The Perioperative Lung Transplant Virome: Torque Teno Viruses Are Elevated in Donor Lungs and Show Divergent Dynamics in Primary Graft Dysfunction.

Primary graft dysfunction (PGD) is a principal cause of early morbidity and mortality after lung transplantation, but its pathogenic mechanisms are not fully clarified. To date, studies using standard clinical assays have not linked microbial factors to PGD. We previously used comprehensive metagenomic methods to characterize viruses in lung allografts >1 mo after transplant and found that levels of Anellovirus, mainly torque teno viruses (TTVs), were significantly higher than in nontransplanted healthy controls. We used quantitative polymerase chain reaction to analyze TTV and shotgun metagenomics to characterize full viral communities in acellular bronchoalveolar lavage from donor organs and postreperfusion allografts in PGD and non-PGD lung transplant recipient pairs. Unexpectedly, TTV DNA levels were elevated 100-fold in donor lungs compared with healthy adults (p = 0.0026). Although absolute TTV levels did not differ by PGD status, PGD cases showed a smaller increase in TTV levels from before to after transplant than did control recipients (p = 0.041). Metagenomic sequencing revealed mainly TTV and bacteriophages of respiratory tract bacteria, but no viral taxa distinguished PGD cases from controls. These findings suggest that conditions associated with brain death promote TTV replication and that greater immune activation or tissue injury associated with PGD may restrict TTV abundance in the lung.

Allergy to ethylenediamine and steroid.

Intravenous preparations combining aminophylline and a steroid are used frequently in the treatment of bronchial asthma attacks. However, anaphylactoid reactions to such preparations have been rarely observed. We report the case of a 31-year-old man with aminophylline and steroid allergy. Aminophylline is the ethylenediamine salt of theophylline. In our patient, aminophylline, ethylenediamine and various steroids were found to be positive in the intradermal test. The challenge test with intravenous aminophylline was positive, while that with oral theophylline was negative. Ethylenediamine is used in everyday products such as shellacs and rubber products. In the case of our patient, his asthma worsened following the remodelling of his restaurant. Occupational asthma due to exposure to ethylenediamine is also discussed.

Characterization of urinary metabolites of a new benzofuroquinoline derivative, 3,9-bis(N,N-dimethylcarbamoyloxy)-5 H-benzofuro[3,2-c]-quinoline-6-one (KCA-098), in dogs.

The metabolism of 3,9-bis(N,N-dimethylcarbamoyloxy)-5 H-benzofuro[3,2-c]-quinoline-6-one (KCA-098), a new inhibitor of bone resorption and stimulator of bone formation, was examined after oral administration to dogs. Nine metabolites and the unchanged KCA-098 were isolated by extraction and HPLC from dog urine. The structures of these metabolites were characterized by LC/MS or LC/MS/MS, and/or were confirmed by comparison with corresponding authentic standards. The presumed main metabolic pathways were hydrolysis, hydroxylation, and N-demethylation of the N,N-dimethyl-carbamate ester group.

[A case report of far advanced gastric cancer with multiple liver metastasis (H3) treated with transarterial intermittent chemotherapy and intradermal administration of low molecular lipopolysaccharide (LPSp) extracted from Pantoea agglomerans].

A case of far advanced gastric cancer with multiple liver metastasis (H3) was treated with transarterial intermittent chemotherapy (5-FU: 250 mg/week, Farmorubicin: 10 mg/4 weeks, MMC: 4 mg/2 weeks) and intradermal administration of low molecular lipopolysaccharide (LPSp) extracted from Pantoea agglomerans. The CT examination and endoscopy showed regression of the tumor and the patient was discharged from the hospital. LPSp was given at the concentration of 0.1 microgram initially, and the dose was gradually increased. Finally, the dose of LPSp was increased up to 70 micrograms. No serious side effect except fever was observed. The serum TNF-alpha levels were elevated and, histologically, CD 8(+) lymphocyte dominantly infiltrated around the tumor. These findings clearly indicated the immunological anticancer effect of LPSp. Intradermal administration of LPSp is a promising new adjuvant therapy to improve QOL without serious side effect.

Effect of dietary treatment on the renal tubular function in a patient with hereditary tyrosinemia.

In a 1 1/2-month-old girl with hereditary tyrosinemia, renal tubular function studies were done. The effect of a low tyrosine and phenylalanine formula on renal tubular functions was also studied. The tubular handling of phosphorus, uric acid, beta 2-microglobulin, and amino acids was disturbed. Low urinary osmolality was also seen. Creatinine clearance was increased during a period of the standard formula. Although treatment with the low tyrosine and phenylalanine diet produces dramatic improvement in plasma tyrosine and tyrosyluria, all tubular symptoms did not revert to normal. It is possible that tubular dysfunction of hereditary tyrosinemia may be irreversible changes.

Urinary retention induced by estrogen injections in mice: an analytical model.

Daily subcutaneous injections of pharmacological doses of 17 beta-estradiol (E2, 0.4 micrograms./gm. body weight) resulted in significant urinary retention in the bladder of castrated mice. Although the urinary retention developed in both male and female mice, the increase in urethral resistance to urinary flow and the dilatation of posterior urethra were observed only in castrated male mice receiving E2. Histological changes common to male and female mice were cornification and stratification of urethral epithelium and fibrosis of connective tissues surrounding the urethra, suggesting that these changes may cause the urinary retention. Although the exact mechanism has not been defined, the urinary retention produced by the present method may be useful as a model of human disease.

Excretion of urinary amino acids in children with postural proteinuria.

The urinary excretion of free amino acids was studied in urine specimens from 12 subjects with postural proteinuria in recumbent posture and after a period of upright lordotic posture. The lordotic posture produced an increased urinary excretion of total amino acid and 12 amino acids, particularly of taurine, glutamic acid, a-amino adipic acid, valine, leucine, ethanolamine and arginine. However, 90 min after the lordotic posture, all amino acids returned to the initial values. Although, many factors must be considered in the evaluation of the urinary excretion of amino acids, an increased urinary excretion of amino acids occurring after the lordotic posture may be the result of reabsorption disturbance of the renal tubules.

Growth and uptake kinetics of a facultatively oligotrophic bacterium at low nutrient concentrations.

In oligotrophic waters, not only community structure but also physiological properties of heterotrophic bacteria are influenced by the concentration of organic matter.The relationship between growth rate of two facultatively oligotrophic strains ofAeromonas sp. No. 6 andFlavobacterium sp. M1 was studied in comparison with that of two eutrophic strains ofEscherichia coli 7020 andFlavobacterium sp. M2. These strains had two or three different substrate constants (Ks values) depending on substrate concentrations: Ks values for the two former were remarkably lower than those for the two latter. For instance, Ks value forAeromonas sp. No. 6 was about 8.9µM when substrate concentration was greater than 53µM and about 1.1µM when substrate concentration was less man 53µM. InE. coli the Ks value was about 260µM at greater than 5600µM and about 47µM at less than 5600µM substrate concentration.Uptake kinetics ofAeromonas sp. grown in a medium containing 2.7 mM glutamate (H-cell) and 0.11µM glutamate (L-cell) have been determined for the intact cells. H-cell had two distinct values of Km for glutamate assimilation and respiration, and L-cell had three distinct values of Km for glutamate assimilation and respiration: In H-cell Km of assimilation was 2.8×10(-7) M and 1.5×10(-4) M, and Km of respiration was 2.3×10(-7) M and 1.7×10(-4) M; in L-cell Km of assimilation was 7.4×10(-8) M, 8.3×10(-6) M, and 1.3×10(-4) M, and Km of respiration was 2.5×10(-7), 8.9×10(-6)M, and 1.7×10(-4) M. More than 60% of glutamate taken up by the H- and L-cells was respired when the substrate concentration was less than 10(-6) M, although at greater than 10(-6) M, 50% and 30% of glutamate was respired by H-cells and L-cells, respectively. These results suggest that the facultatively oligotrophic bacteria grow with high efficiency in environments with extremely low nutrient concentration, such as oligotrophic waters of lakes and ocean, as compared with in their growth in conditions of high nutrient concentraton, such as nutrient broth.

Effects of iodides on the hypothalamic-pituitary-thyroid axis in neurological endemic cretinism: evidence for compensated thyroidal failure in adult life.

Thyroid function studies, performed after iodide administration to five patients with neurological endemic cretinism, were indicative of hypothyroidism. All five subjects had either a low serum thyroxine (T4) or a high basal thyrotrophin (TSH) level and a clearly exaggerated TSH response to thyrotrophin releasing hormone (TRH). These findings are in sharp contrast with those we have previously described in goitrous patients without cretinism from the same geographical area. One interpretation of our observations is that there is an underlying mild defect in thyroid hormone synthesis in endemic cretinism predisposing to iodine induced hypothyroidism.