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Biomedical subjects

E Hammar

Publications and source records attributed to E Hammar.

17 recordsLinked to original sources
PubMed1999

Regulation of the transcriptional activity of the peroxisome proliferator-activated receptor alpha by phosphorylation of a ligand-independent trans-activating domain.

The peroxisome proliferator-activated receptors (PPARs) are a subgroup of nuclear receptors activated by fatty acids and eicosanoids. In addition, they are subject to phosphorylation by insulin, resulting in the activation of PPARalpha, while inhibiting PPARgamma under certain conditions. However, it was hitherto unclear whether the stimulatory effect of insulin on PPARalpha was direct and by which mechanism it occurs. We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution. The characterization of a strong AF-1 region in PPARalpha, stimulating transcription one-fourth as strongly as the viral protein VP16, is compatible with the marked basal transcriptional activity of this isoform in transfection experiments. However, it is intriguing that the activity of this AF-1 region is modulated by the phosphorylation of two serine residues, both of which must be phosphorylated in order to activate transcription. This is in contrast to PPARgamma2, which was previously shown to be phosphorylated at a single site in a motif that is not homologous to the sites now described in PPARalpha. Although the molecular details involved in the phosphorylation-dependent enhancement of the transcriptional activity of PPARalpha remain to be elucidated, we demonstrate that the effect of insulin on the AF-1 region of PPARalpha can be mimicked by the addition of triiodothyronine receptor beta1, a strong binder of corepressor proteins. In addition, a triiodothyronine receptor beta1 mutant deficient in interacting with corepressors is unable to activate PPARalpha. These observations suggest that the AF-1 region of PPARalpha is partially silenced by corepressor proteins, which might interact in a phosphorylation-dependent manner.

Amino Acid Sequence↗
PubMed1998

Metastasizing adenocarcinoma of the female prostate (Skene's paraurethral glands). Histological and immunohistochemical prostate markers studies and first ultrastructural observation.

The case of a 46-year-old women with well-differentiated adenocarcinoma of the female prostate (Skene's paraurethral glands and ducts) with inguinal metastases is reported. Besides adenocarcinomatous structures, also more solid parts of the tumor and anaplastic regions with dark cells were found on histological examination. Clear cancerous cells were typical for glandular and solid tumor parts. The cancerous cells showed distinct immunohistochemical positivity of prostate specific antigen (PSA) and prostate (specific) acid phosphatase [P(S)AcP]. These are the first published results of electron microscopic examination of formalin fixed tissue showing the ultrastructure of female prostate carcinoma, comparable to that of the male prostate carcinoma. In the female, similar to the male, the prostate carcinoma probably originates from the secretory (luminal) cells of the female prostatic glands.

Acid Phosphatase↗
PubMed1993

Clinical significance of dysplasia in gastric remnant biopsy specimens.

BACKGROUND: Dysplasia often is found in biopsy specimens from the gastric stump some 20 years after ulcer surgery. A high frequency of patients with severe dysplasia in the nonoperated stomach develop carcinoma but the clinical significance of dysplasia in the gastric stump is still confounding. METHODS: In the current study, two groups of patients were evaluated. One group of 22 patients, found at the first investigation in an endoscopic screening study with moderate dysplasia in the gastric stump, were regularly followed up to 18 years with endoscopy and biopsies. In the second part of the investigation, the authors evaluated 17 patients from the same endoscopic screening study, who at any instance during the 18 years were found to have severe dysplasia in biopsy specimens from the gastric remnant. RESULTS: In three of the 22 patients with moderate dysplasia, stump carcinoma was diagnosed 2, 2, and 6 years, respectively, after the first endoscopic examination. Severe dysplasia was found in two other patients at one occasion but later investigations only revealed moderate dysplasia. The remainder of the patients in this group had either persisting moderate dysplasia or mild dysplasia at follow-up. Seven (41%) of the 17 patients with severe dysplasia had stump carcinoma within a median time of 2 years (range, 1-11). Two other patients had surgery based on suspicion of carcinoma, but had only severe dysplasia in the surgical specimen. Finally, three men died (after 1, 2, and 17 years, respectively) of unrelated disease without suspicion of stump carcinoma and five patients were followed between 6 and 18 years without signs of malignant development. CONCLUSIONS: Patients with moderate and, especially, severe dysplasia in the gastric remnant are at high risk for gastric carcinoma. Severe dysplasia calls for endoscopic surveillance at short intervals. For patients with moderate dysplasia a close surveillance for 2 years followed by biannual evaluation appears sufficient.

Aged↗
PubMed1991

Role of re-resection in early gastric stump carcinoma.

Between 1971 and 1990, 26 patients were diagnosed as having an early carcinoma in the gastric remnant after ulcer surgery. Three patients with proximal tumour location were operated on with total gastrectomy. The surgical strategy in the remaining patients with tumour adjacent to the anastomosis was re-resection of at least 5-6 cm of the anastomotic area and restoration of gastrointestinal continuity with a Roux-en-Y loop. A margin of at least 2 cm from the carcinoma to the resection line was taken. There was no postoperative mortality. In three cases the preoperative endoscopic and histological judgement of tumour classification and stage was incorrect; when the surgical specimens were examined one patient was found to have advanced carcinoma and in the other two no malignancy could be found. Median follow-up was 15 years (range 3-19 years). During follow-up, six of the re-resected patients developed recurrences, all located in the gastric remnant. Four patients with recurrence underwent reoperation with total gastrectomy, one had exploratory laparotomy and one had no further surgery. No postoperative deaths occurred. Three of the six patients died from gastric carcinoma. We conclude that this surgical strategy failed to prevent local recurrence of an early form of gastric carcinoma, considered to be potentially curable in virtually all cases. Partial resection of the gastric remnant as the treatment of choice in patients with early gastric stump carcinoma cannot be recommended.

Adult↗
PubMed1991

Endoscopic screening during 17 years for gastric stump carcinoma. A prospective clinical trial.

In an attempt to reduce mortality in gastric stump carcinoma a defined cohort of operated peptic ulcer patients was followed up with an endoscopic screening programme. From 1930 and through 1960, 1575 patients were operated on for peptic ulcer disease at the Dept. of Surgery in Lund, Sweden. Of 838 still alive in January 1973, 682 were selected for geographical reasons and were offered endoscopic screening with biopsy at regular intervals. Three hundred and fifty-four patients came to the first examination. The follow-up programme was individualized thereafter with screening at 1- to 3-year intervals, depending on endoscopic and histologic findings. The remaining patients have, since then, constituted a control group, followed up only through death certificates and the Swedish Cancer Registry. By December 1989, 202 patients in the screening group had died and 320 in the control group. During the 17 years of follow-up 12 patients in the screening group died of gastric cancer, compared with 14 in the control group, even though 17 cases of early gastric cancer were diagnosed and operated on in the first group, compared with only 2 in the latter. We conclude that regular endoscopic screening does not reduce gastric cancer mortality and can thus not be recommended in asymptomatic patients previously subjected to partial gastric resection due to peptic ulcer disease.

Adult↗
PubMed1990

An immunoassay for histamine based on monoclonal antibodies.

Monoclonal antibodies with high specificity for histamine as well as for 1-methylhistamine were obtained after immunization of mice with a conjugate where the histamine was coupled via its ring 1-nitrogen to dog serum albumin. An immunoassay was developed for the quantitation of histamine release from basophils and 1-methylhistamine release from mast cells after provocation. The test method is based on competitive inhibition between histamine and a labelled histamine conjugate for the antigen binding sites of the antibodies. The separation step is performed by the addition of solid phase bound anti-mouse subclass specific antibodies. The sensitivity of the assay is 2 micrograms/l for histamine and 0.1 micrograms/l for 1-methylhistamine. No cross-reactivity was obtained with other metabolites of histamine or with histidine. Serotonin and dopamine were detectable, but only in doses (mg/l) well above the normal concentration found in the circulation. The immunoassay has been evaluated for its capacity to measure histamine release in vitro. A good correlation with the conventional fluorometric assay was obtained when histamine released from allergen stimulated leucocytes from allergic patients was tested. Urinary samples from patients undergoing hyposensitization showed a mean excretion of 1-methylhistamine at a level of 131 mumol MeHi/mol creatinine. The release of histamine and 1-methylhistamine in vivo was examined in plasma samples taken during a bronchial provocation test. A significant elevation above the basal analyte level occurred ten minutes after provocation.

Animals↗
PubMed1987

Use and misuse of oral contraceptives by adolescents attending a free-standing clinic.

A total of 216 adolescents attending a free-standing clinic completed a questionnaire on oral contraceptive use. Over 80% knew the brand name of their pill and took it correctly from cycle to cycle. About a third had missed at least one pill in the previous three months. Those who took their pills irregularly were more likely to miss them. In the event of missing a pill only 25% would use additional contraceptive measures such as condoms. Over half thought that not menstruating was harmful. The pill-taking pattern in this group of adolescents does not appear to differ significantly from that in adults. Oral contraceptive packs containing 28 tablets (including placebos) appear to produce fewer cycle-to-cycle problems than packs containing 21 active tablets.

Adolescent↗
PubMed1982

Long-term epidural morphine analgesia.

Long-term treatment for malignant pain with morphine epidurally poses some technical problems: infection and contamination of epidural space, fixation of the epidural cannula, personal hygiene of the patient, etc. We suggest that a solution to these problems is subcutaneous tunnelling of the epidural cannula. This paper describes our technique and presents the case histories of two patients. In one case, a single epidural cannula was used for 207 days for treatment with morphine epidurally without any complication.

Aged↗
PubMed1981

Surgery alone or combined with radiation therapy in esophageal carcinoma.

Two patient-materials with esophageal carcinoma are analyzed: a group of 22 patients who, during the period 1971-1974, were treated with esophageal resection followed by esophagogastrostomy or colonic interpolation; a second group of 28 patients from 1975-1978, who were treated in the same way, but also given either preoperative or postoperative radiation therapy, or both. Surgical mortality was about the same in the two groups: 25-32%. The group given radiation therapy had a one-year survival rate of 50%, as compared with 23% in the group treated solely with surgery. All 24 patients given combined therapy, with all or part of the absorbed dose of 24-47 Gy given preoperatively, showed vital cancer in resected specimens. Vital cancer was found in the periesophageal nodes in only six patients (25%), however; patients given no preoperative radiation therapy had tumor in 20 of 26 cases (77%; P less than 0.01). Celiac nodes were resected at laparotomy; when malignancy was found, the celiac region was irradiated postoperatively. This finding does not appear to exclude long-term survival, as two patients with metastases to the celiac nodes at operation are alive 16 and 20.5 months following surgery. Simple compared to troublesome dissection gives a better rate of survival. The spleen was unintentionally injured in 21 patients at laparotomy and had to be removed. One-year survival was better in patients with intact spleen, especially in those who also had radiation therapy. Patients with resected spleen succumbed from metastases more often than from mediastinal recurrence, as compared with the patients with intact spleen.

Adenocarcinoma↗
PubMed1977

Microanatomy of the intravesical ureter in children with and without reflux.

The microscopical appearance of 37 distal ureteral resection specimens from 27 children with recurrent urinary tract infections and vesicoureteral reflux are compared to postmortem specimens of 51 distal ureters from 28 children with no history or urinary tract disease. The degree of fibrosis and inflammatory change varied a great deal in both groups and it was not possible to find any differences between them.

Child↗
PubMed1976

Enzyme histochemical studies of rabbit bile ducts with and without bile flow.

The histochemical enzyme pattern in normal, extra-hepatic bile ducts from rabbits was studied. A difference between the duct epithelium and the crypt epithelium was noted mainly in the activity of gamma-glutamyl-transpeptidase and alkaline phosphatase which only stained positively in the crypts. No difference from the normal enzyme pattern was noted after diversion of the bile flow for up to 30 days.

Acid Phosphatase↗
PubMed1976

The localization of precancerous changes and carcinoma after previous gastric operation for benign condition.

Sixty-five patients operated on for a benign gastric condition showed at re-operation in 9 cases precancerous changes, in 22 cases carcinoma in situ, and in 34 cases infiltrating carcinoma. The median time to elapse between the two operations was 20 years. The pathological diagnosis established at the first operation was most often benign duodenal ulcer. Investigation revealed in 9 cases precancerous changes and in 47 cases various grades of adenocarcinoma within the anastomosis. In 37 cases of Billroth II operations, 5 precancerous changes, 15 carcinomas in situ and 17 infiltrative cancers were located on the posterior gastric wall near the efferent small intestinal loop. In these cases there were additional changes, one precancerous, 7 carcinomas in situ and two infiltrating cancers, situated against the cephalic part of the afferent small intestinal loop. Nineteen Billroth II patients had precancers or cancers at other sites within the anastomosis or gastric remnant. The remaining 9 cases of Billroth I, gastro-enterostomy and gastric Roux-en-Y procedures are too few to allow conclusions concerning the localization of precancer or cancer in the anastomosis.

Aged↗
PubMed1976

Studies on ciliated epithelia of the human genital tract. I. Swelling of the cilia of Fallopian tube epithelium in organ cultures infected with Mycoplasma hominis.

Organ cultures of human Fallopian tubes were infected with Mycoplasma hominis. Scanning and transmission electron microscopy revealed swelling of the cilia of the tubal epithelial cells in infected cultures. In some, the entire cilia were swollen; in others, only the tips. Uninfected cultures kept for up to 7 days showed no structural changes in the cilia or other surface structures. M. hominis multiplied in organ cultures, but not in culture medium without tissue. A practical organ culture technique for the preparation of specimens for electron microscopy is described.

Cilia↗
PubMed1976

Enzyme histochemistry studies of transverse and longitudinal incisions in the common bile duct in rabbits.

The healing process of longitudinal and transverse incisions of the common bile duct in rabbits was studied by identification of 10 different enzymes in the duct wall at various times after the operation. Bile was deviated during the healing. An almost complete disappearance of the subepithelial alkaline phosphatase activity was noted early after longitudinal incisions in contrast to unchanged alkaline phosphatase activity after transverse incisions. Transversely incised ducts almost uniformly developed stricutre formation. The size of the lumen after longitudinal incisions was generally normal. The difference in enzyme pattern following the two types of lesion might reflect a different response of the tissues to the two different types of trauma.

Acid Phosphatase↗
PubMed1975

Extragonadal endodermal sinus tumours. Report of a case.

A case is described of endodermal sinus tumour originating in the sacro-coccygeal region in a man 20 years of age. Of the hitherto presented cases of endodermal sinus tumour of a gonadal origin, 24 out of 42 patients have died. Of 21 patients in whom the disease was of an extragonadal origin, 18 have died. Thus, the prognosis seems to be less favourable in patients with extragonadal tumours. The best prognosis has been reported in boys with endodermal sinus tumours of a testicular origin operated before the age of 2 years.

Abdominal Neoplasms↗