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Biomedical subjects

B Wiklund

Publications and source records attributed to B Wiklund.

At least 19 recordsLinked to original sources

Patients with atherosclerosis may have increased circulating levels of 27-hydroxycholesterol and cholestenoic acid.

Extrahepatic sterol 27-hydroxylase (CYP27) appears to have a role in the elimination of excess cholesterol from various cells, particularly macrophages, and there is a net flux of 27-hydroxyycholesterol and its metabolites from different extrahepatic sources to the liver. In this study we tested the hypothesis that patients with advanced atherosclerosis may have higher levels of 27-oxygenated products in the circulation than control subjects. Concordant with previous studies, a strong correlation was observed between circulating levels of 27-hydroxycholesterol and cholesterol, in both healthy subjects and subjects with hypercholesterolemia and documented atherosclerosis. A group of male subjects with normal or only slightly elevated serum cholesterol and rapidly progressing carotid atherosclerosis (n = 20) had serum levels of 27-oxygenated cholesterol not statistically different from those of a matched group of subjects with little or no development of atherosclerosis (n = 20). The situation was similar in a group of patients (n = 20) with advanced general atherosclerosis associated with severe clinical symptoms. Among the two groups of patients with atherosclerosis, a few patients had relatively high levels of 27-oxygenated products. Among the healthy controls, two healthy volunteers (brother and sister) were found to have high levels of 27-hydroxycholesterol, most probably due to genetic reasons. The possibility is discussed that the high levels of 27-oxygenated products in the circulation of a few patients with atherosclerosis may be related to high amounts of active macrophages present in atherosclerotic lesions. In view of the number of factors that could affect the levels in the circulation, other explanations cannot be ruled out. At the present state of knowledge, measurements of circulating levels of 27-oxygenated metabolites do not seem to add useful information about the atherosclerotic process.

Arteriosclerosis↗

[Blood lipid derangement common in peripheral artery disease. Lipid-lowering agents may alleviate symptoms and slow the atherosclerotic process].

In the new guidelines from the Swedish Medical Products Agency, an aggressive approach is recommended for the treatment of hyperlipidemia in all patients with manifest atherosclerotic disease. Patients with intermittent claudication should therefore receive lipid-lowering treatment on the same indications as patients with coronary artery disease. The present article reviews our knowledge of hyperlipidemia as a risk factor for the development of peripheral artery disease. Hyperlipidemia is frequently found in these patients and the most common lipid derangements are low levels of HDL-cholesterol and hypertriglyceridemia. Hard end-point data concerning morbidity and mortality during lipid-lowering treatment in this specific population is largely lacking, although previous studies indicate that lipid-lowering treatment slows the atherosclerotic process and induces pain relief.

Adult↗

Note on a method for individual recognition in feed pecking in free running groups of hens.

A system for automatic registration and individual recognition of feed pecking (activity and quantity) in groups of free running hens was tested. A PIT (Passive Integrated Transponder)-tag system was used to separate and register individuals when they were feeding. An electronic balance system placed under the feeder registered the amount eaten by each individual on a PC. A test with two different feed stuffs; oat and wheat was performed on three hens during a total of 6 weeks.

Journal Article↗

Elimination of cholesterol as cholestenoic acid in human lung by sterol 27-hydroxylase: evidence that most of this steroid in the circulation is of pulmonary origin.

Human alveolar macrophages have exceptionally high capacity to convert cholesterol into 27-hydroxycholesterol and cholestenoic acid by the sterol 27-hydroxylase mechanism. It is shown here that the human lung has a higher content of 27-hydroxycholesterol relative to cholesterol than any other organ. In order to evaluate the importance of the sterol 27-hydroxylase mechanism for cholesterol homeostasis in the lung, the production of cholestenoic acid by human lung was investigated. Removal of one lung reduced the level of cholestenoic acid in the circulation by 48 +/- 4% (P < 0.005). The levels of cholestenoic acid in the pulmonary artery and in the pulmonary vein showed significant differences (P < 0.002) with higher levels in the pulmonary vein (108 +/- 16 and 104 +/- 16 ng/mL, respectively). This corresponds to a net flux of cholestenoic acid from the lung of about 14 mg/day, which is more than 80% of the reported removal of this oxysterol and its metabolites from the circulation by the liver per day. Bypassing the lung for 60 min led to a reduction in circulating cholestenoic acid (30%) that fits with a pulmonary origin when taking into account the half-life of cholestenoic acid. The level of circulating cholestenoic acid was found to be less in patients with different lung diseases. It is evident that most of the cholestenoic acid in the circulation is of pulmonary origin. The present results suggest that the sterol 27-hydroxylase in the lung is responsible for at least half of the total flux of 27-oxygenated cholesterol metabolites to the liver and that this enzyme system may be of importance for cholesterol homeostasis in the lung.

Cardiopulmonary Bypass↗

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans.

BACKGROUND: Ketamine in sub-dissociative doses has been shown to have analgesic effects in various pain conditions, including neuropathic and phantom-limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood. METHODS: Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS). RESULTS: Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all the patients at the highest dose (0.45 mg/kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. These 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/kg ketamine doses than for morphine 10 mg. CONCLUSION: We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.

Aged↗

Epitope specificity of 30 monoclonal antibodies against cytokeratin antigens: the ISOBM TD5-1 Workshop.

The epitope specificities of 30 monoclonal antibodies (MAbs) against the most common human cytokeratins. i.e., Nos. 8, 18, and 19, in epithelial cells were investigated in the ISOBM TD-5 Workshop. Seven research groups from universities or companies participated independently in the evaluation of the antibody specificities. The complex assembly of cytokeratins in vivo, with obligatory heterologous dimeric combinations of different cytokeratins from each of the two major groups, comprising together more than 20 different individual cytokeratins, made analysis of the antibody reactivity patterns with isolated single cytokeratins necessary. The concordance of the evaluations was striking and independent of the technologies used. As antigens purified individual cytokeratins, chemically degraded purified cytokeratins, recombinant intact and truncated cytokeratins, as well as specific synthesized shorter peptides were used. In order to elucidate the epitope specificity, reactivity patterns in ELISA assays and immunoblots with partial enzymatic degradation of the antigens were performed. Competitive cross-inhibition experiments between antibodies using antigens and antibodies in all possible combinations were performed with radioimmunometric assays, BIAcore, and ELISA technology. All 30 antibodies could convincingly be classified with regard to target cytokeratin. One MAb (192) had to be deleted due to dual specificities in both isotype and epitope specificity against its target. Six antibodies bound selectively to cytokeratin 8, 14 to cytokeratin 18, and 10 to cytokeratin 19, as demonstrated by using native, recombinant, and synthesized antigens. The immunodominant part of the molecule for all three types of cytokeratins was located in the region of amino acid (aa) 270-400. Out of the six MAbs reactive with cytokeratin 8, four MAbs, i.e., 178, 199, 202, and 206, were reactive with a sequence in the interval aa 340-365, and MAb 191 reacted with a closely related epitope. The remaining antibody, 192, presented dual specificities. At least two closely related major immunogenic epitopes could be identified in cytokeratin 8. In cytokeratin 18 four distinct epitopes could be documented, again with the dominating sequence region 270-429 as target for 10 (181, 184, 186, 188, 189, 190, 193, 196, 198, and 200) out of 14 antibodies. Since MAb 193 is known to react with the M3 epitope, aa 322-342 in cytokeratin 18, this entire group is reactive in the region close to the charge shift, in the middle of the rod 2B region, as shown by competitive binding. The remaining four anticytokeratin 18 antibodies (180, 185, 203, and 205) displayed unique, noncompetitive binding to this filament. Cytokeratin 19, reactive with altogether ten antibodies, displayed two major epitopes, all of them also within the large immunodominant region. MAbs 179, 195, 197, and 204 were reactive with the peptides aa 311-335 also known as the KS 19.1 epitope, and MAbs 182, 183, 187, 194, and 201 bound to peptide aa 346-367, known as the BM 19.21 epitope. One antibody, 231, was selectively reactive with aa 356-370 in cytokeratin 19. A complex pattern of binding specificities comprising at least ten different, noncompetitive epitopes, mainly situated in the rod portion, 2A and 2B, situated close to the charge shift in the rod of all three cytokeratins was documented. Out of the 29 classifiable antibodies, altogether 22 were reactive in this very short region, i.e., from aa 311 to 370 in all cytokeratin filaments. The remaining seven antibodies displayed unique binding properties. The implications of the findings are of significance both for immunohistochemistry and for assaying circulating heterodimeric, partially degraded complexes in patients' blood for tumor marker evaluation.

Amino Acid Sequence↗

Secondary aortoenteric fistulae--changes from 1973 to 1993.

AIM: To investigate a series of patients with secondary aortoenteric fistulas and compare it with a previous series (1985-93 vs. 1973-84). DESIGN: Retrospective study of medical records. SETTING: Sixteen vascular surgical centers in Sweden. PATIENTS: Twenty-seven patients were identified making an overall incidence of 0.5% of all aortoiliac operations. Among aneurysm patients the incidence was significantly lower than in the previous series. One patient record could not be identified. Fourteen primary operations were for aortic aneurysm, 12 for occlusive disease and one was an aortorenal vein bypass. RESULTS: Symptoms of the fistula occurred after a median interval of 90 months which is significantly later than the previous series (32 months; p<0.05). The commonest presentation was bleeding followed by septis. The median diagnostic delay was 10.5 days, which was significantly shorter than in the previous series. Most fistulas involved the duodenum (88%). One patient died before surgery. The postoperative mortality was 28%, significantly lower than in the previous series (58%) (p<0.05). At the end of follow up (median 43 months) significantly more patients were alive than in the previous series (42% vs 18%) (p<0.05). CONCLUSION: Over a 21 year period there seems to have been a decrease in the frequency of secondary aortoenteric fistulas after aneurysm surgery, a longer interval before they occur, a shorter diagnostic delay, and a better survival.

Aorta, Abdominal↗

A novel IRMA and ELISA for quantifying cytokeratin 8 and 18 fragments in the sera of healthy individuals and cancer patients.

Cytokeratins 8 and 18 are most frequently co-expressed in simple epithelia and carcinomas. Fragments of these cytokeratins are released into the systemic circulation where they can be quantified and utilized as tumour markers. The present paper reports on a solid-phase sandwich monoclonal immunoassay, considered "epithelial tissue-specific", which recognizes fragments of human cytokeratins 8 and 18 of different sizes (10-50 kD). The evaluated ELISA and IRMA assays exhibited a detection limit of 0.1 microgram 1-1 and characteristically demonstrated a within-assay coefficient of variation (CV) of 1-4% and a between-assay CV of 3-5%. The long-term (300 days) repeatability of lyophilized samples tested in the assay was estimated to have a less than 10% CV. Of apparently healthy individuals, 95% were found to have serum concentrations of less than 0.95 micrograms 1-1. A highly significant difference was found between apparently healthy individuals and pancreatic cancer patients. Patients with metastatic disease showed a sensitivity of 93% and those with local disease 83%, at 95% specificity. This TPAcyk assay revealed good correlation (0.98) with the TPS assay detecting the specific M3 epitope of the tissue polypeptide antigen. The correlation with the long established polyclonal assay of tissue polypeptide antigen (TPA) was estimated to be 0.9.

Animals↗

Evaluation of a new tumor marker for cytokeratin 8 and 18 fragments in healthy individuals and prostate cancer patients.

The serological results from apparently healthy individuals and prostate cancer patients were evaluated with a new assay called TPAcyk ELISA. This assay has a biochemical specificity for fragments of cytokeratins 8 and 18, and exhibits a low within- and between-assay imprecision. The data indicate a significant difference between the results of males and females, but no significant age-dependent relation was found. The cut-off value (95% specificity) for healthy individuals was estimated to be 1.27 ng/mL (n = 190) for males and 0.95 ng/mL (n = 81) for females. When using a cut-off value of 1.27 ng/mL, we found a sensitivity for prostate cancer patients with T2-3 N0M0 of about 20%. For patients with metastatic disease, a sensitivity of 75% was found. A higher sensitivity was obtained with patient sera analyzed with PSA than with TPAcyk, particularly in patients with early stages of the disease. We conclude that the results from this new TPAcyk assay were significantly elevated in patients initially diagnosed with poorly differentiated tumors, that patients with localized tumors exhibited low concentrations, and that patients with metastatic disease showed, on average, 8 times higher concentrations than patients with localized disease. The combination of the TPAcyk and PSA results increased the sensitivity for prostate cancer, particularly in patients with metastatic disease.

Adult↗

Immunotargeting with monoclonal cytokeratin 8 antibodies of human urothelial cancer transplanted to nude mice.

The possibility of using cytokeratin antibodies for the radioimmunolocalization of urinary bladder cancer was studied. A monoclonal murine IgG antibody was raised against cytokeratin 8 and labelled with iodine-125; normal murine IgG was used for control purposes. The urothelial cancer cell line RT4 was transplanted into immunodeficient nude mice. The anti-cytokeratin 8 antibody was administered intraperitoneally and its uptake in the tumour and other organs was analyzed with a computerized gamma camera. Optimal scintigraphic visualization occurred 11 days after antibody administration. The tumour/blood ratio of the specific antibody was 5.64 (+/- 5.01 SD) on day 11, compared with 0.73 (+/- 0.35 SD) in the control. Autoradiography demonstrated antibody uptake preferentially in viable sections of the tumour. The antibody uptake is presumed to be the result mainly of binding to the released cytokeratin in and around cells lysed during natural cellular death. The monoclonal murine anti-cytokeratin antibody is of potential interest in studies aimed at improving the clinical staging of urinary bladder cancer.

Animals↗

Relation between serum levels of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) and their immunohistochemical identification in benign and malignant gynecological disease.

We studied immunohistochemical stains for TPA and CA125 in patients with benign and malignant gynecologic diseases. The results were as follows: (1) CA125 was not found in ovarian mucinous cystadenocarcinoma but was demonstrated immunohistochemically in 82% of ovarian serous cystadenocarcinomas and 83% of Krukenberg's tumors. (2) TPA was demonstrated in 65% of ovarian serous and 75% of ovarian mucinous cystadenocarcinomas, and in 58% of endometrial carcinomas. (3) TPA was found in all trophoblastic tumors examined, while CA125 was found in none. Eighty-three percent of patients with trophoblastic diseases had raised serum TPA levels. (4) When serum CA125 levels were raised CA125 was demonstrated immunohistochemically in 71% of patients with ovarian serous cystadenocarcinomas, 67% of patients with Krukenberg's tumors and 100% of patients with tubal carcinomas. (5) Despite elevated serum levels, CA125 and TPA were not identified by immunohistochemistry in 64% cases of benign ovarian disease and in 80% of patients with uterine myomata. (6) It would seem that CA125 was more easily released from tumor cells than TPA.

Antigens, Neoplasm↗

Serum levels of six tumor markers in patients with benign and malignant gynecological disease.

We studied the pretreatment serum levels of 6 tumor markers in gynecological patients with and without malignant disease. The tumor markers were carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin, Schwangerschaftsprotein 1 (SP1), Schwangerschaftsprotein 3 (SP3) and cancer antigen 125 (CA125). The results were as follows: (1) Serum CA125 and TPA levels were raised in 81% and 57% of patients with ovarian serous cystadenocarcinoma; CEA and SP3, in 52% and 43% respectively of patients with ovarian mucinous cystadenocarcinoma; CA125, TPA and SP3, in 76%, 48% and 48% respectively of patients with other ovarian malignancies; and TPA and SP3, in 56% and 40% respectively of patients with endometrial carcinoma. (2) Serum levels of TPA, ferritin and CA125 were more often raised with advancing stages of malignant disease. (3) Serum TPA levels were elevated in 55% of patients with stage I endometrial carcinoma, and serum SP3 levels were elevated in 35% of patients with a stage I malignant ovarian neoplasm and in 45% of patients with endometrial carcinoma. (4) One of the 6 tumor markers showed a raised level in 84% of patients with gynecologic malignancy as against 56% in those with benign gynecologic diseases.

Antigens↗

Stomach rupture following ingestion of sodium bicarbonate.

Spontaneous rupture of the stomach is an uncommon condition with a usually poor prognosis. The rupture occurs as a result of a closed loop obstruction with increased pressure against the stomach wall. A case of stomach rupture occurring after hyperdistention of the stomach following ingestion of sodium bicarbonate is described and the pathophysiological mechanism is discussed.

Adult↗

Studies in man on the mechanism by which fat increases the plasma concentration of neurotensin-like immunoreactivity.

We measured the plasma concentration of neurotensin-like immunoreactivity (p-NTLI) after administration of Intralipid (mainly triglycerides), or oleic acid perorally, into the intact proximal jejunum, intact distal jejunum or proximal ileum and together with partly digested Intralipid into an isolated ileal loop in man. Administration per os or into the proximal jejunum gave the highest p-NTLI responses, administration into the intact distal jejunum or proximal ileum gave a lower response and administration into the isolated ileal loop gave no response at all, although approximately 25 percent of the neurotensin producing cells should be located there. As estimation of intestinal tissue content of NTLI showed that in small intestine which for a long time had been out of contact with food there was no sign of depletion of NTLI, we suggest that nervous, humoral or luminal factors provoked by fat in the upper gastrointestinal tract must trigger the N-cells before NTLI can be released by fat exposition.

Administration, Oral↗

Experiences with antireflux valves in jejunoileal bypass surgery.

Intussusception valves were created in the small intestine of jejunoileal bypass-operated dogs and patients with the intention to prevent reflux of chyme into the excluded intestinal loop and thereby increase weight loss. In the dogs the valves were shown to withstand a pressure of at least 100 cm of water. All patients with end-to-side bypass were at X-ray examination found to have sufficient valves whereas only four of fourteen with end-to-end bypass, where the defunctionalized loop was implanted into the cecum, had tight valves. During five years of observation no significant difference in weight loss was seen between the patients with valves and control groups without valves. It is concluded that reflux of chyme only plays a minor role for weight loss after jejunoileal bypass for obesity.

Adult↗

Neurotensin-like immunoreactivity in plasma after fat intake in normal and obese subjects and after jejunoileal bypass.

The plasma concentration of neurotensin-like immunoreactivity (p-NTLI) was measured after oral intake of fat in (a) healthy non-obese volunteers, (b) grossly obese but otherwise healthy persons, and (c) patients who had undergone jejunoileal bypass because of gross obesity. In addition, p-NTLI was measured after intravenous infusion of fat in healthy non-obese volunteers. Basal p-NTLI levels were significantly higher in the patients with bypass than in the obese group. After oral intake of fat, the increase in p-NTLI was much greater and more sustained in the bypass group than in the two other groups. The type of bypass (end-to-end, end-to-side or biliointestinal) and the time after the operation did not correlate with the p-NTLI response. Intravenous infusion of fat evoked no increase in p-NTLI. To produce a rise in p-NTLI level, therefore, the fat does not have to be absorbed and hematogenously distributed to the N-cells (neurotensin-storing cells). This observation may suggest that direct contact between chyme and the N-cells, or local neural or hormonal factors, are required to stimulate release of NTLI. The authors suggest that increase in the postprandial release of neurotensin may promote the diarrhoea after bypass operations, and possibly has other physiologic effects in such patients.

Adult↗

Tissue polypeptide antigen (TPA) is related to the non-epidermal keratins 8, 18 and 19 typical of simple and non-squamous epithelia: re-evaluation of a human tumor marker.

Because of the broad clinical interest which tissue polypeptide antigen (TPA) has attracted as a tumor marker, human cell lines and human tissues have been analyzed for TPA expression using immunofluorescence microscopy. Epithelial cell lines including HeLa, MCF-7, and A-431 are recognized by TPA antibodies whereas human lines of non-epithelial origin are not. The positive staining patterns coincide with keratin-type intermediate filaments of the cytoskeleton. On tissue sections a subset of epithelial cells including uterine epithelium, bile duct cells in liver and tumor cells in breast carcinoma are strongly positive; cells of the squamous epithelia of skin and tongue as well as cells of non-epithelial origin are negative. In immunoblots of human epidermis, human tongue mucosa, human hair follicles, Detroit 562 cells, HeLa cells, MCF-7 and RT-4 cells, only keratins 8, 18 and 19 show TPA antigenicity. Conversely a TPA preparation is recognized by various antibodies known to react with keratins, including alpha-IFA, KG 8.13.2 and two antibodies which recognize keratins 18 (CK2) and 19, respectively. Our results thus relate TPA to human keratins 8, 18 and 19 which are known cytoskeletal components in both normal and malignant epithelial cells of simple and non-squamous origin. We speculate that the elevated levels of circulating TPA antigenicity present in the sera of patients with carcinoma, which are often used to monitor tumor progression, correspond to soluble proteolytic fragments originating from this particular keratin subgroup.

Animals↗