A case of exfoliative esophagitis with pemphigus vulgaris.

Autoimmune blistering skin diseases, including pemphigus vulgaris, rarely involve the esophagus. We report a case of exfoliative esophagitis with pemphigus vulgaris. A sloughing esophageal cast observed by endoscopy was dissected esophageal squamous epithelium in all layers. Our case is the fifth case of pemphigus vulgaris associated with esophageal cast formation recorded in the medical literature. Prednisolone was administered, and both the pemphigus vulgaris and exfoliative esophagitis improved. Upon findings of exfoliative esophagitis by endoscopic examination, we should consider the coexistence of blistering skin diseases, including pemphigus vulgaris.

Initial analysis of relationship between plasma platinum concentration and hematological adverse reaction associated with weekly chemotherapy using nedaplatin in combination with radiotherapy for cervical carcinoma.

PURPOSE: Established therapeutic guidelines for cervical carcinoma recommend concurrent chemo- and radiotherapy as standard treatment for locally advanced cervical carcinoma. Nedaplatin (CDGP) is a platinum agent developed in Japan that is less nephrotoxic than cisplatin (CDDP), but with equivalent antitumor potency. In the standard dosage regimen for cervical carcinoma, CDGP is administered once every four weeks (monthly regimen). We investigated the efficacy and safety of a new dosage regimen, in which CDGP was administered once weekly for five weeks (weekly regimen). METHODS: We measured plasma platinum concentration of patients after administration of CDGP, and analyzed the relationship between plasma platinum concentration and hematological adverse reactions such as thrombocytopenia and leucopenia. RESULTS: The relative rates of change in platelet and white blood cell counts tended to increase as the plasma concentration of platinum increased. Furthermore, the rate of change in platelet counts in relation to the area under the curve was greater for the monthly regimen as compared to weekly. On the other hand, the relative rates of change in WBC were nearly the same between the regimens. CONCLUSIONS: These findings indicate that when using chemotherapy with CDGP for a patient with a cervical carcinoma, a weekly regimen might reduce the severity of thrombocytopenia, while still exhibiting the same therapeutic efficacy as the monthly regimen.

Local massive venous invasion in colorectal cancer: CT-pathological correlation and its clinical implication.

OBJECTIVE: To identify CT findings of massive venous invasion (MVI) in colorectal cancer, compare them to pathological findings and evaluate its clinical implications. METHODS: Among 423 patients who received surgical resection of colorectal cancer, pre-operative CT of 26 patients (15 males, 11 females; mean age, 63.0 ± 12.1 years) with histopathologially proven MVI and 26 patients (14 males, 12 females; mean age, 71.1 ± 9.6 years) with histopathologically proven lymph node (LN) metastases were reviewed and compared with histopathological findings. We evaluated CT detectability of MVI and the morphologic differences between MVI and LN metastasis. All cases were followed up for at least 6 months after surgery. RESULTS: Pre-operative CT correctly diagnosed only one case as tumour thrombus. 9 lesions were not detected on CT, and others were misdiagnosed pre-operatively as regional LN metastasis (14 cases) and juxtatumoural abscess (2 cases). After reviewing these cases, MVIs were identifiable in 20 of 26 cases. MVI was depicted on CT as nodules (oval, lobulated), abscess-like or intravenous tumour thrombus. MVI was significantly larger than LN metastasis (p < 0.05), while contrast enhancement was significantly lower (p < 0.05), and MVI often had an enhanced rim. Ten patients had synchronous metastases, and six patients had metachronous distant metastases within 5 years. CONCLUSION: Many cases of MVI were distinguishable from LN metastases on pre-operative CT of colorectal cancer, but their appearances were varied, reflecting their histopathological behaviours. The distant metastatic rate was much higher in cases with MVI. ADVANCES IN KNOWLEDGE: Radiologists should be aware of CT findings of MVI in colorectal cancer as a sentinel sign of distant metastasis.

G --> A mutation of ras genes and infrequent p53 gene mutation in rat transplantable thyroid carcinoma lines from tumors induced in vivo by N-bis(2-hydroxypropyl)nitrosamine.

In a comparative study, we have investigated mutational activation of three kinds of ras genes and the p53 gene (exons 5-8) in 19 rat transplantable thyroid carcinoma lines derived from in vivo tumors induced by DHPN. Mutations were identified using single-strand conformation polymorphism and DNA sequencing analysis, and activated ras oncogenes were detected in 6 lines (31%). These all had mutations in Ki-ras codons at 12 or 63, and one of them also possessed a Ha-ras mutation at codon 12 as a double mutation. Three mutations of Ki-ras at codon 12 involved the second nucleotide and two the first position, the other being found at the first nucleotide in codon 63. Base alterations of p53 gene were found in two lines. One had an insertion of 1 base (thymine) between codon 206 and codon 207. Historically, it was diagnosed as a poorly differentiated papillary carcinoma (scirrhous pattern). In the another case, there was no amino acid change although one base substitution occurred at codon 283 (GAG --> GAA) of exon 8. These results indicate that, in the ras family, DHPN induces Ki-ras gene activation preferentially and that p53 mutation may be infrequent in thyroid carcinogenesis in rats, our data thus corresponding well with the previous reports that an inactivated p53 gene only plays a major role in human undifferentiated thyroid carcinomas.

p53 tumor suppressor gene and ras oncogene mutations in hypopharyngeal squamous cell carcinomas.

To examine the potential role of p53 and ras gene mutations in hypopharyngeal tumorigenesis, twenty-eight primary hypopharyngeal carcinomas, obtained at biopsy or total pharyngolaryngectomy, were investigated. Exons 5 through 9 of the p53 gene and exons 1 and 2 of the H-, K-, N-ras gene were screened using a combination of immunohistochemistry and single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP). The targeted DNA sequences coding for p53 and ras were confirmed by direct DNA sequencing. Point mutations of p53 were found in 9 (32.1%) of the 28 cases, including one with a double mutation, 3 in exon 5, 1 in exon 6, 2 in exon 7 and 4 in exon 8. Positive nuclear immunostaining for p53 was evident in 14 (50.0%) lesions. Seven (25.0%) of the 28 demonstrated point mutations in the H-rns gene, and 11 (39.3%) showed positive cytoplasmic staining for I as. The 5-year survival rate was worse with than without p53 overexpression (p <0.05). The present results suggest that gene mutations, although they occur at a relatively low incidence, are involved in hypopharyngeal tumorigenesis with p53 expression being a prognostic factor.

"Swimming-induced head twitching" in rats in the forced swimming test induced by overcrowding stress: a new marker in the animal model of depression?

We have used overcrowding stress to study the pathogenesis of depression and the action of antidepressant drugs. In the present study, the influence of overcrowding on behavior was assessed by the forced swimming test. All the stressed rats revealed highly characteristic head twitching movement, which was not inhibited by repeated administration of diazepam and haloperidol, but was markedly suppressed by repeated administration of desipramine and mianserine. A significant positive correlation in the number of twitching episodes in each stressed rat between the first and second forced swimming test was seen. These findings support the use of overcrowding of rats as a stressor in the animal depression model because it fulfills the criteria of the model; face validity, construct validity and predictive validity. We propose the adoption of "swimming head twitching" as a new marker in the animal model of depression.

Structure and expression of rat and mouse mRNAs for Zn-alpha 2-glycoprotein.

Rat and mouse cDNAs for Zn-alpha 2-glycoprotein (Zn alpha 2gp) were isolated from liver libraries (lambda gt11) and compared with the human one. The lengths of cDNA inserts analyzed were 1,233 and 1,273 nucleotides for rat and mouse, respectively. The deduced amino acid sequences suggested that rat and mouse Zn alpha 2gp proteins consist of 279 and 290 amino acid residues in the mature form, respectively. They have 59.4% (rat) and 58.6% (mouse) identities in amino acid sequence with the human counterpart, and between rat and mouse the identity is 88.5%. Among the three domains, domain B is best conserved; the identities are 74.7, 73.6, and 95.6% between human and rat, human and mouse, and rat and mouse, respectively. Four cysteine and eight tryptophan residues are all conserved, and two of the three asparagine residues that carry a glycan in the human protein are conserved. Analysis of rat tissues by Northern blot suggested that its mRNA is expressed in liver, and, to a much lesser extent in submandibular gland, lung, kidney, and stomach. A more detailed study by in situ hybridization demonstrated that some epithelial cells of renal tubules and the isthmus and the neck zone cells of gastric fundic glands express Zn alpha 2gp mRNA.

Effects of ageing on the total number of muscle fibers and motoneurons of the tibialis anterior and soleus muscles in the rat.

The age-related changes in the total number of muscle fibers and motoneurons of the tibialis anterior and soleus muscles were studied using 10-, 65-, and 135-week-old rats. The number of fast twitch muscle fibers was decreased at age 65 weeks, while the numbers of slow twitch fibers and of alpha motoneurons were decreased only later, at age 135 weeks. Therefore, the degenerative process of muscle fibers differs with the fiber type.

Soma size and oxidative enzyme activity of motoneurones supplying the fast twitch and slow twitch muscles in the rat.

The relationship between soma size and oxidative enzyme activity of motoneurones supplying the fast twitch muscle and the slow twitch muscle was examined. Horseradish peroxidase was injected into the extensor digitorum longus (fast twitch) muscle and the soleus (slow twitch) muscle to retrogradely label corresponding motoneurones of the rat spinal cord. There was a negative relation between soma size and oxidative enzyme activity of motoneurones in a particular neurone pool. The alpha motoneurones supplying the slow twitch muscle had higher oxidative enzyme activities than identical size motoneurones supplying the fast twitch muscle. The present results suggest that there is a difference between oxidative capacities of fast twitch and slow twitch neurone pools.

Identification of L-dopa immunoreactivity in some neurons in the human mesencephalic region: a novel dopa neuron group?

The presence of L-3,4-dihydroxyphenylalanine (L-DOPA) immunoreactivity is reported for the first time in some neurons in the human mesencephalic region, using an immunohistochemical method with a newly raised, highly specific anti-L-DOPA antiserum. We have found many L-DOPA-positive/dopamine (DA)-positive and a few L-DOPA-positive/DA-negative cell bodies in dopaminergic regions in the midbrain. The present results suggest the existence of more than one neuronal group of L-DOPA in the human mesencephalon. L-DOPA in one group is an intermediate metabolite for decarboxylation to DA and in another group may exist as an end-product. L-DOPA in the latter neurons could be a neuromodulator and/or neurotransmitter. Thus, we suggest that L-DOPA plays an important role besides being an intermediate of DA in the human mesencephalon.

Ruptured aneurysm at the origin of the accessory middle cerebral artery: case report.

The accessory middle cerebral artery is a rare vascular anomaly of the brain. We describe a case of a ruptured aneurysm at the junction of the accessory middle cerebral artery and the horizontal portion of the anterior cerebral artery. The lesion was demonstrated by angiography and confirmed at surgery. No perforating arteries arising from this accessory artery were found. There have been only four previous reports of aneurysms located at the origin of the accessory middle cerebral artery. The relevant literature is briefly reviewed.

The value of serial auditory brainstem response in patients with subacute sclerosing panencephalitis.

A total of 98 serial auditory brainstem responses from 17 patients (11 boys and 6 girls) with subacute sclerosing panencephalitis were compared with their clinical course and stages. These patients were exposed to measles early in life (at 1.8 +/- 1.4 years old) with the average onset of the disease at 8.8 +/- 0.7 years of age. The main abnormalities of their auditory brainstem responses were a prolongation of waves I, III, and V, and of the I to V interpeak interval. Wave V thresholds were also elevated. These effects on the auditory brainstem responses started 1 to 2 years after onset of neurologic signs. I to V interpeak latency became prolonged with the progress of clinical stages, especially in Jabbour's clinically advanced stage IV. In two patients with an acute progressive type of subacute sclerosing panencephalitis, very rapid deterioration with a distorted wave pattern of later components was observed. These findings suggest rostrocaudal progression in the central nervous system of both long-term and fulminant cases.

Cranial computed tomographic and magnetic resonance imaging studies on the Rett syndrome.

We reported here 5 cases with the Rett syndrome (RS) who fulfilled the criteria for RS. The changes in CT and MRI findings with the clinical course were studied. Cortical atrophy especially in the frontal area, progressed gradually with the clinical progression after 2 years old in CT. In axial sections on MRI, frontal atrophy was also demonstrated. The white matter, basal ganglia, thalamus and hypothalamus area were all normal. In midline sagittal sections, corpus callosum was hypoplastic, and widening of prepontine cistern and narrowing of the brainstem were demonstrated in some cases. There was no significant atrophy of the cerebellum, amygdala and hippocampus. Follow-up studies including CT and MRI are necessary to evaluate brain morphology in RS.

Studies on pediatric patients with absent auditory brainstem response (ABR) later components.

Eleven pediatric patients with only wave I or waves I and II of their ABR were clinically analyzed. The clinical diagnoses of these patients were as follows: 1) anoxic encephalopathy in two cases; 2) neonatal asphyxia in one; 3) infantile Gaucher's disease in one; 4) mitochondrial encephalomyopathy in one; 5) suspected Pelizaeus-Merzbacher disease in three; 6) degenerative disease of unknown etiology in two (presumptive diagnosis were progressive supranuclear palsy and dentate-rubro-pallido-Luysian atrophy); and 7) infantile spasms with congenital malformation of the brain and bones in one. The incidence of the patients with this type of ABR abnormality was 0.67% among 1,650 of our pediatric patients whose ABRs were examined because of audiological or neurological problems. All eleven patients showed severe mental retardation. Nine of the eleven had convulsions and likewise, eight of eleven showed deterioration in mental and/or motor activities. Furthermore seven of eleven had disturbed consciousness and four of these seven were in deep coma. Other brainstem and bulbar signs and symptoms were frequently found in these patients. In our series, patients without the later components of ABR manifested marked neurological abnormalities inside and outside the brainstem.

Poliomyelitis-like syndrome following asthmatic attack (Hopkins syndrome).

A 12-year-old boy is described with a combination of right arm paralysis resembling poliomyelitis and severe asthma. At 4 years of age, he developed flaccid paralysis one day after a severe asthma attack. No etiologic factors could be found for his flaccid paralysis. Nineteen patients with similar poliomyelitis-like illnesses following asthmatic attack are reviewed.

Development of a new cellulose triacetate membrane with a microgradient porous structure for hemodialysis.

Dialytic performance and biocompatibility of a newly developed cellulose triacetate (CTA) membrane with a microgradient porous structure, produced without using polyvinylpyrrolidone (PVP) and liquid paraffin, were compared with those of a conventional polysulfone (PS) membrane dialyzer. In vitro and clinical results demonstrated no significant difference in the dialytic performance and biocompatibility of the two dialyzers, but the CTA dialyzer lost less albumin during dialysis than the PS. These results suggest that a CTA membrane dialyzer with a porous microgradient structure attained comparable performance and biocompatibility to PS, and the risk of albumin loss was suppressed by the new CTA membrane.

Hyperactivation and acrosome reaction in vitro in spermatozoa ejaculated by cryptorchid dogs after orchiopexy.

Orchiopexy of the cryptorchid (CR) testis and castration of the scrotal testis were performed in three unilaterally CR beagles at six months of age. Induction rates for ejaculated sperm hyperactivation (HA) and the acrosome reaction (AR) in vitro in these orchiopexied dogs were compared with five those in normal beagles one year later. Canine spermatozoa were incubated for 9 hr at 38 degrees C under 5% CO2 in air in canine capacitation medium at a concentration of 30 x 10(6) sperm/ml. HA was observed using high-speed videomicrography. The AR spermatozoa were evaluated by the triple stain technique. As a result, there was no significant difference between 'the CR dogs after orchiopexy' (CDO) and the normal dogs (ND) with respect to sperm motility just after ejaculation. However, sperm motility of CDO decreased markedly during incubation. There was a significant difference in sperm motility between CDO (Mean +/- SD; 47 +/- 12%) and ND (80 +/- 9%) after three hours of incubation (p less than 0.01). No significant difference was observed between CDO and ND with respect to the HA rate of motile spermatozoa throughout the incubation period. The peak of HA rate was found in both CDO (58 +/- 5%) and ND (61 +/- 16%) after seven hours of incubation. The AR rate of spermatozoa in CDO was lower than that in ND after six hours of incubation. The AR rate of CDO (26 +/- 4%) was significantly lower than ND (46 +/- 5%) after eight hours of incubation (p less than 0.01). It is assumed that there might be relation between a rapid decrease of motility and low AR rate in spermatozoa of CDO during incubation.

Minute gastric carcinoid tumor with regional lymph node metastasis.

A minute carcinoid tumor of the stomach developed into a regional metastasis around the celiac axis. There was marked lymphangitic and venous invasion of the tumor cell cluster around the tumor, in the submucosal layer. We wish to emphasize that radical gastrectomy with extended lymphadenectomy should be performed, even for a minute carcinoid tumor, as there will probably be a lymph vessel-related metastasis.

Intratumoral administration of tumor necrosis factor-alpha for malignant gliomas--two case reports.

Two patients with histologically verified glioblastoma multiforme and anaplastic astrocytoma were treated with four courses of intratumoral administration of human natural tumor necrosis factor-alpha (TNF) (specific activity 2.0 x 10(6) Japan reference unit [JRU]/mg protein) at intervals of 3-5 months. Each consisted of eight to 10 serial injections, ranging from 5 x 10(3) to 10(4) JRU/injection, at intervals of 3-5 days. There was no simultaneous administration of steroids. Serial neurological examinations and neuroimaging studies with computed tomography and magnetic resonance imaging demonstrated partial responses ranging from 28 and 36 months in duration. No significant TNF-related brain edema, intracerebral bleeding, or neurotoxicity occurred. Local immunotherapy with TNF may be used safely to contribute to therapeutic efficacy.

Structure and function of nitrifying biofilms as determined by molecular techniques and the use of microelectrodes.

The phylogenetic diversity of a nitrifying bacterial community of two types of nitrifying biofilms, a domestic wastewater biofilm and an autotrophic nitrifying biofilm grown on rotating disk reactors (RDR), was characterized by 16S ribosomal DNA (rDNA)-cloning analysis. Thereafter, successional development of nitrifying the bacterial community within both biofilms was visualized in situ by fluorescent in situ hybridization (FISH) wih a set of fluorescently labeled 16S rRNA-targeted DNA probes. In situ hybridization revealed that Nitrosomonas ureae was the numerically dominant species of the ammonia-oxidizing population in the domestic wastewater biofilm and that a population shift from N. urea to N. europaea and N. eutropha occurred when the culture medium was switched to the synthetic media from the domestic wastewater. After reaching the steady-state condition, microprofiles of NH4+, NO2-, NO3-, and O2 in the biofilms were measured by use of microsensors, and the spatial distributions of in situ nitrifying activities were determined. The relationship between the spatial organization of nitrifying bacterial populations and the in situ activity of these populations within the biofilms was discussed. Microelectrode measurements revealed that the active ammonia-oxidizing zone was vertically separated from the active nitrite-oxidizing zone. This vertical separation became more evident with increase of the substrate C/N ratio, leading to deterioration of nitrification efficiency. The combined use of these techniques made it possible to relate in situ nitrifying activity directly to the occurrence of nitrifying bacterial populations.