Viral Pathogenesis:
Mechanism of Acute and
Persistent Infections with
Paramyxoviruses
YOSHIYUKI NAGAI and TETSUYA YOSHIDA
pg(s) 1 - 17
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Paramyxoviruses are a group of infectious agents that cause a variety of diseases in man
and animals, such as mumps, measles, respiratory infections in infants, Newcastle disease in
chickens, and canine distemper. Besides these acute diseases, the viruses of this group are
known to often induce long-term persistent infections and have long been suspected to be
involved in chronic neurological diseases such as subacute sclerosing panencephalitis and
multiple sclerosis.
Viral pathogenesis, the way in which a virus produces a disease, involves a complex
interaction between the virus and the infected organism. Thus, it is, in general, not easy to
define the molecular basis for pathogenesis with any given virus.
A virus is pathogenic for a particular host if it can infect the host and produce signs and
symptoms of disease. A virus strain is said to be more virulent than another if it regularly
produces more severe signs or disease in a host in which both strains are pathogenic. Thus,
one way to study such a difficult problem as pathogenesis is to define the factors responsible
for the differences in virulence. In this context, Newcastle disease virus (NDV) provides a
good research model since it comprises a wide variety of well-characterized strains which
differ markedly in virulence but are indistinguishable from each other by conventional
serology.
The processes of diseases in long-term persistent infections are even more complicated.
Therefore, efforts have mainly concentrated on elucidation of the mechanism of induction of
persistent infections in cultured cells. Of the paramyxoviruses, Sendai virus (hemagglutinating
virus of Japan, HVJ) has probably been best studied in this respect.
In this article, we illustrate our recent attempts to answer the questions related to acute and
persistent infections with NOV and Sendai virus as well as those reported by other authors for
different viruses.
A Study of Sequential Anastomoses
in Aortocoronary Bypass Surgery;
Internal Configurations by the
Casting Injection Technique
KENSUKE SHIOI
pg(s) 19 - 26
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Recently, sequential Aortocoronary (A-C) bypass surgery has been used widely for the
revascularization of multiple coronary vessel disease. In this study the internal configuraitons of
anastomosed portions were investigated by casting models and the following results were obtainted:
1. In crossed side-to-side anastomoses with longitudinal incisions, the anastomosed area for the incised
length was larger than those in other anastomoses procedures.
2. Interrupted sutures consistently produced larger anastomosed area for the incised length than other
suture techniques.
3. As for anastomotic stenosis, crossed side-to-side anastomoses with one longitudinal and one
transverse incision resulted in the most frequent occurrence of narrowings.
The Combined Effects of
60CO Gamma-Rays and
Continuous Low Concentrations
of Bleomycin
on Cultured Mammalian Cells
HIDETOSHI KOBAYASHI and SADAYUKI SAKUMA
pg(s) 27 - 33
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The combined effects of 60Co gamma-rays and continuous, low concentrations of bleomycin on FM3A
(mouse mammary adenocarcinoma cells) were examined, and the clinical application of this combination
was reported in this paper. The combined effect appeared to be synergistic, and bleomycin seemed to
interfere with Elkind recovery.
The Present Status
of an Early Infantile Autism
First Reported in Japan
Thirty Years Ago
SHINICHIRO WAKABAYASHI
and TOSHIRO SUGIYAMA
pg(s) 35 - 39
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This report pertains to a follow-up study of a male autistic patient, the first case of early infatile autism
in Japan reported in 1952. He is presently 38 years old, has continued to have the fundamental
characterisics of early infantile autism, and gives us the impression that he has become an adult
maintaining the traces of infancy. Thus, the initial diagnosis of early infantile autism has been confirmed
during 31 years of follow-up. According to the results of many other follow-up studies of autistic children,
most patients showed poor outcome. To our regret, the outcome of this patient was also poor. We
emphasized in this study that the treatment system must be confirmed immediately and that institutions
for poor-outcome patients are required.
Prophylaxie de l'Hépatite a Virus B
en Début d'Enfance
-Immunoglobulines Spécifiques
Anti-HBs (HBIG)
MINORU TANABE, HIROMICHI NOGUCHI,
KAZUO TSUZUKI, SHIGERU MINOWA,
MASUMI TSUYUKI et SHIGEMITSU ITOH
pg(s) 41 - 47
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To prevent the vertical transmitted HB carrier state. we used hepatitis B immune globulin (HBIG). 16
children of HBs-Ag and HBe-Ag positive carrier mother were given HBIG within 24 hours after birth.
Subsequently they were given HBIG properly during 12 months. Of 16 children, 13 remained HBs-Ag
negative and 3 of 13 gained antibody anti-HBs. In 2 children HBs-Ag became positive and acute hepatitis
occured because the interval of HBIG administration was too long. HBIG is effectivefor the prevention of
pcrinatal transmission of HB virus (HBV) carrier state, but the careful follow up is required.
Prophylaxie de l'Hépatite a Virus B
en Début d'Enfance
-Le Vaccin
contre l'Hépatite B (HBVac)
MINORU TANABE, HIROMICHI NOGUCHI, KAZUO
TSUZUKI, SHIGERU MINOWA, MASUMI TSUYUKI,
AKIHITO TSUJI, SHIGEMITSU ITOH, HIDEYUKI
KANOH, TOSHITO KATOH et MASASHI MIZOKAMI
pg(s) 49 - 54
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Three doses of inactivated hepatitis B vaccine were given to 33 healthy children aged less than 5 years.
Of those HBVac recipients who were seronegative before vaccination, 79% had a specific anti-HBs
response without any side effects. As this vaccine is safe and immunogenic in neonates, it is possible to use
it for the prevention of mother-to-infant transmission of HBV.
Analysis of Human Motion in
Rehabilitation by Micro-Computer
FUJIO ITO
pg(s) 55 - 66
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Analysis of human motion is extremely important in order to obtain fundamental data for training in
the field of rehabilitation. At Nagoya University we are analysing human motion by use of a microcomputer
to elucidate functional characteristics of the locomotion system. After the introduction of
micro-computers, it has become possible to accumulate and integrate more data and process them more
quickly and conveniently. Data obtained from the weight balance analyzer. large force plate and threedimensional
goniometer devised by the authors are subjected to on-line processing through an A/D
convertor. 1. The weight-balance analyzer for the evaluation of dynamic balance ability can be used both
in standing and sitting positions. A computer block-break game is integrated into the program so that
training can be performed enjoyably. 2. A large serial force plate is used to detect the floor reaction force of
individual legs. Three force components in the directions of X. Y and Z are transformed to resultant force.
velocity. acceleration and paths of center of pressure through mathematic processing. 3. The threedimensinal
goniometer describes angular changes of the hip or knee joint in the three planes during
walking. In addition to flexion-cxtension. adduction-abduction and internal-external rotation can be
grasped easily by this device.
Gluconeogenesis and Ammonia Production
in the Isolated Perfused Rat Kidney:
The Effect of Starvation, Acidosis
and Diabetic Ketosis
ENJIRO GOTO, FUMIHIKO SAKAKIBARA,
TOMOATSU NISHIDA, TAKAHIKO KAWAMURA,
TAKAHISA SANO, ISAMU TSUCHIDA
and NOBUO SAKAMOTO
pg(s) 67 - 78
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Isolated rat kidneys were perfused with a cell-free perfusate, and their creatinine clearance was found to
be 106 μl/min./g wet weight. Gluconeogenesis from pyruvate, lactate, fructose, α-oxoglutarate,
oxaloacetate, glutamate and glutamine as the substrates at a concentration of 10 mM and ammonia
production from glutamine were studied in the kidneys from fasted rats, rats with NH4CI-induced
acidosis, and streptozotocin diabetic rats, using cell-free perfusates. 1. Fasting caused the gluconeogenesis
from all substrates except pyruvate and the ammonia production from glutamine to increase. 2. In the
kidneys from the rats with chronic acidosis, the gluconeogenesis from the substrates other than pyruvate,
lactate and fructose was increased, and the gluconeogenesis and ammonia production from glutamine
were both greater than those in the kidneys from the 7-day fasted rats. 3. In the kidneys from the
streptozotocin diabetic rats, the gluconeogenesis from all substrates other than fructose was increased and
was greater than that in the kidneys from the fasted rats and the rats with chronic acidosis. Also, despite
the markedly increased gluconeogenesis from glutamine, ammonia production did not increase. From
these findings, we believe that gluconeogenesis and ammonia production are not always coupled with each
other, especially under some conditions in tho isolated perfused rat kidneys.
Studies on the Blood-Retinal Barrier
After Cryoretinopexy with
Vitreous Fluorophotometry
MIYOKO KATO and FUMITAKA ANDO
pg(s) 79 - 86
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The extent of damage to the blood-retinal barrier, induced by cryoapplication on the sclera, was
measured in adult pigmented rabbits by using a vitreous fluorophotometer. In eight isolated cryopexies.
the intensity of each was equalized by stopping freezing exactly when a white spot started to appear in the
fundus, and the blood-retinal barrier damage was repaired 7-10 days after the operation.
On the other hand, in the eyes treated with double cryoapplication refreezing being initiated just after
the initial ice ball in the fundus disappeared, fluorescein concentration was reduced below the control
value in 3-5 days but histopathological reparation of the retinal pigment epithelium was incomplete in
these cases. The eyes treated with 20 scattered applications showed more profuse leaking of the fluorescein
dye and required 35-42 days before the concentration of fluorescein was reduced below the control value;
however, when the leaking ceased, the regenerated retinal pigment epithelium covered the Bruch's
membrane. The above findings indicate that to prevent protraction of blood-retinal barrier damage
associated with the retinal pigment epithelium, cryoretinopexy twice or more to the same area or
extremely extensive cryoapplications at one time are prohibitive.
Some Properties of Amine Oxidase
from Soybean Seedlings
TAKATOSHI MATSUMOTO, YUJI NIMURA,
TAMAKI FURUTA, NAOKAZU HAYAKAWA,
MASANORI ASAI, YOSHIE KUROKAWA,
TATSUO HATTORI and YOTARO IYOMASA
pg(s) 87 - 94
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The purpose of the present study was to clarify the properties of amine oxidase partially purified from
soybean seedlings, which the authors used as an enzyme sample for the assay of diamines (putrescine,
cadaverine) and polyamines (spermidine, spermine). The enzyme activity was highest with cadaverine
followed by putrescine, spermidine, 1,7-diaminoheptane and spermine. The optimum pH was 7.8 for
putrescine and cadaverine and 8.0 for spermidine and spermine. Carbonyl reagents, such as
semicarbazide, and chelating reagents, such as cuprizone, were effective inhibitots of soybean seedling
amine oxidase (SSAO), suggesting that Cu++ and pyridoxal may be cofactors for SSAO. Therefore, SSAO
appeared to be a diamine oxidase (EC 1.4.3.6). It was stable at 50°C for at least 2 hours, and the apparent
Km, values for all diamines and polyamines were extremely low. Since SSAO is present in great quantities
in soybean seedlings, which can be easily obtained in every season in Japan, it is very suitable asan enzyme
sample for the assay of diamines and polyamines.
Ultrasonograms and
Histological Findings
of the Postmortem Pancreas
KENJI TANEHIRO
pg(s) 95 - 107
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The exact relationship between ultrasonograms and histological findings of the pancreas was
investigated in 24 postmortem materials consisting of II cases of normal pancreas, 9 of pancreatic tumor
and 4 of chronic pancreatitis, Normal pancreas showed a smooth contour and a homogeneous echo
pattern with uniform echo intensity which was 10 dB higher than that of the normal liver. Pancreatic
tumor generally showed an irregular contour, low echo intensity and a heterogeneous echo pattern. Mild
chronic pancreatitis manifesting acinar atrophy, fally replacement and fibrosis showed a smooth contour
and a homogeneous, dense echo pattern with elevated echo intensity. The pancreas with only marked fatty
replacement showed the same ultrasonographic image as mild chronic pancreatitis. Pancreatic calculi
produced scattered reflective echoes making a heterogeneous echo pattern. The pancreas with advanced
chronic pancreatitis, in which the parenchyma was entirely replaced by fibrous tissue associated with
ductal dilatation, showed an irregular contour and low echo intensity, almost the same as that of
pancreatic tumor, but the homogeneous echo pattern enabled the author to differentiate advanced
chronic pancreatitis from pancreatic tumor.
Major Surgery
in Patients Undergoing Hemodialysis
HIROSHI TAKAGI, KAZUHARU UCHIDA,
NOBUO YAMADA, TAKESHI MORIMOTO,
MITSUNORI YASUE, YOSHIHIRO TOMINAGA,
MACHIO KAWAI, TADAYUKI KANO
and KATSUHlKO KAWAHARA
pg(s) 109 - 116
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This report describes our experience with major surgery in hemodialysis patients and discusses special
considerations in their surgical management. Atotal of 359 operations under general anesthesia excluding
blood access operations were performed in hemodialysis patients (kidney transplantation, 168; bilateral
nephrectomy with or without splenectomy, 38; graftectomy. 40; parathyroidectomy. 43; mastectomy. 2;
gastrectomy. 24; biliary tract surgery, 9; surgery of intestinal obstruction, 2; appendectomy, 8; surgery of
colon & rectum, 10; haemorrhoidectomy, 5; etc.). There were six postoperative deaths within 30 days
(cadaveric kidney transplant, 1; graftectomy, 3; pancreaticoduodenectomy, 1; subtotal gastrectomy, 1).
Recently, cadaveric kidney transplants are increasing and HLA-DR matching in cadaveric transplant has
gained acceptance. The introduction of Cyclosporin A has remarkably improved the graft survival rate so
far. Splenectomy has resulted in a significant improvement in the hematologic status of all patients.
Bilaterally excised kidneys for a pretransplant procedure or because of severe hypertension decrease in
weight progressively after the start of hemodialysis. Since the pathogenesis of renal osteodystrophy is
highly complex. image diagnosis of parathyroid glands is valuable for (1) definite diagnosis of secondary
hyperparathyroidism, (2) localization, and (3) diagnosis for effectiveness of conservative treatment.
Fourteen of 18 patients with cancer (thyroid, 1; breast. 2; stomach, 4; bile duct, 1; head of pancreas, 1;
colon & rectum, 8; kidney, 1) underwent curative surgery. Although hemodialysis patients remain
chronically ill despite optimal hemodialysis, they tolerate major emergency or elective surgery rather well
if the necessary precautions are taken.
Gamma Interferon Production by
Peripheral Blood Lymphocytes in
Patients with Gastric Cancer
KAZUO KUSUGAMI, KIMITOMO MORISE
and HAJIME KATO
pg(s) 117 - 123
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The production of gamma interferon (IFN-γ) by peripheral blood lymphocytes was studied in 38
patients with gastric cancer. Purified protein derivative (PPO) as a specific antigen and three kinds of
mitogens, phytohemagglutinin-P (PHA), concanavalin A(Con A) and pokeweed mitogen (PWM), were
used as IFN-γ inducers. IFN-γ production by lymphocytes was markedly reduced in patients with gastric
cancer when these inducers were used. Reduction of IFN-γ production was observed more often in
patients of Stage IV than in those of Stage I when PPO or Con A was used. PPO-induced IFN-γ
production significantly increased in patients who were operated on curatively, while it decreased in those
who were operated on noncuratively. IFN-γ production by lymphocytes, especially when PPO is used as
an IFN-γ inducer, reflects cell-mediated immunity in patients with gastric cancer. It may be useful as
quantitative parameter to predict therapeutic effects and prognosis in cancer patients.
Two Components in L1210 Cells and
Their Growth Characterization
KIKUKO WAKAYAMA, EMMANUEL C. BESA
and STEVEN I. BASKIN
pg(s) 125 - 142
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L1210 cells were separated into two populations by the standardized method of mononuclear cell
purification using Ficoll-Hypaque. One population (L-cells) was obtained in the usual mononuclear layer
above Ficoll-Hypaque and the other (Bo-cells) was found at the bottom of the tubes below FicollHypaque.
The biological characteristics of both populations were evaluated by the following parameters
at every 24 hr and up to 168 hr after intraperitoneal inoculation of 105 L1210 cells into DBA/2J mice:
growth kinetics in vivo and in vitro, viability. morphological features, cell volume, 3H-thymidine (TdR)
uptake, contents of protein. DNA and taurine, and modal chromosome number. Protein content was
generally higher in Bo-cells than in L-cells throughout the observation period. The mean cell volume of
Bo-cells increased and decreased more rapidly compared with L-cells. and its was significantly larger at
earlier time points and smaller at later time points. DNA content and cell proliferation patterns in vitro
and in vivo of Bo-cells showed similar changes. 3H_TdR uptake was significantly higher in Bo-cells at any
time point except for the last 168 hr, and taurine contents in both L- and Bo-cells showed almost mirrorimage
values of their respectivc'H-TdR uptakes. Viability and cytological findings did not show any
specific difference between L- and Bo-cells. These studies demonstrated the heterogeneity of L1210 cells.
which until now have been believed to be very homogeneous tumor cells. The correlation between cell
growth pattern and effectiveness of antineoplastic agents was also discussed.
Comparison of Early Fates of Cadaver
Renal Allografts from Different
Methods of Harvest
HIROSHI TAKAGI,
KAZUHARU UCHIDA,
KUNIO MOROZUMI,
NOBUO YAMADA, MACHIO KAWAI,
TAKAHIRO ISHII, TADAYUKI KANO,
TAKESHI MORIMOTO and TATSUYA AKAZA
pg(s) 143 - 153
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The early fate of cadaveric grafts harvested from four different methods depending on donor categories
(A) in situ flushing with a simple catheter, B) in situ perfusion with a double balloon catheter, C) shipped
kidneys from the United States, and D) from brain death and beating heart donors) were compared
including histological studies of one-hour biopsied specimens. Early initiation of graft functions was
naturally seen first in group D, which was followed by group B. In situ perfusion with a double balloon
catheter is a very valuable method of harvest in those countries where death is declared after cessation of
breathing and heart beat.