BACKGROUND: Most patients with anaplastic carcinoma of the thyroid die within several months of diagnosis, and aggressive treatment is uncommon. We evaluated the effect of active multimodal treatment (surgery, radiotherapy, and chemotherapy) on this disease, including one patient treated with autologous bone marrow transplantation and high-dose chemotherapy. METHODS: The outcome was assessed in 37 patients with anaplastic thyroid carcinoma treated between 1971 and 1993. Patients without distant metastasis when initially seen underwent surgery followed by radiotherapy. From 1984, conventional radiotherapy was replaced by hyperfractionated radiotherapy. RESULTS: All but three patients died within 1 year of diagnosis. Patients with primary lesions less than 5 cm in diameter who had complete resection and radiotherapy survived significantly longer than the other patients, and hyperfractionated radiotherapy was effective for local control. CONCLUSION: Active multimodal therapy is indicated for early-stage anaplastic carcinoma of the thyroid.

Adult↗

PubMedDate not supplied

Comparison of routine and selective endoscopic retrograde cholangiography before laparoscopic cholecystectomy.

To evaluate the role of endoscopic retrograde cholangiography (ERC) before laparoscopic cholecystectomy, we compared the frequency of concomitant common bile duct stones, their clinical outcome, and the frequency of bile duct injury between a group of 128 patients with routine preoperative ERC (group A) and 1010 patients with selective ERC (group B). Overall, 48 patients (4.2%) had duct stones, but the predictive signs were absent in six of them (12.5%). The stones were demonstrated by ERC and removed by sphincterotomy in all 11 patients in group A. Of 37 patients in group B, 22 were diagnosed by selective ERC and underwent endoscopic removal. Of four patients whose stones were found by operative cholangiography, one had immediate open surgery, another passed a stone spontaneously, and the other two underwent postoperative sphincterotomy, which failed in one. The stones were not recognized until pain recurred in the remaining 11 patients. Sphincterotomy was successful in nine patients but failed in the other two. Thus postoperative sphincterotomy failed in 3 of 13 patients (23%), necessitating open surgery. Forty-two patients overall (3.7%) had aberrant biliary tract anatomy, which did not lead to bile duct injury in any of the patients. Morbidity of routine ERC (3.1%) was lower than that of selective ERC (7.4%) (p < 0.05). It should be noted that a certain proportion of duct stones may be missed by selective ERC, necessitating laparotomy when sphincterotomy fails. The routine use of preoperative ERC may be justified at institutions where the expertise is available, at least until laparoscopic lithotomy becomes easy.

Adult↗

PubMedDate not supplied

Age-related deterioration of long-term potentiation in the CA3 and CA1 regions of hippocampal slices from the senescence-accelerated mouse.

Long-term potentiation (LTP) is one candidate for the mechanism underlying memory storage. In the present study, we carried out electrophysiological studies on hippocampal slices prepared from the senescence-accelerated mouse (SAM-P/8), a strain which shows accelerated senescence and failure of certain types of learning in behavioral tests. The findings were compared with those noted in the SAM-R/1 substrain without severe symptoms of senescence. No significant differences were found between SAM-R/1 and SAM-P/8 of the same ages in responses in the absence of tetanic stimulation, and in LTP after tetanic stimulation. However, there were marked decreases in the degree of potentiation with aging in both strains.

Journal Article↗

PubMedDate not supplied

The persistence of high uptake of serum albumin in the olfactory bulbs of mice throughout their adult lives.

Brain to plasma concentration ratios of i.v. administered human serum albumin (HSA) in the olfactory bulb, frontal cortex and cerebellum were evaluated in DDD mice of different ages. We measured the brain uptake of serum albumin excluding intravascular content by using a double isotope technique and examined the time course of the brain uptake to evaluate the brain uptake at different time intervals. In young adult mice, the value was significantly higher in the olfactory bulb than in other brain regions 3-24 h after (125)I-HSA injection. It was about 2.3 times higher in the olfactory bulb than in the cerebellum (P < 0.01). The high concentration ratios in the olfactory bulb were observed in all 4-22-month-old mice. Moreover, the ratio in the olfactory bulb 24 h after (125)I-HSA injection was higher in 22-month-old mice than in younger animals. The high uptake of serum albumin in the olfactory bulb suggests that intravascular macromolecules can be transported into the olfactory bulb more easily than in other brain regions with tight endothelium, and the persistence of high uptake during adult life may be associated with age-related morphological changes in the olfactory bulb.

Journal Article↗

PubMedDate not supplied

Age-related changes in barrier function in mouse brain I. Accelerated age-related increase of brain transfer of serum albumin in accelerated senescence prone SAM-P/8 mice with deficits in learning and memory.

The time course of brain accumulation of radiolabelled human serum albumin ((125)I-HSA) injected intravenously and the transfer of (125)I-HSA from blood to brain were evaluated in DDD mice using a double isotope technique. The brain accumulation of (125)I-HSA at 3 and 9 h but not at 24 h postinjection and the brain transfer rates were significantly higher in 22-month-old DDD mice than in 4-month-old ones. The brain transfer rates of (125)I-HSA were measured also in senescence accelerated prone mice (SAM-P/8) with age-related deficits in learning and memory, and in senescence accelerated resistant mice (SAM-R/I) without these deficits. The brain transfer rates were significantly higher in 13-month-old SAM-P/8 and 22-month-old SAM-R/1 than in 3-month-old mice of the same strains, respectively. The mean brain transfer rates in five regions observed in 22-month-old DDD mice, 22-month-old SAM-R/1 and 13-month-old SAM-P/8 increased by 31%, 41% and 51% compared with corresponding values in 3- or 4-month-old mice of the same strains. DDD mice and SAM-R/1 mice with normal characteristics of aging showed similar age-related significant changes in brain transfer rates. Age-related increase in the brain transfer rate was manifested at the youngest age in SAM-P/8 among the three strains examined. These findings show that the transfer of human serum albumin into the mouse brain increases with aging and suggest that the barrier function in the mouse brain against macromolecules changes with aging.

Journal Article↗

PubMedDate not supplied

A novel murine model of aging, Senescence-Accelerated Mouse (SAM).

Senescence-Accelerated Mouse (SAM) has been under development by our research team at Kyoto University since 1970, based on the AKR/J strain donated by the Jackson Laboratory in 1968. The SAM mouse has an accelerated senescence and age-associated pathologies such as senile amyloidosis, senile osteoporosis, degenerative joint disease, cataract, deficits in learning and memory, brain atrophy, hyperinflation of lungs, hearing impairment and so on. SAM research is advancing world-wide and attempts are being made to clarify fundamental mechanisms involved in primary aging processes, pathogenesis of age-associated pathologies and effective methods to modulate or ameliorate the advance of senescence and disease processes involved in age-associated pathologies.

Journal Article↗

PubMedDate not supplied

Interstitial fluid pressure in the facial nerve: relationship between facial nerve pressure and cerebrospinal fluid pressure.

The possibility of measuring interstitial pressure in the facial nerve using a servo-nulling system was investigated. As a pilot study, interstitial fluid pressure in the extirpated medulla oblongata was measured using this system, and was found to be proportional to the pressure applied to the surrounding tissue block. Interstitial fluid pressure of the facial nerve in guinea pigs was also measurable with this system. The pressure in the facial nerve fluctuated with respiration and/or heart beat, as did CSF pressure. Respiratory fluctuations in facial nerve and CSF pressures ceased when the respirator was stopped. Facial nerve pressure appeared to be closely related to CSF pressure; the injection of saline into the CSF space resulted in an increase in facial nerve pressure. Measurement of facial nerve pressure by a servo-nulling system should be useful in evaluating the pathogenesis underlying facial palsy.

Animals↗

PubMedDate not supplied

Effect of aging on NADPH-diaphorase neurons in laterodorsal tegmental nucleus and striatum of mice.

Age-related changes of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-containing neurons were examined quantitatively in the laterodorsal tegmental nucleus (TLD) and the caudate-putamen of mice. Six 2-month-old and six 25- to 30-month-old DDD mice were studied using computer-assisted image analysis. Although no age-related changes in neuronal counts were found in the TLD, the cell size in this nucleus showed a statistically significant reduction with aging. In addition, the degree of the age-related neuronal shrinkage differed within the TLD; the most significant occurring in the rostral, less in the caudal third and no significant alteration being found in the middle third portion of TLD. In contrast, NADPH-d-positive neurons in the striatum did not show distinct age-related changes. NADPH-d-containing neurons in the TLD correspond to cholinergic cells, which project to the forebrain. Thus, the age-related shrinkage of NADPH-d neurons in the TLD may be related to the cholinergic dysfunctions seen in the forebrain of senescent mice.

Aging↗

PubMedDate not supplied

Age-related cochlear degeneration in senescence-accelerated mouse.

Age-related hair cell loss and strial atrophy were investigated in an accelerated senescence-prone strain, SAMP1 mice, and an accelerated senescence-resistant strain, SAMR1 mice. The loss of inner and outer hair cells in SAMP1 progressed more rapidly than that in SAMR1 with age. In both strains, areas of the loss of inner and outer hair cells were located mainly in the apex and base. Atrophy of the stria vascularis was observed in both strains, but in SAMP1 it appeared to increase earlier than in SAMR1. These results reveal that age-related hair cell loss and atrophy of the stria vascularis comparable to that in the human cochlea occur earlier and progress more rapidly in SAMP1 than in SAMR1. Hearing impairment in SAM may be due to a combination of sensory and strial presbycusis as well as to neural presbycusis, as reported previously. The morphological changes in the cochlea observed in SAMP1 and SAMR1 make these strains suitable for the study of the mechanisms of presbycusis.

Aging↗

PubMedDate not supplied

Acceleration of chromosome aberrations in senescence-accelerated strains of mice.

Age-related changes in the frequency of chromosome aberrations were examined using bone marrow cells of senescence-accelerated strains of mice (SAM). An accelerated senescence-prone strain, SAM-P/1, showed a striking increase in the frequency of chromosome aberrations, from age 3 to 8 months, whereas an accelerated senescence-resistant strain, SAM-R/1, at the same ages showed only a slight increase. Both these strains were derived from the same ancestral strain (AKR/J). The rate of increase of chromosome aberration frequency paralleled the advancement of senescence in both strains. These observations suggest that there are genetic factors which closely relate to chromosomal instability and acceleration of the senescence processes.

Aging↗

PubMedDate not supplied

Effective intervention of low peak bone mass and bone modeling in the spontaneous murine model of senile osteoporosis, SAM-P/6, by Ca supplement and hormone treatment.

SAM-P/6 is a recently developed strain of osteoporotic mice. In this study we tried to determine whether calcium, vitamin D3, parathyroid hormone (PTH), and estrogen modified the peak bone mass of young SAM-P/6 mice, and whether the effect of these medications persisted after treatment had been discontinued. Calcium supplement, PTH, and estrogen treatment increased the peak bone mass of SAM-P/6 mice. To clarify the process by which bone mass was increased in these treated mice, we evaluated their bone formation and resorption by histomorphometry and measured the levels of ions and serum enzymes relevant to bone metabolism. We found that bone formation was increased by calcium supplementation, and bone resorption was decreased by estrogen treatment. Furthermore, the effectiveness of calcium supplement on peak bone mass was retained after treatment had been discontinued, but the effect of estrogen treatment on peak bone mass was reduced after estrogen treatment had been discontinued. The results of this study indicate that calcium supplementation and estrogen and PTH treatment each increased peak bone mass at the midpoint of the femur of SAM-P/6, and that the effect of calcium supplementation, but not that of estrogen treatment, persisted after treatment was discontinued.

Animals↗

PubMedDate not supplied

Factors influencing collagen-induced autoimmune ear disease.

In 1981, the authors described a type II collagen-induced autoimmune ear disease (CIAED) model. The purpose of this study was to gather further evidence that this is a sound animal model to use in evaluating inner ear diseases. The temporal bone lesions of CIAED in Lewis and Wistar rats were characterized by the presence of sensorineural hearing loss with mild atrophy of the organ of Corti and spiral ganglion degeneration, vestibular dysfunction with vacuolar degeneration of the crista ampullaris, otospongiosis-like lesions in the tympanic annules, cochlear vasculitis, and eustachian tube disease. Both cellular and humoral immune responses to type II collagen were demonstrated. The induction of ear lesions depends on many factors. In general, animals immunized with antigens in complete Freund's adjuvant showed relatively more severe lesions than animals immunized with antigens in incomplete Freund's adjuvant, but the duration of the immunization seems to be a more important factor in reproducing severe lesions. The strain and the source of the animals are also important factors in autoimmune inner ear diseases, as is the condition of the host animals. Subclinical or clinical mycoplasma infection in the rat markedly reduced the incidence and severity of lesions in type II collagen-induced arthritis. Many researchers did not consider sialoductal adenovirus, widely present among laboratory rats, a lesion-producing factor in rats. Although many factors influence the induction and severity of CIAED, these animal models provide an excellent new avenue of inner ear research.

Animals↗

PubMedDate not supplied

Senescence-accelerated mouse (SAM): a biogerontological resource in aging research.

The senescence-accelerated mouse (SAM), consisting of 14 senescence-prone inbred strains (SAMP) and 4 senescence-resistant inbred strains (SAMR) has been under development since 1970 through the selective inbreeding of AKR/J strain mice donated by the Jackson laboratory in 1968, based on the data of the grading score of senescence, life span, and pathologic phenotypes. The characteristic feature of aging common to all SAMP and SAMR mice is accelerated senescence and normal aging, respectively. Furthermore, SAMP and SAMR strains manifest various pathobiological phenotypes which include such neurobiological phenotypes as deficits in learning and memory, emotional disorders, abnormal circadian rhythms, brain atrophy, hearing impairment, etc., and are often characteristic enough to differentiate the strains. Various efforts are currently being made using the SAM model to clarify the underlying mechanisms in accelerated senescence as well as the etiopathogenic mechanisms in age-associated pathobiologies. Genetic background and significance of SAM development are discussed.

Aging↗

PubMedDate not supplied

Senescence-accelerated mouse (SAM): a novel murine model of senescence.

The Senescence-Accelerated Mouse (SAM) has been under development by our research team at Kyoto University since 1970 through the selective inbreeding of the AKR/J strain of mice donated by the Jackson Laboratory in 1968, based on a graded score for senescence, life span, and pathologic phenotype. At present, there are 12 lines of SAM: nine senescence-prone inbred strains (SAMP) including SAMP1, SAMP2, SAMP3, SAMP6, SAMP7, SAMP8, SAMP9, SAMP10, and SAMP11; and three senescence-resistant inbred strains (SAMR) including SAMR1, SAMR4, and SAMR5. Data from survival curves, Gompertzian function, and grading score of senescence, together with growth patterns of body weight of these SAMP and SAMR, revealed that the characteristic feature of aging common to all SAMP mice is "accelerated senescence;" early onset and irreversible advance of senescence manifested by several signs and gross lesions such as the loss of normal behavior, various skin lesions, increased lordokyphosis, etc., after a period of normal development. In the course of SAM development, it became evident that SAMP strains manifest various pathologic phenotypes that are characteristic enough to differentiate the SAM strains. The genetic background and significance of SAM development are discussed.

Aging↗