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Biomedical subjects

W Koch

Publications and source records attributed to W Koch.

At least 73 records · Page 4Linked to original sources
PubMed1997

The social networks of older schizophrenia patients. Clinical Research Center on Late Life Psychosis Research Group.

There is a paucity of research that examines the role of family members and friends in the lives of older schizophrenia patients. This study compared 66 middle-aged and elderly outpatients with 31 normal comparison subjects. Five dimensions of social network were assessed: (a) family composition, geographic proximity, and frequency of contact; (b) instrumental support; (c) emotional support and interpersonal difficulties; (d) role of friends; and (e) use of formal service providers as sources of support and assistance. As compared with normal subjects, the schizophrenia patients were less likely to be married, less likely to have children, more likely to live alone, and had fewer friendships. The patients were, however, similar to comparison subjects on the following family-relationship variables: frequency of contact, instrumental support received, presence of a family confidant, and extent of interpersonal difficulties. These findings do not support the stereotype of older schizophrenia patients as being estranged from family members. The need for developing interventions that use key family members to interface with service providers and to monitor treatment compliance and continuity of care is discussed.

Age Factors↗
PubMed1997

Specific phosphatidylethanolamine dependence of Serratia marcescens cytotoxin activity.

The cytolytic and haemolytic activity of Serratia marcescens is determined by the ShlA protein, which is secreted across the outer membrane with the aid of the ShlB protein. In the absence of ShlB, inactive ShlA* remains in the periplasm of Escherichia col transformed with an shlA-encoding plasmid, which indicates that ShlB converts ShlA* to active ShlA. ShlA* in a periplasmic extract and partially purified ShlA* were activated in vitro by partially purified ShlB. When both proteins were highly purified, ShlA* was only activated by ShlB when phosphatidylethanolamine (PE) or phosphatidylserine was added to the assay, while phosphatidylglycerol contributed little to ShlA* activation. Lyso-PE, cardiolipin, phosphatidylcholine, phosphatidic acid, lipopolysaccharide and various detergents could not substitute for PE. Although radioactively labelled PE was so tightly associated with ShlA that it remained bound to ShlA after heating and SDS-PAGE, it was not covalently linked to ShlA as PE could be removed by thin-layer chromatography with organic solvents. The number of PE molecules associated per molecule of ShlA was 3.9 +/- 2.2. Active ShlA was inactivated by treatment with phospholipase A2, which indicated that PE is also required for ShlA activity. ShlA-255 (containing the 255 N-terminal amino acids of ShlA) reversibly complemented ShlA* to active ShlA and was inactivated by phospholipase A2, which demonstrated that PE binds to the N-terminal portion of ShlA; this region has previously been found to be involved in ShlA secretion and activation. Electrospray mass spectroscopy of ShlA-255 determined a molar mass that corresponded to that of unmodified ShlA-255. An E. coli mutant that synthesized only minute amounts of PE did not secrete ShlA but contained residual cell-bound haemolytic activity. Since PE binds strongly to ShlA* in the absence of ShlB without converting ShlA* to haemolytic ShlA, ShlB presumably imposes a conformation on ShlA that brings PE into a position to mediate interaction of the hydrophilic haemolysin with the lipid bilayer of the eukaryotic membrane.

Agar↗
PubMed1997

Arthroscopy for chronic hemophilic synovitis of the knee.

Between 1988 and 1995, 32 knee joints (29 patients) with hemophilic arthropathy underwent arthroscopy. The spectrum of procedures ranged from resection of fibrous plicae to synovectomy. Technical difficulties appeared in cases of scarred fixed patella, pronounced posterior tibia subluxation, and severe fibrous ankylosis. All operations done between 1988 and 1991 (23 operations; 21 patients) were reviewed retrospectively. The mean age of the patients in this series was 30 years and the mean followup was 5 years. On subjective evaluation, 13 operations achieved a definite improvement, five showed slight improvement, and two had no improvement (three operations were excluded). Arthroscopic surgery, as a relatively low risk technique, combined with early functional rehabilitation, can be used to achieve satisfactory results in patients with hemophilic arthropathy.

Adolescent↗
PubMed1996

p16 and p16 beta are potent growth suppressors of head and neck squamous carcinoma cells in vitro.

p16 (CDKN2/MTS1/p16INK4a) is frequently deleted, methylated, or mutated in many malignancies including squamous cell carcinoma of the head and neck (HNSCC). p16 beta is an alternative transcript derived from a newly described exon (exon 1 beta) located more than 15 kb 5' to exon 1 of p16. Moreover, the p16 beta transcript theoretically encodes a protein distinct from p16 derived from a divergent reading frame putatively initiated in exon 1 beta. To test the contribution of both of these transcripts in carcinogenesis, full-length cDNA of p16 and p16 beta were cloned in separate vector constructs and then transfected into HNSCC cell lines characterized for p16 status (p16[+/+], p16[mut/-], and p16[methylated]). Transfection of either p16 or p16 beta resulted in marked growth inhibition in all three HNSCC lines tested, regardless of p16 status. However, p16 beta but not p16 inhibited the growth of HeLa cells, a cell line with inactive pRB due to expression of E7 papillomavirus protein. Moreover, transfection of all three HNSCC lines with either p16 or p16 beta resulted in a marked increase in cells in G0-G1 consistent with a cell cycle arrest in G1. These data are consistent with the hypothesis that p16 and p16 beta are growth-inhibitory genes active in HNSCC and that both act by blocking progression through the G1-S transition of the cell cycle. Furthermore, the suppressive effects of p16 beta on HeLa growth suggest that p16 beta mediates its effect independently from pRB.

Alternative Splicing↗
PubMed1996

High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma.

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) can be inactivated by multiple genetic mechanisms. We analyzed 29 invasive primary head and neck squamous cell carcinomas (HNSCC) for p16 inactivation with immunohistochemistry utilizing a new monoclonal antibody (mAb), DCS-50. p16 staining of the primary lesions was correlated with genetic analysis including: (a) detailed microsatellite analysis of markers at the p16 locus to detect homozygous deletion; (b) sequence analysis of p16; and (c) Southern blot analysis to determine the methylation status of the 5' CpG island of p16. Twenty-four of 29 (83%) head and neck squamous cell carcinoma tumors displayed an absence of p16 nuclear staining using immunohistochemistry. Of these 24 tumors, we found that 16 (67%) harbored homozygous deletions, 5 (21%) were methylated, 1 displayed a rearrangement at the p16 locus, and 1 displayed a frameshift mutation in exon 1. These data suggest that: (a) inactivation of the p16 tumor suppressor gene is a frequent event in squamous cell carcinomas of the head and neck; (b) p16 is inactivated by several distinct and exclusive events including homozygous deletion, point mutation, and promoter methylation; and (c) immunohistochemical analysis for expression of the p16 gene product is an accurate and relatively simple method for evaluating p16 gene inactivation.

Blotting, Southern↗
PubMed1996

Multiple head and neck tumors: evidence for a common clonal origin.

Patients with head and neck cancers have a high (2-3%/year) incidence of second primary lesions. Clinically, these new lesions are identified either simultaneously with the primary lesion (synchronous) or after a period of time (metachronous). This observation has been attributed to the concept of "field carcinogenesis," which is based on the hypothesis that prolonged exposure to carcinogens leads to the independent transformation of multiple epithelial cells at several sites. An alternative theory is based on the premise that any transforming event is rare; following initial transformation, the progeny of the transformed clone spread through the mucosa and give rise to geographically distinct but genetically related tumors. We analyzed the pattern of X-chromosome inactivation in multiple primary tumors from eight female patients with head and neck cancer. In addition, we used microsatellite analysis to examine the pattern of allelic loss on chromosomes 9p and 3p, identified as early events in the progression of head and neck malignancies. In four of four cases, multiple tumors demonstrated the same pattern of X-chromosome inactivation. In the remaining four cases, X-chromosome deletions prevented interpretation (n = 3), or the androgen receptor locus was noninformative (n = 1). In three of nine patients, multiple tumors displayed the same pattern of loss of heterozygosity, two with identical breakpoints on chromosome 9p. In one patient, there was an identical microsatellite alteration at a 3p locus, definitive evidence that these tumors arose from the same clone. Our findings suggest that in at least a proportion of patients with head and neck cancers, multiple primary tumors arise from a single clone.

Chromosomes, Human, Pair 3↗
PubMed1996

Genetic progression model for head and neck cancer: implications for field cancerization.

A genetic progression model of head and neck squamous cell carcinoma has not yet been elucidated, and the genetic basis for "field cancerization" of the aerodigestive tract has also remained obscure. Eighty-seven lesions of the head and neck, including preinvasive lesions and benign lesions associated with carcinogen exposure, were tested using microsatellite analysis for allelic loss at 10 major chromosomal loci which have been defined previously. The spectrum of chromosomal loss progressively increased at each histopathological step from benign hyperplasia to dysplasia to carcinoma in situ to invasive cancer. Adjacent areas of tissue with different histopathological appearance shared common genetic changes, but the more histopathologically advanced areas exhibited additional genetic alterations. Abnormal mucosal cells surrounding preinvasive and microinvasive lesions shared common genetic alterations with those lesions and thus appear to arise from a single progenitor clone. Based on these findings, the local clinical phenomenon of field cancerization seems to involve the expansion and migration of clonally related preneoplastic cells.

Carcinoma, Squamous Cell↗
PubMed1996

Embryotoxicity study of monomeric 4,4'-methylenediphenyl diisocyanate (MDI) aerosol after inhalation exposure in Wistar rats.

One of the uses of MDI is as an alternative to formaldehyde in the manufacture of furniture, its main route of exposure to humans being by inhalation. There have been no previous studies on the potential prenatal toxic effects of this compound. To close this gap in information, gravid Wistar rats, Crl:(WI)BR, were exposed by whole-body inhalation to clean air (control) and to 1, 3, and 9 mg/m3 MDI, respectively, for 6 hr per day from Days 6 to 15 post conception (p.c.). Rats were killed on Day 20 p.c. and the following results were obtained: Treatment caused a dose-dependent decrease in food consumption in all substance-treated groups during exposure, returning to normal values after cessation of treatment. The lung weights in the high-dose group were significantly increased compared to the sham-treated control animals. Treatment did not influence any other material and/or fetal parameters investigated (maternal weight gain, number of corpora lutea, implantation sites, pre- and postimplantation loss, fetal and placental weights, gross and visceral anomalies, degree of ossification), although a slight but significant increase in litters with fetuses displaying asymmetric sternebra(e) was observed after treatment with the highest dose of 9 mg/m3. Although the relevance of an increase of this minor anomaly in doses which cause toxic effects in dams (reduced food consumption, increased lung weights) is limited and the number observed is within the limits of biological variability, a substance-induced effect in the high-dose group cannot be excluded with certainty. Consequently, a no embryotoxic effect level of 3 mg/m3 was determined.

Administration, Inhalation↗
PubMed1996

Biomechanical studies of transthoracic vertebral body replacement with autologous bone grafts (fibula and rib).

Thoracic processes which destroy vertebral bodies leave gaps which usually have to be bridged. The aim of our experiments was to find out whether rib and fibula grafts are suitable vertebral body substitutes from the biomechanical point of view. Therefore, we examined characteristics of vertebral body/bone graft/vertebral body arrangements under the influence of pulsating compression forces in a testing machine. The deformation of the rib graft alone was 0.78 mm under a preselected peak load of 1010 Newton. When the rib graft was placed between two vertebral bodies, the deformation (creeping) was 6 mm under a peak load of 1010 Newton. The deformation of the fibula graft alone was 0.41 mm, and when placed between vertebral bodies maximally 3 mm. The results of our experiments lead to the conclusion that ribs modified according to our design are prinzipally suitable for vertebral body replacement in the thoracic region as far as primary stress resistance is concerned. Characteristics of these bone grafts in the human body are being followed-up.

Biomechanical Phenomena↗
PubMed1996

Evaluation of auditory discrimination in children with ADD and without ADD.

Auditory discrimination abilities of children with and without attention deficits were investigated to measure the variability due to different response modes (verbal [NU-6] and picture pointing [GFW]) and competing messages (GFW). Results showed no differences between response modes in quiet, but significant differences in noise between groups with children having ADD showing poorer speech discrimination. Additionally, differential effects between types of competing messages for the same task were not found in the ADD group. These results are discussed in relation to the clinical use of these tests, the relationships seen between results, and implications for educational management.

Attention↗
PubMed1996

Perception of loudness in children with ADD and without ADD.

Twenty-eight children identified with attention deficits and a comparison group of children without ADD were asked to judge the loudness of speech as comfortable (MCL) or tolerable (TL). Results indicated that children with attention deficits required a softer level to make both of these loudness judgements. Children with ADD had statistically significant differences in their choices of comfort levels (MCL = 51 dBHL) and choices of tolerance levels (TL = 95 dBHL) from their peers without ADD (MCL = 59 dBHL, TL = 100 dBHL). These findings are viewed in relation to perceptual differences between children with and without ADD. Additionally, implications for classroom management are discussed.

Attention↗
PubMed1996

Microsatellite alterations in serum DNA of head and neck cancer patients.

Microsatellite DNA alterations are an integral part of neoplastic progression and are valuable as clonal markers for the detection of human cancers. Moreover, recent evidence suggests that senescent tumor cells may release DNA into the circulation, which is subsequently carried by and therefore enriched in the serum and plasma. We tested 21 patients with primary head and neck squamous cell carcinoma (HNSCC) by polymerase chain reaction (PCR)-based microsatellite analysis of DNA from lymphocytes and paired serum samples. Patients were scored for alterations as defined by the presence of new alleles (shifts) or loss of heterozygosity (LOH) in serum at each of 12 markers and then compared with primary tumor DNA. Six out of 21 patients (29%) were found to have one or more microsatellite alterations in serum precisely matching those in the primary tumors. All six patients had advanced disease (stage III or IV); five of these patients had nodal metastases, three later developed distant metastases, and four died of disease. Microsatellite analysis of serum represents a novel method for the detection of circulating tumor cell DNA. If these results are confirmed in larger studies, microsatellite markers may be useful in assessing tumor burden in cancer patients.

Adult↗
PubMed1996

Parvovirus B19 in anemic liver transplant recipients.

Five hundred thirty-three liver transplant recipients were seen for follow-up care over a 6-month period. Of these, 23 (4.3%) had a hemoglobin level of < or = 9 g/dl, with 19 being eligible for inclusion in this study. The median hemoglobin level was 8.7 g/dl. Two patients had iron-deficiency anemia. All of the patients were on therapeutic drugs which can suppress erythropoiesis or shorten the lifespan of mature erythrocytes. Six patients (31.6%) were viremic for human parvovirus B19 but none was B19 immunoglobulin M seropositive. Two patients were immunoglobulin M seropositive for cytomegalovirus. The patients with circulating B19 DNA were not easily distinguished from those without the virus by their laboratory results. The absence of reticulocyte counts for these patients contributed to this inability to differentiate B19 from other causes of anemia, particularly drug myelotoxicity. The high likelihood of making a specific diagnosis with the increasing availability of PCR should spur the search for this virus in the liver transplant population.

Adult↗
PubMed1995

Transactivating function and expression of the x gene of hepatitis B virus.

BACKGROUND/AIMS: The x gene of hepatitis B virus encodes a transactivating factor of 154 amino acids, termed HBx, which stimulates transcription of multiple viral and cellular genes. The transactivating function is probably associated with a tumorigenic potential of HBx, since x gene sequences, encoding functional HBx, have been repeatedly found integrated into the genome of liver carcinoma cells. METHODS: To identify the transactivating domain of HBx, we constructed x gene plasmids encoding full length HBx or HBx fragments. We determined their transactivating function after cotransfection of cells, along with a plasmid that contains a reporter gene driven by the SV40 early promoter/enhancer region. RESULTS: Our results demonstrate that a 95-amino acid fragment of HBx, encompassing amino acids 49 to 143, contains all the elements that are required for the transactivating function. Within this fragment a sequence element, encompassing amino acids 107 to 130, which contains a relatively high number of amino acids with charged side chains, appears to be crucial for the stimulation of gene expression. The influence of deletion mutations on x mRNA steady-state levels and HBx stability was examined. In essence, stable RNA and protein were produced if at least codons 1-82 or 70-154 were present in the deletion plasmids. CONCLUSION: This finding strongly suggests that the deletion of functional domains between codons 49 and 143, but not an instability of RNA and/or protein, was critical for the loss of transactivation.

Blotting, Northern↗
PubMed1995

Frequency of homozygous deletion at p16/CDKN2 in primary human tumours.

Many tumour types have been reported to have deletion of 9p21 (refs 1-6). A candidate target suppressor gene, p16 (p16INK4a/MTS-1/CDKN2), was recently identified within the commonly deleted region in tumour cell lines. An increasing and sometimes conflicting body of data has accumulated regarding the frequency of homozygous deletion and the importance of p16 in primary tumours. We tested 545 primary tumours by microsatellite analysis with existing and newly cloned markers around the p16 locus. We have now found that small homozygous deletions represent the predominant mechanism of inactivation at 9p21 in bladder tumours and are present in other tumour types, including breast and prostate cancer. Moreover, fine mapping of these deletions implicates a 170 kb minimal region that includes p16 and excludes p15.

Blotting, Southern↗