Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: potential synergistic effects on prognosis

Routinely processed pathological specimens from 119 patients with stage I and II adenocarcinomas or squamous cell carcinomas were examined by immunohistochemical analysis for altered retinoblastoma (RB) and/or p53 protein expression. Absent RB nuclear staining (RB-) indicating loss of RB function occurred in 19 (16%) of the cases studied, whereas expression of a putative mutant p53 nuclear protein (p53(+)) was found in 54 (45%) of the tumors. The median survival was 39 versus 12 months for patients with RB+ and RB- tumors, respectively (P = 0.05 by log rank analysis). Similarly, the median survival was 41 months for patients whose tumors had no expression of mutant p53 (p53(-)) compared with 24 months for individuals with p53 (+) tumors (P = 0.01). These differences in survival, however, were not statistically significant by multivariate analysis. Nevertheless, individuals with RB-/p53(+) tumors had a significantly shorter median survival (12 months) than those with RB+/p53(-) tumors (41 months), as determined by both log rank and multivariate analyses (P = 0.005 and 0.03, respectively). In addition, 66 large cell carcinomas from all stages were examined. Again, a more significant difference in survival (48 versus 8 months) was found between patients with RB+/p53(-) versus RB-/p53(+) tumors (P = 0. 006). These results suggest that RB and p53 status might be used synergistically as prognostic factors in a subset of non-small cell lung carcinomas.     

Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression

In 219 HIV-1-infected men of the Amsterdam cohort we measured CD4+ T cell numbers and in vitro T cell responses to CD3 MoAbs with or without CD28 costimulation and phytohaemagglutinin (PHA). The value of these markers was estimated for disease progression within 4 years. CD28 expression on T cells has been related to T cell responses. CD28 costimulation considerably enhanced T cell reactivity (approximately 8-10-fold) with lower coefficients of variation compared with reactivity to CD3 MoAb alone (median 5 versus 20). T cell reactivity to CD3 plus CD28 MoAb was decreased during HIV-1 infection and was besides CD4+ T cell numbers the only independent predictor for progression to AIDS. Compared with the group with high CD4+ T cell numbers the relative risk (RR) for the group with intermediate levels was 2.28, with low levels 5.20. In the groups with intermediate and low CD3 plus CD28 responses the RR was 2.04 and 4.16, respectively. The combined RR for both was 4.65 and 21.63. The independence of this marker was confirmed when the group with low CD4+ T cell numbers was subdivided into groups with high, intermediate and low T cell responses. The expansion of CD8+CD28- T cells was already apparent in HIV- homosexual men, but CD8+CD28+ T cells specifically decreased in patients with AIDS. CD28 expression on T cells correlated moderately with T cell responses to CD3 plus CD28 MoAb. T cell reactivity to CD3 MoAb in the presence of CD28 MoAb is a stronger prognostic marker than T cell reactivity to CD3 MoAb alone.     

Glucose effectiveness, peripheral and hepatic insulin sensitivity, in obese and lean prepubertal children

Vascular injuries in lumbar disk surgery, although rare, are serious complications which may be overlooked due to a broad range of clinical manifestations. It is important that surgeons and radiologists be aware of these potentially fatal complications and develop an appropriate symptom-based diagnostic paradigm. We reviewed 8099 consecutive cases of lumbar disk surgery, performed over a 14-year period at a single institution, for postoperative vascular complications. We identified four patients (0.05%) with lumbar disk surgery-related vascular complications: intraoperative lacerations of the abdominal aorta and median sacral artery, an arteriovenous fistula between the left common iliac artery and vein detected 19 days postdiskectomy, and a partially thrombosed aortic aneurysm with an arteriovenous fistula between the aneurysm and the inferior vena cava, diagnosed 11 months after surgery. The majority of cases in the literature of vascular injury in lumbar disk surgery were reported prior to 1965. Diagnostic approaches described in that period do not reflect the great range of diagnostic techniques available today. Angiography remains the gold standard for diagnosis and guidance as to surgical repair. However, a high index of suspicion based on clinical signs and/or the use of sonography or CT is important in the detection of these complications.     

CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors

We studied the potential roles of testosterone and serotonin in various forms of aggressive and violent behaviors by measuring each biochemical and behaviour in free-ranging adolescent male nonhuman primates. Our results showed that (1) CSF free testosterone concentrations were positively correlated with overall aggressiveness, but not with measures of impulsivity. (2) CSF 5-HIAA concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression, but not with overall rates of aggression. High rates of impulsive behavior were positively correlated with severe, unrestrained aggression, but not overall rates of aggression. (3) Dimensional analyses showed that while subjects with low CSF 5-HIAA exhibited high rates of aggression, high CSF testosterone further augmented rates and intensity of aggression in subjects with low CSF 5-HIAA. We conclude that high CSF free testosterone concentrations are associated with competitive aggression, while low CSF 5-HIAA concentrations are associated with severe aggression which results from impaired impulse control, and perseverance.     

A PET study of the neural systems of stuttering

The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking.     

Nasopharyngeal Castleman's disease

A 19-year-old male was admitted to our clinic because of nasal obstruction and intermittent postnasal drip of 3 to 4 years' duration. Physical examination revealed a wide-based, smooth-surfaced nasopharyngeal tumor which was suspected to be a nasopharyngeal angiofibroma after examination of computed tomographic scans and an angiogram. However, after the tumor was removed by surgical excision via a transpalatal approach, the pathologic examination revealed Castleman's disease of the hyaline-vascular type. There was neither evidence of recurrence nor nasal problems at 4 years' follow-up. To our knowledge, Castleman's disease, or angiofollicular lymph node hyperplasia, may present as a local or generalized tumor-like condition, usually in the chest or abdomen, and may involve both the lymph nodes and non-nodal tissues. A review of previous articles reveals that there has not been any report of Castleman's disease found in the nasopharynx. This rare disorder is presented and discussed.     

Absorption of isomeric, palmitic acid-containing triacylglycerols resembling human milk fat in the adult rat

The effect of the positional distribution of palmitic acid (16:0) in triacylglycerols (TAG) on 16:0 apparent absorption in adult rats was investigated. The rats were fed two diets which contained 30 energy % as fat with identical total fatty acid compositions, both containing 30% 16:0. The Betapol diet contained TAG with 73% of total 16:0 in the sn-2 position, the control diet contained TAG with 6% of total 16:0 in the sn-2 position. After six weeks on these diets, the rats were killed two or six hours after the last meal, and the small intestine was removed, cut into 10-cm segments, and the fatty acid composition of the segment's contents was determined. At both time points the amount of 16:0 in the intestinal segments starting at 40 cm from the stomach was much lower in the animals fed Betapol than in the animals fed the control diet. Overall absorption of 16:0 and stearic acid was significantly greater in the Betapol group. Absorption of oleic and linoleic acid from the small intestine was similar in both groups, although the overall absorption was significantly greater in the animals fed Betapol. Total fat absorption was significantly higher in the Betapol-fed rats than in the control-fed rats. No effect on calcium and nitrogen absorption, on plasma total cholesterol and TAG levels, and on bodyweights (growth) was seen. The data demonstrate that the positional distribution of the fatty acids in the TAG molecule affects the site of absorption in the small intestine and particularly the net absorption of saturated fatty acids.     

2H( gamma,p)n cross section between 20 and 440 MeV

Rate control in acetylcholinesterase (AChE) involves a single anionic site whose anionic center controls rate-related biochemical and conformational changes in the E (free enzyme) and EA (acylated enzyme) conformers. Change in conformer structure and biochemistry affect binding, acylation, and hydrolysis. It is significant that the anionic-esteratic intersite distance is not altered during conformer change as E is converted to EA. In this enzyme system, cationic acetylcholine and anionic AChE are true structural, functional, and biochemical counterparts. The anionic center in the E conformer lies at the bottom of a sterically restricted, hydrophobic cleft < 8 A wide at the top and > 3 A wide at the bottom, while the anionic center in the EA conformer is relatively open. It is characterized by a decrease in the relative binding of hydrophobic cations and by an ability to bind large organic cations. Binding of acetylcholine, H+, or organic cations at the anionic site controls k2(acylation) in the E conformer and k3(hydrolysis) in the EA conformer. Acetylcholine binding forms the ES complex in which the cation maximizes k2. In the EAS complex, the cation reduces k3 and provides allosteric control. Anionic site structure and biochemistry and the effect of pH on k2 and k3 differentiates AChE from butyrylcholinesterase. This comprehensive study of kinetic and thermodynamic processes in AChE was made possible by the synthesis and/or use of families of over 30 cationic and acylation probes of known stereochemistry. They act as rulers of the E and EA conformers of AChE and provide comparative data on kinetic-based and thermodynamic-based constants. Cationic inhibitors affect decarbamylation rates in AChE and provide an additional set of comparative data related to the mechanism of substrate hydrolysis by AChE. Acridine araphanes are unique neural receptor and cholinergic enzyme probes. Their parallel plane and coplanar conformations are related to bridge length. Two parallel plane acridine araphanes are pure uncompetitive inhibitors of AChE. Scatchard plots of the binding of methylacridinium and 9-aminoacridine with the E conformer and 9-aminoacridine with the EA conformer indicate binding at a single anionic site. No ternary complex (EII or EAII) from two-site binding was detected. In AChE, nonspecific, low-level binding at surface ionic and hydrophobic areas is ubiquitous. Binding affinity differences greater than two orders of magnitude distinguish binding at the anionic site from low level binding at surface moieties. Surface binding provides environmental and stability changes in the enzyme but does not modify the fundamental biochemistry of the E and EA conformers.