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Biomedical subjects

A Koivuniemi

Publications and source records attributed to A Koivuniemi.

At least 19 recordsLinked to original sources

Identification of adenine nucleotide-containing metabolites of bisphosphonate drugs using ion-pair liquid chromatography-electrospray mass spectrometry.

Bisphosphonates are synthetic pyrophosphate analogues, which are used as therapeutic drugs for the treatment of metabolic bone disorders. Some of these bisphosphonates can be metabolised in cells into non-hydrolysable nucleotide analogues. In this paper, we describe an ion-pairing high-performance liquid chromatography method that is compatible with negative ion electrospray mass spectrometry for the separation of these metabolites. Tandem mass spectrometry and collision-induced dissociation (CID) were used for identification of the metabolites. The CID mass spectra of bisphosphonate-adenine nucleotide adducts are very informative, because major fragment ions are formed by cleavage of the bisphosphonate moiety from the conjugate. The method was used for detection of the nucleotide metabolites of clodronate, tiludronate and etidronate in extracts from mammalian cells after treatment with bisphosphonates.

Adenine Nucleotides↗

Degradation of the D1- and D2-proteins of photosystem II in higher plants is regulated by reversible phosphorylation.

The effects of protein phosphorylation and dephosphorylation upon high-light-induced degradation of the photosystem II reaction center proteins D1 and D2 have been studied in isolated thylakoid membranes and photosystem II core complexes. The rate of photoinactivation of photosystem II electron transport is not affected by thylakoid membrane phosphorylation. However, the degradation rate of the D1-protein in its phosphorylated form is drastically reduced under conditions which induce either acceptor- or donor-side photoinhibition of photosystem II. The degradation rate of the D2-protein is also reduced following protein phosphorylation. The stability of the phosphorylated D1-protein is further increased under conditions of reduced phosphatase activity, suggesting that phosphorylated and damaged D1-protein has to be dephosphorylated prior to proteolytic degradation. Our results expand on experiments performed in vivo, which suggest that following photoinhibition the controlled repair of damaged photosystem II centers requires not only proteolytic enzymes but also kinase and phosphatase activities. It is suggested that the phosphorylation of the D1- and D2-proteins allows tight coordination of the degradation of damaged proteins with insertion of new copies of proteins into photosystem II.

Adenosine Triphosphate↗

Reduced content of the quinone acceptor QA in photosystem II complexes isolated from thylakoid membranes after prolonged photoinhibition under anaerobic conditions.

The plastoquinone content of photosystem II complexes isolated from spinach photosystem II-enriched membranes subjected to strong photoinhibitory illumination under anaerobic conditions was determined by HPLC. A pronounced decrease of the plastoquinone content was found in the photoinactivated complexes. These results corroborate earlier models in which photoinhibitory illumination is suggested to eventually lead to release of doubly reduced and protonated QA from its site on the D2-protein.

Binding Sites↗

Reversible and irreversible intermediates during photoinhibition of photosystem II: stable reduced QA species promote chlorophyll triplet formation.

Photoinhibition of photosynthesis was studied in isolated photosystem II membranes by using chlorophyll fluorescence and electron paramagnetic resonance (EPR) spectroscopy combined with protein analysis. Under anaerobic conditions four sequentially intermediate steps in the photoinhibitory process were identified and characterized. These intermediates show high dark chlorophyll fluorescence (Foi) with typical decay kinetics (fast, semistable, stable, and nondecaying). The fast-decaying state has no bound QB but possesses a single reduced QA species with a 30-s decay half-time in the dark (QB, second quinone acceptor; QA, first quinone acceptor). In the semistable state, Q-A is stabilized for 2-3 min, most likely by protonation, and gives rise to the Q-A Fe2+ EPR signal in the dark. In the stable state, QA has become double reduced and is stabilized for 0.5-2 hr by protonation and a protein conformational change. The final, nondecaying state is likely to represent centers where QA H2 has left its binding site. The first three photoinhibitory states are reversible in the dark through reestablishment of QA to QB electron transfer. Significantly, illumination at 4 K of anaerobically photoinhibited centers trapped in all but the fast state gives rise to a spinpolarized triplet EPR signal from chlorophyll P680 (primary electron donor). When oxygen is introduced during anaerobic illumination, the light-inducible chlorophyll triplet is lost concomitant with induction of D1 protein degradation. The results are integrated into a model for the photoinhibitory process involving initial loss of bound QB followed by stable reduction and subsequent loss of QA facilitating chlorophyll P680 triplet formation. This in turn mediates light-induced formation of highly reactive and damaging singlet oxygen.

Journal Article↗

Small light-harvesting antenna does not protect from photoinhibition.

High-light-induced decrease in photosystem II (PSII) electron transfer activity was studied in high- and low-light-grown pumpkin (Cucurbita pepo L.) plants in vivo and in vitro. The PSII light-harvesting antenna of the low-light leaves was estimated to be twice as big as that of the high-light leaves. The low-light leaves were more susceptible to photoinhibition in vivo. However, thylakoids isolated from these two plant materials were equally sensitive to photoinhibition when illuminated in the absence of external electron acceptors. Only the intensity of the photoinhibitory light and the chlorophyll concentration of the sample, not the size of the light-harvesting antenna, determined the rate of PSII photoinhibition in vitro. Because excitation of the reaction center and not only the antenna chlorophylls is a prerequisite for photoinhibition of PSII activity, independence of photoinhibition on antenna size provides support for the hypothesis (Schatz EH, Brock H, Holzwarth AR [1988] Biophys J 54: 397-405) that the excitations of the antenna chlorophylls are in equilibrium with the excitations of the reaction centers. Better tolerance of the high-light leaves in vivo was due to a more active repair process and more powerful protective mechanisms, including photosynthesis. Apparently, some protective mechanism of the high-light-grown plants is at least partially active at low temperature. The protective mechanisms do not appear to function in vitro.

Journal Article↗

Primary small cell cancer of the bladder. Report of a case and review of literature.

We report a case of a primary small cell cancer of the bladder with characteristic cytological, histological, histochemical, and ultrastructural features. The patient refused radical surgery and the tumour was treated by external radiation and chemotherapy. The residual tumour was electroresected transurethrally. After 15 months' follow-up a recurrent tumour was resected, but metastases were not found. Aggressive surgery as well as early institution of radiotherapy or chemotherapy are needed because of the aggressive nature of the tumour.

Aged↗

Interferon-mediated in vivo induction of beta 2-microglobulin on small-cell lung cancers and mid-gut carcinoids.

Selected neuroendocrine tumors, such as small cell lung cancer (SCLC), and neuroblastoma express markedly diminished class I major histocompatibility complex (MHC) antigens (HLA framework and beta 2-microglobulin, beta 2m). Another neuroendocrine tumor, mid-gut carcinoid, also expresses reduced beta 2m antigen as demonstrated herein. Antigen expression is greatly enhanced on SCLC cell lines by in vitro exposure to interferon (IFN). To determine whether IFN mediates similar effects in vivo, we examined by immunoperoxidase staining beta 2m expression in paraffin-embedded tumor tissue sections obtained from 4 SCLC and 7 mid-gut carcinoid patients before and after receiving partially purified human leukocyte IFN-alpha therapy. Before IFN treatment, 3/4 SCLC tumors and 5/7 mid-gut carcinoids did not express beta 2m. By contrast, all tumors showed considerable expression of beta 2m after IFN therapy. Induction of class I antigens on tumor cells deficient in such expression may be one mechanism by which IFN exerts antitumor effects. We believe this is the first report of in vivo induction of class I MHC antigens in epithelial tumor cells in humans.

Carcinoid Tumor↗

Vitrectomy. Clinical data and cytologic findings of vitrectomy specimens.

Fifty vitreous specimens obtained by routine pars plana vitrectomies were examined using Millipore filter processing and Papanicolaou staining technique. Cytological findings comprised of macrophages (melanophages, siderophages) and inflammatory cells, mainly lymphocytes. In a few cases, pigmented an nonpigmented epithelial cells of the ciliary body were encountered, retinal sensory cells only in one case. Fibroblasts and fragments of granulation tissue occurred in four of the 14 diabetic cases, in four of the 21 posttraumatic cases, in one case of chronic uveitis as well as in one case of retrolental fibroplasia. Fragments of ciliary body were in three specimens from injured eyes. In one case of chronic uveitis slight suspicion of ciliary body melanoma was aroused on the basis of distinct cellular atypia. There was agreement between clinical and cytological diagnosis in most cases, but particularly in posttraumatic and inflammatory diseases cytologic examination offered new diagnostic data. This is a new method of microscopical verification of the condition in the vitreous body in various diseases. Our experiences are preliminary but we feel that this method has proven its availability.

Diabetic Retinopathy↗

Peroperative fine needle aspiration biopsy of lung tumors.

The feasibility and reliability of peroperative fine needle aspiration biopsy of lung tumors were studied in a series of 54 patients. The postoperative histologic examination confirmed that 47 of the lesions were malignant. The cytologic examination also showed malignancy in 45 of these cases. The accuracy of fine needle cytology thus was 96%. In the two false negative reports the classification was Papanicolaou grades II and III. The cytologic classification of the histologically benign lesions was only grades I or II. Thus there were no false positive cytologic results. No complications arose from the needle biopsies. Peroperative fine needle aspiration biopsy at thoracotomy is rapid, simple and safe, and has a high degree of accuracy. It is diagnostically useful in cases without preoperative confirmation of suspected lung tumor if excisional biopsy is judged to be hazardous or unlikely to yield a definite diagnosis. The method permits the surgeon to assess the extent of a malignancy and can specify the cell type of the tumor.

Adult↗

Fine-needle aspiration biopsy in the diagnosis of orbital tumours.

Fine-needle aspiration biopsy was used for the diagnosis of 25 consecutive patients with orbital tumours. CT scan was used to locate the lesion accurately. In two cases of orbital sarcoma and three out of four cases of orbital meningeoma, pre-operative fine-needle biopsy provided the correct diagnosis for proper operative treatment. Post-operative histopathological examination of the tumours proved that the cytological diagnoses had been correct. Two cases were diagnosed as metastatic carcinomas, 4 as malignant lymphomas and 11 as chronic inflammatory lesions. Orbitotomies were performed in 3 cases only, and the cases were managed accordingly with radiation, chemotherapy or corticosteroids. With conservative treatment the results varied from arrest of the condition to total disappearance of the lesion. No complications were encountered as a result of orbital fine-needle biopsies. The procedure is simple, requiring only topical anaesthesia and if proper cytological service is available, invaluable diagnostic information is provided for proper clinical management. It can also be used if recurrence of orbital tumour is suspected and a new mass is seen by CT scan. The method may save the patient from unnecessary exploratory orbital surgery.

Adolescent↗

The effect of oral neomycin on the absorption of isoniazid, quinidine and sulphafurazole from the rat small intestine in situ.

The effect of oral neomycin (2 g/kg for 4 or 7 days) on drug absorption from the small intestine was studied in anaesthetized rats in situ. Neomycin did not greatly affect the small intestinal morphology. Only in some cases there were slightly edematous and low villi in the intestines of the rats treated for 7 days, and there was "nuclear debris" in the mucosal cells as a sign of neomycin toxicity. Neomycin did not modify isoniazid or quinidine absorption, nor did it have any effects on intestinal fluid absorption. Sulphafurazole absorption was retarded, but the change was significant only after a 7-day neomycin treatment. The mechanisms of neomycin-induced changes in absorption still remain largely speculative, but the findings support the concept of the rat being fairly resistant to oral neomycin with respect to eventual malabsorption.

Animals↗

Granulocytic sarcoma (chloroma) of the cerebellum and meninges a case report.

A 7-year-old boy, having had headache and vomiting for one month, was operated for a tumour in the left side of the posterior fossa. The tumour, weighing 52 g, infiltrated the dura mater, leptomeninges, and also, superficially, the left cerebellar hemisphere. The patient died five weeks after operation. Light and electron microscopical examination revealed a granulocytic sarcoma (chloroma). Pre- and postoperative blood examinations, together with postoperative and autopsy bone marrow examinations, showed no sign of acute myelogenous leukaemia. This is the second reported case of primary intracranial chloroma with no preceding sign of acute myelogenous leukemia, and the first case with cerebellar infiltration.

Cerebellar Neoplasms↗

Effect of colchicine on drug absorption from the rat small intestine in situ and in vitro.

The effect of colchicine (1 mg/kg intraperitoneally on two successive days) on the absorption of isoniazid, quinidine and sulphafurazole (sulfisoxazole) from the rat small intestine was studied in situ and in vitro. Colchicine produced two different types of histological damage in the small intestine, one with degenerative and the other with regenerative changes predominating. The small intestinal surface area was variably reduced. The colchicine-treated rats were lethargic and hypothermic as compared to controls. Colchicine retarded the disappearance of fluid and all three drugs from the small intestinal lumen in situ 2 days after the first colchicine injection. In vitro the total amounts of fluid and drugs passed through the intestinal wall were not significantly changed by colchicine, although there was a slight tendency towards an increased absorption of quinidine. Hence, colchicine as an antimitotic drug decreases drug absorption from the rat small intestine in situ, apparently due to the decreased surface area of the small intestine, the decreased water flux through the intestinal wall, the retarded intestinal motility and hypothermia of the rats. In vitro the changes are small, which makes the in vitro tests less suitable for studying the effect of colchicine on absorption.

Animals↗

Carcinoma arising in a mesenteric cyst.

A report is presented in which a mesenteric cyst underwent a malignant change. A survey of the origin, symptoms, and treatment of mesenteric cysts is also included. The histologic picture of the case is described, the origin of the cyst discussed, and a comparison made with the two similar cases reported in the literature.

Abdominal Neoplasms↗