Hypothalamic control of thyrotrophin secretion

1. By means of the haemagglutination-inhibition technique, it has been possible to measure the plasma and pituitary levels of thyroid-stimulating hormone (TSH) following unilateral and bilateral electrolytic lesions placed in the supraoptic area of the hypothalamus of female rats.

2. Unilateral lesions after 8 and 48 hr caused a temporary decrease in the percentage of circulating TSH followed by a return to normal.

3. Bilateral lesions caused a fall in plasma TSH to a level 41% below normal at 10 days whereas the pituitary level increased 70%.

4. Rats with bilateral symmetrical supraoptic lesions, kept for 3 days at 4° C, had a lower plasma TSH content (23%) and a higher pituitary TSH content (16%) than the sham operated control animals but the levels of pituitary TSH did not show any significant difference (0·100 > P > 0·050).

5. Thyroidectomized rats with bilateral lesions kept at 26° C for 3 days had a much lower plasma TSH (39%) and a slightly higher pituitary TSH as compared to the normal intact animals, suggesting that the hypothalamus also influences the synthesis of TSH in the pituitary.

6. Thyroidectomized rats with bilateral lesions kept at 4° C for 3 days showed both a plasma and pituitary TSH increase compared to controls at 26° C, suggesting that when a higher demand for thyroid function is present the pituitary gland has some autonomy for both secretion and release of TSH. This autonomy appears to be slight, as there was no statistically significant difference between the pituitary TSH levels of the thyroidectomized animals bearing similar supraoptic lesions and exposed to 4 and 26° C.

     

Clamp loading,unloading and intrinsic stability of the PCNA, β and gp45 sliding clamps of human,E. coli and T4 replicases

Background: The high speed and processivity of replicative DNA polymerases reside in a processivity factor which has been shown to be a ring-shaped protein. This protein (‘sliding clamp’) encircles DNA and tethers the catalytic unit to the template. Although in eukaryotic, prokaryotic and bacteriophage-T4 systems, the processivity factors are ring-shaped, they assume different oligomeric states. The Escherichia coli clamp (the β subunit) is active as a dimer while the eukaryotic and T4 phage clamps (PCNA and gp45, respectively) are active as trimers. The clamp can not assemble itself on DNA. Instead, a protein complex known as a clamp loader utilizes ATP to assemble the ring around the primer-template. This study compares properties of the human PCNA clamp with those of E. coli and T4 phage. Results: The PCNA ring is a stable trimer down to a concentration below 100 nm (K_d ≈ 21 nm ). On DNA, the PCNA clamp slides freely and dissociates from DNA slowly (t_1/2 ≈ 24 min). β is more stable in solution (K_d < 60 pm ) and on DNA (t_1/2 ≈ 1 h) than PCNA which may be explained by its simpler oligomeric state. The T4 gp45 clamp is a much less stable trimer than PCNA (K_d ≈ 250 nm ) and requires association with the polymerase to stabilize it on DNA as observed previously. The consequence of this cooperation between clamp and polymerase is that upon finishing a template and dissociation of the polymerase from DNA, the gp45 clamp spontaneously dissociates from DNA without assistance. However, the greater stability of the PCNA and β clamps on DNA necessitates an active process for their removal. The clamp loaders (RF-C and γ complex) were also capable of unloading their respective clamps from DNA in the presence of ATP. Conclusions: The stability of the different clamps in solution correlates with their stability on DNA. Thus, the low stability of the T4 clamp explains the inability to isolate gp45 on DNA. The stability of the PCNA and β clamps predicts they will require an unloading factor to recycle them on and off DNA during replication. The clamp loaders of PCNA and β double as clamp unloaders presumably for the purpose of clamp recycling.     

EEG and evoked potential changes during gas- and liquid-breathing dives to 1000 msw

To test the hypothesis that compression in helium gas and compression without gas (hydrostatic compression) both produce the same neurological symptoms of high pressure nervous syndrome (HPNS), groups of 4 to 5 dogs were exposed to one of the following: (a) a 2-h surface control breathing He-O2 gas; (b) compression to 700-1000 msw breathing He-O2 gas; (c) a 2-h liquid-breathing control [ventilation with warmed (38 degrees C), oxygenated fluorocarbon liquid, FC-80]; and (d) "near hydrostatic" compression to 700-1000 msw while being ventilated with liquid from a sealed reservoir. Power spectra obtained from scalp-recorded EEG signals revealed a significant compression-related shift of power from the normally dominant 5-8 Hz band to the 8-11 Hz band. This effect was greatest at 600 msw and occurred equally in both dive groups. At very high pressures (greater than 900 msw) power in this 6-10 Hz range became reduced whereas 16-22 Hz activity increased as the EEG flattened. Somatosensory evoked potentials (SEPs) were elicited by subdermal electrical stimulation in the foreleg (n = 120). The latency of P1 (approximately 31 ms) did not change in any group; transmission time to cortex was unaltered by time or pressure. However, the "late-wave" P4 (approximately 250 ms) was slowed by 32-35 ms at 1000 msw in both groups (P less than 0.003 in He-O2). Since these main symptoms were provoked equally in both He-O2 and FC-80 dive groups, helium pressure did not play a significant role in the etiology of HPNS in this animal model. It is concluded that the HPNS is primarily a result of excessive pressure per se or rate of change of pressure per se.     

Afterimages of sinusoidal, square-wave and compound gratings

Negative afterimages were observed after steady fixation of sinusoidal gratings at low spatial frequencies, and quantified using contrast-matching and cancellation methods. Afterimage contrast increased as a power function of "exposure", defined as the product of inspection contrast and inspection duration. A single function, linear on a log-log plot, describes the afterimages of gratings at different spatial frequencies, contrasts and durations. The matching method yielded a lower slope (about 0.42) than the cancellation method (0.62), probably because contrast adaptation attenuates perceived afterimage contrast in the first method, but not the second. Square-wave gratings, and those containing two or three harmonic components gave much weaker afterimages (assessed by contrast-matching) than sine-waves did. Contrast adaptation may again be responsible. Hemi-field asymmetries in contrast perception were noted. The contrast of real gratings and afterimages was nearly additive, especially at lower exposures, but the results cannot distinguish between linear filter and gain control models of "local adaptation".     

Nutritional considerations in the patient with disabling brain disease

Increased nutritional requirements are now recognized as the typical sequellae of head injury. Whether similar nutritional demands routinely accompany nontraumatic, disabling brain diseases is uncertain. Experience with patients suffering from head injury indicates that clinical criteria for differentiating the severity of neurological impairments categorize rather poorly the levels of nutritional need. Based on available data, "nutritional risk" can only be assigned to broad patient categories. Head-injured patients seem to be at nutritional risk and, by virtue of increased caloric and protein requirements, may benefit, in terms of reduced mortality, from early, intensive nutritional intervention. Because the nutritional risk cannot be established, the indications for aggressive nutritional support in the noninjured patient are even less clear than those for the trauma patient. Parenteral nutrition is often required to meet the goals of nutritional support because inadequacies in gastrointestinal function frequently mitigate successful enteral nutrition. Selective nutritional therapies involving the branched chain amino acids may reduce the attrition of the body cell mass seen in head injury patients. Furthermore, improvements in energy nutrient utilization in other than head-injured patients have been suggested when fat is provided in addition to glucose as a caloric source. When clinically feasible, enteral nutrition offers significant economic and physiological benefits over parenteral nutrition. In this regard, increasing attention has been focused on newer techniques of enteral access. These include percutaneous gastrostomies and nasally inserted small bore feeding tubes. The latter achieve duodenal intubation with a high success rate, and they offer the prospects of improved feeding tolerance and reduced tracheobronchial aspiration by allowing the administration of nutrients distal to the pylorus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Psychogenic pain: a study of marital adjustment

The marital adjustment of patients with psychogenic pain disorder was evaluated and compared with a matched group of patients with other neurotic disorders. Pain patients spouses were found to have better marital adjustment and less psychiatric morbidity than the spouses of neurotic patients. These findings are discussed in terms of the concepts of "sick role homeostasis" and "tertiary gain".     

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

FDA's conduct, review, and evaluation of inspections of clinical investigators.

This review of the Food and Drug Administration's Bioresearch Monitoring Program focuses on the inspection of clinical investigators who study investigational drugs. The differences between routine, "for-cause," and bioequivalency/bioavailability inspections are examined, with emphasis on the responsibilities of the clinical investigator, reasons for conducting the inspections, and problems found. Important aspects of the inspection report, such as protocol adherence, records maintenance, informed consent, institutional review board approval, and drug accountability, are outlined. The disqualification and consent agreement processes for investigators with serious problems are explained. FDA policies on third-party notification and remote data entry are noted.