The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology

In order to test its potential application to surgical neuropathology, the monoclonal antibody Ki-67 was used to demonstrate immunohistochemically the proliferating cells in 40 neoplasms of the nervous system. The antibody, which reacts with a nuclear protein expressed in the G1, G2, S, and M phases of the cell cycle, was demonstrated in frozen sections of all lesions. The highest incidence of stained nuclei was found in a metastatic carcinoma (57%). The percentage of stained cells in gliomas was in general agreement with the histologic grade and known biologic behavior of the lesions, ranging from 0.6% in a pilocytic astrocytoma to 12.4% in a glioblastoma multiforme. In the fibrillary astrocytic neoplasms of low cellularity, there were good correlations between the percentages of stained cells and the degrees of nuclear pleomorphism and chromatin density. In meningiomas, schwannomas, and a cerebellar hemangioblastoma, the fractions of labeled nuclei were less than 1%. The percentage of stained cells in pituitary adenomas showed considerable variation among the four cases (0.2-1.5%), the biologic significance of which is unknown. In four of the above cases, Ki-67 staining was performed on air-dried squash preparations with excellent visualization of immunoreactive nuclei. In one case, a hemangioblastoma, no stained nuclei were seen. The results confirm that Ki-67 staining is technically suitable as a diagnostic method, with good correlations between frozen sections and smear preparations. Determination of the replicating cell fraction could become an important additional criterion to predict the biologic behavior of nervous system neoplasms.     

Nuclear magnetic resonance proton imaging of bone pathology

Thirty-two patients with diversified pathology were examined with a supraconductive NMR imager using spin echo with different TR and TE to obtain T1 and T2 weighted images. They included 20 tumors (12 primary, eight metastasis), six osteomyelitis, three fractures, two osteonecrosis, and one diffuse metabolic (Gaucher) disease. In all cases except for the stress fractures, the bone pathology was clearly visualized in spite of the normal lack of signal from the compact cortical bone. Nuclear magnetic resonance (NMR) imaging proved to be at least as sensitive as radionuclide scintigraphy but much more accurate than all other imaging procedures including computed tomography (CT) and angiography to assess the extension of the lesions, especially in tumors extended to soft tissue. This is due both to easy acquisition of sagittal and coronal sections and to different patterns of pathologic modifications of T1 and T2 which are beginning to be defined. It is hoped that more experience in clinical use of these patterns will help to discriminate between tumor extension and soft-tissue edema. We conclude that while radionuclide scintigraphy will probably remain the most sensitive and easy to perform screening test for bone pathology, NMR imaging, among noninvasive diagnostic procedures, appears to be at least as specific as CT. In addition, where the extension of the lesions is concerned, NMR imaging is much more informative than CT. In pathology of the spine, the easy visualization of the spinal cord should decrease the need for myelography.     

Crossed innervation of the superior rectus.

We studied two patients which showed a paralysis of the oculomotor nerve on one side and isolated paralysis of the superior rectus on the other side. On the side of oculomotor nerve paralysis, midbrain infarct extending from the paramedian tegmentum to crus cerebri was demonstrated in one case who showed no recovery, and a small lacuna in midbrain tegmentum in another one who showed complete recovery. On the side of isolated paralysis of the superior rectus, no lesion was demonstrated by CT and MRI, and no clinical signs of the involvement of fiber tracts or nuclei were evident in both cases. A unilateral lesion of oculomotor nerve nucleus caused a paralysis of the contralateral superior rectus.     

Effects of depleting central and peripheral adrenaline stores on blood pressure in stroke-prone spontaneously hypertensive rats

The potential role of adrenaline, both circulating and in the central nervous system, in the maintenance of high blood pressure was examined in stroke-prone spontaneously hypertensive rats (SHRSP). alpha-Monofluoromethyldopa, a long-lasting inhibitor of dopa decarboxylase, was used to induce rapid depletion of central and peripheral catecholamine stores. Subsequent inhibition of phenylethanolamine-N-methyltransferase (PNMT) allowed the gradual restoration of dopamine and noradrenaline but not adrenaline, resulting in a greater relative depletion of adrenaline. Adrenaline was almost totally depleted in the circulation and peripheral tissues. The resting level of blood pressure, however, was unaffected, excepting after administration of a vasopressin (AVP) antagonist. Moreover, there was no reduction in the magnitude of acute pressor responses to electrical stimulation of the rostral ventrolateral medulla oblongata (C1 area), despite extensive loss of adrenaline from the brainstem and spinal cord. The results suggest that adrenaline contributes to the resting level of blood pressure but that its loss can be offset by the pressor activity of AVP. Thus neither central nor peripheral adrenaline stores appear to be essential for the maintenance of hypertension or for centrally-evoked vasoconstriction in adult SHRSP.     

Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice

The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic.     

Effect of morphine on the mechanical activity of common bile duct isolated from the guinea pig

The contractile response of isolated guinea pigs common bile ducts (CBD) to transmural electrical stimulation and the effects of morphine and naloxone was studied. Contractile responses increased as a function of stimulus frequency. In the absence of naloxone morphine inhibited the contractile response to electrical stimulation in a dose-dependent manner. Naloxone prevented the inhibitory effect of morphine on the contractile response to electrical stimulation. We conclude that smooth muscle of the CBD in guinea pig is functional and can contribute to biliary motility, and that opiate receptors exist in nerve elements in the CBD.     

Platelet antibodies in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), the precise cause of the thrombocytopenia is unknown. Since platelet associated IgG is increased in many patients, it has been suggested that the destruction of platelets might be dependent on specific antibodies. In nine patients with SLE, platelet associated immunoglobulins were found together with free serum antibody which bound to platelets from all normal subjects. Using an immunoblotting technique with membrane proteins from normal platelets incubated with patient sera, target antigens were localized on a band of mol wt 108,000 in two cases (B. and N.) and on a band of mol wt 66,000 in a third (M.). When the same technique was applied to autologous platelets of patient N., autoantibody binding to the protein of mol wt 108,000 was demonstrated. The antigenic determinants were not removed from the platelets by enzyme treatment or by disulphide bond reduction, and were localized in the cytoplasmic fraction of the platelets.     

No impact of repeated endoscopic screens on gastric cancer mortality in a prospectively followed Chinese population at high risk.

BACKGROUND: Gastric cancer (GC) is the leading cause of cancer deaths in China. Our study prospectively evaluated the impact of repeated endoscopic screens on GC mortality in a high-risk population in China. METHODS: Between 1989 and 1999, a population-based gastroscopic screening was conducted in 4,394 residents of Linqu County, China, a region with the highest rates of GC worldwide. Residents ages 35 to 64 years received initial gastroscopies with biopsies in 1989. Repeated endoscopies were performed in 1994 and 1999. Cancer occurrences and deaths were actively monitored throughout the entire period until July 2000. Mortality from GC was compared with expected values based on mortality rates obtained for Linqu in the 1990-1992 Chinese Cancer Mortality Survey. RESULTS: Between March 1989 and July 2000, 39,303 person-years were accumulated; 85 new GCs occurred, 29 (34.5%) were in early stage. Fifty-eight cases (68%) were identified at one of the screens. The number of observed deaths from GC (37) was close to the expected (36.8). The standardized mortality ratio was 1.01 (95% CI 0.72-1.37) for the entire cohort, 1.13 (95% CI 0.77-1.57) for males, and 0.65 (95% CI 0.26-1.32) for females. CONCLUSIONS: Despite high population coverage with repeated screens, no reduction in GC mortality was observed in this high-risk population in China.     

A nationwide survey on transient hyperammonemia in newborn infants in Japan: prognosis of life and neurological outcome.

A nationwide survey of transient hyperammonemia in newborns was carried out in Japan. A total of 18 patients, consisting of 12 male and 6 female infants, were reported from 11 facilities. These neonates exhibited hyperammonemia with plasma ammonia levels in the range from 124 to 6256 micrograms/dl. Four newborn infants of the 18 died in the neonatal period, and an additional one died in the early infancy. Among the 13 infants who were alive at the time of this survey, 6 had neurological sequelae, including mental retardation, spastic quadriplegia and epilepsy. The multivariate analysis revealed that the Apgar score at 1 minute, peak plasma ammonia concentration, birth weight and sex were significant factors affecting the prognosis of life.