In situ localization of tau mRNA in developing rat brain

A microtubule-associated protein, tau, promotes microtubule assembly, forms characteristic short cross-bridges (less than 20 nm) between microtubules, and switches isoforms from juvenile to adult at the end of the first postnatal week in the rat brain. The developmental expression of tau was studied in rat central nervous system, mainly the cerebrum and cerebellum, by in situ hybridization. Tau mRNAs were localized in a wide variety of neural cells. The expression of tau mRNAs in the spinal cord appeared to precede that in the brain, and the expression in the brainstem appeared to precede that in the cerebral cortex and cerebellum. On neural cells throughout the cortical plate of the cerebral cortex, tau mRNAs were expressed in large amounts during the first postnatal week, but by the third postnatal week the expression had become reduced. In the cerebellum, tau mRNAs were enriched in granule cells. The expression in the internal granular layer peaked during the second and third postnatal weeks, and the relatively high level of expression persisted to young adulthood. Thin section transmission electron microscopic study revealed that the proportion of neighboring microtubules in parallel fiber axons of cerebellar granule cells with the distance less than 20 nm was as low as 10% at the end of the first postnatal week, but this proportion increased to as high as 35% at the end of the second postnatal week. Northern blot analysis showed that tau mRNAs were congruent to 6 kb as was reported previously, and those detected in the first postnatal week were three- to five-fold more abundant and approximately 0.2 kb smaller than those detected in the second or third postnatal weeks. The data suggest that (a) tau mRNAs are abundantly expressed in a wide variety of neurons in the central nervous system at the stage of neurite formation, and (b) tau mRNAs are expressed in more basal levels at later stages, but may be important in the formation and maintenance of characteristic microtubule bundles typically found in parallel fiber axons and in other axons.     

CATs and HATs: the SLC7 family of amino acid transporters

The SLC7 family is divided into two subgroups, the cationic amino acid transporters (the CAT family, SLC7A1–4) and the glycoprotein-associated amino acid transporters (the gpaAT family, SLC7A5–11), also called light chains or catalytic chains of the hetero(di)meric amino acid transporters (HAT). The associated glycoproteins (heavy chains) 4F2hc (CD98) or rBAT (D2, NBAT) form the SLC3 family. Members of the CAT family transport essentially cationic amino acids by facilitated diffusion with differential trans-stimulation by intracellular substrates. In some cells, they may regulate the rate of NO synthesis by controlling the uptake of l-arginine as the substrate for nitric oxide synthase (NOS). The heterodimeric amino acid transporters are, in contrast, quite diverse in terms of substrate selectivity and function (mostly) as obligatory exchangers. Their selectivity ranges from large neutral amino acids (system L) to small neutral amino acids (ala, ser, cys-preferring, system asc), negatively charged amino acid (system x_c^–) and cationic amino acids plus neutral amino acids (system y⁺L and b^0,+-like). Cotransport of Na⁺ is observed only for the y⁺L transporters when they carry neutral amino acids. Mutations in b^0,+-like and y⁺L transporters lead to the hereditary diseases cystinuria and lysinuric protein intolerance (LPI), respectively.     

Type-specific evolution of amyloid plaque and angiopathy in APPsw mice

To clarify how Aβ deposits start in the brain, we examined the early to late stages of senile plaques and amyloid angiopathy in APPsw mice. All types of human senile plaques were observed in the mouse brains. The premature forms of cored plaques appeared first in the cerebral cortex of mice at 7–8 months old. Then, amyloid angiopathy emerged, followed by diffuse plaques consisting of Aβ1–42. Modifications of the N-terminus of Aβ were late phase phenomena. The premature forms of cored plaques were composed of central Aβ1–40 amyloid cores, surrounding amorphous Aβ1–42 deposits, and accumulation of Aβ1–42 in some peripheral cells. These cells were incorporated in amyloid cores, and these plaques developed to large cored plaques composed of Aβ1–40 and Aβ1–42. The size and number of cored plaques were increased with age. These findings indicate different evolution paths for cored plaques and diffuse plaques, and suggest the presence of a pathway that initiates with the intracellular accumulation of Aβ1–42 and leads to the development of classic plaques in human brain tissues.     

EXFOLIATIVE CYTOPATHOLOGY OF ALVEOLAR RHABDOMYOSARCOMA

Exfoliative cytopathology of alveolar rhabdomyosarcoma is presented. A 34-year-old male was found to have alveolar rhabdomyosarcoma of the retroperitoneum at autopsy. Ascites was recognized in the course of this disease. Cytological features in the ascites were characterized by relatively small-sized ovoid cells observed singly or in loose clusters. The neoplastic cells possessed small amount of rather vesicular cytoplasm and an eccentric nucleus. The nucleus characteristically revealed multiple deep indentations in the nuclear membrane, a few prominent eosinophilic nucleoli and finely granular or evenly distributed chromatin pattern. These cytological findings, especially the nuclear features, might be useful to differentiate alveolar rhabdomyosarcoma from other neoplasms which consist of relatively small-sized ovoid cells even if the striated muscle origin cannot be confirmed by immunoperoxidase staining.     

High-dose (9 MU) long-term (60 weeks) alfa-interferon therapy for chronic hepatitis patients infected with HCV genotype 1b

Summary.  Efficacy of standard regimens (e.g., 3–6 MU for 24 weeks) of alfa-IFN therapy for chronic hepatitis C has been limited, particularly in patients with HCV/1b. To see if higher-dose longer term treatment is more effective, we tried a 9 MU 60-week regimen. HCV/1b-infected chronic hepatitis patients received 9 MU IFNα2a everyday but Sunday for 2 weeks and thrice a week for next 10 weeks, and 76 patients became HCV RNA-negative while 81 remained positive. The RNA-negative patients were then randomized to receive 3 MU (group I, n=37) or 9 MU (group II, n=39) for 48 weeks. Of the RNA-positive patients, only those with normal ALT received another 9 MU 48-week treatment (group III, n=45). Sustained responders (SR) were defined as those with negative RNA and normal ALT 6 months after the therapy. SR rates based on intent-to-treat principle did not differ significantly between groups I and II (30% vs 41%), but those based on the protocol-compatible cases showed a significant difference (32% vs 56%, p=0.034). SR rate in group III was significantly lower than those in group II. Adverse effects of IFN, developed more frequently in groups II and III than in group I, were mostly reversible. In conclusion, our results encourage 9 MU 60-week IFNα treatment in HCV/1b-infected patients with careful attention to adverse effects, and suggest that the treatment should be discontinued if HCV RNA does not disappear within 12 weeks. Received February 18, 1998 Accepted March 19, 1998     

Alpha 1-antichymotrypsin has a trophic effect on hippocampal neurons in vitro

alpha 1-Antichymotrypsin (ACT) has been reported to be present in senile plaques, and ACT level is elevated in the sera of patients with Alzheimer's disease. We found that ACT has a neurotrophic activity in vitro, i.e., it enhanced neuronal survival under the culture conditions used. Hippocampal neurons were cultured in chemically defined medium containing ACT at various concentrations. In order to evaluate the number of surviving neurons semiquantitatively, enzyme immunoassay for microtubule-associated protein2 (MAP2) was carried out using anti-MAP2 antibody. Cells cultured in medium containing 4 micrograms/ml of ACT showed 1.8-fold more neurotrophic activity than those cultured without ACT.     

Exfoliative cytopathology of alveolar rhabdomyosarcoma

Exfoliative cytopathology of alveolar rhabdomyosarcoma is presented. A 34-year-old male was found to have alveolar rhabdomyosarcoma of the retroperitoneum at autopsy. Ascites was recognized in the course of this disease. Cytological features in the ascites were characterized by relatively small-sized ovoid cells observed singly or in loose clusters. The neoplastic cells possessed small amount of rather vesicular cytoplasm and an eccentric nucleus. The nucleus characteristically revealed multiple deep indentations in the nuclear membrane, a few prominent eosinophilic nucleoli and finely granular or evenly distributed chromatin pattern. These cytological findings, especially the nuclear features, might be useful to differentiate alveolar rhabdomyosarcoma from other neoplasms which consist of relatively small-sized ovoid cells even if the striated muscle origin cannot be confirmed by immunoperoxidase staining.     

The effects upon electromagnetic flowmeter sensitivity of non-uniform fields and velocity profiles

The magnetic flux density of implantable electromagnetic blood flowmeter can not be made uniform, since the size of flowmeter probe must be very small for physiological reasons. The velocity distribution of blood flow is axially non-symmetrical everywhere in arteries. Mainly for the above reasons the blood flow can not be measured accurately by implantable electromagnetic flowmeter. In this paper the relation between induced electromotive force and flow rate for implantable electromagnetic flowmeters is presented, and the errors introduced by the factors mentioned above are discussed. In order to measure pulsatile or axially non-symmetrical flow accurately, appropriate flowmeter probes must be used. Some of these flowmeter probes are shown.     

Studies on the fragments of FDP in 4 patients with DIC]

We previously studied fibrinolysis and fibrinogenolysis by analyzing fragments of fibrin/fibrinogen degradation products (FDP) employing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In this report, we characterized the fragments of FDP in four patients with disseminated intravascular coagulation (DIC), that were caused by various diseases. In the patients suffering from acute lymphoblastic leukemia (case 1) and acute suppurative cholangitis (case 3), DD and DY/X fragments resulting from fibrinolysis accounted for the most part of the FDP fragments. In case 3, D fragments resulting from fibrinogenolysis were also observed to much less extent. In a DIC associated with acute myeloblastic leukemia (case 2), both fibrinolysis and fibrinogenolysis were increased and resulted in high levels of D, Y and DY/X fragments, concomitant with moderate levels of DD and high molecular weight (HMW) fragments in the patient's sera. The increased fibrinogenolysis in this case was attributed to accelerated activation of plasmin. In a DIC patient of case 4, who underwent an operation due to hepatocellular carcinoma, marked increase in DY/X and HMW fragments and slight increase in DD fragment were observed on the day of operation. Hyperfibrinolysis documented in case 4 was explained by both increased production of thrombin and moderately accelerated activation of plasmin. Both qualitative and quantitative changes in the fragments of FDP during the courses of treatment in two cases of DIC were also noted. In summary, each underlying disease expresses characteristic pattern of FDP fragments in DIC.