium overnight at 4 degrees C significantly reduced the insulin content of the pancreas compared to pancreata cultured immediately. During culture, the majority of the beta cells (based on insulin content) were found in small, macroscopic clumps attached to the surface of the culture dish, and surrounded by a nearly confluent monolayer of fibroblastoid cells. There was a marked decrease in the insulin content of the tissue during culture, most of it (to less than 25% of the original) occurring over the first 4-6 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Aggregation↗
PubMed1985

Long-term culture and passage of human fetal liver cells that synthesize albumin.

Long-term cultures of hepatocytes were established from livers of human fetuses obtained by abortion at 18 to 23 wk of gestation. Cells obtained by collagenase dissociation of liver were maintained in defined serum-free medium on a substratum of positively charged plastic. Under these conditions, the cells divide and form a confluent monolayer. After multiple passages over a period of 3 mo., the cells retained an epithelioid morphology and continued to synthesize and secrete albumin.

Albumins↗
PubMed1981

Topochemically related hormone structures. Synthesis of partial retro-inverso analogs of LH-RH.

The syntheses of five partial retro-inverso luteinizing hormone-releasing hormone (LH-RH) analogs [g-Tyr5, m-Gly6]LH-RH, [g-Tyr5-r-Gly6, R,S-m-Leu7] LH-RH, [g-p-Glu1, m-His2]LH-RH, [g-p-Glu1-r-D-His-R,S-m-Trp3]LH-RH, and [g-Pro9-propionyl-des-Gly10]LH-RH, have been accomplished by solution methods. The choice of sequence to be reversed was based on suggested biodegradation mechanisms of LH-RH. A (gem)-diamino alkylidene residue, which was produced via Curtius rearrangement of a peptide segment, and a 2-substituted malonyl residue mark the initiating and terminating site, respectively, of the reversed sequence.

Amino Acid Sequence↗
PubMed1978

Late endocrine effects of L-dopa, 5-HTP, and 6-OH-dopa administered to neonatal rats.

Neonatal rats were injected with L-dopa, 5-hydroxytryptophan (5-HTP) or 6-hydroxy-dopa (6-OH-dopa) and allowed to mature. Eye opening, vaginal opening, endocrine organ weights and pituitary hormone concentration in the serum were measured. Treatment with either the dopamine (DA) precursor or the serotonin (5-HT) precursor caused an acceleration in eye opening, a significant decrease in serum TSH (males) an elevation of serum prolactin (Prl; males), and a lowering of serum growth hormone (females). After chemical sympathectomy (6-OH-dopa) vaginal opening was delayed, thyroid weights were increased and serum TSH decreased (males). It is concluded that during the critical neonatal period overloading either of 2 of the principal monaminergic systems results in similar and persistent alterations in pituitary function. Chemical sympathectomy produced a different pattern of abnormalities.

5-Hydroxytryptophan↗
PubMed1977

Nonapeptide ethylamide inhibitors of the luteinizing hormone-releasing hormone (LH-RH) having a D-alanyl residue in position 6 and variations at positions 2 and 3.

A series of ten analogues, of structure des-Gly10-[amino acid2, amino acid3,D-Ala6]-LH-RH ethylamide, was synthesized by solid-phase methods. L-Aromatic and alkylamino acids were substituted into position 2 and alkylamino acids into position 3. Highest in vitro inhibition of LH-RH action was obtained with analogues having aromatic residues in position 2. Des-Gly10-[Trp2,Leu3,D-Ala6]-LH-RH ethylamide inhibited the action of 0.6 ng/mL of LH-RH, in an isolated pituitary assay, at a dosage as low as 1 microgram/mL, and the corresponding Phe2 analogue inhibited the effect of 0.3 ng of LH-RH at 0.1 microgram/mL. The Trp2 analogue inhibited ovulation in rats at the dosage of 1.5 mg per rat.

Amides↗
PubMedDate not supplied

Fatal pulmonary microsporidiosis due to encephalitozoon cuniculi following allogeneic bone marrow transplantation for acute myelogenous leukemia.

Microsporidia are ubiquitous obligate eukaryotic intracellular parasites that are now felt to be more akin to degenerate fungi than to protozoa. Microsporidia can be highly pathogenic, causing a broad range of symptoms in humans, especially individuals who are immunocompromised. The vast majority of human cases of microsporidiosis have been reported during the past 20 years, in patients with HIV/AIDS, while only relatively rare cases have been described in immunocompetent individuals. However, microsporidia infections are being increasingly reported in patients following solid-organ transplanation, where the main symptom has been diarrhea. The authors report the first case of pulmonary microsporidial infection in an allogeneic bone marrow transplant recipient in the United States and only the second case in the world. The patient, with a history of Hodgkin disease followed by acute myelogenous leukemia received a T-cell-depleted graft, but succumbed to respiratory failure 63 days post transplantation. An open lung biopsy, taken just before death, was originally thought to show toxoplasmosis. The correct diagnosis of microsporidiosis was made postmortem by light and electron microscopy. DNA polymerase chain reaction analysis confirmed the diagnosis and furthermore revealed it to be the dog strain of the microsporidia species Encephalitozoon cuniculi. Although to date rarely diagnosed, microsporidial infection should also be considered in the differential diagnosis of, e.g., unexplained pulmonary infection in bone marrow transplant patients.

Acute Disease↗