Temporal bone histopathology in trisomy 22.

Trisomy 22 has multiple physical anomalies, and aural malformations are commonly associated with trisomy 22. However, there has been only one report describing the temporal bone histopathology in trisomy 22. Our case is the second reported temporal bone histopathology of trisomy 22. Aural anomalies in this case were less serious than those earlier described, though showing Mondini dysplasia of the bony and membranous labyrinth. Deafness in patients with trisomy 22 may manifest sensorineural, conductive or mixed hearing losses, and/or vestibular dysfunction of varying degrees, according to the site and severity of aural anomalies.

Temporal bone pathology in Cornelia de Lange syndrome.

OBJECTIVE: This study aimed to demonstrate the temporal bone histopathology of Cornelia de Lange syndrome. STUDY DESIGN: Histopathologic examination of an infant with this syndrome. SETTING: This study was performed at the temporal bone laboratory. Fukushima Medical University, Fukushima. RESULTS: The authors describe interesting temporal bone findings of this syndrome: anomalies of the middle and inner ear and the facial nerves. CONCLUSIONS: This is the second case report describing the histologic findings of the temporal bone in Cornelia de Lange syndrome in the English literature.

Hipposulfates A and B, new sesterterpene sulfates from an Okinawan sponge, Hippospongia cf. metachromia.

Two new sesterterpene sulfates, hipposulfates A (1) and B (2), have been isolated from an Okinawan sponge, Hippospongia cf. metachromia and their structures elucidated by interpretation of spectroscopic data. Both compounds contain an enolsulfate functionality. Hipposulfate A (1) showed moderate cytotoxicity.

Bilateral parotid gland basal cell adenomas. Case report.

We report a 65-year-old female with basal cell adenomas arising in the left and right parotid glands and review the literature. Diagnosis was based on clinical features, ultrasonographic and CT findings as well as histopathological examination. Parotid tumours usually arise on one side and bilateral occurrence is rare, accounting for 1-3% of all parotid tumours. Most bilateral parotid tumours are Warthin's tumours and pleomorphic adenomas, and bilateral basal cell adenomas of the parotid glands are very rare and only 5 cases including ours have been reported. The exact mechanisms contributing to the development of bilateral parotid tumours remain unknown. We speculate on the involvement of environmental and genetic factors since the histological features of both parotid tumours are identical in most cases.

Temporal bone findings in multiple endocrine neoplasia type 2B.

To our knowledge, present case is the first published report of temporal bone findings in multiple endocrine neoplasia type 2B (MEN-2B). We describe a 43-year-old Japanese man with medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuroma and a Marfanoid body habitus. The collateral adrenal tumors and MTC were removed surgically. However, 14 years after surgery, the MTC and pheochromocytoma recurred and the patient died of intracranial hemorrhage due to hypertension. During the autopsy, metastatic MTC was detected in the liver, lungs, kidneys, pancreas and cervical lymph nodes. Recurrent pheochromocytoma was present in the right kidney. Mucosal neuromas were found in the tongue, gastrointestinal tract and vesical nerve plexus. The following histopathological findings were seen in both temporal bones: metastatic MTC was found as well as neuromas and the cochlear aqueduct was widely patent.

Thonningianins A and B, new antioxidants from the African medicinal herb Thonningia sanguinea.

Two new ellagitannins, thonningianins A (1) and B (2), have been isolated from the African medicinal herb Thonningia sanguinea and their structures elucidated by interpretation of spectroscopic data. Both 1 and 2 showed strong free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as shown by ESR analysis.

Dimerumic acid as an antioxidant of the mold, Monascus anka.

We previously reported that the mold Monascus anka, traditionally used for fermentation of food, showed antioxidant and hepatoprotective actions against chemically induced liver injuries. In the present study, the antioxidant component of M. anka was isolated and identified. The antioxidant was elucidated to be dimerumic acid. DPPH (1,1-diphenyl-2-picrylhydrazyl) radical was significantly scavenged by the antioxidant whereas hydroxyl radical and superoxide anion were moderately scavenged. When the antioxidant (12 mg/kg) was given to mice prior to carbon tetrachloride (CCl(4), 20 microl/kg, ip) treatment, the CCl(4)-induced liver toxicity in mice seen in an elevation of serum aspartate aminotransferase and alanine aminotransferase activities was depressed, suggesting the hepatoprotective action of the antioxidant. The liver microsomal glutathione S-transferase activity, which is known to be activated by oxidative stress or active metabolites, was increased by CCl(4) treatment and the increase was also depressed by pretreatment with the mold antioxidant. Thus these data confirmed that the dimerumic acid isolated from M. anka is the potential antioxidant and protective against CCl(4)-induced liver injury.

Temporal bone pathology in Wegener's granulomatosis.

This study aimed to demonstrate the temporal bone histopathology of two cases of Wegener's granulomatosis in which the initial symptoms were profound hearing loss and facial nerve palsy respectively. The first case, a woman of 44, suffered profound hearing loss which was remarkably improved by steroid and cyclophosphamide treatment for a time, and which seemed to be caused by invasion from granulation tissue filled in the tympanic cavity. The second case was a 61-year-old woman presenting with the facial nerve palsy. The bony canal of the horizontal portion of the facial nerve was destroyed due to granulation tissue which filled in the tympanic cavity, and granulomatous involvement was observed in the facial nerve. Wegener's granulomatosis can involve the middle ear and/or inner ear, causing hearing loss of conductive, mixed or sensorineural type. Pathogenesis of facial nerve palsy seems to be related to Wegener's granulomatous involvement of facial nerve, because the facial nerve palsy also resolved by using steroid and cyclophosphamide.

[Examination for prediction of residual cholesteatoma].

Residual cholesteatoma, recurrent cholesteatoma, and the open cavity problem still remain to be solved in the surgical treatment of middle ear cholesteatoma. To avoid residual cholesteatoma, complete removal of the cholesteatoma matrix is necessary, but it is sometimes difficult to completely remove it at the initial operation. It is important to estimate the amount of residual cholesteatoma and to completely remove it before its enlargement causes several complications. We established some criteria in order to estimate the residual cholesteatoma at the initial operation, and analyzed the relationship between the criteria and the actual residual cholesteatoma at the second operation. We divided the degree of expectation of residual cholesteatoma into 4 groups: 'none', 'low-rate', 'high-rate', and 'certain'. 'Certain' means that we intentionally left a small part of the matrix to avoid inner ear damage during the procedures. Of 200 cholesteatoma patients who had undergone tympanoplasty between 1985 and 1993, we reviewed 118 who had also undergone a second look or a second stage surgical procedure. Residual cholesteatoma had developed in 25 patients. In those patients, 5 had two pieces of residual cholesteatoma. The incidence of residuum was 0%, 16.5%, 30% and 83.6% in the 'none', 'low-rate', 'high-rate', and 'certain' groups, respectively. The criteria were statistically analyzed and are discussed from the viewpoint of several parameters which would be expected to influence the development of residual cholesteatoma. The analysis disclosed that only one factor influenced the development. The factor was whether the operator could or could not maintain the continuity of the cholesteatoma matrix during the procedure. According to the result, we revised the criterion. The new criterion was considered to be valuable when residual cholesteatoma was predicted, and when adaptation of an exploratory operation was decided.

Biological behaviour of 6-chloro-2',3'-dideoxyguanosine and 6-chloro-2',3'-dideoxyinosine in the brains of mice.

By using tissue and blood from mice and mice themselves, biological behavior of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG) and 6-chloro-2',3'-dideoxyinosine (6-Cl-ddI) was examined in vitro and in vivo. Both compounds resemble each other in chemical structure. They are converted to ddG and ddI, respectively, by adenosine deaminase in the cells, and express their anti-HIV activity in vitro. According to our recent data about their biological behaviour in vivo; however, it was revealed that they are fairly different especially as the agent working in the brain. After injection of each drug into the body of mice, ddG, or metabolite of 6-Cl-ddG, was observed in the brain, while ddI was not found there.

Enzyme-histochemical localization of carbonic anhydrase in the inner ear of the guinea pig and several improvements of the technique.

We have made several improvements in the method of fixation of the inner ear and the enzyme-histo-chemical technique for carbonic anhydrase (CA) detection. The results confirmed that CA is localized in the hair cells of the organ of Corti, Deiters' cells or nerve endings, inner pillar cells, Boettcher's cells, stria vascularis, spiral ligament, spiral limbus, and spiral ganglion cells. These results generally agree with previous histochemical observations but showed some differences. Our method preserved tissue morphology and showed more detailed localization of CA activity in the inner ear. In particular, the marginal zone of stria vascularis and the epithelial cells of spiral prominence, facing the endolymph, showed no CA activity, while the suprastrial region of the spiral ligament and the supralimbal region of the spiral limbus, juxtaposed to the perilymph, showed CA activity. In outer hair cells, the cuticular plate, which faces the endolymph showed CA activity, but the lateral membrane, which faces the perilymph showed no CA activity. In contrast, the inner hair cell cytoplasm showed diffuse CA activity. These results will be useful in considering ion exchange between endolymph and its adjacent cells, and between perilymph and its adjacent structures.

Histochemical localization of carbonic anhydrase in the trachea of the guinea pig.

Tissue specimens from guinea pigs were examined using an enzyme-histochemical reaction to explore the presence of carbonic anhydrase (CA) activity in the trachea. CA activity was detected in a group of morphologically distinct epithelial cells, in goblet cells, and in glands of the tracheal mucosa. The epithelial cells showing CA activity were distributed singly and sparsely throughout the entire trachea. These cells showed a wide morphological variability and were clearly different from those forming the pseudostratified ciliated epithelium. Their number was higher in sections closer to the tracheal bifurcation than in those near the larynx. Although the nature of these cells is unknown, based on their morphological and histochemical characteristics and their distribution, they may represent a specialized chemoreceptor. To our knowledge, this is the first report of CA localized in tracheal epithelial cells.

Ptilomycalin A, a novel Na+, K(+)- or Ca2(+)-ATPase inhibitor, competitively interacts with ATP at its binding site.

Ptilomycalin A inhibited the brain Na+, K(+)-ATPase and Ca2(+)-ATPase from skeletal sarcoplasmic reticulum with an IC50 value of 2 microM and 10 microM, respectively. Kinetic analysis of the inhibitory effects of ptilomycalin A suggests that the inhibition of Na+, K(+)-ATPase is a competitive-, an uncompetitive- and an anticompetitive-type with respect to ATP, Na+ and K+, respectively. The inhibition of Ca2(+)-ATPase by ptilomycalin A is a competitive- or an uncompetitive-type with respect to ATP or Ca2+, respectively. These results suggest that ptilomycalin A interacts with ATP at the ATP binding site of Na+, K(+)-ATPase or Ca2(+)-ATPase. Ptilomycalin A has become a useful biochemical tool for clarifying the ATP binding site in both enzymes.

Identification of nasal epithelial cells with carbonic anhydrase activity.

Although carbonic anhydrase (CA) plays an important role in respiration, there is little information about CA in the respiratory system except for the lung. We examined the entire nasal cavity of guinea pig to identify CA activity using an enzyme-histochemical method. CA activity was detected in a group of morphologically distinct nasal epithelial cells. These cells were singly and sparsely distributed mainly in the olfactory epithelium and their number increased rostrocaudally. These cells were also detected in the apical portion of the nasal turbinate, particularly on the nasal endoturbinate, with a more complicated structure, rather than on the nasal septum and the roof of nasal cavity. Although the physiological role of these cells in unknown, based on the morphological and histochemical characteristics and the distribution of these cells, we speculated that they may represent a specialized chemoreceptors.

Periodontal conditions in older age cohorts aged 65 years and older in Japan, measured by CPITN and loss of attachment.

Periodontal conditions were assessed by CPITN and loss of attachment in 601 elderly people randomly selected in Kitakyushu, Japan. The percentage of edentulous persons was 21 per cent, 38 per cent and 65 per cent in the 65-74 year, 75-84 year and 85 years and older groups, respectively. In dentate persons, over 60 per cent had pocket probing depths of 4mm or more; in the majority loss of attachment did not exceed 5mm. The mean numbers of sextants with pocket probing depths of 4-5mm (CPITN 3) and probing depths of 6mm and more (CPITN 4) were similar in each age group. The mean numbers of sextants with both pockets and loss of attachment showed no clear difference among groups. Only the mean number of excluded (no, or only one tooth) sextants increased with increasing age from 1.9 to 3.1. It could therefore be suggested that in the population examined the progress of periodontal destruction with increasing age might not be shown by an increase in pocket probing depth, loss of attachment or gingival recession, but only by an increase in tooth loss. The results for the remaining teeth show that a) severe loss of periodontal attachment (6mm or more) was not frequently encountered, b) recession (attachment loss without pocketing) was present at only very low levels, c) the main periodontal problem seemed to be pocketing, which could be treated. It is therefore tempting to suggest that some of the teeth already lost, could have been saved if proper self- and professional care had been applied.

A novel dodecadepsipeptide, cereulide, isolated from Bacillus cereus causes vacuole formation in HEp-2 cells.

A HEp-2 cell-vacuolation factor was extracted and purified from the culture supernatant of a Bacillus cereus strain which caused emetic-syndrome food poisoning. The final preparation was chemically pure, and the toxin was named as cereulide. Mass spectrometry, NMR studies and chemical degradation revealed that the cereulide is a cyclic dodecadepsipeptide, (D-O-Leu-D-Ala-L-O-Val-L-Val)3, which is closely related to the potassium ionophore, valinomycin.

Electron microscopic studies on experimental poisoning in mice induced by cylindrospermopsin isolated from blue-green alga Umezakia natans.

The effects of cylindrospermopsin isolated from a blue-green alga Umezakia natans on mice were examined morphologically and biochemically. The main target of the phycotoxin was the liver. The thymus, kidneys and heart were also affected. There were four consecutive phases of the pathological changes in the liver. The initial phase was that of inhibition of the protein synthesis, the second phase of membrane proliferation followed, and then the third phase of fat droplet accumulation and finally the phase of cell death. Using globin synthesis in the rabbit reticulocytes system, it was clearly demonstrated that cylindrospermopsin is a potent inhibitor of the protein synthesis. Protein in microsomes from the mouse livers treated by cylindrospermopsin decreased in amount more significantly than that of phospholipid in microsomes. Furthermore, the amount of total P450 was extensively diminished in the toxin treated with hepatic microsomes.

Isolation of cylindrospermopsin from a cyanobacterium Umezakia natans and its screening method.

In 1987 a cyanobacterium (blue-green alga) Umezakia natans was isolated from Lake Mikata, Fukui, Japan, as a new member of the family of Stigonemataceae. The crude extract of U. natans showed hepatotoxicity to mice, from which a toxic compound was isolated. The toxin was identical in all respects to a recently reported hepatotoxin, cylindrospermopsin, isolated from an Australian tropical cyanobacterium Cylindrospermopsis raciborskii. Because cylindrospermopsin causes fatty liver and central necroses in mice and is suspected of being an agent causing human hepatoenteritis, its monitoring in drinking water supplies has been required. So a rapid screening method including four steps, extraction, clean-up, separation, and determination, has been proposed for cylindrospermopsin. A combination of a clean-up using HP-20 and C18-cartridge, and HPLC with photodiode array detector made it possible to establish a screening method for the toxin. The established method was applied to five samples and cylindrospermopsin was traced in one of them.

Correlation between blood pressure and plasma insulin in acromegaly.

OBJECTIVES: The aims of this study were to determine the possible role of hyperinsulinaemia in the increase in blood pressure in acromegalic patients. DESIGN: After an overnight fast, blood samples were obtained at 0. 30, 60, 120 and 180 min after 75 g glucose ingestion, and plasma growth hormone (GH) and plasma insulin (IRI) were measured by radioimmunoassay. The blood pressure was measured at 10.00 hours for 3 days in a supine position. SUBJECTS: Nineteen (nine women and 10 men) untreated acromegalic patients, aged 25-69 years. RESULTS: There were no significant correlations between mean blood pressure (MBP; diastolic+one-third pulse pressure) and basal GH, sum of plasma GH at 0, 30, 60, 120 and 180 min or basal IRI. However, significant correlation was observed between MBP and IRI at 120 min (r = 0.57, P < 0.02) or sum of plasma IRI at 0, 30, 60, 120 and 180 min) (r = 0.58, P < 0.02). CONCLUSIONS: We conclude that hyperinsulinaemia may be involved in an increase in blood pressure in active acromegalics.