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Biomedical subjects

C Austin

Publications and source records attributed to C Austin.

At least 19 recordsLinked to original sources
PubMed1997

Evaluation of predictive factors for multiple pregnancies during gonadotropin/IUI treatment.

PURPOSE: Our purpose was to analyze factors for their predictability of multiple pregnancies in patients treated with a combination of human menopausal gonadotropins (hMG) and intrauterine insemination (IUI). METHODS: The records of all patients conceiving through treatment with hMG/IUI were reviewed for factors predictive of multiple pregnancy. RESULTS: Ninety-one pregnancies reviewed included 78 singleton (86%), 8 twin (9%), and 5 higher-order pregnancies (5%). The total number of follicles > 10 mm was greater in the multiple-pregnancy group and there was a decreased number of postwash sperm in the multiple-pregnancy group. Otherwise there was no significant difference in the factors analyzed. CONCLUSIONS: No factor or combination of factors predicts multiple pregnancies to a degree that it would be helpful in managing or counseling patients.

Female↗
PubMed1996

Simultaneous measurement of intracellular pH, calcium, and tension in rat mesenteric vessels: effects of extracellular pH.

In rat mesenteric vessels changes in external pH (pHo) alter tension. Changes in intracellular pH (pHi) and calcium ([Ca2+]i) have both been suggested to underlie the tension changes. As no simultaneous measurements of pHi and [Ca2+]i had been made, however, the relative importance and temporal relationship between pHi [Ca2+]i and tension were unknown. In order therefore to gain a clearer understanding of the mechanisms involved, we have made simultaneous measurements of these parameters using carboxy-SNARF and INDO-1. Raising pHo caused rises in pHi, Ca2+ and tension. The increases in pHi preceded increases in [Ca2+]i, which preceded the increases in tension. Similar but opposite effects were observed when pHo was decreased. We conclude that the change in [Ca2+]i upon alteration of pHo is subsequent to that of pHi.

Animals↗
PubMed1996

Cost-effectiveness of in vitro fertilization.

OBJECTIVE: To estimate the cost per woman delivered of pregnancies from an in vitro fertilization (IVF) program, and to assess what factors contribute to the cost. METHODS: The cost during 2 years' experience of a single IVF program was analyzed retrospectively. Cost analysis included cost of the IVF procedure itself as well as costs incurred because of maternal and neonatal complications. RESULTS: The major contributor to the total cost of IVF was high-order multiple pregnancies. The cost per woman delivered of singleton or twin pregnancies was approximately $39,000, whereas the cost per woman delivered of triplet and quadruplet pregnancies was approximately $340,000. CONCLUSION: In vitro fertilization can be cost-effective if steps are taken to minimize high-order multiple (triplet or more) pregnancies.

Cost-Benefit Analysis↗
PubMed1996

Cost analysis of shared oocyte in vitro fertilization.

OBJECTIVE: To estimate the cost per woman delivered of a shared oocyte in an in vitro fertilization (IVF) program, and to compare these costs with those of a routine IVF program. METHODS: The cost of 23 shared oocyte cycles was analyzed retrospectively and compared with the cost of routine IVF. RESULTS: The cost per woman delivered in the shared oocyte program was approximately $22,000, compared with $66,000 in the routine IVF program. CONCLUSION: Shared IVF is a very cost-effective program and others donors and recipients an otherwise unavailable opportunity.

Adult↗
PubMed1995

The effects of extracellular pH and calcium change on force and intracellular calcium in rat vascular smooth muscle.

1. In order to investigate the mechanism whereby changes in external pH (pHo) alter tone in rat mesenteric resistance vessels, we have made simultaneous measurements of tension and intracellular Ca2+ [Ca2+]i. Strips of mesenteric artery were loaded with the Ca(2+)-sensitive indicator indo-1 and superfused with physiological salt solution at pH 7.4 and 37 degrees C. 2. An increase of pHo from 7.4 to 7.9 produced an increase in tension. This was accompanied by an increase in [Ca2+]i in resting and high-K(+)-depolarized vessels. Acidification to 6.9 reduced tension and was associated with a fall in [Ca2+]i. Over the pHi range examined, 6.6-7.9, parallel changes in [Ca2+]i and tension were found in K(+)-activated vessels. 3. In contrast to the relatively slow change in [Ca2+]i, pHi and tension with change of pHo, depolarization produced rapid changes in [Ca2+]i and tension, consistent with a more direct action on Ca2+ mobilization. 4. Reducing the external [Ca2+] below 1 mM produced a pronounced fall in [Ca2+]i and force. Changes in [Ca2+]i, produced by alteration of external [Ca2+] (Cao2+) were used to examine the relation between [Ca2+]i and tension. A linear relation was found. Alteration of pHo to 6.9 or 7.9 did not significantly change this relation. When the tension data were normalized to their own maxima, no shift in the tension-Ca2+ relation occurred, suggesting little or no effect of pH on the Ca2+ sensitivity of force production by the contractile proteins. 5. To determine further whether the changes in [Ca2+]i produced by alteration of pHo could account for all the changes observed in tension, [Ca2+]i was restored to control levels while maintaining an altered pHo. When this was done, restoration of [Ca2+]i led to restoration of force. Thus, in this preparation, the changes in [Ca2+]i produced by altering pHo in depolarized vessels can account for the changes in vascular tone.

Animals↗
PubMed1995

An investigation of intrinsic buffering power in rat vascular smooth muscle cells.

Intrinsic buffering power (beta i) has been measured in vascular strips and single cells from rat mesenteric artery. Intracellular pH (pHi) regulation was inhibited to prevent overestimation of beta i due to acid extrusion or entry via regulatory processes. At resting values of pHi (7.0-7.2), a mean value of 41 +/- 4 mM/pH unit for beta i was found. beta i increased approximately fivefold from 30 to 150 mM/pH unit over the pHi range 7.5-6.5. The mean data relating beta i to pHi could be described by relating beta i to buffer concentrations and pKa. This gave a value of 310 mM for buffer concentration and a pKa of 6.0. As changes in pHi are known to have marked effects on vascular tone then the increase in beta i as pHi falls may be considered as a means of attenuating pHi decreases, before pH regulation restores pHi to resting levels.

Animals↗
PubMed1995

The influence of 17-beta-oestradiol and the natural oestrous cycle on alpha-adrenoceptor-mediated responses of the cardiovascular system in the rat.

The effect of 17 beta-oestradiol pretreatment and the natural oestrous cycle on responses of rat cardiac and vascular alpha-adrenoceptors was investigated. It was found that treatment with the oestrogen had no effect on cardiac adrenoceptor sensitivity, while pretreatment with the hormone caused a significant increase in vascular alpha 2-, but not vascular alpha 1-adrenoceptor responsiveness. Pressor responses of pithed rats to selective alpha 1- or alpha 2-adrenoceptor agonists did not alter, however, during the natural oestrous cycle. These findings suggest that changes in oestrogen levels are capable of altering alpha-adrenoceptor-mediated vascular responses but that the relatively small changes in oestrogen which may occur throughout the natural oestrous cycle do not appear to alter the responses of these vascular alpha-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1995

Contribution of extracellular calcium to intracellular pH-induced changes in spontaneous force of rat portal vein.

Normal spontaneous mechanical activity of isolated rat portal vein is critically dependent on external calcium as a source of contractile activation and this force is modified by alteration of intracellular pH. We have studied the involvement of the extracellular calcium pool in intracellular pH-induced changes in force. Intracellular pH was changed, at constant external pH, by NH4Cl application and withdrawal in bathing [CaCl2] varying between 3 and 0 mM, and manoeuvres were performed in the presence and absence of either the intracellular calcium mobilizer caffeine or the calcium channel blocker nifedipine. The results indicate that alteration of spontaneous force with intracellular pH has an absolute requirement for calcium entry from outside and calcium release from caffeine-sensitive intracellular stores.

Ammonium Chloride↗
PubMed1995

Cloning and characterization of the cDNA encoding the human neuromedin U (NmU) precursor: NmU expression in the human gastrointestinal tract.

Many peptide precursors encode more than one bioactive peptide. Recent cloning of the rat neuromedin U (NmU) precursor revealed potential proteolytic processing sites which may generate three associated peptides in addition to the NmU peptide, which is known to have potent uterine contractile effects. To assess the degree of evolutionary conservation, which often suggests conserved biological function and hence physiological importance, we have cloned and sequenced the cDNA encoding the human NmU precursor. Sequence analysis revealed a 174 amino acid human precursor containing the 25 residue NmU peptide near the C terminus of the precursor. The human message sequence was 74% homologous with that of the rat, indicating evolutionary conservation of the precursor between these two species. Four out of five of the putative proteolytic processing sites, first revealed in the rat precursor, were conserved in the human precursor, indicating a similar processing mechanism in both species. Two such processing sites flank a 33 residue peptide sequence which differed in only two amino acids compared with the rat homologue. This conservation suggests a possible biological role for this putative peptide. Northern blot analysis of human gastrointestinal tissues revealed a similar level of mRNA throughout the gastrointestinal tract. RIA using a porcine specific assay showed the highest levels of peptide in the jejunum samples.

Amino Acid Sequence↗
PubMed1994

A comparison of the effects of intracellular and extracellular pH on contraction in isolated rat portal vein.

1. The effects of changes in extracellular and intracellular pH on spontaneous contractile activity in isolated rat portal vein have been investigated. 2. Small strips of portal vein were loaded with the pH-sensitive fluorophore carboxy-SNARF and intracellular pH (pHi) and contraction were measured simultaneously at 37 degrees C. The tissue was superfused with oxygenated, Hepes-buffered solutions at pH 7.4. Intracellular pH was altered by isosmotic substitution of weak acids or bases. External pH (pHo) was altered by addition of strong acid or base to the solution. 3. The mean resting value of pHi was 7.06 +/- 0.03 (n = 28). Alteration of pHi led to changes in spontaneous activity. Addition of butyrate (20 mM) reduced pHi by 0.18 +/- 0.01 pH units (n = 8). Decreasing pHi produced an early, brief increase in contractile activity followed by a longer lasting decrease or even abolition of contraction. 4. Addition of 20 mM trimethylamine or NH4Cl increased pHi by around 0.2 pH units and produced an early transient decrease in contractile activity followed by a later maintained increase, both in frequency and magnitude. Removal of base produced a rapid rebound decrease in pHi which was associated with a further transient increase in contractile activity followed by decreased activity. The effects of base on both pHi and contraction were concentration dependent over the range investigated (2.5-30 mM). 5. Alteration of pHo produced a change in pHi in the portal vein. The pHi change was rapid compared to other non-vascular cells (about 1 min to half-maximal response).(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride↗
PubMed1994

A quantitative study of the relation between intracellular pH and force in rat mesenteric vascular smooth muscle.

Strips of rat mesenteric artery were loaded with carboxy-seminaphthorhodafluor (SNARF) to measure intracellular pH (pHi) and force simultaneously. pHi was altered by using weak acids and bases. Alkalinization produced an increase in force. For equal elevations of pHi a greater and faster increase of force was obtained in depolarized (high K+) than in non-depolarised preparations. Acidification produced little change in force unless the tissue was contracted (high-K+), in which case it elicited relaxation. Examination of the relationship between pHi and force in depolarized preparations showed that acidification produced a greater change in force than alkalinization. Removal of weak bases produced a transient acidification that was accompanied by a fall in force in all preparations. This was followed by a secondary contraction in depolarized preparations during the period over which pHi was acidic and being restored to resting values. Some preparations demonstrated a hysteresis in the relation between pHi and force. It is concluded that the relationship between pHi and force in mesenteric vascular smooth muscle is not constant but depends on the previous history of the preparation, and may involve differences in the interactions between H+, Ca2+ and the contractile machinery.

Ammonium Chloride↗
PubMed1994

Differential effects of external pH alteration on intracellular pH in rat coronary and cardiac myocytes.

Changes in extracellular pH (pHo) induce changes in the intracellular pH (pHi) of cardiac myocytes that are slow and attenuated. Little however is known about the effects of changing pHo on the pHi of the coronary smooth muscle cells. We have therefore directly compared the effects of altering pHo on pHi of both coronary and cardiac myocytes. Carboxy-SNARF was used in single cells to measure pHi. Alteration of pHo caused corresponding changes in pHi that were large (70-80% of pHo) and rapid in coronary myocytes compared to cardiac myocytes. In contrast, changes of pHi produced by weak acids or bases produced similar pHi responses in both types of cells. It is suggested that the differential effects of pHo on coronary and cardiac cells may be functionally significant, as it will allow rapid alteration of coronary perfusion to meet tissue needs, while maintaining cardiac output.

Animals↗
PubMed1994

The in-vitro effects of insulin and the effects of acute fasting on cardiac beta-adrenoceptor responses in the short-term streptozotocin-diabetic rat.

This study demonstrates that in-vitro incubation with insulin results in a reduction of the sensitivity of cardiac tissues from streptozotocin-diabetic rats to isoprenaline. Following incubation with insulin, the sensitivity of left atria and papillary muscles from diabetic animals was not significantly different from those of control animals. Insulin incubation had no effect on the sensitivity of diabetic tissues to forskolin or on ventricular beta-adrenoceptor number. Reduction of blood glucose in the absence of insulin by fasting, did not affect the sensitivity of tissues from diabetic animals to isoprenaline. These results suggest that insulin itself can directly reduce beta-adrenoceptor sensitivity without altering receptor number.

Analysis of Variance↗
PubMed1994

Distribution and developmental pattern of neuromedin U expression in the rat gastrointestinal tract.

This study has quantified, for the first time, the relative levels of neuromedin U (NmU) mRNA in the rat gastrointestinal tract using Northern blot analysis. NmU message was detected in all regions of the gastrointestinal tract from the oesophagus to the rectum. The greatest levels were found in the duodenum and jejunum, the principal sites for absorption, which were 2.5- and 3-fold respectively above ileal levels. Quantification of NmU mRNA and peptide contents in the duodenum, jejunum and ileum during postnatal development of the rat showed message and peptide levels to be greater in the maturing rat than in neonates. Message levels in the duodenum, jejunum and ileum showed 14-, 7- and 4-fold increases respectively between 1 and 56 days after birth, whilst the corresponding peptide levels in the duodenum, jejunum and ileum showed 33-, 14- and 25-fold increases respectively. Food deprivation caused a small, but significant, decrease in message levels in the jejunum and colon, but there was no change in the duodenum or ileum. This shows that the presence of food has little effect on NmU mRNA levels in the gut.

Age Factors↗
PubMed1993

Nicotinic neuronal acetylcholine receptor alpha-3 subunit transcription in normal and myasthenic thymus.

Thymic transcription of the alpha-3 subunit of the AChR was studied through sequencing and PCR analysis of thymic cDNA clones, Northern blotting, and ribonuclease protection assays. This analysis revealed at least three, 3' end sequence variants for the alpha-3 subunit as well as a variant that results from the alternative splicing of an antisense 122 bp Alu sequence between exons 5 and 6 of the normal transcript. The spliced Alu sequence not only shifts the exon 6 reading frame but also carries an in-frame stop codon. If translated, this variant transcript would produce a truncated peptide lacking the fourth transmembrane domain of the subunit and carrying a carboxy terminus dodecapeptide not found in any other known AChR subunit sequence. The putative variant subunit may lack biological activity and should differ antigenically from its normal counterpart. In comparing the normal, the MG hypertrophic, and the MG thymoma for transcription of the alpha-3 subunit and its 122 bp variant, it was found that there were no qualitative or quantitative changes in alpha-3 transcript expression in the MG hypertrophic thymi. Thymomas, however, showed an overall decrease in alpha-3 transcription and a comparative increase in beta-amyloid precursor transcription. The decrease in the levels of alpha-3 transcription in thymomas may be related to the proliferation of thymic epithelial cells.

Amyloid beta-Protein Precursor↗
PubMed1993

Substrate-induced activation of dienelactone hydrolase: an enzyme with a naturally occurring Cys-His-Asp triad.

The Cys-His-Asp catalytic triad found in dienelactone hydrolase (DLH) is unusual for several reasons. It has not been observed in other hydrolytic enzymes and it is virtually inactive when it is produced by site-directed mutagenesis in the proteases. We propose a model to explain why this triad is catalytically active in DLH but not in the proteases. In the resting state of DLH, His202 forms an ion pair with Asp171 and Cys123 exists as a thiol. The resting state thiol does not interact with His202 in the active site but instead forms a hydrogen bond with Glu36 in the interior of the molecule. In the absence of substrate, Glu36 is also ion paired with Arg206. When substrate binds, Arg206 forms a second ion pair with the anionic substrate and the Arg206/Glu36 ion pair weakens. The destabilized Glu36 carboxylate shifts towards and deprotonates the Cys123 thiol, thereby activating the nucleophile. As the thiolate anion is not energetically favoured in the hydrophobic interior of the enzyme, it swings into the active site where it can be stabilized by the His202 imidazolium and the dipole of helix C. The Cys123 thiolate which now lies adjacent to the acyl carbon of the substrate, is thus generated only in the presence of substrate. The mode of thiolate activation reduces the susceptibility of DLH towards thiol alkylating agents.

Amino Acid Sequence↗