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Biomedical subjects

J Novotny

Publications and source records attributed to J Novotny.

At least 127 records · Page 7Linked to original sources

Secondary structure of the immunoglobulin J chain.

J chain is a 137-residue polypeptide that is covalently linked to polymeric immunoglobulins and participates in their synthesis and transport to external secretions. To clarify these roles, the secondary structure of J chain was characterized by computer-assisted analyses of human and mouse sequences and by circular dichroism measurements of the isolated J chain. The secondary-structure profiles obtained were very similar to those of superoxide dismutase or immunoglobulin light chain variable domains, suggesting that the J chain folds into an eight-stranded antiparallel beta-barrel and should contain approximately 37% beta-sheet conformation, with the rest of the structure existing as reverse turns (random coil). The circular dichroism measurements indicated that the conformation of denatured, S-carboxymethylated or S-sulfonated J chain consists of 75% random coil and 25% beta-structure. Upon reformation of disulfide bonds the percentage of beta-structure in the air-oxidized J chain increased to 34%, a value that is in good agreement with the secondary-structure analysis. Two alternative models of J-chain structure, a two-domain model [Cann, G., Zaritsky, A. & Koshland, M.E. (1982) Proc. Natl. Acad. Sci. USA 79, 6656-6660] and a single-domain antiparallel beta-sheet bilayer model (proposed in this paper), are compared.

Animals↗

Photoradiation therapy of head and neck cancer.

We have embarked upon a pilot study of photoradiation therapy (PRT) in the treatment of persistent or recurrent cancer of the head and neck, utilizing the photosensitizing agent, hematoporphyrin derivative (HPD). This treatment is based upon selective concentration of HPD within malignant tissue, with resultant necrosis upon illumination with light of the appropriate wavelength (640 nm). Patients entered in this trial have failed all forms of conventional therapy. Twenty-one patients with local recurrence were treated. Sites of recurrence were: tongue (9); nasopharynx (3); floor of mouth (2); soft palate (2); oropharynx (1); buccal mucosa (1); maxilla (1); larynx (1); and basal cell nevus (1). There were six complete responses and twelve partial responses (greater than 50% reduction). These responses are clinically significant, with some complete responses lasting over 1 year after a single course of therapy. Ten patients with cutaneous metastases from head and neck primary tumors were also treated. There were two complete responses and three partial responses. However, these patients rapidly developed new tumors in areas adjacent to those previously treated. Less than complete responses could be augmented by repeated applications of this technique. The success of this pilot study combined with the accessibility of head and neck primaries suggest that there should be a clinical trial of HPD-PRT in early mucosal cancer of the head and neck region.

Bronchoscopy↗

Photoradiation therapy of head and neck cancer.

We have embarked upon a pilot study of photoradiation therapy (PRT) in the treatment of persistent or recurrent cancer of the head and neck utilizing the photosensitizing agent hematoporphyrin derivative (HPD). This treatment is based upon selective concentration of HPD within malignant tissue with resultant necrosis upon illumination with light of the appropriate wave length (630 nm). Patients entered in this trial have failed all forms of conventional therapy. Twenty-one patients with local recurrence were treated. Sites of recurrence were: tongue (9), nasopharynx (3), floor of mouth (2), soft palate (2), oropharynx (1), buccal mucosa (1), maxilla (1), larynx (1), basal cell nevus (1). There were six complete responses and twelve partial responses (greater than 50% reduction). These responses are clinically significant with some complete responses lasting over one year after a single course of therapy. Ten patients with cutaneous metastases from head and neck primary tumors were also treated. There were two complete responses and three partial responses. However, these patients rapidly developed new tumors in areas adjacent to those previously treated. Less than complete responses could be augmented by repeated applications of this technique. The success of this pilot study combined with the accessibility of head and neck primaries suggest that HPD-PRT should be given a clinical trial in early mucosal cancer of the head and neck region.

Antineoplastic Agents↗

Matrix program to analyze primary structure homology.

A FORTRAN program to analyze homology of letter strings (nucleotide or amino acid sequences) and to display the result in the form of a dot matrix is presented. The program is generally usable, user-friendly and has a number of options (filtering, "fudging," i.e., consideration of groups of homologous residues, and screening, i.e., display of only particular groups of residues) which greatly potentiate its analytical power.

Amino Acid Sequence↗

The Clq receptor site on immunoglobulin G.

We propose that, the binding site for the complement subcomponent Clq on immunoglobulin G involves the last two (C-terminal) beta-strands of the C gamma 2 domain. This region contains a large number of accessible and highly conserved charged residues and charge is postulated as an important component of the Clq-IgG interaction. The conclusions are reached on the basis of accessibility and sequence conservation analyses of C gamma 2 amino acid residues, the use of specific inhibitors and chemical modification studies.

Amino Acid Sequence↗

The amino-terminal sequence of the VHIII subgroup of pooled porcine IgG.

Pig gamma-chains contain a significant fraction of the unblocked VHIII variable region subgroup. The amino terminal sequence (30 residues) was found to be uniform and more than 90% homologous with the prototype sequence of the human VHIII subgroup. An additional VHIII phylogenetically associated residue, glutamic acid in position 2 was identified in these porcine heavy chains.

Amino Acid Sequence↗

Thermoluminescence dosimetry in clinical radiation dose measurements.

A simple method using thermoluminescent dosimeters (TLD) to measure the doses where large shaped fields are used as mantle, breast and chest wall will be described. Measurements of doses in the gastrointestinal tract while treating nasopharynx, postcricoid and upper third of esophagus as well as in the rectum while treating cervix with intracavitary radium will be also discussed.

Digestive System↗

Radiation protection of the patient during radiotherapy.

Systematic studies of gonadal doses to patients undergoing therapy on 60Co and X-ray machines were carried out using thermoluminescence dosimeters (TLD). Phantom and in vivo measurements were performed for various field sizes and for different positions of the centre of the field on the patient's body with exception of fields including the gonads during radiotherapeutic treatment. It was shown that there is no effect of various SSD and that most radiation reaching gonads is transmitted axially through the body and therefore, it is impossible to reduce this dose with a simple shielding. The figures presented allow prediction of gonadal doses at various conditions. The efficiency of lung, mouth etc. shielding during radiotherapy was also investigated.

Gonads↗

Outcome of peripheral blood stem cell mobilization in advanced phases of CML is dependent on the type of chemotherapy applied.

High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a novel investigational approach to treating chronic myelogenous leukemia (CML) patients not responsive to conventional therapy with interferon-alpha (IFN-alpha) and not eligible for allogeneic transplantation. PBSC mobilization using either '5+2/7+3'-type chemotherapy or 'mini-ICE/ ICE' chemotherapy was investigated in 43 patients with advanced phases of Philadelphia (Ph)-positive CML. Thirty patients were in late chronic phase (>12 months post diagnosis) and 13 patients in accelerated phase (AP) or blast crisis (BC). Contamination with Ph-positive cells was evaluated in harvests from 37/43 patients. The outcome of PBSC mobilization was dependent on the type of chemotherapy administered: a complete or major cytogenetic response (<35% Ph-positive metaphases) in leukapheresis collections was obtained in ten of 15 patients treated with 'mini-ICE/ICE' but in only three of 28 patients treated with '5 + 2/7 + 3' chemotherapy. One patient (1/43) in blast crisis died during mobilization therapy (2%). Twenty-five patients underwent PBSC transplantation and all of them engrafted successfully. Transplantation-related mortality was 0%. The data show that in advanced phases of CML the chance of harvesting Ph-negative peripheral blood stem cells depends on the type of chemotherapy used for mobilization.

Adult↗

Inappropriate antibiotic therapy in febrile cancer patients with bacteremia.

OBJECTIVE: The aim of the study was to assess the outcome of inappropriately treated cancer patients with documented bacteremia. DESIGN/SETTING: 95 cases of inappropriately treated bacteremias in febrile cancer patients in a tertiary-care center were analyzed and compared with a group of appropriately treated bacteremias to assess risk factors for inappropriate therapy and outcome. RESULTS: Among 285 bacteremias, 95 (33.3%) were not treated appropriately, with 42 receiving the wrong antibiotics and 17 having too short a therapeutic course of appropriate antibiotics. In 13, therapy was delayed for more than 48 hours after the onset of fever. Twenty-three patients did not receive antibiotic therapy at all despite bacteremia. A group of 95 inappropriately treated bacteremias was compared to 190 appropriately treated bacteremias occurring in the same period. Microbiological cure after the initial course of therapy was achieved more often (76.8% vs 38.9%, P < .001) in the group of appropriately treated bacteremias in all cases and also in the subgroup of leukemic patients (P < .01). Overall and attributable mortality were significantly lower in patients who were treated appropriately. There was no difference in the number of antibiotics administered in appropriately versus inappropriately treated bacteremias. Cost of therapy between both groups was similar. CONCLUSIONS: Inappropriately treated bacteremic cancer patients had outcomes that were significantly worse than patients who were treated appropriately. The reasons for inappropriate therapy were selection of the wrong antimicrobials, too short a duration of therapy, delayed onset of therapy, or absence of antimicrobial therapy.

Anti-Bacterial Agents↗