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Biomedical subjects

M Hess

Publications and source records attributed to M Hess.

At least 109 records · Page 6Linked to original sources
PubMed1997

Detection of the t(2;5)(p23;q35) and NPM-ALK fusion in non-Hodgkin's lymphoma by two-color fluorescence in situ hybridization.

The non-Hodgkin's lymphoma (NHL) subset commonly referred to as large cell lymphoma (LCL) has historically been characterized by it's marked cytological, immunological, and clinical heterogeneity. One potential defining feature of these lymphomas, the t(2;5)(p23;q35), occurs in 25% to 30% of anaplastic LCLs and is also found in cases with diffuse large cell or immunoblastic morphology. We recently identified nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) as the genes on chromosomes 5 and 2, respectively, that are juxtaposed by this translocation. To provide a complementary approach to the use of classical cytogenetics or polymerase chain reaction-based methods for the detection of this abnormality, we have developed a two-color fluorescent in situ hybridization (FISH) assay for the t(2;5) that may be used for the analysis of both interphase nuclei and metaphase chromosomes. Three overlapping chromosome 5 cosmid clones located immediately centromeric to the NPM gene locus and an ALK P1 clone located telomeric to the chromosome 2 breakpoint were labeled with digoxigenin or biotin, respectively, and used to visualize the derivative chromosome 5 produced by the t(2;5), evident as juxtaposed or overlapping red and green fluorescent signals. This NPM-ALK FISH assay was initially validated by analysis of a series of cytogenetically characterized cell lines, with the presence of the der(5) chromosome showed specifically only in those lines known to contain the t(2;5). The assay was then applied in a blinded fashion to a series of eight cytogenetically t(2;5)-positive clinical specimens and seven known t(2;5)-negative cases, including three NHL and four Hodgkin's disease biopsy samples. Whereas the t(2;5)-negative cases were negative by FISH, all eight t(2;5)-positive cases were positive. One additional case, initially thought to be positive for the translocation by cytogenetics, was proven to not be a classic t(2;5) by interphase and metaphase FISH. These data indicate that the FISH assay described is a highly specific and rapid test that should prove to be a useful adjunct to the currently available methods for detection of the t(2;5).

Anaplastic Lymphoma Kinase↗
PubMed1997

Identification and characterization of penton base and pVIII protein of egg drop syndrome virus.

The nucleotide sequence and location of the penton base and pVIII genes of the egg drop syndrome (EDS) virus an avian adenovirus, were determined. The penton base gene is located at 34.8-38.8 map units. The coding sequence has a length of 1359 nt and encodes a polypeptide of 452 amino acids (aa) with a molecular weight of 51 105 Da. The amino acid sequence shows a homology of 57.3 and 55.3% to the structural protein IH of human adenovirus serotype 2 (HAd2) and fowl adenovirus serotype 1 (FAV1). The penton base protein lacks the integrin binding motifs RGD (Arg-Gly-Asp) and LDV (Leu-Asp-Val). At 65.1-67.3 map units an open reading frame of 753 nucleotides was identified which encodes the structural protein pVIH. It forms a protein of 250 aa with an expected molecular weight of 28 501 Da. Possible protease cleavage sites were identified. Amino acid homologies of 30.8 and 27.7% were found to the HAd2 and FAV1 pVIII genes. Remarkably, the overall amino acid identity with ovine adenovirus pVIII is 52%. The start codons of both genes are shifted leftwards compared with the respective structural elements on the HAd2 or FAV1 genomes which indicates a different genomic organization of the EDS virus.

Amino Acid Sequence↗
PubMed1997

Functional urinary bladder wall substitute using a free innervated latissimus dorsi muscle flap.

This study was designed to investigate the ability of the latissimus dorsi muscle in situ to evacuate a bladder reservoir and to study the functional, anatomic, and histopathologic results of partial or subtotal bladder reconstruction with an innervated free latissimus dorsi muscle in mongrel dogs. In group I (four dogs), the latissimus dorsi muscle was dissected and tailored in situ. Then the so-formed pedicled latissimus dorsi muscle flap was wrapped around tissue expanders of varying sizes (volumes of 50, 100, and 150 cc, respectively) to form a bladder-like reservoir. Electromyography and intraluminal pressure measurements were done at the time of surgery and 6 months thereafter using a standard electromyograph and a Dantec urodynamic unit. In group II (four dogs), the dome of the bladder wall was removed, with up to 50 percent of the mucosal layer being left intact. The resulting muscular defect was repaired with a free innervated latissimus dorsi muscle flap. The transferred latissimus dorsi muscle was shaped and wrapped around the bladder in a spiral form, with particular attention to the resting tension. The thoracodorsal vessels were anastomosed to the pelvic branches of the hypogastric vessels, and the thoracodorsal nerve was coapted to a pelvic motor nerve that was selected by use of a nerve stimulator. Cystography and urodynamic studies were performed after 3, 6, and 9 months. Electromyography was done after 9 months, before sacrifice of the animals, which was followed by regular histologic and electron microscopic examinations. Stimulation of the thoracodorsal nerve of the reconfigured latissimus dorsi muscle reservoirs in situ after 6 months yielded average intraluminal pressures of 190 cmH2O at maximum capacity and 35 cmH2O at a minimum capacity of 10 to 15 cc. Stimulation of the latissimus dorsi muscle transferred to the bladder resulted in a visible and measurable contraction of the transplanted muscle after 9 months. Urodynamic values preoperatively and postoperatively were basically unchanged. During cystography, the bladder outline was smooth during both filling and voiding. Light and electron microscopic examinations confirmed viable, reinnervated muscle. The reconfigured pedicled latissimus dorsi muscle has the ability to evacuate a bladder-like reservoir after nerve stimulation. A detrusor function of the bladder can be induced through the contractility of a reinnervated free latissimus dorsi muscle that was wrapped around the bladder. An innervated free latissimus dorsi muscle flap does not undergo severe muscle fibrosis, contracture, and atrophy such as occur after transfer of completely or partially denervated, pedicled muscle. This means that a functional bladder reconstruction/augmentation can be achieved by microneurovascular transfer of a latissimus dorsi muscle flap.

Animals↗
PubMed1997

Prostanoid formation during feeding of a preterm formula with long-chain polyunsaturated fatty acids in healthy preterm infants during the first weeks of life.

The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on prostanoid formation in preterm infants during their first weeks of life. In a prospective, randomized, double-blind study, healthy infants received either formula enriched with LCP (n = 10), standard preterm formula (n = 10), or (expressed) breast milk (n = 10). Urine was sampled, and anthropometric measurements were taken at study entry and after the study period of 3 wk. In vivo formation of prostaglandin E2, thromboxane A2, and prostacyclin was evaluated by measuring the urinary excretion of the respective index metabolities by gas chromatography-mass spectrometry. There were no significant differences in urinary prostanoid excretion and anthropometric data between the groups at the end of the study period. We conclude that neither conventional formula nor supplementation of a preterm formula with LCP for a period of 3 wk substantially influence prostanoid formation in healthy preterm infants.

Anthropometry↗
PubMed1997

Free neurovascular transfer of latissimus dorsi muscle to the bladder. I. Experimental studies.

OBJECTIVES: Experimental studies were undertaken to investigate the practicability of a microneurovascular transfer of latissimus dorsi muscle to the bladder, and to look for possible techniques enhancing evacuation of a reservoir such as the bladder by striated muscle. MATERIALS AND METHODS: Twelve dogs were used for the studies. They were divided into 3 groups. Group I: Evacuation proficiency of a re-configured latissimus dorsi under tension was hydrodynamically tested after 6 months. Group II: Microneurovascular latissimus dorsi transposition anastomosing thoracodorsal vessels and nerve to circumflexa ilium profunda vessels and a lumbar plexus motor nerve, respectively, was performed to cover the bladder devoid of up to 50% of the detrusor muscle. Group III: Microneurovascular latissimus dorsi transposition was used to reconstruct the bladder after supratrigonal cystectomy. Urodynamic and radiographic in vivo studies were done after 6 and 9 months. RESULTS: Stimulation of the thoracodorsal nerve of geometrically reconfigurated non-transposed latissimus dorsi reservoirs after 6 months yielded average intraluminar pressures of 190 cm. H2O at maximum capacity, and 35 cm. H2O at a minimum capacity of 10 to 15 cc. Stimulation of latissimus dorsi transposed to the bladder resulted in a visible and measurable contraction of the transplanted muscle after 9 months. Mean bladder volumes in group II animals pre- and postoperatively were 267.5 and 270 cc, respectively. During cystography the bladder outline was smooth both during filling and voiding. Light and electron microscopic examination confirmed viable, re-innervated muscle. CONCLUSIONS: The "tension-torsion" reconfiguration produced intraluminal pressures which should enable stimulated striated muscle to evacuate bladder-like reservoirs successfully. Microneurovascular free transfer of latissimus dorsi muscle resulted in reinnervated, functional muscle in the pelvis. Augmentation cystoplasty using the latissimus dorsi in conjunction with a free omental flap for substitution of an accompanying mucosal defect was unsuccessful. The concept of microneurovascular transfer of latissimus dorsi muscle to the pelvis may be used for complicated fistula of the lower urinary tract, and may be a possible solution for the therapy resistent acontractile bladder.

Animals↗
PubMed1996

Molecular Pathology of Dilated Cardiomyopathies.

The term idiopathic, defined as being of unknown etiology or mechanism, is no longer applicable to the dilated cardiomyopathies. The tools of molecular biology and clinical investigation have made significant progress, and it is now to the rare and exceptional case that one is forced to apply the term idiopathic. Further, having arrived at more precise cause, direct therapeutic intervention will become possible. The concept of gene insertion and "genetic therapy" is under active investigation. Unfortunately, the significant advances in the cause and disease mechanisms of DCM have not been matched in therapeutics. With few exceptions, we indirectly treat the DCMs by managing the CHF syndrome. However, several important points have emerged. The concept of LV afterload reduction is valid and efficacious. The use of vasodilator therapy has significantly reduced both mortality and morbidity and, in certain forms of cardiomyopathy (e.g., hypertensive, alcoholic, and doxorubicin-related), have significantly altered hemodynamics and permitted the injured heart to heal and return to a near normal functional state. However, as much as we want to congratulate ourselves on the progress bought with the use of vasodilators and ACE inhibitors, one must keep in mind that under the best of circumstances, the DCMs still carry an unacceptably high morbidity and mortality. A 40% to 50% 4- to 5-year mortality rate is depressing. Herein lies the challenge. With the significant progress in pathogenesis and etiology, we now stand at the threshold of new, innovative advances in therapeutics. These new concepts in both therapeutics and prevention will require courage, dedication, and hard work. But bit by bit, these seemingly insolvable problems will yield to the discipline and imagination of the investigator. The DCMs will continue to be a challenging problem for future investigators. Progress has been dramatic, and it should continue even at an accelerated pace as we approach the twenty-first century.

Animals↗
PubMed1996

Design and development of a pressure relief seating apparatus for individuals with quadriplegia.

Persons with spinal cord injury above C7 lack the ability to extend their elbows and grip with their hands. Consequently, when seated, they are unable to press down to shift their weight to relieve pressure on the ischial tuberosities. This can ultimately cause serious pressure sores to develop on the buttocks. Those with adequate insurance coverage can eliminate this problem with an electric power recliner wheelchair. With the touch of a button, the backrest will fold down to a laying position, thus relieving the pressure on the ischial tuberosity. Unfortunately, not all individuals with quadriplegia possess this type of coverage. Therefore, the problem requires an alternate design that will utilize mechanical rather than electrical power to produce a cost-effective solution. The purpose of this project was thus to design and build an affordable apparatus adaptable to wheelchairs that allows individuals with quadriplegia to shift their weight from one side to the other thus relieving the pressure on the ischial tuberosities. A pneumatic system that utilizes two inflatable air bladders was employed. One cushion is placed under each buttock and inflated separately to tilt the user from one side to the other. The inflated cushion elevates one side of the buttock, which relieves the pressure from the other side. The power required to operate the system is generated using repetitions of elbow flexion. The system was evaluated on an individual with C6 quadriplegia. The subject demonstrated independent pressure relief without intrusion on cosmesis or independence.

Cost-Benefit Analysis↗
PubMed1996

High rate of prolonged remissions following combined modality therapy for patients with localized low-grade lymphoma.

PURPOSE: Involved field (IF) radiation can cure as many as 40% to 50% of patients with stage I-II low-grade lymphoma. We sought to improve these results by prospectively evaluating the combination of IF radiation and chemotherapy consisting of 10 courses of cyclophosphamide, vincristine, prednisone, and bleomycin, with doxorubicin added in a risk-adapted manner (COP/CHOP-Bleo). PATIENTS AND METHODS: From 1984 until December 1992, 91 patients, median age 56 years (range 28 to 77 years), with clinical stage I-II low-grade lymphoma were treated. No patients were excluded on the basis of age or organ function. RESULTS: A complete response was attained in 99% of evaluable patients. Treatment-related toxicity was mild, and no deaths occurred during therapy. With a median follow-up of 60 months, there have been only 16 relapses. The actuarial freedom from relapse rate at five years is 82% (95% confidence interval 71% to 89%) and at 10 years is 73%. At five years the overall survival rate is 90% (95% confidence interval 81% to 95%) and at ten years it is 82%. Of the clinical features examined, only older age (> 56 years; p = 0.07) was associated with shorter survival. No features examined were predictive of disease relapse. CONCLUSION: The combination of IF radiation and risk-adapted COP/CHOP-Bleo chemotherapy is well-tolerated, produces a very high rate of complete remission, and with a median follow-up of five years, has produced lower rates of relapse and better overall survival than has been reported for IF radiation alone in patients with clinically-staged I-II low-grade lymphoma.

Adult↗
PubMed1996

High-speed imaging of vocal fold vibrations and larynx movements within vocalizations of different vowels.

Theoretic investigations of the "source-filter" model have indicated a pronounced acoustic interaction of glottal source and vocal tract. Empirical investigations of formant pattern variations apart from changes in vowel identity have demonstrated a direct relationship between the fundamental frequency and the patterns. As a consequence of both findings, independence of phonation and articulation may be limited in the speech process. Within the present study, possible interdependence of phonation and phoneme was investigated: vocal fold vibrations and larynx position for vocalizations of different vowels in a healthy man and woman were examined by high-speed light-intensified digital imaging. We found 1) different movements of the vocal folds for vocalizations of different vowel identities within one speaker and at similar fundamental frequency, and 2) constant larynx position within vocalization of one vowel identity, but different positions for vocalizations of different vowel identities. A possible relationship between the vocal fold vibrations and the phoneme is discussed.

Adult↗
PubMed1995

The avian adenovirus penton: two fibres and one base.

The penton capsomer of mammalian adenoviruses consists of a trimeric, long and thin fibre inserted into a pentameric base. The avian adenoviruses possess a penton which presents another symmetry mismatch: each pentameric base is associated with two fibres. Here we have studied the morphology of the penton of CELO virus, an avian adenovirus, and we have determined the sequence of both fibres, one long and one short. The short fibre is probably associated with the base in the same way as the mammalian viral fibres and we will discuss how the long fibre could be attached. The shafts of all known adenovirus fibres consist of a series of 15-residue repeats. The avian virus fibres show a more complicated and less regular shaft repeat structure with single, double and triple repeats. The sequences of the receptor binding (head) domains of both fibres are very different from all other known fibre head domains and very different from each other, suggesting that the two fibres might bind to different receptors. The genome organization of the sequenced region is rather different from that in human adenoviruses. In particular, a region homologous to the human virus E3 region was not found at the position where it normally occurs in the human virus genome.

Amino Acid Sequence↗
PubMed1995

The gag homologue of retrotransposon Ty1 assembles into spherical particles in Escherichia coli.

Expression of TyA (reading frame A) of the yeast retrotransposon Ty1 in Escherichia coli is possible by using efficient transcriptional and translational initiation signals. When expressed in E. coli, the gag homologue of Ty1 assembles into spherical particles similar, but not identical to virus-like particles in the natural host of Ty1, Saccharomyces cerevisiae. Deletion analysis reveals a domain in the C-terminus of TyA that is essential for the assembly process. These findings indicate that an early step of the retroelement life cycle, assembly of the gag homologue into spherical particles, does not depend on specific host factors. The experiments also demonstrate that Ty1 Gag fusion proteins, potential tools for immunization, can be produced in E. coli, an organism that lacks endogenous retrotransposons.

Amino Acid Sequence↗
PubMed1995

Molecular characterization of two strains of the avian adeno-associated virus (AAAV).

An avian adeno-associated virus (AAAV) was isolated after propagating a field isolate of the CELO virus (fowl adenovirus serotype 1 (FAV1)) in embryonated eggs. The isolated dependovirus was compared with the known AAAV obtained from the American Type Culture Collection (ATCC VR-865). The genomes were analysed by digestion with several restriction endonucleases. Although both DNAs have the same size, most restriction enzymes produced different restriction patterns. Double digests were used to construct for the first time restriction maps for avian dependoviruses. The two DNAs rendered different restriction maps in which the different restriction sites were mainly located in the middle and right part of the genomes. The effect of these differences on the structure proteins was shown by western blot analysis. In the immunoblot, the immunofluorescence and immunodiffusion test the two dependoviruses were serologically indistinguishable and therefore can be regarded as two different strains of the same virus. To differentiate between both strains we named the original one as AAAV VR-865 compared with the isolated AAAV DA-1.

Animals↗
PubMed1995

Comparison of DNA content in non-Hodgkin's lymphoma as measured by flow cytometry and cytogenetics.

Specific cytogenetic changes such as t(14;18) and t(8;14) are associated with specific histologic subtypes of non-Hodgkin's lymphoma (NHL) and may predict disease outcome. Nonspecific cytogenetic changes include other structural rearrangements or numerical changes such as monosomies and trisomies, which may cause changes in total cellular DNA content. In many solid tumors, the presence of abnormal DNA content may be predictive of clinical behavior. NHL biopsies, however, contain normal (diploid) as well as abnormal cells, and DNA changes in the peridiploid range are detectable by cytogenetic analysis, but not consistently by flow cytometry. In the present study, we performed flow cytometric and cytogenetic analysis of DNA on biopsies from 129 patients with non-Hodgkin's lymphoma (NHL). Cytogenetic studies were successful on 88 (68%) of the samples. There was 55% concordance between flow cytometric and cytogenetic techniques in detecting aneuploid DNA content, with the majority of discrepancies occurring in the peridiploid range. We also detected six samples which were aneuploid by flow cytometry, but diploid by cytogenetics. We suggest that a reasonable approach to determine DNA content, as it relates to prediction of outcome in NHL, would be to combine data from both of these techniques and analyze the results in terms of ranges of DNA rather than by categorizing as diploid versus aneuploid.

Aneuploidy↗
PubMed1995

Testicular lymphoma: late relapses and poor outcome despite doxorubicin-based therapy.

PURPOSE: To determine the significance of the International Prognostic Index (IPI) score in adults with testicular lymphoma treated with doxorubicin-based regimens. PATIENTS AND METHODS: Untreated adults with testicular lymphoma who presented between 1969 and 1993 were studied. Those with Ann Arbor stages III and IV were included if they had a testicular mass at presentation. RESULTS: We identified 22 patients, 21 with intermediate-grade and one with high-grade lymphoma. All 10 patients with an IPI score < or = 1 had Ann Arbor stage I disease, whereas the 12 with an IPI score more than 1 had Ann Arbor stage II to IV disease. Complete remission (CR) was achieved in 73% of patients. At 153 months, 22% of all complete responders and 40% and 0% of those with IPI scores < or = 1 and more than 1, respectively, remained in CR (P = .01). With a median follow-up time of 113 months for survivors, the failure-free survival (FFS) rate at 153 months was 16% for all patients or 32% and 0% for those with IPI scores < or = 1 and more than 1, respectively (P = .02). The CNS or contralateral testis were involved in all patients who failed to respond to primary therapy and in 50% of those who relapsed from CR. CONCLUSION: The prognosis of patients with testicular lymphoma appears poor despite doxorubicin-based chemotherapy. On the basis of failures in the CNS and contralateral testis, we recommend prophylactic intrathecal chemotherapy and scrotal radiotherapy for all patients. Those with an IPI score < or = 1 can be treated with conventional doxorubicin-based regimens, but those with an IPI score more than 1 should be considered for investigational systemic therapy.

Adult↗
PubMed1995

Activation of cyclic nucleotide phosphodiesterases in FRTL-5 thyroid cells expressing a constitutively active Gs alpha.

The expression of a constitutively activated Gs alpha protein in the rat thyroid cell line FRTL-5 causes an increase in the hormone-independent adenylyl cyclase activity and promotes TSH-independent growth of the cells. In spite of the constitutive activation of the adenylyl cyclase, the basal cAMP levels in these cells are only marginally increased. To define the role of phosphodiesterases (PDEs) in the genesis of this phenotype, cyclic nucleotide hydrolysis was determined in two cell lines expressing a mutated Gs alpha (Q227L). In these cells, the hydrolysis of both cAMP and cGMP was markedly increased in comparison with normal cells. This increase is the result of the activation of different forms of PDEs. Analysis of the cGMP hydrolysis and Ca++/calmodulin stimulation of the PDE activity indicated that the activity of a Ca++/calmodulin-stimulated PDE is increased in both cell lines. In addition, an increase in high-affinity, rolipram-sensitive cAMP-PDE activity was associated in both cell lines with the appearance of a 67-68 kilodalton (kDa) protein that cross-reacts with two antibodies against cAMP-PDEs. This form had the properties of ratPDE3.2/PDE4D2, a cAMP-PDE that is inducible by TSH in wild type cells. That an increase in cAMP-specific, rolipram-sensitive PDE plays a role in the phenotype induced by Q227L Gs alpha was confirmed by measurements of the mitogenic activity. Incubation with rolipram, which had no effect on wild type cells, caused an increase in cAMP levels and further stimulated TSH-independent proliferation in both cell lines carrying the mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides.

Food ingestion induces a rapid increase in the insulinotropic glucagon-like peptide-1 (GLP-1) in plasma. Paradoxically, GLP-1 originates from the lower intestines and therefore a complex regulation of postprandial GLP-1 secretion must exist. This was addressed in the present study by utilizing an isolated vascularly perfused rat ileum preparation. Peptides and neurotransmitters thought to be candidate mediators triggering GLP-1 secretion were arterially infused and GLP-1 was measured in the venous effluent. Arterial infusion of cholinergic agonists strongly enhanced GLP-1 secretion which was counteracted by the addition of atropine. Histamine, dopamine, 5-hydoxytryptamine, gamma-aminobutyric acid, and norepinephrine had no effect. Peptides of the bombesin family were strong stimulants whereas tachykinins, enkephalins, dynorphin, TRH, calcitonin-gene-related peptide and members of the secretin family, vasoactive intestinal peptide, peptide histidine isoleucine and neuropeptide Y, were less effective. The second incretin hormone, gastric inhibitory polypeptide (GIP), was the most potent stimulant of GLP-1 secretion in our study. It enhanced GLP-1 release up to sixfold above basal during the early phase followed by a sustained secretion at 400% above basal. This stimulation remained unaffected by atropine. In conclusion, in addition to luminal stimulation of nutrients, a cholinergic impulse as well as peptidergic mediators (among them possibly GIP and GRP) may have an impact on postprandial GLP-1 secretion from the rat ileum.

Animals↗
PubMed1995

Proliferative fraction and DNA content are lower in B-cell non-Hodgkin's lymphomas with the t(14;18).

The t(14;18), which juxtaposes the immunoglobulin enhancer region from chromosome 14 to the bcl-2 gene on chromosome 18, is a recurrent cytogenetic abnormality in the majority of follicular lymphomas (FL). This translocation results in overexpression of bcl-2, which increases cellular life span of the mutated cells by decreasing apoptosis. The t(14;18) also occurs in a subgroup of diffuse large cell lymphomas (DLCL), and current thought is that the majority of these represent transformation of FL. Low grade FL are characterized by low proliferation, and diploid/peridiploid DNA content. In this study, we compared proliferative activity (PF) and DNA content (DI) in FL containing the t(14;18) to DLCL with and without the t(14;18). The mean PF and DI were lower in the NHL containing t(14;18) irregardless of histologic subtype. We conclude that increased life span due to the presence of t(14;18) provides the conditions for accumulation of a different set of mutations as compared to those NHL developing from mutations in more rapidly proliferating precursors. This has implications for prognosis of patients with DLCL depending upon the presence or absence of t(14;18).

Cell Division↗