Renal arteriolar hyalinosis, not intimal thickening in large arteries, is associated with cardiovascular events in people with biopsy-proven diabetic nephropathy.

AIMS: Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. METHODS: This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy-proven diabetic nephropathy, with a median follow-up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. RESULTS: Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow-up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan-Meier analysis than those without these lesions (P = 0.005, log-rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. CONCLUSIONS: Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy.

Diffusion-weighted images and vasogenic edema in eclampsia.

BACKGROUND: In eclampsia, it is mandatory to recognize specific cerebrovascular complications before initiation of treatment. Diffusion-weighted magnetic resonance imaging (MRI) is a new technique that differentiates between cerebral infarction and hypertensive encephalopathy with vasogenic edema. CASE: A 23-year-old primigravida developed eclampsia at 29 weeks' gestation. Focal neurologic signs and neuroimaging findings by computed tomography and MRI were consistent with acute infarction or vasogenic edema. Diffusion-weighted MRI did not show an abnormal signal, indicating vasogenic edema. Control of the severe hypertension without anticoagulation therapy was begun. After delivery, the woman's neurologic abnormalities disappeared. CONCLUSION: Diffusion-weighted MRI differentiated between cerebral infarction and vasogenic edema, helping in the management of eclampsia.

DNA-directed magnetic network formations with ferromagnetic nanoparticles.

We formed a DNA network embedding ferromagnetic cobalt nanoparticles with a 12-nm diameter through a nanoscale self-assembly of DNA molecules on large-scale mica surfaces (12 mm x 12 mm); we then confirmed its structural characteristics with an atomic force microscope. Moreover, noncontact magnetic force microscope measurement revealed that some embedded cobalt nanoparticles have different directions of magnetization, similar to "bits" in magnetic data storage devices.

Immortalization of human primary B lymphocytes by simian virus 40 early region DNA.

We obtained several immortalized human primary B-lymphocyte cultures by transfection of the plasmid DNA, which consisted of simian virus 40 early-region DNA (pSVTbsr). These immortalized B lymphocytes grew in a suspension culture forming cell clumps, expressed CD23, and had an interleukin-6 (IL-6) susceptibility for immunoglobulin (Ig) production, although there was an absence of Epstein-Barr nuclear antigen. Therefore, the action of introduced pSVTbsr is equivalent to the Epstein-Barr virus infection through induction and maintenance of immortalized state of the primary B lymphocytes.

Bursal role in the synthesis of gamma-chain messenger ribonucleic acid in young chickens.

Incomplete bursectomy was performed in 3-day-old chickens by treatment with .5% testosterone propionate on the 3rd day of incubation. The purpose of this experimental approach was to determine the role of the bursa of Fabricius in the translation activity of messenger ribonucleic acids (RNA) coding immunoglobulin-isotypes. The bursal poly(A) RNA, prepared from bursae of normal and hormone-treated chickens, directed the synthesis of 72, 43, 38, and 25-kilodalton molecules as revealed by immune precipitation and sodium dodecylsulphate acrylamide gel electrophoresis. However, unlike the messenger RNA from normal bursae, the messenger from bursae of hormonal-treated embryos failed to direct the synthesis of 68-kilodalton gamma-polypeptide.

[Experimental studies on tumor implanted into cerebrospinal fluid: with special reference to tumor growth].

The incidence of metastasis to another organs of the intracranial tumors is rare, while the intracranial dissemination of brain tumor is often experienced clinically. For this purpose of the formation and growth of the intracranial tumor dissemination, VX2 carcinomas implanted into cisterna magna of 24 New Zealand rabbits are studied by neuroradiological and pathological methods. Twenty-one out of 24 (87%) had tumors intracranially. Nineteen cases out of 24 rabbits developed intraventricular tumors selectively. Two cases without the development of tumors showed moderate dilated lateral ventricles. Thiry-seven percent of implanted tumor cases were demonstrated by 3 times magnification cerebral angiography. While CT presented 67 percent of tumors indicating about two times higher detection than magnification cerebral angiography. From the result of these experiment, the detection of tumors by CT was two times higher than the magnification angiography.

[Head injuries in patients with pre-existing skull defects].

The mechanism of impact head injuries has generally been discussed on the basis of the cranium is a rigid box completely filled with incompressible contents. In this paper, two cases of head injuries in patients with severe craniectomized skull defects are reported and their conditions are discussed. The 1st case was a 46 year-old female with a large frontoparietal skull defect following surgery on a brain tumor. While hospitalized, she fell down from her bed (50 cm in height) and suffered strong impact on the craniectomized area. From immediately after the injury, there was flaccid hemiparesis, but CT scans showed no morphological changes. The 2nd case was a 12 year-old female with a major frontal craniectomized skull defect following surgery. She fell down in a corridor at school and suffered an impact injury in the defect area. For several days after the fall, she had a headache and nausea, but there were no other neurological deficits. In CT scans, there were findings of a cortical contusional hemorrhage. Wounds of the skull with a partial defect, i.e. "a semiclosed box" in the narrow sense, cause conditions which are difficult to explain by conventional dynamic traumatology. In this paper, these rare head injuries are discussed on the basis of these two cases experienced by the authors and the literature.

[A case of traumatic cerebrospinal fluid rhinorrhea manifested ten years after head injury].

In patients with head injury, the total incidence of CSF rhinorrhea was 1 - 3%, and in almost all cases, CSF rhinorrhea occurred within the first three months after injury. We report here a case of a 26 year-old male with CSF rhinorrhea manifested with meningitis who had once been admitted to hospital 10 years previously with a head injury. He had a fracture which we thought had caused a CSF leakage in the left frontal skull base. After conservative treatment for a month we eventually undertook bifrontal craniotomy and repaired the cleft of the skull base with dura and fibrin. In cases in which CSF rhinorrhea had occurred more than 10 years after head injury, including several reports in Japan, surgical treatment had always been required. We think bifrontal craniotomy should be performed in such cases in which it is difficult to locate a cleft in the skull base before the operation. The field of view is wider during the intradural approach. To restore an area with a lack of dura, highly anti-infectionary convexity dura is used a lot, and it is also thought that fibrin is effective in dural repair. The dural deficient areas take 3 to 4 months to repair perfectly, and postoperative observation of the patient's progress is required.

[Cleidocranial dysplasia: a case report].

A 3-month-old female infant who presented with patent sagittal suture and loss of weight is described. Physical examination revealed a large sagittal and metopic suture showing delayed closure, a high-arched palate, saddle nose, hypertelorism and nonpalpable edges of the bilateral clavicles. The clavicles also showed undue mobility. Radiological investigations of the cranial skeletal abnormalities revealed enlargement of the sagittal and metopic sutures, and the anterior and posterior fontanelles. A chest radiograph showed a small, bell-shaped thoracic rib cage with partial aplasia of both clavicles. On the basis of the clinical findings, cleidocranial dysplasia was diagnosed. Cleidocranial dysplasia is an uncommon generalized skeletal disorder which, as its name implies, shows striking involvement of the cranial vault and clavicles. The clinical features reflect a generalized defect of both membranous and endochondral bone formation. It is characterized by delayed ossification of the skull, aplastic or hypoplastic clavicles, delayed deciduous dentition, and hereditary characteristics. The amount of calvarial growth is generally small, and the shape remains nearly unaltered. In all cases, calvarial bone thickness increases with age, but in the midline, the fontanelle area, which is shown to be defective at the first examination, remains open in all cases. The midfrontal area is poorly developed and exhibits a groove in many patients. It is inherited as an autosomal dominant trait, with wide variability of expression but a high degree of penetrance. Cytogenetic abnormalities involving chromosome 6p21 have been reported with a cleidocranial dysplasia phenotype. Although psychosocial disorders associated with the abnormal facial and body features may occur, patients have a good overall prognosis and life expectancy. Skull deformity, and delayed closure of the fontanelles and cranial sutures are the most important problems for neurosurgeons. The postero-lateral fontanelle closes before adulthood, whereas the opening in the midfrontal sutural area may persist. Many children with cleidocranial dysplasia whom we have encountered have persisting fontanelles and patent sutures, but this does not seem to predispose them to an abnormal calvarial growth pattern, at least in the age groups investigated. Congenital midface retrusion in the presence of relative or absolute mandibular prognathism is also a major deformity. Care is supportive, including attention to neurosurgical, orthopedic, pediatric and dental problems.

["Skip lesions" in neurological deficits caused by tethered cord syndrome].

The neurological deficits caused by tethered cord syndrome do not necessarily follow a dermatomal pattern of the affected spinal cord from caudal to cephalic fashion. The authors defined these neurological deficits as "skip lesions", and reviewed the neurological deficits in tethered cord syndrome. Among 29 cases, inconsecutive segmental motor weakness in 3 cases, inconsecutive segmental sensory impairment in 6 cases, positive Babinski reflex in 8 cases, supranuclear neurogenic bladder in 3 cases and lumbago or leg pain in 4 cases were observed and they were thought to be compatible with the neurological deficits called "skip lesions". The basic mechanism of this sign is that the cephalic portion of the spinal cord is functionally impaired during flexion of the lumbosacral spine, while the caudal spinal cord with decreased visco-elasticity dose not elongate. Inconsecutive motor-sensory disturbance, accelerated deep tendon reflexes in the lower extremities, positive Babinski or other pathological reflexes in the lower extremities, uninhibited neurogenic bladder, lumbago and pain in the legs were considered to belong to the category of "skip lesions" and they can be treated by the untethering procedure. The authors concluded that preoperative careful insight into the mechanism of "skip lesions" revealed surgical efficacy for the reversible neurological deficits by the untethering procedure, or the efficacy of decompression of the lipoma or neurolysis around the involved spinal nerve roots.

[Serious pitfalls which can be encountered in a course of hypertension-hypervolemia therapy for vasospasm].

Hypertension-hypervolemia therapy (HHT) is widely employed for treatment against vasospasm after subarachnoid hemorrhage (SAH). A few investigations have been reported to establish the fact that HHT results in a high incidence of congestive heart failure and pulmonary edema as well as deterioration of brain edema. From the point of view that the cerebral circulation is not independent of the systemic circulation, the authors investigated the effect of HHT on the systemic circulation of patients with SAH. In 72 patients, intracranial pressure (ICP), pulmonary catheter wedge pressure (PCWP), pulmonary arterial pressure (PA), central venous pressure (CVP), arterial pressure (AP), cardiac index (CI), arterial blood gas (ABGS), electrocardiogram (ECG), serum and urine electrolytes were monitored postoperatively. Furthermore, among these patients, the flow (Flow), volume (Volume) and velocity (Velocity) of the cortical vessels were monitored by means of a Laser Doppler in 25 patients. A cisternal or spinal drain was placed in all of the patients. Elevation of PCWP and CVP and Flow were observed when 300ml of 10% glycerol was administered within a period of 30 minutes, whereas administration of the same dose of glycerol over a period of 60 or 120 minutes caused no significant changes on these parameters. Elevation of PCWP and CVP and decrease of CI and Flow, occasionally associated with premature ventricular contraction (PVC), were observed in some patients when 100ml of 25% albumin was administered. However, administration of the same dose of albumin over a period of 120 or 240 minutes did not cause deterioration of the cardiac function. These facts could be explained by Guyton's law in which massive transfusion causes cardiac dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of an cerebello-pontine angle pineoblastoma].

An extremely rare case of a left cerebello-pontine angle (CP angle) pineoblastoma has been reported. The patient was a 32-year-old male whose initial manifestations were those of increased intracranial pressure. CT scan showed a large enhancing mass located at the left CP angle, associated with a moderate occlusive hydrocephalus. Left suboccipital craniectomy was performed. The mass was an extramedullary tumor which had compressed the left cerebellar hemisphere, and was easily separable from the adjacent tissue. The tumor was totally resected, and the patient had a temporary release from the symptoms. Recurrence and spinal dissemination were found within the ensuing few months. The tumor had invaded deeply through the left CP angle into the cerebellar parenchyme, and showed no anatomical connection with the pineal body. The tumor dissemination was also observed widely in the spinal subarachnoid space. No abnormalities at the pineal region were able to be confirmed using CT and MRI studies. Irradiation to the whole brain, to the localized left CP angle and to the spinal cord with additional chemotherapy was given. The patient died half a year after the first operation. Autopsy was not performed. Histopathologically, the tumor was delineated into lobular structures by reticulin fibrils and vimentin-positive interstitial tissue. Tumor cells were small in size, and had irregularly shaped hyperchromatic nuclei with increased mitotic figures, and formed various types of rosettes; pineocytomatous, Flexner-Wintersteiner, Homer-Wright and perivascular. Fine argyrophilic cell processes with club-shaped expansions were demonstrated inside the pineocytomatous rosettes.(ABSTRACT TRUNCATED AT 250 WORDS)

[Biochemical investigation of normal pressure hydrocephalus in the assessment of shunt effectiveness].

It is well known that, among patients of normal pressure hydrocephalus (NPH), there is a group in which a shunting procedure had no effect on improving clinical signs (shunt-ineffective group). To differentiate the shunt-effective group from the shunt-ineffective group, we performed measurements of cerebrospinal fluid (CSF) levels of uric acid (UA) and gamma-aminobutyric acid (GABA) in patients of NPH. We investigated the age-related CSF levels of UA and GABA in the normal subjects and compared them with those in the patients of NPH including the shunt-ineffective group and other related states, that is, multi-infarct dementia (MID) and patients with full recovery after subarachnoid hemorrhage (SAH) due to the ruptured aneurysm. In the normal subjects, CSF UA levels of second and over seventh decades were significantly higher than those of third, fourth, and fifth decades. On the other hand, CSF GABA levels of second and over seventh decades were significantly lower than those of the others. In the patients of MID, CSF UA levels were much higher and CSF GABA levels were much lower in comparison with the normal controls. These results suggested that, in the aged normal subjects, some degree of brain damage is responsible for high CSF UA levels and low CSF GABA levels. There was no difference in the values of CSF UA and GABA between normal subjects and the patients with full recovery after SAH. In the patients of NPH, CSF UA levels were low in general, while CSF GABA levels were all high. After the shunting operation, CSF UA and GABA levels became normal in the shunt-effective group.(ABSTRACT TRUNCATED AT 250 WORDS)

Immortalization of plasma cells by plasmid DNA and its hybridoma.

Human plasma cell lines producing IgG were cloned by the limiting dilution method from polyclonally immortalized B-cell lines with the plasmid DNA (pSVTLbsr) containing simian virus 40 (SV40)-gene from primary peripheral blood mononuclear cells of healthy and nonimmune volunteers. The plasma cell lines fused well with conventional partner cells and became evenly IgG-producing hybridomas at high efficiency, especially with the partner cell from human origin. One of the difficulties in obtaining stable IgG-producing hybridoma using Epstein-Barr virus (EBV) transformation followed by back fusion with partner cells, might mainly be attributed to the inability to immortalize plasma cells on account of the very low density of CD21 (EBV receptor) on the cell surface. The present CD21-independent immortalization by plasmid DNA and by the infection with SV40 protein-coated plasmid DNA will be a potentially effective method to obtain IgG-producing human monoclonal antibodies.

Cell-free translation of immunoglobulin G polypeptides by chicken bursal RNA.

The acquisition of messenger RNA controlling the translation of immunoglobulin G was studied in the chicken bursa of Fabricius, using the cell-free translation system of wheat germ lysate. Total cellular RNA extracted by phenol-1% sodium dodecylsulphate (pH 5.0 at 50 degrees) incorporated [3H]-leucine maximally. Sodium dodecylsulphate polyacrylamide gel electrophoresis of the immune precipitates of cell-free products with anti-chick IgG showed that polypeptides of gamma- and light chains were synthesized by bursal RNA from 20-day embryos and one-week-old chicks; in addition, a polypeptide with a molecular size of about 4 x 10(4) was synthesized. No appreciable synthesis of gamma- and light chains by bursal RNA from 12-day embryos was found.