Conditions of Alzheimer-type dementia in the old-old and oldest-old patients with special reference to extreme conditions of brain aging

A neuropathological study on 1540 consecutive autopsy brains ranging from 60 to 107 years of age revealed the following points. (1) Of the of the demented cases of the plaque-predominant type, 93% were complicated with multiple tiny cortical infarcts. They showed a tendency for dementia to develop before or after the appearance or worsening of a systemic disorder such as cardiovascular disease, respiratory infection and cancer. However, there was no case showing Alzheimer-type dementia (ATD). (2) The plaque-predominant type might be an extreme condition of brain aging in terms of senile plaques (SP). It is likely that although the pathological appearance of SP alone is not responsible for dementia, its coexistence with multiple cortical infarcts could be the cause of dementia. Therefore, this type should be distinguished from ATD. (3) Primary hippocampal degeneration could also be an extreme condition of brain aging in terms of neurofibrillary tangles. This condition was different pathologically from the hippocampal lesion in ATD. (4) Several characteristics of old-old and oldest-old patients were clarified.     

Thyroplasty Type I with Ceramic Shim

Abstract: To prevent side effects from a silicone shim in Isshiki thyroplasty type I, we used a ceramic shim in 10 patients with unilateral recurrent laryngeal nerve paralysis. No published reports have described the use of ceramic in this type of surgery. According to the degree of glottic insufficiency, ceramic shims of various heights were inserted into the fenestration made in the thyroid ala. All patients experienced subjective improvement of voice postoperatively. Laryngoscopies in most cases showed that glottic insufficiency improved postoperatively. In the postoperative examination, the maximum phonation time improved an average of 3.7 s, and the mean flow rate improved an average of 331 ml/s. We have analyzed the relationship of these improvements to the degree of glottic insufficiency and have compared our results with those of other investigators.     

Effects of Intestinal and Hepatic Metabolism on the Bioavailability of Tacrolimus in Rats

Purpose. Tacrolimus, an immunosuppressive agent, has poor and variable bioavailability following oral administration in clinical use. We investigated the contribution of intestinal metabolism to the first pass effect of tacrolimus in rats. Methods. Tacrolimus was administered intravenously, intraportally or intraintestinally to rats. Blood samples were collected over a 240-min period, and blood tacrolimus concentrations were measured. The extraction ratios of tacrolimus in the intestine and liver were investigated. In addition, the metabolism of tacrolimus in the everted sacs of the small intestine was examined. Results. The rate of absorption of tacrolimus in the intestine was rapid, and tacrolimus was almost completely absorbed after intestinal administration. The bioavailability of tacrolimus was about 40% and 25% after intraportal and intraintestinal administration, respectively, indicating that tacrolimus is metabolized in both the intestine and the liver. In addition, tacrolimus was significantly metabolized in the everted sacs of the rat intestine. Conclusions. The present study suggested that the metabolism of tacrolimus in the intestine contributes to its extensive and variable first pass metabolism following the oral administration.     

Rhythmical contractions in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats

Rhythmical contractions accompanied by an increase in cytosolic Ca2+ concentrations were produced in ring preparations of endothelium-denuded pulmonary arteries from monocrotaline-treated rats, but not in those from vehicle-treated rats, 2-3 h after a resting tension of 15 mN (150-180% of the initial wall length of the artery) was applied. The rhythmical contractions were abolished by nicardipine and ryanodine. Cyclopiazonic acid reduced the relaxation phase of the rhythmical contractions, finally leading to a sustained contraction. Similarly, apamin caused a sustained contraction, whereas charybdotoxin increased the amplitude of the rhythmical contractions. Glibenclamide had no apparent effects on them. Indomethacin and the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 abolished the rhythmical contractions and reduced the tension, but the thromboxane synthase inhibitor ozagrel had no effect. These results suggest that optimal stretch induces rhythmical contractions in the pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats, to which both Ca2+ influx through voltage-operated Ca2+ channels and Ca2+ release from the endoplasmic reticulum seem to contribute. It is also suggested that small-conductance Ca(2+)-activated K+ channels participate in the relaxation phase of rhythmical contractions. Furthermore, prostaglandin H2 released from nonendothelial cells is likely to play a pivotal role in the induction of rhythmical contractions.     

Split tolerance between spleen and lymph node cells in severe combined immunodeficiency mice grafted with AKR fetal liver cells

Severe combined Immunodeficient (SCID) mice defective in stemcells for T and B cells appear to be an ideal host for constructionof chimeric mice. When bone marrow cells are used as a sourceof stem cells, however, host SCID mice do not always show sufficientreconstitutlon. In this study, fetal liver cells from AKR embryoswere transplanted into SCID mice without prior irradiation.This treatment induced full reconstltution of lymphopoiesisas evaluated by flow cytometry analysis and serum Ig production2 months after transplantation. Thus, fetal liver cells seemto be a better source for reconstitutlon of SCID mice than bonemarrow cells. Lymph node (LN) cells of these mice (FLT mice)had no proliferatlve or cytotoxlc activities against eitherhost-type (C.B-17) or donor-type (AKR) spleen cells. However,spleen cells from FLT mice exhibited marked proliferatlve andcytotoxlc activities against C.B-17 cells, with no activitiesagainst AKR cells. Spirt tolerance against C.B-17 cells In spleenand LN cells was not a transient phenomenon, since similar resultswere obtained from a cytotoxic T lymphocyte assay 4 months later.In spite of the strong host reactivity in vitro, aberrationof clonal deletion or development of a graft-versus-host diseasewas not seen in FLT mice. As IL-2 induced the host reactivityof LN cells in a mixed lymphocyte reaction, potentially host-reactiveT cells were present in LN but were rendered anerglc. Tolerancein FLT mice seems to be regulated by a peripheral mechanism.We supposed that the split tolerance in FLT mice was inducedby the different antigenicity between the spleen and LN.     

Electron microscopic investigation of transplanted squamous cell carcinoma in nude mice

Extirpated specimens of a squamous cell carcinoma from a human thigh were transplanted to the subcutaneous tissue of nude mice. Fourteen days later, the transplanted tumor masses were, again, extirpated from the nude mice. The transplanted chimera of the squamous cell carcinoma as seen with the electron microscope resembled the tumor cells before transplantation. It is concluded that ultrastructural investigation of transplanted chimera from squamous cell carcinoma cases may be useful for examining the site of action and clinical effects of anticancer drugs on this kind of tumor.     

Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production

The effects of prostaglandin E₂ (PGE₂) on cytokine productionand proliferation of the CD4⁺ human helper T cell clone SP-B21were investigated. In cells stimulated with antl-CD3 mAb, PGE₂inhibited cell proliferation and the production of all the cytokinesexamined. Addition of rlL-2 fully restored the prollferatlveresponse and partially restored the production of IL-4 and IL-5,but not that of other cytokines. In contrast, In cells stimulatedwith phorbol myrlstate acetate (PMA)/A23187, PGE₂ enhanced theproduction of IL-4 and IL-5, and only partially inhibited theproduction of other cytokines. Therefore, the effects of PGE₂vary depending on the mode of T cell activation, and the IL-4and IL-5 are regulated differently from other cytokines. Ina mobility shift assay, only the NF-B (p50/p5O) homodlmer wasobserved in a complex formed with the B sequence in unstlmulatedSP-B21 cells. When cells were stimulated with antl-CD3 mAb orPMA/A23187, a complex formation of NF-B (p50/p65) heterodlmerwith the B sequence was induced. Interestingly, PGE₂ or di-butyryl(Bt₂cAMP abolished the binding of NF-B (p50/p65) heterodlmerto the B sequence in cells stimulated with antl-CD3 mAb butnot with PMA/A23187. Our results suggest that the target ofPGE₂ action is a component in the signal transductlon pathwayleading to the activation of protein klnase C. However, theinhibition of the T cell activation signals by PGE₂ is selective.PGE₂ enhanced the complex formation with NF-AT, AP-1 and CLEOsequences when the cells were activated by either anti-CD3 mAbor PMA/A23187 stimulation. It seems therefore that PGE₂, byelevating cAMP levels, interferes with the activation pathwayfor NF-B but not for NF-AT, AP-1 or CLEO binding protein.     

Effect of increased task procedures on correlation dimensions of the electroencephalogram

Changes in correlation dimensions of the electroencephalogram (EEG) were examined in three different tasks. These three tasks differed from each other with respect to the number of procedures. In the present experiment, left-hand movement and mental arithmetic were controlled, respectively, during an auditory linguistic task. Subjects were 13 healthy right-handed males. EEG signals from eight electrode sites were analyzed and the correlation dimensions were obtained. In addition, the relative power was obtained for the alpha band. An increase in the number of procedures yielded high dimensionality on the occipital EEG. In contrast, left-hand movement had no significant effect on EEG dimensions over the motor area. The relative power of the alpha band was seen to decrease in all channels as the number of procedures increased. The fact that changes in EEG dimensions did not necessarily exhibit a simple correspondence to changes in alpha wave activity was also discussed.     

Evaluation of the theory of cardiac-output computation from transthoracic impedance plethysmogram

To analyse the limit of the stimation of stroke volume by thoracic impedance plethysmography (SV_z), we considered an elastic tube forced with a trapezoidal flow input as a model of the aorta, and, based on Kubicek's equation, the volume input (SV_a) was related to its impedance change via the model system parameters such as elasticity, fiuid inertia, peripheral resistance, total impedance across the tube and the rise and fall time of the input. SV_z is equal to SV_a only when the inflow is a square wave. The ratio SV_z/SV_a decreases with increasing input rise time, while it increases with increasing fall time, if the maximum flow rate and ejection time of the inflow are held constant. SV_z hardly changes in association with changes in elasticity, fluid inertia, peripheral resistance or total impedance. A part of the results, the relationship between SV_z, transthoracic total impedance and aortic flow waveform, was also demonstrated in dogs.