Enhancement of norepinephrine-induced transient contraction in aortic smooth muscle of diabetic mice

Changes in norepinephrine-induced transient contractions in Ca2+-deficient solution were investigated in the aortic smooth muscles of diabetic ALS (alloxan-induced diabetes susceptible) mice. The transient contractions in diabetic mice were significantly larger than those in normal mice. The longer incubation of the muscle preparations in Ca2+-deficient solution made the transient contractions smaller, probably due to the leakage and decrease in norepinephrine-releasable stored Ca2+. The rate of this reduction in contraction was slower in diabetic mice. These results suggest that the leakage of intracellular stored Ca2+ caused by extracellular Ca2+ deficiency is attenuated in diabetic mice, contributing to enhanced norepinephrine-induced transient contractions.     

TRANSSYNAPTIC DEGENERATION IN THE INFERIOR OLIVARY NUCLEUS ASSOCIATED WITH PONTINE GLIOBLASTOMA

A case of glioblastoma arising in the pons of a 14-year-old boy in whom transsynaptic degeneration was found in the inferior olivary nucleus is reported. The tumor occupied most of the pons including the tegmental tract and invaded into the midbrain, medulla oblongata, cerebellar peduncles, thalamus, basal ganglia, and meninges. The right inferior olivary nucleus was devoid of the tumorous lesion, but many neurons were severely vacuolated. An im-munohistochemical study using glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and S-100 protein was performed. GFAP and S-100 protein were positive in the reactive glia of the nucleus and NSE gave a faint reaction in some degenerated neurons. These degenerative changes found in neurons of the inferior olivary nucleus were considered to be transsynaptic degeneration due to the destruction of the tegmental tract at the pons and of cerebellar peduncles by invasive pontine glioblastoma. ACTA PATHOL. JPN. 35: 1495–1500, 1985.     

Mutational screening of APP gene in patients with early-onset Alzheimer disease utilizing mismatched PCR-RFLP

To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early-onset Alzheimer disease, we designed a mismatched PCR-RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR-RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS-1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early-onset Alzheimer disease.     

INTRAUTERINE CANDIDA INFECTION IN PREMATURE BABY

An autopsy case of pulmonary candidiasis occurring in a neonatal girl was reported. The mycological examination of the lung taken at autopsy revealed only Candida albicans and followed by the elucidation under the microscopic sections prepared with special stains; periodic acid-Schiff and methenamine silver, in the lung, stomach, umbilical cord, and amnion. The presence of Candida vaginitis in her mother supported the concept that Candida albicans was the etiological agent of the pulmonary candidiasis.     

Pathogenesis of Rinderpest Virus Infection in Rabbits I. Clinical Signs, Immune Response, Histological Changes, and Virus Growth Patterns

Rabbits were intravenously inoculated with an attenuated rinderpest virus (L strain), and general patterns of the disease were investigated. The rabbits developed fever with concomitant occurrence of diarrhea and lymphopenia. Early production of interferon was followed by a rise of neutralizing antibody. Histological examinations revealed an involvement of all of the lymphoid tissues, with primary lesions consisting of necrosis of the lymphoid follicles and formation of giant cells. Immunofluorescent examinations suggested that the virus growth was present in almost all of the lymphoid tissues. The possibility of application of this experimental system for the study of systemic infection by measles virus was discussed.     

C to T transition at the first nucleotide of codon 63 of the β-globin gene corresponding to hemoglobin M-Saskatoon in an Indonesian boy

Summary Hemoglobin (Hb) M-Saskatoon, a variant of methemoglobin, is characterized by mild hemolysis. It is caused by the substitution of a histidine by a tyrosine at the 63rd amino acid residue of the -globin chain. Amplification and sequence analysis of genomic -globin DNA from an Indonesian boy diagnosed as having the more severe disease thalasemia demonstrated the presence of a C to T transition at nucleotide 473 in one of the two -blogin genes resulting in a histidine to tyrosine substitution at 63rd residue. This amino acid change matched with that reported in Hb M-Saskatoon. This nucleotide change abolished a recognition site for the restriction endonucleaseNlaIII.NalIII digestion of the corresponding -globin DNA amplified from the patient's parents indicated that the mutation was inherited through from his mother. This result shows that the world-wide distribution of Hb M-Saskatoon extends to Indonesia, where it was not previously identified. Possible causes of the unusually severe symptoms observed in the case are discussed.     

Ultrastructural changes of bile duct epithelium in primary biliary cirrhosis in relation to progression of bile duct loss

Summary Using wedge liver biopsies from patients with primary biliary cirrhosis (PBC), ultrastructural features of the intrahepatic bile ducts in livers with slight or no bile duct loss were compared with those in livers with advanced bile duct loss and in extrahepatic cholestasis (EHC).Most changes in the biliary epithelium in PBC were similar to those in EHC. Microvillous loss and bleb formation, mitochondrial damage and increase in endoplasmic reticulum and ribosomes were found in PBC irrespective of the degree of bile duct loss, and also in EHC. These changes were present almost equally at any level of the biliary tree, and are presumed to represent a variety of non-specific lesions of biliary epithelial cells. As the loss of bile ducts in PBC progressed, cytoskeletal filaments and cytophagosomes increased in number and basement membranes were more thickened and reduplicated. These changes were more or less conspicuous in smaller branches of the biliary tree, and were also prominent in EHC. They might be causally related to the bile flow disturbance in the liver. Lateral intercellular spaces were irregularly dilated and contained osmiophilic membranous and/or granular material, similar to that found in duct lumena, within and without the basement membrane, and in the cytoplasm of periductal macrophages. Furthermore, pinocytotic vesicles were increased in the biliary cytoplasm facing periphery. These findings suggest possible alteration of the permeability of biliary epithelial cells, probably in the direction from the lumena to the periductal tissue. Such changes were found in PBC livers with virtual absence of bile duct loss, and the significance of this phenomenon is discussed.     

Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma

AIMS: Galectin-3, a member of the beta-galactoside binding family of lectins, has been regarded as a useful tool for discriminating malignant tumours from benign nodules of the thyroid, including the distinction between follicular carcinoma and adenoma. However, there are follicular tumours with unclear vascular or capsular invasion, which makes diagnosis more difficult. In this study, we investigated the relationship between galectin-3 expression and the degree of vascular or capsular invasion of follicular tumours. METHODS: We immunohistochemically investigated galectin-3 expression in 260 cases of follicular tumour with various degrees of vascular or capsular invasion classified into four categories. RESULTS: The galectin-3 expression level significantly increased with the degree of vascular or capsular invasion (p<0.0001). However, its diagnostic value for follicular carcinoma was not high because the sensitivity and specificity were 68.7% and 57.5%, respectively. CONCLUSIONS: Our findings suggest that galectin-3 plays a role in the transformation of follicular tumours from benign to malignant; however, when diagnosing follicular tumours, the presence of this protein should not be required for diagnosing malignant transformation in all cases. Therefore, we must conclude that galectin-3 should only be considered an adjuvant marker for follicular carcinoma.     

Differing Patterns of P-Selectin Expression in Lung Injury

Using two models of acute lung inflammatory injury in rats (intrapulmonary deposition of immunoglobulin G immune complexes and systemic activation of complement after infusion of purified cobra venom factor), we have analyzed the requirements and patterns for upregulation of lung vascular P-selectin. In the immune complex model, upregulation of P-selectin was defined by Northern and Western blot analysis of lung homogenates, by immunostaining of lung tissue, and by vascular fixation of ¹²⁵I-labeled anti-P-selectin. P-selectin protein was detected by 1 hour (long before detection of mRNA) and expression was sustained for the next 7 hours, in striking contrast to the pattern of P-selectin expression in the cobra venom factor model, in which upregulation was very transient (within the 1st hour). In the immune complex model, injury and neutrophil accumulation were P-selectin dependent. Upregulation of P-selectin was dependent on an intact complement system, and the presence of blood neutrophils was susceptible to the antioxidant dimethyl sulfoxide and required C5a but not tumor necrosis factor α. In contrast, in the cobra venom factor model, upregulation of P-selectin, which is C5a dependent, was also dimethyl sulfoxide sensitive but neutrophil independent. Different mechanisms that may explain why upregulation of lung vascular P-selectin is either transient or sustained are discussed.