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Biomedical subjects

S V Kozlov

Publications and source records attributed to S V Kozlov.

At least 19 recordsLinked to original sources

[Functional results of the surgery of esophageal opening hernia].

The article presents an original method of laparoscopic anti-reflux surgery, immediate and long-term results of the treatment of 132 patients with esophageal opening hernia. It also describes the analysis of the life quality of patients with the gastroesophageal reflux disease before and after the surgery.

Adult↗

[Experimental grounds for the formation of an increased pressure zone in the area of "impaired" lower esophageal sphincter].

A method of the formation of an artificial lower esophageal sphincter (LES) with the help of superelastic threads made of a nickelide-titan alloy was developed in the experiment. An experimental model of an artificial LES was tested on cadaver organic combinations of the esophagus and stomach in ten watchdogs and ten rabbits. Tests of the esophageal passage and antireflux features of the artificial lower esophageal sphincter (LES) and assessment of morphological changes in esophageal wall layers with the emphasis on changes of the esophageal wall structure and gastroesophageal passage near the thread were made. This experiment proved that the passage in the artificial lower esophageal sphincter (LES) area is not disturbed and a zone of increased pressure is created.

Animals↗

[Method of treatment of reflux-esophagitis after gastrectomy].

A new method of treatment of reflux-esophagitis developed for patients after gastrectomy has a distinctive moment: the formation of a restraining mechanism in the field of esophago-gastric anastomosis, without opening the intestinal tube lumen. The carried on trials of clinical application of the method have shown its high effectiveness for prophylactics ofjejuno-esophageal reflux both in the early and distant terms after operation. The method of operating was given a patent of the Russian Federation.

Adult↗

[Surgical treatment of gastroesophageal reflux].

One hundred and seventy-five patients with gastroesophageal reflux disease (GERD) were treated, 144 (82.2%) of them underwent surgery. In 106 (73.6%) patients laparotomy was used, in 38 (26.4%) -- laparoscopic surgeries. Transabdominal USE of the esophagus, stomach and duodenum, endoscopic ultrasonoraphy (EUS) of the esophagus were used for diagnosis of GERD in addition to standard tests. Based on EUS data, classification of severity of reflux-esophagitis was proposed. New method of laparoscopic creation of artificial lower esophageal sphincter (LES) with super thin (95, 45 mm) and super elastic filaments made of nikelid-titan alloy was developed in experiment and introduced into clinical practice. Thirty-four laparoscopic surgeries were performed, 26 (76.4%) of them -- with creation of artificial LES. In this group 94.4% of patients demonstrated excellent and good results in long-term period. Pressure in the area of LES in these patients increased by 70%, on the average, after surgery.

Adult↗

Crystal structure of neuroserpin: a neuronal serpin involved in a conformational disease.

The protease inhibitor neuroserpin regulates the development of the nervous system and its plasticity in the adult. Neuroserpins carrying the Ser53Pro or Ser56Arg mutation form polymers in neuronal cells. We describe here the structure of wild-type neuroserpin in a cleaved form. The structure provides a basis to understand the role of the mutations in the polymerization process. We propose that these mutations could delay the insertion of the reactive center loop into the central beta-sheet A, an essential step in the inhibition and possibly in the polymerization of neuroserpin.

Alzheimer Disease↗

A direct interaction of axonin-1 with NgCAM-related cell adhesion molecule (NrCAM) results in guidance, but not growth of commissural axons.

An interaction of growth cone axonin-1 with the floor-plate NgCAM-related cell adhesion molecule (NrCAM) was shown to play a crucial role in commissural axon guidance across the midline of the spinal cord. We now provide evidence that axonin-1 mediates a guidance signal without promoting axon elongation. In an in vitro assay, commissural axons grew preferentially on stripes coated with a mixture of NrCAM and NgCAM. This preference was abolished in the presence of anti-axonin-1 antibodies without a decrease in neurite length. Consistent with these findings, commissural axons in vivo only fail to extend along the longitudinal axis when both NrCAM and NgCAM interactions, but not when axonin-1 and NrCAM or axonin-1 and NgCAM interactions, are perturbed. Thus, we conclude that axonin-1 is involved in guidance of commissural axons without promoting their growth.

Animals↗

Neuronal depolarization enhances the transcription of the neuronal serine protease inhibitor neuroserpin.

Neuroserpin is an axonally secreted neuronal serine protease inhibitor. Based on its inhibitory activity towards tissue plasminogen activator (tPA) and its predominant expression in the cerebral cortex, the hippocampus, and the amygdala, a role for neuroserpin in the regulation of neural plasticity has been suggested. We recently found that neuroserpin mRNA is increased in cultured hippocampal neurons upon depolarization with elevated extracellular KCl. Using luciferase reporter constructs containing segments of the promoter region of the neuroserpin gene, we identified a 200-bp segment near the transcription initiation site that is responsible for both the neuron-specific expression of the neuroserpin gene and the enhanced transcription resulting from depolarization. Nerve growth factor, which alone had no effect on the expression of neuroserpin mRNA in hippocampal neurons, had a marked potentiating effect when supplied in combination with elevated extracellular KCl. In contrast, the transcription factor zif/268 blocked neuroserpin transcription. These results implicate neuroserpin as an activity-regulated modulator of tPA activity at the synapse and provide further support for the occurrence of activity-regulated proteolytic processes at the synapse.

Animals↗

Structure of the mouse gene for the serine protease inhibitor neuroserpin (PI12).

Neuroserpin (PI12), initially identified as an axonally secreted protein in cultured chicken dorsal root ganglion neurons, belongs to the serpin family of the serine protease inhibitors and is mainly expressed by neurons of both the developing and the adult nervous system. Here we report on the cloning and structural characterization of the neuroserpin gene of the mouse. The murine neuroserpin gene spans over more than 55kb and consists of nine exons. The positions and phases of the exonīntron borders are completely conserved between neuroserpin and its nearest homologues, protease nexin-1 and plasminogen activator inhibitor-1. A single transcription initiation site, which is colocalized with a potential initiation (Inr) sequence, has been determined by primer extension and RNase protection. Sequence analysis revealed a TATA-less promoter with a CAAT box and several sites for the general transcription factor Sp1 and the neuron-specific transcription factor AP-2.

Amino Acid Sequence↗

Human neuroserpin (PI12): cDNA cloning and chromosomal localization to 3q26.

Neuroserpin is a novel serine protease inhibitor of the serpin family. It has been reported as a 55-kDa glycoprotein that is secreted from the axons of cultured central and peripheral nervous system neurons. In situ hybridization and Northern blot analyses at different developmental stages of the chicken revealed that neuroserpin is predominantly expressed in the nervous system and that most cells expressing neuroserpin can be qualified as bona fide neurons. We have isolated the full-length cDNA for human neuroserpin from a fetal retina cDNA library. The open reading frame of the cDNA of human neuroserpin, like that of its chicken counterpart, encodes a protein of 410 amino acids. The human and the chicken neuroserpin exhibit an amino acid sequence identity of 80%. Northern blot analysis of human organs demonstrated predominant expression of neuroserpin in the brain. By fluorescence in situ hybridization the human neuroserpin gene (HGMW-approved symbol PI12) was mapped to region q26 of chromosome 3.

Amino Acid Sequence↗

Neurotrypsin, a novel multidomain serine protease expressed in the nervous system.

We have cloned a novel murine cDNA encoding a multidomain serine protease, termed neurotrypsin, which exhibits an unprecedented domain composition. The deduced amino acid sequence defines a mosaic protein of 761 amino acids consisting of a kringle domain, followed by three scavenger receptor cysteine-rich repeats, and a serine protease domain. Based on comparisons of the primary structure, the protease domain belongs to the subfamily of trypsin-like serine proteases. In situ hybridization revealed that the expression of neurotrypsin in the adult murine nervous system is confined to distinct subsets of neurons. The most prominent expression was found in the cerebral cortex, the hippocampus, and the amygdala. Le., structures engaged in the processing and storage of learned behaviors and memories. Together with the recently obtained evidence that extracellular serine proteases play a role in neural plasticity, this expression pattern suggests that the extracellular proteolytic action of neurotrypsin subserves structural reorganizations associated with learning and memory operations.

Amino Acid Sequence↗