Immunohistochemical study of oncogene-related products in human gastrointestinal malignancies--expression of ras p 21, fes p 85 and EGF receptor

An immunohistochemical examination by the avidin-biotin-peroxidase complex method was carried out to assess the expression of oncogene-related products, i.e., ras p 21 protein, fes p 85 protein and epidermal-growth-factor (EGF) receptors, in human gastrointestinal malignancies. The presence of ras p 21, fes p 85 and EGF receptors was detected in 48%, 62%, and 62% of 29 colorectal carcinomas and in 65%, 65% and 40% of 20 gastric cancers, respectively. More than one oncogene protein was demonstrated in 18 of 29 colorectal carcinomas and in 10 of 20 gastric cancers. These results suggest that multiple oncogenes are important in the occurrence and progress of gastrointestinal malignancies.     

Interdisciplinary treatment of a patient with severe pathologic tooth migration caused by localized aggressive periodontitis.

An interdisciplinary approach was used to treat a patient with pathologic migration of teeth, with severe anterior proclination and molar mesial inclination due to localized aggressive periodontitis. The combination of regenerative periodontal therapy, prosthodontic rehabilitation, and orthodontic treatment greatly improved function and esthetics.     

Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1 receptors and promotes non-rapid eye movement sleep

Adenosine has been proposed to promote sleep through A₁ receptors (A₁R's) and/or A_2A receptors in the brain. We previously reported that A_2A receptors mediate the sleep-promoting effect of prostaglandin D₂, an endogenous sleep-inducing substance, and that activation of these receptors induces sleep and blockade of them by caffeine results in wakefulness. On the other hand, A₁R has been suggested to increase sleep by inhibition of the cholinergic region of the basal forebrain. However, the role and target sites of A₁R in sleep–wake regulation remained controversial. In this study, immunohistochemistry revealed that A₁R was expressed in histaminergic neurons of the rat tuberomammillary nucleus (TMN). In vivo microdialysis showed that the histamine release in the frontal cortex was decreased by microinjection into the TMN of N⁶-cyclopentyladenosine (CPA), an A₁R agonist, adenosine or coformycin, an inhibitor of adenosine deaminase, which catabolizes adenosine to inosine. Bilateral injection of CPA into the rat TMN significantly increased the amount and the delta power density of non-rapid eye movement (non-REM; NREM) sleep but did not affect REM sleep. CPA-promoted sleep was observed in WT mice but not in KO mice for A₁R or histamine H₁ receptor, indicating that the NREM sleep promoted by A₁R-specific agonist depended on the histaminergic system. Furthermore, the bilateral injection of adenosine or coformycin into the rat TMN increased NREM sleep, which was completely abolished by coadministration of 1,3-dimethyl-8-cyclopenthylxanthine, a selective A₁R antagonist. These results indicate that endogenous adenosine in the TMN suppresses the histaminergic system via A₁R to promote NREM sleep.     

Reconstruction of basement membrane in recombinants of epidermis and dermis of chick embryonic skin in vitro: An electron microscopic study

The tarsometatarsal skin from 13-day-old chick embryos was treated with EDTA and/or Dispase to separate it into epidermis and dermis, and the basal lamina was removed. The isolated epidermis and dermis were then recombined and cultured on Millipore filters in a chemically defined medium (BGJb). Beginning at 3–4 days after recombination, short fragments of new basal lamina and subbasal dense plaque were formed along the epidermal basal cell outer surface immediately subjacent to hemidesmosomes. After 6–8 days of culture, fragments of the basal lamina started to fuse together and the lamina became progressively continuous. At the same time, anchoring fibrils were formed to attach to the basal lamina. The hemidesmosome formation preceded the basement membrane formation. When normal embryonic epidermis was recombined with retinolpretreated dermis and cultured for 7 days in BGJb, short fragments of the basal lamina, the subbasal dense plaque, and anchoring fibrils were formed, but the basement membrane remained discontinuous with many interruptions in the interspace between hemidesmosomes. These results demonstrate that pretreatment of dermis with retinol causes the changes noted in the basement membrane.     

Effects of Proteolytic Enzyme Inhibitors on the Nasal Absorption of Vasopressin and an Analogue

Proteolytic enzyme inhibitors were examined as absorption enhancers for the nasal delivery of vasopressin (AVP) and desmopressin (l-d-8-DAVP) in rats. Aprotinin, soybean trypsin inhibitor, and camostat mesilate were used as enzyme inhibitors. The nasal absorption of AVP and l-d-8-DAVP was evaluated by measuring its antidiuretic effect. Nasal administration of AVP (0.005 IU/kg) or l-d-8-DAVP alone (2.5 ng/kg) produced a small antidiuretic effect. Coadministration with aprotinin (1000 and 10000 KIU/kg) or soybean trypsin inhibitor (1.25 and 6.25 mM) did not change the antidiuretic effect. However, coadministration with camostat mesilate (1 to 50 mM) significantly increased the antidiuretic effect and, thus, the nasal absorption of AVP and l-d-8-DAVP. The activities of aminopeptidase, cathepsin-B, and trypsin in the nasal mucosal tissue of rats were 7 nmol/min/mg protein, 0.7 nmol/min/mg protein, and 4.6 pmol/min/mg protein, respectively. Aprotinin and soybean trypsin inhibitor inhibited only the trypsin activity, whereas camostat mesilate inhibited aminopeptidase and trypsin activities. Aprotinin (MW 6500) and soybean trypsin inhibitor (MW 8000), with relatively high molecular weights, may not permeate into the nasal mucosal tissue. In contrast, camostat mesilate is slowly absorbed (8%/hr) and could inhibit the proteolytic activity in the nasal mucosa, resulting in enhanced nasal absoprtion of AVP and l-d-8-DAVP.     

Effects of Viscous Hyaluronate–Sodium Solutions on the Nasal Absorption of Vasopressin and An Analogue

The effects of viscous solutions of hyaluronate-sodium of various average molecular weights (MW) on the nasal absorption of vasopressin (AVP) and its analogue, l-deamino-8-D-arginine vasopressin (l-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 × 10⁵ daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 × 10⁴ daltons were not effective. The enhancing effects on the nasal absorption of AVP and l-d-8-DAVP were dependent on the concentration in the range of 0–1.5% (w/v) hyaluronate (MW 1.4 × 10⁶ daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and l-d-8-DAVP in hyaluronate solutions (MW 1.4 × 10⁶ and 2 × 10⁶ daltons) increased more than 2- and 1.6-fold as compared to nasal administration of AVP and 1-d-8-DAVP in buffer solutions (pH 7.0), respectively. Hyaluronate solution (MW 1.4 × 10⁶ daltons) did not affect the ciliary beat frequency of rabbit nasal mucosal membranes in vitro. Therefore, hyaluronate solution may be useful as a vehicle for nasal delivery of AVP and l-d-8-DAVP.     

Leptin gene and leptin receptor gene polymorphisms are associated with sweet preference and obesity

Leptin is an adipocyte-secreted hormone that regulates food intake and body weight, and that was recently reported to suppress sweet sensitivity in an animal model. We investigated the associations among sweet preference, obesity, and polymorphisms of the leptin gene (LEP) or leptin receptor gene (LEPR). A total of 3,653 residents randomly selected from among the citizens of Suita City, Osaka, Japan were enlisted as subjects, in whom we investigated sweet preference, clinical characteristics, including obesity and serum leptin level, and the polymorphisms of LEP and LEPR (G-2548A and A19G for LEP; R109K, R223Q, and rs3790439 for LEPR). We determined the associations among the parameters using logistic regression analysis, in order to consider potential confounding factors for sweet preference and/or obesity. The LEP A19G and LEPR R109K polymorphisms were associated with sweet preference, whereas the serum leptin level was not. Further, the LEPR 109KK genotype was found to be associated with obesity along with sweet preference. In conclusion, our results are the first to show associations of LEP and LEPR polymorphisms with sweet preference, and may provide useful information for diagnosis and treatment of lifestyle-related diseases.     

Sinus thrombosis in idiopathic hypereosinophilic syndrome causing fatal cerebral haemorrhage.

Idiopathic hypereosinophilic syndrome (HES) is a leukoproliferative disorder that is characterized by sustained overproduction of eosinophils and a trend towards damage to specific organs, usually the cardiovascular system. We report the case of a 76-year-old woman who was affected by idiopathic HES, which had an unusual and rapidly fatal course. Sinus thrombosis in the transverse and sigmoid sinuses was evident on cranial CT and CT angiography. In our review of the English-language literature we were unable to find any previously published direct images of sinus thrombosis in idiopathic HES.     

Stability of mandibular position in continuous vowel phonation

The stability of the mandibular positions during continuous phonation of the five vowels [( a], [e], [i], [o], [u]) and the relationship between each position and the rest position were examined for 30 subjects (males, 23 to 35 years of age) using the mandibular kinesiograph. Each subject had a complete or nearly complete natural dentition with no marked occlusal abnormalities. The mandibular position during continuous phonation of the vowel [i] appeared stable and was closely related to the rest position. It is thus suggested that the use of continuous [i] phonation is a viable method for determining the occlusal vertical dimension.