Biotin deficiency in amino acid formula nutrition for an infant with milk protein allergy]

We reported a 4-month-old girl with biotin deficiency caused by amino acid formula. Two weeks after birth, she was diagnosed as having a milk protein allergy. After switching to amino acid formula from usual formula, her symptoms and laboratory findings became normal. About three weeks after the beginning of amino acid formula, she developed intractable skin erosions around the eyes, mouth, neck, and anogenital area. By measuring concentrations of some trace elements, she was diagnosed as having a biotin deficit, because of the organic aciduria and undetectable serum biotin concentration. Her serum biotinidase level was normal. Upon administration of oral biotin supplementation, all her symptoms and laboratory findings were dramatically improved. Since amino acid formula contains very few biotin, we should pay attention to biotin deficiency when infants receiving amino acid formula.     

Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span

Transgenic (Tg) mice overexpressing human thioredoxin (TRX), a small redox-active protein, were produced to investigate the role of the protein in a variety of stresses. Bone marrow cells from TRX-Tg mice were more resistant to ultraviolet C-induced cytocide compared with those from wild type (WT) C57BL/6 mice. TRX-Tg mice exhibited extended median and maximum life spans compared with WT mice. Telomerase activity in spleen tissues in TRX-Tg mice was higher than that in WT mice. These results suggest that overexpression of TRX results in resistance against oxidative stress and a possible extension of life span without apparent abnormality in mammals.     

Novel Fluorinated Polymer by Radiation‐Induced Polyaddition of Bisperfluoroisopropenyl Terephthalate with 1,4‐Dioxane

Radical polyaddition of bis(α‐trifluoromethyl‐β,β‐difluorovinyl) terephthalate [CF₂?C(CF₃)OCOC₆H₄COOC(CF₃)?CF₂] (BFP) with 1,4‐dioxane (DOX) was investigated under γ‐rays radiation from a ⁶⁰Co source to produce higher molecular weight polymers compared to those yielded by benzoyl peroxide initiation. Prior to polyaddition, the addition reactions of 2‐benzoxypentafluoropropene [CF₂?C(CF₃)OCOC₆H₅] (BPFP) with tetrahydrofuran (THF) and DOX, and BFP with THF were examined in order to develop probable polyaddition reaction conditions. The polymer bearing 1.5 × 10⁴ as a molecular weight was obtained under the feed molar ratio of DOX/BFP = 16 with an irradiation dose of 2 000 kGy at 40 °C, which is a much higher molecular weight compared to that yielded by benzoyl peroxide.

     

Glomerulosclerosis develops in Thy-1 nephritis under persistent accumulation of macrophages

To clarify the relationship between macrophages and development of glomerulosclerosis, the authors developed a new experimental nephritis model with macrophages persisting in Thy-1 nephritis. Methyl-cellulose was administered intraperitoneally in addition to the intravenous injection of the anti-Thy-1 antibody to Wistar rats. Foamy macrophages influxed into the lytic mesangium and stayed to form nodular aggregates. Mesangial cells proliferated with the formation of extracellular matrices around these nodular aggregates of macrophages. Immunohistochemical analyses revealed that alpha-smooth muscle actin (alpha-SMA) was expressed in the proliferative area around these nodules of foamy macrophages from day 7. Type I collagen and type IV collagen were also expressed around the foamy macrophages in correspondence with alpha-SMA expression from day 7. The electron microscopic study revealed that collagen fibrils were formed around the transformed mesangial cells. The expression of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), a marker of glomerular vasculature endothelial cells, was not found in the area occupied by the foamy macrophages, suggesting the impairment of glomerular reconstruction. Macrophages may participate in the progression of glomerulosclerosis in Thy-1 nephritis by enhancing the production of the extracellular matrix through transformed mesangial cells and preventing reconstruction of the capillary network.     

Nature of optokinetic response and zonal organization of climbing fiber afferents in the vestibulocerebellum of the pigmented rabbit

Summary In pigmented rabbits anesthetized with N₂O (70%) and halothane (2–4%), Purkinje cells were extracellularly recorded in the nodulus. Large field (60°×60°) optokinetic stimulation (OKS) with constant velocity was delivered to either the ipsi- or contralateral eye, and the direction and velocity selectivities of complex spike responses were examined. To ipsilateral OKS (n = 181), the preferred direction was forward (F, n = 72), upward (U, n = 38) or downward (D, n = 10), while the remaining cells (n = 61) showed no response (N). To contralateral OKS (n = 117), the preferred direction was backward (B, n = 22), upward (U, n = 7) or downward (D, n = 22), while the rest (n = 66) showed N. Cells tested with both eyes (n = 95) fell into 8 categories based on the preferred direction to ipsi- and contralateral OKS: (1) ipsi-F and contra-B (F/B type, n = 20), (2) ipsi-F but contra-N (F/N type, n = 12), (3) ipsi-U and contra-D (U/D type, n = 15), (4) ipsi-U but contra-N (U/N type, n = 13), (5) ipsi-N but contra-D (N/D type, n = 1), (6) ipsi-D but contra-N (D/N type, n = 5), (7) ipsi-N but contra-U (N/U type, n = 6), and (8) N to both eyes (N/N type, n = 23). The optimum velocity was in the range 0.1–2.0°/s for all cells responsive to OKS. In the ventral lamella, four medio-laterally aligned zones were demonstrated. In the most medial zone (0–0.5 mm from the midline), the majority of cells showed ipsi-N or contra-N responses. In the second zone (0.5–1.5 mm), most cells preferred ipsi-F or contra-B directions. In the third zone (1.5–2.5 mm), most cells preferred ipsi-U or contra-D directions. In the most lateral zone (2.5–3.5 mm), most cells preferred ipsi-F or contra-B directions. In the dorsal lamella, a longitudinal zone characterized with cells preferring ipsi-U or contra-D directions was found about 1.5–2.5 mm from the midline. This zone seemed to be the continuation of the third zone in the ventral lamella. Cells preferring ipsi-D or contra-U directions were scattered in the medial half of both the dorsal and ventral lamellae. Most cells responsive to electrical stimulation of the contralateral optic tract (OT) preferred the ipsi-F direction and were localized in the second and the most lateral zones of the ventral lamella. As for cells activated by a climbing fiber with a branching axon to the flocculus, no characteristic feature was found in terms of the preferred direction to OKS, except that none of the cells preferring ipsi-D or contra-U directions were activated by such branching climbing fibers. The results indicate that the nodulus consists of at least four functionally distinct zones in terms of direction selectivity of visual climbing fiber afferents.     

Nature of optokinetic response and zonal organization of climbing fiber afferents in the vestibulocerebellum of the pigmented rabbit

In pigmented rabbits anesthetized with N2O (70%) and halothane (2-4%), Purkinje cells were extracellularly recorded in the flocculus. A large central visual field (60 degrees x 60 degrees) was used to optokinetically stimulate either the ipsi- or contralateral eye, and the direction and velocity selectivities of complex spike responses were examined. For optokinetic stimulation (OKS) delivered to the ipsilateral eye (n = 129), the preferred direction was forward (F, n = 57) or upward (U, n = 37), while the remaining cells (n = 35) showed no response (N). For OKS delivered to the contralateral eye (n = 107), the preferred direction was backward (B, n = 11), downward (D, n = 42) or upward (U, n = 2), and the rest (n = 52) showed N. Cells tested with both eyes (n = 89) fell into five categories based on the preferred direction to ipsi- and contralateral OKS: (1) ipsi-F and contra-B (F/B type, n = 9), (2) ipsi-F but contra-N (F/N type, n = 28), (3) ipsi-U and contra-D (U/D type, n = 13), (4) ipsi-U but contra-N (U/N type, n = 17), and (5) ipsi-N but contra-D (N/D type, n = 22). The optimum velocity was within 0.1-2.0 degrees/s for all cells. On the average, the best response was obtained at 0.2-0.5 degrees/s stimulation. All ipsi-F cells responded to electrical stimulation of the optic tract (OT), while most cells preferring ipsi-U, contra-B and contra-D directions did not respond. No characteristic feature was found in cells innervated with collateralized climbing fiber branches to the nodulus. In the flocculus, cells preferring horizontal orientation (H cells, preferring ipsi-F and/or contra-B directions) were localized in a narrow dorsoventral zone (less than 1.0 mm) along the caudal border of the rostral one third, while those preferring the vertical orientation (V cells, preferring ipsi-U and/or contra-D directions) were in two distinct narrow zones located rostral and caudal to the H cell zone. H and V cells were intermingled in the central portion of the ventral flocculus. These four zones are in good agreement with previously defined H, anterior V, posterior V and R zones, respectively. The results indicate that the subdivision of the flocculus which controls horizontal (vertical) eye movements receives information regarding movements of the visual surround in the horizontal (vertical) orientation through visual climbing fiber afferents, thus being organized in olivo-cortico-nuclear functional units for control of eye movements.     

Role of prostaglandin E receptor subtypes in gastroduodenal HCO3- secretion

Gastroduodenal HCO3- secretion is a key process that aids in preventing acid-peptic injury. Endogenous prostaglandins (PGs) play a particularly important role in the local control of this secretion. The secretion of HCO3- in both the stomach and duodenum was increased in response to PGE2 as well as mucosal acidification, the latter occurring with concomitant enhancement of mucosal PG generation. These HCO3- responses in the duodenum were markedly reduced by prior administration of the EP4 antagonist in rats, and profoundly decreased in the animals lacking EP3 receptors but not EP1 receptors. In contrast, gastric HCO3- responses induced by PGE2 and mucosal acidification were prevented by the EP1 antagonist and disappeared in EP1, but not EP3-knockout mice. Consistent with these findings, duodenal HCO3- secretion was stimulated by both EP3 and EP4 agonists but not EP1 or EP2 agonists, while gastric HCO3- secretion was increased by the EP1 agonist but not EP2, EP3 or EP4 agonists. In addition, the HCO3- stimulatory action of sulprostone (EP1/EP3 agonist) in the stomach was inhibited by the Ca2+ antagonist verapamil but not affected by IBMX, the inhibitor of phosphodiesterase, while that in the duodenum was inhibited by verapamil and enhanced by IBMX. Forskolin, the stimulator of adenylate cyclase, increased HCO3- secretion in the duodenum but not the stomach. Thus, the HCO3- stimulatory action of PGE2 in the duodenum is mediated by both EP3 and EP4 receptors being coupled intracellularly with both Ca2+ and cAMP, while that in the stomach is mediated by EP1 receptors, coupled with Ca2+.     

Effect of basic amino acids on susceptibility to carbapenems in clinical Pseudomonas aeruginosa isolates

We evaluated effects of medium composition, including basic amino acid content and pH, on susceptibility to carbapenems such as imipenem, panipenem and meropenem, in clinical isolates of Pseudomonas aeruginosa. Susceptibility to carbapenems was reduced by basic amino acids in the medium, while susceptibilities to ceftazidime and aztreonam were not. Among carbapenems, susceptibility to panipenem was most sharply reduced by addition of basic amino acids to 1:16 Mueller-Hinton agar (MHA). In 174 of 175 clinical isolates, MICs for carbapenems were affected to different degrees by medium composition. One isolate, in which MICs for carbapenems did not differ between MHA and 1:16 MHA, showed reduced production of porin (OprD). Our results suggest that susceptibility to individual carbapenems, especially panipenem, is difficult to evaluate based on MICs for other carbapenems determined on MHA. For a better prediction of antibiotic efficacy, it may be important to evaluate the susceptibility for each carbapenem individually.