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Biomedical subjects

J E Kihlström

Publications and source records attributed to J E Kihlström.

At least 19 recordsLinked to original sources

A comparison of human lung, brain, CSF and plasma angiotensin-converting enzyme with regard to neuropeptide metabolism.

Human ACE obtained from different tissues and body fluids was assayed with regard to degradative action on tachykinins and various opioid peptides. Substance P (1-9) was easily cleaved, whereas substance P and neurokinin A seemed stable against ACE activity. However, endopeptidase-24.11 easily degraded both of these amidated peptides. When the same peptides were assayed as potential inhibitors of the hydrolysis of hippuryl-His-Leu (specific substrate for ACE activity), substance P and its (1-9) fragment were equally potent, whereas neurokinin A was inactive. The beta-casomorphins, beta-casein derived opioid peptides, with a proline residue at their C-terminus also showed inhibitory action on ACE activity, without being cleaved by the enzyme. These results indicate a modulatory action of these peptides. No differences between ACE originating from different tissues or body fluids could be demonstrated in this regard.

Amino Acid Sequence↗

ACE-inhibitor-induced enhancement of spontaneous and IgE-mediated histamine release from mast cells and basophilic leukocytes and the modulatory effect of capsaicin sensitive nerves.

Frequently reported adverse inflammatory skin and airway reactions have been reported in subjects being medicated with angiotensin converting enzyme (ACE)-inhibitors. Intradermally evoked wheal and flare reactions to ovalbumin, capsaicin and bradykinin, in ovalbumin sensitized guinea pigs, was previously demonstrated to be enhanced by pretreatment with the ACE-inhibitor MK 422 (the active parent diacid of enalapril). In vitro results from this study demonstrate that the ACE-inhibitor MK 422 degranulated guinea pig lung and skin mast cells as well as human basophils, and enhanced allergen-evoked histamine release. Local capsaicin pretreatment in vivo of guinea pig skin decreased spontaneous and allergen-triggered release of histamine in vitro from skin mast cells. No clear enhancing effect of MK 422 was seen on the allergen-triggered histamine release in vitro from capsaicin pretreated skin, and the spontaneous release was unaffected by the ACE-inhibitor. The allergen-triggered wheal and flare reaction in ovalbumin sensitized guinea pigs was potentiated by MK 422 and the late phase reaction of the inflammatory response was especially augmented. Capsaicin pretreatment of the guinea pigs abolished this late phase reaction as well as the inflammatory enhancing effect of MK 422. Our in vitro results from capsaicin pretreated skin indicate that the reduced inflammatory response in vivo in capsaicin pretreated skin is due not only to capsaicin induced depletion of neuropeptides from sensory nerves, but also to secondary degranulation of mast cells by one or more of these peptides.

Angiotensin-Converting Enzyme Inhibitors↗

Perinatal growth retardation caused by triethyl lead chloride treatment of mice during late gestation.

Female mice were injected intraperitoneally daily from day 18 of gestation and throughout lactation with triethyl lead chloride (TEL; 0.0, 0.5 and 1.0 mg/kg body wt). Off-spring of treated mothers displayed a slight perinatal growth retardation. Male off-spring appeared to be more sensitive to TEL, as indicated by their lower body weights. During the latter half of the lactation period the treated sucklings grew faster than controls, thereby compensating for their initially retarded growth, by the time of weaning. The hepatic cytochrome P-450 content of 9 to 10-day old sucklings of treated mothers was lower than in corresponding controls. We suggest that perinatal growth retardation is initiated by a disturbance in the uterus, e.g. reduced nutrient transport across the placenta.

Animals↗

Effects of a hexachlorinated biphenyl on lymphoid organs and resorption of foetuses in pregnant mice.

Syngeneically and allogeneically mated CBA mice were daily given orally either pure peanut oil or peanut oil containing 0.5 mg 2,2', 4,4', 5,5'-hexachlorobiphenyl (HCB) beginning at the day of implantation. The mice were dissected on day 12 and 18 of gestation when the weight of thymus, spleen, and liver were recorded. The spontaneous mitotic activity of spleen cells was evaluated in vitro, and the number of resorbed foetuses was recorded. Neither spleen weight nor thymus weight was altered, but the liver weight was significantly increased by HCB treatment. The spontaneous mitotic activity of spleen cells did not differ significantly between HCB-treated and control mice. The frequency of resorbed foetuses was not increased by HCB treatment either in syngeneically or allogeneically mated mice, but it was observed that mice fed HCB were less sensitive to environmental disturbance than control mice.

Animals↗

An improved technique for perfusion of the guinea pig placenta in situ giving viable conditions demonstrated by placental transport of amino acids (L- and D-alanine).

An improved technique for perfusing the fetal guinea pig placenta in situ is described. The result shows linear pressure-flow relations in the rane of 15-50 mm Hg. assumed to be physiological. The preparation shows impermeability for trypan blue. The placental transfer is stereoselective for L-alanine compared with D-alanine. This transfer is ouabain-sensitive, and proceeds against a concentration gradient.

Alanine↗

Distribution of an adenohypophysial constituent in the body. I. Wholebody autoradiographical studies in the mouse.

A peptide with a molecular weight of about 5 000 has previously been shown to affect the output of semen in frogs and probably also in mammals. This sperm-releasing substance is not part of any known gonadotropic hormone. The distribution of this substance has been investigated using whole-body autoradiography. Radioactive material is incorporated into the epididymis, the adenohypophysis and probably also into the ovary.

Animals↗

Distribution of an adenohypophysial constituent in the body. II. Quantitative tissue distribution in the rat.

A peptide with a molecular weight of about 5000 has previously been shown to affect the output of semen in frogs and probably also in mammals. This sperm-releasing substance is not part of any known gonadotropic hormone. The tissue distribution of this substance has been investigated. The iodinated substance has been injected into rats and the radioactivity content of the different tissues has been determined. Iodinated rat albumin has been injected into other rats, to determine the content of blood in the different tissues. A formula has been derived to obtain a figure for real accumulation, using the radioacitivity content of the blood and of the tissues after injection of the sperm-releasing substance and albumin, respectively. The sperm-releasing substance is incorporated into the adenohypophysis, neurohypophysis, liver, kidney, lung, ovary, uterus and some male sexual organs. The causes for this distribution are discussed.

Animals↗

Sexual functions of mice neonatally exposed to DDT or pcb.

Since DDT and PCB occur in milk, young animals may ingest these substances during the critical period of neonatal life; For this reason lactating mice were given injections of DDT or PCB, 50 mg/kg body weight, once a week for four weeks, the first injection being administered on the day of delivery. The reproductive capacity of their young was studied by measuring the frequency of implanted ova. When both the male and the female of a mating pair had been nursed by DDT- or PCB-treated mothers this frequency decreased from 94% in the controls to 79 and 75% respectively. No significant decrease were found when only one of the mated animals in the pair had been nursed by a treated mother.

Animals↗