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Biomedical subjects

M R Rubin

Publications and source records attributed to M R Rubin.

At least 19 recordsLinked to original sources

Parathyroid hormone as an anabolic therapy for women and men.

The quest for effective treatment of osteoporosis merits great attention because of the widespread, worldwide prevalence of this disease. Antiresorptive drugs reduce bone turnover, increase bone density and improve other aspects of bone quality. This article concentrates on another approach, namely the use of anabolic therapy in which the prospects for improving bone quality are even greater. Parathyroid hormone is available as the aminoterminal fragment, PTH(1-34), known as teriparatide, and is being studied in its full-length form, PTH(1-84). Teriparatide improves bone quality by actions on bone turnover, bone density, bone size and microarchitecture. In women, teriparatide reduces both vertebral and non-vertebral fractures. In individuals who have been treated previously with an antiresorptive agent, the ability of PTH to increase bone density may be reduced. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive does not appear, at this time, to offer advantages over the use of parathyroid hormone alone. In order to maintain the densitometric gains in bone density with parathyroid hormone, it is important to follow its use with an antiresorptive agent.

Anabolic Agents↗

Influence of muscle strength and total work on exercise-induced plasma growth hormone isoforms in women.

The purpose of this investigation was to determine the influence of physical strength and the ability to do more total work on human growth hormone (GH) variants to a heavy resistance exercise protocol in untrained women. From a distribution of 100 healthy, untrained women, the strongest 10 women (S) and the weakest 10 women (W) were compared for GH responses pre- and post an acute heavy resistance exercise test (AHRET, 6 sets of 10 RM squats, 2 minutes rest between sets). Blood samples were obtained pre-exercise and immediately post-exercise and subsequently analysed in total as well as fractionated by Sephacryl S-100R column chromatography into three molecular weight size classes: fraction A: > 60 kD, fraction B: 30-60 kD, fraction C: < 30 kD. For each total sample as well as each fraction, immunoreactive GH was measured via the Nichols IRMA, while bioactive GH was measured via the hypox rat tibial line bioassay and Diagnostic Systems Laboratory's immunofunctional GH ELISA. No exercise-induced changes or differences between groups were observed in the tibial line bioassay. However, the S group displayed a significantly higher pre-exercise resting value in the total fraction than the W group. Conversely, the W group exhibited a significantly higher pre-exercise value in the smaller molecular weight fraction C. With regards to the immunofunctional and immunoreactive assays, the total fraction, fraction A, and fraction B demonstrated significant (P < or = 0.05) exercise-induced increases in both the S and W group despite no group differences. For the Nichols and immunofunctional assays significant exercise-induced changes were observed in the smaller molecular weight C fraction in the W group but not the S group. However, the S group displayed a significantly higher pre-exercise value in fraction C relative to the W group. These data demonstrate for the first time that differences exist in the GH molecular weight variants between strong and weak untrained women, with the lower molecular weight variants seemingly less responsive to greater amounts of exercise in stronger women, thus suggesting differential regulation of GH molecular weight variants during resistance exercise due to pre-existing physical parameters.

Animals↗

Sarcoidosis within a pituitary adenoma.

A 54 year old man presented with frontal headaches for one year. A CT scan of the head revealed a pituitary mass. He denied a change in vision or galactorrhea, but did have decreased frequency of erections and a recent episode of renal stones. On physical exam, the cranial nerves were normal. Visual field exam revealed mild bilateral temporal defects. The genitalia were normal and the testes were soft. Laboratory evaluation revealed: Na, 134 mM/l; K, 6.7 mM/l; Cl, 104 mM/l; HCO3, 22 mM/l; BUN, 47 mg/dl; Cr, 8.3 mg/dl; Ca, 12.5 mg/dl; Phos, 5.5 mg/dl; prolactin, 32.0 ng/ml; T4, 4.46 microg/dl; TSH, 2.07 microU/ml; LH, 18.1 mIU/ml; FSH 3.2 mIU/ml; alpha subunit 1.6 ng/ml; testosterone 255 ng/dl; cortisol, 20.3 microg/dl; cortisol after 250 microg cortrosyn, 38.5 microg/dl (time 60 minutes); growth hormone, 1.4 ng/ml; IGF-1, 47 ng/ml; PTH, <1 pg/ml; 25-hydroxyvitamin D, 14 ng/ml; 1,25-dihydroxyvitamin D, 69 pg/ml. These results were felt to be consistent with a non-PTH-mediated hypercalcemia, such as humoral hypercalcemia of malignancy, or a vitamin D-mediated hypercalcemia, such as lymphoma, sarcoidosis or tuberculosis. Head MRI demonstrated a 3.5 x 3.5 x 2.5 cm heterogeneous mass enlarging the sella, deforming the clivus and compressing the cavernous sinus, basilar artery and left side of the optic chiasm. There was a small focus of high signal in the superior part of the mass on the T1-weighted image from either a proteinaceous cyst with early calcium deposition or sub-acute blood. These radiographic findings were felt to be consistent with a pituitary adenoma. The patient was treated with intravenous hydration and thyroxine 50 microg daily and underwent a transsphenoidal resection of the pituitary lesion. Pathologic examination revealed a pituitary adenoma with multiple granulomas and crystalline material; this was consistent with sarcoid within the adenoma. Post-operatively, the serum LH fell to 5.5 mIU/ml. A subsequent transbronchial biopsy revealed multiple non-caseating granulomas. A serum ACE level was elevated at 132.6 U/l. He received oral prednisone 60 mg daily with resolution of the hypercalcemia. Neurosarcoidosis occurs in 5 to 15% of patients with sarcoidosis and can involve the hypothalamus and pituitary gland. This is the first reported case of sarcoidosis occurring within a pituitary adenoma.

Adenoma↗

Resistance training combined with bench-step aerobics enhances women's health profile.

PURPOSE: The purpose of this study was to investigate the comprehensive physiological alterations that take place during the combination of bench-step aerobics (BSA) and resistance exercise training. METHODS: Thirty-five healthy, active women were randomly assigned to one of four groups that either a) performed 25 min of BSA only (SA25); b) performed a combination of 25 min of BSA and a multiple-set upper and lower body resistance exercise program (SAR); c) performed 40 min of BSA only (SA40); or d) served as a control group (C), only performing activities of daily living. Direct assessments for body composition, aerobic fitness, muscular strength, endurance, power, and cross-sectional area were performed 1 wk before and after 12 wk of training. RESULTS: All training groups significantly improved peak VO(2) (3.7 to 5.3 mL O(2).kg(-1).min(-1)), with the greatest improvement observed in the SAR group (P = 0.05). Significant reductions in preexercise heart rates (8-9 bpm) and body fat percent (5--6%) were observed in all training groups after training. Significant reductions in resting diastolic blood pressure were observed for the SAR and SA40 groups (6.7 and 5.8 mm Hg, respectively). Muscular strength and endurance only improved significantly in the SAR group (21 and 11% respectively). All groups demonstrated increased lower body power (11--14%), but only the SAR group significantly improved upper body power (32%). Thigh muscle cross-sectional areas measured via magnetic resonance imaging (MRI) increased primarily for the SAR group. CONCLUSION: BSA is an exercise modality effective for improving physical fitness and body composition in healthy women. The addition of resistance exercise appears to enhance the total fitness profile by improving muscular performances, muscle morphology, and cardiovascular fitness greater than from performing BSA alone. Therefore, the inclusion of both modalities to an exercise program is most effective for improving total body fitness and a woman's health profile.

Adult↗

Physiological and performance responses to tournament wrestling.

PURPOSE: The purpose of this study was to investigate the physiological and performance responses to a simulated freestyle wrestling tournament after typical weight loss techniques used by amateur wrestlers. METHODS: Twelve Division I collegiate wrestlers (mean +/- SD;19.33 +/- 1.16 yr) lost 6% of total body weight during the week before a simulated, 2-d freestyle wrestling tournament. A battery of tests was performed at baseline and before and immediately after each individual match of the tournament. The test battery included assessment for body composition, reaction/movement time, lower and upper body power and isokinetic strength, and a venous blood sample. RESULTS: Lower body power and upper body isometric strength were significantly reduced as the tournament progressed (P < or = 0.05). Significant elevations in testosterone, cortisol, and lactate were observed after each match (P < or = 0.05). However, there was a significant reduction (P < or = 0.05) in resting testosterone values in the later matches. Norepinephrine increased significantly (P < or = 0.05) after each match, whereas epinephrine increased significantly (P < or = 0.05) after each match except the last match of each day. Plasma osmolality was consistently higher than normal values at all times including baseline, with significant increases observed after each match (P < or = 0.05). CONCLUSIONS: Tournament wrestling augments the physiological and performance decrements of weight loss and its impact is progressive over 2 d of competition. The combined effects of these stresses may ultimately be reflected in a wrestler's ability to maintain physical performance throughout a tournament.

Adolescent↗

Safety measures of L-carnitine L-tartrate supplementation in healthy men.

The purpose of this investigation was to examine the effects of ingestion of L-CARNIPURE (L-carnitine L-tartrate [LCLT]) on alterations in a complete blood cell profile and in circulating metabolic enzymes. Using a balanced, placebo (P), cross-over design (1 week washout), 10 healthy, active men volunteered and acted as their own control taking either a P or LCLT supplement (3 g.day(-1)) for 3 weeks. Postabsorptive morning blood samples were obtained both before and after 21 days of P and LCLT supplementation. Serum samples were analyzed for clinical chemistries including a complete chemistry panel with markers of liver and renal function along with various minerals and electrolytes. In addition, whole blood was analyzed for a complete blood count with differential. It was determined that there were no statistically significant differences between the LCLT and the placebo conditions for any of the variables examined. The results of this study suggest that LCLT, when used as a dietary supplement, has no adverse effects on metabolic and hematological safety variables in normally healthy men.

Adult↗

Induction of formation of presynaptic terminals in neuroblastoma cells by synapsin IIb.

The synapsins are a family of closely related phosphoproteins (termed synapsins Ia, Ib, IIa and IIb) associated with synaptic vesicles and implicated in the short-term regulation of neurotransmitter release from nerve endings. During development, expression of the synapsins correlates temporally with synapse formation, but there has been no direct evidence that they are involved in synaptogenesis. Here we report that overexpression of synapsin IIb in the neuroblastoma x glioma hybrid clonal cell line NG108-15 leads, during cell differentiation, to marked increases in the number of neuritic varicosities and in the numbers of small clear vesicles and large dense core vesicles per varicosity, as well as to the appearance of synapse-like cell-cell contacts. Thus, synapsin IIb may be involved in the regulation of synapse formation and, as a result, in long-term neuronal signalling.

Animals↗

Murine embryonic spinal cord and adult testis Hox-1.4 cDNAs are identical 3' to the homeo box.

The Hox-1.4 murine homeo box containing gene is expressed in both embryonic spinal cord and adult testis where different sized Hox-1.4 transcripts are detected. In order to compare the sequences of these transcripts, Hox-1.4 cDNA clones were isolated from cDNA libraries prepared from mouse embryonic spinal cord and mouse adult testis. Sequence analysis showed these clones to be identical and extend from an internal EcoRI site at position 55 in the homeo box to a poly (A) stretch 20 nucleotides 3' to the polyadenylation signal. These data indicate that murine Hox-1.4 mRNAs expressed in embryonic spinal cord and adult testis are identical 3' to the homeo box and utilize the same polyadenylation signal.

Amino Acid Sequence↗

Alternatively spliced Hox-1.7 transcripts encode different protein products.

Two Hox-1.7 cDNAs, GPK5 and GPK6, were isolated from an adult guinea-pig kidney cDNA library by hybridization at low stringency using a Hox-1.7 cDNA probe, MH-1, cloned from mouse F9 teratocarcinoma cells. Sequence analysis of these two Hox-1.7 cDNAs showed that (a) GPK5 contains a putative initiation codon preceding an open reading frame which includes the homeo box, and may represent the complete protein coding region for the corresponding Hox-1.7 transcript; (b) the amino acids encoded by GPK6 and MH-1 are nearly identical (with two changes); (c) both adult guinea-pig kidney cDNA clones share identical homeo domains with the mouse Hox-1.7 cDNA; and (d) both adult guinea-pig kidney cDNA clones are identical in the homeo box region and in the 3' untranslated region but differ significantly starting from the 12th codon upstream from the homeo box. These data, supported by Southern blot analysis, indicate that a splice site is present 5' to the homeo box and that alternative splicing results in transcripts encoding different protein products.

Amino Acid Sequence↗

Murine Hox-1.7 homeo-box gene: cloning, chromosomal location, and expression.

A new murine homeo-box, called Hox-1.7, has been identified in a rare cDNA from F9 teratocarcinoma stem cells. The Hox-1.7 homeo-box is 68 and 72% homologous to the Drosophila antennapedia (Antp) and iab-7 homeo-boxes, respectively. A major 2.5-kilobase transcript and several minor transcripts were detected by Northern blot (RNA blot) analysis in adult tissues as well as in midgestational embryos. The posterior spinal cord was found to be a major site of Hox-1.7 expression in 12.5-day-old embryos. Somatic cell hybrids were used to map the Hox-1.7 gene to mouse chromosome 6. Restriction fragment length polymorphisms associated with either the Hox-1.7 gene or the previously known Hox-1 complex were identified. Their distribution patterns in recombinant inbred mouse strains were used to determine the linkage between the two loci as well as to other loci on chromosome 6. This maps Hox-1 and Hox-1.7 close to two mouse loci that affect morphogenesis, postaxial hemimelia (px) and hypodactyly (Hd).

Amino Acid Sequence↗

A mouse homeo box gene is expressed in spermatocytes and embryos.

The MH-3 gene, which contains a homeo box that is expressed specifically in the adult testis, was identified and mapped to mouse chromosome 6. By means of in situ hybridization with adult testis sections and Northern blot hybridization with testis RNA from prepuberal mice and from Sl/Sld mutant mice, it was demonstrated that this gene is expressed in male germ cells during late meiosis. In the embryo, MH-3 transcripts were present at day 11.5 post coitum, a stage in mouse development when gonadal differentiation has not yet occurred. The MH-3 gene may have functions in spermatogenesis and embryogenesis.

Animals↗

Improvement in exercise performance with nisoldipine, a new second-generation calcium blocker, in stable angina patients.

Safety and efficacy of a new dihydropyridine calcium antagonist, nisoldipine, were studied in 15 patients with proved coronary artery disease and positive exercise treadmill tests. After withdrawal of current therapy and a 2-week placebo phase, patients were given nisoldipine 10, 20, and 40 mg daily (divided into two daily doses), each dose for a 2-week period. Exercise treadmill testing was performed twice during the placebo and once at the end of each nisoldipine phase. Maximal duration of exercise increased with all doses of nisoldipine. Time to 1 mm ST segment depression also increased with all doses of nisoldipine. Peak time to angina was similarly prolonged. Peak exercise double product (heart rate X systolic blood pressure) was unaffected by all doses of nisoldipine. Angina frequency and nitroglycerin consumption decreased during nisoldipine therapy in all patients. Side effects from therapy were only minor. Twice daily therapy compared to three to four times daily therapy with other calcium blockers is an advantage of nisoldipine.

Adult↗

Emergency coronary artery bypass graft surgery for threatened acute myocardial infarction related to coronary artery catheterization.

In 20 patients undergoing cardiac catheterization, usually involving balloon-catheter dilation or streptokinase infusion, catheter-induced coronary artery intimal damage resulted in severe chest pain, electrocardiographic evidence of obstruction or dissection of a major coronary artery. These patients were surgically revascularized within 8 hours after the onset of the acute chest pain syndrome. Our experience with pharmacological and catheter-related manipulations to improve coronary blood flow after the ischemic episode but before operation suggested that the additional time spent in the catheterization laboratory was worthwhile. The injured coronary artery was the left anterior descending in 10 patients, the right in 8, the left main in 1 patient, and an obtuse marginal branch of the circumflex in 1. The average number of grafts per patient was 2.5; only 6 patients had single bypass grafts. In 5 patients, intraaortic balloon pumping was used either preoperatively or postoperatively. Inotropic support was used postoperatively in 5 patients, and 7 patients received lidocaine for ventricular irritability. Abnormal elevation of the serum isoenzyme of creatine kinase (CK-MB) was seen in 8 patients, and new Q waves were noted in 4 patients; 3 of these 4 patients with new Q waves also had abnormal serum CK-MB levels. Global ejection fraction obtained by the equilibrium-gated blood pool scan postoperatively was 60 +/- 3%, which was similar to the 62 +/- 3% obtained from the contrast-determined ventriculogram done preoperatively prior to the catheter-related injury. There were no early or late deaths, but morbidity was much higher in the group who had emergency coronary artery bypass grafting (CABG) compared with those who had elective CABG.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

Properties of the cat ileocecal sphincter muscle.

The purpose of this study was to determine the length-tension properties and the response to neurohumoral agents of the feline ileocecal sphincter (ICS) circular smooth muscle in vitro. The ICS muscle during stretch maintained a higher resting tension at lower degrees of stretch than did the adjacent ileum and colon. Sodium nitroprusside (10(-3) M) or calcium-free Krebs solution with EGTA (5.0 mM) reduced the resting tension of ICS muscle by 15.8 +/- 2.1 and 19.1 +/- 2.5%, respectively. The ICS response to KCl depolarization was lower (0.37 +/- 0.03 kg/cm2) than colonic muscle (0.55 +/- 0.06 kg/cm2) oe ileal muscle (0.51 +/- 0.04 kg/cm2) (P less than 0.05). However, in response to acetylcholine, ICS muscle tension was minimal (0.06 +/- 0.02 kg/cm2) was compared with the colon (0.49 +/- 0.05 kg/cm2) or ileum (0.53 +/- 0.05 kg/cm2) (P less than 0.01). The ICS muscle contracted in response to phenylephrine, whereas other muscles were inhibited. Secretin, gastrin, glucagon, and cholecystokinin failed to act on the ICS muscle while other muscles did respond. These studies suggest that ICS muscle differs from adjacent ileal and colonic circular muscle in that a) in response to stretch it develops a high resting tension that is relatively resistant to calcium withdrawal, and b) it also shows quantitative and qualitative differences in response to neurohumoral agents.

Acetylcholine↗