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Biomedical subjects

R Kaul

Publications and source records attributed to R Kaul.

At least 127 records · Page 7Linked to original sources

Dissociation between apparent volumes of distribution for inulin and sodium by salt adaptation in ducks.

In domestic ducks acclimated to 2% saltwater (SW ducks), chronic elevations of plasma osmolality and sodium concentration, and of the circulating levels of antidiuretic hormone and angiotensin II indicate a trend towards dehydration when compared to ducks maintained on freshwater (FW ducks). Under steady state conditions of salt and water balance, with prevailing antidiuresis and no salt gland secretion, the apparent volumes of distribution of 22Na and of radiolabeled inulin were calculated after single injections of the tracers. The sodium spaces as percent body mass of FW ducks (33.3 +/- 0.9) and SW ducks (31.5 +/- 0.5) were not different, but apparent volumes for inulin distribution differed significantly between FW ducks (31.2 +/- 0.7) and SW ducks (24.8 +/- 0.7). Plasma volumes and rates of inulin disappearance from the plasma during both the non-uniform and uniform phases of tracer distribution were closely similar in FW and SW ducks and support the hypothesis that the difference between apparent volumes of inulin distribution reflects a difference in extracellular fluid volume which was estimated as 20.9% in FW ducks and 17.2% in SW ducks. For SW ducks the difference between inulin and sodium spaces was significantly greater than for FW ducks. In relation to the extracellular fluid compartment SW ducks have a larger pool of non-extracellular exchangeable sodium.

Acclimatization↗

Cloning, expression, and primary structure of a Chlamydia trachomatis binding protein.

The gene encoding an 18,000-dalton eucaryotic cell-binding protein of Chlamydia trachomatis serovar L2 was cloned into Escherichia coli, and the nucleotide sequence of a 1,658-base-pair PstI restriction endonuclease fragment encoding this protein was determined. The recombinant chlamydial gene consists of a 486-base-pair open reading frame encoding a polypeptide of molecular weight 18,314. The resultant polypeptide, comprising 162 amino acids, possesses a highly charged carboxy-terminal end. The expression of this recombinant protein is under the control of a vector promoter. The recombinant 18,000-dalton protein possessed the same eucaryotic cell-binding characteristics as did the native chlamydial 18,000-dalton protein when electrophoresed and transferred to nitrocellulose. Polyclonal antibodies to the recombinant protein exhibited neutralizing activity.

Amino Acid Sequence↗

Thermoregulation and diurnal rhythms in 1-week-old rat pups.

This paper reviews the ontogeny of thermoregulation and diurnal rhythmicity in rats. Additionally, original data are presented that indicate the emergence of an endogenous circadian core temperature rhythm during the first postnatal week. Despite neurological immaturity, newborn rats display autonomic and behavioral thermoregulatory responses within 24 h of birth. Their "biological clock" is already running before birth. The thermal environment of pups changes cyclically owing to diurnal variations in maternal behavior, but the core temperatures of 1-week-old pups huddling in the absence of the dam also show marked diurnal fluctuations. Five- to 8-day-old lean Zucker rat pups artificially reared in the absence of 24-h cycles of ambient temperature and food intake show diurnal changes in core temperature similar to those in huddling mother-reared pups. Diurnal core temperature changes, evident only when regulatory effectors are not overwhelmed, are one of the first self-maintained diurnal rhythms to appear. Because thermoregulation and circadian rhythmicity both appear before maturation of the neural networks believed to be critical for their control in adult animals, studying the immature rat might increase our understanding of the control of these processes in the more complex mature central nervous system.

Aging↗

Cold-rearing normalizes capacity for norepinephrine-stimulated thermogenesis but not body temperature in 16-day-old fatty Zucker rats.

The effects of a lowered rearing temperature on body weight, core temperature (Tc) and norepinephrine(NE)-stimulated thermogenesis were investigated in 16- to 17-day-old Zucker rat pups. 16-day-old fatty pups were significantly heavier (9%) than lean littermates in litters reared at 18 degrees C ("cold-reared") but not in litters reared at 25 degrees C ("normally-reared"). After 2 h isolation at 25 degrees C, Tc of lean pups was slightly higher (37.1 degrees C) in cold-reared litters than in normally-reared litters (36.4 degrees C), while fatty pups reared at either temperature were severely hypothermic (Tc = 33 - 34 degrees C). At an ambient temperature of 25 degrees C Tc in fatty and lean cold-reared pups increased to 39.5 degrees C after subcutaneous injection of 800 micrograms/kg NE. Normally-reared lean pups reached the same peak Tc after NE injection, while their fatty littermates reached a significantly lower peak Tc of 38.4 degrees C. The hypothermia associated with the onset of excess fat deposition in suckling fatty Zucker rats is not caused by a reduced capacity for NE-stimulated thermogenesis.

Adipose Tissue, Brown↗

Cyclic AMP inhibits developmental regulation of Chlamydia trachomatis.

The effect of cyclic AMP (cAMP) on the chlamydial growth cycle was studied with Chlamydia trachomatis-infected HeLa cells. At concentrations of 1 mM, cAMP had a profound effect on the chlamydial developmental cycle, resulting in small, immature inclusions. Immunoblot analysis revealed the absence of elementary body (EB)-specific antigens in the cAMP-treated cells. This effect was observed only if cAMP was added within the first 12 h of incubation and continued thereafter. Its withdrawal at any time from the medium led to the reappearance of fully mature, infectious organisms. Analogs or breakdown products of cAMP exerted no inhibitory effect on chlamydial development. Intracellular inclusions from the cAMP-treated cells were unable to infect fresh HeLa monolayers, in contrast to the completely infectious nontreated inclusions. Protein profiles of the cAMP-treated organisms (at any time point) resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis very closely resembled reticulate bodies (RB) and did not possess characteristic EB-binding proteins. Collectively, these observations suggest an inhibitory role for cAMP at the RB stage of intracellular development. We also identified a cAMP receptor protein which is associated with RB and not with EB, further supporting a role for this system in the developmental regulation of chlamydiae.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Arginine vasotocin and glomerular filtration rate in saltwater-acclimated ducks.

We examined the relationship between whole kidney glomerular filtration rate (GRF) and the plasma concentration of immunoreactive arginine vasotocin (AVT), the avian antidiuretic hormone, in saltwater-acclimated ducks. During steady-state diuresis, driven by infusion of sodium chloride solutions, transient reductions of [14C]inulin clearance (3 ml X min-1 X kg-1) occurred when plasma AVT concentrations were roughly doubled by systemic injection of synthetic AVT or after stimulation of endogenous AVT release by perfusion of the third ventricle with hypertonic artificial cerebrospinal fluid (CSF). Transient increases in GFR occurred when plasma AVT was reduced during inhibition of its endogenous release by hypotonic ventricle perfusion. GFR also increased after injection of AVT antiserum but returned to control values within 30 min, while plasma AVT concentration remained very low for at least 1 day. During antidiuresis evoked by infusion of strongly hypertonic saline, GFR values estimated from plasma disappearance curves of [125I]iothalamate were not different from the GFR values estimated subsequently with the same method in the same ducks made diuretic by hypotonic saline infusions, although AVT concentrations were depressed during the latter as compared with the former infusion. Factors other than AVT must be important for the control of GFR during sustained osmotic stress.

Adaptation, Physiological↗

Maturation of thermoregulation in Zucker rats.

We compared the development of thermoregulatory abilities of fatty (fa/fa) and lean (Fa/-) Zucker rats as they grew from two weeks to eight months of age. The rectal temperature of lightly restrained littermates was continuously recorded for 2-6 h, and at ages before body weights of fatty and lean pups became significantly different, oxygen consumption was simultaneously measured. At the rearing temperature of 25 degrees C, hypothermia with a 30 percent lower oxygen consumption was apparent in fatty pups at 16 but not at 24 days. At 5 degrees C on day 25 fatty pups became hypothermic with a metabolic rate only 10-15 percent lower than lean pups. Three-month old fatty and lean rats defended the same core temperature not only at 25 degrees C, but even during 6 h without food at 5 degrees C. The core temperature of 5-8 month old fatty rats fell slightly but significantly below that of lean rats only during the sixth hour at 25 degrees C, but not during 6 h at 5 degrees C. If the capacity for thermogenesis in brown adipose tissue of fatty rats is less than in lean rats, its decreased contribution to cold defense must be completely made up in 25 degrees C-acclimated adults by more insulation and/or shivering.

Aging↗

[Isolation and identification of metabolites of 5-ethyl-2'-deoxyuridine from rat urine].

The metabolites of 5-ethyl-2'-deoxyuridine (Aedurid) have been isolated and purified from rat urine by preparative thin-layer and column chromatography. With the aid of 1H-NMR and mass spectroscopy and by comparison with an authentic sample, the major metabolite could be identified as 5-(1-hydroxyethyl)uracil. The minor metabolite was identified as 5-ethyluracil.

Animals↗

[Pharmacokinetics of 5-ethyl-2'-desoxyuridine in the rat].

The pharmacokinetic behaviour of the virostatic drug 5-ethyl-2'-deoxyuridine (EtUdR, Aedurid) and its metabolite 5-ethyluracil was determined after intravenous and oral application in a nonindividual study using inbred rats. EtUdR is metabolized and eliminated rapidly. The saturation of the metabolic pathway could not be achieved. Higher initial blood levels resulted from a pretreatment of rats with probenecid or the application of the better water-soluble compound 5-ethyl-2'-deoxyuridine-5'-monophosphate; the elimination characteristic of EtUdR could not be altered by these methods.

Animals↗

Combined modality therapy for Stage IIIMO non-small cell lung cancer. A five-year experience.

Between 1975 and 1980, 101 patients with inoperable Stage IIIMO non-small cell lung carcinoma were entered into combined radiotherapy and chemotherapy trials at Michael Reese Hospital and University of Chicago Hospital. Sixty-four percent of the patients responded. Median survival for all patients was 8.8 months. Responders survived 13.7 months and nonresponders 4.6 months (P = 0.002). Patients treated with 4200 rad had a higher response rate than those treated with 3000 rad (74% versus 54%, P = 0.04) but there was no difference in survival. Although all patients with squamous cell carcinoma died by 30 months, 18% of patients with adenocarcinoma and 20% of patients with large cell carcinoma are long-term survivors. Brain metastases occurred more frequently in patients with large cell or adenocarcinoma than in patients with squamous cell carcinoma (P = 0.02). The prognostic effect of age, initial performance status, sex, histology, and tumor extent are examined. Toxicity was substantial with a 13% treatment-related mortality. Combined modality therapy may benefit selected patients with non-squamous cell types, but more effective chemotherapeutic agents are needed. Prophylactic cranial irradiation in patients with large cell carcinoma or adenocarcinoma may decrease the incidence of subsequent brain metastases.

Adenocarcinoma↗

Body temperature of huddling newborn Zucker rats.

Daily mean core temperature (Tc) in huddling Zucker rat pups reared at 25 degrees C revealed the onset of a significantly lower Tc in fa/fa pups on day 6. The difference between any pup's Tc and the mean Tc of that half of the litter with the highest Tc on any given day was an early marker for genotype. Calculating the mean difference for any 2 consecutive days from day 6 onwards gave values for each fa/fa pup that were outside the 99% confidence limits for the individual observations in the Fa/- pups.

Animals↗

Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment.

Hemophilia B or Christmas disease is an X-linked condition caused by absent or reduced levels of functional coagulation factor IX. Based upon the peptide sequence of bovine factor IX, we synthesized a 17-base pair oligonucleotide probe to screen a human liver cDNA library. A recombinant clone was identified with a 917-nucleotide insert whose sequence corresponds to 70% of the coding region of human factor IX. This factor IX cDNA was used to probe restriction endonuclease digested human DNA to identify a Taq I polymorphism associated with the genomic factor IX gene as well as to verify that there is a single copy of this gene per haploid genome. The factor IX cDNA was also used to map the locus for factor IX to a region from Xq26 to Xqter. The cloning of human factor IX cDNA and identification of a Taq I polymorphism and its regional localization will provide a means to study the molecular genetics of hemophilia B and permit linkage analysis with nearby loci.

Amino Acid Sequence↗