Abrogation of c-kit/Steel factor-dependent tumorigenesis by kinase defective mutants of the c-kit receptor: c-kit kinase defective mutants as candidate tools for cancer gene therapy.

The growth and survival of many types of cancer cells are known to be supported by specific growth factor/cytokine systems. Among these, the activation of c-kit receptor and its ligand steel factor participates in several types of human carcinogenesis. W mutations of laboratory mouse strains are loss of functional mutations of the c-kit receptor. To examine the validity of these mutants in investigating c-kit-mediated carcinogenesis and in the treatment of c-kit-dependent tumors, we introduced various W mutations (W, Wv, and W42) into a transgenic mouse strain carrying human papillomavirus oncogenes, in which c-kit/Steel-mediated tumorigenesis occurs with a very high incidence. In all transgenic strains carrying a W mutation, the c-kit deficiency affected the tumorgenic process to various degrees. Tumor development was markedly suppressed in transgenic strains carrying kinase defective mutations (Wv and W42) in a heterozygous condition. In null-type (W) heterozygous transgenic mice, tumorigenesis was suppressed at a lower level. Moreover, minimal focal legions or, in some cases, no focal legions were found in the testes of W/Wv heterozygous transgenic mice, showing a close relationship between tumor cell growth and the degree of c-kit inactivation. These results indicated that c-kit activity is a pivotal determinant of testicular tumor development and that the kinase defective mutants of c-kit are valuable for treating c-kit-dependent cancer, as well as for clarifying the c-kit-mediated carcinogenesis.

Recent-onset bell palsy complicated by diabetes: comparison of steroid and lipoprostaglandin E(1) therapy.

OBJECTIVE: To compare megadose steroid therapy (n = 17; group S) and lipoprostaglandin E(1) (lipo-PGE(1)) therapy (n = 14; group L) in patients with recent-onset Bell palsy complicated by diabetes. DESIGN: A nonrandomized controlled trial was performed. The 2 groups were almost identical in age, sex distribution, and laterality, and there was no difference in the average palsy scores in the 2 groups either at the time of the first visit or when the palsy was at its worst. RESULTS: There was no statistically significant difference in the cumulative rates of improvement in the 2 groups 4 weeks, 2 months, or 6 months after the first visit, revealing no difference in the therapeutic effects of the 2 agents. During the therapy, fasting blood glucose concentrations were increased in all patients in group S, whereas they were not increased in group L. Complicated diabetes was aggravated in group S, while it was not aggravated in group L. CONCLUSIONS: Lipo-PGE(1) therapy may have improved vascular flow in the facial nerves and accelerated recovery, resulting in a rate of improvement comparable with that obtained through megadose steroid therapy. Lipo-PGE(1) is a useful treatment method for patients with Bell palsy complicated by diabetes.

A case of cerebello-pontine angle infarction found by vertebral angiography.

A patient was admitted complaining of sudden vertigo. Otoneurological examinations, electronystagmography (ENG), and vertebral angiography (VAG) showed constriction of vertebral artery and anterior inferior cerebellar artery, and basilar artery obstruction. Based on these findings, we diagnosed the case as posterior cranial fossa infarction. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were negative. The authors conclude that VAG should be performed in certain cases of vertigo thought to be of central nervous origin when CT and MRI findings are both negative.

A case of polyradiculitis with hearing loss: analysis of auditory brain stem response.

A case of acute polyradiculoneuritis accompanied by rare complications of the VII, VIII and IX cranial nerve disorder was described. There was an elevation of the rubella virus antibody titer, which suggested the case had been infected before. Thirty-eight year-old woman complained of bilateral tinnitus and was proven audiometrically to have sensori-neural hearing loss. Electroacoustical examination disclosed that all the waves were suppressed and that wave I and V were barely detected, while wave II, III and IV were absent. The neurological and audiological disorders were successfully treated with corticosteroid, and the patient had neither sequelae nor recurrence.

[Superior oblique myokymia--a case report and pathogenetic consideration].

A 30-year-old male visited us with complaints of dizziness and diplopia of abrupt onset in September, 1988. Neurological studies demonstrated paroxysmal rotatory to-and-fro oscillations of the left eye. There has been the same clinical episode at 25 years of age, lasting approximately 6 months. The characteristics of his ocular involuntary movement with the mild IVth cranial nerve paresis were as follows: quick, nonrhythmic, initially counterclockwise-rolling, more prominent in moving the left eye to the lower medial side, persisting for 1-10 seconds and rapidly repeated oscillations. When oscillations were prominent, he complained of faintness in addition to double vision. Except for the ocular signs, other neurological and laboratory examinations including cerebrospinal fluid, brain MRI and brain stem auditory evoked response, failed to disclose the precise location and nature of the lesion. Abnormal ocular movement was fluctuating for 4 months and gradually disappeared without any medication. In conclusion, the faintness could be considered to result from a lesion of reticular activating system adjacent to the IVth cranial nerve nucleus and its rostral (excitatory or inhibitory) supranuclei, and it suggests that a responsible lesion of the abnormal ocular movement is located at a region of the dorsomedial midbrain.

[MRI findings in patients with vertigo and dizziness possibly arising from vertebrobasilar insufficiency].

In order to evaluate diagnostic usefulness of MRI in vertebrobasilar insufficiency (VBI), we performed magnetic resonance imaging (MRI) and MR angiography (MRA) in 90 patients presenting vertigo and dizziness as an initial and cardinal complaint. High signals observed by T2-weighted imaging in the basal ganglia (44.4%) or pontine base (48.9%) were more frequently seen in the possible VBI group than in the controls (p < 0.001). The electronystagmographical abnormalities were commonly observed in the patients with a high signal in the pontine base, reflecting diffuse ischemic lesion in the territory of the vertebrobasilar system. Vertebral artery asymmetry (45.6%) or basilar artery twisting (41.1%) as shown by MRA was also significantly more frequent in the patients than in the controls (p < 0.05). In conclusion, MRI and MRA were considered to be useful in making a clinical diagnosis of VBI in such patients.

Effect of aging on the expression of iNOS and cell death in the mouse cochlear spiral ganglion.

The age-related induction of inducible nitric synthase (iNOS) and apoptotic cell death in spiral ganglion cells (SGCs) of ddy strain mice were studied with immunohistochemical method and TdT-mediated dUTP-biotin nick end labeling (TUNEL), respectively. A large amount of iNOS was expressed in SGCs of 18- to 24-month-old mice, but not in those of the mice less than 12 months of age. Moreover, these mice were accompanied by a great rise in auditory brainstem response threshold as well as a great decrease in the number of SGCs that seemed to be due to preceding cell death of the cells. However, we were unable to find apoptotic TUNEL-positive cells in the spiral ganglions. This was assumed to be due to a very short clearance time of the dead cell bodies of less than one hour. As has been known, NO produced by iNOS can implicate in causes for either protection of cells from peroxidation and cell death. In the present study, therefore, the steep augmentation of iNOS in the SGCs of senescent mice implies that the iNOS initially induced to protect SGCs from the cytotoxicity of cellular peroxidation eventually contribute to the cell death of SGCs themselves.

Immunohistochemical demonstration of inducible nitric oxide and nuclear factor-kappa B with reference to age-related changes in the mouse spiral and vestibular ganglion.

The morphology and immunohistochemistry of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-kappa B) were studied on the spiral and vestibular ganglion of young and old ddy mice. The significant decrease in the number of the spiral ganglion cells and a significant expression of iNOS and NF-kappa B were observed in old mice. In contrast, in the vestibular ganglion of all animals examined, decrease in the number of the ganglion cells or expression of iNOS and NF-kappa B were not observed. Although the relevance of enzymatic systems for the protection of vestibular ganglion cells in old individuals from harmful oxidative stress increased with aging should be further clarified, lack of harmful stress due to nitric oxide (NO) may be one of the plausible reasons for that the vestibular ganglion cells were not decreased in number with aging, since iNOS was not detected in the vestibular ganglion cells in the animals tested in the present study.

[Clinical effect of a cephalosporin derivative, cefotiam, on otorhinolaryngologic infections].

CTM was administered at dose levels of 1 to 3 g a day to 77 cases of otorhinolaryngological infections, and the following results were obtained: The effect of the drug was determined in 75 cases. The responders were 3 out of 5 (60.0%) in acute suppurative otitis media, 4 out of 11 (36.4%) in chronic suppurative otitis media, 39 out of 43 (90.7%) in tonsillitis and peritonsillar abscess and 12 out of 16 (75.0%) in other diseases, a total of 58 out of 75 cases (77.3%). The bacteriological effect of CTM was evaluated in 53 cases, and bacterial eradication was demonstrated in 41 cases (77.4%). Also, its antibacterial potency was 2 to 4 times superior in comparison to that of CEZ against isolated bacteria in which MICs were measurable. Side effects which were neither severe nor specific were recognized in 3 out of 77 cases (3.9%). In the cases with abnormal laboratory values, none was determinable to be attributed to CTM.

Differential diagnosis of obstructive sleep apnea syndrome patients and snorers using cephalograms.

Severe snoring is thought by many to be an early stage of obstructive sleep apnea syndrome (OSAS), but the anatomical relation between snoring and OSAS, if any, has remained unclear. To compare the morphology of the airway between snorers and OSAS patients for possible similarities, we conducted a cephalometric analysis of Japanese OSAS patients (n=10), habitual snorers (n=10), and non-snoring controls (n=50). There was no significant difference in SNB (the angle formed by the sella, nasion and point B) between OSAS patients and the control subjects. Obstructive sleep apnea syndrome patients tended to have an anteriorly positioned maxilla, and an anteroposterior misalignment between the maxilla and mandible. There was also a tendency toward skeletal openbite. Both OSAS patients and snorers had large tongues and large soft palates, thus causing constriction of the airway with resultant smaller airway diameter and smaller airway surface area. Significant differences between OSAS patients and snorers were found in thickness and length of soft palate surface area, and thickness, length, and position of the hyoid bone. These results suggest that cephalographic measurements may be of considerable use in determining the seriousness of a patient's condition.

A scanning electron microscopic study of the guinea pig cochlear aqueduct. With emphasis on fracture preparation.

The cochlear aqueduct is the duct that connects the perilymphatic space of the scala tympani with the subarachnoid space. However, its functions are not yet fully elucidated. In the present study on the cochlear aqueduct of the guinea pig, a fracture preparation method was used to obtain new findings by scanning electron microscopy.