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Biomedical subjects

J Hammer

Publications and source records attributed to J Hammer.

At least 145 records · Page 8Linked to original sources
PubMed1994

Rules for peptide binding to MHC class II molecules.

CD4+ T lymphocytes recognize peptide fragments of antigens that lie in the antigen binding pocket of class II major histocompatibility complex (MHC) molecules expressed on antigen-presenting cells. Specificity of T cells is determined by structural features of both the MHC molecule and antigenic peptide. MHC class II amino acid sequences are highly polymorphic within a population, and correlate with individual differences in response to infectious agents, vaccines, tumour antigens, and autoantigens. In the last few years several important breakthroughs and technological advances have made it possible to clarify the role of polymorphism and the molecular events in peptide interaction with major histocompatibility complex (MHC) class II proteins. The X-ray structural analysis of a MHC class II molecule together with the use of peptide libraries has permitted determination of the structural features of the complex between peptide antigen fragments and MHC class II proteins. The purpose of this article is to review our own studies and those of others on the requirements for peptide-class II molecule interaction and discuss possible implications for active immune intervention.

Amino Acid Sequence↗
PubMed1994

Breast cancer: primary treatment with external-beam radiation therapy and high-dose-rate iridium implantation.

PURPOSE: To evaluate a treatment for breast cancer and to demonstrate the safe use of iridium-192 high-dose-rate (HDR) implantations. MATERIALS AND METHODS: In December 1984, the authors began to use HDR Ir-192 brachytherapy to deliver an interstitial boost to the primary site in conservative breast cancer treatment. By December 1989, 212 patients with 216 tumors were treated with external-beam irradiation of 45-50 Gy to the whole breast, which was followed by an interstitial 10-Gy boost. Median follow-up was 62 months (range, 36-101 months). RESULTS: Ten patients (10 of 216 breasts, 4.6%) developed local tumor recurrences, and 36 (17.0%) had distant metastases. At 5 years, overall survival was 88%, local tumor control was 96%, and disease-free survival was 81%. There were no serious complications. CONCLUSION: The use of an HDR source as a boost to the primary tumor site after external-beam radiation therapy with a dose of 10 Gy in one fraction is a safe procedure and does not negatively affect cosmetic appearance.

Adult↗
PubMed1994

Measurement of high lung volumes by nitrogen washout method.

Studies on human infants suggested that thoracic gas volume (TGV) measured at end exhalation may not depict the true TGV and may differ from TGV measured from a series of higher lung volumes and corrected for the volume added. This was explained by gas trapping. If true, we should expect the discrepancy to be more pronounced when functional residual capacity (FRC) and higher lung volumes are measured by gas dilution techniques. We studied lung volumes above FRC by the nitrogen washout technique in 12 spontaneously breathing rhesus monkeys (5.0-11.3 kg wt; 42 compared measurements). Lung volumes directly measured were compared with preset lung volumes achieved by artificial inflation of the lungs above FRC with known volumes of air (100-260 ml). Measured lung volume strongly correlated with and was not significantly different from present lung volume (P = 0.05; r = 0.996). The difference between measured and preset lung volume was 0-5% in 41 of 42 cases [1 +/- 0.4% (SE)]. The direction of the difference was unpredictable; in 22 of 42 cases the measured volume was larger than the preset volume, but in 17 of 42 cases it was smaller. The difference was not affected by the volume of gas artificially inflated into the lungs. We conclude that, overall, lung volumes above FRC can be reliably measured by the nitrogen washout technique and that FRC measurements by this method reasonably reflect true FRC.

Animals↗
PubMed1994

[Color doppler ultrasonography of uterine vessels during radiotherapy of advanced cervix cancers].

In tumor vessels of 14 patients with an advanced squamous cell carcinoma of the cervix uteri, an increase of the resistant index (RI) and the pulsatility index (PI) of tumor vessels was found later than the decrease of the volume of the tumor. For the uterine arteries these indices remained unchanged for patients with a complete remission, while for patients with incomplete remission there was a decrease of RI and PI.

Adult↗
PubMed1994

Case report: salvage fractionated high dose rate after-loading brachytherapy in the treatment of a recurrent tumour in the middle ear.

Re-irradiation of previously irradiated head and neck sites is associated with a high complication rate. In an attempt to reduce this complication risk, multiple fractions of high dose rate (HDR) intracavitary irradiation were used in a young patient who had developed recurrent transitional cell carcinoma in the tympanic cavity one year after radical radiotherapy. After gross surgical removal of the tumour, an afterloading probe was placed into the middle ear by a surgical approach. In 11 treatments of 3 Gy each over 4 days, a total dose of 33 Gy was delivered to a spherical volume, 1.7 cm in diameter. The patient was 24 months free of disease at the start of 1993. Audiometry shows no severe deterioration of hearing. We concluded that fractionated HDR brachytherapy can be used to achieve local control in small volume recurrences at previously irradiated sites, without the inevitability of complications.

Adult↗
PubMed1994

[Quality assurance of interstitial irradiation in the breast-conserving therapy of breast cancer].

PURPOSE: The purpose of this communication is to describe the procedure of interstitial implant planning in definitive irradiation of early breast cancer. There are some reports about localization techniques of the boost volume for external irradiation. Less has been reported about the target volume localization of HDR implants of the breast. METHODS: Conservative surgery and following radiation therapy have become a standard treatment in the management of early breast cancer. The use of a boost irradiation in the area of the primary tumour seems to be promising in decreasing local recurrence rates. Most of our patients received a boost dose by interstitial HDR iridium-192 therapy. Therefore we have improved the method of interstitial implantation by CT under general anesthesia. The implant is planned in the simulator room by localizing the radiopaque clips of the tumor bed, the entrance and exit points of the needles are determined by marking the skin. Then the implantation is done in the operating and afterloading room. A device for patient transportation between brachytherapy unit and CT has been constructed. So patients can be shifted under general anesthesia between the different devices without any problems. The implanted needles and the clips are visualized by the means of CT. The target volume can be defined and the source dwell positions determined. CONCLUSION: This method improves the accuracy of target localization. Therefore the treated volume can be adapted and minimized, resulting in less side effects and may contribute to maximize local control.

Brachytherapy↗
PubMed1994

[External irradiation and interstitial HDR brachytherapy in the treatment of breast cancer].

PURPOSE: In the breast conserving management of mammary cancer a high-dose-rate (HDR)-Iridium-192 source is used for interstitial boosting of the primary tumor site after external radiotherapy. We want to show the clinical results and side effects and to demonstrate the safe use of a HDR source. PATIENTS AND METHOD: From December 1984 until November 1988, 154 patients with breast cancer stage T1-2, N0-1 were treated by conservative surgery and radiation. A dose of 45 to 50 Gy was given to the whole breast by external radiotherapy, and the previous tumor area was boosted by an interstitial implant with Iridium-192 HDR. We applied 10 Gy in one or two fractions. RESULTS: The mean follow-up period of survivors is 76 months (range 57 to 107 months). In 36 patients failures occurred: eight patients (5%) developed local recurrences, 31 patients (20%) had distant metastases, and 19 (12%) died with cancer. The Kaplan-Meier estimation for five year overall survival is 86.9%, for disease-specific survival 89.3%, for local control 95.8%, and for disease free survival 80.1%. The most frequent late effects were telangiectasia (11%), fibrotic masses in the previous tumor area (6.5%), and lymphedema of the arm (6.5%). No serious complications could be observed. CONCLUSION: With the HDR-Boost of 10 Gy in addition to external beam radiotherapy in the treatment of breast cancer we obtained good clinical results without serious side effects.

Brachytherapy↗
PubMed1993

Promiscuous and allele-specific anchors in HLA-DR-binding peptides.

The major histocompatibility complex (MHC) class II molecules are highly polymorphic membrane glycoproteins that bind peptide fragments of proteins and display them for recognition by CD4+ T cells. To understand the effect of human MHC class II polymorphism on peptide-MHC interaction, we have isolated M13 phage from a large M13 peptide display library by selection with DRB1*0401 and DRB1*1101 molecules, as recently described for DRB1*0101. Sequence analysis of the peptide-encoding region of DR-bound phage led to the identification of position-specific anchor residues, defining motifs for peptide binding to DR molecules. The three DR motifs share two anchor residues at relative positions 1 and 4, while allele-specific anchor residues have been identified at position 6. These results provide a biophysical basis for both the promiscuity and the specificity of peptide recognition by DR molecules.

Alleles↗
PubMed1993

Fluid loading of the human colon: effects on segmental transit and stool composition.

BACKGROUND: Because segmental storage by the colon is relevant to diarrheal states, we quantified colonic transit in 13 healthy volunteers. METHODS: We infused radiolabelled liquids and solids into the cecum. Gamma camera images were obtained for 48 hours and counts measured in ascending (AC), transverse (TC), descending (DC), and rectosigmoid (RS) colons. Bowel movements were scored for consistency and stool outputs of isotopes were quantified. RESULTS: No volunteers developed diarrhea. Times for isotopes to transverse AC and TC were shorter with rapid infusions (P < 0.001). Counts remaining in AC and TC were also correlated with infusion volumes for 9 hours but not thereafter. Solids were initially delayed in AC but solids and liquids were stored equally in TC. Transit through DC was rapid, but RS stored contents for many hours. First appearance of counts in stools and total counts excreted after 48 hours were not dependent on the infusion rate. Fecal consistency and water content correlated significantly with colonic transit times. CONCLUSIONS: Fluids moved ahead of solids in the AC, but liquids and solids were stored equally in the TC. The DC acted mainly as a conduit during fluid overload but the RS stored both isotopes extensively. Stool consistency was a valid reflection of total colonic transit.

Adolescent↗
PubMed1993

Combined external and high dose rate intracavitary radiotherapy in the primary treatment of cancer of the uterine cervix.

From August 1980 to December 1985, 153 patients with stage I, II and III carcinomas of the uterine cervix were treated with external beam irradiation and high dose rate (HDR) Cs-137 and Ir-192 Curietherapy at the Barmherzige Schwestern Hospital in Linz, Austria. Complete remission was achieved in 146 patients (95.4%). The 5-year overall survival probabilities (Kaplan-Meier) in stages I, II and III were 79.3%, 62.6% and 40.8%, respectively. The 5-year recurrence-free survival rates were 91.5%, 59.6% and 52.9%. These results are equivalent to those achieved by treatments incorporating low dose rate (LDR) Ra-226 applications in regard to the limitations of historical comparisons. Use of the high dose rate afterloading methods lead to similar rates of local failures and complications.

Adenocarcinoma↗
PubMed1993

Effect of a 5HT3-antagonist (ondansetron) on rectal sensitivity and compliance in health and the irritable bowel syndrome.

In some patients with the irritable bowel syndrome, rectal urgency and discomfort are major clinical problems and, under experimental conditions, these symptoms are perceived at lesser volumes of rectal distension than they are in asymptomatic controls. Further, a 5-hydroxytryptamine type-3 receptor antagonist increased the threshold for rectal discomfort in irritable bowel syndrome. Our aims were, (a) to measure rectal sensation during isobaric distensions of the rectum, and (b) to test the effect of another selective 5HT3-antagonist, ondansetron 0.15 mg/kg, on rectal sensitivity, colonic tone, rectal tone and manometric responses. Ten healthy volunteers and five patients with diarrhoea-predominant irritable bowel syndrome were studied. A multilumen barostat-manometric assembly was placed in the descending colon, and a second barostat balloon was positioned in the rectum. Tone in the wall of the colon and rectum was measured by the barostat balloon volume during a constant pressure clamp, while intraluminal pressures were recorded by manometry; perceived sensations were also recorded before and after the intravenous administration of ondansetron or placebo in blinded fashion. Rectal resistance to stretch was greater and rectal urgency was induced by lower distending pressures in irritable bowel syndrome, however, basal tone in the rectum was similar in health and irritable bowel syndrome. Ondansetron did not change rectal sensitivity (first sensation or urgency) or tone. Rectal distension did not alter tone in the descending colon or colonic manometry; ondansetron did not influence any index of colonic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Does the ileocolonic junction differentiate between solids and liquids?

Previous observations from our laboratory have suggested that colonic filling from the ileum is characterised by a series of bolus movements. The present experiments were designed to test the hypothesis that bolus transit of ileal contents into the colon would not distinguish between solids and liquids. After a manometric infusion assembly was positioned by mouth into the ileum of 13 healthy volunteers, a mixture of nutrients (75 kcal), incorporating a solid phase radiolabel (111In labeled resin pellets) and a liquid phase marker (99mTc-DTPA), was infused into the ileum. Transit of both labels from the ileum to colon was quantified scintigraphically and ileal motility was also recorded. When markers were infused into the proximal ileum, 100 cm proximal to the ileocolonic junction (six), there were clear cut examples of discriminant transit, when liquids moved more rapidly from the small to the large bowel than did solids. When isotopes were instilled into the distal ileum, less than 50 cm from the ileocolonic junction, no separate transit of the solid and liquid phases was observed. No specific motor pattern of the ileum was regularly associated with bolus filling of the colon. These results support the hypothesis that the distal ileum can discriminate between solids and liquids but that the ileocecal junction cannot.

Adult↗
PubMed1992

Identification of a motif for HLA-DR1 binding peptides using M13 display libraries.

Oligonucleotides encoding peptides known to bind to HLA-DR1 molecules have been inserted into the gene III of filamentous M13 phages. DR1 molecules purified from human lymphoblastoid cell lines could specifically bind to these peptide sequences expressed on the phage surface. A M13 phage peptide library was next constructed and screened with DR1 molecules. After four rounds of selection, more than 80% of the phages were able to bind to DR1. Competition experiments with both isolated phages and corresponding synthetic peptides showed that the binding was specific. Sequence analysis of the peptide encoding region of 60 phages binding to DR1 molecules and comparison with phages of the original library revealed two potential anchor positions. The first was an aromatic residue (Tyr, Phe, or Trp) at the NH2 terminus of the peptide sequences, and the second was located three residues downstream and consisted of Met or Leu. In addition, the negatively charged amino acids Asp and Glu were mostly excluded from the DR1 binding sequences, and the small amino acid residues Gly and Ala were enriched at position 6. As for DR1, this approach should enable one to easily determine the binding motifs of other MHC class II alleles and isotypes. Furthermore, it could have interesting applications in the design of major histocompatibility complex-specific antagonists.

Amino Acid Sequence↗
PubMed1992

The activation of major histocompatibility complex class I genes by interferon regulatory factor-1 (IRF-1).

We have investigated the role of interferon regulatory factor-1 (IRF-1), an interferon-gamma (IFN-gamma) inducible transcriptional activator, on major histocompatibility complex (MHC) class I gene transcription. IRF-1 alone is sufficient to trans-activate both transfected and endogenous class I genes and the effect of IRF-1 appears to be direct and sequence-specific. These data suggest that IRF-1 is involved in the IFN-gamma mediated induction of MHC class I expression.

Base Sequence↗
PubMed1992

Hyperfractionated radiotherapy and polychemotherapy in brain stem tumors in children.

Between October 1989 and January 1991 five children with brain stem tumors were treated with sequential chemo- and radiotherapy. The polychemotherapy consisted of procarbazine, ifosfamide, etoposide, methotrexate, cisplatin and cytosine arabinoside. Locally, hyperfractionated radiotherapy was delivered at a total dose of 63.8 Gy (1.1 Gy twice daily, 10 fractions per week). After a median observation time of 11.8 (range 4-23) months from diagnosis three children are alive and without evidence of tumor progression. Two patients died from tumor progression 11 and 16 months respectively after initiation of therapy.

Adolescent↗
PubMed1992

[MCA and CA 15-3 in the follow-up of patients with breast cancer].

After surgery and radiotherapy circulating serum levels of the tumour markers MCA and Ca 15-3 were evaluated in 226 clinically disease-free breast cancer patients. 15 of them presented with local recurrences and/or distant metastases after a follow-up period of twelve months. Six patients belonged to the group of 180 with both markers negative, two belonged to the 32 patients with only one marker positive, and seven to the group of 14 with both markers positive. After twelve months the probability of disease-free survival (calculated by the method of Kaplan-Meier) is 96% in patients with negative tumour markers and only 51.4% in patients with both markers positive (p less than 0.001). After 16 months these values are 96% versus 25.7% with the same statistical significance. The value of tumour marker examinations in the regular follow-up of patients with breast cancer lies in the early detection of tumour activity and therefore in a better chance of response to subsequent treatment. The diagnostic sensitivity of MCA was 75.5%, and for Ca 15-3 70.24%.

Antigens, Neoplasm↗