PubMed HealthSearch

Biomedical subjects

P Katz

Publications and source records attributed to P Katz.

At least 19 recordsLinked to original sources

Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase.

Eukaryotic cells respond to different extracellular stimuli by recruiting homologous signalling pathways that use members of the MEKK, MEK and ERK families of protein kinases. The MEKK-->MEK-->ERK core pathways of Saccharomyces cerevisiae may themselves be regulated by members of the STE20 family of protein kinases. Here we report specific activation of the mammalian stress-activated protein kinase (SAPK) pathway by germinal centre kinase (GCK), a human STE20 homologue. SAPKs, members of the ERK family, are activated in situ by inflammatory stimuli, including tumour-necrosis factor (TNF) and interleukin-1, and phosphorylate and probably stimulate the transactivation function of c-Jun. Although GCK is found in many tissues, its expression in lymphoid follicles is restricted to the cells of the germinal centre, where it may participate in B-cell differentiation. Activation of the SAPK pathway by GCK illustrates further the striking conservation of eukaryotic signalling mechanisms and defines the first physiological function of a mammalian Ste20.

Anisomycin

The psychotherapeutic treatment of suicidal adolescents.

The therapeutic work with a suicidal adolescent begins with the therapist's recognition that there are a multitude of causes for suicidal behavior and that the risk of a serious suicide attempt lies in the patient's feeling of desperation about his situation, the feeling that he faces intolerable pain due to shame or embarrassment, degradation, guilt or loss. The patient can not assess whether his view of his situation is realistic or not, and he is unable to conceive of alternative solutions. The therapist must throw the patient a lifeline to give him hope of escaping from his belief that he is trapped in a world of unending pain. That lifeline may be an active intervention in the life of a patient, reality testing of the patient's perceptions that he is trapped, or both. The choice of interventions is based on an exploration of the psychodynamic and psychopathological constellations that have caused the patient to feel so trapped. Patients, in their anguish, will resort to extremes of coercion and manipulation; the therapist must be able to tolerate and work with these behaviors. The therapist must maintain his belief that he can find ways to help the patient, while accepting the possibility that some day he might fail. He can succeed only if he is prepared to fail. Meeks (1984) summed up his article on suicidal adolescents in the following way: Success in the therapy of these youngsters does not depend on brilliant insights as much as on persistence, patience, and a sustained hope for the future. The treatment process may become a demonstrated proof that the therapist can stand to feel the patient's feelings and live the patient's painful existence, without giving up on life or the patient [p. 5].

Adolescent

Differential expression of a novel protein kinase in human B lymphocytes. Preferential localization in the germinal center.

B lymphocytes which reside in the germinal center region of lymphoid follicles are functionally and phenotypically distinct from the surrounding mantle zone B cells. We have isolated cDNA clones for several genes that are differentially expressed between these two populations of B lymphocytes. One such gene, BL44, is preferentially expressed in germinal center B cells. The nucleotide sequence of a 2,874-base pair BL44 cDNA was determined and a 2,451-bp open reading frame found that encodes for a 97-kDa serine/threonine protein kinase referred to as GC kinase. It has an NH2-terminal catalytic domain most similar to that of the Drosophila NinaC protein and the yeast STE20 protein. GC kinase mRNA transcripts are not unique to germinal center B cells and are found in several other tissues, including brain, lung, and placenta. The GC kinase protein was immunoprecipitated from transfected COS cells and from the Burkitt cell line RAMOS. GC kinase immunoprecipitated from transfected COS cells phosphorylated the substrates casein and myelin basic protein. In addition, a 97-kDa phosphoprotein likely to be GC kinase itself was detected. GC kinase may participate in an important signal transduction pathway in germinal center B cells.

3T3 Cells

Dyspnea and pulmonary function in the L-tryptophan-associated eosinophilia-myalgia syndrome.

We reviewed the pulmonary history, dyspnea ratings, and pulmonary function test results in 16 patients with L-tryptophan-induced eosinophilia myalgia syndrome to determine the correlation between reported pulmonary complaints and pulmonary function abnormalities. All patients reported pulmonary symptoms. Dyspnea, seen in 14 of 16 (87 percent) patients, was the most common symptom. The severity of dyspnea was graded by the baseline dyspnea index and the oxygen cost diagram. Pulmonary function testing including maximal static inspiratory and expiratory pressures were measured. The DCO was diminished in 12 of 16 (75 percent) patients. The MSIP was decreased in seven out of ten (70 percent) and the MSEP was decreased in nine out of ten (90 percent) of those patients tested. There was a statistically significant correlation between the severity of dyspnea as graded by the BDI and OCD, and the decrease in DCO. These results and a review of the literature of the pulmonary manifestations of EMS lead us to conclude that patients with EMS have a high prevalence of dyspnea, and it appears to be caused by both lung parenchymal involvement, as well as respiratory muscle weakness.

Adult

Cost of and payment source for pelvic inflammatory disease. Trends and projections, 1983 through 2000.

Pelvic inflammatory disease (PID) and its sequelae affect millions of women in the United States at substantial costs. To estimate these total costs annually and to determine payment sources, we analyzed data from local, state, and national sources. Direct costs for PID and PID-associated ectopic pregnancy and infertility were estimated to be $2.7 billion, and indirect costs were estimated to be $1.5 billion, for a total cost of $4.2 billion in 1990. Overall, private insurance covered the largest portion of the direct costs of PID (41%), followed by public payment sources (30%). However, the proportion of payments made by private insurance appears to be decreasing, while that by public payment sources is increasing. In the year 2000, costs associated with PID are projected to approach $10 billion if the current PID incidence persists, with an increasing proportion of this expense burdening public institutions. Prevention of PID is needed both to reduce human suffering and to contain rising costs.

Adult

How surgical rituals enhance surgical science.

1. Although OR rituals seem to be anomalous with clinical training, they are adaptive and necessary for the performance of scientific and clinical roles and, in particular, the practice of surgery. 2. Surgical rituals maintain order, stability, and predictability while increasing the autonomy of the surgical staff to perform their clinical roles, which are based on scientific principles. 3. To remain scientific, clinicians must continuously question, test, and abandon outdated practices and accept new practices based on empirical knowledge.

Clinical Competence

[Value of echography in salivary pathology].

Major advances in echography techniques over the past few years include the development of simple high performance units adapted to investigating the salivary glands. This non-traumatic, painless and inexpensive technique offers a means of rapid examination and is fully complementary to X-ray and xero and sialographic imagery, particularly in tumor pathology. The author gives a review of normal images then presents different lesions of the salivary gland.

Humans

[Endoscopy of the salivary glands].

The author has developed an original method of exploration of the salivary glands: ultrafine fibroscopy. After briefly describing the equipment, the method and the indications, he demonstrates how it is now possible to extract stones via the natural passages using a miniaturized basket catheter, avoiding the need for more extensive surgery.

Endoscopy

Effect of dystrophin gene deletions on mRNA levels and processing in Duchenne and Becker muscular dystrophies.

Muscle dystrophin mRNAs from Duchenne (DMD) and Becker (BMD) patients with internal deletion of the DMD gene were quantitated and sequenced. In all cases (eight DMD and three BMD), truncated mature transcripts were found, and their amount was correlated to the clinical phenotype and to the reading frame. We focused on four cases that were apparently not in agreement with the reading frame rule. In two DMD cases, slightly reduced amounts of in-frame truncated mRNA are present but no dystrophin is detected, suggesting impaired translation and/or instability of the protein. In two BMD patients with out-of-frame deletions, the presence of minor in-frame alternatively spliced mRNA species is congruent with the observed truncated dystrophin and the mild phenotype.

Base Sequence

The association of cyclosporine with the 1-year costs of cadaver-donor kidney transplants.

Cyclosporine is associated with lower hospitalization costs for transplantation of cadaver kidneys. Whether this cost-lowering effect persists after discharge was assessed for 203 patients who received cadaver kidneys at the University of California, San Francisco, between July 1982 and June 1986. During the transplantation hospitalization period, cyclosporine was associated with significantly better graft survival (88.7% vs 71.0%) and lower (standardized) costs ($37,174 vs $52,983). Following discharge, however, there were no significant differences in graft survival, total charges ($29,716 vs $34,434), the number of readmissions, the total number of days hospitalized, or physician charges, although cyclosporine was associated with higher drug costs ($3885 vs $373). The results suggest that the initial association of cyclosporine with lower costs diminished substantially over time. For grafts that survive beyond several months, there may be little additional cost-reducing benefits of cyclosporine.

Adolescent

Tryptophan-associated eosinophilic connective-tissue disease. A new clinical entity?

Seven patients who developed a syndrome of eosinophilia, connective-tissue disease, and cutaneous abnormalities while ingesting tryptophan were examined. Other clinical manifestations commonly seen were pulmonary symptoms, fever, lymphadenopathy, and the development of myopathy. Laboratory features included mild elevations of aldolase and lactate dehydrogenase levels, with essentially normal creatine kinase levels, erythrocyte sedimentation rates, and C-reactive protein levels. Biopsy findings included features of scleroderma, small-vessel vasculitis, fasciitis, and myopathy. Discontinuation of tryptophan administration and implementation of corticosteroid therapy were of some benefit in relieving the intense myalgias and cutaneous findings that developed. Although temporally related to tryptophan ingestion, it is unclear whether this substance, a metabolite, or a contaminant were causal. We speculate that the pathogenesis of this syndrome may relate to abnormalities in tryptophan metabolism.

Adult

Natural killer cell-mediated lysis of Mycobacterium-avium complex-infected monocytes.

Since the precise mechanism of host responses to infection with Mycobacterium-avium complex (MAC) is unclear and since cytotoxic lymphocytes may be involved in the destruction of cells infected with intracellular pathogens, we investigated the ability of normal peripheral blood lymphocytes to kill MAC-infected monocytes in a short-term isotope release assay. Nylon wool-passed lymphocytes lysed MAC-infected but not uninfected monocytes during a 4-hr assay. Infected monocytes were less sensitive to cell-mediated killing than the standard natural killer (NK) cell-sensitive cell line K562, although the kinetics of lysis were similar. The release of lymphocyte-derived mediators such as tumor necrosis factor, interleukin-2 (IL-2), and interferon-alpha and -gamma could not be implicated as a cause of monocyte death. Through the use of cell-specific monoclonal antibodies plus complement, the phenotype of the effector cell was that of an NK cell (CD3 negative, partially CD8 negative, and CD16 positive). The use of highly purified, negatively selected NK cells confirmed these results. NK cell-mediated lysis of infected monocytes decreased MAC viability, indicating that this cytotoxic activity would not favor dissemination of the organism. The killing of MAC-infected monocytes was reduced by K562 cells, suggesting that these targets shared common recognition/binding structures. These results suggest that NK-cell function may be important in the prevention of or response to MAC infection and may help explain the predilection of AIDS patients to develop widespread disease.

Acquired Immunodeficiency Syndrome

Increased risk of neisserial infections in systemic lupus erythematosus.

Survival in systemic lupus erythamatosus (SLE) continues to improve because of better ancillary care, earlier diagnosis, and earlier treatment. However, infection remains a leading cause of morbidity and mortality in this disease. Although corticosteroids and immunosuppresives increase the risk of opportunistic infection, the SLE patient is still most at risk from common bacterial pathogens. As the prototypic immune-complex disease, patients with active SLE have low circulating complement as well as a reticuloendothelial system (RES) saturated with immune complexes. It seems intuitive that SLE patients should be most at risk for organisms dependent for their removal on the RES or complement for opsonization or bacteriolysis. The current series presents four patients with SLE and disseminated neisseria infection and brings to 14 the number of patients in the literature with disseminated neisserial infection. They are typically young, female, with renal disease, and either congenital or acquired hypocomplementemia, and may present with all features of a lupus flare. Surprisingly, they are not all on corticosteroids or immunosuppressives and have some features that are unusual for non-SLE patients with these infections. There seems to be an over-representation of Nisseria meningitidis (despite potential reporting bias), and there ironically may be better tolerance with fewer fulminant complications in patients who have complement deficiencies. The best approach for the physician treating SLE is to immunize all SLE patients with available bacterial vaccines to N meningitidis and Streptococcus pneumonia, have a low threshold of suspicion for the diagnosis of disseminated neisserial or other encapsulated bacterial infection in the SLE patient who is sick, and to treat empirically with third generation cephalosporins after appropriate cultures.

Adolescent

Modulation of suppression of mitogen-induced T cell-dependent B cell responses by natural killer cells.

We examined the ability of human natural killer (NK) cells to modualte pokeweed mitogen (PWM)-induced polyclonal antibody production. Highly purified NK cells inhibited plaque-forming cell (PFC) responses and this suppression could be substantially increased by preincubation of NK cells with the known enhancers of NK cell lytic activity, interferon (IFN)-alpha, IFN-gamma, and interleukin-2. Additionally, costimulation of NK cells with two anti-CD2 antibodies (9-1 and 9.6), which recognize different epitopes on the CD2 molecule, also augmented the inhibitory effect. When subpopulations of NK cells were assayed for suppressor cell activity, this activity was primarily mediated by NK cells bearing Leu-7 but not Leu-2 (CD8) antigens. Thus, alteration of NK cell lytic activity may have significant effects on the immunoregulatory functions of these cells, which may have important implications for the in vivo manipulation of cytotoxic responses.

Antibodies, Monoclonal