Benzodiazepine ([3H]flunitrazepam) binding in cat visual cortex: ontogenesis of normal characteristics and the effects of dark rearing

[3H]Flunitrazepam (FNZ) binding sites were characterized in homogenates of cat visual cortex during normal postnatal development and following dark rearing from birth. In parallel experiments, the distribution and density of [3H]FNZ binding sites were examined by in vitro autoradiographic or 'scrape' methods. In homogenates, Bmax measurements showed low early values, rising to a peak in receptor density at about 60 days postnatal, followed by a decline in adulthood. At all ages, gamma-aminobutyric acid (GABA) altered the Kd, but not the Bmax of [3H]FNZ binding sites. Kd values showed a general increase with age, parallelled by an increased sensitivity to GABA. Receptor autoradiography revealed that the highest density of [3H]FNZ binding sites was in layer IV of cats of all ages. Deafferentation of extrinsic inputs to the visual cortex by surgical undercutting did not alter this pattern of laminar distribution, indicating that the receptors were associated with intrinsic cortical elements rather than subcortical inputs. Dark rearing had no effect on [3H]FNZ laminar distribution in the visual cortex. The Bmax was higher at 30 days postnatal, but did not differ significantly thereafter. Modulation by GABA was concomitantly higher at 30 days, but lower than normal in dark-reared animals at ages greater than 30 days postnatal. The results are discussed in relation to the normal and abnormal development of GABA receptors in the cat visual cortex.     

Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin

Bone-marrow regeneration after chemo- and radiotherapy-induced aplasia can be monitored by serum levels of myeloperoxidase (MPO), lysozyme (LYS) and lactoferrin (LF). In 10 patients with leukemia, serum measurements were performed before and after bone-marrow transplantation. Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood. LF started to rise 4.5 d before detectable circulating PMNs. 2 patients with early relapses of leukemia post transplantation are shown to display atypical patterns of serum MPO and LYS. We conclude that serum measurements of MPO, LYS and LF may be used as early and sensitive means to monitor bone-marrow activity during hematological regeneration. However, the findings also strongly support the earlier proposal that MPO alone may be used to reflect myeloid activity in the bone-marrow in general.     

Phase II study of iproplatin in metastatic breast carcinoma

Thirty patients with progressive metastatic breast cancer and one prior chemotherapy regimen were treated with iproplatin at a starting dose of 300 mg/m2 iv every 3 weeks. After the first 11 patients, the starting dose was decreased to 270 mg/m2. There were one complete remission, three partial remissions, and two minor responses. Responses were observed in soft tissue and osseous and visceral areas. Grade 3 nausea and vomiting were observed in 38% of patients, and grade 3 diarrhea occurred in 31%. The dose-limiting toxicity was thrombocytopenia, which required dose de-escalation in 15 patients. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Iproplatin has modest antitumor activity in this group of previously treated patients with metastatic breast cancer.     

Fate of TR-2, the hepatic metabolite of the tremorgenic mycotoxin verruculogen, in sheep

1. Verruculogen is eliminated in bile after transformation to TR-2, only a trace of which was excreted as such in faeces of sheep given verruculogen per os. Negligible TR-2 was present free in urine; no glucuronide was found. 2. An isomer of TR-2, a minor component of the bile of sheep given verruculogen, has been defined by 1H-n.m.r. spectroscopy and the isomerism involves the disposition of the two adjacent hydroxyl groups with a concomitant change in the conformation of the ring adjacent to the indole. 3. 14C-TR-2, added to the perfusate of isolated rat liver, was excreted unchanged in the bile, implying no significant loss of any biliary TR-2 subject to enterohepatic recycling in vivo. 4. 14C-TR-2 incubated anaerobically in sheep ileum contents was 95% transformed into more polar metabolites, the majority of the radiolabelled metabolites isolated being water soluble. 5. The principal fate of biliary TR-2 is as a metabolic substrate for the intestinal microflora.     

Isolation from the serum of cancer patients and molecular structure determination of a ketone derivative of D3 vitamin

In a previous article we have reported our finding of an unknown vitamin derivative in the serum of cancer patients and in rats transplanted by a malignant tumor. Analysis of this compound extracted from serum of cancer patients, was carried out by I.R., U.V., mass spectrography and nuclear magnetic resonance (N.M.R.) determination. This analysis led us to the conclusion that the compound was a ketone derivative of D3 vitamin: 1-ceto-24-methyl-25-hydroxycholecalciferol, provisionally designated D3C. Enzymatic pathways involved in the biosynthesis of this substance and its possible role in normal and pathological cell division are discussed.     

Young adult chronic patients: visibility and style of interaction in treatment

To explore the concept of the young adult chronic patient as a distinct clinical entity, the author analyzed a sample of 134 chronic patients on six variables relating to style of interaction with service providers and on diagnostic and demographic variables. The results showed that the 105 younger chronic patients in the sample were more likely than the older patients to be male, to be referred to treatment for suicidal and homicidal gestures and ideation, to have a diagnosis of personality disorder, and to be overrepresented in the treatment population. The author believes the combination of these factors helps create disproportionately high visibility for young adult chronic patients and requires special provisions for their engagement in treatment.     

Cerebral type 2 astroglia are heterogeneous with respect to their ability to respond to neuroligands linked to calcium mobilization.

Very little information is available concerning the pharmacology of type 2 astroglia. During the past decade it has become apparent that two distinct lineages of astroglial cells can be defined in vitro. These two lineages are commonly referred to as type 1 and type 2 and are distinguished from each other on the basis of their morphological features and antigenic phenotypes. In contrast to type 1 astroglia, very little is known about the pharmacology of type 2 astroglia. The lack of information concerning the responsiveness of these cells stems primarily from difficulties encountered in isolating large numbers of type 2 astroglia free of other cell types. In the present study video- and photometer-based imaging systems were used to monitor the influence of a series of neuroligands on the intracellular calcium levels of individual cerebral type 2 astroglia in order to assess their expression of calcium-mobilizing receptors. The responses of 85 immunocytochemically identified cerebral type 2 astroglia to bradykinin (BK), norepinephrine (NE), histamine (HIST), carbachol (CARB), 2-methyl-thio ATP (2MT-ATP), glutamate (GLUT), and serotonin (5-HT) were analyzed. Approximately 50% of cerebral type 2 astroglia responded to BK, NE, HIST, CARB, and 2MT-ATP whereas only 16% and 9% of the cells responded to GLUT and 5-HT, respectively. The number of neuroligands that increased calcium in individual cells ranged from 0 to 6. These responses are quite similar to those previously demonstrated in cultured cerebral type 1 astroglia. No pattern of receptor co-expression was observed for the different neuroligands tests.(ABSTRACT TRUNCATED AT 250 WORDS)