Measurement of airway resistance in anesthetized and paralyzed subjects: Proposal for evaluation of K1 values

The effects of lung volume and respiratory airflow on airway resistance were studied in five anesthetized and paralyzed patients. Airway resistance measured during the inspiratory phase with intermittent constant airflow inflatoins decreased in inverse correlationship to increases in lung volume. Airway resistance measured during the expiratory phase with an airway interruption technique, on the other hand, increased with a linear relationship to the expiratory airflow as expressed by a function of Y = K₁ + K₂X. K₁, calculated from the values of airway resistance corresponding to three different airflows, was unaffected by intentional expiratory resistance loading. Thus, simultaneously with the measurement of airway resistance by this method, expiratory gas sampling with a Douglas bag can be done if necessary. Since the K₂ value of the endotracheal tube used in this study (Portex^® I.D. 8mm, length 26cm) was quite high (5.0cmH₂O·1^–2·sec²), depending on the airflow, the presence of the endotracheal tube strongly affected the measurement of airway resistance during general anesthesia. K₁ measured by the above method, however, may be considered as the best way to evaluate the lower airway resistance independent of either lung volume or expiratory airflow.(Sakai T, Yoshida H, Yano H et al.: Measurement of airway resistance in anesthetized and paralyzed subjects: proposal for evaluation of K₁ values. J Anesth 2: 139–145, 1988)     

Muscular involvement in lysosomal acid lipase deficiency in rats.

We investigated the pathological and biochemical changes of skeletal muscle in rats with lysosomal acid lipase deficiency, which is an animal counterpart of human Wolman's disease. In the affected rats, the acid lipase activity for three different substrates, 4-methylumbelliferyl-oleate (18.9% of the normal control level), [14C]cholesteryl oleate (23.5%), and [14C]triolein (26.9%), was similarly decreased in the lysosomal fraction of skeletal muscle which was obtained by differential centrifugation. Histochemical studies showed that acid phosphatase activity was high in the endomysium and perimysium and in some muscle fibers. Some fibers showed vacuolar degeneration resembling "rimmed vacuoles". Ultrastructural studies demonstrated many membrane-bound lipid droplets in the muscle fibers, especially in the subsarcolemmal space, indicating that a low density lipoprotein (LDL) uptake pathway apparently existed in the muscle cells. However, such lipid accumulation was much greater in the interstitial cells and the endothelial cells. This distribution also suggests that LDL/cholesterol is supplied to muscle cells predominantly through endothelial cells.     

Basic and clinical evaluation of an immunoradiometric competitive inhibition assay for 2----6 sialyl Lewis a antigen--1. Evaluation of assay conditions and normal values

We describe an immunoradiometric competitive inhibition assay of the serum levels of the 2----6 sialyl Lewisa antigen, using "SLA 2-6 Otsuka" kits. The assay required only duplicate 50-microliters samples, and the concentration of 2----6 sialyl Lewisa antigen in serum was determined by reference to a standard curve ranging from 0 to 160 arbitrary U/ml. The intra- and inter-assays reproducibilities were good and analytical recovery of antigen were excellent. The serum levels of the antigen were highly dependent on the Lewis blood types of the tested individuals; i.e., the levels of the antigen in the sera of the Lewisa-b- individuals were significantly lower than those of the antigen obtained with the Lewisa+b- and Lewisa-b+ individuals. The cut-off value (42 U/ml) was obtained as mean + 2SD, which was carefully calculated from the antigen levels in sera of the non-Lewisa-b- individuals.     

Expression of Jun activation domain-binding protein 1 and p27 (Kip1) in thyroid medullary carcinoma

AIMS: p27 is a prominent regulator of cell proliferation by universally inhibiting the cell cycle, while Jun activation domain-binding protein 1 (Jab1), a multifunctional cell signaling protein, contributes to carcinoma progression by degrading p27. In this study, we investigated the expression of these proteins in medullary thyroid carcinoma. METHODS: We immunohistochemically examined Jab1 and p27 expression in 64 medullary thyroid carcinomas. RESULTS: Of the 64 cases examined, decreased p27 expression was observed in 38 cases (59.4%). The p27 expression level was inversely linked to tumour size as well as plasma calcitonin level. Jab1 expression level was generally high, and 46 cases (71.9%) were classified as overexpressing Jab1. The incidence was higher than those in papillary and follicular carcinomas, which were previously reported. Jab1 expression level was inversely linked to that of p27, and all five cases with only cytoplasmic but not nuclear staining of p27 overexpressed Jab1. CONCLUSIONS: These findings suggest that (1) decrease in p27 expression may contribute to local tumour growth; (2) Jab1 expression is related to the progression of medullary carcinoma by decreasing the amount of p27 in the cell and accelerating its degradation; and (3) Jab1 may play a more vital role in the pathogenesis of medullary carcinoma than papillary and follicular carcinomas.     

Inflammatory mediators in culture filtrates of Escherichia coli.

Escherichia coli, when cultured on a simple medium containing only glucose and inorganic compounds, release soluble factors which have a variety of biologic effects on cells in vitro. These low molecular weight (less than 12,000) substances are capable of: a) reversibly inhibiting the migration of macrophages, b) causing chemotactic attraction of neutrophils, c) inducing blast transformation of lymphocytes, and d) producing cytotoxic effects on mouse fibroblasts in culture. Although these activities are functionally similar to those which have been described for various lymphokines obtained from antigen-activated lymphocyte cultures, lymphocyte and bacterial factors which share a given property do not appear to be identical. For example, the bacterial factor which inhibits macrophage migration is partially heat labile and is dialyzable, characteristics which distinguish it from conventional migration inhibition factor. Nevertheless, similarity of function may imply the existence of some degree of chemical homology which would have importance implications concerning the evolution of host-defense reactions. In any case, as is the situation for the lymphokines, the in vitro behavior of the bacterial factors suggest a role for them in in vivo inflammatory responses.     

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.     

T-cell acute lymphoblastic leukemia with add(1)(p36) and del(12)(p11) following acute myelocytic leukemia with partial deletion of 9p

We describe the case of a 40-year-old man whose disease was initially diagnosed as acute myelocytic leukemia. The patient achieved remission with chemotherapy, but relapsed shortly afterwards with an acute T-cell lymphoblastic leukemia. He died of intracranial bleeding. Karyotyping analysis showed a del(9p?) as a common abnormality in the leukemic cells at onset and relapse. Fluorescence in situ hybridization analysis demonstrated allelic loss of the CDKN2A gene in cells from both stages of the disease. At relapse the leukemia cells had additional abnormalities such as add(1)(p36) and del(12)(p11). We postulate that the loss of CDKN2A is involved in leukemogenesis but does not determine the lineage of the leukemic cells. Instead, abnormalities of genes at 1p36, 12p11, or both may be involved in driving a lymphoid phenotype.     

A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia

Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.